Using a Human Challenge Model of Infection to Measure Vaccine Efficacy: A Randomised, Controlled Trial Comparing the Typhoid Vaccines M01ZH09 with Placebo and Ty21a.

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Darton, Thomas C; Jones, Claire; Blohmke, Christoph J; Waddington, Claire S; Zhou, Liqing; Peters, Anna; Haworth, Kathryn; Sie, Rebecca; Green, Christopher A; Jeppesen, Catherine A; Moore, Maria; Thompson, Ben A V; John, Tessa; Kingsley, Robert A; Yu, Ly-Mee; Voysey, Merryn; Hindle, Zoe; Lockhart, Stephen; Sztein, Marcelo B; Dougan, Gordon; Angus, Brian; Levine, Myron M; Pollard, Andrew J

2016-08-01

Typhoid persists as a major cause of global morbidity. While several licensed vaccines to prevent typhoid are available, they are of only moderate efficacy and unsuitable for use in children less than two years of age. Development of new efficacious vaccines is complicated by the human host-restriction of Salmonella enterica serovar Typhi (S. Typhi) and lack of clear correlates of protection. In this study, we aimed to evaluate the protective efficacy of a single dose of the oral vaccine candidate, M01ZH09, in susceptible volunteers by direct typhoid challenge. We performed a randomised, double-blind, placebo-controlled trial in healthy adult participants at a single centre in Oxford (UK). Participants were allocated to receive one dose of double-blinded M01ZH09 or placebo or 3-doses of open-label Ty21a. Twenty-eight days after vaccination, participants were challenged with 104CFU S. Typhi Quailes strain. The efficacy of M01ZH09 compared with placebo (primary outcome) was assessed as the percentage of participants reaching pre-defined endpoints constituting typhoid diagnosis (fever and/or bacteraemia) during the 14 days after challenge. Ninety-nine participants were randomised to receive M01ZH09 (n = 33), placebo (n = 33) or 3-doses of Ty21a (n = 33). After challenge, typhoid was diagnosed in 18/31 (58.1% [95% CI 39.1 to 75.5]) M01ZH09, 20/30 (66.7% [47.2 to 87.2]) placebo, and 13/30 (43.3% [25.5 to 62.6]) Ty21a vaccine recipients. Vaccine efficacy (VE) for one dose of M01ZH09 was 13% [95% CI -29 to 41] and 35% [-5 to 60] for 3-doses of Ty21a. Retrospective multivariable analyses demonstrated that pre-existing anti-Vi antibody significantly reduced susceptibility to infection after challenge; a 1 log increase in anti-Vi IgG resulting in a 71% decrease in the hazard ratio of typhoid diagnosis ([95% CI 30 to 88%], p = 0.006) during the 14 day challenge period. Limitations to the study included the requirement to limit the challenge period prior to treatment to 2

A forecast of typhoid conjugate vaccine introduction and demand in typhoid endemic low- and middle-income countries to support vaccine introduction policy and decisions.

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Mogasale, Vittal; Ramani, Enusa; Park, Il Yeon; Lee, Jung Seok

2017-09-02

A Typhoid Conjugate Vaccine (TCV) is expected to acquire WHO prequalification soon, which will pave the way for its use in many low- and middle-income countries where typhoid fever is endemic. Thus it is critical to forecast future vaccine demand to ensure supply meets demand, and to facilitate vaccine policy and introduction planning. We forecasted introduction dates for countries based on specific criteria and estimated vaccine demand by year for defined vaccination strategies in 2 scenarios: rapid vaccine introduction and slow vaccine introduction. In the rapid introduction scenario, we forecasted 17 countries and India introducing TCV in the first 5 y of the vaccine's availability while in the slow introduction scenario we forecasted 4 countries and India introducing TCV in the same time period. If the vaccine is targeting infants in high-risk populations as a routine single dose, the vaccine demand peaks around 40 million doses per year under the rapid introduction scenario. Similarly, if the vaccine is targeting infants in the general population as a routine single dose, the vaccine demand increases to 160 million doses per year under the rapid introduction scenario. The demand forecast projected here is an upper bound estimate of vaccine demand, where actual demand depends on various factors such as country priorities, actual vaccine introduction, vaccination strategies, Gavi financing, costs, and overall product profile. Considering the potential role of TCV in typhoid control globally; manufacturers, policymakers, donors and financing bodies should work together to ensure vaccine access through sufficient production capacity, early WHO prequalification of the vaccine, continued Gavi financing and supportive policy.

Identification of Novel Serodiagnostic Signatures of Typhoid Fever Using a Salmonella Proteome Array

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Thomas C. Darton

2017-09-01

Full Text Available Current diagnostic tests for typhoid fever, the disease caused by Salmonella Typhi, are poor. We aimed to identify serodiagnostic signatures of typhoid fever by assessing microarray signals to 4,445 S. Typhi antigens in sera from 41 participants challenged with oral S. Typhi. We found broad, heterogeneous antibody responses with increasing IgM/IgA signals at diagnosis. In down-selected 250-antigen arrays we validated responses in a second challenge cohort (n = 30, and selected diagnostic signatures using machine learning and multivariable modeling. In four models containing responses to antigens including flagellin, OmpA, HlyE, sipC, and LPS, multi-antigen signatures discriminated typhoid (n = 100 from other febrile bacteremia (n = 52 in Nepal. These models contained combinatorial IgM, IgA, and IgG responses to 5 antigens (ROC AUC, 0.67 and 0.71 or 3 antigens (0.87, although IgA responses to LPS also performed well (0.88. Using a novel systematic approach we have identified and validated optimal serological diagnostic signatures of typhoid fever.

Using a Human Challenge Model of Infection to Measure Vaccine Efficacy: A Randomised, Controlled Trial Comparing the Typhoid Vaccines M01ZH09 with Placebo and Ty21a.

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Thomas C Darton

2016-08-01

Full Text Available Typhoid persists as a major cause of global morbidity. While several licensed vaccines to prevent typhoid are available, they are of only moderate efficacy and unsuitable for use in children less than two years of age. Development of new efficacious vaccines is complicated by the human host-restriction of Salmonella enterica serovar Typhi (S. Typhi and lack of clear correlates of protection. In this study, we aimed to evaluate the protective efficacy of a single dose of the oral vaccine candidate, M01ZH09, in susceptible volunteers by direct typhoid challenge.We performed a randomised, double-blind, placebo-controlled trial in healthy adult participants at a single centre in Oxford (UK. Participants were allocated to receive one dose of double-blinded M01ZH09 or placebo or 3-doses of open-label Ty21a. Twenty-eight days after vaccination, participants were challenged with 104CFU S. Typhi Quailes strain. The efficacy of M01ZH09 compared with placebo (primary outcome was assessed as the percentage of participants reaching pre-defined endpoints constituting typhoid diagnosis (fever and/or bacteraemia during the 14 days after challenge. Ninety-nine participants were randomised to receive M01ZH09 (n = 33, placebo (n = 33 or 3-doses of Ty21a (n = 33. After challenge, typhoid was diagnosed in 18/31 (58.1% [95% CI 39.1 to 75.5] M01ZH09, 20/30 (66.7% [47.2 to 87.2] placebo, and 13/30 (43.3% [25.5 to 62.6] Ty21a vaccine recipients. Vaccine efficacy (VE for one dose of M01ZH09 was 13% [95% CI -29 to 41] and 35% [-5 to 60] for 3-doses of Ty21a. Retrospective multivariable analyses demonstrated that pre-existing anti-Vi antibody significantly reduced susceptibility to infection after challenge; a 1 log increase in anti-Vi IgG resulting in a 71% decrease in the hazard ratio of typhoid diagnosis ([95% CI 30 to 88%], p = 0.006 during the 14 day challenge period. Limitations to the study included the requirement to limit the challenge period prior to treatment to

Formative investigation of acceptability of typhoid vaccine during a typhoid fever outbreak in Neno District, Malawi.

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Blum, Lauren S; Dentz, Holly; Chingoli, Felix; Chilima, Benson; Warne, Thomas; Lee, Carla; Hyde, Terri; Gindler, Jacqueline; Sejvar, James; Mintz, Eric D

2014-10-01

Typhoid fever affects an estimated 22 million people annually and causes 216,000 deaths worldwide. We conducted an investigation in August and September 2010 to examine the acceptability of typhoid vaccine in Neno District, Malawi where a typhoid outbreak was ongoing. We used qualitative methods, including freelisting exercises, key informant and in-depth interviews, and group discussions. Respondents associated illness with exposure to "bad wind," and transmission was believed to be airborne. Typhoid was considered extremely dangerous because of its rapid spread, the debilitating conditions it produced, the number of related fatalities, and the perception that it was highly contagious. Respondents were skeptical about the effectiveness of water, sanitation, and hygiene (WaSH) interventions. The perceived severity of typhoid and fear of exposure, uncertainty about the effectiveness of WaSH measures, and widespread belief in the efficacy of vaccines in preventing disease resulted in an overwhelming interest in receiving typhoid vaccine during an outbreak. © The American Society of Tropical Medicine and Hygiene.

Typhoid toxin provides a window into typhoid fever and the biology of Salmonella Typhi.

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Galán, Jorge E

2016-06-07

Salmonella Typhi is the cause of typhoid fever, a disease that has challenged humans throughout history and continues to be a major public health concern. Unlike infections with most other Salmonellae, which result in self-limiting gastroenteritis, typhoid fever is a life-threatening systemic disease. Furthermore, in contrast to most Salmonellae, which can infect a broad range of hosts, S. Typhi is a strict human pathogen. The unique features of S. Typhi pathogenesis and its stringent host specificity have been a long-standing puzzle. The discovery of typhoid toxin not only has provided major insight into these questions but also has offered unique opportunities to develop novel therapeutic and prevention strategies to combat typhoid fever.

Impact of a Targeted Typhoid Vaccination Campaign Following Cyclone Tomas, Republic of Fiji, 2010

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Scobie, Heather M.; Nilles, Eric; Kama, Mike; Kool, Jacob L.; Mintz, Eric; Wannemuehler, Kathleen A.; Hyde, Terri B.; Dawainavesi, Akanisi; Singh, Sheetalpreet; Korovou, Samuel; Jenkins, Kylie; Date, Kashmira

2014-01-01

After a category 4 cyclone that caused extensive population displacement and damage to water and sanitation infrastructure in Fiji in March 2010, a typhoid vaccination campaign was conducted as part of the post-disaster response. During June–December 2010, 64,015 doses of typhoid Vi polysaccharide vaccine were administered to persons ≥ 2 years of age, primarily in cyclone-affected areas that were typhoid endemic. Annual typhoid fever incidence decreased during the post-campaign year (2011) relative to preceding years (2008–2009) in three subdivisions where a large proportion of the population was vaccinated (incidence rate ratios and 95% confidence intervals: 0.23, 0.13–0.41; 0.24, 0.14–0.41; 0.58, 0.40–0.86), and increased or remained unchanged in 12 subdivisions where little to no vaccination occurred. Vaccination played a role in reducing typhoid fever incidence in high-incidence areas after a disaster and should be considered in endemic settings, along with comprehensive control measures, as recommended by the World Health Organization. PMID:24710618

Systemic and Terminal Ileum Mucosal Immunity Elicited by Oral Immunization With the Ty21a Typhoid Vaccine in HumansSummary

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Jayaum S. Booth

2017-11-01

Full Text Available Background & Aims: Systemic cellular immunity elicited by the Ty21a oral typhoid vaccine has been extensively characterized. However, very limited data are available in humans regarding mucosal immunity at the site of infection (terminal ileum [TI]. Here we investigated the host immunity elicited by Ty21a immunization on terminal ileum–lamina propria mononuclear cells (LPMC and peripheral blood in volunteers undergoing routine colonoscopy. Methods: We characterized LPMC-T memory (TM subsets and assessed Salmonella enterica serovar Typhi (S Typhi–specific responses by multichromatic flow cytometry. Results: No differences were observed in cell yields and phenotypes in LPMC CD8+-TM subsets following Ty21a immunization. However, Ty21a immunization elicited LPMC CD8+ T cells exhibiting significant S Typhi–specific responses (interferon-γ, tumor necrosis factor-α, interleukin-17A, and/or CD107a in all major TM subsets (T-effector/memory [TEM], T-central/memory, and TEM-CD45RA+, although each TM subset exhibited unique characteristics. We also investigated whether Ty21a immunization elicited S Typhi–specific multifunctional effectors in LPMC CD8+ TEM. We observed that LPMC CD8+ TEM responses were mostly multifunctional, except for those cells exhibiting the characteristics associated with cytotoxic responses. Finally, we compared mucosal with systemic responses and made the important observation that LPMC CD8+ S Typhi–specific responses were unique and distinct from their systemic counterparts. Conclusions: This study provides the first demonstration of S Typhi–specific responses in the human terminal ileum mucosa and provides novel insights into the generation of mucosal immune responses following oral Ty21a immunization. Keywords: Lamina Propria Mononuclear Cells, Multifunctional T Cells, CD8+-T Memory Cells, Typhoid, Vaccines

Antimicrobial resistance problems in typhoid fever

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Saragih, R. H.; Purba, G. C. F.

2018-03-01

Typhoid fever (enteric fever) remains a burden in developing countries and a major health problem in Southern and Southeastern Asia. Salmonella typhi (S. typhi), the causative agent of typhoid fever, is a gram-negative, motile, rod-shaped, facultative anaerobe and solely a human pathogen with no animal reservoir. Infection of S. typhi can cause fever, abdominal pain and many worsenonspecific symptoms, including gastrointestinal symptoms suchas nausea, vomiting, constipation, and diarrhea. Chloramphenicol, ampicillin,and cotrimoxazole were the first-recommended antibiotics in treating typhoid fever. In the last two decades though, these three traditional drugs started to show resistance and developed multidrug resistance (MDR) S. typhi strains. In many parts of the world, the changing modes ofpresentation and the development of MDR have made typhoid fever increasingly difficult to treat.The use of first-line antimicrobials had been recommended to be fluoroquinolone as a replacement. However, this wassoonfollowedbyreportsof isolates ofS. typhi showing resistancetofluoroquinolones as well. These antimicrobial resistance problems in typhoid fever have been an alarming situation ever since and need to be taken seriously or else typhoid fever will no longer be taken care completely by administering antibiotics.

Burden of typhoid fever in Sulaimania, Iraqi Kurdistan.

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Dworkin, Jonathan; Saeed, Rebeen; Mykhan, Hawar; Kanan, Shwan; Farhad, Dlawer; Ali, Kocher Omer; Abdulwahab, Runak Hama Kareem; Palardy, John; Neill, Marguerite A

2014-10-01

Typhoid fever imposes a high disease burden worldwide, but resource limitations mean that the burden of typhoid fever in many countries is poorly understood. The authors conducted a prospective surveillance study at the adult and pediatric teaching hospitals in Sulaimania, Iraqi Kurdistan. All patients presenting with an undifferentiated febrile illness consistent with typhoid were eligible for enrollment. Enrolled patients had blood cultures and Brucella serologies performed. Incidence was calculated with reference to census data. Both typhoid fever and brucellosis were common, and the incidence of typhoid fever was 21 cases/100 000 patient-years. Classic disease symptoms were uncommonly observed. Cost-effective surveillance projects to calculate disease burden of typhoid fever are practical and replicable. Typhoid has successfully adapted to the healthcare environment in Sulaimania. Additional work in the region should focus on antibiotic resistance and other enteric pathogens such as Brucella spp. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Liver function assessment in malaria, typhoid and malaria-typhoid co-infection in Aba, Abia State, Nigeria.

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Enemchukwu, B N; Ibe, C C; Udedi, S C; Iroha, A; Ubaoji, K I; Ogundapo, S S

2014-06-01

Malaria and typhoid fever are among the most endemic diseases in the tropics and are associated with poverty and underdevelopment with significant morbidity and mortality. Both diseases can lead to liver damage if not properly treated. The liver function assessment was therefore conducted on (90) volunteer patients; comprising (30) patients with malaria only, (30) with typhoid only and (30) with malaria-typhoid co-infection randomly selected from Abia State University Teaching Hospital, Aba, Abia State, Nigeria and (20) healthy individuals were used as control. Blood samples collected from these subjects were screened for malaria parasite and Staphylococcus typhi using standard methods. Mean serum levels of ALP (112.55±84.23), AST (31.33±12.80), ALT (23.10±11.84), TB (19.43±5.02), CB (5.91±3.03) and ALP (116.69±48.68), AST (28.33±11.72), ALT (22.8±5.94), TB (19.31±5.84),CB (5.60±2.50) were obtained for those subjects with malaria and typhoid respectively and subjects with malaria-typhoid co-infection recorded the following; ALP (134.33±56.62), AST (33.97±8.43), ALT (24.40±4.37),TB (21.27±2.96),CB (6.58±3.10) while the control subjects had mean serum levels ofALP (71.05±18.18), AST (16.65±7.45), ALT (13.85±6.09), TB (10.05±4.85) and CB (3.00±1.67). These mean values were subjected to a statistical test using students t-test which revealed a significant increase (p<0.05).The results suggest that malaria, typhoid and malaria-typhoid co-infection can elevate ALP, AST, ALT, TB and CB serum levels and can lead to liver damage if not properly treated.

Radiological observation in typhoid fever

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Lim, K Y; Park, H Y; Kim, J D; Rhee, H S [Presbyterian Medical Center, Jeonju (Korea, Republic of)

1985-12-15

Radiographic findings in plain abdominal films, chest PA and liver scanning are considered to be ancillary diagnostic methods for uncomplicated typhoid fever and a valuable method for detection of complication such as intestinal perforation. 189 cases of clinically proven typhoid fever from Mar. 1973 to Feb. 1979 in this Hospital were reviewed and radiographic findings were analyzed carefully. The results are as follows: 1. Most (73.6%) cases were between 20 and 40 years of age. 2. Three of the most common radiographic findings were as follows: 1) Localized paralytic ileus in RLQ or diffuse paralytic ileus (96.3%). 2) Hepatomegaly (56.5%). 3) Splenomegaly (49.7%). 3. In cases of typhoid fever with intestinal perforation there were additional significant findings such as free air under diaphragm (85%), free fluid in peritoneal cavity (90%) and air fluid levels in RLQ (80%). 4. The most frequent chest x-ray finding was elevation of diaphragm (11.1%). 5. 8 cases of complicated typhoid fever which eventually came to operation were diagnosed only by radiographic method.

Radiological observation in typhoid fever

International Nuclear Information System (INIS)

Lim, K. Y.; Park, H. Y.; Kim, J. D.; Rhee, H. S.

1985-01-01

Radiographic findings in plain abdominal films, chest PA and liver scanning are considered to be ancillary diagnostic methods for uncomplicated typhoid fever and a valuable method for detection of complication such as intestinal perforation. 189 cases of clinically proven typhoid fever from Mar. 1973 to Feb. 1979 in this Hospital were reviewed and radiographic findings were analyzed carefully. The results are as follows: 1. Most (73.6%) cases were between 20 and 40 years of age. 2. Three of the most common radiographic findings were as follows: 1) Localized paralytic ileus in RLQ or diffuse paralytic ileus (96.3%). 2) Hepatomegaly (56.5%). 3) Splenomegaly (49.7%). 3. In cases of typhoid fever with intestinal perforation there were additional significant findings such as free air under diaphragm (85%), free fluid in peritoneal cavity (90%) and air fluid levels in RLQ (80%). 4. The most frequent chest x-ray finding was elevation of diaphragm (11.1%). 5. 8 cases of complicated typhoid fever which eventually came to operation were diagnosed only by radiographic method.

Typhoid Fever in South Africa in an Endemic HIV Setting.

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Keddy, Karen H; Sooka, Arvinda; Smith, Anthony M; Musekiwa, Alfred; Tau, Nomsa P; Klugman, Keith P; Angulo, Frederick J

2016-01-01

Typhoid fever remains an important disease in Africa, associated with outbreaks and the emerging multidrug resistant Salmonella enterica serotype Typhi (Salmonella Typhi) haplotype, H58. This study describes the incidence of, and factors associated with mortality due to, typhoid fever in South Africa, where HIV prevalence is high. Nationwide active laboratory-based surveillance for culture-confirmed typhoid fever was undertaken from 2003-2013. At selected institutions, additional clinical data from patients were collected including age, sex, HIV status, disease severity and outcome. HIV prevalence among typhoid fever patients was compared to national HIV seroprevalence estimates. The national reference laboratory tested Salmonella Typhi isolates for antimicrobial susceptibility and haplotype. Unadjusted and adjusted logistic regression analyses were conducted determining factors associated with typhoid fever mortality. We identified 855 typhoid fever cases: annual incidence ranged from 0.11 to 0.39 per 100,000 population. Additional clinical data were available for 369 (46.8%) cases presenting to the selected sites. Among typhoid fever patients with known HIV status, 19.3% (29/150) were HIV-infected. In adult females, HIV prevalence in typhoid fever patients was 43.2% (19/44) versus 15.7% national HIV seroprevalence (P Typhoid fever incidence in South Africa was largely unchanged from 2003-2013. Typhoid fever mortality was associated disease severity. HIV infection may be a contributing factor. Interventions mandate improved health care access, including to HIV management programmes as well as patient education. Further studies are necessary to clarify relationships between HIV infection and typhoid fever in adults.

Vaxchora: A Single-Dose Oral Cholera Vaccine.

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Cabrera, Adriana; Lepage, Jayne E; Sullivan, Karyn M; Seed, Sheila M

2017-07-01

To review trials evaluating the efficacy and safety of Vaxchora, a reformulated, single-dose, oral, lyophilized Vibrio cholerae CVD 103-HgR vaccine for the prevention of travel-related cholera caused by V cholerae serogroup O1. A literature search was conducted using MEDLINE (1946 to January week 3, 2017) and EMBASE (1996 to 2017 week 3). Keywords included oral cholera vaccine, single-dose, Vaxchora, and CVD 103-HgR. Limits included human, clinical trials published in English since 2010. ClinicalTrials.gov was used as a source for unpublished data. Additional data sources were obtained through bibliographic review of selected articles. Studies that addressed the safety and efficacy of Vaxchora, the reformulated, single-dose oral CVD 103-HgR cholera vaccine, were selected for analysis. Approval of Vaxchora, was based on efficacy of the vaccine in human trials demonstrating 90.3% protection among those challenged with V cholerae 10 days after vaccination and in immunogenicity studies with 90% systemic vibriocidal antibody conversion at 6 months after a single-dose of vaccine. Tolerability was acceptable, with the most common adverse effects reported to be fatigue, headache, and abdominal pain. Vaxchora is the only FDA-approved, single-dose oral vaccine for the prevention of cholera caused by V cholerae serogroup O1 in adult travelers from the United States going to cholera-affected areas. Safety and efficacy has not been established in children, immunocompromised persons, and pregnant or breastfeeding women or those living in cholera-endemic areas.

EpiReview: Typhoid fever, NSW, 2005-2011.

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Gunaratnam, Praveena; Tobin, Sean; Seale, Holly; Musto, Jennie

2013-11-01

To examine trends in the incidence of typhoid fever in NSW to inform the development of prevention strategies. Typhoid fever case notification data for the period 2005-2011 were extracted from the NSW Notifiable Conditions Information Management System. Population incidence rates were calculated and analysed by demographic variables. There were 250 case notifications of typhoid fever in NSW from 2005 to 2011, of which 240 are likely to have been acquired overseas. Case notifications remained relatively stable over the review period with the highest rates in Western Sydney Local Health District (10.9 per 100,000 population). Two-thirds (66.4%) of all case notifications are likely to have been acquired in South Asia, and about half of overseas-acquired case notifications were most likely to have been associated with travel to visit friends and relatives. Hospitalisation was required for 79.6% of cases where hospitalisation status was known. Prior typhoid vaccination was reported in 7% of cases in 2010 and 2011 where vaccination status was known. While typhoid fever rates remain low in NSW, case notifications of this preventable infection continue to be reported, particularly in travellers visiting friends and relatives in South Asia. Further research to better understand barriers to the use of preventive measures may be useful in targeting typhoid fever prevention messages in high-risk groups, particularly South Asian communities in NSW.

Vaccination for typhoid fever in sub-Saharan Africa.

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Slayton, Rachel B; Date, Kashmira A; Mintz, Eric D

2013-04-01

Emerging data on the epidemiologic, clinical and microbiologic aspects of typhoid fever in sub-Saharan Africa call for new strategies and new resources to bring the regional epidemic under control. Areas with endemic disease at rates approaching those in south Asia have been identified; large, prolonged and severe outbreaks are occurring more frequently; and resistance to antimicrobial agents, including fluoroquinolones is increasing. Surveillance for typhoid fever is hampered by the lack of laboratory resources for rapid diagnosis, culture confirmation and antimicrobial susceptibility testing. Nonetheless, in 2010, typhoid fever was estimated to cause 725 incident cases and 7 deaths per 100,000 person years in sub-Saharan Africa. Efforts for prevention and outbreak control are challenged by limited access to safe drinking water and sanitation and by a lack of resources to initiate typhoid immunization. A comprehensive approach to typhoid fever prevention including laboratory and epidemiologic capacity building, investments in water, sanitation and hygiene and reconsideration of the role of currently available vaccines could significantly reduce the disease burden. Targeted vaccination using currently available typhoid vaccines should be considered as a short- to intermediate-term risk reduction strategy for high-risk groups across sub-Saharan Africa.

Advancing the management and control of typhoid fever: a review of the historical role of human challenge studies.

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Waddington, Claire S; Darton, Thomas C; Woodward, William E; Angus, Brian; Levine, Myron M; Pollard, Andrew J

2014-05-01

Typhoid infection causes considerable morbidity and mortality worldwide, particularly in settings where lack of clean water and inadequate sanitation facilitate disease spread through faecal-oral transmission. Improved understanding of the pathogenesis, immune control and microbiology of Salmonella Typhi infection can help accelerate the development of improved vaccines and diagnostic tests necessary for disease control. S. Typhi is a human-restricted pathogen; therefore animal models are limited in their relevance to human infection. During the latter half of the 20th century, induced human infection ("challenge") studies with S. Typhi were used effectively to assess quantitatively the human host response to challenge and to measure directly the efficacy of typhoid vaccines in preventing clinical illness. Here, the findings of these historic challenge studies are reviewed, highlighting the pivotal role that challenge studies have had in improving our understanding of the host-pathogen interaction, and illustrating issues relevant to modern typhoid challenge model design. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

Microscopic haematuria: A rare presentation of typhoid fever.

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Nisahan, Balasingam; Thirunavukarasu, Kumanan; Selvaratnam, Gowry

2015-04-01

Typhoid fever can cause a number of renal manifestations heretofore dubbed 'nephrotyphoid'. Haematuria in the absence of renal impairment is extremely rare among typhoid patients. We report a case of an adult who presented with a prolonged febrile illness and microscopic haematuria. Blood culture confirmed the diagnosis of typhoid and the patient was treated successfully with ceftriaxone. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Oral pulsed high-dose dexamethasone for myositis

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van der Meulen, M. F.; Hoogendijk, J. E.; Wokke, J. H.; de Visser, M.

2000-01-01

To study the short-term effect of oral pulsed high-dose dexamethasone for myositis we treated eight newly diagnosed patients with three 28-day cycles of oral dexamethasone. Primary outcome measures were muscle strength, pain, and serum creatine kinase activity. Six patients responded. Side effects

Cluster analysis of typhoid cases in Kota Bharu, Kelantan, Malaysia

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Nazarudin Safian

2008-09-01

Full Text Available Typhoid fever is still a major public health problem globally as well as in Malaysia. This study was done to identify the spatial epidemiology of typhoid fever in the Kota Bharu District of Malaysia as a first step to developing more advanced analysis of the whole country. The main characteristic of the epidemiological pattern that interested us was whether typhoid cases occurred in clusters or whether they were evenly distributed throughout the area. We also wanted to know at what spatial distances they were clustered. All confirmed typhoid cases that were reported to the Kota Bharu District Health Department from the year 2001 to June of 2005 were taken as the samples. From the home address of the cases, the location of the house was traced and a coordinate was taken using handheld GPS devices. Spatial statistical analysis was done to determine the distribution of typhoid cases, whether clustered, random or dispersed. The spatial statistical analysis was done using CrimeStat III software to determine whether typhoid cases occur in clusters, and later on to determine at what distances it clustered. From 736 cases involved in the study there was significant clustering for cases occurring in the years 2001, 2002, 2003 and 2005. There was no significant clustering in year 2004. Typhoid clustering also occurred strongly for distances up to 6 km. This study shows that typhoid cases occur in clusters, and this method could be applicable to describe spatial epidemiology for a specific area. (Med J Indones 2008; 17: 175-82Keywords: typhoid, clustering, spatial epidemiology, GIS

Typhoid Fever in nineteenth-century Colombia: between medical geography and bacteriology.

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García, Mónica

2014-01-01

This paper analyses how the Colombian medical elites made sense of typhoid fever before and during the inception of bacteriological ideas and practices in the second half of the nineteenth century. Assuming that the identity of typhoid fever has to be understood within the broader concerns of the medical community in question, I show how doctors first identified Bogotá's epidemics as typhoid fever during the 1850s, and how they also attached specificity to the fever amongst other continuous fevers, such as its European and North American counterparts. I also found that, in contrast with the discussions amongst their colleagues from other countries, debates about typhoid fever in 1860-70 among doctors in Colombia were framed within the medico-geographical scheme and strongly shaped by the fear of typhoid fever appearing alongside 'paludic' fevers in the highlands. By arguing in medico-geographical and clinical terms that typhoid fever had specificity in Colombia, and by denying the medico-geographical law of antagonism between typhoid and paludic fevers proposed by the Frenchman Charles Boudin, Colombian doctors managed to question European knowledge and claimed that typhoid fever had distinct features in Colombia. The focus on paludic and typhoid fevers in the highlands might explain why the bacteriological aetiology of typhoid fever was ignored and even contested during the 1880s. Anti-Pasteurian arguments were raised against its germ identity and some physicians even supported the idea of spontaneous origin of the disease. By the 1890s, Pasteurian knowledge had come to shape clinical and hygienic practices.

Same species, different diseases: how and why typhoidal and non-typhoidal Salmonella enterica serovars differ

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Ohad eGal-Mor

2014-08-01

Full Text Available Human infections by the bacterial pathogen Salmonella enterica represent major disease burdens worldwide. This highly ubiquitous species consists of more than 2600 different serovars that can be divided into typhoidal and non-typhoidal Salmonella (NTS serovars. Despite their genetic similarity, these two groups elicit very different diseases and distinct immune responses in humans. Comparative analyses of the genomes of multiple Salmonella serovars have begun to explain the basis of the variation in disease manifestations. Recent advances in modeling both enteric fever and intestinal gastroenteritis in mice will facilitate investigation into both the bacterial- and host-mediated mechanisms involved in salmonelloses. Understanding the genetic and molecular mechanisms responsible for differences in disease outcome will augment our understanding of Salmonella pathogenesis, host immunity, and the molecular basis of host specificity. This review outlines the differences in epidemiology, clinical manifestations, and the human immune response to typhoidal and NTS infections and summarizes the current thinking on why these differences might exist.

Clinical Features Of Malaria And Typhoid Fever | Mba | Journal of ...

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Features to distinguish Malaria from Typhoid fever. These can be discerned from a good and detailed clinical history, in addition to a thorough physical examination. The following would help. The paroxysms of malaria fever as against the step ladder pattern fever of typhoid fever. The prominence of headaches in typhoid ...

Modifiable risk factors for typhoid intestinal perforations during a large outbreak of typhoid fever, Kampala Uganda, 2015.

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Bulage, Lilian; Masiira, Ben; Ario, Alex R; Matovu, Joseph K B; Nsubuga, Peter; Kaharuza, Frank; Nankabirwa, Victoria; Routh, Janell; Zhu, Bao-Ping

2017-09-25

Between January and June, 2015, a large typhoid fever outbreak occurred in Kampala, Uganda, with 10,230 suspected cases. During the outbreak, area surgeons reported a surge in cases of typhoid intestinal perforation (TIP), a complication of typhoid fever. We conducted an investigation to characterize TIP cases and identify modifiable risk factors for TIP. We defined a TIP case as a physician-diagnosed typhoid patient with non-traumatic terminal ileum perforation. We identified cases by reviewing medical records at all five major hospitals in Kampala from 2013 to 2015. In a matched case-control study, we compared potential risk factors among TIP cases and controls; controls were typhoid patients diagnosed by TUBEX TF, culture, or physician but without TIP, identified from the outbreak line-list and matched to cases by age, sex and residence. Cases and controls were interviewed using a standard questionnaire from 1st -23rd December 2015. We used conditional logistic regression to assess risk factors for TIP and control for confounding. Of the 88 TIP cases identified during 2013-2015, 77% (68/88) occurred between January and June, 2015; TIPs sharply increased in January and peaked in March, coincident with the typhoid outbreak. The estimated risk of TIP was 6.6 per 1000 suspected typhoid infections (68/10,230). The case-fatality rate was 10% (7/68). Cases sought care later than controls; Compared with 29% (13/45) of TIP cases and 63% (86/137) of controls who sought treatment within 3 days of onset, 42% (19/45) of cases and 32% (44/137) of controls sought treatment 4-9 days after illness onset (OR adj  = 2.2, 95%CI = 0.83-5.8), while 29% (13/45) of cases and 5.1% (7/137) of controls sought treatment ≥10 days after onset (OR adj  = 11, 95%CI = 1.9-61). 68% (96/141) of cases and 23% (23/100) of controls had got treatment before being treated at the treatment centre (OR adj  = 9.0, 95%CI = 1.1-78). Delay in seeking treatment increased the risk of TIPs

Gallbladder perforation complicating typhoid fever: report of two cases.

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Gali, B M; Ali, N; Agbese, G O; Duna, V D; Dawha, S D; Ismai, G I; Mohammed, M

2011-01-01

Gallbladder perforation (GBP) is rare and as a complication of typhoid fever is extremely rare. We present two consecutive patients with GBP diagnosed incidentally at laparotomy. Information on the management of two patients with gallbladder perforation seen at Federal Medical Centre Azare in June and October 2008 was extracted from their case records. The two patients were both males aged 13 years and 16 years. They both presented with high fever of more than 2 weeks duration; and abdominal pain and distension. Both patients had features of generalised peritonitis. Pre-operative diagnoses of typhoid enteric perforation were made based on a positive Widal test. Intra-operative findings however, were that of bile peritonitis and gallbladder perforation. Both had cholecystectomy. Culture of the bile aspirate yielded Salmonella typhi. Gallbladder perforation secondary to typhoid fever should be considered as a differential diagnosis in patients with suspected typhoid enteric perforation in typhoid fever endemic region.

Oral desensitization to milk: how to choose the starting dose!

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Mori, Francesca; Pucci, Neri; Rossi, Maria Elisabetta; de Martino, Maurizio; Azzari, Chiara; Novembre, Elio

2010-01-01

Mori F, Pucci N, Rossi ME, de Martino M, Azzari C, Novembre E. Oral desensitization to milk: how to choose the starting dose! Pediatr Allergy Immunol 2010: 21: e450–e453. © 2009 John Wiley & Sons A/S A renewed interest in oral desensitization as treatment for food allergy has been observed in the last few years. We studied a novel method based on the end point skin prick test procedure to establish the starting dose for oral desensitization in a group of 30 children higly allergic to milk. The results (in terms of reactions to the first dose administered) were compared with a group of 20 children allergic to milk as well. Such control group started to swallow the same dose of 0.015 mg/ml of milk. None reacted to the first dose when administered according to the end point skin prick test. On the other side, ten out of 20 children (50%) from the control group showed mild allergic reactions to the first dose of milk. In conclusion the end point skin prick test procedure results safe and easy to be performed in each single child in order to find out the starting dose for oral desensitization to milk, also by taking into account the individual variability. PMID:19624618

A Case Report of Typhoidal Acute Acalculous Cholecystitis

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Neeha Rajan

2014-01-01

Full Text Available Introduction. Acalculous cholecystitis in the setting of typhoid fever in adults is an infrequent clinical encounter, reported sparsely in the literature. In this case report we review the presentation and management of enteric fever involving the biliary system and consider the literature surrounding this topic. The aim of this case report is to alert clinicians to the potential diagnosis of extraintestinal complications in the setting of typhoid fever in the returned traveller, requiring surgical intervention. Presentation of Case. We report the case of a 23-year-old woman with acalculous cholecystitis secondary to Salmonella Typhi. Discussion. There is scarce evidence surrounding the optimal treatment and prognosis of typhoidal acalculous cholecystitis. In the current case, surgical invention was favoured due to failure of medical management. Conclusion. Clinical judgement dictated surgical intervention in this case of typhoidal acute acalculous cholecystitis, and cholecystectomy was safely performed.

Pulmonary affectation in a patient with typhoid fever

International Nuclear Information System (INIS)

Duenas C, Carmelo; Martinez, Adel; Maza, Augusto

1997-01-01

Typhoid fever is a rare disease in the USA with no more of 500 cases per year. In Latin America, it occurs four to five times more frequently. Pulmonary symptoms are found in less than 20% of the cases. The development of pneumonia is more common in immunocompromised patients. In last 10 years, the frequency of typhoid pneumonia has increased because of the HIV epidemic and the advance of other forms of immunosuppression. We presented the case of a young adult male with typhoid multilobar pneumonia who did not have VIH infection or any demonstrated immunosuppression

Reproducible diagnostic metabolites in plasma from typhoid fever patients in Asia and Africa.

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Näsström, Elin; Parry, Christopher M; Vu Thieu, Nga Tran; Maude, Rapeephan R; de Jong, Hanna K; Fukushima, Masako; Rzhepishevska, Olena; Marks, Florian; Panzner, Ursula; Im, Justin; Jeon, Hyonjin; Park, Seeun; Chaudhury, Zabeen; Ghose, Aniruddha; Samad, Rasheda; Van, Tan Trinh; Johansson, Anders; Dondorp, Arjen M; Thwaites, Guy E; Faiz, Abul; Antti, Henrik; Baker, Stephen

2017-05-09

Salmonella Typhi is the causative agent of typhoid. Typhoid is diagnosed by blood culture, a method that lacks sensitivity, portability and speed. We have previously shown that specific metabolomic profiles can be detected in the blood of typhoid patients from Nepal (Näsström et al., 2014). Here, we performed mass spectrometry on plasma from Bangladeshi and Senegalese patients with culture confirmed typhoid fever, clinically suspected typhoid, and other febrile diseases including malaria. After applying supervised pattern recognition modelling, we could significantly distinguish metabolite profiles in plasma from the culture confirmed typhoid patients. After comparing the direction of change and degree of multivariate significance, we identified 24 metabolites that were consistently up- or down regulated in a further Bangladeshi/Senegalese validation cohort, and the Nepali cohort from our previous work. We have identified and validated a metabolite panel that can distinguish typhoid from other febrile diseases, providing a new approach for typhoid diagnostics.

Epidemiological analysis of typhoid fever in Kelantan from a retrieved registry

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Ismail, A.

2013-01-01

Full Text Available Aim: Despite the endemicity of typhoid in Kelantan, epidemiological data showing typhoid association to age, sex,ethnicity and district of patients is limited. This retrospective study investigated the statistical association of thesevariables from a retrieved registry.Methodology and results: Cross-tabulation using SPSS was used to analyze 1394 cases of confirmed typhoid patientsadmitted to various hospitals in Kelantan state over a six-year period. Fourteen age groups with a five-year rangeinterval were generated. There was a significant association between typhoid infection and sex of subjects, wherebyfemales were generally more susceptible than males. Ethnicity and district of typhoid patients did not show significantassociation.Conclusion, significance and impact of study: The observation of an increased number of typhoid cases with a malepredominance in the age group 5-14 and female predominance in the 20-60 age group calls for improved hygiene,continued public health education, together with better laboratory diagnostics to identify carriers, are some measures tocontrol this disease.

The emergence and outbreak of multidrug-resistant typhoid fever in China.

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Yan, Meiying; Li, Xinlan; Liao, Qiaohong; Li, Fang; Zhang, Jing; Kan, Biao

2016-06-22

Typhoid fever remains a severe public health problem in developing countries. The emergence of resistant typhoid, particularly multidrug-resistant typhoid infections, highlights the necessity of monitoring the resistance characteristics of this invasive pathogen. In this study, we report a typhoid fever outbreak caused by multidrug-resistant Salmonella enterica serovar Typhi strains with an ACSSxtT pattern. Resistance genes conferring these phenotypes were harbored by a large conjugative plasmid, which increases the threat of Salmonella Typhi and thus requires close surveillance for dissemination of strains containing such genes.

Salmonella enterica serovar Typhimurium lacking hfq gene confers protective immunity against murine typhoid.

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Uday Shankar Allam

Full Text Available Salmonella enterica is an important enteric pathogen and its various serovars are involved in causing both systemic and intestinal diseases in humans and domestic animals. The emergence of multidrug-resistant strains of Salmonella leading to increased morbidity and mortality has further complicated its management. Live attenuated vaccines have been proven superior over killed or subunit vaccines due to their ability to induce protective immunity. Of the various strategies used for the generation of live attenuated vaccine strains, focus has gradually shifted towards manipulation of virulence regulator genes. Hfq is a RNA chaperon which mediates the binding of small RNAs to the mRNA and assists in post-transcriptional gene regulation in bacteria. In this study, we evaluated the efficacy of the Salmonella Typhimurium Δhfq strain as a candidate for live oral vaccine in murine model of typhoid fever. Salmonella hfq deletion mutant is highly attenuated in cell culture and animal model implying a significant role of Hfq in bacterial virulence. Oral immunization with the Salmonella hfq deletion mutant efficiently protects mice against subsequent oral challenge with virulent strain of Salmonella Typhimurium. Moreover, protection was induced upon both multiple as well as single dose of immunizations. The vaccine strain appears to be safe for use in pregnant mice and the protection is mediated by the increase in the number of CD4(+ T lymphocytes upon vaccination. The levels of serum IgG and secretory-IgA in intestinal washes specific to lipopolysaccharide and outer membrane protein were significantly increased upon vaccination. Furthermore, hfq deletion mutant showed enhanced antigen presentation by dendritic cells compared to the wild type strain. Taken together, the studies in murine immunization model suggest that the Salmonella hfq deletion mutant can be a novel live oral vaccine candidate.

Typhoid outbreak investigation in Dzivaresekwa, suburb of Harare

African Journals Online (AJOL)

abp

2014-08-18

Aug 18, 2014 ... Abstract. Introduction: Typhoid fever is a systemic infection caused by a Gram negative bacterium, Salmonella typhi. Harare City reported 1078 cases of suspected typhoid fever cases from October 2011 to January 2012. We initiated an investigation to identify possible source of transmission so as to.

Biomagnetic Pair Therapy and Typhoid Fever: A Pilot Study.

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Frank, Bryan L

2017-10-01

Objective: This pilot study examined the laboratory responses of patients with laboratory-documented typhoid fever who were treated with Biomagnetic Pair Therapy (BPT; medical biomagnetism), a specific application of pairs of magnets for various ailments that are infectious and otherwise. Materials and Methods: This study was an assessment of patients' response to treatment with only BPT for Salmonella typhi infections (typhoid fever) using standard conventional laboratory techniques. The research was conducted in an outpatient village clinic in Kenya. There were 52 participants who were evaluated for possible systemic illness, including typhoid fever, from an open-label study. Participants who felt sick and requested testing for possible typhoid fever were tested with a standard Widal test by a certified laboratory technician. Participants who tested positive (13 patients) were then treated with BPT (a "First Aid" approach) only. These participants then returned for follow-up laboratory and clinical evaluations after 2 days. Results: Most of the participants (10 of 13) retested as negative, and all patients reported symptomatic clinical improvement. Conclusions: As a significant majority of participants demonstrated clearing of their S. typhi after BPT, this technique should be studied further in larger trials for its efficacy in treating typhoid fever.

Unusual complication of toxic megacolon in typhoid colitis.

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Arun Babu, Thirunavukkarasu; Ananthakrishnan, Shanthi; Jayakumar, P; Kullu, Poonam

2014-05-01

Colitis is a rare manifestation of enteric fever in children. Toxic megacolon complicating typhoid colitis is even rarer and requires early recognition and aggressive management due to the high mortality associated with this condition. The authors report a rare case of Toxic megacolon secondary to typhoid colitis in a seven-year-old girl.

Non-Typhoidal Salmonella Aortitis in a transplant patient

International Nuclear Information System (INIS)

Tarif, N.; Azam, M.N.; Mitwalli, Ahmad H.; Al-Wakeel, Jamal S.; El-Kheder, A. Al-Aboud

2002-01-01

Non-typhoidal salmonella bacteremia may result in extra gastrointestinallocalization of infection. Aortitis due to non-typhoidal salmonella wasreported to be the cause of 38-42% of all infected abdominal aortitis.Underlying atherosclerosis is a frequent site for salmonella aortitis. Wedescribe here a case of possible salmonella aortitis in a renal transplantpatient. (author)

A rabbit model of non-typhoidal Salmonella bacteremia.

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Panda, Aruna; Tatarov, Ivan; Masek, Billie Jo; Hardick, Justin; Crusan, Annabelle; Wakefield, Teresa; Carroll, Karen; Yang, Samuel; Hsieh, Yu-Hsiang; Lipsky, Michael M; McLeod, Charles G; Levine, Myron M; Rothman, Richard E; Gaydos, Charlotte A; DeTolla, Louis J

2014-09-01

Bacteremia is an important cause of morbidity and mortality in humans. In this study, we focused on the development of an animal model of bacteremia induced by non-typhoidal Salmonella. New Zealand White rabbits were inoculated with a human isolate of non-typhoidal Salmonella strain CVD J73 via the intra-peritoneal route. Blood samples were collected at specific time points and at euthanasia from infected rabbits. Additionally, tissue samples from the heart, lungs, spleen, gastrointestinal tract, liver and kidneys were obtained at euthanasia. All experimentally infected rabbits displayed clinical signs of disease (fever, dehydration, weight loss and lethargy). Tissues collected at necropsy from the animals exhibited histopathological changes indicative of bacteremia. Non-typhoidal Salmonella bacteria were detected in the blood and tissue samples of infected rabbits by microbiological culture and real-time PCR assays. The development of this animal model of bacteremia could prove to be a useful tool for studying how non-typhoidal Salmonella infections disseminate and spread in humans. Copyright © 2014 Elsevier Ltd. All rights reserved.

Typhoid fever : aspects of environment, host and pathogen interaction

NARCIS (Netherlands)

Ali, Soegianto

2006-01-01

In a surveillance study in Jakarta, Indonesia, 88 typhoid and 26 paratyphoid fever patients were identified by blood culture. Risk factors for transmission of typhoid fever were mainly intra-household factors (poor hand-washing hygiene, recent household contacts), whereas paratyphoid was mainly

Typhoid fever: case report and literature review.

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Sanhueza Palma, Natalia Carolina; Farías Molina, Solange; Calzadilla Riveras, Jeannette; Hermoso, Amalia

2016-06-21

Typhoid fever remains a major health problem worldwide, in contrast to Chile, where this disease is an isolated finding. Clinical presentation is varied, mainly presenting with fever, malaise, abdominal discomfort, and nonspecific symptoms often confused with other causes of febrile syndrome. We report a six-year-old, male patient presenting with fever of two weeks associated with gastrointestinal symptoms, malaise, hepatomegaly and elevated liver enzymes. Differential diagnoses were considered and a Widal reaction and two blood cultures were requested; both came back positive, confirming the diagnosis of typhoid fever caused by Salmonella typhi. Prior to diagnosis confirmation, empirical treatment was initiated with ceftriaxone and metronidazole, with partial response; then drug therapy was adjusted according to ciprofloxacin susceptibility testing with a favorable clinical response. We discuss diagnostic methods and treatment of enteric fever with special emphasis on typhoid fever.

Continuous low-dose oral chemotherapy in recurrent and persistent carcinoma of cervix following chemoradiation: A comparative study between prolonged oral cyclophosphamide and oral etoposide

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Upasana Baruah

2014-01-01

Full Text Available Aim: To compare the efficacy and toxicities of low-dose oral cyclophosphamide and oral etoposide in patients with persistent and recurrent cervical cancer with gross pelvic disease following full course of chemoradiation therapy. Materials and Methods: 30 patients with recurrent and persistent cervical cancer with gross pelvic disease were enrolled in this trial. The patients were randomly divided into two groups of 15 patients each with one group receiving low dose oral cyclophosphamide (100 mg/day and the other group receiving low-dose oral etoposide (50 mg/day. Results were statistically analysed by IBM SPSS Statistics 19. Results: Oral etoposide was not well tolerated with grade 2 neutropenia occurring in 33.3% and grade 3 neutropenia in 6.6% and thrombocytopenia occurring in 13.3%. Oral cyclophosphamide group on the other hand was better tolerated with none of the patients having thrombocytopenia and 6.6% patients having grade 2 neutropenia. There were two complete response (15.38% and one partial response at the end of study (7.6% in the cyclophosphamide group whereas there was no complete response and two partial response (16.6% in the oral etoposide group. Conclusion: Long-term, low-dose oral etoposide was found to be less tolerated without any significant effect with patients with persistent and recurrent cervical cancer with gross pelvic disease following full course of chemoradiation therapy in contrast to oral cyclophosphamide which was found to be effective and well-tolerated by the patients.

Clinical and Haematological Manifestations of Typhoid Fever in Children in Eastern Turkey.

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Akbayram, S; Parlak, M; Dogan, M; Karasin, G; Akbayram, H T; Karaman, K

2016-01-12

Typhoid fever can involve various organs, leading to a wide range of presentations: from uncomplicated to complicated typhoid fever. The haematological changes are common in typhoid fever and include anaemia, leucopaenia, thrombocytopaenia and bleeding diathesis. This study was undertaken in order to determine the clinical and haematological presentation of typhoid fever in children. In this study, records of children and adolescents with typhoid fever aged under or equal to 16 years, admitted to Yuzuncu Yil University Hospital between 2010 and 2014, were analysed retrospectively. The cases (56%) were admitted to our hospital in July and October. Major symptoms of patients were abdominal pain (24%), arthralgia (21%) and fever (11%). In our study, decreased mean platelet volume (31%), eosinopaenia 20%), abnormal platelet count (19%), anaemia (16%), leucocytosis (16%) and eosinophilia (12%) were the most common haematological findings in the children. Typhoid fever is predominant in children at school age with a slight male predominance. Decreased mean platelet volume and abdominal pain might be useful as early diagnostic clues.

Typhoid fever in a South African in-patient population

NARCIS (Netherlands)

Khan, Mohammad Enayet Hossain

2004-01-01

In conclusion, the data presented herein show that no single clinical or paraclinical parameter is reliable in arriving at a correct clinical diagnosis of typhoid fever and that bacteriologic confirmation is necessary for the diagnosis of typhoid fever. Patients ’ age and sex influence the clinical

Pharmacokinetics of Escalating Doses of Oral Psilocybin in Healthy Adults.

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Brown, Randall T; Nicholas, Christopher R; Cozzi, Nicholas V; Gassman, Michele C; Cooper, Karen M; Muller, Daniel; Thomas, Chantelle D; Hetzel, Scott J; Henriquez, Kelsey M; Ribaudo, Alexandra S; Hutson, Paul R

2017-12-01

Psilocybin is a psychedelic tryptamine that has shown promise in recent clinical trials for the treatment of depression and substance use disorders. This open-label study of the pharmacokinetics of psilocybin was performed to describe the pharmacokinetics and safety profile of psilocybin in sequential, escalating oral doses of 0.3, 0.45, and 0.6 mg/kg in 12 healthy adults. Eligible healthy adults received 6-8 h of preparatory counseling in anticipation of the first dose of psilocybin. The escalating oral psilocybin doses were administered at approximately monthly intervals in a controlled setting and subjects were monitored for 24 h. Blood and urine samples were collected over 24 h and assayed by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for psilocybin and psilocin, the active metabolite. The pharmacokinetics of psilocin were determined using both compartmental (NONMEM) and noncompartmental (WinNonlin) methods. No psilocybin was found in plasma or urine, and renal clearance of intact psilocin accounted for less than 2% of the total clearance. The pharmacokinetics of psilocin were linear within the twofold range of doses, and the elimination half-life of psilocin was 3 h (standard deviation 1.1). An extended elimination phase in some subjects suggests hydrolysis of the psilocin glucuronide metabolite. Variation in psilocin clearance was not predicted by body weight, and no serious adverse events occurred in the subjects studied. The small amount of psilocin renally excreted suggests that no dose reduction is needed for subjects with mild-moderate renal impairment. Simulation of fixed doses using the pharmacokinetic parameters suggest that an oral dose of 25 mg should approximate the drug exposure of a 0.3 mg/kg oral dose of psilocybin. Although doses of 0.6 mg/kg are in excess of likely therapeutic doses, no serious physical or psychological events occurred during or within 30 days of any dose. NCT02163707.

Early detection of typhoid by polymerase chain reaction

International Nuclear Information System (INIS)

Haque, A.; Qureshi, Javed A.; Ahmed, J.

1999-01-01

Typhoid is a common problem in developing countries. Cultivation ofbacteria and serology (especially Widal test) gives unacceptable levels offalse-negative and false-positive results respectively. In this study, arecently introduced polymerase chain reaction based technique (which has 100%specificity for Salmonella typhi) was compared with blood culture and Widaltest during the first week of illness of 82 suspected cases of typhoid. Therespective figures of positivity for PCR, blood culture and Widal test were71.95%, 34.1% and 36.5%. A control group of 20 healthy persons gave figuresof 0%, 0% and 33.3%, respectively. We conclude that this PCR-based techniqueis not only absolutely specific, but also very sensitive and therefore muchsuperior to blood culture and, Widal test for the early diagnosis of typhoid.(author)

Pan-oral dose assessment: a comparative report of methodologies

International Nuclear Information System (INIS)

Shafford, J.; Pryor, M.; Hollaway, P.; Peet, D.; Oduko, J.

2015-01-01

National guidance from the Institute of Physics and Engineering in Medicine (IPEM Report 91) currently recommends that the patient dose for a pan-oral X-ray unit is measured as dose area product (DAP) replacing dose width product described in earlier guidance. An investigation identifying different methods available to carry out this measurement has been undertaken and errors in the methodologies analysed. It has been shown that there may be up to a 30 % variation in DAP measurement between methods. This paper recommends that where possible a DAP meter is used to measure the dose-area product from a pan-oral X-ray unit to give a direct DAP measurement. However, by using a solid-state dose measurement and film/ruler to calculate DAP the authors have established a conversion factor of 1.4. It is strongly recommended that wherever a DAP value is quoted the methodology used to obtain that value is also reported. (authors)

Fecal-orally transmitted diseases among travelers are decreasing due to better hygienic standards at travel destination.

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Baaten, Gijs G; Sonder, Gerard J B; Van Der Loeff, Maarten F Schim; Coutinho, Roel A; Van Den Hoek, Anneke

2010-01-01

To evaluate whether changes in attack rates of fecal-orally transmitted diseases among travelers are related to changes in pretravel vaccination practices or better hygienic standards at travel destination. National surveillance data on all laboratory-confirmed cases of travel-related hepatitis A, shigellosis, and typhoid fever diagnosed in the Netherlands from 1995 to 2006 were matched with the number of Dutch travelers to developing countries to calculate region-specific annual attack rates. Trends in attack rates of non-vaccine-preventable shigellosis were compared with those of vaccine-preventable hepatitis A and typhoid fever. Trends were also compared with three markers for hygienic standards of the local population at travel destinations, drawn from the United Nations Development Programme database: the human development index, the sanitation index, and the water source index. Attack rates among Dutch travelers to developing regions declined for hepatitis A, shigellosis, and typhoid fever. Region-specific trends in attack rates of shigellosis resembled trends of hepatitis A and typhoid fever. Declining attack rates of the three fecal-orally transmitted diseases correlated with improvements in socioeconomic, sanitary, and water supply conditions of the local population at travel destination. These findings suggest that improved hygienic standards at travel destination strongly contributed to the overall decline in attack rates of fecal-orally transmitted diseases among visiting travelers. © 2010 International Society of Travel Medicine.

[Individualization of low-dose oral contraceptives. Pharmacological principles and practical indications for oral contraceptives].

Science.gov (United States)

Cianci, A; De Leo, V

2007-08-01

The contraceptive pill has been a revolution of the last 40 years. In Italy, however, it is much less widely used than in other countries. Explanations for this phenomenon range from religious implications and customs to misinformation and word-of-mouth communication of negative experiences. The oral contraceptive pill is often used to correct menstrual disorders, leading to poor results and side-effects. Recent advances in oral contraception have led to a substantial reduction in doses and side-effects. Low-dose pills contain minimal doses of progesterones and estrogens and ensure good control of the menstrual cycle. Although reduction of ethinyl estradiol (EE) concentrations has reduced the incidence of negative systemic side effects such as water retention, edema and swollen breasts, the low estrogen dose may be associated with spotting and hypomenorrhea or amenorrhea in the long term, as well as dyspareunia due to reduced vaginal trophism, which may induce women to suspend use of the drug. It is also true that only one type of estrogen is used in the pill, albeit at different doses, whereas the progesterone may differ and in many cases is the cause of common side-effects. The choice of progesterone therefore involves not only its effect on the endometrium in synergy with estrogen, but also possible residual androgenic activity which may have negative metabolic repercussions. Indeed, addition of a progesterone, especially androgen-derived, attenuates the positive metabolic effects of estrogen. Two new monophasic oral contraceptives were recently released. They contain 30 microg (Yasmin) or 20 muicrog (Yasminelle) EE and a new progesterone, drospirenone, derived from spirolactone, which has antiandrogenic and antimineralcorticoid activity similar to endogenous progesterone. Like progesterone, the drospirenone molecule is an aldosterone antagonist and has a natriuretic effect that opposes the sodium retention effect of EE. It may, therefore, help to prevent the

Risk Factors of Typhoid Infection in the Indonesian Archipelago.

Directory of Open Access Journals (Sweden)

Sandra Alba

Full Text Available Knowledge of risk factors and their relative importance in different settings is essential to develop effective health education material for the prevention of typhoid. In this study, we examine the effect of household level and individual behavioural risk factors on the risk of typhoid in three Indonesian islands (Sulawesi, Kalimantan and Papua in the Eastern Indonesian archipelago encompassing rural, peri-urban and urban areas.We enrolled 933 patients above 10 years of age in a health facility-based case-control study between June 2010 and June 2011. Individuals suspected of typhoid were tested using the typhoid IgM lateral flow assay for the serodiagnosis of typhoid fever followed by blood culture testing. Cases and controls were defined post-recruitment: cases were individuals with a culture or serology positive result (n = 449; controls were individuals negative to both serology and culture, with or without a diagnosis other than typhoid (n = 484. Logistic regression was used to examine the effect of household level and individual level behavioural risk factors and we calculated the population attributable fraction (PAF of removing each risk significant independent behavioural risk factor.Washing hands at critical moments of the day and washing hands with soap were strong independent protective factors for typhoid (OR = 0.38 95% CI 0.25 to 0.58 for each unit increase in hand washing frequency score with values between 0 = Never and 3 = Always; OR = 3.16 95% CI = 2.09 to 4.79 comparing washing hands with soap sometimes/never vs. often. These effects were independent of levels of access to water and sanitation. Up to two thirds of cases could be prevented by compliance to these practices (hand washing PAF = 66.8 95% CI 61.4 to 71.5; use of soap PAF = 61.9 95%CI 56.7 to 66.5. Eating food out in food stalls or restaurant was an important risk factor (OR = 6.9 95%CI 4.41 to 10.8 for every unit increase in frequency score.Major gains could

New approach for food allergy management using low-dose oral food challenges and low-dose oral immunotherapies.

Science.gov (United States)

Yanagida, Noriyuki; Okada, Yu; Sato, Sakura; Ebisawa, Motohiro

2016-04-01

A number of studies have suggested that a large subset of children (approximately 70%) who react to unheated milk or egg can tolerate extensively heated forms of these foods. A diet that includes baked milk or egg is well tolerated and appears to accelerate the development of regular milk or egg tolerance when compared with strict avoidance. However, the indications for an oral food challenge (OFC) using baked products are limited for patients with high specific IgE values or large skin prick test diameters. Oral immunotherapies (OITs) are becoming increasingly popular for the management of food allergies. However, the reported efficacy of OIT is not satisfactory, given the high frequency of symptoms and requirement for long-term therapy. With food allergies, removing the need to eliminate a food that could be consumed in low doses could significantly improve quality of life. This review discusses the importance of an OFC and OIT that use low doses of causative foods as the target volumes. Utilizing an OFC or OIT with a low dose as the target volume could be a novel approach for accelerating the tolerance to causative foods. Copyright © 2015 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

Brachytherapy for early oral tongue cancer. Low dose rate to high dose rate

International Nuclear Information System (INIS)

Yamazaki, Hideya; Inoue, Takehiro; Yoshida, Ken; Yoshioka, Yasuo; Shimizutani, Kimishige; Inoue, Toshihiko; Furukawa, Souhei; Kakimoto, Naoya

2003-01-01

To examine the compatibility of low dose rate (LDR) with high dose rate (HDR) brachytherapy, we reviewed 399 patients with early oral tongue cancer (T1-2N0M0) treated solely by brachytherapy at Osaka University Hospital between 1967 and 1999. For patients in the LDR group (n=341), the treatment sources consisted of Ir-192 pin for 227 patients (1973-1996; irradiated dose, 61-85 Gy; median, 70 Gy), Ra-226 needle for 113 patients (1967-1986; 55-93 Gy; median, 70 Gy). Ra-226 and Ir-192 were combined for one patient. Ir-192 HDR (microSelectron-HDR) was used for 58 patients in the HDR group (1991-present; 48-60 Gy; median, 60 Gy). LDR implantations were performed via oral and HDR via a submental/submandibular approach. The dose rates at the reference point for the LDR group were 0.30 to 0.8 Gy/h, and for the HDR group 1.0 to 3.4 Gy/min. The patients in the HDR group received a total dose of 48-60 Gy (8-10 fractions) during one week. Two fractions were administered per day (at least a 6-h interval). The 3- and 5-year local control rates for patients in the LDR group were 85% and 80%, respectively, and those in the HDR group were both 84%. HDR brachytherapy showed the same lymph-node control rate as did LDR brachytherapy (67% at 5 years). HDR brachytherapy achieved the same locoregional result as did LDR brachytherapy. A converting factor of 0.86 is applicable for HDR in the treatment of early oral tongue cancer. (author)

Pharmacokinetics of sulfamethoxazole and trimethoprim in Pacific white shrimp, Litopenaeus vannamei, after oral administration of single-dose and multiple-dose.

Science.gov (United States)

Ma, Rongrong; Wang, Yuan; Zou, Xiong; Hu, Kun; Sun, Beibei; Fang, Wenhong; Fu, Guihong; Yang, Xianle

2017-06-01

The tissue distribution and depletion of sulfamethoxazole (SMZ) and trimethoprim (TMP) were studied in Pacific white shrimp, Litopenaeus vannamei, after single-dose and multiple-dose oral administration of SMZ-TMP (5:1) via medicated feed. In single-dose oral administration, shrimps were fed once at a dose of 100 mg/kg (drug weight/body weight). In multiple-dose oral administration, shrimps were fed three times a day for three consecutive days at a dose of 100mg/kg. The results showed the kinetic characteristic of SMZ was different from TMP in Pacific white shrimp. In the single-dose administration, the SMZ was widely distributed in the tissues, while TMP was highly concentrated in the hepatopancreas. The t 1/2z values of SMZ were larger and persist longer than TMP in Pacific white shrimp. In the multiple-dose administration, SMZ accumulated well in the tissues, and reached steady state level after successive administrations, while TMP did not. TMP concentration even appeared the downward trend with the increase of drug times. Compared with the single dose, the t 1/2z values of SMZ in hepatopancreas (8.22-11.33h) and muscle (6.53-10.92h) of Pacific white shrimps rose, but the haemolymph dropped (13.76-11.03) in the multiple-dose oral administration. Meanwhile, the corresponding values of TMP also rose in hepatopancreas (4.53-9.65h) and muscle (2.12-2.71h), and declined in haemolymph (7.38-5.25h) following single-dose and multiple-dose oral administration in Pacific white shrimps. In addition, it is worth mentioning that the ratios of SMZ and TMP were unusually larger than the general aim ratio. Copyright © 2017 Elsevier B.V. All rights reserved.

Reproducible diagnostic metabolites in plasma from typhoid fever patients in Asia and Africa

NARCIS (Netherlands)

Näsström, Elin; Parry, Christopher M.; Vu Thieu, Nga Tran; Maude, Rapeephan R.; de Jong, Hanna K.; Fukushima, Masako; Rzhepishevska, Olena; Marks, Florian; Panzner, Ursula; Im, Justin; Jeon, Hyonjin; Park, Seeun; Chaudhury, Zabeen; Ghose, Aniruddha; Samad, Rasheda; van, Tan Trinh; Johansson, Anders; Dondorp, Arjen M.; Thwaites, Guy E.; Faiz, Abul; Antti, Henrik; Baker, Stephen

2017-01-01

Salmonella Typhi is the causative agent of typhoid. Typhoid is diagnosed by blood culture, a method that lacks sensitivity, portability and speed. We have previously shown that specific metabolomic profiles can be detected in the blood of typhoid patients from Nepal (Näsström et al., 2014). Here, we

Risk factors for typhoid and paratyphoid fever in Jakarta, Indonesia.

NARCIS (Netherlands)

Vollaard, A.M.; Ali, S.; Asten, H.A.G.H. van; Widjaja, S.; Visser, L.G.; Surjadi, C.; Dissel, J.T. van

2004-01-01

CONTEXT: The proportion of paratyphoid fever cases to typhoid fever cases may change due to urbanization and increased dependency on food purchased from street vendors. For containment of paratyphoid a different strategy may be needed than for typhoid, because risk factors for disease may not

SODIUM BICARBONATE FACILITATES LOW-DOSE ORAL TOLERANCE TO PEANUT IN MICE

Science.gov (United States)

Rationale: Oral tolerance specifically inhibits production of allergic IgE antibody and is therefore a potential method for suppressing food allergy. We have previously demonstrated that a single oral dose of one mg is sufficient to induce oral tolerance to egg white but not pean...

Interferon-driven alterations of the host's amino acid metabolism in the pathogenesis of typhoid fever.

Science.gov (United States)

Blohmke, Christoph J; Darton, Thomas C; Jones, Claire; Suarez, Nicolas M; Waddington, Claire S; Angus, Brian; Zhou, Liqing; Hill, Jennifer; Clare, Simon; Kane, Leanne; Mukhopadhyay, Subhankar; Schreiber, Fernanda; Duque-Correa, Maria A; Wright, James C; Roumeliotis, Theodoros I; Yu, Lu; Choudhary, Jyoti S; Mejias, Asuncion; Ramilo, Octavio; Shanyinde, Milensu; Sztein, Marcelo B; Kingsley, Robert A; Lockhart, Stephen; Levine, Myron M; Lynn, David J; Dougan, Gordon; Pollard, Andrew J

2016-05-30

Enteric fever, caused by Salmonella enterica serovar Typhi, is an important public health problem in resource-limited settings and, despite decades of research, human responses to the infection are poorly understood. In 41 healthy adults experimentally infected with wild-type S. Typhi, we detected significant cytokine responses within 12 h of bacterial ingestion. These early responses did not correlate with subsequent clinical disease outcomes and likely indicate initial host-pathogen interactions in the gut mucosa. In participants developing enteric fever after oral infection, marked transcriptional and cytokine responses during acute disease reflected dominant type I/II interferon signatures, which were significantly associated with bacteremia. Using a murine and macrophage infection model, we validated the pivotal role of this response in the expression of proteins of the host tryptophan metabolism during Salmonella infection. Corresponding alterations in tryptophan catabolites with immunomodulatory properties in serum of participants with typhoid fever confirmed the activity of this pathway, and implicate a central role of host tryptophan metabolism in the pathogenesis of typhoid fever. © 2016 Blohmke et al.

Should close contacts of returning travellers with typhoid fever be protected by vaccination?

Science.gov (United States)

Kantele, A

2015-03-17

Increasing international travel to areas endemic for typhoid fever correlates with increased risk for travellers to contract the disease. At home, the acutely ill/convalescent patients may pose some risk to their close contacts. In Finland an unofficial guideline suggests vaccination for close contacts of patients with acute typhoid fever; in other developed countries, routine typhoid vaccinations are only recommended to contacts of chronic carriers. This paper discusses the possibilities and limitations of prophylactic/post-exposure typhoid vaccination for contacts of patients with acute disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

Typhoid Fever Presenting With Acute Renal Failure And Hepatitis Simultaneously - A Rare Presentation

Directory of Open Access Journals (Sweden)

Rajput R.

2016-05-01

Full Text Available Typhoid fever is an important health problem worldwide but its incidence is more in developing countries. Hepatic involvement is common, but both hepatic and renal involvement is rare in typhoid fever. We report a case of typhoid fever presenting with hepatitis and acute renal failure. A 17 year old male presenting with fever and pain abdomen was found to have raised blood urea, creatinine, liver enzymes and bilirubin. Widal and typhidot (IgM,IgG test were positive. His symptoms subsided and deranged parameters resolved with treatment of typhoid fever.

Limitations of typhoid fever diagnostics and the need for prevention

NARCIS (Netherlands)

Smits, Henk L.

2013-01-01

Evaluation of: Siba V, Horwood PF, Vanuga K et al. Evaluation of serological diagnostic tests for typhoid fever in Papua New Guinea using a composite reference standard. Clin. Vaccine Immunol. 19(11), 1833-1837 (2012). The study under review evaluated serological tests for typhoid fever against PCR

Typhoid ileal perforation: a 13-year experience

Directory of Open Access Journals (Sweden)

Poras Chaudhary

2015-07-01

Full Text Available Typhoid fever is endemic in many developing countries with a high rate of complications. Aim of this study is to analyse epidemiological features, clinical presentations, complications and therapeutic outcomes of enteric perforation peritonitis diagnosed and treated in our hospital. Records of total number of 646 patients, who presented with perforation peritonitis due to enteric fever in the surgical emergency unit of Dr Ram Manohar Lohia hospital, New Delhi between January 2001 and December 2013, were reviewed retrospectively. Descriptive statistics was used to analyze the data. Out of 646 patients, 62 (9.59% presented in shock. Stomal, peristomal, local and systemic complications were high in these patients. Primary closure was done in 212 (33.12 patients, primary ileostomy was created in 410 (64.06 patients, and resection and anastomosis was done in 24 (3.75 patients. Thirteen patients (2.01% died of typhoid intestinal perforation. To prevent complications of typhoid fever, in addition to control sanitation, it is also important to control quackery and malpractices. Awareness and education about the disease, its nature and complications will also be of great help.

The Molecular and Spatial Epidemiology of Typhoid Fever in Rural Cambodia.

Science.gov (United States)

Pham Thanh, Duy; Thompson, Corinne N; Rabaa, Maia A; Sona, Soeng; Sopheary, Sun; Kumar, Varun; Moore, Catrin; Tran Vu Thieu, Nga; Wijedoru, Lalith; Holt, Kathryn E; Wong, Vanessa; Pickard, Derek; Thwaites, Guy E; Day, Nicholas; Dougan, Gordon; Turner, Paul; Parry, Christopher M; Baker, Stephen

2016-06-01

Typhoid fever, caused by the bacterium Salmonella Typhi, is an endemic cause of febrile disease in Cambodia. The aim of this study was to better understand the epidemiology of pediatric typhoid fever in Cambodia. We accessed routine blood culture data from Angkor Hospital for Children (AHC) in Siem Reap province between 2007 and 2014, and performed whole genome sequencing (WGS) on the isolated bacteria to characterize the S. Typhi population. The resulting phylogenetic information was combined with conventional epidemiological approaches to investigate the spatiotemporal distribution of S. Typhi and population-level risk factors for reported disease. During the study period, there were 262 cases of typhoid within a 100 km radius of AHC, with a median patient age of 8.2 years (IQR: 5.1-11.5 years). The majority of infections occurred during the rainy season, and commune incidences as high as 11.36/1,000 in children aged typhoid fever in rural communes in Cambodia. Our data provide a platform for additional population-based typhoid fever studies in this location, and suggest that this would be a suitable setting in which to introduce a school-based vaccination programme with Vi conjugate vaccines.

Antibody response to the lipopolysaccharide and protein antigens of Salmonella typhi during typhoid infection

International Nuclear Information System (INIS)

Tsang, R.S.W.; Chau, P.Y.; Lam, S.K.

1981-01-01

Serum antibody responses to the lipopolysaccharide and protein antigens of S. typhi in typhoid patients were studied using a solid-phase radioimmunoassay technique with 125 I labelled anti-immunoglobulin antibody. Sera from 24 adult typhoid patients and 20 non-typhoid adult controls were compared. As a group, sera from typhoid patients showed increased IgA, IgG and IgM immunoglobulin levels and gave significantly higher anti-LPS and anti-protein antibody titres in all three major immunoglobulin classes than did non-typhoid controls. Levels of antibodies against LPS or protein in sera of typhoid patients were highly variable with a skew distribution. A good correlation was found between antibody titres to the LPS antigen and those to a protein antigen. No correlation, however, was found between the anti-LPS antibody titres measured by radioimmunoassay and the anti-O antibody titres measured by the Widal agglutination test. Titration of anti-LPS or anti-protein antibodies by radioimmunoassay was found to be more sensitive and specific than Widal test for the serological diagnosis of typhoid fever. The advantages of measuring antibody response by radioimmunoassay over conventional Widal test are discussed. (author)

Multifocal choroiditis following simultaneous hepatitis A, typhoid, and yellow fever vaccination

Directory of Open Access Journals (Sweden)

Escott S

2013-02-01

Full Text Available Sarah Escott, Ahmad B Tarabishy, Frederick H DavidorfHavener Eye Institute, The Ohio State University, Columbus, OH, USAAbstract: The paper describes the first reported case of multifocal choroiditis following simultaneous hepatitis-A, typhoid, and yellow fever vaccinations. A 33-year-old male developed sudden onset of flashing lights and floaters in his right eye 3 weeks following hepatitis A, typhoid, and yellow fever vaccinations. Fundus examination and angiography confirmed the presence of multiple peripheral chorioretinal lesions. These lesions demonstrated characteristic morphologic changes over a period of 8 weeks which were consistent with a diagnosis of self-resolving multifocal choroiditis. Vaccine-induced intraocular inflammation has been described infrequently. We demonstrate the first case of self-resolving multifocal choroiditis following simultaneous administration of hepatitis A, yellow fever, and typhoid immunizations.Keywords: multifocal choroiditis, vaccination, hepatitis A, typhoid, yellow fever

Poor food hygiene and housing as risk factors for typhoid fever in Semarang, Indonesia.

NARCIS (Netherlands)

Gasem, M.H.; Dolmans, W.M.V.; Keuter, M.; Djokomoeljanto, R.J.

2001-01-01

To identify risk factors for typhoid fever in Semarang city and its surroundings, 75 culture-proven typhoid fever patients discharged 2 weeks earlier from hospital and 75 controls were studied. Control subjects were neighbours of cases with no history of typhoid fever, not family members, randomly

Comparative Evaluation of Tubex TF (Inhibition Magnetic Binding Immunoassay) for Typhoid Fever in Endemic Area.

Science.gov (United States)

Khanna, Ashish; Khanna, Menka; Gill, Karamjit Singh

2015-11-01

Typhoid fever remains a significant health problem in endemic countries like India. Various serological tests for the diagnosis of typhoid fever are available commercially. We assessed the usefulness of rapid test based on magnetic particle separation to detect Immunoglobulin against Salmonella typhi O9 lipopolysaccharide. Aim of this study was to compare the sensitivity and specificity of widal test, typhidot and tubex TF test for the diagnosis of typhoid fever in an endemic country like India. Serum samples collected from 50 patients of typhoid fever, 50 patients of non typhoid fever and 100 normal healthy individuals residing in Amritsar were subjected to widal test, typhidot test and tubex TF test as per manufacturer's instructions. Data collected was assessed to find sensitivity and specificity of these tests in an endemic area. Significant widal test results were found positive in 68% of patients of typhoid fever and only 4% of non typhoid fever patients. Typhidot (IgM or IgG) was positive in 72% of typhoid fever patients and 10% and 6% in non typhoid fever and normal healthy individuals respectively. Tubex TF showed higher sensitivity of 76% and specificity of 96-99% which was higher than typhidot and comparable to widal test. This was the first evaluation of rapid tubex TF test in northern India. In countries which can afford high cost of test, tubex TF should be recommended for the diagnosis in acute stage of the disease in clinical setting. However, there is urgent need for a highly specific and sensitive test for the diagnosis of typhoid fever in clinical settings in endemic areas.

The burden of typhoid fever in low- and middle-income countries: A meta-regression approach.

Science.gov (United States)

Antillón, Marina; Warren, Joshua L; Crawford, Forrest W; Weinberger, Daniel M; Kürüm, Esra; Pak, Gi Deok; Marks, Florian; Pitzer, Virginia E

2017-02-01

Upcoming vaccination efforts against typhoid fever require an assessment of the baseline burden of disease in countries at risk. There are no typhoid incidence data from most low- and middle-income countries (LMICs), so model-based estimates offer insights for decision-makers in the absence of readily available data. We developed a mixed-effects model fit to data from 32 population-based studies of typhoid incidence in 22 locations in 14 countries. We tested the contribution of economic and environmental indices for predicting typhoid incidence using a stochastic search variable selection algorithm. We performed out-of-sample validation to assess the predictive performance of the model. We estimated that 17.8 million cases of typhoid fever occur each year in LMICs (95% credible interval: 6.9-48.4 million). Central Africa was predicted to experience the highest incidence of typhoid, followed by select countries in Central, South, and Southeast Asia. Incidence typically peaked in the 2-4 year old age group. Models incorporating widely available economic and environmental indicators were found to describe incidence better than null models. Recent estimates of typhoid burden may under-estimate the number of cases and magnitude of uncertainty in typhoid incidence. Our analysis permits prediction of overall as well as age-specific incidence of typhoid fever in LMICs, and incorporates uncertainty around the model structure and estimates of the predictors. Future studies are needed to further validate and refine model predictions and better understand year-to-year variation in cases.

Interferon-driven alterations of the host’s amino acid metabolism in the pathogenesis of typhoid fever

Science.gov (United States)

Jones, Claire; Waddington, Claire S.; Zhou, Liqing; Hill, Jennifer; Clare, Simon; Mukhopadhyay, Subhankar; Schreiber, Fernanda; Roumeliotis, Theodoros I.; Yu, Lu; Ramilo, Octavio; Sztein, Marcelo B.; Kingsley, Robert A.; Levine, Myron M.

2016-01-01

Enteric fever, caused by Salmonella enterica serovar Typhi, is an important public health problem in resource-limited settings and, despite decades of research, human responses to the infection are poorly understood. In 41 healthy adults experimentally infected with wild-type S. Typhi, we detected significant cytokine responses within 12 h of bacterial ingestion. These early responses did not correlate with subsequent clinical disease outcomes and likely indicate initial host–pathogen interactions in the gut mucosa. In participants developing enteric fever after oral infection, marked transcriptional and cytokine responses during acute disease reflected dominant type I/II interferon signatures, which were significantly associated with bacteremia. Using a murine and macrophage infection model, we validated the pivotal role of this response in the expression of proteins of the host tryptophan metabolism during Salmonella infection. Corresponding alterations in tryptophan catabolites with immunomodulatory properties in serum of participants with typhoid fever confirmed the activity of this pathway, and implicate a central role of host tryptophan metabolism in the pathogenesis of typhoid fever. PMID:27217537

Current antimicrobial sensitivity pattern of typhoidal salmonellae in a referral diagnostic centre

Directory of Open Access Journals (Sweden)

Umer Shujat

2016-03-01

Full Text Available Background: Infections caused by typhoidal salmonellae are an important public health concern in Pakistan. Inappropriate and injudicious use of fluoroquinolones has reduced their efficacy due to development of high level resistance. Aim: To ascertain the current susceptibility pattern of typhoidal salmonellae thus guiding the physicians for better management of typhoid patients.Materials and Methods: A study was conducted at our institution from January 2012 through December 2013 to investigate current susceptibility pattern of typhoidal salmonellae. Results: Out of 200 isolates, 107 (53.5% were identified as Salmonella Typhi and 93 (46.5% as Salmonella Paratyphi A. Sensitivities of Salmonella Typhi were as follows: ampicillin (48.6%, chloramphenicol (45.8%, co-trimoxazole (40.1%, ciprofloxacin (11.2%. Sensitivities of Salmonella Paratyphi A were: ampicillin (80.6%, chloramphenicol (89.2%, co-trimoxazole (90.3%, and ciprofloxacin (16.1%. No resistance was detected against third generation cephalosporins. Conclusions: Typhoidal salmonellae are still entirely susceptible to third generation cephalosporins in our setting. Marked rise in resistance to fluoroquinolones has reduced their empirical usage. Sensitivity of Salmonella Paratyphi A to conventional antityphoid drugs was encouraging.

Localised transmission hotspots of a typhoid fever outbreak in the ...

African Journals Online (AJOL)

Introduction: in a semi-urban setting in the Democratic Republic of Congo, this study aims to understand the dynamic of a typhoid fever (TF) outbreak and to assess: a) the existence of hot spots for TF transmission and b) the difference between typhoid cases identified within those hot spots and the general population in ...

Intraocular levels of methotrexate after oral low-dose treatment in chronic uveitis.

Science.gov (United States)

Puchta, Joachim; Hattenbach, Lars-Olof; Baatz, Holger

2005-01-01

To determine the intraocular levels of methotrexate in low-dose treatment of noninfectious uveitis. One day after oral administration, the methotrexate level was measured in the aqueous humor and serum of a patient with noninfectious uveitis, who underwent cataract surgery. A fluorescence polarization immunoassay was used for determination. After oral administration, methotrexate was only measurable in aqueous humor but not in serum. In uveitis, orally administered low-dose methotrexate reaches detectable levels in aqueous humor, even in the absence of detectable levels in serum. Copyright (c) 2005 S. Karger AG, Basel.

[Report of Relapse Typhoid Fever Cases from Kolkata, India: Recrudescence or Reinfection?

Science.gov (United States)

Samajpati, Sriparna; Das, Surojit; Ray, Ujjwayini; Dutta, Shanta

2018-05-24

Three relapse cases were reported out of 107 hospital-attending typhoid cases within a period of 2 years (2014-2016) from Apollo Gleneagles Hospital, Kolkata, India. During the first episode of typhoid fever, 2 of the 3 cases were treated with ceftriaxone (CRO) for 7 days, and 1 was treated for 14 days. Six Salmonella Typhi (S. Typhi) isolates, obtained from the 3 patients during both typhoid episodes, were subjected to antimicrobial susceptibility testing, detection of quinolone resistance-determining region (QRDR) mutation and molecular subtyping by pulsed-field gel electrophoresis (PFGE), multiple-locus variable number tandem repeat analysis (MLVA), multilocus sequence typing (MLST), clustered regularly interspaced short palindromic repeats (CRISPR), and H58 haplotyping. Pairs of the S. Typhi strains isolated from two of the patients during the 1st and 2nd episodes were similar with respect to the antimicrobial resistance (AMR) profiles, QRDR mutations, and molecular subtypes; whereas, the S. Typhi strain pair isolated from the 3rd patient were different in their AMR profiles, QRDR mutations, and MLVA profiles. From these observations, it may be concluded that in spite of treating typhoid cases with CRO for 7-14 days, relapse of typhoid fever might occur. The article also showed the advantage of MLVA typing over PFGE, MLST, and CRISPR typing for the discrimination of strains isolated from the same patient in case of relapse of typhoid fever.

Overlapping epidemiologies of hepatitis A and typhoid fever: the needs of the traveler.

Science.gov (United States)

Luxemburger, Christine; Dutta, Anil K

2005-04-01

Hepatitis A and typhoid fever are endemic infectious diseases in many parts of the world. They share a common, simple mode of transmission--the fecal--oral route-associated with poor hygiene. The low endemicity of both diseases in developed countries, and the rise in travel to exotic destinations for business and leisure, mean that increasing numbers of travelers are being exposed to infection. Effective, established vaccines are available against both diseases, and recently new formulations combining both vaccines in one injection have been licensed. We review the present epidemiologic situation for both diseases, to determine the necessity to routinely vaccinate travelers against both diseases.

The death of Alexander the Great: malaria or typhoid fever?

Science.gov (United States)

Cunha, Burke A

2004-03-01

Alexander the Great had a profound effect on world history. His conquests covered the entire known world at the time, and he was responsible for the spread of Greek culture throughout the ancient world. In Babylon in 323 BC, Alexander died when he was nearly 33 years old. Possible explanations for his death have included alcoholic liver disease and strychnine poisoning, but little data support either condition as the cause of his death. Alexander most likely died from malaria or typhoid fever, which were rampant in ancient Babylon. The description of his final illness from the royal diaries is consistent with typhoid fever or malaria but is most characteristic of typhoid fever.

Latex agglutination test (LAT) for the diagnosis of typhoid fever.

Science.gov (United States)

Sahni, Gopal Shankar

2013-06-01

The efficacy of latex agglutination test in the rapid diagnosis of typhoid fever was studied and the result compared with that of blood culture. This study included 80 children suffering from typhoid fever, among which 40 were confirmed by blood culture isolation and 40 had possible typhoid fever based on high Widal's titre (a four-fold rise in the titre of antibody to typhi "O" and "H" antigen was considered as a positive Widal's test result). Eighty children, 40 with febrile illness confirmed to be other than typhoid and 40 normal healthy children were used as negative controls. The various groups were: (i) Study group ie, group I had 40 children confirmed by culture isolation of Salmonella typhi(confirmed typhoid cases). (ii) Control groups ie, (a) group II with 40 febrile controls selected from paediatrics ward where cause other than S typhi has been established, (b) group III with 40 afebrile healthy controls that were siblings of the children admitted in paediatric ward for any reason with no history of fever and TAB vaccination in the last one year, and (c) group IV with 40 children with high Widal's titre in paired sera sample. Widal's test with paired sera with a one week interval between collections were done in all 40 patients. Latex aggtutination test which could detect 900 ng/ml of antigen as observed in checker board titration, was positive in all 40 children from group I who had positive blood culture and in 30 children from group IV who had culture negative and had high Widal's titre positive. Latex agglutination test was positive in 4 children in group II and none in group III. Using blood culture positive cases as true positive and children in groups II and III as true negative, the test had a sensitivity of 100% and specificity of 96%. Latex agglutination test was found to be significantly sensitive (100%) and specific (96%) and could detect 75% more cases in group IV (possible typhoid cases). Thus latex agglutination test can be used for rapid

High dose rate brachytherapy for oral cancer.

Science.gov (United States)

Yamazaki, Hideya; Yoshida, Ken; Yoshioka, Yasuo; Shimizutani, Kimishige; Furukawa, Souhei; Koizumi, Masahiko; Ogawa, Kazuhiko

2013-01-01

Brachytherapy results in better dose distribution compared with other treatments because of steep dose reduction in the surrounding normal tissues. Excellent local control rates and acceptable side effects have been demonstrated with brachytherapy as a sole treatment modality, a postoperative method, and a method of reirradiation. Low-dose-rate (LDR) brachytherapy has been employed worldwide for its superior outcome. With the advent of technology, high-dose-rate (HDR) brachytherapy has enabled health care providers to avoid radiation exposure. This therapy has been used for treating many types of cancer such as gynecological cancer, breast cancer, and prostate cancer. However, LDR and pulsed-dose-rate interstitial brachytherapies have been mainstays for head and neck cancer. HDR brachytherapy has not become widely used in the radiotherapy community for treating head and neck cancer because of lack of experience and biological concerns. On the other hand, because HDR brachytherapy is less time-consuming, treatment can occasionally be administered on an outpatient basis. For the convenience and safety of patients and medical staff, HDR brachytherapy should be explored. To enhance the role of this therapy in treatment of head and neck lesions, we have reviewed its outcomes with oral cancer, including Phase I/II to Phase III studies, evaluating this technique in terms of safety and efficacy. In particular, our studies have shown that superficial tumors can be treated using a non-invasive mold technique on an outpatient basis without adverse reactions. The next generation of image-guided brachytherapy using HDR has been discussed. In conclusion, although concrete evidence is yet to be produced with a sophisticated study in a reproducible manner, HDR brachytherapy remains an important option for treatment of oral cancer.

Diarrhea associated with typhoid fever

NARCIS (Netherlands)

Roy, S. K.; Speelman, P.; Butler, T.; Nath, S.; Rahman, H.; Stoll, B. J.

1985-01-01

To study the pathogenesis of diarrhea occurring with typhoid fever, we selected 42 patients with diarrhea and blood cultures positive for Salmonella typhi or Salmonella paratyphi A, but without diarrheal copathogens, for measurement of stool output and examination of fecal composition. The mean

Salmonella Typhi-specific multifunctional CD8+ T cells play a dominant role in protection from typhoid fever in humans.

Science.gov (United States)

Fresnay, Stephanie; McArthur, Monica A; Magder, Laurence; Darton, Thomas C; Jones, Claire; Waddington, Claire S; Blohmke, Christoph J; Angus, Brian; Levine, Myron M; Pollard, Andrew J; Sztein, Marcelo B

2016-03-01

Typhoid fever, caused by the human-restricted organism Salmonella Typhi (S. Typhi), is a major public health problem worldwide. Development of novel vaccines remains imperative, but is hampered by an incomplete understanding of the immune responses that correlate with protection. Recently, a controlled human infection model was re-established in which volunteers received ~10(3) cfu wild-type S. Typhi (Quailes strain) orally. Twenty-one volunteers were evaluated for their cell-mediated immune (CMI) responses. Ex vivo PBMC isolated before and up to 1 year after challenge were exposed to three S. Typhi-infected targets, i.e., autologous B lymphoblastoid cell-lines (B-LCL), autologous blasts and HLA-E restricted AEH B-LCL cells. CMI responses were evaluated using 14-color multiparametric flow cytometry to detect simultaneously five intracellular cytokines/chemokines (i.e., IL-17A, IL-2, IFN-g, TNF-a and MIP-1b) and a marker of degranulation/cytotoxic activity (CD107a). Herein we provide the first evidence that S. Typhi-specific CD8+ responses correlate with clinical outcome in humans challenged with wild-type S. Typhi. Higher multifunctional S. Typhi-specific CD8+ baseline responses were associated with protection against typhoid and delayed disease onset. Moreover, following challenge, development of typhoid fever was accompanied by decreases in circulating S. Typhi-specific CD8+ T effector/memory (TEM) with gut homing potential, suggesting migration to the site(s) of infection. In contrast, protection against disease was associated with low or no changes in circulating S. Typhi-specific TEM. These studies provide novel insights into the protective immune responses against typhoid disease that will aid in selection and development of new vaccine candidates.

Widal agglutination titre: a rapid serological diagnosis of typhoid fever in developing countries

International Nuclear Information System (INIS)

Aftab, R.; Khurshid, R.

2009-01-01

To study the reliability of a single Widal test and to find out the diagnostic significance of 'O' and 'H' agglutinin titre in the diagnosis of typhoid fever. Community-based case-control study conducted from Jan 2001 to June 2007. The blood samples were collected from the medical and out door department of Sir Ganga Ram Hospitals, Lahore. The diagnostic value of an acute phase single Widal agglutination test for suspected typhoid fever was evaluated in 733 consecutive patients with fever lasting 6 or more days. In 733 patients with fever 84 (11.45%) were positive for Widal test. A noteworthy rise 1/320 of H and/or O agglutinin titre was observed in 86 (11.3%) of patients with typhoid fever. In the absence of vaccination an elevated level of H and/or O agglutinin titre of 1: 320 is of diagnostic value for typhoid fever especially in our setting where a single sample of serum is relied on for the diagnosis of typhoid fever. (author)

Widal agglutination titre: a rapid serological diagnosis of typhoid fever in developing countries

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Aftab, R [Fatima Jinnah Medical College Lahore, Lahore (Pakistan). Dept. of Pathology; Khurshid, R [Fatima Jinnah Medical College Lahore, Lahore (Pakistan). Dept. of Biochemistry

2009-01-15

To study the reliability of a single Widal test and to find out the diagnostic significance of 'O' and 'H' agglutinin titre in the diagnosis of typhoid fever. Community-based case-control study conducted from Jan 2001 to June 2007. The blood samples were collected from the medical and out door department of Sir Ganga Ram Hospitals, Lahore. The diagnostic value of an acute phase single Widal agglutination test for suspected typhoid fever was evaluated in 733 consecutive patients with fever lasting 6 or more days. In 733 patients with fever 84 (11.45%) were positive for Widal test. A noteworthy rise 1/320 of H and/or O agglutinin titre was observed in 86 (11.3%) of patients with typhoid fever. In the absence of vaccination an elevated level of H and/or O agglutinin titre of 1: 320 is of diagnostic value for typhoid fever especially in our setting where a single sample of serum is relied on for the diagnosis of typhoid fever. (author)

Comparison of the sensitivity of typhi dot test with blood culture in typhoid

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Rizvi, Q [Hamdard College of Medicine, Karachi (Pakistan). Dept. of Pharmacology

2006-10-15

To evaluate the sensitivity of Typhi Dot test in comparison to Blood Culture for the diagnosis of Typhoid Fever in our setup. Fifty patients who fulfilled the clinical criteria of having Typhoid Fever. The data of all the patients was documented, and they were submitted to the Typhi Dot and Blood Culture tests, apart from other routine investigations. Out of the total 50 patients, 47(94%) had their Blood Culture positive for Typhoid bacillus, while in 49 (98%) the Typhi Dot test was positive. Two patients which were found positive on Typhi dot test, gave negative results on Blood Culture. One patient with the signs and symptoms of Typhoid Fever was found neither positive on Typhi Dot test nor upon Blood Culture. There was no significant difference between the results of Blood Culture and Typhi Dot test in the diagnosis of Typhoid Fever. However, Typhi Dot has the advantages of being less expensive and quicker in giving results with excellent sensitivity. (author)

Comparison of the sensitivity of typhi dot test with blood culture in typhoid

International Nuclear Information System (INIS)

Rizvi, Q.

2006-01-01

To evaluate the sensitivity of Typhi Dot test in comparison to Blood Culture for the diagnosis of Typhoid Fever in our setup. Fifty patients who fulfilled the clinical criteria of having Typhoid Fever. The data of all the patients was documented, and they were submitted to the Typhi Dot and Blood Culture tests, apart from other routine investigations. Out of the total 50 patients, 47(94%) had their Blood Culture positive for Typhoid bacillus, while in 49 (98%) the Typhi Dot test was positive. Two patients which were found positive on Typhi dot test, gave negative results on Blood Culture. One patient with the signs and symptoms of Typhoid Fever was found neither positive on Typhi Dot test nor upon Blood Culture. There was no significant difference between the results of Blood Culture and Typhi Dot test in the diagnosis of Typhoid Fever. However, Typhi Dot has the advantages of being less expensive and quicker in giving results with excellent sensitivity. (author)

The burden of typhoid fever in low- and middle-income countries: A meta-regression approach.

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Marina Antillón

2017-02-01

Full Text Available Upcoming vaccination efforts against typhoid fever require an assessment of the baseline burden of disease in countries at risk. There are no typhoid incidence data from most low- and middle-income countries (LMICs, so model-based estimates offer insights for decision-makers in the absence of readily available data.We developed a mixed-effects model fit to data from 32 population-based studies of typhoid incidence in 22 locations in 14 countries. We tested the contribution of economic and environmental indices for predicting typhoid incidence using a stochastic search variable selection algorithm. We performed out-of-sample validation to assess the predictive performance of the model.We estimated that 17.8 million cases of typhoid fever occur each year in LMICs (95% credible interval: 6.9-48.4 million. Central Africa was predicted to experience the highest incidence of typhoid, followed by select countries in Central, South, and Southeast Asia. Incidence typically peaked in the 2-4 year old age group. Models incorporating widely available economic and environmental indicators were found to describe incidence better than null models.Recent estimates of typhoid burden may under-estimate the number of cases and magnitude of uncertainty in typhoid incidence. Our analysis permits prediction of overall as well as age-specific incidence of typhoid fever in LMICs, and incorporates uncertainty around the model structure and estimates of the predictors. Future studies are needed to further validate and refine model predictions and better understand year-to-year variation in cases.

Split high-dose oral levothyroxine treatment as a successful therapy option in myxedema coma.

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Charoensri, Suranut; Sriphrapradang, Chutintorn; Nimitphong, Hataikarn

2017-10-01

High-dose intravenous thyroxine (T4) is the preferable treatment for myxedema coma. We describe the clinical course of a 69-year-old man who presented with myxedema coma and received oral levothyroxine (LT4) therapy (1 mg) in a split dose. This suggests split high-dose oral LT4 as a therapeutic option in myxedema coma.

Induction of oral tolerance with micro-doses of ovomucoid depends on the length of the feeding period

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Kjær, Tanja; Frøkiær, Hanne

2002-01-01

Oral administration of antigen induces antigen-specific immunologic tolerance, which is known to be dose-dependent. We studied the influence of continuous oral administration of nanogram and microgram doses of antigen on oral tolerance induction. Mice were continuously exposed to varying doses (1...

Typhoid Fever and Acute Appendicitis: A Rare Association Not Yet Fully Formed

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Daniel J. Sartori

2017-08-01

Full Text Available Infections caused by foodborne enteric pathogens including typhoidal and non-typhoidal Salmonella species can mimic symptoms of acute appendicitis. The association between such bacterial pathogens and pathology-proven acute appendicitis has been described, but this link is poorly understood. Here we describe a case of a young man with typhoid fever presenting with histology-proven acute appendicitis requiring urgent appendectomy, and provide a brief review of relevant literature to prompt more widespread recognition of this rare cause of a common surgical emergency.

Factors Associated with Non-typhoidal Salmonella Bacteremia versus Typhoidal Salmonella Bacteremia in Patients Presenting for Care in an Urban Diarrheal Disease Hospital in Bangladesh.

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K M Shahunja

Full Text Available Non-typhoidal Salmonella (NTS and Salmonella enterica serovar Typhi bacteremia are the causes of significant morbidity and mortality worldwide. There is a paucity of data regarding NTS bacteremia in South Asia, a region with a high incidence of typhoidal bacteremia. We sought to determine clinical predictors and outcomes associated with NTS bacteremia compared with typhoidal bacteremia.We performed a retrospective age-matched case-control study of patients admitted to the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh, between February 2009 and March 2013. We compared demographic, clinical, microbiological, and outcome variables of NTS bacteremic patients with age-matched S. Typhi bacteremic patients, and a separate comparison of patients with NTS bacteremia and patients with NTS gastroenteritis.Of 20 patients with NTS bacteremia, 5 died (25% case fatality, compared to none of 60 age-matched cases of S. Typhi bacteremia. In univariate analysis, we found that compared with S. Typhi bacteremia, cases of NTS bacteremia had more severe acute malnutrition (SAM in children under five years of age, less often presented with a duration of fever ≥ 5 days, and were more likely to have co-morbidities on admission such as pneumonia and clinical signs of sepsis (p<0.05 in all cases. In multivariable logistic regression, SAM, clinical sepsis, and pneumonia were independent risk factors for NTS bacteremia compared with S. Typhi bacteremia (p<0.05 in all cases. Notably, we found marked differences in antibiotic susceptibilities, including NTS strains resistant to antibiotics commonly used for empiric therapy of patients suspected to have typhoid fever.Diarrheal patients with NTS bacteremia more often presented with co-morbidities and had a higher case fatality rate compared to those with typhoidal bacteremia. Clinicians in regions where both typhoid and NTS bacteremia are prevalent need to be vigilant about the

Split high‐dose oral levothyroxine treatment as a successful therapy option in myxedema coma

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Charoensri, Suranut; Sriphrapradang, Chutintorn; Nimitphong, Hataikarn

2017-01-01

Key Clinical Message High‐dose intravenous thyroxine (T4) is the preferable treatment for myxedema coma. We describe the clinical course of a 69‐year‐old man who presented with myxedema coma and received oral levothyroxine (LT4) therapy (1 mg) in a split dose. This suggests split high‐dose oral LT4 as a therapeutic option in myxedema coma.

High dose rate brachytherapy for oral cancer

International Nuclear Information System (INIS)

Yamazaki, Hideya; Yoshida, Ken; Yoshioka, Yasuo; Shimizutani, Kimishige; Koizumi, Masahiko; Ogawa, Kazuhiko; Furukawa, Souhei

2013-01-01

Brachytherapy results in better dose distribution compared with other treatments because of steep dose reduction in the surrounding normal tissues. Excellent local control rates and acceptable side effects have been demonstrated with brachytherapy as a sole treatment modality, a postoperative method, and a method of reirradiation. Low-dose-rate (LDR) brachytherapy has been employed worldwide for its superior outcome. With the advent of technology, high-dose-rate (HDR) brachytherapy has enabled health care providers to avoid radiation exposure. This therapy has been used for treating many types of cancer such as gynecological cancer, breast cancer, and prostate cancer. However, LDR and pulsed-dose-rate interstitial brachytherapies have been mainstays for head and neck cancer. HDR brachytherapy has not become widely used in the radiotherapy community for treating head and neck cancer because of lack of experience and biological concerns. On the other hand, because HDR brachytherapy is less time-consuming, treatment can occasionally be administered on an outpatient basis. For the convenience and safety of patients and medical staff, HDR brachytherapy should be explored. To enhance the role of this therapy in treatment of head and neck lesions, we have reviewed its outcomes with oral cancer, including Phase I/II to Phase III studies, evaluating this technique in terms of safety and efficacy. In particular, our studies have shown that superficial tumors can be treated using a non-invasive mold technique on an outpatient basis without adverse reactions. The next generation of image-guided brachytherapy using HDR has been discussed. In conclusion, although concrete evidence is yet to be produced with a sophisticated study in a reproducible manner, HDR brachytherapy remains an important option for treatment of oral cancer. (author)

Effect of beam arrangement on oral cavity dose in external beam radiotherapy of nasopharyngeal carcinoma

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Wu, Vincent W.C.; Yang Zhining; Zhang Wuzhe; Wu Lili; Lin Zhixiong

2012-01-01

This study compared the oral cavity dose between the routine 7-beam intensity-modulated radiotherapy (IMRT) beam arrangement and 2 other 7-beam IMRT with the conventional radiotherapy beam arrangements in the treatment of nasopharyngeal carcinoma (NPC). Ten NPC patients treated by the 7-beam routine IMRT technique (IMRT-7R) between April 2009 and June 2009 were recruited. Using the same computed tomography data, target information, and dose constraints for all the contoured structures, 2 IMRT plans with alternative beam arrangements (IMRT-7M and IMRT-7P) by avoiding the anterior facial beam and 1 conventional radiotherapy plan (CONRT) were computed using the Pinnacle treatment planning system. Dose-volume histograms were generated for the planning target volumes (PTVs) and oral cavity from which the dose parameters and the conformity index of the PTV were recorded for dosimetric comparisons among the plans with different beam arrangements. The dose distributions to the PTVs were similar among the 3 IMRT beam arrangements, whereas the differences were significant between IMRT-7R and CONRT plans. For the oral cavity dose, the 3 IMRT beam arrangements did not show significant difference. Compared with IMRT-7R, CONRT plan showed a significantly lower mean dose, V30 and V-40, whereas the V-60 was significantly higher. The 2 suggested alternative beam arrangements did not significantly reduce the oral cavity dose. The impact of varying the beam angles in IMRT of NPC did not give noticeable effect on the target and oral cavity. Compared with IMRT, the 2-D conventional radiotherapy irradiated a greater high-dose volume in the oral cavity.

Disposition of 2,4-dichlorophenoxyacetic acid dimethylamine by Fischer 344 rats dosed orally and dermally

International Nuclear Information System (INIS)

Pelletier, O.; Ritter, L.; Caron, J.; Somers, D.

1989-01-01

The dimethylamine salt of 14C-ring-labeled 2,4-D was administered to Fischer 344 rats orally (1 and 0.4 mg/kg body weight) and dermally (10 mg/kg body weight). Absorption, distribution, and elimination were determined from 14C-labeled 2,4-D in blood, tissues, and excreta. Quantitatively, most of the orally administered dose (94-96%) became systemically available within 6 h. Following dermal administration 10% of the dose became systemically available over 72 h. However, peak concentrations in blood and kidneys were achieved within 30 min of dosing by either route. By 1.5 h after dosing, 2,4-D concentrations in blood, muscle, liver, and kidneys had decreased in both the orally dosed and dermally dosed animals. Between 2 and 8 h, the blood, muscle, liver and kidney concentrations in dermally dosed animals maintained a plateau while urinary excretion increased, presumably due to continued absorption of 2,4-D from the skin. The concentrations in orally dosed animals continued to decrease. Following 7 h of dermal exposure, skin cleansing removed about 63% of the applied dose; about 17% of the applied dose remained at the site of dermal dosing. At 8 h, 2,4-D concentrations in blood, muscle, liver, and kidneys of dermally dosed animals began to decrease, most likely a result of the removal of the reservoir on the skin. However, 2,4-D continued to be absorbed from skin site, resulting in a slower decline of the 2,4-D concentrations in these tissues over remainder of the 72-h study period. By comparison, in animals that had been orally dosed, the absorbed dose was almost completely excreted within 24 h

Frequency of typhoid fever and its association with seasonal variations in Taxila, Pakistan

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Naeem Bukhari

2016-08-01

Full Text Available Objective: To analyse seropositivity rates of salmonella with seasonal variations in the population of Taxila and the surrounding rural areas. Methods: The study was conducted among 760 suspected patients with symptoms of fever, headache, nausea and decreased white blood cells count screened for the typhoid fever. Blood samples collected from the suspected patients were tested for seropositivity by slide agglutination (Widal test and Immunochromatographic test, i.e. Typhidot. Results: From overall 760 suspected patients of typhoid fever only 192 (25.26% samples were positive for Widal and Typhidot test. The peak seropositivity rates were identified during the months of April–June, while decreased cases were observed from January to March. Age wise distribution of typhoid fever reflected that age groups of 10–15 years and 25–35 years were at higher risks of developing enteric fever with respect to age groups of 5–10 years and 61–70 years, respectively. On gender basis evaluation, females (24.49% were slightly at low risks of developing typhoid fever than males (25.9%. Conclusions: The present study highlights a higher burden of typhoid fever in Taxila and the surrounding areas population that directly reflects the poor hygienic condition and contamination of drinking water. The frequency of typhoid fever fluctuates with seasonal variations as higher rates found during the summer as compared to winter season.

A comparison of the oral application and injection routes using the Onderstepoort Biological Products Fowl Typhoid vaccine, its safety, efficacy and duration of protection in commercial laying hens : article

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C. Purchase

2008-05-01

Full Text Available This study was undertaken to establish whether the Onderstepoort Biological Products Fowl Typhoid (OBPft vaccine registered as an injectable vaccine was effective and safe when administered orally to commercial layers. Its efficacy and duration of protection were compared with application by intramuscular injection. Commercial brown layer hens were used as they were found to be highly susceptible to Salmonella gallinarum infections. In the vaccine safety trial birds were euthanased at timed intervals spanning 4 weeks post-vaccination. Necropsies were performed and samples were taken and tested. No clinical signs or mortalities could be attributed to the OBPft vaccine nor could active shedding of the vaccine strain be detected. Slight pathological changes were noted with both routes of vaccination; however, these changes were transient, returning to normal within the observation period. The injected groups showed a better serological response with the rapid serum plate agglutination (RSPA test than the orally vaccinated groups. In the duration of protection trial, birds were challenged at 3-8-week intervals post-vaccination. All unvaccinated birds died. Protection 8 and 16 weeks after vaccination was above 60 %, by 24 weeks after challenge, the vaccine protection was below 30 %. It was found that there was no significant difference (P < 0.05 in the protection offered by either the oral or injected route of vaccination with the OBPft vaccine.

Role of Abdominal Ultrasound in the Diagnosis of Typhoid Fever in Pediatric Patients

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Niranjan Sahu

2016-12-01

Full Text Available An early diagnosis of typhoid fever caused by Salmonella typhi is difficult because of several spectra of clinical findings, identical to those of several other types of infections. A definitive diagnosis of typhoid fever is made by hemoculture as well as the Widal test. With pediatric patients, this life-threatening infection remains inherently long enough, demanding urgent attention. In typhoid fever, splenomegaly, enlarged mesenteric lymph nodes (MLNs, bowel wall thickening, acalculus cholecystitis, and hepatomegaly occur, which are diagnosed by the ultrasonography (USG test. USG is a noninvasive, easily available, economical, fairly acceptable, and fairly sensitive test. The high-resolution real-time gray-scale USG method has simplified the evaluation of pathologic conditions, with remarkable clarity; consequently, an accurate assessment of the associated lesions can be done. In typhoid-endemic areas, USG findings as cited above could be used for diagnosis of typhoid fever, particularly when serology is equivocal and hemocultures are negative or not available. It was evident from USG studies that 12 of 52 patients had calculus cholecystitis; these individuals as well as eight patients without cholecystitis having hemocultures negative for S. typhi were excluded from the study. The rest of the cases (n=32 were included in this USG-based study for evaluation of features specific for typhoid fever. The following observations were recorded: splenomegaly in 32 patients, enlarged MLNs in 30 patients, bowel wall thickening in 25 patients, acalculus cholecystitis in 20 patients, and hepatomegaly in 10 patients. It can be concluded that these USG features—hepatosplenomegaly, enlarged MLNs, bowel wall thickening, and acalculus cholecystitis—should strongly favor the diagnosis of typhoid.

Review of current typhoid fever vaccines, cross-protection against paratyphoid fever, and the European guidelines.

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Zuckerman, Jane N; Hatz, Christoph; Kantele, Anu

2017-10-01

Typhoid and paratyphoid fever remain a global health problem, which - in non-endemic countries - are mainly seen in travelers, particularly in VFRs (visiting friends and relatives), with occasional local outbreaks occurring. A rise in anti-microbial resistance emphasizes the role of preventive measures, especially vaccinations against typhoid and paratyphoid fever for travelers visiting endemic countries. Areas covered: This state-of-the-art review recapitulates the epidemiology and mechanisms of disease of typhoid and paratyphoid fever, depicts the perspective of non-endemic countries and travelers (VFRs), and collectively presents current European recommendations for typhoid fever vaccination. We provide a brief overview of available (and developmental) vaccines in Europe, present current data on cross-protection to S. Paratyphi, and aim to provide a background for typhoid vaccine decision-making in travelers. Expert commentary: European recommendations are not harmonized. Experts must assess vaccination of travelers based on current country-specific recommendations. Travel health practitioners should be aware of the issues surrounding vaccination of travelers and be motivated to increase awareness of typhoid and paratyphoid fever risks.

Typhoid fever among hospitalized febrile children in Siem Reap, Cambodia.

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Wijedoru, Lalith P M; Kumar, Varun; Chanpheaktra, Ngoun; Chheng, Kheng; Smits, Henk L; Pastoor, Rob; Nga, Tran Vu Thieu; Baker, Stephen; Wuthiekanun, Vanaporn; Peacock, Sharon J; Putchhat, Hor; Parry, Christopher M

2012-02-01

Typhoid fever was confirmed by positive blood culture in 5 (3.7%) of 134 febrile children hospitalized in Cambodia. Typhoid was suspected in an additional 25 (18.7 %) blood culture-negative children based on: a positive immunoglobulin M lateral flow assay (IgMFA) (16); a positive polymerase chain reaction (PCR) for Salmonella typhi (2); or clinical assessment (7). The specificity of the IgMFA and PCR assays requires further study.

Concurrent malaria and typhoid fever in the tropics: the diagnostic challenges and public health implications.

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Uneke, C J

2008-06-01

Malaria and typhoid fever still remain diseases of major public health importance in the tropics. Individuals in areas endemic for both the diseases are at substantial risk of contracting both these diseases, either concurrently or an acute infection superimposed on a chronic one. The objective of this report was to systematically review scientific data from studies conducted in the tropics on concurrent malaria and typhoid fever within the last two decades (1987-2007), to highlight the diagnostic challenges and the public health implications. Using the MedLine Entrez-PubMed search, relevant publications were identified for the review via the key words Malaria and Typhoid fever, which yielded 287 entries as of January 2008. Most of the studies reviewed expressed concern that poor diagnosis continues to hinder effective control of concurrent malaria and typhoid fever in the tropics due to: non-specific clinical presentation of the diseases; high prevalence of asymptomatic infections; lack of resources and insufficient access to trained health care providers and facilities; and widespread practice of self-treatment for clinically suspected malaria or typhoid fever. There were considerably higher rates of concurrent malaria and typhoid fever by Widal test compared to the bacteriological culture technique. Although culture technique remains the gold standard in typhoid fever diagnosis, Widal test is still of significant diagnostic value provided judicious interpretation of the test is made against a background of pertinent information. Malaria could be controlled through interventions to minimize human-vector contact, while improved personal hygiene, targeted vaccination campaigns and intensive community health education could help to control typhoid fever in the tropics.

Typhoid Fever surveillance and vaccine use - South-East Asia and Western Pacific regions, 2009-2013.

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Date, Kashmira A; Bentsi-Enchill, Adwoa D; Fox, Kimberley K; Abeysinghe, Nihal; Mintz, Eric D; Khan, M Imran; Sahastrabuddhe, Sushant; Hyde, Terri B

2014-10-03

Typhoid fever is a serious, systemic infection resulting in nearly 22 million cases and 216,500 deaths annually, primarily in Asia. Safe water, adequate sanitation, appropriate personal and food hygiene, and vaccination are the most effective strategies for prevention and control. In 2008, the World Health Organization (WHO) recommended use of available typhoid vaccines to control endemic disease and outbreaks and strengthening of typhoid surveillance to improve disease estimates and identify high-risk populations (e.g., persons without access to potable water and adequate sanitation). This report summarizes the status of typhoid surveillance and vaccination programs in the WHO South-East Asia (SEAR) and Western Pacific regions (WPR) during 2009-2013, after the revised WHO recommendations. Data were obtained from the WHO/United Nations Children's Fund (UNICEF) Joint Reporting Form on Immunization, a supplemental survey of surveillance and immunization program managers, and published literature. During 2009-2013, 23 (48%) of 48 countries and areas of SEAR (11) and WPR (37) collected surveillance or notifiable disease data on typhoid cases, with most surveillance activities established before 2008. Nine (19%) countries reported implementation of typhoid vaccination programs or recommended vaccine use during 2009-2013. Despite the high incidence, typhoid surveillance is weak in these two regions, and vaccination efforts have been limited. Further progress toward typhoid fever prevention and control in SEAR and WPR will require country commitment and international support for enhanced surveillance, targeted use of existing vaccines and availability of newer vaccines integrated within routine immunization programs, and integration of vaccination with safe water, sanitation, and hygiene measures.

Management of Typhoid Fever and Bacterial Meningitis by Chloramphenicol in Infants and Children

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Gian Maria Pacifici

2018-01-01

Full Text Available Chloramphenicol inhibits protein synthesis in bacteria and is usually bacteriostatic but is bactericidal against Haemophilus influenzae, Streptococcus pneumoniae, and Neisseria meningitis. Chloramphenicol penetrates all body tissues well. The cerebrospinal fluid concentration averages 60% of the serum level, while brain levels are 9 times higher because of high lipid solubility of this drug. Chloramphenicol acts primarily by binding reversibly to the 50S ribosomal subunit. This antibiotic is the drug of choice for the treatment of typhoid and paratyphoid fevers and bacterial meningitis. Chloramphenicol possesses a broad-spectrum of antimicrobial activity. Strains are considered sensitive if they are inhibited by chloramphenicol concentrations of ≤ 8 µg/ml. Neisseria gonorrhea, Brucella species, Bordetella pertussis, gram-positive cocci, Clostridium species, and gram-negative rods including Bacillus fragilis are inhibited by chloramphenicol. Most anaerobic bacteria including Mycoplasma, Chlamydia, Rickettsiae, Vibrio cholera, Escherichia coli and Klebsiella pneumoniae are inhibited by this antibiotic. The doses of chloramphenicol are 40.5 mg/kg/day for neonates and 75.5 mg/kg/day for older children. The therapeutic concentrations of chloramphenicol are 10-25 µg/ml. Peak therapeutic concentrations are obtained in 60% and therapeutic trough concentrations are found in 42% of children. Children affected by typhoid fever are cu red by chloramphenicol and the sensitivity to this antibiotic is 100%. Acute bacterial meningitis is the most dangerous infections disease in children. The causative organisms are gram-positive and gram-negative bacteria, and chloramphenicol is effective in killing these microorganisms. The aim of this study is to review the management of typhoid fever and bacterial meningitis in infants and children by chloramphenicol.

What Have We Learned From the Typhoid Fever Surveillance in Africa Program?

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Baker, Stephen; Hombach, Joachim; Marks, Florian

2016-03-15

The Typhoid Fever Surveillance in Africa Program (TSAP) was established in 2009 to fill the data void concerning invasive Salmonella disease in sub-Saharan Africa, and to specifically estimate the burden of bloodstream infections caused by the key pathogen, Salmonella enterica serovar Typhi. TSAP has achieved this ambitious target, finding high incidences of typhoid fever in both rural and urban populations in several countries in sub-Saharan Africa. The results of TSAP will undoubtedly dictate the direction of future typhoid fever research in Africa, and at last provides a key piece of the disease burden jigsaw puzzle. With the dawn of new Vi conjugate vaccines against Salmonella Typhi, the next priority for the typhoid community must be providing the required data on these vaccines so they can be licensed and provided to those in high-risk groups and locations across sub-Saharan Africa. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

Typhoid fever as a cause of opportunistic infection: case report

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Tumminia Salvatore

2006-02-01

Full Text Available Abstract Background Typhoid fever is a systemic infection caused by the bacterium Salmonella enterica subspecies enterica serotype typhi, which is acquired by ingestion of contaminated food and water. Each year the disease affects at least 16 million persons world-wide, most of whom reside in the developing countries of Southeast Asia and Africa. In Italy the disease is uncommon with a greater number of cases in Southern regions than in Northern ones. Case presentation We report on a 57-year-old Sri-Lankan male affected by typhoid fever, the onset of which was accompanied by oropharyngeal candidiasis. This clinical sign was due to a transient cell-mediated immunity depression (CD4+ cell count was 130 cells/mm3 probably caused by Salmonella typhi infection. Human immunodeficiency virus infection was ruled out. Diagnosis of typhoid fever was made by the isolation of Salmonella typhi from two consecutive blood cultures. The patient recovered after a ten days therapy with ciprofloxacin and his CD4+ cell count improved gradually until normalization within 3 weeks. Conclusion Our patient is the first reported case of typhoid fever associated with oropharyngeal candidiasis. This finding suggests a close correlation between Salmonella typhi infection and transitory immunodepression.

A review of typhoid fever transmission dynamic models and economic evaluations of vaccination.

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Watson, Conall H; Edmunds, W John

2015-06-19

Despite a recommendation by the World Health Organization (WHO) that typhoid vaccines be considered for the control of endemic disease and outbreaks, programmatic use remains limited. Transmission models and economic evaluation may be informative in decision making about vaccine programme introductions and their role alongside other control measures. A literature search found few typhoid transmission models or economic evaluations relative to analyses of other infectious diseases of similar or lower health burden. Modelling suggests vaccines alone are unlikely to eliminate endemic disease in the short to medium term without measures to reduce transmission from asymptomatic carriage. The single identified data-fitted transmission model of typhoid vaccination suggests vaccines can reduce disease burden substantially when introduced programmatically but that indirect protection depends on the relative contribution of carriage to transmission in a given setting. This is an important source of epidemiological uncertainty, alongside the extent and nature of natural immunity. Economic evaluations suggest that typhoid vaccination can be cost-saving to health services if incidence is extremely high and cost-effective in other high-incidence situations, when compared to WHO norms. Targeting vaccination to the highest incidence age-groups is likely to improve cost-effectiveness substantially. Economic perspective and vaccine costs substantially affect estimates, with disease incidence, case-fatality rates, and vaccine efficacy over time also important determinants of cost-effectiveness and sources of uncertainty. Static economic models may under-estimate benefits of typhoid vaccination by omitting indirect protection. Typhoid fever transmission models currently require per-setting epidemiological parameterisation to inform their use in economic evaluation, which may limit their generalisability. We found no economic evaluation based on transmission dynamic modelling, and no

Severity of infection and seasonal variation of non-typhoid Salmonelle occurence in humans

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Gradel, K.O.; Dethlefsen, Claus; Schønheyder, H.C.

2007-01-01

Non-typhoid Salmonella infections may present as severe gastroenteritis necessitatinghospitalization and some patients become septic with bacteraemia. We hypothesized that theseasonal variation of non-typhoid Salmonella occurrence in humans diminishes with increasedseverity of infection. We...... examined the seasonal variation of non-typhoid Salmonella infections inthree patient groups with differing severity of infection: outpatients treated for gastroenteritis(n=1490); in-patients treated for gastroenteritis (n=492); and in-patients treated for bacteraemia(n=113). The study was population......-based and included all non-typhoid Salmonella patients ina Danish county from 1994 to 2003. A periodic regression model was used to compute thepeak-to-trough ratio for the three patient groups. The peak-to-trough ratios were 4·3 [95%confidence interval (CI) 3·6–5.0] for outpatients with gastroenteritis, 3·2 (95% CI...

Severe thrombocytopenia in a child with typhoid fever: a case report.

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Al Reesi, Mohammed; Stephens, Glenn; McMullan, Brendan

2016-11-30

Although thrombocytopenia is common in typhoid fever, its course, response to treatment, and need for specific therapies such as platelet transfusion are not well characterized. We report a case of typhoid fever in a 4-year-old Asian male returned traveler, admitted with prolonged fever and found to have severe thrombocytopenia (platelets 16 × 10 9 /L). Despite appropriate antibiotic therapy, his platelet recovery was slow, but did not lead to complications and he did not require platelet transfusion. There is no consensus in the medical literature guiding the optimal management of severe thrombocytopenia in typhoid fever, but it may improve with conservative management, as in our case. The epidemiology and management of this condition merits further research to guide clinical practice.

Implementation research: reactive mass vaccination with single-dose oral cholera vaccine, Zambia.

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Poncin, Marc; Zulu, Gideon; Voute, Caroline; Ferreras, Eva; Muleya, Clara Mbwili; Malama, Kennedy; Pezzoli, Lorenzo; Mufunda, Jacob; Robert, Hugues; Uzzeni, Florent; Luquero, Francisco J; Chizema, Elizabeth; Ciglenecki, Iza

2018-02-01

To describe the implementation and feasibility of an innovative mass vaccination strategy - based on single-dose oral cholera vaccine - to curb a cholera epidemic in a large urban setting. In April 2016, in the early stages of a cholera outbreak in Lusaka, Zambia, the health ministry collaborated with Médecins Sans Frontières and the World Health Organization in organizing a mass vaccination campaign, based on single-dose oral cholera vaccine. Over a period of 17 days, partners mobilized 1700 health ministry staff and community volunteers for community sensitization, social mobilization and vaccination activities in 10 townships. On each day, doses of vaccine were delivered to vaccination sites and administrative coverage was estimated. Overall, vaccination teams administered 424 100 doses of vaccine to an estimated target population of 578 043, resulting in an estimated administrative coverage of 73.4%. After the campaign, few cholera cases were reported and there was no evidence of the disease spreading within the vaccinated areas. The total cost of the campaign - 2.31 United States dollars (US$) per dose - included the relatively low cost of local delivery - US$ 0.41 per dose. We found that an early and large-scale targeted reactive campaign using a single-dose oral vaccine, organized in response to a cholera epidemic within a large city, to be feasible and appeared effective. While cholera vaccines remain in short supply, the maximization of the number of vaccines in response to a cholera epidemic, by the use of just one dose per member of an at-risk community, should be considered.

Effect of ionizing radiation on the antigenic composition of typhoid bacteria

International Nuclear Information System (INIS)

Sinilova, N.G.; Nikolaeva, L.A.; Tumanyan, M.A.

1978-01-01

Changes in the antigenic composition of typhoid bacteria occurring during the exposure of microbial suspension to different doses of gamma radiation ( 60 Co) ranging between 0.5 and 3.0 Mrad were studied. Immunoelectrophoresis in agar was used to determine the antigenic composition of different samples of irradiated bacteria. The antigenic composition of bacteria irradiated with doses up to 2.5 Mrad was found to be similar to that of non-irradiated bacteria. Antigens demonstrated by means of Vi, H and O antisera are preserved in these bacteria. However, all irradiated bacteria in general slightly differ from non-irradiated bacteria; this is manifest in a different configuration and position of the precipitation lines in the cathodic part of the immunophoreograms. The content of the component migrating rapidly towards the cathode, evidently the O antigen in the R form, in the irradiated bacteria increases with the dose of radiation. No new serologically active substances, non-existent in non-irradiated bacteria, were found to appear in the process of irradiation. (author)

Role of computed tomography of abdomen in difficult to diagnose typhoid fever: a case series.

Science.gov (United States)

Hafeez, Wajid; Rajalakshmi, S; Sripriya, S; Madhu Bashini, M

2018-04-01

Background and Aim Diagnosis of typhoid is challenging when blood cultures fail to isolate Salmonella species. We report our experience with interpreting computed tomography (CT) abdomen findings in a case series of typhoid fever. Methods The case series consisted of patients who had a CT abdomen done as part of their investigations and a final diagnosis of typhoid fever. The CT films were reviewed and findings evaluated for distinctive features. Results During 2011-2017, 11 patients met the inclusion criteria. Indication for CT was pyrexia of unknown origin in the majority of patients. Review of CT films revealed mesenteric lymphadenopathy (100%), terminal ileum thickening (85%), hepatosplenomegaly (45%), retroperitoneal lymphadenopathy (18%) and ascites (9%). Conclusions Enhancing discrete mesenteric lymphadenopathy and terminal ileum thickening are non-specific findings noted in typhoid fever. Absence of matted necrotic nodes and peritoneal thickening rule out tuberculosis and raise suspicion of typhoid fever in endemic regions.

The unrecognized burden of typhoid fever.

Science.gov (United States)

Obaro, Stephen K; Iroh Tam, Pui-Ying; Mintz, Eric Daniel

2017-03-01

Typhoid fever (TF), caused by Salmonella enterica serovar Typhi, is the most common cause of enteric fever, responsible for an estimated 129,000 deaths and more than 11 million cases annually. Although several reviews have provided global and regional TF disease burden estimates, major gaps in our understanding of TF epidemiology remain. Areas covered: We provide an overview of the gaps in current estimates of TF disease burden and offer suggestions for addressing them, so that affected communities can receive the full potential of disease prevention offered by vaccination and water, sanitation, and hygiene interventions. Expert commentary: Current disease burden estimates for TF do not capture cases from certain host populations, nor those with atypical presentations of TF, which may lead to substantial underestimation of TF cases and deaths. These knowledge gaps pose major obstacles to the informed use of current and new generation typhoid vaccines.

Expression of intra- and extracellular granzymes in patients with typhoid fever.

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de Jong, Hanna K; Garcia-Laorden, Maria Isabel; Hoogendijk, Arie J; Parry, Christopher M; Maude, Rapeephan R; Dondorp, Arjen M; Faiz, Mohammed Abul; van der Poll, Tom; Wiersinga, Willem Joost

2017-07-01

Typhoid fever, caused by the intracellular pathogen Salmonella (S.) enterica serovar Typhi, remains a major cause of morbidity and mortality worldwide. Granzymes are serine proteases promoting cytotoxic lymphocytes mediated eradication of intracellular pathogens via the induction of cell death and which can also play a role in inflammation. We aimed to characterize the expression of extracellular and intracellular granzymes in patients with typhoid fever and whether the extracellular levels of granzyme correlated with IFN-γ release. We analyzed soluble protein levels of extracellular granzyme A and B in healthy volunteers and patients with confirmed S. Typhi infection on admission and day of discharge, and investigated whether this correlated with interferon (IFN)-γ release, a cytokine significantly expressed in typhoid fever. The intracellular expression of granzyme A, B and K in subsets of lymphocytic cells was determined using flow cytometry. Patients demonstrated a marked increase of extracellular granzyme A and B in acute phase plasma and a correlation of both granzymes with IFN-γ release. In patients, lower plasma levels of granzyme B, but not granzyme A, were found at day of discharge compared to admission, indicating an association of granzyme B with stage of disease. Peripheral blood mononuclear cells of typhoid fever patients had a higher percentage of lymphocytic cells expressing intracellular granzyme A and granzyme B, but not granzyme K, compared to controls. The marked increase observed in extra- and intracellular levels of granzyme expression in patients with typhoid fever, and the correlation with stage of disease, suggests a role for granzymes in the host response to this disease.

Host-pathogen interactions in typhoid fever

NARCIS (Netherlands)

de Jong, H.K.

2015-01-01

This thesis focuses on host-pathogen interactions in Salmonella Typhi and Burkholderia pseudomallei infections and explores the interplay between these bacteria and the innate immune system. Typhoid fever is one of the most common causes of bacterial infection in low-income countries. With adequate

Risk factors for the development of severe typhoid fever in Vietnam.

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Parry, Christopher M; Thompson, Corinne; Vinh, Ha; Chinh, Nguyen Tran; Phuong, Le Thi; Ho, Vo Anh; Hien, Tran Tinh; Wain, John; Farrar, Jeremy J; Baker, Stephen

2014-02-10

Typhoid fever is a systemic infection caused by the bacterium Salmonella enterica serovar Typhi. Age, sex, prolonged duration of illness, and infection with an antimicrobial resistant organism have been proposed risk factors for the development of severe disease or fatality in typhoid fever. We analysed clinical data from 581 patients consecutively admitted with culture confirmed typhoid fever to two hospitals in Vietnam during two periods in 1993-1995 and 1997-1999. These periods spanned a change in the antimicrobial resistance phenotypes of the infecting organisms i.e. fully susceptible to standard antimicrobials, resistance to chloramphenicol, ampicillin and trimethoprim-sulphamethoxazole (multidrug resistant, MDR), and intermediate susceptibility to ciprofloxacin (nalidixic acid resistant). Age, sex, duration of illness prior to admission, hospital location and the presence of MDR or intermediate ciprofloxacin susceptibility in the infecting organism were examined by logistic regression analysis to identify factors independently associated with severe typhoid at the time of hospital admission. The prevalence of severe typhoid was 15.5% (90/581) and included: gastrointestinal bleeding (43; 7.4%); hepatitis (29; 5.0%); encephalopathy (16; 2.8%); myocarditis (12; 2.1%); intestinal perforation (6; 1.0%); haemodynamic shock (5; 0.9%), and death (3; 0.5%). Severe disease was more common with increasing age, in those with a longer duration of illness and in patients infected with an organism exhibiting intermediate susceptibility to ciprofloxacin. Notably an MDR phenotype was not associated with severe disease. Severe disease was independently associated with infection with an organism with an intermediate susceptibility to ciprofloxacin (AOR 1.90; 95% CI 1.18-3.07; p = 0.009) and male sex (AOR 1.61 (1.00-2.57; p = 0.035). In this group of patients hospitalised with typhoid fever infection with an organism with intermediate susceptibility to ciprofloxacin was

Descriptive epidemiology of typhoid fever during an epidemic in Harare, Zimbabwe, 2012.

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Polonsky, Jonathan A; Martínez-Pino, Isabel; Nackers, Fabienne; Chonzi, Prosper; Manangazira, Portia; Van Herp, Michel; Maes, Peter; Porten, Klaudia; Luquero, Francisco J

2014-01-01

Typhoid fever remains a significant public health problem in developing countries. In October 2011, a typhoid fever epidemic was declared in Harare, Zimbabwe - the fourth enteric infection epidemic since 2008. To orient control activities, we described the epidemiology and spatiotemporal clustering of the epidemic in Dzivaresekwa and Kuwadzana, the two most affected suburbs of Harare. A typhoid fever case-patient register was analysed to describe the epidemic. To explore clustering, we constructed a dataset comprising GPS coordinates of case-patient residences and randomly sampled residential locations (spatial controls). The scale and significance of clustering was explored with Ripley K functions. Cluster locations were determined by a random labelling technique and confirmed using Kulldorff's spatial scan statistic. We analysed data from 2570 confirmed and suspected case-patients, and found significant spatiotemporal clustering of typhoid fever in two non-overlapping areas, which appeared to be linked to environmental sources. Peak relative risk was more than six times greater than in areas lying outside the cluster ranges. Clusters were identified in similar geographical ranges by both random labelling and Kulldorff's spatial scan statistic. The spatial scale at which typhoid fever clustered was highly localised, with significant clustering at distances up to 4.5 km and peak levels at approximately 3.5 km. The epicentre of infection transmission shifted from one cluster to the other during the course of the epidemic. This study demonstrated highly localised clustering of typhoid fever during an epidemic in an urban African setting, and highlights the importance of spatiotemporal analysis for making timely decisions about targetting prevention and control activities and reinforcing treatment during epidemics. This approach should be integrated into existing surveillance systems to facilitate early detection of epidemics and identify their spatial range.

Current trends of antimicrobial susceptibility of typhoidal salmonellae isolated at tertiary care hospital

International Nuclear Information System (INIS)

Zehra, N.M.; Irfan, F.

2017-01-01

To determine the current trend of antimicrobial susceptibility of typhoidal Salmonellae. Study Design: Descriptive cross-sectional study. Place and Duration of Study: The study was carried out in the Department of Microbiology, PNS Shifa Hospital, Karachi, from January 2014 to December 2015. Methodology: Blood culture samples received from the wards and outpatient departments were included. Isolates of Salmonella were dealt with standard microbiological procedures. The antimicrobial sensitivity against the typhoidal Salmonellae was determined using Kirby-Bauer disc diffusion method as per the guidelines of Clinical and Laboratory Standards Institute (2013). Results: A total of 460 typhoidal Salmonellae were isolated; out of which 270 were Salmonella typhi and 190 were Salmonella paratyphiA. The percentage of MDR isolates of S. typhi was 57% and that of S. paratyphiA was 42%. None of the isolates were resistant to ceftriaxone, while sensitivity to ciprofloxacin (07% and 0% for S. typhiand S. paratyphiA, respectively) was very low. Conclusion: There is high percentage of MDR isolates of typhoidal Salmonellae in our region. The antimicrobial sensitivity of typhoidal Salmonellae to conventional agent has not improved enough to recommend their empirical use. There is almost complete resistance to fluoroquinolones as well, leaving very limited available treatment options. (author)

Typhoid outbreak investigation in Dzivaresekwa, suburb of Harare ...

African Journals Online (AJOL)

Typhoid outbreak investigation in Dzivaresekwa, suburb of Harare City, Zimbabwe, 2011. Monica Muti, Notion Gombe, Mufuta Tshimanga, Lucia Takundwa, Donewell Bangure, Stanley Mungofa, Prosper Chonzi ...

Epidemiology and risk factors for typhoid fever in Central Division, Fiji, 2014-2017: A case-control study.

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Prasad, Namrata; Jenkins, Aaron P; Naucukidi, Lanieta; Rosa, Varanisese; Sahu-Khan, Aalisha; Kama, Mike; Jenkins, Kylie M; Jenney, Adam W J; Jack, Susan J; Saha, Debasish; Horwitz, Pierre; Jupiter, Stacy D; Strugnell, Richard A; Mulholland, E Kim; Crump, John A

2018-06-01

Typhoid fever is endemic in Fiji, with high reported annual incidence. We sought to identify the sources and modes of transmission of typhoid fever in Fiji with the aim to inform disease control. We identified and surveyed patients with blood culture-confirmed typhoid fever from January 2014 through January 2017. For each typhoid fever case we matched two controls by age interval, gender, ethnicity, and residential area. Univariable and multivariable analysis were used to evaluate associations between exposures and risk for typhoid fever. We enrolled 175 patients with typhoid fever and 349 controls. Of the cases, the median (range) age was 29 (2-67) years, 86 (49%) were male, and 84 (48%) lived in a rural area. On multivariable analysis, interrupted water availability (odds ratio [OR] = 2.17; 95% confidence interval [CI] 1.18-4.00), drinking surface water in the last 2 weeks (OR = 3.61; 95% CI 1.44-9.06), eating unwashed produce (OR = 2.69; 95% CI 1.48-4.91), and having an unimproved or damaged sanitation facility (OR = 4.30; 95% CI 1.14-16.21) were significantly associated with typhoid fever. Frequent handwashing after defecating (OR = 0.57; 95% CI 0.35-0.93) and using soap for handwashing (OR = 0.61; 95% CI 0.37-0.95) were independently associated with a lower odds of typhoid fever. Poor sanitation facilities appear to be a major source of Salmonella Typhi in Fiji, with transmission by drinking contaminated surface water and consuming unwashed produce. Improved sanitation facilities and protection of surface water sources and produce from contamination by human feces are likely to contribute to typhoid control in Fiji.

[Some information regarding the historical development of typhoid fever in Chile].

Science.gov (United States)

Laval, Enrique

2017-10-01

During the historical development of typhoid fever in Chile, its confusion with other infectious diseases is particularly noteworthy, especially with murine typhus, a problem that was mainly resolved during the 1918 epidemic. The importance of chloramphenicol treatment is also highlighted, which meant an enormous improvement in typhoid/paratyphoid fevers, in combination with public health and health education actions that allowed to almost eliminate these infectious diseases in our country.

Neurologic manifestations associated with an outbreak of typhoid fever, Malawi--Mozambique, 2009: an epidemiologic investigation.

Science.gov (United States)

Sejvar, James; Lutterloh, Emily; Naiene, Jeremias; Likaka, Andrew; Manda, Robert; Nygren, Benjamin; Monroe, Stephan; Khaila, Tadala; Lowther, Sara A; Capewell, Linda; Date, Kashmira; Townes, David; Redwood, Yanique; Schier, Joshua; Barr, Beth Tippett; Demby, Austin; Mallewa, Macpherson; Kampondeni, Sam; Blount, Ben; Humphrys, Michael; Talkington, Deborah; Armstrong, Gregory L; Mintz, Eric

2012-01-01

The bacterium Salmonella enterica serovar Typhi causes typhoid fever, which is typically associated with fever and abdominal pain. An outbreak of typhoid fever in Malawi-Mozambique in 2009 was notable for a high proportion of neurologic illness. Describe neurologic features complicating typhoid fever during an outbreak in Malawi-Mozambique Persons meeting a clinical case definition were identified through surveillance, with laboratory confirmation of typhoid by antibody testing or blood/stool culture. We gathered demographic and clinical information, examined patients, and evaluated a subset of patients 11 months after onset. A sample of persons with and without neurologic signs was tested for vitamin B6 and B12 levels and urinary thiocyanate. Between March - November 2009, 303 cases of typhoid fever were identified. Forty (13%) persons had objective neurologic findings, including 14 confirmed by culture/serology; 27 (68%) were hospitalized, and 5 (13%) died. Seventeen (43%) had a constellation of upper motor neuron findings, including hyperreflexia, spasticity, or sustained ankle clonus. Other neurologic features included ataxia (22, 55%), parkinsonism (8, 20%), and tremors (4, 10%). Brain MRI of 3 (ages 5, 7, and 18 years) demonstrated cerebral atrophy but no other abnormalities. Of 13 patients re-evaluated 11 months later, 11 recovered completely, and 2 had persistent hyperreflexia and ataxia. Vitamin B6 levels were markedly low in typhoid fever patients both with and without neurologic signs. Neurologic signs may complicate typhoid fever, and the diagnosis should be considered in persons with acute febrile neurologic illness in endemic areas.

Single and Multiple Ascending-dose Studies of Oral Delafloxacin: Effects of Food, Sex, and Age.

Science.gov (United States)

Hoover, Randall; Hunt, Thomas; Benedict, Michael; Paulson, Susan K; Lawrence, Laura; Cammarata, Sue; Sun, Eugene

2016-01-01

The objective of this report is describe the results of 2 studies that examined the pharmacokinetic parameters, safety profile, and tolerability of single and multiple ascending doses of oral delafloxacin and the effects of food, sex, and age on oral delafloxacin pharmacokinetic parameters, safety profile, and tolerability. The first study contained 3 parts and used unformulated delafloxacin in a capsule. Part 1 was a randomized, double-blind, placebo-controlled, single (50, 100, 200, 400, 800, 1200, and 1600 mg) ascending-dose study of oral delafloxacin in healthy men. Part 2 was a single-dose crossover study in which 20 men received 250 mg delafloxacin with or without food. Part 2 also included a parallel group, double-blind, placebo-controlled study in 16 women and 16 elderly men and women who were randomized (3:1) to receive 250 mg delafloxacin or placebo. Part 3 was a randomized, double-blind, placebo-controlled, multiple (100, 200, 400, 800, 1200 mg once daily for 5 days) ascending-dose study of oral delafloxacin in healthy men. The second study was a single-dose, randomized, 3-period crossover study in which participants received 900 mg delafloxacin (2 × 450-mg tablets) under fasted conditions, with a high-fat meal, or fasted with a high-fat meal 2 hours after dosing. Serial blood samples were collected, and plasma pharmacokinetic parameters of delafloxacin were determined. Delafloxacin Cmax and AUC0-∞ increased with increasing oral dose over the dose range of 50 to 1600 mg. The increases in delafloxacin AUC0-∞ were dose proportional at doses of ≥200 mg. Steady state was reached by day 3 of dosing with minimal accumulation of delafloxacin. The Cmax of delafloxacin was decreased slightly in the presence of food. No sex difference in delafloxacin pharmacokinetic parameters was observed. In the elderly men and women, mean delafloxacin Cmax and AUC0-∞ were 35% higher than observed for young adults, which could be partially explained by a decrease in

Immunoproteomic analysis of antibody in lymphocyte supernatant in patients with typhoid fever in Bangladesh.

Science.gov (United States)

Charles, Richelle C; Liang, Li; Khanam, Farhana; Sayeed, M Abu; Hung, Chris; Leung, Daniel T; Baker, Stephen; Ludwig, Albrecht; Harris, Jason B; Larocque, Regina C; Calderwood, Stephen B; Qadri, Firdausi; Felgner, Philip L; Ryan, Edward T

2014-03-01

We have previously shown that an assay based on detection of anti-Salmonella enterica serotype Typhi antibodies in supernatant of lymphocytes harvested from patients presenting with typhoid fever (antibody in lymphocyte supernatant [ALS] assay) can identify 100% of patients with blood culture-confirmed typhoid fever in Bangladesh. In order to define immunodominant proteins within the S. Typhi membrane preparation used as antigen in these prior studies and to identify potential biomarkers unique to S. Typhi bacteremic patients, we probed microarrays containing 2,724 S. Typhi proteins with ALS collected at the time of clinical presentation from 10 Bangladeshis with acute typhoid fever. We identified 62 immunoreactive antigens when evaluating both the IgG and IgA responses. Immune responses to 10 of these antigens discriminated between individuals with acute typhoid infection and healthy control individuals from areas where typhoid infection is endemic, as well as Bangladeshi patients presenting with fever who were subsequently confirmed to have a nontyphoid illness. Using an ALS enzyme-linked immunosorbent assay (ELISA) format and purified antigen, we then confirmed that immune responses against the antigen with the highest immunoreactivity (hemolysin E [HlyE]) correctly identified individuals with acute typhoid or paratyphoid fever in Dhaka, Bangladesh. These observations suggest that purified antigens could be used with ALS and corresponding acute-phase activated B lymphocytes in diagnostic platforms to identify acutely infected patients, even in areas where enteric fever is endemic.

Typhoid fever cases in the U.S. military.

Science.gov (United States)

Sorrell, Tia; Selig, Daniel J; Riddle, Mark S; Porter, Chad K

2015-10-14

Salmonella enterica, serovar Typhi (S. Typhi), a causative agent of enteric fever (typhoid fever), predominately affects populations in developing regions with poor access to clean food and water. In addition, travelers to these regions are at risk of exposure. We report the epidemiological characteristics of S. Typhi cases among active duty United States military personnel from 1998 to 2011 using data obtained from the Defense Medical Surveillance System. Cases were identified based on International Classification for Disease Ninth Edition - Clinical Modification codes. We identified a total of 205 cases S. Typhi for an incidence of 1.09 per 100,000 person-years. Cases were on average 31.7 years old, predominately married (n = 129, 62.9 %), Caucasian (n = 142, 69.3 %), male (n = 176, 85.9 %), and had a high school education (n = 101, 49.3 %). Of the identified cases, 122 had received a Typhoid vaccination within 4 years of diagnosis. This study provides an overview of enteric fever in the United States military. The incidence was similar to the general U.S. population except for increased incidence from 1998 to 2000, perhaps attributable to operational deployments in that period. Given that vaccination is an effective primary prevention measure against typhoid fever, active monitoring of pre-deployment vaccine history is warranted.

Early diagnosis of typhoid fever by nested PCR for flagellin gene of Salmonella enterica serotype Typhi.

Science.gov (United States)

Khan, S; Harish, B N; Menezes, G A; Acharya, N S; Parija, S C

2012-11-01

Typhoid fever caused by Salmonella Typhi continues to be a major health problem in spite of the use of antibiotics and the development of newer antibacterial drugs. Inability to make an early laboratory diagnosis and resort to empirical therapy, often lead to increased morbidity and mortality in cases of typhoid fever. This study was aimed to optimize a nested PCR for early diagnosis of typhoid fever and using it as a diagnostic tool in culture negative cases of suspected typhoid fever. Eighty patients with clinical diagnosis of typhoid fever and 40 controls were included in the study. The blood samples collected were subjected to culture, Widal and nested PCR targeting the flagellin gene of S. Typhi. The sensitivity of PCR on blood was found to be 100 per cent whereas the specificity was 76.9 per cent. The positive predictive value (PPV) of PCR was calculated to be 76.9 per cent with an accuracy of 86 per cent. None of the 40 control samples gave a positive PCR. Due to its high sensitivity and specificity nested PCR can be used as a useful tool to diagnose clinically suspected, culture negative cases of typhoid fever.

Cholestatic hepatitis in a patient with typhoid fever - a case report

Directory of Open Access Journals (Sweden)

Wijesiriwardena Bandula C

2011-10-01

Full Text Available Abstract Typhoid fever is a very common infectious disease, particularly in developing countries such as Sri Lanka. Although multiple organs are known to be affected by the disease, hepatic involvement could be considered the most important as studies have showed that it is associated with a higher relapse rate. We report a young patient who presented with fever and jaundice and found to have cholestatic hepatitis secondary to typhoid fever.

Mouse single oral dose toxicity test of bupleuri radix aqueous extracts.

Science.gov (United States)

Kim, Kyung-Hu; Gam, Cheol-Ou; Choi, Seong-Hun; Ku, Sae-Kwang

2012-03-01

The aim of this study was to evaluate the single oral dose toxicity of Bupleuri Radix (BR) aqueous extracts, it has been traditionally used as anti-inflammatory agent, in male and female mice. BR extracts (yield = 16.52%) was administered to female and male ICR mice as an oral dose of 2,000, 1,000 and 500 mg/kg (body weight) according to the recommendation of Korea Food and Drug Administration (KFDA) Guidelines. Animals were monitored for the mortality and changes in body weight, clinical signs and gross observation during 14 days after dosing, upon necropsy; organ weight and histopathology of 14 principal organs were examined. As the results, no BR extracts treatment related mortalities, clinical signs, changes on the body and organ weights, gross and histopathological observations against 14 principal organs were detected up to 2,000 mg/kg in both female and male mice, except for soft feces and related body weight decrease detected in male mice treated with 2,000 mg/kg. Therefore, LD50 (50% lethal dose) and approximate LD of BR aqueous extracts after single oral treatment in female and male mice were considered over 2000 mg/kg, respectively. Although it was also observed that the possibilities of digestive disorders, like soft feces when administered over 2,000 mg/kg of BR extracts in the present study, these possibilities of digestive disorders can be disregard in clinical use because they are transient in the highest dosages male only.

Safety, immunogenicity and dose ranging of a new Vi-CRM₁₉₇ conjugate vaccine against typhoid fever: randomized clinical testing in healthy adults.

Science.gov (United States)

van Damme, Pierre; Kafeja, Froukje; Anemona, Alessandra; Basile, Venere; Hilbert, Anne Katrin; De Coster, Ilse; Rondini, Simona; Micoli, Francesca; Qasim Khan, Rana M; Marchetti, Elisa; Di Cioccio, Vito; Saul, Allan; Martin, Laura B; Podda, Audino

2011-01-01

Typhoid fever causes more than 21 million cases of disease and 200,000 deaths yearly worldwide, with more than 90% of the disease burden being reported from Asia. Epidemiological data show high disease incidence in young children and suggest that immunization programs should target children below two years of age: this is not possible with available vaccines. The Novartis Vaccines Institute for Global Health developed a conjugate vaccine (Vi-CRM₁₉₇) for infant vaccination concomitantly with EPI vaccines, either starting at 6 weeks with DTP or at 9 months with measles vaccine. We report the results from a Phase 1 and a Phase 2 dose ranging trial with Vi-CRM₁₉₇ in European adults. Following randomized blinded comparison of single vaccination with either Vi-CRM₁₉₇ or licensed polysaccharide vaccines (both containing 25·0 µg of Vi antigen), a randomised observer blinded dose ranging trial was performed in the same center to compare three concentrations of Vi-CRM₁₉₇ (1·25 µg, 5·0 µg and 12·5 µg of Vi antigen) with the polysaccharide vaccine. All vaccines were well tolerated. Compared to the polysaccharide vaccine, Vi-CRM₁₉₇ induced a higher incidence of mild to moderate short lasting local pain. All Vi-CRM₁₉₇ formulations induced higher Vi antibody levels compared to licensed control, with clear dose response relationship. Vi-CRM₁₉₇ did not elicit safety concerns, was highly immunogenic and is therefore suitable for further clinical testing in endemic populations of South Asia. ClinicalTrials.gov NCT01123941 NCT01193907.

Multidrug-resistant typhoid fever with neurologic findings on the Malawi-Mozambique border.

Science.gov (United States)

Lutterloh, Emily; Likaka, Andrew; Sejvar, James; Manda, Robert; Naiene, Jeremias; Monroe, Stephan S; Khaila, Tadala; Chilima, Benson; Mallewa, Macpherson; Kampondeni, Sam D; Lowther, Sara A; Capewell, Linda; Date, Kashmira; Townes, David; Redwood, Yanique; Schier, Joshua G; Nygren, Benjamin; Tippett Barr, Beth; Demby, Austin; Phiri, Abel; Lungu, Rudia; Kaphiyo, James; Humphrys, Michael; Talkington, Deborah; Joyce, Kevin; Stockman, Lauren J; Armstrong, Gregory L; Mintz, Eric

2012-04-01

Salmonella enterica serovar Typhi causes an estimated 22 million cases of typhoid fever and 216 000 deaths annually worldwide. We investigated an outbreak of unexplained febrile illnesses with neurologic findings, determined to be typhoid fever, along the Malawi-Mozambique border. The investigation included active surveillance, interviews, examinations of ill and convalescent persons, medical chart reviews, and laboratory testing. Classification as a suspected case required fever and ≥1 other finding (eg, headache or abdominal pain); a probable case required fever and a positive rapid immunoglobulin M antibody test for typhoid (TUBEX TF); a confirmed case required isolation of Salmonella Typhi from blood or stool. Isolates underwent antimicrobial susceptibility testing and subtyping by pulsed-field gel electrophoresis (PFGE). We identified 303 cases from 18 villages with onset during March-November 2009; 214 were suspected, 43 were probable, and 46 were confirmed cases. Forty patients presented with focal neurologic abnormalities, including a constellation of upper motor neuron signs (n = 19), ataxia (n = 22), and parkinsonism (n = 8). Eleven patients died. All 42 isolates tested were resistant to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole; 4 were also resistant to nalidixic acid. Thirty-five of 42 isolates were indistinguishable by PFGE. The unusual neurologic manifestations posed a diagnostic challenge that was resolved through rapid typhoid antibody testing in the field and subsequent blood culture confirmation in the Malawi national reference laboratory. Extending laboratory diagnostic capacity, including blood culture, to populations at risk for typhoid fever in Africa will improve outbreak detection, response, and clinical treatment.

Clinical features and outcome of typhoid fever and invasive non-typhoidal salmonellosis in a tertiary hospital in Belgium: analysis and review of the literature.

Science.gov (United States)

Yombi, J C; Martins, L; Vandercam, B; Rodriguez-Villalobos, H; Robert, A

2015-08-01

Typhoid fever (TF) occurs rarely in industrialized countries because of advances in health care and improvement of drinking water. Conversely, non-typhoid salmonellosis (NTS) remains widespread, because of food contamination or asymptomatic carriage. Non-typhoid salmonellosis can be severe when becoming invasive non-typhoid salmonellosis (iNTS). Although established prognostic indicators of the two pathologies are different, direct comparisons between iNTS and TF in the literature remain scarce. The purpose of this study was to analyse and compare demographic, clinical features and outcome of hospitalized patients with TF and iNTS. Demographic, clinical features and outcome were retrospectively analysed in a series of patients hospitalized between 2007 and 2012. A total of 33 patients were enrolled, including 13 with established TF and 20 with iNTS. No differences between TF and iNTS patients were observed in incidence of fever, abdominal cramps, diarrhoea, headache, nausea and vomiting and duration of antibiotic therapy (≤ 7 days in both groups). Although the clinical outcome of TF patients was identical to that of iNTS patients, including incidence of complications, length of hospitalization and mortality (1/13 (7.7%) vs 2/20 (10%), P = 0.43), comorbidities were less frequent in the TF group than in the iNTS group (2/13 vs 15/20, P = 0.003). The clinical profile and outcome of TF patients are similar to those with iNTS. Although comorbidities are more often associated with iNTS, the results of our study suggest that clinical management of these two diseases should remain similar.

Typhoid Intestinal Perforation: 24 Perforations in One Patient

African Journals Online (AJOL)

Intestinal perforation is a common cause of peritonitis necessitating emergency surgical intervention. Perforation ... Mortality rates of typhoid intestinal perforation (TIP) cases are ... may be obscured clinical features with resultant delays in.

Estimated percentage of typhoid fever in adult pakistani population (TAP) study

International Nuclear Information System (INIS)

Mehboob, F.; Arshad, A.; Firdous, S.; Ahmed, S.; Rehma, S.

2013-01-01

Typhoid fever is a serious infection with high morbidity and mortality in untreated cases. It is one of the very common infections in developing countries due to various factors involving hygiene and sanitation. Objective: To determine the estimated percentage of typhoid fever in Pakistani population and to find the commonly prescribed antibiotics for the disease. Material and Methods: This cross sectional study was conducted on 1036 patients, selected from forty five general practitioner clinics, between June to October 2010. Patients of > 18 years of age with > 3 days history of fever (> 100 degree F) and high index of suspicion for typhoid fever were tested for typhoid fever using Typhidot kits and positive cases were recruited for monitoring response to treatment. The febrile patients with clear cut history of urinary or respiratory infect-ion, hypovolemic shock or hepatobiliary disease were excluded and not tested by typhidot kit. The antibiotics prescribed to study population by various general practitioners were noted. Data was analysed on SPSS. Results were expressed in percentages and proportions. Results: Total 1036 patients were recruited. Typhoidot test was negative in 63.9% and positive in 36.1% patients with highest percentages of positive cases in Karachi, Rawalpindi and Hyderabad. The maximum number of cases were reported in summer season especially from June to August. Most of the patients were between ages of 19 - 39 years. The commonest anti-biotics prescribed were Ofloxacin, Ciprofloxacin and Levofloxacin. Conclusion: Typhoid fever is very common infection in Pakistan caused by Salmonella typhi which is transmitted among humans through faecooral route. Disease can be controlled not only by antibiotics like fluoroquinolones but by patient education, improvement in hygiene and sanitation, safe supply of clean drinking water and prophylactic vaccination as well. However, timely diagnosis and appropriate management with proper antibiotics is the key

Estimated percentage of typhoid fever in adult pakistani population (TAP) study

Energy Technology Data Exchange (ETDEWEB)

Mehboob, F.; Arshad, A.; Firdous, S.; Ahmed, S.; Rehma, S. [Mayo Hospital, Lahore (Pakistan). Dept. of Medicine

2013-01-15

Typhoid fever is a serious infection with high morbidity and mortality in untreated cases. It is one of the very common infections in developing countries due to various factors involving hygiene and sanitation. Objective: To determine the estimated percentage of typhoid fever in Pakistani population and to find the commonly prescribed antibiotics for the disease. Material and Methods: This cross sectional study was conducted on 1036 patients, selected from forty five general practitioner clinics, between June to October 2010. Patients of > 18 years of age with > 3 days history of fever (> 100 degree F) and high index of suspicion for typhoid fever were tested for typhoid fever using Typhidot kits and positive cases were recruited for monitoring response to treatment. The febrile patients with clear cut history of urinary or respiratory infect-ion, hypovolemic shock or hepatobiliary disease were excluded and not tested by typhidot kit. The antibiotics prescribed to study population by various general practitioners were noted. Data was analysed on SPSS. Results were expressed in percentages and proportions. Results: Total 1036 patients were recruited. Typhoidot test was negative in 63.9% and positive in 36.1% patients with highest percentages of positive cases in Karachi, Rawalpindi and Hyderabad. The maximum number of cases were reported in summer season especially from June to August. Most of the patients were between ages of 19 - 39 years. The commonest anti-biotics prescribed were Ofloxacin, Ciprofloxacin and Levofloxacin. Conclusion: Typhoid fever is very common infection in Pakistan caused by Salmonella typhi which is transmitted among humans through faecooral route. Disease can be controlled not only by antibiotics like fluoroquinolones but by patient education, improvement in hygiene and sanitation, safe supply of clean drinking water and prophylactic vaccination as well. However, timely diagnosis and appropriate management with proper antibiotics is the key

The Molecular and Spatial Epidemiology of Typhoid Fever in Rural Cambodia.

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Duy Pham Thanh

2016-06-01

Full Text Available Typhoid fever, caused by the bacterium Salmonella Typhi, is an endemic cause of febrile disease in Cambodia. The aim of this study was to better understand the epidemiology of pediatric typhoid fever in Cambodia. We accessed routine blood culture data from Angkor Hospital for Children (AHC in Siem Reap province between 2007 and 2014, and performed whole genome sequencing (WGS on the isolated bacteria to characterize the S. Typhi population. The resulting phylogenetic information was combined with conventional epidemiological approaches to investigate the spatiotemporal distribution of S. Typhi and population-level risk factors for reported disease. During the study period, there were 262 cases of typhoid within a 100 km radius of AHC, with a median patient age of 8.2 years (IQR: 5.1-11.5 years. The majority of infections occurred during the rainy season, and commune incidences as high as 11.36/1,000 in children aged <15 years were observed over the study period. A population-based risk factor analysis found that access to water within households and increasing distance from Tonle Sap Lake were protective. Spatial mapping and WGS provided additional resolution for these findings, and confirmed that proximity to the lake was associated with discrete spatiotemporal disease clusters. We confirmed the dominance of MDR H58 S. Typhi in this population, and found substantial evidence of diversification (at least seven sublineages within this single lineage. We conclude that there is a substantial burden of pediatric typhoid fever in rural communes in Cambodia. Our data provide a platform for additional population-based typhoid fever studies in this location, and suggest that this would be a suitable setting in which to introduce a school-based vaccination programme with Vi conjugate vaccines.

High dose rate versus low dose rate brachytherapy for oral cancer--a meta-analysis of clinical trials.

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Zhenxing Liu

Full Text Available To compare the efficacy and safety of high dose rate (HDR and low dose rate (LDR brachytherapy in treating early-stage oral cancer.A systematic search of MEDLINE, EMBASE and Cochrane Library databases, restricted to English language up to June 1, 2012, was performed to identify potentially relevant studies.Only randomized controlled trials (RCT and controlled trials that compared HDR to LDR brachytherapy in treatment of early-stage oral cancer (stages I, II and III were of interest.Two investigators independently extracted data from retrieved studies and controversies were solved by discussion. Meta-analysis was performed using RevMan 5.1. One RCT and five controlled trials (607 patients: 447 for LDR and 160 for HDR met the inclusion criteria. The odds ratio showed no statistically significant difference between LDR group and HDR group in terms of local recurrence (OR = 1.12, CI 95% 0.62-2.01, overall mortality (OR = 1.01, CI 95% 0.61-1.66 and Grade 3/4 complications (OR = 0.86, CI 95% 0.52-1.42.This meta-analysis indicated that HDR brachytherapy was a comparable alternative to LDR brachytherapy in treatment of oral cancer. HDR brachytherapy might become a routine choice for early-stage oral cancer in the future.

PHARMACOKINETICS OF SINGLE-DOSE ORALLY ADMINISTERED CIPROFLOXACIN IN CALIFORNIA SEA LIONS (ZALOPHUS CALIFORNIANUS).

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Barbosa, Lorraine; Johnson, Shawn P; Papich, Mark G; Gulland, Frances

2015-06-01

Ciprofloxacin is commonly selected for clinical use due to its broad-spectrum efficacy and is a frequently administered antibiotic at The Marine Mammal Center, a marine mammal rehabilitation facility. Ciprofloxacin is used for treatment of California sea lions ( Zalophus californianus ) suffering from a variety of bacterial infections at doses extrapolated from other mammalian species. However, as oral absorption is variable both within and across species, a more accurate determination of appropriate dosage is needed to ensure effective treatment and avoid emergence of drug-resistant bacterial strains. A pharmacokinetic study was performed to assess plasma concentrations of ciprofloxacin in California sea lions after a single oral dose. Twenty healthy California sea lions received a single 10-mg/kg oral dose of ciprofloxacin administered in a herring fish. Blood was then collected at two of the following times from each individual: 0.5, 0.75, 1, 2, 4, 8, 10, 12, 18, and 24 hr postingestion. Plasma ciprofloxacin concentration was assessed via high-performance liquid chromatography. A population pharmacokinetics model demonstrated that an oral ciprofloxacin dose of 10 mg/kg achieved an area under the concentration vs. time curve of 6.01 μg hr/ml. Absorption was rapid, with ciprofloxacin detectable in plasma 0.54 hr after drug administration; absorption half-life was 0.09 hr. A maximum plasma concentration of 1.21 μg/ml was observed at 1.01 hr, with an elimination half-life of 3.09 hr. Ciprofloxacin administered orally at 10 mg/kg produced therapeutic antibacterial exposure for only some of the most susceptible bacterial organisms commonly isolated from California sea lions.

[Surveillance data on typhoid fever and paratyphoid fever in 2015, China].

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Liu, F F; Zhao, S L; Chen, Q; Chang, Z R; Zhang, J; Zheng, Y M; Luo, L; Ran, L; Liao, Q H

2017-06-10

Objective: Through analyzing the surveillance data on typhoid fever and paratyphoid fever in 2015 to understand the related epidemiological features and most possible clustering areas of high incidence. Methods: Individual data was collected from the passive surveillance program and analyzed by descriptive statistic method. Characteristics on seasonal, regional and distribution of the diseases were described. Spatial-temporal clustering characteristics were estimated, under the retrospective space-time method. Results: A total of 8 850 typhoid fever cases were reported from the surveillance system, with incidence rate as 0.65/100 000. The number of paratyphoid fever cases was 2 794, with incidence rate as 0.21/100 000. Both cases of typhoid fever and paratyphoid fever occurred all year round, with high epidemic season from May to October. Most cases involved farmers (39.68 % ), children (15.89 % ) and students (12.01 % ). Children under 5 years showed the highest incidence rate. Retrospective space-time analysis for provinces with high incidence rates would include Yunnan, Guangxi, Guizhou, Hunan and Guangdong, indicating the first and second class clusters were mainly distributed near the bordering adjacent districts and counties among the provinces. Conclusion: In 2015, the prevalence rates of typhoid fever and paratyphoid fever were low, however with regional high prevalence areas. Cross regional transmission existed among provinces with high incidence rates which might be responsible for the clusters to appear in these areas.

Oral dosing by voluntary  administration of jellybeans. Refinement and reduction of variability

DEFF Research Database (Denmark)

Pakula, Malgorzata Maria; Dagnæs-Hansen, Frederik

2016-01-01

Administration of substances by oral gavage is a common procedure in biomedical research involving laboratory animals, however although highly efficient, the procedure includes fixation of the animals and is technically challenging. Oral gavage is a precise way to dose animals, however it may ind...

Simple, rapid, and affordable point-of-care test for the serodiagnosis of typhoid fever

NARCIS (Netherlands)

Pastoor, Rob; Hatta, Mochammad; Abdoel, Theresia H.; Smits, Henk L.

2008-01-01

We developed a point-of-care test for the serodiagnosis of typhoid fever in the format of an immunochromatographic lateral flow assay. The flow assay for typhoid fever is based on the detection of Salmonella enterica serotype Typhi lipopolysaccharide-specific immunoglobulin M (IgM) antibodies. The

Dengue hemorrhagic fever and typhoid fever association based on spatial standpoint using scan statistics in DKI Jakarta

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Hervind, Widyaningsih, Y.

2017-07-01

Concurrent infection with multiple infectious agents may occur in one patient, it appears frequently in dengue hemorrhagic fever (DHF) and typhoid fever. This paper depicted association between DHF and typhoid based on spatial point of view. Since paucity of data regarding dengue and typhoid co-infection, data that be used are the number of patients of those diseases in every district (kecamatan) in Jakarta in 2014 and 2015 obtained from Jakarta surveillance website. Poisson spatial scan statistics is used to detect DHF and typhoid hotspots area district in Jakarta separately. After obtain the hotspot, Fisher's exact test is applied to validate association between those two diseases' hotspot. The result exhibit hotspots of DHF and typhoid are located around central Jakarta. The further analysis used Poisson space-time scan statistics to reveal the hotspot in term of spatial and time. DHF and typhoid fever more likely occurr from January until May in the area which is relatively similar with pure spatial result. Preventive action could be done especially in the hotspot areas and it is required further study to observe the causes based on characteristics of the hotspot area.

Occlusion-amblyopia following high dose oral levodopa combined with part time patching

OpenAIRE

Mihir Kothari

2014-01-01

Part time occlusion therapy is not reported to cause occlusion (reverse) amblyopia. However, when combined with high dose oral levodopa, an increase in the plasticity of the visual cortex can lead to occlusion amblyopia. In this case report, we describe a six year old child who developed occlusion amblyopia following part time patching combined with oral levodopa.

Occlusion-amblyopia following high dose oral levodopa combined with part time patching.

Science.gov (United States)

Kothari, Mihir

2014-12-01

Part time occlusion therapy is not reported to cause occlusion (reverse) amblyopia. However, when combined with high dose oral levodopa, an increase in the plasticity of the visual cortex can lead to occlusion amblyopia. In this case report, we describe a six year old child who developed occlusion amblyopia following part time patching combined with oral levodopa.

Antimicrobial susceptibility pattern in children with typhoid fever and serotype of Salmonella typhi in Jakarta

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Mirari Prasadajudio, Mulya Rahma Karyanti, Lia Waslia

2017-03-01

Full Text Available Objectives: Indonesia is known for high incidence of typhoid fever especially in children. This study aimed to observe antibiotic susceptibility in circulating Salmonella typhi serotypes in children with typhoid. Methods: A cross sectional study design was conducted. A total of 142 blood samples from children between 1-18 years old clinically diagnosed with suspected typhoid fever were recruited between January 2012 and July 2013 from six health centers in Jakarta. Confirmed cases were retrieved based on S. typhi isolate finding in blood culture. Antimicrobial susceptibility was investigated and PCR was used to detect S. typhi serotypes using fliB, fliC and aroC genes. Results: The prevalence of confirmed typhoid case based on isolate finding was 22 (15.5%. Twenty of S. typhi isolates expressed fliC gene carrying H:d allele, the other two expressed j allele, while only two samples expressed fliB, all showed no difference in pathogenicity and antimicrobial resistance. Conclusions: Circulating serotypes found in typhoid children in Jakarta, Indonesia are still susceptible even to the firstline antimicrobials. Thus, chloramphenicol, ampicillin and co-trimoxazole are still recommended. J Microbiol Infect Dis 2017; 7(1: 29-35

The use of antibiotics in hospitalized adult typhoid patients in an Indonesian hospital

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Anggita Bunga Anggraini

2014-08-01

Full Text Available AbstrakLatar belakang:Demam tifoid menduduki peringkat ke tiga dari 10 besar penyakit terbanyak pada pasien rawat inap di rumah sakit (RS di Indonesia pada tahun 2010. Selain itu terdapat peningkatan resistensi dan kasus-kasus karier, dan relaps. Penelitian ini menyajikan hasil analisis data tentang penggunaan antibiotik pada pasien tifoid dewasa rawat inap di suatu RS di Indonesia. Metode: Data penelitian diekstrak dari rekam medik pasien tifoid dewasa yang dirawat inap di RS PMI Bogor periode Juli-Desember 2012. Analisis dilakukan dengan kualitatif (DU90% dan kuantitatif (DDD/shr dengan menggunakan metode ATC/DDD. Hasil: Dari 459 pasien tifoid dewasa rawat inap diperoleh DDD/shr pasien tifoid dewasa rawat inap yang menggunakan antibiotik selama dari Juli sampai Desember 2012 sebesar 6,35 DDD/shr. Seftriakson merupakan antibiotika yang dipakai tertinggi yang setara 4,10 DDD/shr, yang berarti bahwa di antara 100 pasien tifoid, 4 pasien memakai seftriakson 2 g setiap hari. Selanjutnya, obat pada segmen 10% lebih banyak dibandingkan pada segmen 90%. Di antara 26 jenis antibiotika, 7 jenis di antaranya termasuk pada segmen DU 90% yaitu seftriakson (64,54%; levofloksasin (13,90%; ciprofloksasin (3,57%; meropenem (2,80%; metronidazol (2,52%; ampisilin-sulbaktam (1,65%; dan sefditoren pivoksil (1,60%.Kesimpulan:Antibiotik seftriakson yang paling banyak digunakan pada perawatan tifoid pasien dewasa rawat inap di rumah sakit. (Health Science Indones 2014;1:40-3Kata kunci:antibiotik, tifoid, ATC/DDD, DU 90%AbstractBackground: Typhoid fever was the third ranked disease among the top 10 diseases in hospitalized patients in Indonesia in 2011. There were increased drug resistance, increased number of carrier, and number of relapse cases. This study aimed to analyze the use of antibiotics in hospitalized adult typhoid patients in a hospital in Indonesia. Methods: The data were extracted from medical records of drug use in adult typhoid patients hospitalized

Usefulness of low dose oral contrast media in FDG PET/CT

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An, Y. S.; Yun, J. G.; Lee, M. H.; Cho, C. W.; Yun, S. N [Ajou University Medical Center, Suwon (Korea, Republic of)

2004-07-01

Oral contrast media might help in interpreting PET/CT images, allowing better discrimination between physiologic and pathologic abdominal uptake. The aim of this study was to evaluate the usefulness of low dose oral contrast on FDG PET/CT. A total of 435 cancer patients received 200mL of oral Barium with water(200mL) immediately before FDG injection. PET images were reconstructed using attenuation correction and iterative reconstruction. The FDG uptake in gastrointestinal(GI) tract were analyzed by visual and semiquantitative method in transaxial, coronal and sagittal planes. Seventy patients(16%, 113 sites) of 435 images showed high FDG uptake(pSUV>4.0) : 50(74%, 84 sites) with diffuse uptake and 20(26%, 29sites) with focal uptake. The most common distribution site of oral contrast media was small bowel (n=27, 39%) and others were small bowel with transverse colon(n=6, 8%), small bowel with ascending and sigmoid colon(n=6, 8%) and etc. In PET/CT images, FDG uptake coexisted with oral contrast was showed in 26 patients(54%) with diffuse pattern and 9(45%) with focal pattern, and by sites, those were 38(45%) and 9(31%), respectively. In small bowel regions, the most common distribution site, the proportion of coexistence reached as high as 61% (29 in the total 47 sites). Application of low dose contrast agent can be helpful in the evaluation of intestinal uptake in FDG PET/CT image.

Usefulness of low dose oral contrast media in FDG PET/CT

International Nuclear Information System (INIS)

An, Y. S.; Yun, J. G.; Lee, M. H.; Cho, C. W.; Yun, S. N

2004-01-01

Oral contrast media might help in interpreting PET/CT images, allowing better discrimination between physiologic and pathologic abdominal uptake. The aim of this study was to evaluate the usefulness of low dose oral contrast on FDG PET/CT. A total of 435 cancer patients received 200mL of oral Barium with water(200mL) immediately before FDG injection. PET images were reconstructed using attenuation correction and iterative reconstruction. The FDG uptake in gastrointestinal(GI) tract were analyzed by visual and semiquantitative method in transaxial, coronal and sagittal planes. Seventy patients(16%, 113 sites) of 435 images showed high FDG uptake(pSUV>4.0) : 50(74%, 84 sites) with diffuse uptake and 20(26%, 29sites) with focal uptake. The most common distribution site of oral contrast media was small bowel (n=27, 39%) and others were small bowel with transverse colon(n=6, 8%), small bowel with ascending and sigmoid colon(n=6, 8%) and etc. In PET/CT images, FDG uptake coexisted with oral contrast was showed in 26 patients(54%) with diffuse pattern and 9(45%) with focal pattern, and by sites, those were 38(45%) and 9(31%), respectively. In small bowel regions, the most common distribution site, the proportion of coexistence reached as high as 61% (29 in the total 47 sites). Application of low dose contrast agent can be helpful in the evaluation of intestinal uptake in FDG PET/CT image

Cost of illness due to typhoid Fever in pemba, zanzibar, East Africa.

Science.gov (United States)

Riewpaiboon, Arthorn; Piatti, Moritz; Ley, Benedikt; Deen, Jacqueline; Thriemer, Kamala; von Seidlein, Lorenz; Salehjiddawi, Mohammad; Busch, Clara Jana-Lui; Schmied, Wolfgang H; Ali, Said Mohammed; The Typhoid Economic Study Group GiDeok Pak Leon R Ochiai Mahesh K Puri Na Yoon Chang Thomas F Wierzba And John D Clemens

2014-09-01

The aim of this study was to estimate the economic burden of typhoid fever in Pemba, Zanzibar, East Africa. This study was an incidence-based cost-of-illness analysis from a societal perspective. It covered new episodes of blood culture-confirmed typhoid fever in patients presenting at the outpatient or inpatient departments of three district hospitals between May 2010 and December 2010. Cost of illness was the sum of direct costs and costs for productivity loss. Direct costs covered treatment, travel, and meals. Productivity costs were loss of income by patients and caregivers. The analysis included 17 episodes. The mean age of the patients, was 23 years (range=5-65, median=22). Thirty-five percent were inpatients, with a mean of 4.75 days of hospital stay (range=3-7, median=4.50). The mean cost for treatment alone during hospital care was US$ 21.97 at 2010 prices (US$ 1=1,430.50 Tanzanian Shilling─TSH). The average societal cost was US$ 154.47 per typhoid episode. The major expenditure was productivity cost due to lost wages of US$ 128.02 (83%). Our results contribute to the further economic evaluation of typhoid fever vaccination in Zanzibar and other sub-Saharan African countries.

Pharmacokinetics of voriconazole after oral administration of single and multiple doses in Hispaniolan Amazon parrots (Amazona ventralis).

Science.gov (United States)

Sanchez-Migallon Guzman, David; Flammer, Keven; Papich, Mark G; Grooters, Amy M; Shaw, Shannon; Applegate, Jeff; Tully, Thomas N

2010-04-01

To determine the pharmacokinetics and safety of voriconazole administered orally in single and multiple doses in Hispaniolan Amazon parrots (Amazona ventralis). 15 clinically normal adult Hispaniolan Amazon parrots. Single doses of voriconazole (12 or 24 mg/kg) were administered orally to 15 and 12 birds, respectively; plasma voriconazole concentrations were determined at intervals via high-pressure liquid chromatography. In a multiple-dose trial, voriconazole (18 mg/kg) or water was administered orally to 6 and 4 birds, respectively, every 8 hours for 11 days (beginning day 0); trough plasma voriconazole concentrations were evaluated on 3 days. Birds were monitored daily, and clinicopathologic variables were evaluated before and after the trial. Voriconazole elimination half-life was short (0.70 to 1.25 hours). In the single-dose experiments, higher drug doses yielded proportional increases in the maximum plasma voriconazole concentration (C(max)) and area under the curve (AUC). In the multiple-dose trial, C(max), AUC, and plasma concentrations at 2 and 4 hours were decreased on day 10, compared with day 0 values; however, there was relatively little change in terminal half-life. With the exception of 1 voriconazole-treated parrot that developed polyuria, adverse effects were not evident. In Hispaniolan Amazon parrots, oral administration of voriconazole was associated with proportional kinetics following administration of single doses and a decrease in plasma concentration following administration of multiple doses. Oral administration of 18 mg of voriconazole/kg every 8 hours would require adjustment to maintain therapeutic concentrations during long-term treatment. Safety and efficacy of voriconazole treatment in this species require further investigation.

Revisiting typhoid fever surveillance in low and middle income countries: lessons from systematic literature review of population-based longitudinal studies.

Science.gov (United States)

Mogasale, Vittal; Mogasale, Vijayalaxmi V; Ramani, Enusa; Lee, Jung Seok; Park, Ju Yeon; Lee, Kang Sung; Wierzba, Thomas F

2016-01-29

The control of typhoid fever being an important public health concern in low and middle income countries, improving typhoid surveillance will help in planning and implementing typhoid control activities such as deployment of new generation Vi conjugate typhoid vaccines. We conducted a systematic literature review of longitudinal population-based blood culture-confirmed typhoid fever studies from low and middle income countries published from 1(st) January 1990 to 31(st) December 2013. We quantitatively summarized typhoid fever incidence rates and qualitatively reviewed study methodology that could have influenced rate estimates. We used meta-analysis approach based on random effects model in summarizing the hospitalization rates. Twenty-two papers presented longitudinal population-based and blood culture-confirmed typhoid fever incidence estimates from 20 distinct sites in low and middle income countries. The reported incidence and hospitalizations rates were heterogeneous as well as the study methodology across the sites. We elucidated how the incidence rates were underestimated in published studies. We summarized six categories of under-estimation biases observed in these studies and presented potential solutions. Published longitudinal typhoid fever studies in low and middle income countries are geographically clustered and the methodology employed has a potential for underestimation. Future studies should account for these limitations.

Occlusion-amblyopia following high dose oral levodopa combined with part time patching

Directory of Open Access Journals (Sweden)

Mihir Kothari

2014-01-01

Full Text Available Part time occlusion therapy is not reported to cause occlusion (reverse amblyopia. However, when combined with high dose oral levodopa, an increase in the plasticity of the visual cortex can lead to occlusion amblyopia. In this case report, we describe a six year old child who developed occlusion amblyopia following part time patching combined with oral levodopa.

Cases of typhoid fever in Copenhagen region

DEFF Research Database (Denmark)

Barrett, Freja Cecille; Knudsen, Jenny Dahl; Johansen, Isik Somuncu

2013-01-01

Typhoid fever is a systemic illness which in high-income countries mainly affects travellers. The incidence is particularly high on the Indian subcontinent. Travellers who visit friends and relatives (VFR) have been shown to have a different risk profile than others. We wished to identify main...

Results in patients treated with high-dose-rate interstitial brachytherapy for oral tongue cancer

International Nuclear Information System (INIS)

Yamamoto, Michinori; Shirane, Makoto; Ueda, Tsutomu; Miyahara, Nobuyuki

2006-01-01

Eight patients were treated with high-dose-rate interstitial brachytherapy for oral tongue cancer between September 2000 and August 2004. The patient distribution was 1 T1, 5 T2, 1 T3, and 1 T4a. Patients received 50-60 Gy in 10 fractions over seven days with high-dose-rate brachytherapy. Six of the eight patients were treated with a combination of external beam radiotherapy (20-30 Gy) and interstitial brachytherapy. The two-year primary local control rate was 83% for initial case. High-dose-rate brachytherapy was performed safely even for an aged person, and was a useful treatment modality for oral tongue cancer. (author)

Pharmacokinetics of orally administered low-dose rapamycin in healthy dogs.

Science.gov (United States)

Larson, Jeanne C; Allstadt, Sara D; Fan, Timothy M; Khanna, Chand; Lunghofer, Paul J; Hansen, Ryan J; Gustafson, Daniel L; Legendre, Alfred M; Galyon, Gina D; LeBlanc, Amy K; Martin-Jimenez, Tomas

2016-01-01

To determine the pharmacokinetics of orally administered rapamycin in healthy dogs. 5 healthy purpose-bred hounds. The study consisted of 2 experiments. In experiment 1, each dog received rapamycin (0.1 mg/kg, PO) once; blood samples were obtained immediately before and at 0.5, 1, 2, 4, 6, 12, 24, 48, and 72 hours after administration. In experiment 2, each dog received rapamycin (0.1 mg/kg, PO) once daily for 5 days; blood samples were obtained immediately before and at 3, 6, 24, 27, 30, 48, 51, 54, 72, 75, 78, 96, 96.5, 97, 98, 100, 102, 108, 120, 144, and 168 hours after the first dose. Blood rapamycin concentration was determined by a validated liquid chromatography-tandem mass spectrometry assay. Pharmacokinetic parameters were determined by compartmental and noncompartmental analyses. Mean ± SD blood rapamycin terminal half-life, area under the concentration-time curve from 0 to 48 hours after dosing, and maximum concentration were 38.7 ± 12.7 h, 140 ± 23.9 ng•h/mL, and 8.39 ± 1.73 ng/mL, respectively, for experiment 1, and 99.5 ± 89.5 h, 126 ± 27.1 ng•h/mL, and 5.49 ± 1.99 ng/mL, respectively, for experiment 2. Pharmacokinetic parameters for rapamycin after administration of 5 daily doses differed significantly from those after administration of 1 dose. Results indicated that oral administration of low-dose (0.1 mg/kg) rapamycin to healthy dogs achieved blood concentrations measured in nanograms per milliliter. The optimal dose and administration frequency of rapamcyin required to achieve therapeutic effects in tumor-bearing dogs, as well as toxicity after chronic dosing, need to be determined.

Safety, immunogenicity and dose ranging of a new Vi-CRM₁₉₇ conjugate vaccine against typhoid fever: randomized clinical testing in healthy adults.

Directory of Open Access Journals (Sweden)

Pierre van Damme

Full Text Available Typhoid fever causes more than 21 million cases of disease and 200,000 deaths yearly worldwide, with more than 90% of the disease burden being reported from Asia. Epidemiological data show high disease incidence in young children and suggest that immunization programs should target children below two years of age: this is not possible with available vaccines. The Novartis Vaccines Institute for Global Health developed a conjugate vaccine (Vi-CRM₁₉₇ for infant vaccination concomitantly with EPI vaccines, either starting at 6 weeks with DTP or at 9 months with measles vaccine. We report the results from a Phase 1 and a Phase 2 dose ranging trial with Vi-CRM₁₉₇ in European adults.Following randomized blinded comparison of single vaccination with either Vi-CRM₁₉₇ or licensed polysaccharide vaccines (both containing 25·0 µg of Vi antigen, a randomised observer blinded dose ranging trial was performed in the same center to compare three concentrations of Vi-CRM₁₉₇ (1·25 µg, 5·0 µg and 12·5 µg of Vi antigen with the polysaccharide vaccine.All vaccines were well tolerated. Compared to the polysaccharide vaccine, Vi-CRM₁₉₇ induced a higher incidence of mild to moderate short lasting local pain. All Vi-CRM₁₉₇ formulations induced higher Vi antibody levels compared to licensed control, with clear dose response relationship.Vi-CRM₁₉₇ did not elicit safety concerns, was highly immunogenic and is therefore suitable for further clinical testing in endemic populations of South Asia.ClinicalTrials.gov NCT01123941 NCT01193907.

A large outbreak of typhoid fever associated with a high rate of intestinal perforation in Kasese District, Uganda, 2008-2009.

Science.gov (United States)

Neil, Karen P; Sodha, Samir V; Lukwago, Luswa; O-Tipo, Shikanga; Mikoleit, Matthew; Simington, Sherricka D; Mukobi, Peter; Balinandi, Stephen; Majalija, Samuel; Ayers, Joseph; Kagirita, Atek; Wefula, Edward; Asiimwe, Frank; Kweyamba, Vianney; Talkington, Deborah; Shieh, Wun-Ju; Adem, Patricia; Batten, Brigid C; Zaki, Sherif R; Mintz, Eric

2012-04-01

Salmonella enterica serovar Typhi (Salmonella Typhi) causes an estimated 22 million typhoid fever cases and 216 000 deaths annually worldwide. In Africa, the lack of laboratory diagnostic capacity limits the ability to recognize endemic typhoid fever and to detect outbreaks. We report a large laboratory-confirmed outbreak of typhoid fever in Uganda with a high proportion of intestinal perforations (IPs). A suspected case of typhoid fever was defined as fever and abdominal pain in a person with either vomiting, diarrhea, constipation, headache, weakness, arthralgia, poor response to antimalarial medications, or IP. From March 4, 2009 to April 17, 2009, specimens for blood and stool cultures and serology were collected from suspected cases. Antimicrobial susceptibility testing and pulsed-field gel electrophoresis (PFGE) were performed on Salmonella Typhi isolates. Surgical specimens from patients with IP were examined. A community survey was conducted to characterize the extent of the outbreak. From December 27, 2007 to July 30, 2009, 577 cases, 289 hospitalizations, 249 IPs, and 47 deaths from typhoid fever occurred; Salmonella Typhi was isolated from 27 (33%) of 81 patients. Isolates demonstrated multiple PFGE patterns and uniform susceptibility to ciprofloxacin. Surgical specimens from 30 patients were consistent with typhoid fever. Estimated typhoid fever incidence in the community survey was 8092 cases per 100 000 persons. This typhoid fever outbreak was detected because of an elevated number of IPs. Underreporting of milder illnesses and delayed and inadequate antimicrobial treatment contributed to the high perforation rate. Enhancing laboratory capacity for detection is critical to improving typhoid fever control.

Use of a monophasic, low dose oral contraceptive in relation to mental functioning

NARCIS (Netherlands)

Deijen, J.B.; Jansen, W.A.; Klitsie, J.; Duyn, K.

1992-01-01

The objective of the study was to evaluate the effect of Minulet, a new low-dose oral contraceptive on mood in two groups and to compare the effect with a control group of women not taking oral contraceptives (OC). The women participating were between 16 and 45 years of age. They completed the

Diagnosis of imported Ugandan typhoid fever based on local outbreak information: A case report.

Science.gov (United States)

Ota, Shinichiro; Maki, Yohei; Mori, Kazuma; Hamamoto, Takaaki; Kurokawa, Atsushi; Ishihara, Masashi; Yamamoto, Takayuki; Imai, Kazuo; Misawa, Kazuhisa; Yuki, Atsushi; Fujikura, Yuji; Maeda, Takuya; Kawana, Akihiko

2016-11-01

Re-emerging multidrug-resistant typhoid fever is becoming a worldwide threat, especially in East Africa. At the beginning of 2015, an outbreak of typhoid fever started in the capital city of Uganda, and 1940 suspected cases were reported by 5 March 2015. In this report, we describe a case of typhoid fever caused by a MDR strain with HIV infection and hemoglobin S-syndrome thalassemia in an Ugandan from Kampala City. It is essential to consider MDR strains of Salmonella enterica serovar Typhi infections, including fluoroquinolone-resistant strains, in patients from Africa and Southeast Asia. Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Clinical and epidemiological features of typhoid fever in Pemba, Zanzibar: assessment of the performance of the WHO case definitions.

Science.gov (United States)

Thriemer, Kamala; Ley, Benedikt; Ley, Benedikt B; Ame, Shaali S; Deen, Jaqueline L; Pak, Gi Deok; Chang, Na Yoon; Hashim, Ramadhan; Schmied, Wolfgang Hellmut; Busch, Clara Jana-Lui; Nixon, Shanette; Morrissey, Anne; Puri, Mahesh K; Ochiai, R Leon; Wierzba, Thomas; Clemens, John D; Ali, Mohammad; Jiddawi, Mohammad S; von Seidlein, Lorenz; Ali, Said M

2012-01-01

The gold standard for diagnosis of typhoid fever is blood culture (BC). Because blood culture is often not available in impoverished settings it would be helpful to have alternative diagnostic approaches. We therefore investigated the usefulness of clinical signs, WHO case definition and Widal test for the diagnosis of typhoid fever. Participants with a body temperature ≥37.5°C or a history of fever were enrolled over 17 to 22 months in three hospitals on Pemba Island, Tanzania. Clinical signs and symptoms of participants upon presentation as well as blood and serum for BC and Widal testing were collected. Clinical signs and symptoms of typhoid fever cases were compared to other cases of invasive bacterial diseases and BC negative participants. The relationship of typhoid fever cases with rainfall, temperature, and religious festivals was explored. The performance of the WHO case definitions for suspected and probable typhoid fever and a local cut off titre for the Widal test was assessed. 79 of 2209 participants had invasive bacterial disease. 46 isolates were identified as typhoid fever. Apart from a longer duration of fever prior to admission clinical signs and symptoms were not significantly different among patients with typhoid fever than from other febrile patients. We did not detect any significant seasonal patterns nor correlation with rainfall or festivals. The sensitivity and specificity of the WHO case definition for suspected and probable typhoid fever were 82.6% and 41.3% and 36.3 and 99.7% respectively. Sensitivity and specificity of the Widal test was 47.8% and 99.4 both forfor O-agglutinin and H- agglutinin at a cut-off titre of 1:80. Typhoid fever prevalence rates on Pemba are high and its clinical signs and symptoms are non-specific. The sensitivity of the Widal test is low and the WHO case definition performed better than the Widal test.

Open study of short course Fleroxacin for Typhoid and Paratyphoid Fever

Directory of Open Access Journals (Sweden)

R. H.H. Nelwan

2002-03-01

Full Text Available The objective of this study was to evaluate clinical and bacteriological effect of short course fleroxacin in uncomplicated typhoid and paratyphoid fever patients. Four hundred mg of fleroxacin was given oraly once daily for a period of 3 to 5 days. The diagnosis of typhoid and paratyphoid fever was established by clinical picture as well as blood culture or Widal serology test. Thirty patients in whom the clinical picture was confirmed as a typhoid or paratyphoid infection were eligible for this investigation. They consisted of 15 males and 15 females ranging in age from 18-38 years average 27.5 years of whom 18 were diagnosed by blood culture consisting of 16 S.typhi positive cases and two S.paratyphi A, while 12 other cases were positively confirmed by serial Widal agglutination serology. These cases suffered from fever between 3-14 days with a minimum recorded body temperature elevation of 38.5 degrees Celsius. Clinical response with defervescence of fever was obtained in the positive blood culture group within 3 days (8 patients including 2 cases positive for S.paratyphi A and within two additional days (5 days in the remaining 10 cases. In the twelve cases with a positive serology for typhoid fever a clinical response was obtained for defervescence within 3 days (6 cases with 4 of these cases were on 3 days of fleroxacin and 2 cases on 5 days of fleroxacin. In the remaining 6 serologic positive cases fever resolved after 4-6 days with an average of 5 days with one on 3 days of fleroxacin and the rest (5 cases on 5 days of fleroxacin. All positive blood culture cases reverted to negative after the fleroxacin course. No relapse or carrier state was recorded in this serie. It may be concluded that a 3 to 5 days closely monitored course of fleroxacin has excellent clinical as well as bacteriological efficacy in noncomplicated typhoid and paratyphoid fever. (Med J Indones 2002; 11: 41-7Keywords: fluoroquinolones, enteric infections, short

Risk Analysis of Typhoid Fever Based on Personal Hygiene and Street Food Consumption Habit at Home

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Hilda Nuruzzaman

2016-11-01

Full Text Available Typhoid fever is disease caused by Salmonella typhi bacteria transmission trought contaminated food and drink. Data from RSUD dr. Abdoer Rahem showing that from 2011–2013 typhoid fever case always increase and often happened to children age 5–14 years old. The objective research to analysis risk factor of typhoid fever according to snacking habit at school and at house of children age 7–12 years old. This research was observasional case control study. Data for case in this research are taken from medical record of ‘Unit Teratai’ for the past 1 year in RSUD dr. Abdoer Rahem Situbondo, whereas for control are case group. There are eighty person taken for this research as sample. This result was the risk of typhoid fever children which has habit of hand washing had after defecation at home OR 3.67 (1.29 < OR < 10.64, children which has habit of hand washing before eating had OR 4.33 (1.54 < OR < 12.44, children with short dirty fingernails had OR 7.79 (1.46 < OR < 46.18 frequent street food consumption OR 3.89 (1.39 < OR < 11.06, buy snack at food street OR 3.95 (1.40 < OR < 11.30, buy some snack with packing had OR 3.5 (1.26 < OR < 9.38. The conclusion is that habit hand washing after defecation, habit hand washing before eating, short dirty fingernail, frequent food street consumption, buy food street and buy some food with sealed packing can secrease the risk of typhoid fever for children age 7–12 years Keywords: typhoid fever, risk factor of typhoid fever, personal hygiene, street food consumption habit

Typhoid outbreak investigation in Dzivaresekwa, suburb of Harare

African Journals Online (AJOL)

abp

2014-08-18

Aug 18, 2014 ... typhoid fever carry the bacteria in their bloodstream and intestinal tract [1,2]. ... preparedness and response of the Harare City Health Department. Records of .... Treated shallow well water had residual chlorine of 0.1 mg/litre.

Single dose oral piroxicam for acute postoperative pain

Science.gov (United States)

Moore, R Andrew; Edwards, Jayne; Loke, Yoon; Derry, Sheena; McQuay, Henry J

2014-01-01

Background This is an updated version of the original Cochrane review published in Issue 2, 2000. Piroxicam is a non-steroidal anti-inflammatory drug (NSAID) with analgesic properties, and is used mainly for treating rheumatic disorders. Some drugs have been directly compared against each other within a trial setting to determine their relative efficacies, whereas other have not. It is possible, however, to compare analgesics indirectly by examining the effectiveness of each drug against placebo when used in similar clinical situations. Objectives To determine the analgesic efficacy and adverse effects of single-dose piroxicam compared with placebo in moderate to severe postoperative pain. To compare the effects of piroxicam with other analgesics. Search methods Published studies were identified from systematic searching of MEDLINE, Biological Abstracts, EMBASE, CENTRAL and the Oxford Pain Relief Database in December 2007. Additional studies were identified from the reference lists of retrieved reports. Selection criteria The following inclusion criteria were used: full journal publication, randomised placebo controlled trial, double-blind design, adult participants, postoperative pain of moderate to severe intensity at the baseline assessment, postoperative administration of oral or intramuscular piroxicam. Data collection and analysis Summed pain intensity and pain relief data were extracted and converted into dichotomous information to yield the number of participants obtaining at least 50% pain relief. This was used to calculate estimates of relative benefit and number-needed-to-treat-to-benefit (NNT) for one participant to obtain at least 50% pain relief. Information was collected on adverse effects and estimates of relative risk and number-needed-to-treat-to-harm (NNH) were calculated. Main results In this update no further studies were found. The original search identified three studies (141 participants) which compared oral piroxicam 20 mg with placebo and

Expression and function of S100A8/A9 (calprotectin) in human typhoid fever and the murine Salmonella model.

Science.gov (United States)

De Jong, Hanna K; Achouiti, Ahmed; Koh, Gavin C K W; Parry, Christopher M; Baker, Stephen; Faiz, Mohammed Abul; van Dissel, Jaap T; Vollaard, Albert M; van Leeuwen, Ester M M; Roelofs, Joris J T H; de Vos, Alex F; Roth, Johannes; van der Poll, Tom; Vogl, Thomas; Wiersinga, Willem Joost

2015-04-01

Typhoid fever, caused by the Gram-negative bacterium Salmonella enterica serovar Typhi, is a major cause of community-acquired bacteremia and death worldwide. S100A8 (MRP8) and S100A9 (MRP14) form bioactive antimicrobial heterodimers (calprotectin) that can activate Toll-like receptor 4, promoting lethal, endotoxin-induced shock and multi-organ failure. We aimed to characterize the expression and function of S100A8/A9 in patients with typhoid fever and in a murine invasive Salmonella model. S100A8/A9 protein levels were determined in acute phase plasma or feces from 28 Bangladeshi patients, and convalescent phase plasma from 60 Indonesian patients with blood culture or PCR-confirmed typhoid fever, and compared to 98 healthy control subjects. To functionally characterize the role of S100A8/A9, we challenged wildtype (WT) and S100A9-/- mice with S. Typhimurium and determined bacterial loads and inflammation 2- and 5- days post infection. We further assessed the antimicrobial function of recombinant S100A8/A9 on S. Typhimurium and S. Typhi replication in vitro. Typhoid fever patients demonstrated a marked increase of S100A8/A9 in acute phase plasma and feces and this increases correlated with duration of fever prior to admission. S100A8/A9 directly inhibited the growth of S. Typhimurium and S. Typhi in vitro in a dose and time dependent fashion. WT mice inoculated with S. Typhimurium showed increased levels of S100A8/A9 in both the liver and the systemic compartment but S100A9-/- mice were indistinguishable from WT mice with respect to bacterial growth, survival, and inflammatory responses, as determined by cytokine release, histopathology and organ injury. S100A8/A9 is markedly elevated in human typhoid, correlates with duration of fever prior to admission and directly inhibits the growth of S. Typhimurium and S. Typhi in vitro. Despite elevated levels in the murine invasive Salmonella model, S100A8/A9 does not contribute to an effective host response against S

Expression and function of S100A8/A9 (calprotectin in human typhoid fever and the murine Salmonella model.

Directory of Open Access Journals (Sweden)

Hanna K De Jong

2015-04-01

Full Text Available Typhoid fever, caused by the Gram-negative bacterium Salmonella enterica serovar Typhi, is a major cause of community-acquired bacteremia and death worldwide. S100A8 (MRP8 and S100A9 (MRP14 form bioactive antimicrobial heterodimers (calprotectin that can activate Toll-like receptor 4, promoting lethal, endotoxin-induced shock and multi-organ failure. We aimed to characterize the expression and function of S100A8/A9 in patients with typhoid fever and in a murine invasive Salmonella model.S100A8/A9 protein levels were determined in acute phase plasma or feces from 28 Bangladeshi patients, and convalescent phase plasma from 60 Indonesian patients with blood culture or PCR-confirmed typhoid fever, and compared to 98 healthy control subjects. To functionally characterize the role of S100A8/A9, we challenged wildtype (WT and S100A9-/- mice with S. Typhimurium and determined bacterial loads and inflammation 2- and 5- days post infection. We further assessed the antimicrobial function of recombinant S100A8/A9 on S. Typhimurium and S. Typhi replication in vitro. Typhoid fever patients demonstrated a marked increase of S100A8/A9 in acute phase plasma and feces and this increases correlated with duration of fever prior to admission. S100A8/A9 directly inhibited the growth of S. Typhimurium and S. Typhi in vitro in a dose and time dependent fashion. WT mice inoculated with S. Typhimurium showed increased levels of S100A8/A9 in both the liver and the systemic compartment but S100A9-/- mice were indistinguishable from WT mice with respect to bacterial growth, survival, and inflammatory responses, as determined by cytokine release, histopathology and organ injury.S100A8/A9 is markedly elevated in human typhoid, correlates with duration of fever prior to admission and directly inhibits the growth of S. Typhimurium and S. Typhi in vitro. Despite elevated levels in the murine invasive Salmonella model, S100A8/A9 does not contribute to an effective host response

Comparison of Strategies and Incidence Thresholds for Vi Conjugate Vaccines Against Typhoid Fever: A Cost-effectiveness Modeling Study.

Science.gov (United States)

Lo, Nathan C; Gupta, Ribhav; Stanaway, Jeffrey D; Garrett, Denise O; Bogoch, Isaac I; Luby, Stephen P; Andrews, Jason R

2018-02-12

Typhoid fever remains a major public health problem globally. While new Vi conjugate vaccines hold promise for averting disease, the optimal programmatic delivery remains unclear. We aimed to identify the strategies and associated epidemiologic conditions under which Vi conjugate vaccines would be cost-effective. We developed a dynamic, age-structured transmission and cost-effectiveness model that simulated multiple vaccination strategies with a typhoid Vi conjugate vaccine from a societal perspective. We simulated 10-year vaccination programs with (1) routine immunization of infants (aged typhoid fever and defined strategies as highly cost-effective by using the definition of a low-income country (defined as a country with a gross domestic product of $1045 per capita). We defined incidence as the true number of clinically symptomatic people in the population per year. Vi conjugate typhoid vaccines were highly cost-effective when administered by routine immunization activities through the EPI in settings with an annual incidence of >50 cases/100000 (95% uncertainty interval, 40-75 cases) and when administered through the EPI plus a catch-up campaign in settings with an annual incidence of >130 cases/100000 (95% uncertainty interval, 50-395 cases). The incidence threshold was sensitive to the typhoid-related case-fatality rate, carrier contribution to transmission, vaccine characteristics, and country-specific economic threshold for cost-effectiveness. Typhoid Vi conjugate vaccines would be highly cost-effective in low-income countries in settings of moderate typhoid incidence (50 cases/100000 annually). These results were sensitive to case-fatality rates, underscoring the need to consider factors contributing to typhoid mortality (eg, healthcare access and antimicrobial resistance) in the global vaccination strategy. © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America.

Orbital cellulitis in course of typhoid fever

International Nuclear Information System (INIS)

Nowacka, K.; Szreter, M.; Mikolajewicz, J.

1993-01-01

In 18 months girl with exophthalmus of the left eye and extensive swelling of the soft tissues in both orbits during continued fever was observed. Typhoid fever with a non-typical course and ophthalmic complications were diagnosed on the basis of serological tests. Complete cure after treatment with augmenting was obtained. (author)

Concentrations of amoxicillin and clindamycin in teeth following a single dose of oral medication.

Science.gov (United States)

Schüssl, Yvonne; Pelz, Klaus; Kempf, Jürgen; Otten, Jörg-Elard

2014-01-01

The main purpose of this study is the detection of amoxicillin and clindamycin concentrations in teeth. Eleven patients received 2 g of amoxicillin, and 11 patients received 600 mg of clindamycin in a single dose of oral medication at least 60 min prior to tooth extraction due to systemic diseases. The concentrations were determined in crowns and roots separately using liquid chromatography-tandem mass spectrometry (LC-MS-MS). Amoxicillin (13 samples) and clindamycin (12 samples) were detected in the samples of the root and crown preparations of the extracted teeth. The mean concentration of amoxicillin was 0.502 μg/g in the roots and 0.171 μg/g in the crowns. The mean concentration of clindamycin was 0.270 μg/g in the roots and 0.064 μg/g in the crowns. A single dose of oral amoxicillin and clindamycin leads to concentrations of both antibiotics in teeth which exceed the minimal inhibition concentration of some oral bacteria. The proof of antibacterial activity in dental hard tissue after oral single-dose application is new. The antimicrobial effect of amoxicillin and clindamycin concentrations in roots of teeth may be of clinical relevance to bacterial reinfection from dentinal tubules.

Typhi–Induced Septic Shock and Acute Respiratory Distress Syndrome in a Previously Healthy Teenage Patient Treated With High-Dose Dexamethasone

Directory of Open Access Journals (Sweden)

Melissa Brosset Ugas MD

2016-05-01

Full Text Available Typhoid fever is commonly characterized by fever and abdominal pain. Rare complications include intestinal hemorrhage, bowel perforation, delirium, obtundation, and septic shock. Herein we describe the case of a previously healthy 16-year-old male without history of travel, diagnosed with typhoid fever complicated by septic shock and acute respiratory distress syndrome treated with high-dose dexamethasone. This case details severe complications of typhoid fever that are uncommonly seen in developed countries, and the successful response to high-dose dexamethasone as adjunct therapy. High-dose dexamethasone treatment has reportedly decreased Salmonella Typhi mortality, but controlled studies specifically performed in children are lacking, and most reports of its use are over 30 years old and all have originated in developing countries. Providers should include Salmonella Typhi in the differential diagnosis of the pediatric patient with fever, severe abdominal pain, and enteritis, and be aware of its potentially severe complications and the limited data on safety and efficacy of adjunctive therapies that can be considered in addition to antibiotics.

Typhoid outbreak in Songkhla, Thailand 2009-2011: clinical outcomes, susceptibility patterns, and reliability of serology tests.

Directory of Open Access Journals (Sweden)

Wannee Limpitikul

Full Text Available OBJECTIVE: To determine the clinical manifestations and outcomes, the reliability of Salmonella enterica serotype Typhi (S ser. Typhi IgM and IgG rapid tests, and the susceptibility patterns and the response to treatment during the 2009-2011 typhoid outbreak in Songkhla province in Thailand. METHOD: The medical records of children aged <15 years with S ser. Typhi bacteremia were analysed. The efficacy of the typhoid IgM and IgG rapid tests and susceptibility of the S ser. Typhi to the current main antibiotics used for typhoid (amoxicillin, ampicillin, cefotaxime, ceftriaxone, co-trimoxazole, and ciprofloxacin, were evaluated. RESULTS: S ser. Typhi bacteremia was found in 368 patients, and all isolated strains were susceptible to all 6 antimicrobials tested. Most of the patients were treated with ciprofloxacin for 7-14 days. The median time (IQR of fever before treatment and duration of fever after treatment were 5 (4, 7 days and 4 (3, 5 days, respectively. Complications of ascites, lower respiratory symptoms, anemia (Hct <30%, and ileal perforation were found in 7, 7, 22, and 1 patients, respectively. None of the patients had recurrent infection or died. The sensitivities of the typhoid IgM and IgG tests were 58.3% and 25.6% respectively, and specificities were 74.1% and 50.5%, respectively. CONCLUSION: Most of the patients were diagnosed at an early stage and treated with a good outcome. All S ser. Typhi strains were susceptible to standard first line antibiotic typhoid treatment. The typhoid IgM and IgG rapid tests had low sensitivity and moderate specificity.

Rapid diagnostic tests for typhoid and paratyphoid (enteric) fever

Science.gov (United States)

Wijedoru, Lalith; Mallett, Sue; Parry, Christopher M

2017-01-01

Background Differentiating both typhoid (Salmonella Typhi) and paratyphoid (Salmonella Paratyphi A) infection from other causes of fever in endemic areas is a diagnostic challenge. Although commercial point-of-care rapid diagnostic tests (RDTs) for enteric fever are available as alternatives to the current reference standard test of blood or bone marrow culture, or to the widely used Widal Test, their diagnostic accuracy is unclear. If accurate, they could potentially replace blood culture as the World Health Organization (WHO)-recommended main diagnostic test for enteric fever. Objectives To assess the diagnostic accuracy of commercially available rapid diagnostic tests (RDTs) and prototypes for detecting Salmonella Typhi or Paratyphi A infection in symptomatic persons living in endemic areas. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register, MEDLINE, Embase, Science Citation Index, IndMED, African Index Medicus, LILACS, ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) up to 4 March 2016. We manually searched WHO reports, and papers from international conferences on Salmonella infections. We also contacted test manufacturers to identify studies. Selection criteria We included diagnostic accuracy studies of enteric fever RDTs in patients with fever or with symptoms suggestive of enteric fever living in endemic areas. We classified the reference standard used as either Grade 1 (result from a blood culture and a bone marrow culture) or Grade 2 (result from blood culture and blood polymerase chain reaction, or from blood culture alone). Data collection and analysis Two review authors independently extracted the test result data. We used a modified QUADAS-2 extraction form to assess methodological quality. We performed a meta-analysis when there were sufficient studies for the test and heterogeneity was reasonable. Main results Thirty-seven studies met the inclusion

Antibody response to the lipopolysaccharide and protein antigens of Salmonella typhi during typhoid infection. I. Measurement of serum antibodies by radioimmunoassay

Energy Technology Data Exchange (ETDEWEB)

Tsang, R S.W.; Chau, P Y; Lam, S K [Hong Kong Univ.; La Brooy, J T; Rowley, D [Adelaide Univ. (Australia)

1981-12-01

Serum antibody responses to the lipopolysaccharide and protein antigens of S. typhi in typhoid patients were studied using a solid-phase radioimmunoassay technique with /sup 125/I labelled anti-immunoglobulin antibody. Sera from 24 adult typhoid patients and 20 non-typhoid adult controls were compared. As a group, sera from typhoid patients showed increased IgA, IgG and IgM immunoglobulin levels and gave significantly higher anti-LPS and anti-protein antibody titres in all three major immunoglobulin classes than did non-typhoid controls. Levels of antibodies against LPS or protein in sera of typhoid patients were highly variable with a skew distribution. A good correlation was found between antibody titres to the LPS antigen and those to a protein antigen. No correlation, however, was found between the anti-LPS antibody titres measured by radioimmunoassay and the anti-O antibody titres measured by the Widal agglutination test. Titration of anti-LPS or anti-protein antibodies by radioimmunoassay was found to be more sensitive and specific than Widal test for the serological diagnosis of typhoid fever. The advantages of measuring antibody response by radioimmunoassay over conventional Widal test are discussed.

The role of abdominal ultrasound in the diagnosis of typhoid fever: an observational study.

Science.gov (United States)

Younis, Saeed Nadhim

2014-01-01

To study the usefulness of abdominal ultrasound in the diagnosis of typhoid fever and to determine the common ultrasound findings early in the course of the disease. Abdominal ultrasound examination was performed within the first week of initiation of symptoms in 350 cases with clinical diagnosis of typhoid fever. Subsequent ultrasound follow-up examination was done 15 days later (beginning of the third week). All the patients proved to have positive Widal test and Sallmonella culture. The study was performed in Erbil-Iraq from the period January 1993 to October 2010. The following ultrasound findings were reported: hepatomegaly (31.4%), prominent intrahepatic bile ducts (64.85%), splenomegaly (100%), mesenteric lymphadenopathy (42.85%), bowel wall thickening (35.71%), acalculous cholecystitis (16.28%), perforations (1.14%), and ascites in (3.4%). The current study showed that the findings are typical enough to justify initiation of treatment for typhoid fever when serology is equivocal and culture is negative, and is fairly safe to say that normal ultrasound examination early in the course of febrile illness rules out typhoid fever. Copyright © 2013 Elsevier Ltd. All rights reserved.

Pulmonary affectation in a patient with typhoid fever; Compromiso pulmonar en un paciente con fiebre tifoidea

Energy Technology Data Exchange (ETDEWEB)

Duenas C, Carmelo; Martinez, Adel; Maza, Augusto

1997-04-01

Typhoid fever is a rare disease in the USA with no more of 500 cases per year. In Latin America, it occurs four to five times more frequently. Pulmonary symptoms are found in less than 20% of the cases. The development of pneumonia is more common in immunocompromised patients. In last 10 years, the frequency of typhoid pneumonia has increased because of the HIV epidemic and the advance of other forms of immunosuppression. We presented the case of a young adult male with typhoid multilobar pneumonia who did not have VIH infection or any demonstrated immunosuppression.

Comparative pharmacokinetics of oxytetracycline in blunt-snout bream (Megalobrama amblycephala) with single and multiple-dose oral administration.

Science.gov (United States)

Li, Ru-Qin; Ren, Yu-Wei; Li, Jing; Huang, Can; Shao, Jun-Hui; Chen, Xiao-Xuan; Wu, Zhi-Xin

2015-06-01

Research into the pharmacokinetics and residue elimination of oxytetracycline (OTC) is important both to determine the optimal dosage regimens and to establish a safe withdrawal time in fish. A depletion study is presented here for OTC in Megalobrama amblycephala with a single-dose (100 mg/kg) and multiple-dose (100 mg/kg for five consecutive days) oral administration. The study was conducted at 25 °C. As a result, a one-compartment model was developed. For the single dose, the absorption half-life was 5.79, 9.40, 6.96, and 8.06 h in the plasma, liver, kidney, and muscle, respectively. However, the absorption half-life was 3.62, 7.33, 4.59, and 6.02 h with multiple-dose oral administration. The elimination half-time in the plasma, liver, kidney, and muscle was 58.63, 126.43, 65.1, and 58.85 h when M. amblycephala was treated with a single dose. However, the elimination half-time changed to 91.75, 214.87, 126.22, and 135.84 h with multiple-dose oral administration.

Social and Economic Burden Associated With Typhoid Fever in Kathmandu and Surrounding Areas: A Qualitative Study.

Science.gov (United States)

Kaljee, Linda M; Pach, Alfred; Garrett, Denise; Bajracharya, Deepak; Karki, Kshitu; Khan, Imran

2017-07-29

Typhoid fever is a significant contributor to infectious disease mortality and morbidity in low- and middle-income countries, particularly in South Asia. With increasing antimicrobial resistance, commonly used treatments are less effective and risks increase for complications and hospitalizations. During an episode of typhoid fever, households experience multiple social and economic costs that are often undocumented. In the current study, qualitative interview data from Kathmandu and surrounding areas provide important insights into the challenges that affect those who contract typhoid fever and their caregivers, families, and communities, as well as insight into prevention and treatment options for health providers and outreach workers. When considering typhoid fever cases confirmed by blood culture, our data reveal delays in healthcare access, financial and time costs burden on households, and the need to increase health literacy. These data also illustrate the impact of limited laboratory diagnostic equipment and tools on healthcare providers' abilities to distinguish typhoid fever from other febrile conditions and treatment challenges associated with antimicrobial resistance. In light of these findings, there is an urgent need to identify and implement effective preventive measures including vaccination policies and programs focused on at-risk populations and endemic regions such as Nepal. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Guaifenesin Pharmacokinetics Following Single‐Dose Oral Administration in Children Aged 2 to 17 Years

Science.gov (United States)

Thompson, Gary A.; Solomon, Gail; Albrecht, Helmut H.; Reitberg, Donald P.

2016-01-01

Abstract This study characterized guaifenesin pharmacokinetics in children aged 2 to 17 years (n = 40) who received a single oral dose of guaifenesin (age‐based doses of 100‐400 mg) 2 hours after breakfast. Plasma samples were obtained before and for 8 hours after dosing and analyzed for guaifenesin using liquid chromatography‐tandem mass spectrometry. Pharmacokinetic parameters were estimated using noncompartmental methods, relationships with age were assessed using linear regression, and dose proportionality was assessed on 95% confidence intervals. Based on the upper dose recommended in the monograph (for both children and adolescents), area under the curve from time zero to infinity and maximum plasma concentration both increased with age. However, when comparing the upper dose for children aged 2 to 11 years with the lower dose for adolescents aged 12 to 17 years, similar systemic exposure was observed. As expected due to increasing body size, oral clearance (CLo) and terminal volume of distribution (Vz/F) increased with age. Due to a larger increase in Vz/F than CLo, an increase in terminal exponential half‐life was also observed. Allometric scaling indicated no maturation‐related changes in CLo and Vz/F. PMID:26632082

Typhoid fever

DEFF Research Database (Denmark)

Wain, John; Hendriksen, Rene S.; Mikoleit, Matthew L.

2015-01-01

Control of typhoid fever relies on clinical information, diagnosis, and an understanding for the epidemiology of the disease. Despite the breadth of work done so far, much is not known about the biology of this human-adapted bacterial pathogen and the complexity of the disease in endemic areas...... with shifting trends in enteric fever. This knowledge is crucial, both to control the disease and to manage cases. Additionally, salmonella serovars that cause human infection can change over time and location. In areas of Asia, multidrug-resistant Salmonella enterica serovar Typhi (S Typhi) has been the main...... cause of enteric fever, but now S Typhi is being displaced by infections with drug-resistant S enterica serovar Paratyphi A. New conjugate vaccines are imminent and new treatments have been promised, but the engagement of local medical and public health institutions in endemic areas is needed to allow...

Application of a point-of-care test for the serodiagnosis of typhoid fever in Nigeria and the need for improved diagnostics

NARCIS (Netherlands)

Smith, Stella Ifeanyi; Bamidele, Moses; Fowora, Muinah; Goodluck, Helen T.; Omonigbehin, Emmanuel A.; Akinsinde, Kehinde A.; Fesobi, Toun; Pastoor, Rob; Abdoel, Theresia H.; Smits, Henk L.

2011-01-01

There is an urgent need for affordable point-of-care diagnostics for the differentiation of febrile illnesses and the confirmation of typhoid in endemic countries. Blood samples were collected from febrile patients with clinical suspicion of typhoid and screened for typhoid fever using the Widal and

Single-dose intravenous iron infusion or oral iron for treatment of fatigue after postpartum haemorrhage

DEFF Research Database (Denmark)

Holm, C; Thomsen, L L; Norgaard, A

2017-01-01

BACKGROUND AND OBJECTIVES: To evaluate the clinical efficacy of a single-dose intravenous infusion of iron isomaltoside compared with current treatment practice with oral iron measured by physical fatigue in women after postpartum haemorrhage. MATERIALS AND METHODS: Single-centre, open-label, ran......BACKGROUND AND OBJECTIVES: To evaluate the clinical efficacy of a single-dose intravenous infusion of iron isomaltoside compared with current treatment practice with oral iron measured by physical fatigue in women after postpartum haemorrhage. MATERIALS AND METHODS: Single-centre, open...

A case of typhoidal tularemia in a male Japanese farmer

Directory of Open Access Journals (Sweden)

Kiwamu Nakamura

2018-06-01

Full Text Available In Japan, most tularemia cases occur after contact with hares (hunting, cooking and involve the glandular or ulceroglandular form. Here, we present a case of typhoidal tularemia in a 72-year-old Japanese male farmer who presented with fever, fatigue, and right lower abdominal pain. Computed tomography revealed intestinal wall thickening at the ascending colon, pleural effusion, and ascites. Following an initial diagnosis of bacterial enteric infection, his symptoms deteriorated after a week-long cephalosporin treatment course. The patient lived in an area endemic for scrub typhus; the antibiotic was changed to a tetracycline on suspicion of scrub typhus infection. His symptoms rapidly improved after initiation of minocycline treatment. Later, blood tests revealed marked increases in serological tests against Francisella tularensis exclusively, and the patient was diagnosed with typhoidal tularemia. Typhoidal tularemia may be characterized by any combination of general symptoms, but does not exhibit the local manifestations associated with other forms of tularemia. The patient, in this case, had no direct contact with hares or other wild animals and did not present with local manifestations of tularemia. Physicians should consider this disease, especially when tick-borne disease is suspected in the absence of local wounds, eschar, ulcers, or lymphadenopathy.

An evaluation of purified Salmonella Typhi protein antigens for the serological diagnosis of acute typhoid fever

NARCIS (Netherlands)

Tran Vu Thieu, Nga; Trinh van, Tan; Tran Tuan, Anh; Klemm, Elizabeth J.; Nguyen Ngoc Minh, Chau; Voong Vinh, Phat; Pham Thanh, Duy; Ho Ngoc Dan, Thanh; Pham Duc, Trung; Langat, Pinky; Martin, Laura B.; Galan, Jorge; Liang, Li; Felgner, Philip L.; Davies, D. Huw; de Jong, Hanna K.; Maude, Rapeephan R.; Fukushima, Masako; Wijedoru, Lalith; Ghose, Aniruddha; Samad, Rasheda; Dondorp, Arjen M.; Faiz, Abul; Darton, Thomas C.; Pollard, Andrew J.; Thwaites, Guy E.; Dougan, Gordon; Parry, Christopher M.; Baker, Stephen

2017-01-01

The diagnosis of typhoid fever is a challenge. Aiming to develop a typhoid diagnostic we measured antibody responses against Salmonella Typhi (S. Typhi) protein antigens and the Vi polysaccharide in a cohort of Bangladeshi febrile patients. IgM against 12 purified antigens and the Vi polysaccharide

Serology of Typhoid Fever in an Area of Endemicity and Its Relevance to Diagnosis

Science.gov (United States)

House, Deborah; Wain, John; Ho, Vo A.; Diep, To S.; Chinh, Nguyen T.; Bay, Phan V.; Vinh, Ha; Duc, Minh; Parry, Christopher M.; Dougan, Gordon; White, Nicholas J.; Hien, Tran Tinh; Farrar, Jeremy J.

2001-01-01

Currently, the laboratory diagnosis of typhoid fever is dependent upon either the isolation of Salmonella enterica subsp. enterica serotype Typhi from a clinical sample or the detection of raised titers of agglutinating serum antibodies against the lipopolysaccharide (LPS) (O) or flagellum (H) antigens of serotype Typhi (the Widal test). In this study, the serum antibody responses to the LPS and flagellum antigens of serotype Typhi were investigated with individuals from a region of Vietnam in which typhoid is endemic, and their usefulness for the diagnosis of typhoid fever was evaluated. The antibody responses to both antigens were highly variable among individuals infected with serotype Typhi, and elevated antibody titers were also detected in a high proportion of serum samples from healthy subjects from the community. In-house enzyme-linked immunosorbent assays (ELISAs) for the detection of specific classes of anti-LPS and antiflagellum antibodies were compared with other serologically based tests for the diagnosis of typhoid fever (Widal TO and TH, anti-serotype Typhi immunoglobulin M [IgM] dipstick, and IDeaL TUBEX). At a specificity of ≥0.93, the sensitivities of the different tests were 0.75, 0.55, and 0.52 for the anti-LPS IgM, IgG, and IgA ELISAs, respectively; 0.28 for the antiflagellum IgG ELISA; 0.47 and 0.32 for the Widal TO and TH tests, respectively; and 0.77 for the anti-serotype Typhi IgM dipstick assay. The specificity of the IDeaL TUBEX was below 0.90 (sensitivity, 0.87; specificity, 0.76). The serological assays based on the detection of IgM antibodies against either serotype Typhi LPS (ELISA) or whole bacteria (dipstick) had a significantly higher sensitivity than the Widal TO test when used with a single acute-phase serum sample (P ≤ 0.007). These tests could be of use for the diagnosis of typhoid fever in patients who have clinical typhoid fever but are culture negative or in regions where bacterial culturing facilities are not available

Single oral dose toxicity test of platycodin d, a saponin from platycodin radix in mice.

Science.gov (United States)

Lee, Won-Ho; Gam, Cheol-Ou; Ku, Sae-Kwang; Choi, Seong-Hun

2011-12-01

The object of this study was to evaluate the single oral dose toxicity of platycodin D, a saponin from the root of Platycodon grandiflorum in male and female mice. Platycodin D was administered to female and male mice as an oral dose of 2000, 1000, 500, 250 and 125 mg/kg (body wt.). Animals were monitored for the mortality and changes in body weight, clinical signs and gross observation during 14 days after treatment, upon necropsy, organ weight and histopathology of 14 principle organs were examined. As the results, no platycodin D treatment related mortalities, clinical signs, changes on the body and organ weights, gross and histopathological observations against 14 principle organs were detected up to 2000 mg/kg in both female and male mice. Therefore, LD50 (50% lethal dose) and approximate LD of playtcodin D after single oral treatment in female and male mice were considered over 2000 mg/kg - the limited dosages recommended by KFDA Guidelines [2009-116, 2009], respectively.

Investigation of the response to the enterobacterial common antigen after typhoid vaccination

Directory of Open Access Journals (Sweden)

Arlete M. Milhomem

1987-03-01

Full Text Available Antibodies against the Salmonella typhi enterobacterial common antigen (ECA and the O and H antigens were investigated in sera from healthy male subjects who had been previously vaccinated with the typhoid vaccine. No serological response to ECA was observed. Sera from subjects not previously vaccinated presented titers of ECA hemagglutinins which quantitatively were related to the presence ofH titers, but not to O agglutinins but with no statistical significance. The results are discussed in relation to the possible protective immunological mechanisms in typhoid fever.

Evaluation Of Blood Collected From Clinically Diagnosed Typhoid ...

African Journals Online (AJOL)

Blood culture revealed that 216 (42.8%) bacterial pathogens were isolated from the Widal positive patients yielded out of which 101 (46.8%) isolates were of ... fatal illness such as malaria and other parasitaemia, non-typhoid salmonellosis, endocarditis and other gastro-intestinal infections may have been responsible.

Pharmacokinetics of terbinafine after oral administration of a single dose to Hispaniolan Amazon parrots (Amazona ventralis).

Science.gov (United States)

Evans, Erika E; Emery, Lee C; Cox, Sherry K; Souza, Marcy J

2013-06-01

To determine pharmacokinetics after oral administration of a single dose of terbinafine hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis). 6 healthy adult Hispaniolan Amazon parrots. A single dose of terbinafine hydrochloride (60 mg/kg) was administered orally to each bird, which was followed immediately by administration of a commercially available gavage feeding formula. Blood samples were collected at the time of drug administration (time 0) and 0.25, 0.5, 1, 2, 4, 8, 12, and 24 hours after drug administration. Plasma concentrations of terbinafine were determined via high-performance liquid chromatography. Data from 1 bird were discarded because of a possible error in the dose of drug administered. After oral administration of terbinafine, the maximum concentration for the remaining 5 fed birds ranged from 109 to 671 ng/mL, half-life ranged from 6 to 13.5 hours, and time to the maximum concentration ranged from 2 to 8 hours. No adverse effects were observed. Analysis of the results indicated that oral administration of terbinafine at a dose of 60 mg/kg to Amazon parrots did not result in adverse effects and may be potentially of use in the treatment of aspergillosis. Additional studies are needed to determine treatment efficacy and safety.

Desirability for a typhoid fever vaccine among rural residents, Pemba Island, Tanzania.

Science.gov (United States)

Kaljee, Linda M; Pach, Alfred; Thriemer, Kamala; Ley, Benedikt; Jiddawi, Mohamed; Puri, Mahesh; Ochiai, Leon; Wierzba, Thomas; Clemens, John; Ali, Said M

2013-06-24

Surveillance data indicate that Salmonella enterica serotype Typhi (S. Typhi) is a significant cause of morbidity and mortality in Africa. With limited anticipated short-term improvements in sanitation and water infrastructure, targeted vaccination campaigns may be an important prevention tool for typhoid fever. A cross-sectional survey was conducted with 435 randomly selected households in four rural villages on Pemba Island, Tanzania. A dichotomous 'readiness to pay' variable was created to assess vaccine desirability. Data analyses included univariate and bivariate descriptive statistics and binary logistic regression. Bivariate outcomes (ANOVA, t-tests, and chi-square) and odds ratios with 95% confidence intervals are reported. A total of 66% respondents stated that they would pay for a typhoid fever vaccine in the future. Readiness to pay was not significantly associated with household expenditures. Readiness to pay was associated with use of local Primary Health Care Units (PHCUs) compared to use of cottage or district hospitals (OR 1.8 [95% CI, 1.2-2.7]: p=.007) and with knowledge of someone being sick from typhoid fever (OR 2.2 [95% CI, 1.0-4.5]: p=.039). Respondents perceiving prevention measures as more effective (OR 1.0 [95% CI, 1.0-1.2]: p=.009) were also more likely ready to pay. Preferred methods of communication of information about a typhoid fever vaccine included broadcasting via microphone ('miking'), radio, and door-to-door visits. With rapid increase in numbers of licensed and promising vaccines, policy makers and health administrators are faced with decisions regarding allocation of scarce health resources for competing interventions. Community residents need to be informed about diseases which may not be readily recognized, diagnosed, and treated. Perceived vulnerability to the disease may increase likelihood of vaccine desirability. A better local understanding of typhoid fever is needed for general prevention measures, increasing treatment

Mathematical Modeling to Assess the Drivers of the Recent Emergence of Typhoid Fever in Blantyre, Malawi.

Science.gov (United States)

Pitzer, Virginia E; Feasey, Nicholas A; Msefula, Chisomo; Mallewa, Jane; Kennedy, Neil; Dube, Queen; Denis, Brigitte; Gordon, Melita A; Heyderman, Robert S

2015-11-01

Multiyear epidemics of Salmonella enterica serovar Typhi have been reported from countries across eastern and southern Africa in recent years. In Blantyre, Malawi, a dramatic increase in typhoid fever cases has recently occurred, and may be linked to the emergence of the H58 haplotype. Strains belonging to the H58 haplotype often exhibit multidrug resistance and may have a fitness advantage relative to other Salmonella Typhi strains. To explore hypotheses for the increased number of typhoid fever cases in Blantyre, we fit a mathematical model to culture-confirmed cases of Salmonella enterica infections at Queen Elizabeth Central Hospital, Blantyre. We explored 4 hypotheses: (1) an increase in the basic reproductive number (R0) in response to increasing population density; (2) a decrease in the incidence of cross-immunizing infection with Salmonella Enteritidis; (3) an increase in the duration of infectiousness due to failure to respond to first-line antibiotics; and (4) an increase in the transmission rate following the emergence of the H58 haplotype. Increasing population density or decreasing cross-immunity could not fully explain the observed pattern of typhoid emergence in Blantyre, whereas models allowing for an increase in the duration of infectiousness and/or the transmission rate of typhoid following the emergence of the H58 haplotype provided a good fit to the data. Our results suggest that an increase in the transmissibility of typhoid due to the emergence of drug resistance associated with the H58 haplotype may help to explain recent outbreaks of typhoid in Malawi and similar settings in Africa. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

Typhoid fever in a Tertiary Hospital in Nigeria: Another look at the Widal agglutination test as a preferred option for diagnosis.

Science.gov (United States)

Enabulele, Osahon; Awunor, Simeon Nyemike

2016-01-01

Single Widal agglutination test rather than blood culture, is commonly employed to diagnose typhoid fever in Nigeria. We took another look at the Widal agglutination test as a preferred option for diagnosis of typhoid fever by determining the specificity and sensitivity of Widal agglutination test in febrile adult patients. Two hundred and seventy-one blood samples from consecutive adults (>18 years) with febrile illness attending the General Practice Clinic of the University of Benin Teaching Hospital were tested using the Widal agglutination test, blood culture, and malaria parasite test on each sample to establish the diagnosis of typhoid fever. Of the 271 blood samples 124 (45.76%) were positive following a Widal agglutination test, 60 (22.10%) blood samples grew Salmonella organisms on blood culture while 55 (20.29%) blood samples showed a co-infection of typhoid fever and malaria. A sensitivity of 35%, specificity of 51%, positive predictive value of 17%, and a negative predictive value of 73% were observed for Widal agglutination test as a diagnostic modality for typhoid fever infection. A single Widal agglutination test is not a valid diagnostic option for typhoid fever while co-infection with malaria parasite is the preponderant microbiological finding in typhoid fever infections. The severity of malaria parasitemia is associated with positive titers on Widal test.

diagnosis of malaria and typhoid fevers using basic tools

African Journals Online (AJOL)

userpc

retrospective analysis was conducted on the positivity rate for malaria parasite and typhoid fever among .... the size of the data, using a statistical software .... The frequency of the request for Malaria .... parameters vary with the change in the.

Laboratory evaluation of a simple and rapid latex agglutination assay for the serodiagnosis of typhoid fever

NARCIS (Netherlands)

Abdoel, Theresia H.; Pastoor, Rob; Smits, Henk L.; Hatta, Mochammad

2007-01-01

A latex agglutination assay for the serodiagnosis of typhoid fever was evaluated on samples collected from patients with clinical suspicion of typhoid fever in South Sulawesi, Indonesia, where the disease is endemic. The latex assay is very easy to use, gives a rapid result and may be used as a

Missed doses of oral antihyperglycemic medications in US adults with type 2 diabetes mellitus: prevalence and self-reported reasons.

Science.gov (United States)

Vietri, Jeffrey T; Wlodarczyk, Catherine S; Lorenzo, Rose; Rajpathak, Swapnil

2016-09-01

Adherence to antihyperglycemic medication is thought to be suboptimal, but the proportion of patients missing doses, the number of doses missed, and reasons for missing are not well described. This survey was conducted to estimate the prevalence of and reasons for missed doses of oral antihyperglycemic medications among US adults with type 2 diabetes mellitus, and to explore associations between missed doses and health outcomes. The study was a cross-sectional patient survey. Respondents were contacted via a commercial survey panel and completed an on-line questionnaire via the Internet. Respondents provided information about their use of oral antihyperglycemic medications including doses missed in the prior 4 weeks, personal characteristics, and health outcomes. Weights were calculated to project the prevalence to the US adult population with type 2 diabetes mellitus. Outcomes were compared according to number of doses missed in the past 4 weeks using bivariate statistics and generalized linear models. Approximately 30% of adult patients with type 2 diabetes mellitus reported missing or reducing ≥1 dose of oral antihyperglycemic medication in the prior 4 weeks. Accidental missing was more commonly reported than purposeful skipping, with forgetting the most commonly reported reason. The timing of missed doses suggested respondents had also forgotten about doses missed, so the prevalence of missed doses is likely higher than reported. Outcomes were poorer among those who reported missing three or more doses in the prior 4 weeks. A substantial number of US adults with type 2 diabetes mellitus miss doses of their oral antihyperglycemic medications.

Population-based incidence of typhoid fever in an urban informal settlement and a rural area in Kenya: implications for typhoid vaccine use in Africa.

Directory of Open Access Journals (Sweden)

Robert F Breiman

Full Text Available BACKGROUND: High rates of typhoid fever in children in urban settings in Asia have led to focus on childhood immunization in Asian cities, but not in Africa, where data, mostly from rural areas, have shown low disease incidence. We set out to compare incidence of typhoid fever in a densely populated urban slum and a rural community in Kenya, hypothesizing higher rates in the urban area, given crowding and suboptimal access to safe water, sanitation and hygiene. METHODS: During 2007-9, we conducted population-based surveillance in Kibera, an urban informal settlement in Nairobi, and in Lwak, a rural area in western Kenya. Participants had free access to study clinics; field workers visited their homes biweekly to collect information about acute illnesses. In clinic, blood cultures were processed from patients with fever or pneumonia. Crude and adjusted incidence rates were calculated. RESULTS: In the urban site, the overall crude incidence of Salmonella enterica serovar Typhi (S. Typhi bacteremia was 247 cases per 100,000 person-years of observation (pyo with highest rates in children 5-9 years old (596 per 100,000 pyo and 2-4 years old (521 per 100,000 pyo. Crude overall incidence in Lwak was 29 cases per 100,000 pyo with low rates in children 2-4 and 5-9 years old (28 and 18 cases per 100,000 pyo, respectively. Adjusted incidence rates were highest in 2-4 year old urban children (2,243 per 100,000 pyo which were >15-fold higher than rates in the rural site for the same age group. Nearly 75% of S. Typhi isolates were multi-drug resistant. CONCLUSIONS: This systematic urban slum and rural comparison showed dramatically higher typhoid incidence among urban children <10 years old with rates similar to those from Asian urban slums. The findings have potential policy implications for use of typhoid vaccines in increasingly urban Africa.

Association of carcinoma of the gallbladder with typhoid carriage in a typhoid endemic area using nested PCR.

Science.gov (United States)

Nath, Gopal; Singh, Yogesh Kumar; Kumar, Kailash; Gulati, Anil Kumar; Shukla, Vijay Kumar; Khanna, Ajay Kumar; Tripathi, Sunil Kumar; Jain, Ashok Kumar; Kumar, Mohan; Singh, Tej Bali

2008-08-30

Although well studied the association between chronic typhoid carrier state and carcinoma of the gallbladder (CaGB) remains unproven. The study was performed at a tertiary care medical center in North India and involved 52 patients with CaGB, 223 patients with benign gallbladder diseases, 508 healthy individuals and, 424 corpses. For the detection of Salmonella enterica serovar Typhi, hepatobiliary specimens were subjected to DNA extraction for specific nested- PCR amplification of the S. Typhi flagellin gene. Anti-Vi S. Typhi antibodies were detected in serum samples from patients by indirect haemagglutination. Thirty five of the 52 (67.3%) CaGB patients were PCR-positive for the S. Typhi flagellin gene; significantly higher than for patients with benign gallbladder diseases (95/223, 42.6%; p or = 160) in their serum were 20/52 (38.5%) for CaGB patients, 31/223 (13.9%) for patients with benign gallbladder diseases, and 47/508 (9.2%) for healthy individuals. Specific nested-PCR amplification of the S. Typhi flagellin gene in hepato-biliary specimens was more sensitive for detection of S. Typhi carriage than anti-Vi antibody titres in serum. The results demonstrate an association between typhoid carriage and gallbladder diseases, both CaGB and benign. S. Typhi specific immunosuppression is also suggested in patients with gallbladder diseases.

Serodiagnosis of Acute Typhoid Fever in Nigerian Pediatric Cases by Detection of Serum IgA and IgG Against Hemolysin E and Lipopolysaccharide.

Science.gov (United States)

Davies, D Huw; Jain, Aarti; Nakajima, Rie; Liang, Li; Jasinskis, Algis; Supnet, Medalyn; Felgner, Philip L; Teng, Andy; Pablo, Jozelyn; Molina, Douglas M; Obaro, Stephen K

2016-08-03

Inexpensive, easy-to-use, and highly sensitive diagnostic tests are currently unavailable for typhoid fever. To identify candidate serodiagnostic markers, we have probed microarrays displaying the full Salmonella enterica serovar Typhi (S. Typhi) proteome of 4,352 different proteins + lipopolysaccharides (LPSs), with sera from Nigerian pediatric typhoid and other febrile cases, Nigerian healthy controls, and healthy U.S. adults. Nigerian antibody profiles were broad (∼500 seropositive antigens) and mainly low level, with a small number of stronger "hits," whereas the profile in U.S. adults was typhoid cases. The response to LPS was also a strong discriminator of healthy controls and typhoid, although LPS did not discriminate between typhoid and nontyphoidal Salmonella (NTS) disease. As a first step toward the development of a point-of-care diagnostic, t1477 and LPS were evaluated on immunostrips. Both provided good discrimination between healthy controls and typhoid/NTS disease. Such a test could provide a useful screen for salmonellosis (typhoid and NTS disease) in suspected pediatric cases that present with undefined febrile disease. © The American Society of Tropical Medicine and Hygiene.

Lack of dose dependent kinetics of methyl salicylate-2-O-β-D-lactoside in rhesus monkeys after oral administration.

Science.gov (United States)

He, Yangyang; Yan, Yu; Zhang, Tiantai; Ma, Yinzhong; Zhang, Wen; Wu, Ping; Song, Junke; Wang, Shuang; Du, Guanhua

2015-04-22

Methyl salicylate-2-O-β-d-lactoside (MSL) is one of the main active components isolated from Gaultheria yunnanensis, which is a traditional Chinese medicine used to treat arthritis and various aches and pains. Pharmacological researches showed that MSL had various effective activities in both in vivo and in vitro experiments. However, the pharmacokinetics features and oral bioavailability of MSL in primates were not studied up to now. To study the pharmacokinetics of different doses of MSL in rhesus monkeys and investigate the absolute bioavailability of MSL after oral administration. Male and female rhesus monkeys were either orally administrated with MSL 200, 400 and 800 mg/kg or received an intravenous dose of 20mg/kg randomly. The levels of MSL and salicylic acid (SA) in plasma were simultaneous measured by a simple, sensitive and reproducible high performance liquid chromatography method. Mean peak plasma concentration values for groups treated with 200, 400 and 800 mg/kg doses ranged from 48.79 to 171.83 μg/mL after single-dose oral administration of MSL, and mean area under the concentration-time curve values ranged from 195.16 to 1107.76 μg/mL h. Poor linearity of the kinetics of SA after oral administration of MSL was observed in the regression analysis of the Cmax-dose plot (r(2)=0.812), CL-dose plot (r(2)=0.225) and AUC(0-t)-dose plot (r(2)=0.938). Absolute bioavailability of MSL was assessed to be 118.89 ± 57.50, 213.54 ± 58.98 and 168.72 ± 76.58%, respectively. Bioavailability of MSL after oral administration in rhesus monkeys was measured for the first time. Pharmacokinetics parameters did not appear to be dose proportional among the three oral doses of treatments, and MSL showed an apparent absolute bioavailability in excess of 100% in rhesus monkeys based on the present study. In addition, a rapid, sensitive and reliable HPLC method was established and demonstrated for the research of traditional Chinese medicine in this study. Copyright �

Analysis of TLR polymorphisms in typhoid patients and ...

African Journals Online (AJOL)

Ilakkia Sivaji

2016-01-20

Jan 20, 2016 ... implicated the genetic variations (polymorphisms) in TLR genes to influence the host susceptibility to infectious diseases. However, the available literature on TLR polymorphism and susceptibility to typhoid fever is unclear. Aim: This study aimed to investigate the polymorphism of TLRs 1, 2, 4 and 5 in ...

Single dose oral ketoprofen or dexketoprofen for acute postoperative pain in adults.

Science.gov (United States)

Gaskell, Helen; Derry, Sheena; Wiffen, Philip J; Moore, R Andrew

2017-05-25

This review is an update of "Single dose oral ketoprofen and dexketoprofen for acute postoperative pain in adults" last updated in Issue 4, 2009. Ketoprofen is a non-selective nonsteroidal anti-inflammatory drug (NSAID) used to treat acute and chronic painful conditions. Dexketoprofen is the (S)-enantiomer, which is believed to confer analgesia. Theoretically dexketoprofen is expected to provide equivalent analgesia to ketoprofen at half the dose, with a consequent reduction in gastrointestinal adverse events. This review is one of a series on oral analgesics for acute postoperative pain. Individual reviews have been brought together in two overviews to provide information about the relative efficacy and harm of the different interventions. To assess the efficacy and safety of single dose oral ketoprofen and oral dexketoprofen compared with placebo for acute postoperative pain, using methods that permit comparison with other analgesics evaluated in the same way, and criteria of efficacy recommended by an in-depth study at the individual patient level. For this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase from 2009 to 28 March 2017. We also searched the reference lists of retrieved studies and reviews, and two online clinical trial registries. Randomised, double-blind, placebo-controlled trials of single dose orally administered ketoprofen or dexketoprofen in adults with moderate to severe acute postoperative pain. Two review authors independently considered studies for inclusion in the review, examined issues of study quality and potential bias, and extracted data. For dichotomous outcomes, we calculated risk ratio (RR) and number needed to treat for an additional beneficial outcome (NNT) or harmful outcome (NNH) with 95% confidence intervals (CI) for ketoprofen and dexketoprofen, compared with placebo, where there were sufficient data. We collected information on the number of participants with at least 50

Comparison between DOT EIA IgM and Widal Test as early diagnosis of typhoid fever.

Science.gov (United States)

Begum, Z; Hossain, M A; Musa, A K; Shamsuzzaman, A K; Mahmud, M C; Ahsan, M M; Sumona, A A; Ahmed, S; Jahan, N A; Alam, M; Begum, A

2009-01-01

A recently developed DOT enzyme immunoassay known as "Typhidot" for detecting IgM antibody against 50 KDa OMP antigen of Salmonella typhi, was evaluated on 100 clinically suspected typhoid fever cases and 40 age-sex matched controls, in the Department of Microbiology, Mymensingh Medical College during, the period from June 2006 to July 2007. Blood culture, Widal test, and DOT EIA for IgM test were performed in all patients. Among 100 clinically suspected typhoid fever cases, 35 were subsequently confirmed on the basis of positive blood culture for S. typhi and/or significant rising titre of Widal test. The DOT EIA IgM test could produce results within 1 hour. The result of the DOT EIA IgM test showed a good diagnostic value for typhoid fever. The sensitivity, specificity, positive and negative predictive value of the test was found as 91.42%, 90.00%, 88.88% and 92.30% respectively. On the other hand corresponding values for Widal test were of 42.85%, 85.00%, 71.42% and 62.96% respectively. Thus, The DOT EIA IgM seems to be a practical alternative to Widal test for early diagnosis of typhoid fever.

Efficacy and safety of vi-tetanus toxoid conjugated typhoid vaccine (PedaTyph™) in Indian children: School based cluster randomized study.

Science.gov (United States)

Mitra, Monjori; Shah, Nitin; Ghosh, Apurba; Chatterjee, Suparna; Kaur, Iqbal; Bhattacharya, Nisha; Basu, Suparna

2016-04-02

Vi polysaccharide typhoid vaccines cannot be used in children vaccine prepared by binding Vi to tetanus toxoids (Vi-TT) induces protective levels even in children safety following vaccination with a Vi-TT vaccine in children 6 months to 12 years of age. Overall, 1765 subjects were recruited from two registered municipal urban slums of southern Kolkata. Most of the children of the slum dwellers attended the schools in the locality which was selected with permission from the school authority. Schools were randomly divided into vaccinated (Test group) and unvaccinated group (Control group). Children and their siblings of test group received 2-doses of PedaTyph™ vaccine at 6 weeks interval. Control group received vaccines as per national guidelines. Adverse events (AEs) were examined after 30 minutes, 1 month and clinical events were observed till 12 months post-vaccination. Incidence of culture positive typhoid fever in the control group was 1.27% vis-a-vis none in vaccine group during 12 months. In subgroup evaluated for immunogenicity, an antibody titer value of 1.8 EU/ml (95% CI: 1.5 EU/ml, 2.2 EU/ml), 32 EU/ml (95% CI: 27.0 EU/ml, 39.0 EU/ml) and 14 EU/ml (95% CI: 12.0 EU/ml, 17.0 EU/ml) at baseline, 6 weeks and 12 months, respectively was observed. Sero-conversion among the sub-group was 100% after 6 weeks of post-vaccination and 83% after 12 months considering 4-fold rise from baseline. The efficacy of vaccine was 100 % (95% CI: 97.6%, 100%) in the first year of follow-up with minimal AEs post vaccination. Vi conjugate typhoid vaccine conferred 100% protection against typhoid fever in 1765 children 6 months to 12 years of age with high immunogenicity in a subgroup from the vaccine arm.

Preoperative chemoradiotherapy with oral doxifluridine plus low-dose oral leucovorin in unresectable primary rectal cancer

International Nuclear Information System (INIS)

Seong, Jinsil; Cho, Jae Ho; Kim, Nam Kyu; Min, Jin Sik; Suh, Chang Ok

2001-01-01

Purpose: The use of oral chemotherapeutic agents in chemoradiotherapy provides several advantages. Doxifluridine, an oral 5-FU prodrug, has been shown to be effective in colorectal cancer. We attempted a Phase II trial of preoperative chemoradiotherapy with doxifluridine plus a low-dose oral leucovorin in unresectable primary rectal cancer patients. In this study, toxicity and efficacy were evaluated. Methods and Materials: There were 23 patients with primary unresectable rectal cancer in this trial, 21 of whom were available for analysis. The patients were treated with oral doxifluridine (900 mg/day) plus oral leucovorin (30 mg/day) from days 1 to 35, and pelvic radiation of 45 Gy over 5 weeks. Surgical resection was performed 5-6 weeks after the treatment. Results: Acute toxicity involved thrombocytopenia, nausea/vomiting, diarrhea, and skin reaction. All were in Grade 1/2, except diarrhea, which was not only the most frequent (7 patients, 33.3%), but also the only toxicity of Grade 3 (2 patients). The clinical tumor response was shown in 5 patients (23.8%) as a complete response and 13 patients (61.9%) as a partial response. A complete resection with negative resection margin was done in 18 patients (85.7%), in 2 of whom a pathologic complete response was shown (9.5%). The overall downstaging rate in the T- and N-stage groupings was 71.4% (15 patients). Conclusion: This study demonstrated the efficacy and low toxicity of chemoradiotherapy with doxifluridine. Currently, a Phase III randomized trial of chemoradiotherapy is ongoing at our institute to compare the therapeutic efficacy of oral 5-FU with respect to i.v. 5-FU in locally advanced and unresectable rectal cancer

Comparação da eficácia de doses iguais de acetaminofeno retal e oral em crianças Comparison of antipyretic effectiveness of equal doses of rectal and oral acetaminophen in children

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Sedigha Akhavan Karbasi

2010-06-01

Full Text Available OBJETIVO: Comparar uma dose de acetaminofeno oral e retal e avaliar a aceitabilidade do acetaminofeno retal, uma vez que o acetaminofeno oral e retal é amplamente usado como agente antipirético em crianças com febre e a eficiência comparativa dessas duas preparações não está bem estabelecida. MÉTODOS: Neste estudo prospectivo de grupos paralelos, foram incluídas 60 crianças admitidas na emergência ou clínica ambulatorial pediátrica em um hospital terciário, com idade entre 6 meses e 6 anos e com temperatura retal acima de 39 °C. Os pacientes foram distribuídos aleatoriamente em dois grupos de mesmo tamanho. O grupo 1 recebeu 15 mg/kg de acetaminofeno retal, e o grupo 2 recebeu a mesma dose oralmente. A temperatura foi registrada no tempo zero e 1 e 3 horas após administração da droga. RESULTADOS: No primeiro grupo, a redução média de temperatura, 1 e 3 horas após administração do acetaminofeno, foi de 1,07±0,16 (p 0,05. CONCLUSÃO: As preparações oral e retal de acetaminofeno têm eficácia antipirética equivalente em crianças. A via retal mostrou ser tão aceitável quanto a oral entre os pais.OBJECTIVE: To compare a dose of oral and rectal acetaminophen and to evaluate acceptability of rectal acetaminophen, since oral and rectal acetaminophen is widely used as an antipyretic agent in febrile children and the comparative effectiveness of these two preparations is not well established. METHODS: In this prospective parallel group designed study, 60 children who presented to the emergency department or outpatient pediatric clinic at a tertiary hospital and aged from 6 months to 6 years with rectal temperature over 39 °C were enrolled. Patients were randomly assigned to two equal-sized groups. Group 1 received 15 mg/kg acetaminophen rectally and group 2 received the same dose orally. Temperature was recorded at baseline and 1 and 3 hours after drug administration. RESULTS: In the first group, mean decrease in

Pharmacokinetics of voriconazole after oral administration of single and multiple doses in African grey parrots (Psittacus erithacus timneh).

Science.gov (United States)

Flammer, Keven; Nettifee Osborne, Julie A; Webb, Donna J; Foster, Laura E; Dillard, Stacy L; Davis, Jennifer L

2008-01-01

To determine the pharmacokinetics and safety of orally administered voriconazole in African grey parrots. 20 clinically normal Timneh African grey parrots (Psittacus erithacus timneh). In single-dose trials, 12 parrots were each administered 6, 12, and 18 mg of voriconazole/kg orally and plasma concentrations of voriconazole were determined via high-pressure liquid chromatography. In a multiple-dose trial, voriconazole (18 mg/kg) was administered orally to 6 birds every 12 hours for 9 days; a control group (2 birds) received tap water. Treatment effects were assessed via observation, clinicopathologic analyses (3 assessments), and measurement of trough plasma voriconazole concentrations (2 assessments). Voriconazole's elimination half-life was short (1.1 to 1.6 hours). Higher doses resulted in disproportional increases in the maximum plasma voriconazole concentration and area under the curve. Trough plasma voriconazole concentrations achieved in the multiple-dose trial were lower than those achieved after administration of single doses. Polyuria (the only adverse treatment effect) developed in treated and control birds but was more severe in the treatment group. In African grey parrots, voriconazole has dose-dependent pharmacokinetics and may induce its own metabolism. Oral administration of 12 to 18 mg of voriconazole/kg twice daily is a rational starting dose for treatment of African grey parrots infected with Aspergillus or other fungal organisms that have a minimal inhibitory concentration for voriconazole treatment. Safety and efficacy of various voriconazole treatment regimens in this species require investigation.

Failure of antimony trioxide to induce micronuclei or chromosomal aberrations in rat bone-marrow after sub-chronic oral dosing.

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Kirkland, David; Whitwell, James; Deyo, James; Serex, Tessa

2007-03-05

Antimony trioxide (Sb2O3, CAS 1309-64-4) is widely used as a flame retardant synergist in a number of household products, as a fining agent in glass manufacture, and as a catalyst in the manufacture of various types of polyester plastics. It does not induce point mutations in bacteria or mammalian cells, but is able to induce chromosomal aberrations (CA) in cultured cells in vitro. Although no CA or micronuclei (MN) have been induced after acute oral dosing of mice, repeated oral dosing for 14 or 21 days resulted in increased CA in one report, but did not result in increased MN in another. In order to further investigate its in vivo genotoxicity, Sb2O3 was dosed orally to groups of rats for 21 days at 250, 500 and 1000 mg/kg day. There were no clinical signs of toxicity in the Sb2O3-exposed animals except for some reductions in body-weight gain in the top dose group. Toxicokinetic measurements in a separate study confirmed bone-marrow exposure, and at higher levels than would have been achieved by single oral dosing. Large numbers of cells were scored for CA (600 metaphases/sex group) and MN (12,000 PCE/sex group) but frequencies of CA or MN in Sb2O3-treated rats were very similar to controls, and not biologically or statistically different, at all doses. These results provide further indication that Sb2O3 is not genotoxic to the bone marrow of rodents after 21 days of oral administration at high doses close to the maximum tolerated dose.

Brief oral cryotherapy for the prevention of high-dose melphalan-induced stomatitis in allogeneic hematopoietic stem cell transplant recipients.

Science.gov (United States)

Mori, Takehiko; Yamazaki, Rie; Aisa, Yoshinobu; Nakazato, Tomonori; Kudo, Masumi; Yashima, Tomoko; Kondo, Sakiko; Ikeda, Yasuo; Okamoto, Shinichiro

2006-04-01

We previously reported the efficacy of oral cryotherapy for the prevention of high-dose melphalan-induced stomatitis. The purpose of this study was to evaluate whether the further shortening of the duration of oral cryotherapy could minimize its side effects while sparing its efficacy. Seventeen consecutive recipients of allogeneic hematopoieic stem cell transplant conditioned with high-dose melphalan in combination with fludarabine alone or with fludarabine and additional radiation were enrolled in the study. The severity of stomatitis was graded according to the National Cancer Institute-Common Toxicity Criteria. Patients were kept on oral cryotherapy shortly before, during, and for additional 30 min after the completion of melphalan administration (60-min oral cryotherapy). Patients who were also enrolled in our previous study received the same type of oral cryotherapy but for additional 90 min after the completion of melphalan administration (120-min oral cryotherapy), and they served as controls. Only 2 (11.8%) of 17 patients receiving 60-min oral cryotherapy and 2 (11.1%) of 18 patients receiving 120-min oral cryotherapy developed grade 2 or 3 stomatitis, respectively. The difference between groups was not statistically significant (P = 0.677). The incidence of unpleasant symptoms such as chills and nausea during oral cryotherapy decreased significantly with 60-min oral cryotherapy, as compared with that associated with 120-min oral cryotherapy (P cryotherapy is as effective as 120-min oral cryotherapy at preventing high-dose melphalan-induced stomatitis, and shorter treatment might have contributed to relieve patient discomfort during oral cryotherapy.

Modelling typhoid risk in Dhaka metropolitan area of Bangladesh: the role of socio-economic and environmental factors.

Science.gov (United States)

Corner, Robert J; Dewan, Ashraf M; Hashizume, Masahiro

2013-03-16

Developing countries in South Asia, such as Bangladesh, bear a disproportionate burden of diarrhoeal diseases such as cholera, typhoid and paratyphoid. These seem to be aggravated by a number of social and environmental factors such as lack of access to safe drinking water, overcrowdedness and poor hygiene brought about by poverty. Some socioeconomic data can be obtained from census data whilst others are more difficult to elucidate. This study considers a range of both census data and spatial data from other sources, including remote sensing, as potential predictors of typhoid risk. Typhoid data are aggregated from hospital admission records for the period from 2005 to 2009. The spatial and statistical structures of the data are analysed and principal axis factoring is used to reduce the degree of co-linearity in the data. The resulting factors are combined into a quality of life index, which in turn is used in a regression model of typhoid occurrence and risk. The three principal factors used together explain 87% of the variance in the initial candidate predictors, which eminently qualifies them for use as a set of uncorrelated explanatory variables in a linear regression model. Initial regression result using ordinary least squares (OLS) were disappointing, this was explainable by analysis of the spatial autocorrelation inherent in the principal factors. The use of geographically weighted regression caused a considerable increase in the predictive power of regressions based on these factors. The best prediction, determined by analysis of the Akaike information criterion (AIC) was found when the three factors were combined into a quality of life index, using a method previously published by others, and had a coefficient of determination of 73%. The typhoid occurrence/risk prediction equation was used to develop the first risk map showing areas of Dhaka metropolitan area whose inhabitants are at greater or lesser risk of typhoid infection. This, coupled with

Helicobacter pylori infection and typhoid fever in Jakarta, Indonesia.

NARCIS (Netherlands)

Vollaard, A.M.; Verspaget, H.W.; Ali, S.; Visser, L.G.; Veenendaal, R.A.; Asten, H.A.G.H. van; Widjaja, S.; Surjadi, C.; Dissel, J.T. van

2006-01-01

We evaluated the association between typhoid fever and Helicobacter pylori infection, as the latter microorganism may influence gastric acid secretion and consequently increase susceptibility to Salmonella typhi infection. Anti-H. pylori IgG and IgA antibody titres (ELISA) and gastrin concentration

A cross-sectional seroepidemiological survey of typhoid fever in Fiji.

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Conall H Watson

2017-07-01

Full Text Available Fiji, an upper-middle income state in the Pacific Ocean, has experienced an increase in confirmed case notifications of enteric fever caused by Salmonella enterica serovar Typhi (S. Typhi. To characterize the epidemiology of typhoid exposure, we conducted a cross-sectional sero-epidemiological survey measuring IgG against the Vi antigen of S. Typhi to estimate the effect of age, ethnicity, and other variables on seroprevalence. Epidemiologically relevant cut-off titres were established using a mixed model analysis of data from recovering culture-confirmed typhoid cases. We enrolled and assayed plasma of 1787 participants for anti-Vi IgG; 1,531 of these were resident in mainland areas that had not been previously vaccinated against S. Typhi (seropositivity 32.3% (95%CI 28.2 to 36.3%, 256 were resident on Taveuni island, which had been previously vaccinated (seropositivity 71.5% (95%CI 62.1 to 80.9%. The seroprevalence on the Fijian mainland is one to two orders of magnitude higher than expected from confirmed case surveillance incidence, suggesting substantial subclinical or otherwise unreported typhoid. We found no significant differences in seropositivity prevalences by ethnicity, which is in contrast to disease surveillance data in which the indigenous iTaukei Fijian population are disproportionately affected. Using multivariable logistic regression, seropositivity was associated with increased age (odds ratio 1.3 (95% CI 1.2 to 1.4 per 10 years, the presence of a pit latrine (OR 1.6, 95%CI 1.1 to 2.3 as opposed to a septic tank or piped sewer, and residence in settlements rather than residential housing or villages (OR 1.6, 95% CI 1.0 to 2.7. Increasing seropositivity with age is suggestive of low-level endemic transmission in Fiji. Improved sanitation where pit latrines are used and addressing potential transmission routes in settlements may reduce exposure to S. Typhi. Widespread unreported infection suggests there may be a role for typhoid

A cross-sectional seroepidemiological survey of typhoid fever in Fiji.

Science.gov (United States)

Watson, Conall H; Baker, Stephen; Lau, Colleen L; Rawalai, Kitione; Taufa, Mere; Coriakula, Jerimaia; Thieu, Nga Tran Vu; Van, Tan Trinh; Ngoc, Dung Tran Thi; Hens, Niel; Lowry, John H; de Alwis, Ruklanthi; Cano, Jorge; Jenkins, Kylie; Mulholland, E Kim; Nilles, Eric J; Kama, Mike; Edmunds, W John

2017-07-01

Fiji, an upper-middle income state in the Pacific Ocean, has experienced an increase in confirmed case notifications of enteric fever caused by Salmonella enterica serovar Typhi (S. Typhi). To characterize the epidemiology of typhoid exposure, we conducted a cross-sectional sero-epidemiological survey measuring IgG against the Vi antigen of S. Typhi to estimate the effect of age, ethnicity, and other variables on seroprevalence. Epidemiologically relevant cut-off titres were established using a mixed model analysis of data from recovering culture-confirmed typhoid cases. We enrolled and assayed plasma of 1787 participants for anti-Vi IgG; 1,531 of these were resident in mainland areas that had not been previously vaccinated against S. Typhi (seropositivity 32.3% (95%CI 28.2 to 36.3%)), 256 were resident on Taveuni island, which had been previously vaccinated (seropositivity 71.5% (95%CI 62.1 to 80.9%)). The seroprevalence on the Fijian mainland is one to two orders of magnitude higher than expected from confirmed case surveillance incidence, suggesting substantial subclinical or otherwise unreported typhoid. We found no significant differences in seropositivity prevalences by ethnicity, which is in contrast to disease surveillance data in which the indigenous iTaukei Fijian population are disproportionately affected. Using multivariable logistic regression, seropositivity was associated with increased age (odds ratio 1.3 (95% CI 1.2 to 1.4) per 10 years), the presence of a pit latrine (OR 1.6, 95%CI 1.1 to 2.3) as opposed to a septic tank or piped sewer, and residence in settlements rather than residential housing or villages (OR 1.6, 95% CI 1.0 to 2.7). Increasing seropositivity with age is suggestive of low-level endemic transmission in Fiji. Improved sanitation where pit latrines are used and addressing potential transmission routes in settlements may reduce exposure to S. Typhi. Widespread unreported infection suggests there may be a role for typhoid

Typhoid Fever Complicated by Hemophagocytic Lymphohistiocytosis and Rhabdomyolysis.

Science.gov (United States)

Non, Lemuel R; Patel, Rupa; Esmaeeli, Amir; Despotovic, Vladimir

2015-11-01

Hemophagocytic lymphohistiocytosis (HLH) and rhabdomyolysis are rare complications of typhoid fever from Salmonella enterica serovar Typhi. Herein, we describe the clinical features in a 21-year-old female from India who presented to the intensive care unit with fever, severe pancytopenia, and rhabdomyolysis. © The American Society of Tropical Medicine and Hygiene.

Diagnosis and Treatment of Typhoid Fever and Associated Prevailing Drug Resistance in Northern Ethiopia.

Science.gov (United States)

Wasihun, Araya Gebreyesus; Wlekidan, Letemichael Negash; Gebremariam, Senay Aregawi; Welderufael, Abadi Luel; Muthupandian, Saravanan; Haile, Tadesse Dejenie; Dejene, Tsehaye Asmelash

2015-06-01

To determine diagnostic value of the Widal test, treatment pattern of febrile patients and antimicrobial drug susceptibility pattern of blood isolates. Using cross sectional methods, blood samples were collected for culture and Widal test from 502 febrile outpatients attending Mekelle hospital and Mekelle health center with similar symptoms to typhoid. Sensitivity, specificity for anti-TH and anti-TO titers using culture confirmed typhoid fever cases, and Kappa agreement between Titer and slide Widal tests were calculated. Treatment pattern of patients and antimicrobial susceptibility pattern of the blood isolates was assessed. From the 502 febrile patients, 8(1.6%) of them had culture-proven typhoid fever. However, patients who have results indicative of recent infection by O and H antigens of the Widal slide agglutination test were 343 (68.5%), with specificity and sensitivity of 33% and 100%, respectively. Over prescription of antibiotics was seen by Widal slide test for Ciprofloxacin 268 (76.1%), Amoxicillin- Clavulanic acid 9(2.6%), Amoxicillin 8(2.4%) and Chloranphenicol 8(2.4%). Tube titer positivity was seen in 23(5.3%) patients with 75% sensitivity and 95.8% specificity. Widal slide and Tube titer tests showed poor agreement for both antigens (kappa=0.02 for O) and (Kappa=0.09 for H). A single anti-TH titer of ≥ 1:160 and anti-TO titer ≥ 1:80 higher in our study showed an indication for typhoid fever infection. Drug resistance pattern of blood isolates ranges from 0-89.7% for gram positive and 0-100% for Gram negative, with an overall multi-drug resistance rate of 61.7%. Patients were wrongly diagnosed and treated for typhoid fever by Widal test. The tube titration method was relatively good but still had poor sensitivity. Blood isolates showed multi drug resistance, which may be due to the indiscriminate prescription as seen in this study. Based on our results, the slide Widal test is not helpful in the diagnosis of typhoid, hence other tests with

Risk of venous thromboembolism from use of oral contraceptives containing different progestogens and oestrogen doses: Danish cohort study, 2001-9

DEFF Research Database (Denmark)

Lidegaard, Øjvind; Nielsen, Lars Hougaard; Skovlund, Charlotte Wessel

2011-01-01

To assess the risk of venous thromboembolism from use of combined oral contraceptives according to progestogen type and oestrogen dose.......To assess the risk of venous thromboembolism from use of combined oral contraceptives according to progestogen type and oestrogen dose....

A Review of Prognostic Models on Diagnosis and Therapeutic Strategies of Typhoid Fever

Directory of Open Access Journals (Sweden)

Aslam Babar

2018-05-01

Full Text Available Background:      Typhoid infection is an insidious onset type of fever and some other gastrointestinal disorders which may have a fatal outcome. The causative agents are Salmonella typhi, Salmonella paratyphi A, and Salmonella paratyphi B.  Clinical features include, gradual rising fever, white coated tongue, and severe degree of malaise, drowsiness and pain in abdomen, perforation with bleeding in the intestines, shock and death. It involves mostly male victims of school going age. It is water born disease which spreads due to poor sanitation mostly in congested populated areas. According to World Health Organization sixteen to seventeen million typhoid fever cases were reported annually, out of which 600,000 died. Typhoid fever is 10 to 29 times more in subcontinent than China. Infection only occurs when food is handled by infected person. Isolated strains of Salmonella spp from suspected cases show resistance against routine antibiotics and the modern antibiotics are much more expensive and un affordable.Conclusion:    Need of this review is especially for Silver Nanoparticles (AgNPs manufactured by some types of fungi introduced by recent researchers have an edge to control or treat some sort of infections due to their antibacterial properties. In this study these (AgNPs in the form of suspension, give positive results against the Salmonella species. It enables us to treat the typhoid infection in a less expensive way.

The Typhoid Fever Surveillance in Africa Program (TSAP): Clinical, Diagnostic, and Epidemiological Methodologies.

Science.gov (United States)

von Kalckreuth, Vera; Konings, Frank; Aaby, Peter; Adu-Sarkodie, Yaw; Ali, Mohammad; Aseffa, Abraham; Baker, Stephen; Breiman, Robert F; Bjerregaard-Andersen, Morten; Clemens, John D; Crump, John A; Cruz Espinoza, Ligia Maria; Deerin, Jessica Fung; Gasmelseed, Nagla; Sow, Amy Gassama; Im, Justin; Keddy, Karen H; Cosmas, Leonard; May, Jürgen; Meyer, Christian G; Mintz, Eric D; Montgomery, Joel M; Olack, Beatrice; Pak, Gi Deok; Panzner, Ursula; Park, Se Eun; Rakotozandrindrainy, Raphaël; Schütt-Gerowitt, Heidi; Soura, Abdramane Bassiahi; Warren, Michelle R; Wierzba, Thomas F; Marks, Florian

2016-03-15

New immunization programs are dependent on data from surveillance networks and disease burden estimates to prioritize target areas and risk groups. Data regarding invasive Salmonella disease in sub-Saharan Africa are currently limited, thus hindering the implementation of preventive measures. The Typhoid Fever Surveillance in Africa Program (TSAP) was established by the International Vaccine Institute to obtain comparable incidence data on typhoid fever and invasive nontyphoidal Salmonella (iNTS) disease in sub-Saharan Africa through standardized surveillance in multiple countries. Standardized procedures were developed and deployed across sites for study site selection, patient enrolment, laboratory procedures, quality control and quality assurance, assessment of healthcare utilization and incidence calculations. Passive surveillance for bloodstream infections among febrile patients was initiated at thirteen sentinel sites in ten countries (Burkina Faso, Ethiopia, Ghana, Guinea-Bissau, Kenya, Madagascar, Senegal, South Africa, Sudan, and Tanzania). Each TSAP site conducted case detection using these standardized methods to isolate and identify aerobic bacteria from the bloodstream of febrile patients. Healthcare utilization surveys were conducted to adjust population denominators in incidence calculations for differing healthcare utilization patterns and improve comparability of incidence rates across sites. By providing standardized data on the incidence of typhoid fever and iNTS disease in sub-Saharan Africa, TSAP will provide vital input for targeted typhoid fever prevention programs. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Usefulness of low dose oral contrast media in 18F-FDG PET/CT

International Nuclear Information System (INIS)

An, Young Sil; Yoon, Joon Kee; Hong, Seon Pyo; Joh, Chul Woo; Yoon, Seok Nam

2006-01-01

The standard protocol using large volume of oral contrast media may cause gastrointestinal discomfort and contrast-related artifacts in PET/CT. The aim of this study was to evaluate the usefulness of low dose oral contrast in 18 F-FDG PET/CT. We retrospectively reviewed the whole-body PET/CT images in a total of 435 patients. About 200 ml of oral contrast agent (barium sulfate) was administered immediately before injection of 18 F-FDG. The FDG uptake of intestines was analyzed by visual and semi-quantitative method on transaxial, coronal and saggital planes. Seventy (16%, 113 sites) of 435 images showed high FDG uptake (peak SUV > 4); 50 (74%, 84 sites) with diffuse and 20 (26%, 29 sites) with focal uptake. The most commonly delivered site of oral contrast media was small bowel (n = 27, 39%). On PET/CT images, FDG uptake coexisted with oral contrast media in 26 patients (54%, 38 sites) with diffuse pattern and 9 (45%, 9 sites) with focal pattern, and by sites, those were 38 (45%) and 9 (31%), respectively. In small bowel regions, the proportion of coexistence reached as high as 61% (29/47 sites). A visual analysis of available non-attenuation corrected PET images of 27 matched regions revealed no contrast-related artifact. We concluded that the application of low dose contrast media could be helpful in the evaluation of abdominal uptake in the FDG PET/CT image

Errors detected in pediatric oral liquid medication doses prepared in an automated workflow management system.

Science.gov (United States)

Bledsoe, Sarah; Van Buskirk, Alex; Falconer, R James; Hollon, Andrew; Hoebing, Wendy; Jokic, Sladan

2018-02-01

The effectiveness of barcode-assisted medication preparation (BCMP) technology on detecting oral liquid dose preparation errors. From June 1, 2013, through May 31, 2014, a total of 178,344 oral doses were processed at Children's Mercy, a 301-bed pediatric hospital, through an automated workflow management system. Doses containing errors detected by the system's barcode scanning system or classified as rejected by the pharmacist were further reviewed. Errors intercepted by the barcode-scanning system were classified as (1) expired product, (2) incorrect drug, (3) incorrect concentration, and (4) technological error. Pharmacist-rejected doses were categorized into 6 categories based on the root cause of the preparation error: (1) expired product, (2) incorrect concentration, (3) incorrect drug, (4) incorrect volume, (5) preparation error, and (6) other. Of the 178,344 doses examined, 3,812 (2.1%) errors were detected by either the barcode-assisted scanning system (1.8%, n = 3,291) or a pharmacist (0.3%, n = 521). The 3,291 errors prevented by the barcode-assisted system were classified most commonly as technological error and incorrect drug, followed by incorrect concentration and expired product. Errors detected by pharmacists were also analyzed. These 521 errors were most often classified as incorrect volume, preparation error, expired product, other, incorrect drug, and incorrect concentration. BCMP technology detected errors in 1.8% of pediatric oral liquid medication doses prepared in an automated workflow management system, with errors being most commonly attributed to technological problems or incorrect drugs. Pharmacists rejected an additional 0.3% of studied doses. Copyright © 2018 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Low-level quinolone-resistance in multi-drug resistant typhoid

Energy Technology Data Exchange (ETDEWEB)

Mirza, S H; Khan, M A [Armed Forces Inst. of Pathology, Rawalpindi (Pakistan). Dept. of Microbiolgy

2008-01-15

To find out the frequency of low-level quinolone-resistance in Multi-Drug Resistant (MDR) typhoid using nalidixic acid screening disc. Blood was obtained from suspected cases of typhoid fever and cultured in to BacT/ALERT. The positive blood cultures bottles were subcultured. The isolates were identified by colony morphology and biochemical tests using API-20E galleries. Susceptibility testing of isolates was done by modified Kirby-Bauer disc diffusion method on Muellar Hinton Agar. For the isolates, which were resistant to nalidixic acid by disc diffusion method, Minimal Inhibitory Concentrations (MICs) of ciprofloxacin and nalidixic acid were determined by using the E-test strips. Disc diffusion susceptibility tests and MICs were interpreted according to the guidelines provided by National Committee for Control Laboratory Standard (NCCLS). A total of 21(65.5%) out of 32 isolates of Salmonellae were nalidixic acid-resistant by disk diffusion method. All the nalidixic acid-resistant isolates by disc diffusion method were confirmed by MICs for both ciprofloxacin and nalidixic acid. All the nalidixic acid-resistant isolates had a ciprofloxacin MIC of 0.25-1 microg/ml (reduced susceptibility) and nalidixic acid MICs > 32 microg (resistant). Out of all Salmonella isolates, 24 (75%) were found to be MDR, and all were S. typbi. Low-level quinolone-resistance in typhoid was high in this small series. Screening for nalidixic acid resistance with a 30 microg nalidixic acid disk is a reliable and cost-effective method to detect low-level fluoroquinolone resistance, especially in the developing countries. (author)

Low-level quinolone-resistance in multi-drug resistant typhoid

International Nuclear Information System (INIS)

Mirza, S.H.; Khan, M.A.

2008-01-01

To find out the frequency of low-level quinolone-resistance in Multi-Drug Resistant (MDR) typhoid using nalidixic acid screening disc. Blood was obtained from suspected cases of typhoid fever and cultured in to BacT/ALERT. The positive blood cultures bottles were subcultured. The isolates were identified by colony morphology and biochemical tests using API-20E galleries. Susceptibility testing of isolates was done by modified Kirby-Bauer disc diffusion method on Muellar Hinton Agar. For the isolates, which were resistant to nalidixic acid by disc diffusion method, Minimal Inhibitory Concentrations (MICs) of ciprofloxacin and nalidixic acid were determined by using the E-test strips. Disc diffusion susceptibility tests and MICs were interpreted according to the guidelines provided by National Committee for Control Laboratory Standard (NCCLS). A total of 21(65.5%) out of 32 isolates of Salmonellae were nalidixic acid-resistant by disk diffusion method. All the nalidixic acid-resistant isolates by disc diffusion method were confirmed by MICs for both ciprofloxacin and nalidixic acid. All the nalidixic acid-resistant isolates had a ciprofloxacin MIC of 0.25-1 microg/ml (reduced susceptibility) and nalidixic acid MICs > 32 microg (resistant). Out of all Salmonella isolates, 24 (75%) were found to be MDR, and all were S. typbi. Low-level quinolone-resistance in typhoid was high in this small series. Screening for nalidixic acid resistance with a 30 microg nalidixic acid disk is a reliable and cost-effective method to detect low-level fluoroquinolone resistance, especially in the developing countries. (author)

An evaluation of purified Salmonella Typhi protein antigens for the serological diagnosis of acute typhoid fever.

Science.gov (United States)

Tran Vu Thieu, Nga; Trinh Van, Tan; Tran Tuan, Anh; Klemm, Elizabeth J; Nguyen Ngoc Minh, Chau; Voong Vinh, Phat; Pham Thanh, Duy; Ho Ngoc Dan, Thanh; Pham Duc, Trung; Langat, Pinky; Martin, Laura B; Galan, Jorge; Liang, Li; Felgner, Philip L; Davies, D Huw; de Jong, Hanna K; Maude, Rapeephan R; Fukushima, Masako; Wijedoru, Lalith; Ghose, Aniruddha; Samad, Rasheda; Dondorp, Arjen M; Faiz, Abul; Darton, Thomas C; Pollard, Andrew J; Thwaites, Guy E; Dougan, Gordon; Parry, Christopher M; Baker, Stephen

2017-08-01

The diagnosis of typhoid fever is a challenge. Aiming to develop a typhoid diagnostic we measured antibody responses against Salmonella Typhi (S. Typhi) protein antigens and the Vi polysaccharide in a cohort of Bangladeshi febrile patients. IgM against 12 purified antigens and the Vi polysaccharide was measured by ELISA in plasma from patients with confirmed typhoid fever (n = 32), other confirmed infections (n = 17), and healthy controls (n = 40). ELISAs with the most specific antigens were performed on plasma from 243 patients with undiagnosed febrile disease. IgM against the S. Typhi protein antigens correlated with each other (rho > 0.8), but not against Vi (rho Typhoid patients exhibited higher IgM against 11/12 protein antigens and Vi than healthy controls and those with other infections. Vi, PilL, and CdtB exhibited the greatest sensitivity and specificity. Specificity and sensitivity was improved when Vi was combined with a protein antigen, generating sensitivities and specificities of 0.80 and >0.85, respectively. Applying a dynamic cut-off to patients with undiagnosed febrile disease suggested that 34-58% had an IgM response indicative of typhoid. We evaluated the diagnostic potential of several S. Typhi antigens; our assays give good sensitivity and specificity, but require further assessment in differing patient populations. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Risk Factors and Dose-Effect Relationship for Mandibular Osteoradionecrosis in Oral and Oropharyngeal Cancer Patients

International Nuclear Information System (INIS)

Lee, Ik Jae; Koom, Woong Sub; Lee, Chang Geol; Kim, Yong Bae; Yoo, Sei Whan; Keum, Ki Chang; Kim, Gwi Eon; Choi, Eun Chang; Cha, In Ho

2009-01-01

Purpose: To analyze risk factors and the dose-effect relationship for osteoradionecrosis (ORN) of the mandible after radiotherapy of oral and oropharyngeal cancers. Materials and Methods: One-hundred ninety-eight patients with oral (45%) and oropharyngeal cancer (55%) who had received external radiotherapy between 1990 and 2000 were retrospectively reviewed. All patients had a dental evaluation before radiotherapy. The median radiation dose was 60 Gy (range, 16-75 Gy), and the median biologically effective dose for late effects (BED late ) in bone was 114 Gy 2 (range, 30-167 Gy 2 ). Results: The frequency of ORN was 13 patients (6.6%). Among patients with mandibular surgery, eight had ORN at the surgical site. Among patients without mandibular surgery, five patients had ORN on the molar area of the mandible. The median time to ORN was 22 months (range, 1-69 months). Univariate analysis revealed that mandibular surgery and Co-60 were significant risk factors for ORN (p = 0.01 and 0.04, respectively). In multivariate analysis, mandibular surgery was the most important factor (p = 0.001). High radiation doses over BED 102.6 Gy 2 (conventional dose of 54 Gy at 1.8 Gy/fraction) were also a significant factor for ORN (p = 0.008) and showed a positive dose-effect relationship in logistic regression (p = 0.04) for patients who had undergone mandibular surgery. Conclusions: Mandibular surgery was the most significant risk factor for ORN of mandible in oral and oropharyngeal cancers patients. A BED of 102.6 Gy 2 or higher to the mandible also significantly increases the risk of ORN.

Serum toxicokinetics after intravenous and oral dosing of larkspur toxins in goats

Science.gov (United States)

Poisoning of cattle by larkspur plants (Delphinium spp.) is a concern for cattle ranchers in western North America. Previous research studies have evaluated the toxicokinetic profile of multiple larkspur toxins in several livestock species. However, those studies were all performed by orally dosing ...

Colonoscopic findings and management of patients with outbreak typhoid fever presenting with lower gastrointestinal bleeding.

Science.gov (United States)

Shaikhani, Mohammad A R; Husein, Hiwa A B; Karbuli, Taha A; Mohamed, Mohamed Abdulrahman

2013-09-01

Lower gastrointestinal bleeding (LGIB) along with intestinal perforation is a well-known complication of typhoid fever. Reports of colonoscopic appearance and intervention of typhoid perforation involve only few cases. This series reports the colonoscopic findings and the role of colonoscopic hemostatic interventions in controlling the bleeding ileocolonic lesions. During the typhoid fever outbreak in Sulaymaniyah City in Iraqi Kurdistan Region, we received 52 patients with LGIB manifesting as fresh bleeding per rectum or melena. We performed total colonoscopy with ileal intubation for all cases. The findings were recorded and endoscopic hemostatic intervention with adrenaline-saline injection and argon plasma coagulation was applied to actively bleeding lesion. These patients were young, 11-30 years of age, with female preponderance. Blood culture was positive in 50 %. Colonoscopic findings were mostly located in the ileocecal region, although other areas of the colon were involved in many cases. Twenty-four percent of the cases required endoscopic hemostatic intervention by adrenaline injection with argon plasma coagulation which was effective in all patients except one who died in spite of surgical intervention in addition of endoscopic hemostasis. Dual endoscopic hemostatic intervention can be a safe and effective management option for patients with LGIB due to typhoid fever.

Single-layer closure of typhoid enteric perforation: Our experience ...

African Journals Online (AJOL)

Materials and Methods: We retrospectively studied the effects of single versus double layer intestinal closure after typhoid enteric perforation with peritonitis in 902 pediatric patients from September 2007 to April 2012. All the patients underwent laparotomy after resuscitation and antibiotic cover. The patients were divided ...

The Incidence and Management of Typhoid Fever in Nigeria ...

African Journals Online (AJOL)

Typhoid or enteric fever is caused by Salmonella typhi. It is largely a disease of developing nations due to their poor standard of hygiene and ... Symptoms such as diarrhoea, constipation, abdominal pain and encephalopathy may occur. Complications like intestinal perforation and gastrointestinal haemorrhage may occur ...

Miltefosine Lipid Nanocapsules for Single Dose Oral Treatment of Schistosomiasis Mansoni: A Preclinical Study.

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Maha M Eissa

Full Text Available Miltefosine (MFS is an alkylphosphocholine used for the local treatment of cutaneous metastases of breast cancer and oral therapy of visceral leishmaniasis. Recently, the drug was reported in in vitro and preclinical studies to exert significant activity against different developmental stages of schistosomiasis mansoni, a widespread chronic neglected tropical disease (NTD. This justified MFS repurposing as a potential antischistosomal drug. However, five consecutive daily 20 mg/kg doses were needed for the treatment of schistosomiasis mansoni in mice. The present study aims at enhancing MFS efficacy to allow for a single 20mg/kg oral dose therapy using a nanotechnological approach based on lipid nanocapsules (LNCs as oral nanovectors. MFS was incorporated in LNCs both as membrane-active structural alkylphospholipid component and active antischistosomal agent. MFS-LNC formulations showed high entrapment efficiency (EE%, good colloidal properties, sustained release pattern and physical stability. Further, LNCs generally decreased MFS-induced erythrocyte hemolytic activity used as surrogate indicator of membrane activity. While MFS-free LNCs exerted no antischistosomal effect, statistically significant enhancement was observed with all MFS-LNC formulations. A maximum effect was achieved with MFS-LNCs incorporating CTAB as positive charge imparting agent or oleic acid as membrane permeabilizer. Reduction of worm load, ameliorated liver pathology and extensive damage of the worm tegument provided evidence for formulation-related efficacy enhancement. Non-compartmental analysis of pharmacokinetic data obtained in rats indicated independence of antischistosomal activity on systemic drug exposure, suggesting possible gut uptake of the stable LNCs and targeting of the fluke tegument which was verified by SEM. The study findings put forward MFS-LNCs as unique oral nanovectors combining the bioactivity of MFS and biopharmaceutical advantages of LNCs

Effect of single oral dose of tramadol on gastric secretions pH

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Khan Mueen Ullah

2015-01-01

Full Text Available Background: Tramadol is an atypical analgesic agent. It has been shown that intramuscular or intravenous injection tramadol is able to inhibit M3 muscarinic receptors. Tramadol is able to mediate smooth muscles contraction and glandular secretions. We have evaluated the effects of single oral dose of tramadol given preoperatively on gastric juices pH in patients electively scheduled for laparoscopic cholecystectomy. Materials and Methods: Sixty adult, American Society of Anesthesiologist I and II patients scheduled for laparoscopic cholecystectomy were included in the study. Patients were randomly assigned to receive either placebo (n = 30 or oral tramadol 50 mg (n = 30. General anesthesia was induced using propofol, fentanyl and cisatracurium. After induction of anesthesia 5 ml of gastric fluid was aspirated through orogastric tube. The gastric fluid pH was measured using pH meter. Result: There was no significant difference in the pH between the groups. Gastric pH of the placebo and tramadol groups was 1.97 versus 1.98 (P = 0.092 respectively. Conclusion: Preoperatively single oral dose of tramadol was unable to elevate the desired level of gastric acid secretions pH (>2.5. This may be due to pharmacokinetic disparity between the analgesic and pH elevating properties of tramadol.

Oral cryotherapy for the prevention of high-dose melphalan-induced stomatitis in allogeneic hematopoietic stem cell transplant recipients.

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Aisa, Yoshinobu; Mori, Takehiko; Kudo, Masumi; Yashima, Tomoko; Kondo, Sakiko; Yokoyama, Akihiro; Ikeda, Yasuo; Okamoto, Shinichiro

2005-04-01

The purpose of this study was to evaluate the efficacy of oral cryotherapy to prevent high-dose melphalan-induced stomatitis. Eighteen consecutive recipients of allogeneic hematopoietic stem cell transplant conditioned with high-dose melphalan (140 mg/m2) in combination with fludarabine alone or with fludarabine and additional chemotherapy or radiation were enrolled. The severity of stomatitis was graded according to the National Cancer Institute Common Toxicity Criteria. Patients were kept on oral cryotherapy using ice chips and ice-cold water shortly before, during, and for additional 90 min after completion of melphalan administration. Only two of 18 patients (11.1%) developed grade 2 or 3 stomatitis while six of seven patients in the historical control developed it (85.7%; P=0.001). These results suggested that oral cryotherapy could effectively prevent stomatitis caused by high-dose melphalan, and we recommend that it should be incorporated into the conditioning regimen with high-dose melphalan.

Rapid diagnostic tests for typhoid and paratyphoid (enteric) fever.

Science.gov (United States)

Wijedoru, Lalith; Mallett, Sue; Parry, Christopher M

2017-05-26

Differentiating both typhoid (Salmonella Typhi) and paratyphoid (Salmonella Paratyphi A) infection from other causes of fever in endemic areas is a diagnostic challenge. Although commercial point-of-care rapid diagnostic tests (RDTs) for enteric fever are available as alternatives to the current reference standard test of blood or bone marrow culture, or to the widely used Widal Test, their diagnostic accuracy is unclear. If accurate, they could potentially replace blood culture as the World Health Organization (WHO)-recommended main diagnostic test for enteric fever. To assess the diagnostic accuracy of commercially available rapid diagnostic tests (RDTs) and prototypes for detecting Salmonella Typhi or Paratyphi A infection in symptomatic persons living in endemic areas. We searched the Cochrane Infectious Diseases Group Specialized Register, MEDLINE, Embase, Science Citation Index, IndMED, African Index Medicus, LILACS, ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) up to 4 March 2016. We manually searched WHO reports, and papers from international conferences on Salmonella infections. We also contacted test manufacturers to identify studies. We included diagnostic accuracy studies of enteric fever RDTs in patients with fever or with symptoms suggestive of enteric fever living in endemic areas. We classified the reference standard used as either Grade 1 (result from a blood culture and a bone marrow culture) or Grade 2 (result from blood culture and blood polymerase chain reaction, or from blood culture alone). Two review authors independently extracted the test result data. We used a modified QUADAS-2 extraction form to assess methodological quality. We performed a meta-analysis when there were sufficient studies for the test and heterogeneity was reasonable. Thirty-seven studies met the inclusion criteria and included a total of 5080 participants (range 50 to 1732). Enteric fever prevalence

Bioavailability of higher dose methotrexate comparing oral and subcutaneous administration in patients with rheumatoid arthritis

NARCIS (Netherlands)

Hoekstra, Monique; Haagsma, C.; Neef, C; Proost, Johannes H; Knuif, A.; van der Laar, M.

Objective. To determine the bioavailability of higher oral doses of methotrexate (MTX) in adult patients with rheumatoid arthritis (RA). Methods. A pharmacokinetic analysis was performed in 15 patients with RA taking a stable dose of MTX (greater than or equal to25 mg weekly). Separated by 2 weeks,

A Meta-Analysis of Typhoid Diagnostic Accuracy Studies: A Recommendation to Adopt a Standardized Composite Reference.

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Helen L Storey

Full Text Available Novel typhoid diagnostics currently under development have the potential to improve clinical care, surveillance, and the disease burden estimates that support vaccine introduction. Blood culture is most often used as the reference method to evaluate the accuracy of new typhoid tests; however, it is recognized to be an imperfect gold standard. If no single gold standard test exists, use of a composite reference standard (CRS can improve estimation of diagnostic accuracy. Numerous studies have used a CRS to evaluate new typhoid diagnostics; however, there is no consensus on an appropriate CRS. In order to evaluate existing tests for use as a reference test or inclusion in a CRS, we performed a systematic review of the typhoid literature to include all index/reference test combinations observed. We described the landscape of comparisons performed, showed results of a meta-analysis on the accuracy of the more common combinations, and evaluated sources of variability based on study quality. This wide-ranging meta-analysis suggests that no single test has sufficiently good performance but some existing diagnostics may be useful as part of a CRS. Additionally, based on findings from the meta-analysis and a constructed numerical example demonstrating the use of CRS, we proposed necessary criteria and potential components of a typhoid CRS to guide future recommendations. Agreement and adoption by all investigators of a standardized CRS is requisite, and would improve comparison of new diagnostics across independent studies, leading to the identification of a better reference test and improved confidence in prevalence estimates.

20 YEARS OF PROGRESS IN TYPHOID RESEARCH

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Narain H. Punjabi

2012-09-01

Full Text Available In 1981, the reported number of cases of typhoid fever in Indonesia was 19,596, increasing to 26,606 m 1986, most of the increase was due to improved detection and recognition of the pathogen. A more realistic estimate of incidence for this underreported and underdiagnosed disease would be from 540,000 to 1,210,000 cases per year. This was based on results of a household survey done by Budiarso R. et al. in 1980 and 1986, and on result of a community surveillance done by Ruwido and Simanjuntak et al. from 1983-1988. These studies were done in Plaju, South Sumatera, representing an urban area and Paseh, West Java, representing a semi-rural area. The results showed that the incidence rate of typhoid fever in the semi rural area was 358/100,000 population/year, and between 760-810/100,000 population/year in the urban area. These studies also indicated that the high risk group in the population was school age children between ages of 3-19 years. From other observations, it is also noted that the case fatality in urbanized and growing areas of Indonesia, may be higher than it is reported in other areas of the world

Prospective Evaluation to Establish a Dose Response for Clinical Oral Mucositis in Patients Undergoing Head-and-Neck Conformal Radiotherapy

International Nuclear Information System (INIS)

Narayan, Samir; Lehmann, Joerg; Coleman, Matthew A.; Vaughan, Andrew; Yang, Claus Chunli; Enepekides, Danny; Farwell, Gregory; Purdy, James A.; Laredo, Grace; Nolan, Kerry A.S.; Pearson, Francesca S.; Vijayakumar, Srinivasan

2008-01-01

Purpose: We conducted a clinical study to correlate oral cavity dose with clinical mucositis, perform in vivo dosimetry, and determine the feasibility of obtaining buccal mucosal cell samples in patients undergoing head-and-neck radiation therapy. The main objective is to establish a quantitative dose response for clinical oral mucositis. Methods and Materials: Twelve patients undergoing radiation therapy for head-and-neck cancer were prospectively studied. Four points were chosen in separate quadrants of the oral cavity. Calculated dose distributions were generated by using AcQPlan and Eclipse treatment planning systems. MOSFET dosimeters were used to measure dose at each sampled point. Each patient underwent buccal sampling for future RNA analysis before and after the first radiation treatment at the four selected points. Clinical and functional mucositis were assessed weekly according to National Cancer Institute Common Toxicity Criteria, Version 3. Results: Maximum and average doses for sampled sites ranged from 7.4-62.3 and 3.0-54.3 Gy, respectively. A cumulative point dose of 39.1 Gy resulted in mucositis for 3 weeks or longer. Mild severity (Grade ≤ 1) and short duration (≤1 week) of mucositis were found at cumulative point doses less than 32 Gy. Polymerase chain reaction consistently was able to detect basal levels of two known radiation responsive genes. Conclusions: In our sample, cumulative doses to the oral cavity of less than 32 Gy were associated with minimal acute mucositis. A dose greater than 39 Gy was associated with longer duration of mucositis. Our technique for sampling buccal mucosa yielded sufficient cells for RNA analysis using polymerase chain reaction

Poor food hygiene and housing as risk factors for typhoid fever in Semarang, Indonesia.

Science.gov (United States)

Gasem, M H; Dolmans, W M; Keuter, M M; Djokomoeljanto, R R

2001-06-01

To identify risk factors for typhoid fever in Semarang city and its surroundings, 75 culture-proven typhoid fever patients discharged 2 weeks earlier from hospital and 75 controls were studied. Control subjects were neighbours of cases with no history of typhoid fever, not family members, randomly selected and matched for gender and age. Both cases and controls were interviewed at home by the same trained interviewer using a standardized questionnaire. A structured observation of their living environment inside and outside the house was performed during the visit and home drinking water samples were tested bacteriologically. Univariate analysis showed the following risk factors for typhoid fever: never or rarely washing hands before eating (OR = 3.28; 95% CI = 1.41-7.65); eating outdoors at least once a week (OR = 3.00; 95% CI = 1.09-8.25); eating outdoors at a street food stall or mobile food vendor (OR = 3.86; 95% CI = 1.30-11.48); consuming ice cubes in beverage in the 2-week period before getting ill (OR = 3.00, 95% CI = 1.09-8.25) and buying ice cubes from a street vendor (OR = 5.82; 95% CI = 1.69-20.12). Water quality and living environment of cases were worse than that of controls, e.g. cases less often used clean water for taking a bath (OR = 6.50; 95% CI = 1.47-28.80), for brushing teeth (OR = 4.33; 95% CI = 1.25-15.20) and for drinking (OR = 3.67; 95% CI = 1.02-13.14). Cases tended to live in houses without water supply from the municipal network (OR=11.00; 95% CI = 1.42-85.2), with open sewers (OR = 2.80; 95% CI = 1.0-7.77) and without tiles in the kitchen (OR = 2.67; 95% CI = 1.04-6.81). Multivariate analysis showed that living in a house without water supply from the municipal network (OR = 29.18; 95% CI = 2.12-400.8) and with open sewers (OR = 7.19; 95% CI = 1.33-38.82) was associated with typhoid fever. Never or rarely washing hands before eating (OR = 3.97; 95% CI = 1.22-12.93) and being unemployed or having a part-time job (OR = 31.3; 95% CI = 3

Typhoid fever in children: Clinical presentation and risk factors ...

African Journals Online (AJOL)

and prevention (CDC) case definition for typhoid fever, between 1st. January and 31st December 2010, were consecutively reviewed using a structured questionnaire. Results: A total of 42 patients were admitted out of which 35 were analysed, the remaining 7 were excluded because consent was not obtained. The disease ...

High-dose-rate brachytherapy using molds for oral cavity cancer. The technique and its limitations

International Nuclear Information System (INIS)

Nishimura, Yasumasa; Yokoe, Yoshihiko; Nagata, Yasushi; Okajima, Kaoru; Nishida, Mitsuo; Hiraoka, Masahiro

1998-01-01

With the availability of a high-dose-rate (HDR) remote afterloading device, a Phase I/II protocol was initiated at our institution to assess the toxicity and efficacy of HDR intracavitary brachytherapy, using molds, in the treatment of squamous cell carcinomas of the oral cavity. Eight patients with squamous cell carcinoma of the oral cavity were treated by the technique. The primary sites of the tumors were the buccal mucosa, oral floor, and gingiva. Two of the buccal mucosal cancers were located in the retromolar trigon. For each patient, a customized mold was fabricated, in which two to four afterloading catheters were placed for an 192 Ir HDR source. Four to seven fractions of 3-4 Gy, 5 mm below the mold surface, were given following external radiation therapy of 40-60 Gy/ 2 Gy. The total dose of HDR brachytherapy ranged from 16 to 28Gy. Although a good initial complete response rate of 7/8 (88%) was achieved, there was local recurrence in four of these seven patients. Both of the retromolar trigon tumors showed marginal recurrence. No serious (e.g., ulcer or bone exposure) late radiation damage has been observed thus far in the follow up period of 15-57 months. High-dose-rate brachytherapy using the mold technique seems a safe and useful method for selected early and superficial oral cavity cancer. However, it is not indicated for thick tumors and/or tumors located in the retromolar trigon. (author)

High Dose Oral Calcium Treatment in Patients with Vitamin D-dependent Rickets Type II

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R Vakili

2017-02-01

Full Text Available BACKGROUND AND OBJECTIVE: Vitamin D-dependent rickets type II (VDDR2 is a rare genetic disorder caused by mutations in vitamin D receptor (VDR and leads to resistance to biological effects of calcitriol. Based on the type of mutation, this disease is resistant to calcitriol even at high doses of calcitriol and successful treatment of these patients requires hypocalcemic modification through administration of high doses of calcium and bypassing the intestinal defect in VDR signaling. In addition to the need for frequent hospitalization and high costs, intravenous administration of calcium is associated with complications and problems such as arrhythmia and sepsis, venous catheter infection and hypercalciuria. This study aims to report the positive treatment effects of high doses of oral calcium in 4 patients with vitamin D-dependent rickets type II. CASE REPORT: In this study, 4 patients with vitamin D-dependent rickets type II, diagnosed based on clinical and biochemical symptoms of rickets with alopecia, underwent therapy using high doses of oral calcium (300 mg/kg/day in pediatric endocrinology and metabolism center of Imam Reza hospital. After a short period, increased growth rate in height, strength and elasticity of muscles was observed in addition to biochemical improvements without serious side effects and even one patient started walking independently within the first week of therapy for the first time. Patients were regularly followed up in terms of height and weight, growth rate and biochemical factors including calcium, phosphorus and alkaline phosphatase every 3 months for one year. CONCLUSION: Regardless of the type of mutation in vitamin D receptor, it is suggested that a 3-6 months trial of high dose oral calcium be started in each patient with vitamin D-dependent rickets type II, particularly for patients whose disease was diagnosed at lower ages.

Burden of typhoid fever in low-income and middle-income countries: a systematic, literature-based update with risk-factor adjustment.

Science.gov (United States)

Mogasale, Vittal; Maskery, Brian; Ochiai, R Leon; Lee, Jung Seok; Mogasale, Vijayalaxmi V; Ramani, Enusa; Kim, Young Eun; Park, Jin Kyung; Wierzba, Thomas F

2014-10-01

No access to safe water is an important risk factor for typhoid fever, yet risk-level heterogeneity is unaccounted for in previous global burden estimates. Since WHO has recommended risk-based use of typhoid polysaccharide vaccine, we revisited the burden of typhoid fever in low-income and middle-income countries (LMICs) after adjusting for water-related risk. We estimated the typhoid disease burden from studies done in LMICs based on blood-culture-confirmed incidence rates applied to the 2010 population, after correcting for operational issues related to surveillance, limitations of diagnostic tests, and water-related risk. We derived incidence estimates, correction factors, and mortality estimates from systematic literature reviews. We did scenario analyses for risk factors, diagnostic sensitivity, and case fatality rates, accounting for the uncertainty in these estimates and we compared them with previous disease burden estimates. The estimated number of typhoid fever cases in LMICs in 2010 after adjusting for water-related risk was 11·9 million (95% CI 9·9-14·7) cases with 129 000 (75 000-208 000) deaths. By comparison, the estimated risk-unadjusted burden was 20·6 million (17·5-24·2) cases and 223 000 (131 000-344 000) deaths. Scenario analyses indicated that the risk-factor adjustment and updated diagnostic test correction factor derived from systematic literature reviews were the drivers of differences between the current estimate and past estimates. The risk-adjusted typhoid fever burden estimate was more conservative than previous estimates. However, by distinguishing the risk differences, it will allow assessment of the effect at the population level and will facilitate cost-effectiveness calculations for risk-based vaccination strategies for future typhoid conjugate vaccine. Copyright © 2014 Mogasale et al. Open Access article distributed under the terms of CC BY-NC-SA. Published by .. All rights reserved.

A 4-Week Repeated-Dose Oral Toxicity Study of Bojungikgi-Tang in Crl:CD Sprague Dawley Rats

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Sae-Rom Yoo

2017-01-01

Full Text Available Traditional herbal medicines have been used for centuries in Asian countries. However, recent studies have led to increasing concerns about the safety and toxicity of herbal prescriptions. Bojungikgi-tang (BJIGT, a herbal decoction, has been used in Korea to improve physical strength. To establish the safety information, BJIGT water extract was evaluated in a 4-week repeated-dose oral toxicity test in Crl:CD Sprague Dawley rats. BJIGT was orally administered in daily doses of 0, 500, 1000, and 2000 mg/kg/day for 4 weeks via oral gavage in male and female rats. We examined the mortality, clinical signs, body weight change, food intake, organ weights, hematology, serum biochemistry, and urinalysis parameters. No significant changes were observed in mortality, clinical sings, body weight, food intake, organ weights, hematology, serum biochemistry, and urinalysis parameters between the control group and the BJIGT-treated groups in the rats of both sexes. The results indicate that BJIGT did not induce toxic effects at a dose level up to 2000 mg/kg in rats. Thus, this concentration is considered the nonobservable effect dose in rats and is appropriate for a 13-week subchronic toxicity study.

[Oral loading dose of phenytoin in the treatment of serial seizures, prevention of seizure recurrence and rapid drug substitution].

Science.gov (United States)

Sokić, D; Janković, S M

1994-01-01

Over a period of nine months twenty-five epileptic patients were treated with the oral loading dose of phenytoin. The dose ranged from 12 to 23 mg/kg body weight during 1 to 12 hours. In 20 patients with serial seizures or intolerance to other antiepileptic drugs this treatment was effective. Seizures also stopped in 2 of 4 patients with serial partial motor seizures. These 2 patients required both higher loading dose and faster rate of administration than the other patients. A patient with epilepsia partialis continua failed to respond to the treatment. Patients that received phenytoin through the naso-gastric tube, in respect to oral administration, required higher doses to obtain therapeutic plasma levels of phenytoin. One patient had mild nausea, 3 mild dizziness, and 1 tinitus on the first day of the treatment. There was no correlation between a given dose and the achieved phenytoin plasma levels. In our opinion the therapy with oral loading dose of phenytoin is highly effective in the treatment of serial generalized seizures and rapid antiepileptic drug substitution, and partially effective in the prevention of partial motor seizures. It produces only mild and transient side-effects.

Comparing the effects of low-dose contraceptive pills to control dysfunctional uterine bleeding by oral and vaginal methods.

Science.gov (United States)

Mehrabian, Ferdous; Abbassi, Fariba

2013-09-01

Background and Objective : Contraceptive pills are generally taken orally and can cause side effects such as nausea, vomiting and hypertension. The vaginal use of these pills can reduce such complications. Our objective was to compare the efficacy and side effects of low dose contraceptive pills by oral and vaginal route in the management of dysfunctional uterine bleeding-(DUB) Methods: This comparative observational study was conducted at Beheshti and Alzahra (SA) teaching hospitals, affiliated to Isfahan University of Medical Sciences in 2010-2011. One hundred women who presented with DUB were randomly assigned into two groups of equal number, receiving the low dose oral contraceptive pills by oral or vaginal route for three month. The amount and duration of bleeding were compared at the beginning and at the end of the study and side effects by these two methods compared. The results of this study showed that both oral and vaginal routes effectively reduced the duration and amount of bleeding due to DUB after three courses of treatment. This effect was better in the vaginal method compared with oral administration (P = 0.03). Regarding the side effects, nausea and vomiting were significantly higher in the oral group than in the vaginal group (P = 0.03). Vulvovaginitis infection was more frequent in the vaginal group than in the oral group (P = 0.03). Low dose contraceptive pills are effective in reducing the amount, time, and duration of bleeding in patients with DUB. In addition, reduction of gastrointestinal side effects by vaginal route helps to use these pills by the patient with proper training of physicians, midwives and patients.

Utilization and Accessibility of Healthcare on Pemba Island, Tanzania: Implications for Health Outcomes and Disease Surveillance for Typhoid Fever

Science.gov (United States)

Kaljee, Linda M.; Pach, Alfred; Thriemer, Kamala; Ley, Benedikt; Ali, Said M.; Jiddawi, Mohamed; Puri, Mahesh; von Seidlein, Lorenz; Deen, Jacqueline; Ochiai, Leon; Wierzba, Thomas; Clemens, John

2013-01-01

Salmonella enterica serotype Typhi (S. Typhi) was estimated to cause over 200,000 deaths and more than 21 million illnesses worldwide, including over 400,000 illnesses in Africa. The current study was conducted in four villages on Pemba Island, Zanzibar, in 2010. We present data on policy makers', health administrators', and village residents' and leaders' perceptions of typhoid fever, and hypothetical and actual health care use among village residents for typhoid fever. Qualitative data provided descriptions of home-based treatment practices and use of western pharmaceuticals, and actual healthcare use for culture-confirmed typhoid fever. Survey data indicate health facility use was associated with gender, education, residency, and perceptions of severity for symptoms associated with typhoid fever. Data have implications for education of policy makers and health administrators, design and implementation of surveillance studies, and community-based interventions to prevent disease outbreaks, decrease risks of complications, and provide information about disease recognition, diagnosis, and treatment. PMID:23208887

The diagnostic accuracy of three rapid diagnostic tests for typhoid fever at Chittagong Medical College Hospital, Chittagong, Bangladesh.

Science.gov (United States)

Maude, Rapeephan R; de Jong, Hanna K; Wijedoru, Lalith; Fukushima, Masako; Ghose, Aniruddha; Samad, Rasheda; Hossain, Mohammed Amir; Karim, Mohammed Rezaul; Faiz, Mohammed Abul; Parry, Christopher M

2015-10-01

To determine the diagnostic accuracy of three rapid diagnostic tests (RDTs) for typhoid fever in febrile hospitalised patients in Bangladesh. Febrile adults and children admitted to Chittagong Medical College Hospital, Bangladesh, were investigated with Bact/Alert(®) blood cultures and real-time PCR to detect Salmonella enterica Typhi and Paratyphi A and assays for Rickettsia, leptospirosis and dengue fever. Acute serum samples were examined with the LifeAssay (LA) Test-it™ Typhoid IgM lateral flow assay detecting IgM antibodies against S. Typhi O antigen, CTKBiotech Onsite Typhoid IgG/IgM Combo Rapid-test cassette lateral flow assay detecting IgG and IgM antibodies against S. Typhi O and H antigens and SD Bioline line assay for IgG and IgM antibodies against S. Typhi proteins. In 300 malaria smear-negative febrile patients [median (IQR) age of 13.5 (5-31) years], 34 (11.3%) had confirmed typhoid fever: 19 positive by blood culture for S. Typhi (three blood PCR positive) and 15 blood culture negative but PCR positive for S. Typhi in blood. The respective sensitivity and specificity of the three RDTs in patients using a composite reference standard of blood culture and/or PCR-confirmed typhoid fever were 59% and 61% for LifeAssay, 59% and 74% for the CTK IgM and/or IgG, and 24% and 96% for the SD Bioline RDT IgM and/or IgG. The LifeAssay RDT had a sensitivity of 63% and a specificity of 91% when modified with a positive cut-off of ≥2+ and analysed using a Bayesian latent class model. These typhoid RDTs demonstrated moderate diagnostic accuracies, and better tests are needed. © 2015 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.

Proposed Oral Reference Dose (RfD) for Barium and Compounds (Final Report, 2004)

Science.gov (United States)

This document is the final report from the 2004 external peer review of the Proposed Oral Reference Dose (RfD) for Barium and Compounds, prepared by the U.S. Environmental Protection Agency (EPA), National Center for Environmental Assessment (NCEA), for the Integrated Risk...

NNDSS - Table II. Salmonellosis (excluding typhoid fever and paratyphoid fever) to Shigellosis

Data.gov (United States)

U.S. Department of Health & Human Services — NNDSS - Table II. Salmonellosis (excluding typhoid fever and paratyphoid fever) to Shigellosis - 2018. In this Table, provisional cases of selected notifiable...

Typhoid fever outbreak associated with frozen mamey pulp imported from Guatemala to the western United States, 2010.

Science.gov (United States)

Loharikar, Anagha; Newton, Anna; Rowley, Patricia; Wheeler, Charlotte; Bruno, Tami; Barillas, Haroldo; Pruckler, James; Theobald, Lisa; Lance, Susan; Brown, Jeffrey M; Barzilay, Ezra J; Arvelo, Wences; Mintz, Eric; Fagan, Ryan

2012-07-01

Fifty-four outbreaks of domestically acquired typhoid fever were reported between 1960 and 1999. In 2010, the Southern Nevada Health District detected an outbreak of typhoid fever among persons who had not recently travelled abroad. We conducted a case-control study to examine the relationship between illness and exposures. A case was defined as illness with the outbreak strain of Salmonella serotype Typhi, as determined by pulsed-field gel electrophoresis (PFGE), with onset during 2010. Controls were matched by neighborhood, age, and sex. Bivariate and multivariate statistical analyses were completed using logistic regression. Traceback investigation was completed. We identified 12 cases in 3 states with onset from 15 April 2010 to 4 September 2010. The median age of case patients was 18 years (range, 4-48 years), 8 (67%) were female, and 11 (92%) were Hispanic. Nine (82%) were hospitalized; none died. Consumption of frozen mamey pulp in a fruit shake was reported by 6 of 8 case patients (75%) and none of the 33 controls (matched odds ratio, 33.9; 95% confidence interval, 4.9). Traceback investigations implicated 2 brands of frozen mamey pulp from a single manufacturer in Guatemala, which was also implicated in a 1998-1999 outbreak of typhoid fever in Florida. Reporting of individual cases of typhoid fever and subtyping of isolates by PFGE resulted in rapid detection of an outbreak associated with a ready-to-eat frozen food imported from a typhoid-endemic region. Improvements in food manufacturing practices and monitoring will prevent additional outbreaks.

Pharmacokinetics of orally administered low-dose rapamycin in healthy dogs: A pilot study

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Larson, Jeanne C.; Allstadt, Sara D.; Fan, Timothy M.; Khanna, Chand; Lunghofer, Paul J.; Hansen, Ryan J.; Gustafson, Daniel L.; Legendre, Alfred M.; Galyon, Gina D.; LeBlanc, Amy K.; Martin-Jimenez, Tomas

2017-01-01

Objective To determine the pharmacokinetics of orally administered rapamycin in healthy dogs. Animals 5 healthy purpose-bred hounds. Procedures The study consisted of 2 experiments. In experiment 1, each dog received rapamycin (0.1 mg/kg, PO) once; blood samples were obtained immediately before and at 0.5, 1, 2, 4, 6, 12, 24, 48, and 72 hours after administration. In experiment 2, each dog received (0.1 mg/kg, PO) once daily for 5 days; blood samples were obtained immediately before and at 3, 6, 24, 27, 30, 48, 51, 54, 72, 75, 78, 96, 96.5, 97, 98, 100, 102, 108, 120, 144, and 168 hours after the first dose. Blood rapamycin concentration was determined by a validated liquid chromatography-tandem mass spectrometry assay. Pharmacokinetic parameters were determined by compartmental and non-compartmental analyses. Results Mean ± SD blood rapamycin terminal half-life, area under the concentration-time curve from 0 to 48 hours after dosing, and maximum concentration were 38.7 ± 12.7 h, 140 ± 23.9 ng•h/mL, and 8.39 ± 1.73 ng/mL, respectively, for experiment 1, and 99.5 ± 89.5 h, 126 ± 27.1 ng•h/mL, and 5.49 ± 1.99 ng/mL, respectively, for experiment 2. Pharmacokinetic parameters for rapamycin after administration of 5 daily doses differed significantly from those after administration of 1 dose. Conclusions and Clinical Relevance Results indicated that oral administration of low-dose (0.1 mg/kg) rapamycin to healthy dogs achieved blood concentrations measured in ng/mL. The optimal dose and administration frequency of rapamcyin required to achieve therapeutic effects in tumor-bearing dogs, as well as toxicity after chronic dosing, needs to be determined. PMID:26709938

[Enzyme-linked immunosorbent assay (ELISA) for detection of antibodies to Salmonella Typhi lipopolysaccharide O and capsular polysaccharide Vi antigens in persons from outbreak of typhoid fever].

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Rastawicki, Waldemar; Kałużewski, Stanisław

2015-01-01

The laboratory diagnosis of typhoid fever is dependent upon either isolation of S. Typhi from a clinical sample or the detection of raised titers of serum antibodies in the Widal test or the passive hemagglutination assay (PHA). In this study we evaluated the usefulness of ELISA for detection of antibodies to S. Typhi lipopolysaccharide O and capsular polysaccharide Vi antigens in the sera of persons from outbreak of typhoid fever. Fifteen serum samples from patients with laboratory confirmed typhoid fever and 140 sera from persons suspected for contact with typhoid fever patients from outbreak in 1974/75 in Poland were tested by ELISA. Additionally, as the control group, we tested 115 sera from blood donors for the presence of S. Typhi anti-LPS and anti-Vi antibodies. Anti-LPS and anti-Vi antibodies were detected in 80% and 53.3% of sera obtained from patients with laboratory confirmed typhoid fever, respectively. The high percentages of positive results in ELISA were also noted in the group of persons suspected for contact with typhoid fever patients (51.4% and 45%) but not in the group of blood donors (7.8% and 6.1%, respectively). The ELISA could be a useful tool for the serological diagnosis of typhoid fever in patients who have clinical symptoms but are culture negative, especially during massive outbreaks of typhoid fever.

[Epidemiological characteristics of typhoid fever and antibiotic susceptibility testing of Salmonella Typhi isolates in Guangxi, 1994-2013].

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Wang, Mingliu; Kan, Biao; Yang, Jin; Lin, Mei; Yan, Meiying; Zeng, Jun; Quan, Yi; Liao, Hezhuang; Zhou, Lingyun; Jiang, Zhenling; Huang, Dehui

2014-08-01

Through analyzing the typhoid epidemics and to determine and monitor regional resistance characteristics of the shift of drug resistant profile on Salmonella (S.) Typhi, to understand the related epidemiological characteristics of typhoid fever and to provide evidence for the development of strategies, in Guangxi. Data of typhoid fever from surveillance and reporting system between 1994 to 2013 was collected and statistically analyzed epidemiologically. The susceptibility of 475 S. Typhi isolates from patients on ten antibiotics was tested by broth micro-dilution method and minimum inhibition concentration was obtained and interpreted based on the CLSI standard. From 1994 to 2013, a total of 57 928 cases of typhoid fever were reported in Guangxi province with an annual incidence of 6.29/100 000 and mortality as 0.03%. The higher incidence was observed in the population under 20 years of age. There was no significant difference on incidence between male and female, but farmers and students were among the hardest hit groups. More cases were seen from the northern part of the province. Cases appeared all year round with the peak from May to October. A total of 13 major outbreaks during 2001 to 2013 were reported and the main transmission route was water-borne. All the strains were sensitive to third generation cephalosporins cefotaxime and fluoroquinolones norfloxacin. The susceptibility rates to tetracycline, chloramphenicol, ampicillin and gentamicin was around 98% but relative lower susceptible rate to ciprofloxacin was seen as 89.89% . The lowest susceptibility was found for streptomycin and sulfamethoxazole agents, with the rates as 67.73% and 65.89% , respectively. One strain was found to have been resistant to ciprofloxacin and another 47 isolates with reduced susceptibility to ciprofloxacin. Twenty eight isolates were found to be resistant to multiple antibiotics and one displayed ampicillin, chloramphenicol, streptomycin, sulfamethoxazole tetracycline and

Rapidly changing treatment options adding burden to the management of typhoid fever

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Jaspal Kaur

2015-01-01

Full Text Available Typhoid fever continues to be a global public health problem. It is caused by the facultative intracellular organisms Salmonella enteric serotype Typhi and Salmonella paratyphi. Antimicrobial therapy is the mainstay for treatment of typhoid fever. Chloramphenicol, ampicillin, and cotrimoxazole had been in use for decades for treating enteric fever. But the emergence and rapid spread of drug resistance has resulted in rapid shift of treatment options from chloramphenicol to fluoroquinolones to third generation cephalosporins to azithromycin with tigecycline and carbapenems in line, thus adding burden to the health-care sector in developing countries. Rational and judicious antibiotic prescribing practices by health professionals are necessary to prevent further development of drug resistance and help in re-emergence of sensitive strains.

Pharmacokinetics after oral and intravenous administration of a single dose of tramadol hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis).

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Souza, Marcy J; Sanchez-Migallon Guzman, David; Paul-Murphy, Joanne R; Cox, Sherry K

2012-08-01

To determine pharmacokinetics after IV and oral administration of a single dose of tramadol hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis). 9 healthy adult Hispaniolan Amazon parrots (3 males, 5 females, and 1 of unknown sex). Tramadol (5 mg/kg, IV) was administered to the parrots. Blood samples were collected from -5 to 720 minutes after administration. After a 3-week washout period, tramadol (10 and 30 mg/kg) was orally administered to parrots. Blood samples were collected from -5 to 1,440 minutes after administration. Three formulations of oral suspension (crushed tablets in a commercially available suspension agent, crushed tablets in sterile water, and chemical-grade powder in sterile water) were evaluated. Plasma concentrations of tramadol and its major metabolites were measured via high-performance liquid chromatography. Mean plasma tramadol concentrations were > 100 ng/mL for approximately 2 to 4 hours after IV administration of tramadol. Plasma concentrations after oral administration of tramadol at a dose of 10 mg/kg were 100 ng/mL for approximately 6 hours after administration. Oral administration of the suspension consisting of the chemical-grade powder resulted in higher plasma tramadol concentrations than concentrations obtained after oral administration of the other 2 formulations; however, concentrations differed significantly only at 120 and 240 minutes after administration. Oral administration of tramadol at a dose of 30 mg/kg resulted in plasma concentrations (> 100 ng/mL) that have been associated with analgesia in Hispaniolan Amazon parrots.

A chewable low-dose oral contraceptive: a new birth control option?

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Weisberg E

2012-04-01

Full Text Available Edith Weisberg1,21Sydney Centre for Reproductive Health Research, Research Division of Family Planning NSW, 2Department of Obstetrics and Gynaecology, Queen Elizabeth II Research Institute for Mothers and Infants, University of Sydney, Sydney, AustraliaAbstract: A new chewable combined oral contraceptive pill containing ethinyl estradiol (EE 0.025 mg and norethindrone (NE 0.8 mg in a 24/4 regimen was approved for marketing in December 2010. Each of the four inactive tablets contains 75 mg ferrous fumarate, which has no therapeutic benefit. The tablet can be taken with food but not water as this affects the absorption of EE. The Pearl index based on intention to treat women aged 18–35 years has been reported at 2.01 (confidence interval [CI] 1.21, 3.14 and for the whole population 1.65 (CI 1.01, 2.55. The effect of a body mass index of >35 was not studied. Regular withdrawal bleeding occurred for 78.6% of women in Cycle 1, but by Cycle 13 almost half the women failed to have a withdrawal bleed. This new formulation provides an intermediate dose of an EE/NE combination that will be useful for women experiencing breakthrough bleeding on the lower-dose EE/NE pill. The convenience of a low-dose pill, which can be chewed without the need for water, will be useful to enable women who have forgotten a pill to take one whenever they remember, provided they carry it with them. The advantage of a 24/4 regimen is better suppression of follicular development in the pill-free interval and may be beneficial for women who experience menstrual cycle-related problems, such as heavy bleeding or dysmenorrhea.Keywords: combined oral contraceptive, low dose, ethinyl estradiol, norethindrone

Toll-like receptor 4 Asp299Gly and Thr399Ile polymorphisms and typhoid susceptibility in Asian Malay population in Malaysia.

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Bhuvanendran, Saatheeyavaane; Hussin, Hani M; Meran, Lila P; Anthony, Amy A; Zhang, Leilei; Burch, Lauranell H; Phua, Kia K; Ismail, Asma; Balaram, Prabha

2011-09-01

Typhoid fever is a major health problem with frequent outbreaks in Kelantan, Malaysia. Prevalence of TLR4 gene polymorphisms varies with ethnic groups (0-20%) and predisposean individual to gram-negative infections. The prevalence rate of TLR4 Asp299Gly and Thr399lle polymorphisms in the Malay population or the influence of these on typhoid fever susceptibility is not yet reported. 250 normal and 304 susceptible Malay individuals were investigated for these polymorphisms using allele-specific PCR and analysed for its association with typhoid fever susceptibility. The total prevalence of polymorphisms in the normal population was 4.8% in comparison to 12.5% in the susceptible population (p = 0.002). An increased frequency of both polymorphisms was observed in the susceptible population (p population and suggests that these polymorphisms confer a higher risk for typhoid, infection. The higher incidence of typhoid fever in Kelantan could be attributed to the higher percentage of Malays (95%) in this state. In order to reduce the incidence of this disease, people with these polymorphisms, can be prioritised for prophylactic strategies. Copyright © 2011 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Expression of intra- and extracellular granzymes in patients with typhoid fever

NARCIS (Netherlands)

de Jong, Hanna K.; Garcia-Laorden, Maria Isabel; Hoogendijk, Arie J.; Parry, Christopher M.; Maude, Rapeephan R.; Dondorp, Arjen M.; Faiz, Mohammed Abul; van der Poll, Tom; Wiersinga, Willem Joost

2017-01-01

Background Typhoid fever, caused by the intracellular pathogen Salmonella (S.) enterica serovar Typhi, remains a major cause of morbidity and mortality worldwide. Granzymes are serine proteases promoting cytotoxic lymphocytes mediated eradication of intracellular pathogens via the induction of cell

Single, 14-Day, and 13-Week Repeated Dose Toxicity Studies of Daily Oral Gelidium elegans Extract Administration to Rats.

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Choi, Jia; Ryu, Su-Jung; Kim, Kui-Jin; Kim, Hyung-Min; Chung, Hee-Chul; Lee, Boo-Yong

2018-01-20

Gelidium elegans extract (GEE) is derived from a red alga from the Asia-Pacific region, which has antioxidant, anti-adipogenic, and anti-hyperglycemic effects. However, detailed studies of the toxicology of GEE have not been performed. We evaluated the single oral dose toxicity of GEE in male and female Sprague-Dawley (CD) rats. GEE did not cause deaths or have toxic effects at dosages of 5000 mg/kg/day, although compound-colored stools and diarrhea were observed in both sexes, which lasted 5000 mg/kg. We next evaluated the repeated oral dose toxicity of GEE in CD rats over 14 days and 13 weeks. GEE did not induce any significant toxicological changes in either sex at 2000 mg/kg/day. Repeated oral dose toxicity studies showed no adverse effects, in terms of clinical signs, mortality, body mass, food consumption, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy, organ masses, or histopathology, at dosages of 500, 1000, or 2000 mg/kg/day. The no observed adverse effect level (NOAEL) for GEE is thus likely to be >2000 mg/kg/day, and no pathology was identified in potential target organs. Therefore, this study indicates that repeated oral dosing with GEE is safe in CD rats.

Formulation design of oral pediatric Acetazolamide suspension: dose uniformity and physico-chemical stability study.

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Santoveña, Ana; Suárez-González, Javier; Martín-Rodríguez, Cristina; Fariña, José B

2017-03-01

The formulation of an active pharmaceutical ingredient (API) as oral solution or suspension in pediatrics is a habitual practice, due to the non-existence of many commercialized medicines in pediatric doses. It is also the simplest way to prepare and administer them to this vulnerable population. The design of a formulation that assures the dose and the system stability depends on the physico-chemical properties of the API. In this study, we formulate a class IV API, Acetazolamide (AZM) as suspension for oral administration to pediatric population. The suspension must comply attributes of quality, safety and efficacy for this route of administration. We use simple compounding procedures, as well as fewer pure excipients, as recommended for children. Mass and uniformity content assays and physical and chemical stability studies were performed. To quantify the API an UPLC method was used. We verified the physico-chemical stability of the suspensions and that they passed the mass test of the European Pharmacopeia (EP), but not the dose uniformity test. This reveals that AZM must be formulated as liquid forms with a more complex system of excipients (not usually indicated in pediatrics), or otherwise solid forms capable of assuring uniformity of mass and dose for every dosage unit.

Oral dosing of chemical indicators for in vivo monitoring of Ca2+ dynamics in insect muscle.

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Ferdinandus

Full Text Available This paper proposes a remarkably facile staining protocol to visually investigate dynamic physiological events in insect tissues. We attempted to monitor Ca2+ dynamics during contraction of electrically stimulated living muscle. Advances in circuit miniaturization and insect neuromuscular physiology have enabled the hybridization of living insects and man-made electronic components, such as microcomputers, the result of which has been often referred as a Living Machine, Biohybrid, or Cyborg Insect. In order for Cyborg Insects to be of practical use, electrical stimulation parameters need to be optimized to induce desired muscle response (motor action and minimize the damage in the muscle due to the electrical stimuli. Staining tissues and organs as well as measuring the dynamics of chemicals of interest in muscle should be conducted to quantitatively and systematically evaluate the effect of various stimulation parameters on the muscle response. However, existing staining processes require invasive surgery and/or arduous procedures using genetically encoded sensors. In this study, we developed a non-invasive and remarkably facile method for staining, in which chemical indicators can be orally administered (oral dosing. A chemical Ca2+ indicator was orally introduced into an insect of interest via food containing the chemical indicator and the indicator diffused from the insect digestion system to the target muscle tissue. We found that there was a positive relationship between the fluorescence intensity of the indicator and the frequency of electrical stimulation which indicates the orally dosed indicator successfully monitored Ca2+ dynamics in the muscle tissue. This oral dosing method has a potential to globally stain tissues including neurons, and investigating various physiological events in insects.

Oral dosing of chemical indicators for in vivo monitoring of Ca2+ dynamics in insect muscle.

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Ferdinandus; Arai, Satoshi; Ishiwata, Shin'ichi; Suzuki, Madoka; Sato, Hirotaka

2015-01-01

This paper proposes a remarkably facile staining protocol to visually investigate dynamic physiological events in insect tissues. We attempted to monitor Ca2+ dynamics during contraction of electrically stimulated living muscle. Advances in circuit miniaturization and insect neuromuscular physiology have enabled the hybridization of living insects and man-made electronic components, such as microcomputers, the result of which has been often referred as a Living Machine, Biohybrid, or Cyborg Insect. In order for Cyborg Insects to be of practical use, electrical stimulation parameters need to be optimized to induce desired muscle response (motor action) and minimize the damage in the muscle due to the electrical stimuli. Staining tissues and organs as well as measuring the dynamics of chemicals of interest in muscle should be conducted to quantitatively and systematically evaluate the effect of various stimulation parameters on the muscle response. However, existing staining processes require invasive surgery and/or arduous procedures using genetically encoded sensors. In this study, we developed a non-invasive and remarkably facile method for staining, in which chemical indicators can be orally administered (oral dosing). A chemical Ca2+ indicator was orally introduced into an insect of interest via food containing the chemical indicator and the indicator diffused from the insect digestion system to the target muscle tissue. We found that there was a positive relationship between the fluorescence intensity of the indicator and the frequency of electrical stimulation which indicates the orally dosed indicator successfully monitored Ca2+ dynamics in the muscle tissue. This oral dosing method has a potential to globally stain tissues including neurons, and investigating various physiological events in insects.

Prevalence of malaria and typhoid co-infections in University of ...

African Journals Online (AJOL)

Mixed infection of malaria caused by Plasmodium species and typhoid fever caused by Salmonella species is often observed in areas where malaria is endemic, and the infection with Salmonella species has been considered by some medical and non-medical personnels to be associated with the malaria parasite infection ...

Reduced time for urinary alkalinization before high-dose methotrexate with preadmission oral bicarbonate.

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Kintzel, Polly E; Campbell, Alan D; Yost, Kathleen J; Brinker, Brett T; Arradaza, Nicole V; Frobish, Daniel; Wehr, Alison M; O'Rourke, Timothy J

2012-06-01

Hydration and urinary alkalinization are essential for reducing renal dysfunction with high dose methotrexate (HDMTX). This report presents an analysis of institutional methods used to achieve adequate urinary alkalinization and output for patients receiving single agent HDMTX. Renal and metabolic parameters of tolerance were examined. Medical records of adult patients receiving HDMTX during the calendar years of 2008-2009 were retrospectively reviewed to determine the time to achieve urine pH > 7. Number of hospital days, bicarbonate dose, ordered hydration rate, urine output, and urine pH were assessed. A survival analysis model was run for time to urine pH > 7 using preadmission oral bicarbonate as a predictor variable and including a frailty term. Observational statistics were performed for other parameters. The analysis included 79 encounters for ten patients. Urine pH > 7 was achieved more rapidly in patients receiving preadmission oral bicarbonate (P = 0.012). The number of patients receiving HDMTX on the same day as admission was greater for those receiving preadmission oral bicarbonate (47%) in comparison to those who did not (2%), and they spent less time in the hospital. A standard regimen for hydration and urinary alkalinization based on this project is reported. The nature and frequency of adverse events were as expected for this treatment. At our institution, the time to achieve urinary alkalinization was reduced for patients receiving preadmission oral bicarbonate which facilitated chemotherapy infusion on the same day as admission and decreased the number of calendar days that patients stayed in the hospital.

Assessment of water, sanitation and hygiene interventions in response to an outbreak of typhoid fever in Neno District, Malawi.

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Bennett, Sarah D; Lowther, Sara A; Chingoli, Felix; Chilima, Benson; Kabuluzi, Storn; Ayers, Tracy L; Warne, Thomas A; Mintz, Eric

2018-01-01

On May 2, 2009 an outbreak of typhoid fever began in rural villages along the Malawi-Mozambique border resulting in 748 illnesses and 44 deaths by September 2010. Despite numerous interventions, including distribution of WaterGuard (WG) for in-home water treatment and education on its use, cases of typhoid fever continued. To inform response activities during the ongoing Typhoid outbreak information on knowledge, attitudes, and practices surrounding typhoid fever, safe water, and hygiene were necessary to plan future outbreak interventions. In September 2010, a survey was administered to female heads in randomly selected households in 17 villages in Neno District, Malawi. Stored household drinking water was tested for free chlorine residual (FCR) levels using the N,N diethyl-p-phenylene diamine colorimetric method (HACH Company, Loveland, CO, USA). Attendance at community-wide educational meetings was reported by 56% of household respondents. Respondents reported that typhoid fever is caused by poor hygiene (77%), drinking unsafe water (49%), and consuming unsafe food (25%), and that treating drinking water can prevent it (68%). WaterGuard, a chlorination solution for drinking water treatment, was observed in 112 (56%) households, among which 34% reported treating drinking water. FCR levels were adequate (FCR ≥ 0.2 mg/L) in 29 (76%) of the 38 households who reported treatment of stored water and had stored water available for testing and an observed bottle of WaterGuard in the home. Soap was observed in 154 (77%) households, among which 51% reported using soap for hand washing. Educational interventions did not reach almost one-half of target households and knowledge remains low. Despite distribution and promotion of WaterGuard and soap during the outbreak response, usage was low. Future interventions should focus on improving water, sanitation and hygiene knowledge, practices, and infrastructure. Typhoid vaccination should be considered.

Surgical treatment of peritonitis due to typhoid fever in a Hospital in Mozambique

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Arnulfo Gallego Mariño

2015-07-01

Full Text Available Background: Typhoid fever is a cause of peritonitis by perforation of the intestinal loops and provokes the death of many people; therefore it constitutes a health problem in Mozambique.Objective: To describe the patients operated on, with the diagnosis of peritonitis resulting from typhoid fever, at the surgery department of the Provincial Hospital in Quelimane, Zambezia Province, Mozambique, from November 1, 2011 to April 30, 2012.Methods: A descriptive study of the patients operated on with the diagnosis of peritonitis resulting from typhoid fever, at the hospital and period herein mentioned, was performed. The study population consisted of 96 patients who were operated on. The variables that were measured were: age, sex, onset of symptoms, total perforations, performed surgical treatment and complications.Results: Male patients of the 25 to 50 age group prevailed; most of them visited the service after 72 hours of the onset of symptoms; in 66 patients only one perforation was found and the surgical procedure mostly used was the suture of the perforation and the washout of the abdominal cavity.Conclusions: Most of the patients visited the service 72 hours after the onset of symptoms; they underwent surgery; and wound infection was the most frequent complication.

Oral High-Dose Multivitamins and Minerals or Post Myocardial Infarction Patients in TACT

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Lamas, Gervasio A.; Boineau, Robin; Goertz, Christine; Mark, Daniel B.; Rosenberg, Yves; Stylianou, Mario; Rozema, Theodore; Nahin, Richard L.; Lindblad, Lauren; Lewis, Eldrin F.; Drisko, Jeanne; Lee, Kerry L.

2014-01-01

Background Oral multivitamins and minerals are often used in conjunction with ethylenediamine tetra acetic acid infusions to treat atherosclerotic disease. Whether high-dose multivitamins are effective as secondary prevention of atherosclerotic disease, however, has not been established. Objective The vitamin component of the Trial to Assess Chelation Therapy assessed whether oral multivitamins reduced cardiovascular events, and were safe. Design The Trial to Assess Chelation Therapy was designed as a double-blind placebo-controlled 2×2 factorial multicenter randomized trial. Setting 134 US and Canadian academic and clinical sites participated. Patients 1708 patients, age ≥50 years, ≥6 weeks post myocardial infarction, with creatinine level ≤ 176.8 µmol/L (2.0 mg/dL). (ClinicalTrials.gov: NCT00044213). Intervention Patients were randomly assigned to an oral 28-component high-dose multivitamin and multimineral mixture or placebo. Measurements Study results were analyzed per randomized group. The primary endpoint was time to total mortality, recurrent myocardial infarction, stroke, coronary revascularization, or hospitalization for angina. Limited secondary endpoints and subgroup analyses were also pre-specified. Results The median age was 65 years, 18% female. The qualifying myocardial infarction had occurred 4.6 (1.6, 9.2) years prior to enrollment. The median duration of follow-up was 55 months (IQR 26, 60) overall. The median number of months during which patients took their vitamins was 31 (13, 59) in the active treatment group, and 35 (13, 60) in the placebo group (p=0.65). There were 645 (76%) vitamin patients and 646 (76%) placebo patients who completed at least 1 year of oral therapy (p=0.98); and 400 (46.9%) vitamin patients and 426 (49.8%) placebo patients who completed at least 3 years of oral therapy (p=0.23). There were 783 (46%) of patients who discontinued their vitamin regimen (390 (46%) in placebo, 394 (46%) in active; p=0.67), and 17% of

Identifying the Risk Factors for Typhoid Fever among the Residents of Rural Islamabad

International Nuclear Information System (INIS)

Javed, N.; Bashir, F.; Abbasi, S.; Tahir, M.

2017-01-01

Background: During August 2015, unusually high typhoid fever cases were reported from rural Islamabad at Federal General Hospital (FGH), Islamabad. Objectives: To determine the risk factors for typhoid fever outbreak and recommend preventive measures. Study design, settings and duration: Outbreak investigation study conducted in Union Councils 19 and 22 of rural Islamabad in the catchment area for Federal General Hospital, from 7 th July-30 th August 2015. Subjects and Methods: A questionnaire was used to identify risk factors of typhoid fever. A case was defined as any resident of the rural Islamabad within the mauza Chatta Bakhtawar and Terlai Kalan presenting with high grade fever (>101 F) with one of the following signs/symptoms; headache, abdominal pain and vomiting with positive typhidot test from 7 th July-30 th August 2015. Two age and sex matched controls for each case was selected from the neighborhood. Epi Info 7 was used for analysis. Results: Total of 50 cases and 100 controls were enrolled. Among cases 30 (61 percent) were females and 20 (39 percent) males with M;F ratio of 1:1.5. Mean age was 23.0 years (9.9 +- SD). The most affected age group was 15-25 years (AR 0.19 percent, n=21). Only one case died (CFR 2percent). Use of untreated public water after rains (OR 3.7 CI 1.6-9.7 p< 0.0002), reconstruction areas and bursting/leaking of water pipes (OR 4.017 CI 1.6-9.7 p < 0.001) and presence of confirmed typhoid cases at home/close contacts (OR 5.7 CI 2.019-16.18 p < 0.0003) were the significant risk factors found associated with the disease. Whereas using well/private bore (OR 0.29 CI 0.329-0.653 p < 0.001) and hand washing practices (OR 0.7 CI 0.297-1.9 < 0.5) had a protective effect. Multivariate analysis showed that use of untreated public water (OR: 3.34, CI: 1.52-7.29, p < 0.002), bursting/leaking pipes (OR 2.86, CI 0.96-8.48, p < 0.05) were significantly associated with typhoid disease. Conclusion: Contamination of drinking water with sewage

Bioavailibility of higher dose methotrexate comparing oral and subcutaneous route of administration in patients with rheumatoid arthritis

NARCIS (Netherlands)

Hoekstra, Monique; Hoekstra, M.; Haagsma, Cees; Neef, Cees; Proost, Johannes; van de Laar, Mart A F J; Knuif, Antonius

2004-01-01

OBJECTIVE: To determine the bioavailability of higher oral doses of methotrexate (MTX) in adult patients with rheumatoid arthritis (RA). METHODS: A pharmacokinetic analysis was performed in 15 patients with RA taking a stable dose of MTX (> or = 25 mg weekly). Separated by 2 weeks, a pharmacokinetic

STUDY ON FEASIBILITY AND LOGISTICS OF VACCINATION WITH TYPHOID VI-VACCINE ON SCHOOL CHILDREN IN NORTH JAKARTA INDONESIA: ANALYSIS OF THE VACCINATION COST

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Roy G.A. Massie

2012-11-01

Full Text Available Background: In recent years, Indonesia government has become increasingly concerned with the issues of financing childhood vaccines and immunization programs including vaccine for typhoid  fever. The objective of the analysis is to provide alternative resources and to provide understandable data generated from the Study on Feasibility and Logistics of Vaccination School Age Children With Typhoid Vi-Vaccine in North Jakarta Indonesia. Methods: The analysis was focus on measurement of the cost for vaccinating school children with Typhoid Vi-vaccine from 18 selected primary schools in North Jakarta. The primary source of data was generated from the actual expenditures that were used in the vaccine delivery program in Indonesia. Results: The Vaccination Cost from the Study on Feasibility and Logistics of Vaccination School Age Children with Typhoid Vi-Vaccine conducted by DOMI project is not applicable for public vaccination program. The program might be feasible to be delivered only in private health sector settings.   Key words: Immunization expenditure, vaccine for typhoid fever, North Jakarta Indonesia

Low and declining attack rates of imported typhoid fever in the Netherlands 1997-2014, in spite of a restricted vaccination policy

NARCIS (Netherlands)

Suryapranata, F. S. T.; Prins, M. [= Maria; Sonder, G. J. B.

2016-01-01

Typhoid fever mainly occurs in (sub) tropical regions where sanitary conditions remain poor. In other regions it occurs mainly among returning travelers or their direct contacts. The aim of this study was to evaluate the current Dutch guidelines for typhoid vaccination. Crude annual attack rates

Typhoid fever: hurdles to adequate hand washing for disease prevention among the population of a peri-urban informal settlement in Fiji.

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Greenwell, James; McCool, Judith; Kool, Jacob; Salusalu, Mosese

2013-01-01

The Pacific island nation of Fiji Islands has high rates of endemic typhoid fever which is difficult to diagnose and often underreported. However, the majority of cases are preventable through use of safe water; adequate sanitation; vaccination; and, most sustainable of all, simple hygienic behaviour, such as hand washing with soap (HWWS). Despite many attempts by public health authorities, little progress has been made in the area of environmental adaptation and behaviour change. To explore perceptions of typhoid fever risk among urban squatters and behavioural determinants surrounding HWWS, indigenous Fijians living in informal settlements with high typhoid fever incidence were invited to participate in focus group discussions. In-depth interviews were conducted with community leaders. Perceptions of typhoid fever suggest confusion about risk factors, symptoms and communicability. Environmental barriers for hand washing were related to water and soap access. Standard social marketing approaches have been trialled with little clear evidence of impact. Despite this, we continue to advocate for the social and cultural determinants of typhoid prevention to remain central to future public health strategies. Despite behaviour change being notoriously difficult, we argue that community-driven behaviour adaptation initiatives based on sound epidemiological evidence and health communication theory are likely to have significant impact and greater likelihood of sustainability.

Effects of monophasic low-dose oral contraceptives on fibrin formation and resolution in young women

DEFF Research Database (Denmark)

Petersen, K R; Sidelmann, Johannes Jakobsen; Skouby, S O

1993-01-01

OBJECTIVE: The purpose of this study was to examine key variables in the regulation of coagulation and fibrinolysis during intake of low-dose oral contraceptives containing newly developed progestogens. STUDY DESIGN: Thirty-four healthy young women were allocated to 12 consecutive cycles of treat......OBJECTIVE: The purpose of this study was to examine key variables in the regulation of coagulation and fibrinolysis during intake of low-dose oral contraceptives containing newly developed progestogens. STUDY DESIGN: Thirty-four healthy young women were allocated to 12 consecutive cycles...... and concentration of plasminogen activator inhibitor. Thrombin-antithrombin III complexes and fibrin degradation products were unchanged, signifying no effect of hormonal intake on the degree of activation of the coagulation system or the efficacy of fibrinolysis. CONCLUSION: The overall dynamic balance between...

Low-dose intranasal versus oral midazolam for routine body MRI of claustrophobic patients

Energy Technology Data Exchange (ETDEWEB)

Tschirch, Frank T.C.; Goepfert, Kerstin; Brunner, Genevieve; Weishaupt, Dominik [University Hospital Zuerich, Institute of Diagnostic Radiology, Zuerich (Switzerland); Froehlich, Johannes M. [Klus-Apotheke, Zuerich (Switzerland)

2007-06-15

The purpose of this study was to assess prospectively the potential of low-dose intranasal midazolam compared to oral midazolam in claustrophobic patients undergoing routine body magnetic resonance imaging (MRI). Seventy-two adult claustrophobic patients referred for body MRI were randomly assigned to one of two treatment groups (TG1 and TG2). The 36 patients of TG1 received 7.5 mg midazolam orally 15 min before MRI, whereas the 36 patients of TG2 received one (or, if necessary, two) pumps of a midazolam nasal spray into each nostril immediately prior to MRI (in total, 1 or 2 mg). Patients' tolerance, anxiety and sedation were assessed using a questionnaire and a visual analogue scale immediately before and after MRI. Image quality was evaluated using a five-point-scale. In TG1, 18/36 MRI examinations (50%) had to be cancelled, the reduction of anxiety was insufficient in 12/18 remaining patients (67%). In TG2, 35/36 MRI examinations (97%) were completed successfully, without relevant adverse effects. MRI image quality was rated higher among patients of TG2 compared to TG1 (p<0.001). Low-dose intranasal midazolam is an effective and patient-friendly solution to overcome anxiety in claustrophobic patients in a broad spectrum of body MRI. Its anxiolytic effect is superior to that of the orally administrated form. (orig.)

Single, 14-Day, and 13-Week Repeated Dose Toxicity Studies of Daily Oral Gelidium elegans Extract Administration to Rats

Directory of Open Access Journals (Sweden)

Jia Choi

2018-01-01

Full Text Available Gelidium elegans extract (GEE is derived from a red alga from the Asia–Pacific region, which has antioxidant, anti-adipogenic, and anti-hyperglycemic effects. However, detailed studies of the toxicology of GEE have not been performed. We evaluated the single oral dose toxicity of GEE in male and female Sprague-Dawley (CD rats. GEE did not cause deaths or have toxic effects at dosages of 5000 mg/kg/day, although compound-colored stools and diarrhea were observed in both sexes, which lasted <2 days. Therefore, the LD50 of GEE is likely to be >5000 mg/kg. We next evaluated the repeated oral dose toxicity of GEE in CD rats over 14 days and 13 weeks. GEE did not induce any significant toxicological changes in either sex at 2000 mg/kg/day. Repeated oral dose toxicity studies showed no adverse effects, in terms of clinical signs, mortality, body mass, food consumption, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy, organ masses, or histopathology, at dosages of 500, 1000, or 2000 mg/kg/day. The no observed adverse effect level (NOAEL for GEE is thus likely to be >2000 mg/kg/day, and no pathology was identified in potential target organs. Therefore, this study indicates that repeated oral dosing with GEE is safe in CD rats.

Estimates of dose to systematic organs and GI tract based on data from miniature swine orally intubated with a single dose of Am-241 citrate

International Nuclear Information System (INIS)

Bernard, S.R.; Nestor, C.W. Jr.; Eisele, G.R.; Eckerman, K.F.

1982-01-01

A model is presented for the internal radiation dose to the small intestine wall of miniature swine given Americium 241 citrate by oral intubation. The model incorporates the uptake of the Am-241 by the intestinal wall. About equal contributions of dose to the small intestine were observed from the intestinal contents and the wall itself

[Spatial and temporal clustering characteristics of typhoid and paratyphoid fever and its change pattern in 3 provinces in southwestern China, 2001-2012].

Science.gov (United States)

Wang, L X; Yang, B; Yan, M Y; Tang, Y Q; Liu, Z C; Wang, R Q; Li, S; Ma, L; Kan, B

2017-11-10

Objective: To analyze the spatial and temporal clustering characteristics of typhoid and paratyphoid fever and its change pattern in Yunnan, Guizhou and Guangxi provinces in southwestern China in recent years. Methods: The incidence data of typhoid and paratyphoid fever cases at county level in 3 provinces during 2001-2012 were collected from China Information System for Diseases Control and Prevention and analyzed by the methods of descriptive epidemiology and geographic informatics. And the map showing the spatial and temporal clustering characters of typhoid and paratyphoid fever cases in three provinces was drawn. SaTScan statistics was used to identify the typhoid and paratyphoid fever clustering areas of three provinces in each year from 2001 to 2012. Results: During the study period, the reported cases of typhoid and paratyphoid fever declined with year. The reported incidence decreased from 30.15 per 100 000 in 2001 to 10.83 per 100 000 in 2006(annual incidence 21.12 per 100 000); while during 2007-2012, the incidence became stable, ranging from 4.75 per 100 000 to 6.83 per 100 000 (annual incidence 5.73 per 100 000). The seasonal variation of the incidence was consistent in three provinces, with majority of cases occurred in summer and autumn. The spatial and temporal clustering of typhoid and paratyphoid fever was demonstrated by the incidence map. Most high-incidence counties were located in a zonal area extending from Yuxi of Yunnan to Guiyang of Guizhou, but were concentrated in Guilin in Guangxi. Temporal and spatial scan statistics identified the positional shifting of class Ⅰ clustering area from Guizhou to Yunnan. Class Ⅰ clustering area was located around the central and western areas (Zunyi and Anshun) of Guizhou during 2001-2003, and moved to the central area of Yunnan during 2004-2012. Conclusion: Spatial and temporal clustering of typhoid and paratyphoid fever existed in the endemic areas of southwestern China, and the clustering area

Evaluation of serological diagnostic tests for typhoid fever in Papua New Guinea using a composite reference standard.

Science.gov (United States)

Siba, Valentine; Horwood, Paul F; Vanuga, Kilagi; Wapling, Johanna; Sehuko, Rebecca; Siba, Peter M; Greenhill, Andrew R

2012-11-01

Typhoid fever remains a major global health problem. A major impediment to improving outcomes is the lack of appropriate diagnostic tools, which have not significantly improved in low-income settings for 100 years. We evaluated two commercially available rapid diagnostic tests (Tubex and TyphiDot), a prototype (TyphiRapid TR-02), and the commonly used single-serum Widal test in a previously reported high-burden area of Papua New Guinea. Samples were collected from 530 outpatients with axillary temperatures of ≥37.5°C, and analysis was conducted on all malaria-negative samples (n = 500). A composite reference standard of blood culture and PCR was used, by which 47 participants (9.4%) were considered typhoid fever positive. The sensitivity and specificity of the Tubex (51.1% and 88.3%, respectively) and TyphiDot (70.0% and 80.1%, respectively) tests were not high enough to warrant their ongoing use in this setting; however, the sensitivity and specificity for the TR-02 prototype were promising (89.4% and 85.0%, respectively). An axillary temperature of ≥38.5°C correlated with typhoid fever (P = 0.014). With an appropriate diagnostic test, conducting typhoid fever diagnosis only on patients with high-grade fever could dramatically decrease the costs associated with diagnosis while having no detrimental impact on the ability to accurately diagnose the illness.

The impact of migration and antimicrobial resistance on the transmission dynamics of typhoid fever in Kathmandu, Nepal: A mathematical modelling study.

Science.gov (United States)

Saad, Neil J; Bowles, Cayley C; Grenfell, Bryan T; Basnyat, Buddha; Arjyal, Amit; Dongol, Sabina; Karkey, Abhilasha; Baker, Stephen; Pitzer, Virginia E

2017-05-01

A substantial proportion of the global burden of typhoid fever occurs in South Asia. Kathmandu, Nepal experienced a substantial increase in the number of typhoid fever cases (caused by Salmonella Typhi) between 2000 and 2003, which subsequently declined but to a higher endemic level than in 2000. This epidemic of S. Typhi coincided with an increase in organisms with reduced susceptibility against fluoroquinolones, the emergence of S. Typhi H58, and an increase in the migratory population in Kathmandu. We devised a mathematical model to investigate the potential epidemic drivers of typhoid in Kathmandu and fit this model to weekly data of S. Typhi cases between April 1997 and June 2011 and the age distribution of S. Typhi cases. We used this model to determine if the typhoid epidemic in Kathmandu was driven by heightened migration, the emergence of organisms with reduced susceptibility against fluoroquinolones or a combination of these factors. Models allowing for the migration of susceptible individuals into Kathmandu alone or in combination with the emergence of S. Typhi with reduced susceptibility against fluoroquinolones provided a good fit for the data. The emergence of organisms with reduced susceptibility against fluoroquinolones organisms alone, either through an increase in disease duration or increased transmission, did not fully explain the pattern of S. Typhi infections. Our analysis is consistent with the hypothesis that the increase in typhoid fever in Kathmandu was associated with the migration of susceptible individuals into the city and aided by the emergence of reduced susceptibility against fluoroquinolones. These data support identifying and targeting migrant populations with typhoid immunization programmes to prevent transmission and disease.

Intralesional Versus Oral Chloroquine in Cutaneous Leishmaniasis: Comparison of Outcome, Duration of Treatment and Total Dose of Drug

International Nuclear Information System (INIS)

Hanif, M. M.; Akram, K.; Mustafa, G.

2016-01-01

Objective: To compare intralesional versus oral chloroquine in cutaneous leishmaniasis and determine the cure rate, duration of treatment, and total dose of drug. Study Design: Randomized controlled study. Place and Duration of Study: Department of Dermatology, Sheikh Zayed Medical College/Hospital, Rahim Yar Khan, from November 2013 to June 2014. Methodology: Consecutive 86 patients of cutaneous leishmaniasis, with single to multiple lesions of various sizes were enrolled and divided randomly into group A and B for the purpose of intralesional and oral chloroquine administration, respectively to compare the effect of the two routes on duration of treatment and total dose of the drug. SPSS version 16 was used for data analysis after data entry into it. Quantitative variables like, duration, cost and total dose of treatment were calculated as mean and standard deviation and compared by using T-test. P-value of less than 0.05 was taken as significant. Results: Cure rate was 100% in both groups towards the end of treatment. Mean duration of treatment was 9.17 ± 3 weeks in intralesional (A) group as against 11.37 ± 3 weeks in oral (B) group (p = 0.0028). Mean total dose of the drug given to each patient in group A was 5.8 ± 0.5 gm and in group B, it was 19.2 ± 1.5 gm, which is significantly higher (p=0.001). The total cost of treatment in group A was Rs. 90 ± 8 and in group B it was Rs. 91 ± 1 (p=0.446). Conclusion: Duration of treatment is significantly shorter and total dose is lesser with intralesional compared to oral chloroquine in treatment of cutaneous leishmaniasis. (author)

Black workers, typhoid fever and the construction of the Berg River – Saldanha military water pipeline, 1942 – 1943

Directory of Open Access Journals (Sweden)

Lieutenant Colonel GE (Deon Visser

2008-04-01

Full Text Available War creates a huge need for labour to support the war efforts of the belligerent parties. In South Africa tens of thousands of ‘non-white’ workers were mobilised during the Second World War to satisfy the Union Defence Force’s (UDF’s labour needs at home and abroad. This article, firstly, outlines the role of ‘non-white people’, particularly black Africans, in the UDF with special reference to those employed within the Union of South Africa. Secondly, it briefly delineates typhoid fever as an historical thorn in the flesh of military forces up to the early 20th century. It then looks briefly into the incidence of and perceptions on typhoid fever as a killer disease in South Africa on the eve of the Second World War. Against that background, the article investigates the employment of black workers on the construction of the Berg River-Saldanha Bay military water pipeline and the UDF’s response to the threat and subsequent outbreak of typhoid fever amongst the workers at the Berg River intake site in 1943. The article concludes that the public health authorities and UDF were aware of the threat of typhoid fever with regard to the Berg River water scheme, but did not take sufficient precautionary measures, which could have had serious repercussions for the Allied war effort. This incident should serve as a warning to the South African National Defence Force when deploying on peace support operations on the African continent where typhoid fever remains a serious threat next to Hiv/Aids.

Fluralaner as a single dose oral treatment for Caparinia tripilis in a pygmy African hedgehog.

Science.gov (United States)

Romero, Camilo; Sheinberg Waisburd, Galia; Pineda, Jocelyn; Heredia, Rafael; Yarto, Enrique; Cordero, Alberto M

2017-12-01

African pygmy hedgehogs (Atelerix albiventris) are popular pets belonging to the Erinaceidae family of spined mammals. Amongst the most common skin diseases occurring in this species is infestation caused by the mite Caparinia spp. Due to their skin anatomy and spiny coat, detection of skin lesions in these hedgehogs can be difficult. This may result in delays in seeking medical care, which may lead to secondary bacterial infection and self-inflicted trauma. Multiple therapies have been used in the treatment of this skin condition including ivermectin, amitraz, fipronil and selamectin. A drug which could be administered as a single oral dose would be advantageous to these pets and their owners. To evaluate the effect of a single oral dose (15 mg/kg) of fluralaner on Caparinia tripilis infestation in the African pygmy hedgehog. A 10-month-old African pygmy hedgehog weighing 184 g. Response to treatment was monitored by dermatological examination and superficial skin scrapings repeated at 7, 14, 21, 30, 60, 90 and 120 days following fluralaner administration. On Day 7 after treatment, adult mites were observed exhibiting normal movement. On Day 14, only dead mites were observed. No life stages of the mites were found after Day 21. A single oral dose at 15 mg/kg of fluralaner was effective within 21 days after treatment for capariniasis in this case. Further studies are required to evaluate the drug's safety and toxicology in hedgehogs, and to confirm efficacy. © 2017 ESVD and ACVD.

High-dose superselective intra-arterial cisplatin and concomitant radiation therapy for carcinoma of the oral cavity

International Nuclear Information System (INIS)

Suzuki, Gen; Tanaka, Norimitsu; Ogo, Etuyo

2007-01-01

The purpose of this study was to evaluate the effect of high-dose superselective intra-arterial cisplatin and concomitant radiation therapy for carcinoma of the oral cavities. The subjects consisted of 18 patients with carcinoma of the oral, and cavity treated with superselective intra-arterial infusion of high dose cisplatin (100 mg/body) concomitant with delivery of external beam radiotherapy (median total dose, 60.8 Gy) between 2001 and 2004. Sodium thiosulfate was administered intravenously to provide effective cisplatin neutlization. They were International Union Against Cancer (UICC)1997 stage II-IV (stage II: 4 patients, stage III: 4 patients, stage IV: 10 patients). Patients ranged from 43-81 years of age, with a median of 60 years, and included 14 men and 4 women. A follow-up period was 6 months minimum from the atart of the radiation therapy, the median follow up period at 28 months. The three-year overall survival rate was 71%. The three-year disease free rate and local control rate were 60% and 65%, respectively. Three-year local control rate of the T2-3 was achieved at 83%, and that for T4 at 50%. There was borderline significant difference in local control rate between T2-3 and T4 (p=0.05). We conclude that the high-dose superselective intra-arterial cisplatin and concomitant radiation therapy provides effective results in organ preservation for cancer of oral cavities. Further studies are also required to determine the validity of this method. (author)

Typhoid fever acquired in the United States, 1999-2010: epidemiology, microbiology, and use of a space-time scan statistic for outbreak detection.

Science.gov (United States)

Imanishi, M; Newton, A E; Vieira, A R; Gonzalez-Aviles, G; Kendall Scott, M E; Manikonda, K; Maxwell, T N; Halpin, J L; Freeman, M M; Medalla, F; Ayers, T L; Derado, G; Mahon, B E; Mintz, E D

2015-08-01

Although rare, typhoid fever cases acquired in the United States continue to be reported. Detection and investigation of outbreaks in these domestically acquired cases offer opportunities to identify chronic carriers. We searched surveillance and laboratory databases for domestically acquired typhoid fever cases, used a space-time scan statistic to identify clusters, and classified clusters as outbreaks or non-outbreaks. From 1999 to 2010, domestically acquired cases accounted for 18% of 3373 reported typhoid fever cases; their isolates were less often multidrug-resistant (2% vs. 15%) compared to isolates from travel-associated cases. We identified 28 outbreaks and two possible outbreaks within 45 space-time clusters of ⩾2 domestically acquired cases, including three outbreaks involving ⩾2 molecular subtypes. The approach detected seven of the ten outbreaks published in the literature or reported to CDC. Although this approach did not definitively identify any previously unrecognized outbreaks, it showed the potential to detect outbreaks of typhoid fever that may escape detection by routine analysis of surveillance data. Sixteen outbreaks had been linked to a carrier. Every case of typhoid fever acquired in a non-endemic country warrants thorough investigation. Space-time scan statistics, together with shoe-leather epidemiology and molecular subtyping, may improve outbreak detection.

Typhoid fever: hurdles to adequate hand washing for disease prevention among the population of a peri-urban informal settlement in Fiji

Directory of Open Access Journals (Sweden)

Mosese Salusalu

2013-01-01

Full Text Available Problem/context: The Pacific island nation of Fiji Islands has high rates of endemic typhoid fever which is difficult to diagnose and often underreported. However, the majority of cases are preventable through use of safe water; adequate sanitation; vaccination; and, most sustainable of all, simple hygienic behaviour, such as hand washing with soap (HWWS. Despite many attempts by public health authorities, little progress has been made in the area of environmental adaptation and behaviour change. Action: To explore perceptions of typhoid fever risk among urban squatters and behavioural determinants surrounding HWWS, indigenous Fijians living in informal settlements with high typhoid fever incidence were invited to participate in focus group discussions. In-depth interviews were conducted with community leaders. Outcome: Perceptions of typhoid fever suggest confusion about risk factors, symptoms and communicability. Environmental barriers for hand washing were related to water and soap access. Standard social marketing approaches have been trialled with little clear evidence of impact. Despite this, we continue to advocate for the social and cultural determinants of typhoid prevention to remain central to future public health strategies. Discussion: Despite behaviour change being notoriously difficult, we argue that community-driven behaviour adaptation initiatives based on sound epidemiological evidence and health communication theory are likely to have significant impact and greater likelihood of sustainability.

Studies to Control Endemic Typhoid Fever in Chile

Science.gov (United States)

1983-01-30

Bol. Inst. Bacteriol. Chile 1976; 18:33-37. 30. Escaff, M, Urbina, A, Mary, J. Contaminacion de repollos regados con aguas servidas. Agricultura...Tecnica 1979; 39:59-62. - 31. Lobos, H, Greive, R, Quijada, M, Brandt, H. Pesquisa del genero Vibrio en aguas servidas. Bol. Inst. Bact. Chile 1974; 16:40...REPORT #2 0") STUDIES TO CONTROL ENDEMIC TYPHOID N FEVER IN CHILE 0) ANNUAL REPORT U’ Contract Period 1/1/82-12/31/82 • I REPORT PREPARED BY: L

Effect of rare earth filtration on patient exposure, dose reduction, and image quality in oral panoramic radiology

International Nuclear Information System (INIS)

Tyndall, D.A.; Washburn, D.B.

1987-01-01

Rare earth intensifying screen material (Gd2O2S:Tb) was added to the standard Al filtration of an oral panoramic x-ray unit, resulting in a beam capable of achieving reductions in patient dose without a loss of image quality. The added rare earth filtration technique resulted in patient dose reductions of 21-56%, depending on anatomic sites, when compared to the conventional Al filtration technique. Films generated from both techniques were measured densitometrically and evaluated by a panel of practicing clinicians. Diagnostically significant differences were minimal. The results indicate that use of rare earth filters in oral panoramic radiography is an effective means of reducing exposures of dental patients to ionizing radiation

Blood culture-PCR to optimise typhoid fever diagnosis after controlled human infection identifies frequent asymptomatic cases and evidence of primary bacteraemia.

Science.gov (United States)

Darton, Thomas C; Zhou, Liqing; Blohmke, Christoph J; Jones, Claire; Waddington, Claire S; Baker, Stephen; Pollard, Andrew J

2017-04-01

Improved diagnostics for typhoid are needed; a typhoid controlled human infection model may accelerate their development and translation. Here, we evaluated a blood culture-PCR assay for detecting infection after controlled human infection with S. Typhi and compared test performance with optimally performed blood cultures. Culture-PCR amplification of blood samples was performed alongside daily blood culture in 41 participants undergoing typhoid challenge. Study endpoints for typhoid diagnosis (TD) were fever and/or bacteraemia. Overall, 24/41 (59%) participants reached TD, of whom 21/24 (86%) had ≥1 positive blood culture (53/674, 7.9% of all cultures) or 18/24 (75%) had ≥1 positive culture-PCR assay result (57/684, 8.3%). A further five non-bacteraemic participants produced culture-PCR amplicons indicating infection; overall sensitivity/specificity of the assay compared to the study endpoints were 70%/65%. We found no significant difference between blood culture and culture-PCR methods in ability to identify cases (12 mismatching pairs, p = 0.77, binomial test). Clinical and stool culture metadata demonstrated that additional culture-PCR amplification positive individuals likely represented true cases missed by blood culture, suggesting the overall attack rate may be 30/41 (73%) rather than 24/41 (59%). Several participants had positive culture-PCR results soon after ingesting challenge providing new evidence for occurrence of an early primary bacteraemia. Overall the culture-PCR assay performed well, identifying extra typhoid cases compared with routine blood culture alone. Despite limitations to widespread field-use, the benefits of increased diagnostic yield, reduced blood volume and faster turn-around-time, suggest that this assay could enhance laboratory typhoid diagnostics in research applications and high-incidence settings. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Low and declining attack rates of imported typhoid fever in the Netherlands 1997-2014, in spite of a restricted vaccination policy.

Science.gov (United States)

Suryapranata, F S T; Prins, M; Sonder, G J B

2016-12-01

Typhoid fever mainly occurs in (sub) tropical regions where sanitary conditions remain poor. In other regions it occurs mainly among returning travelers or their direct contacts. The aim of this study was to evaluate the current Dutch guidelines for typhoid vaccination. Crude annual attack rates (AR) per 100,000 Dutch travelers were calculated during the period 1997 to 2014 by dividing the number of typhoid fever cases by the estimated total number of travelers to a specific country or region. Regions of exposure and possible risk factors were evaluated. During the study period 607 cases of typhoid fever were reported. Most cases were imported from Asia (60%). Almost half of the cases were ethnically related to typhoid risk regions and 37% were cases visiting friends and relatives. The overall ARs for travelers to all regions declined significantly. Countries with the highest ARs were India (29 per 100,000), Indonesia (8 per 100,000), and Morocco (10 per 100,000). There was a significant decline in ARs among travelers to popular travel destinations such as Morocco, Turkey, and Indonesia. ARs among travelers to intermediate-risk areas according to the Dutch guidelines such as Latin America or Sub-Saharan Africa remained very low, despite the restricted vaccination policy for these areas compared to many other guidelines. The overall AR of typhoid fever among travelers returning to the Netherlands is very low and has declined in the past 20 years. The Dutch vaccination policy not to vaccinate short-term travelers to Latin-America, Sub-Saharan Africa, Thailand and Malaysia seems to be justified, because the ARs for these destinations remain very low. These results suggest that further restriction of the Dutch vaccination policy is justified.

Non-typhoidal Salmonella and Campylobacter infections among HIV-positive patients in Denmark

DEFF Research Database (Denmark)

Larsen, I.K.; Gradel, Kim Oren; Helms, M.

2011-01-01

Non-typhoidal Salmonella (NTS) and Campylobacter are common causes of diarrhoea in human immunodeficiency virus (HIV)-positive patients. To investigate if incidence has changed since the introduction of highly active antiretroviral therapy (HAART), we combined data from The Danish Surveillance Re...... population. Moreover our study suggests that there is an increased incidence of Campylobacter-related illness among homosexual men in the HIV-positive population.......Non-typhoidal Salmonella (NTS) and Campylobacter are common causes of diarrhoea in human immunodeficiency virus (HIV)-positive patients. To investigate if incidence has changed since the introduction of highly active antiretroviral therapy (HAART), we combined data from The Danish Surveillance...... Registry for Enteric Pathogens and The Danish National Hospital Registry. We found that the incidences of NTS- and Campylobacter-related illness among HIV-positive patients in Denmark have declined since the introduction of HAART, although the incidences remained higher compared to the background...

A comparative study of Widal test with blood culture in the diagnosis of typhoid fever in febrile patients.

Science.gov (United States)

Andualem, Gizachew; Abebe, Tamrat; Kebede, Nigatu; Gebre-Selassie, Solomon; Mihret, Adane; Alemayehu, Haile

2014-09-17

Typhoid fever is a major health problem in developing countries and its diagnosis on clinical ground is difficult. Diagnosis in developing countries including Ethiopia is mostly done by Widal test. However, the value of the test has been debated. Hence, evaluating the result of this test is necessary for correct interpretation of the result. The main aim of this study was to compare the result of Widal test and blood culture in the diagnosis of typhoid fever in febrile patients. Blood samples were collected from 270 febrile patients with symptoms clinically similar to typhoid fever and visiting St. Paul's General Specialized Hospitals from mid December 2010 to March 2011. Blood culture was used to isolate S.typhi and S.paratyphi. Slide agglutination test and tube agglutination tests were used for the determination of antibody titer. An antibody titer of ≥1:80 for anti TO and ≥1:160 for anti TH were taken as a cut of value to indicate recent infection of typhoid fever. One hundred and eighty six (68.9%) participants were females and eighty four (31.1%) were males. 7 (2.6%) cases of S. typhi and 4 (1.5%) cases of S. paratyphi were identified with the total prevalence of typhoid fever 4.1%. The total number of patients who have indicative of recent infection by either of O and H antigens Widal test is 88 (32.6%). The sensitivity, specificity, Positive predictive Value and Negative predictive Value of Widal test were 71.4%, 68.44%, 5.7% and 98.9% respectively. Widal test has a low sensitivity, specificity and PPV, but it has good NPV which indicates that negative Widal test result have a good indication for the absence of the disease.

Validation of the Dri-Dot Latex agglutination and IgM lateral flow assays for the diagnosis of typhoid fever in an Egyptian population

NARCIS (Netherlands)

Nakhla, Isabelle; El Mohammady, Hanan; Mansour, Adel; Klena, John D.; Hassan, Khaled; Sultan, Yehia; Pastoor, Rob; Abdoel, Theresia H.; Smits, Henk

2011-01-01

Laboratory confirmation of typhoid fever is essential for appropriate medical treatment. Blood culture is a standard test for diagnosis of typhoid fever, but well-equipped diagnostic facilities to perform culture are seldom available in endemic areas. We retrospectively compared 2 diagnostic field

Long-term high-dose oral morphine in phantom limb pain with no addiction risk

Directory of Open Access Journals (Sweden)

Vinod Kumar

2015-01-01

Full Text Available Chronic phantom limb pain (PLP is a type of neuropathic pain, which is located in the missing/amputated limb. Phantom pain is difficult to treat as the exact basis of pain mechanism is still unknown. Various methods of treatment for PLP have been described, including pharmacological (NSAIDs, opioids, antiepileptic, antidepressants and non-pharmacological (TENS, sympathectomy, deep brain stimulation and motor cortex stimulation. Opioids are used for the treatment of neuropathic pain and dose of opioid is determined based on its effect and thus there is no defined ceiling dose for opioids. We report a case where a patient receiving high-dose oral morphine for chronic cancer pain did not demonstrate signs of addiction.

Time, dose and volume factors in interstitial brachytherapy combined with external irradiation for oral tongue carcinoma

International Nuclear Information System (INIS)

Yorozu, Atsunori

1996-01-01

This is a retrospective analysis of 136 patients with squamous cell carcinoma of stages I and II of the oral tongue who were treated with interstitial brachytherapy alone or in combination with external irradiation between 1976 and 1991. Control of the primary lesion and the occurrence of late complications were analyzed with respect to dose, time and tumor size with the Cox hazard model. The 5-year survival rates for stages I and II were 84.5% and 75.6%. The 5-year primary control rate was 91.3% for stage I and 77.3% for stage II (p 50 Gy compared with a brachytherapy dose 30 mm. Late complications should be reduced by using a spacer, improvements in dental and oral hygiene, and a sophisticated implant method. (author)

Efficacy and safety of a single oral 150 mg dose of fluconazole for the treatment of vulvovaginal candidiasis in Japan.

Science.gov (United States)

Mikamo, Hiroshige; Matsumizu, Miyako; Nakazuru, Yoshiomi; Okayama, Akifumi; Nagashima, Masahito

2015-07-01

Vulvovaginal candidiasis is the second most common cause of vaginal infections following bacterial vaginosis. For the treatment of vulvovaginal candidiasis, antifungal agents are used either as topical (vaginal tablets and cream) or oral formulations. A single oral 150 mg dose of fluconazole has been recommended as the standard therapy for uncomplicated, acute vulvovaginal candidiasis in global guidelines; however, in Japan oral fluconazole therapy has not been approved. We conducted a phase 3 study to evaluate the efficacy and safety of a single oral 150 mg dose of fluconazole in Japanese subjects with vulvovaginal candidiasis for regulatory submission. A total of 157 subjects received a single oral 150 mg dose of fluconazole. Candida species (104 strains) were identified by fungal culture from 102 subjects at baseline, including Candida albicans (100 strains). The efficacy rate for the therapeutic outcome (assessed based on a comprehensive evaluation of the clinical and mycological efficacy in each subject) was 74.7% (74/99) on Day 28 in the modified Intent-To-Treat (m-ITT) population. Concerning the clinical and mycological efficacy on Day 28 in the m-ITT population, the cure, cure or improvement, and eradication rates were 81.6%, 95.9%, and 85.9%, respectively. The most common treatment-related adverse events were diarrhea and nausea (1.9% for each). No clinically significant safety issues were reported. A single oral 150 mg dose of fluconazole demonstrated excellent therapeutic efficacy and was well tolerated in Japanese subjects with vulvovaginal candidiasis. NCT01806623. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Single dose oral flurbiprofen for acute postoperative pain in adults

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Sultan, Asquad; McQuay, Henry J; Moore, R Andrew; Derry, Sheena

2014-01-01

Background Flurbiprofen is a non-selective non-steroidal anti-inflammatory drug (NSAID), related to ibuprofen and naproxen, used to treat acute and chronic painful conditions. There is no systematic review of its use in acute postoperative pain. Objectives To assess efficacy, duration of action, and associated adverse events of single dose oral flurbiprofen in acute postoperative pain in adults. Search methods We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to January 2009. Selection criteria Randomised, double blind, placebo-controlled trials of single dose orally administered flurbiprofen in adults with moderate to severe acute postoperative pain. Data collection and analysis Two review authors independently assessed trial quality and extracted data. Pain relief or pain intensity data were extracted and converted into the dichotomous outcome of number of participants with at least 50% pain relief over 4 to 6 hours, from which relative risk (RR) and number needed to treat to benefit (NNT) were calculated. Numbers of participants using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Information on adverse events and withdrawals were collected. Main results Eleven studies compared flurbiprofen (699 participants) with placebo (362 participants) in studies lasting 6 to 12 hours. Studies were of adequate reporting quality, and most participants had pain following dental extractions. The dose of flurbiprofen used was 25 mg to 100 mg, with most information for 50 mg and 100 mg. The NNT for at least 50% pain relief over 4 to 6 hours for flurbiprofen 50 mg compared with placebo (692 participants) was 2.7 (2.3 to 3.3) and for 100 mg (416 participants) it was 2.5 (2.0 to 3.1). With flurbiprofen 50 mg and 100 mg 65% to 70% of participants experienced at least 50% pain relief, compared with 25% to 30% with placebo. Rescue medication was used by 25

Clinical outcome of high-dose-rate interstitial brachytherapy in patients with oral cavity cancer

International Nuclear Information System (INIS)

Lee, Sung Uk; Cho, Kwan Ho; Moon, Sung Ho; Choi, Sung Weon; Park, Joo Yong; Yun, Tak; Lee, Sang Hyun; Lim, Young Kyung; Jeong, Chi Young

2014-01-01

To evaluate the clinical outcome of high-dose-rate (HDR) interstitial brachytherapy (IBT) in patients with oral cavity cancer. Sixteen patients with oral cavity cancer treated with HDR remote-control afterloading brachytherapy using 192Ir between 2001 and 2013 were analyzed retrospectively. Brachytherapy was administered in 11 patients as the primary treatment and in five patients as salvage treatment for recurrence after the initial surgery. In 12 patients, external beam radiotherapy (50-55 Gy/25 fractions) was combined with IBT of 21 Gy/7 fractions. In addition, IBT was administered as the sole treatment in three patients with a total dose of 50 Gy/10 fractions and as postoperative adjuvant treatment in one patient with a total of 35 Gy/7 fractions. The 5-year overall survival of the entire group was 70%. The actuarial local control rate after 3 years was 84%. All five recurrent cases after initial surgery were successfully salvaged using IBT +/- external beam radiotherapy. Two patients developed local recurrence at 3 and 5 months, respectively, after IBT. The acute complications were acceptable (< or =grade 2). Three patients developed major late complications, such as radio-osteonecrosis, in which one patient was treated by conservative therapy and two required surgical intervention. HDR IBT for oral cavity cancer was effective and acceptable in diverse clinical settings, such as in the cases of primary or salvage treatment.

Single dose oral ketoprofen and dexketoprofen for acute postoperative pain in adults.

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Barden, Jodie; Derry, Sheena; McQuay, Henry J; Moore, R Andrew

2009-10-07

Ketoprofen is a non-selective non-steroidal anti-inflammatory drug (NSAID) used to treat acute and chronic painful conditions. Dexketoprofen is the (S)-enantiomer, which is believed to confer analgesia. Theoretically dexketoprofen is expected to provide equivalent analgesia to ketoprofen at half the dose, with a consequent reduction in gastrointestinal adverse events. To assess efficacy, duration of action, and associated adverse events of single dose oral ketoprofen and dexketoprofen in acute postoperative pain in adults. We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to August 2009. Randomised, double blind, placebo-controlled trials of single dose orally administered ketoprofen and dexketoprofen in adults with moderate to severe acute postoperative pain. Two review authors independently assessed trial quality and extracted data. Pain relief or pain intensity data were extracted and converted into the dichotomous outcome of number of participants with at least 50% pain relief over 4 to 6 hours, from which relative risk and number-needed-to-treat-to-benefit (NNT) were calculated. Numbers of participants using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Information on adverse events and withdrawals was collected. Fourteen studies compared ketoprofen (968 participants) at mainly 25 mg and 50 mg with placebo (520 participants). Seven studies compared dexketoprofen (681 participants) at mainly 10 mg to 25 mg with placebo (289 participants). Studies were of adequate reporting quality, and participants had pain following dental, orthopaedic, obstetric, gynaecological and general surgery. There was considerable clinical heterogeneity between studies in dental and other types of surgery, particularly bunionectomy, which limited analysis.Ketoprofen at doses between 12.5 mg and 100 mg produced NNTs for at least 50% pain relief over 4 to 6

SU-D-16A-02: A Novel Methodology for Accurate, Semi-Automated Delineation of Oral Mucosa for Radiation Therapy Dose-Response Studies

International Nuclear Information System (INIS)

Dean, J; Welsh, L; Gulliford, S; Harrington, K; Nutting, C

2014-01-01

Purpose: The significant morbidity caused by radiation-induced acute oral mucositis means that studies aiming to elucidate dose-response relationships in this tissue are a high priority. However, there is currently no standardized method for delineating the mucosal structures within the oral cavity. This report describes the development of a methodology to delineate the oral mucosa accurately on CT scans in a semi-automated manner. Methods: An oral mucosa atlas for automated segmentation was constructed using the RayStation Atlas-Based Segmentation (ABS) module. A radiation oncologist manually delineated the full surface of the oral mucosa on a planning CT scan of a patient receiving radiotherapy (RT) to the head and neck region. A 3mm fixed annulus was added to incorporate the mucosal wall thickness. This structure was saved as an atlas template. ABS followed by model-based segmentation was performed on four further patients sequentially, adding each patient to the atlas. Manual editing of the automatically segmented structure was performed. A dose comparison between these contours and previously used oral cavity volume contours was performed. Results: The new approach was successful in delineating the mucosa, as assessed by an experienced radiation oncologist, when applied to a new series of patients receiving head and neck RT. Reductions in the mean doses obtained when using the new delineation approach, compared with the previously used technique, were demonstrated for all patients (median: 36.0%, range: 25.6% – 39.6%) and were of a magnitude that might be expected to be clinically significant. Differences in the maximum dose that might reasonably be expected to be clinically significant were observed for two patients. Conclusion: The method developed provides a means of obtaining the dose distribution delivered to the oral mucosa more accurately than has previously been achieved. This will enable the acquisition of high quality dosimetric data for use in

Typhoid fever acquired in the United States, 1999–2010: epidemiology, microbiology, and use of a space–time scan statistic for outbreak detection

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IMANISHI, M.; NEWTON, A. E.; VIEIRA, A. R.; GONZALEZ-AVILES, G.; KENDALL SCOTT, M. E.; MANIKONDA, K.; MAXWELL, T. N.; HALPIN, J. L.; FREEMAN, M. M.; MEDALLA, F.; AYERS, T. L.; DERADO, G.; MAHON, B. E.; MINTZ, E. D.

2016-01-01

SUMMARY Although rare, typhoid fever cases acquired in the United States continue to be reported. Detection and investigation of outbreaks in these domestically acquired cases offer opportunities to identify chronic carriers. We searched surveillance and laboratory databases for domestically acquired typhoid fever cases, used a space–time scan statistic to identify clusters, and classified clusters as outbreaks or non-outbreaks. From 1999 to 2010, domestically acquired cases accounted for 18% of 3373 reported typhoid fever cases; their isolates were less often multidrug-resistant (2% vs. 15%) compared to isolates from travel-associated cases. We identified 28 outbreaks and two possible outbreaks within 45 space–time clusters of ⩾2 domestically acquired cases, including three outbreaks involving ⩾2 molecular subtypes. The approach detected seven of the ten outbreaks published in the literature or reported to CDC. Although this approach did not definitively identify any previously unrecognized outbreaks, it showed the potential to detect outbreaks of typhoid fever that may escape detection by routine analysis of surveillance data. Sixteen outbreaks had been linked to a carrier. Every case of typhoid fever acquired in a non-endemic country warrants thorough investigation. Space–time scan statistics, together with shoe-leather epidemiology and molecular subtyping, may improve outbreak detection. PMID:25427666

Spatial and temporal structure of typhoid outbreaks in Washington, D.C., 1906–1909: evaluating local clustering with the Gi* statistic

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Curtis Andrew

2006-03-01

Full Text Available Abstract Background To better understand the distribution of typhoid outbreaks in Washington, D.C., the U.S. Public Health Service (PHS conducted four investigations of typhoid fever. These studies included maps of cases reported between 1 May – 31 October 1906 – 1909. These data were entered into a GIS database and analyzed using Ripley's K-function followed by the Gi* statistic in yearly intervals to evaluate spatial clustering, the scale of clustering, and the temporal stability of these clusters. Results The Ripley's K-function indicated no global spatial autocorrelation. The Gi* statistic indicated clustering of typhoid at multiple scales across the four year time period, refuting the conclusions drawn in all four PHS reports concerning the distribution of cases. While the PHS reports suggested an even distribution of the disease, this study quantified both areas of localized disease clustering, as well as mobile larger regions of clustering. Thus, indicating both highly localized and periodic generalized sources of infection within the city. Conclusion The methodology applied in this study was useful for evaluating the spatial distribution and annual-level temporal patterns of typhoid outbreaks in Washington, D.C. from 1906 to 1909. While advanced spatial analyses of historical data sets must be interpreted with caution, this study does suggest that there is utility in these types of analyses and that they provide new insights into the urban patterns of typhoid outbreaks during the early part of the twentieth century.

The route of administration (oral vs intravenous) does not influence dose or outcome in Graves' disease and unifocal autonomy

International Nuclear Information System (INIS)

Schneider, Peter; Biko, Johannes; Haenscheid, Heribert; Hilliger, Stephan; Koutsampelas, Christos; Kranzfelder, Michael; Ladner, Stephan; Reiners, Christoph

2005-01-01

In a prospective randomised study, we investigated the influence of the route of administration of radioiodide on dosimetry and therapy outcome. Fifty-four patients suffering from Graves' disease (GD) and 60 patients with unifocal autonomy (UA) participated in the study and were randomly treated with either orally or intravenously administered radioiodide. Pretherapeutic dosimetry was based on single uptake measurements with a calibrated uptake probe system. The radioiodine kinetics during hospitalisation was assessed by daily bedside uptake measurements. Therapeutic dose was determined by half-life and thyroid uptake at the time of discharge using the same uptake probe as for the radioiodine test. No improvement in accuracy of dosimetry was achieved when radioiodide was administered intravenously. Mean therapeutic doses were identical following intravenous or oral administration. Variation in the achieved dose was slightly higher in the patients receiving oral administration, this being attributable to larger deviations in discrete activities of the capsules administered as compared with the values determined by dosimetry. No differences according to treatment modality were found with regard to therapeutic outcome. Eighty-seven patients attended 6-month follow-up after therapy. In the UA group, successful treatment, defined as a normal or elevated TSH level, was observed in 94% of patients after oral administration and in 80% after intravenous administration; corresponding figures in the GD group were 68% and 65%. The causes of individual differences between targeted and therapeutically achieved doses remain undetermined. Variations in the bioavailability of radioiodide or other parameters affecting thyroid status may be involved, and further investigations are needed to clarify this. (orig.)

Single fixed-dose oral dexketoprofen plus tramadol for acute postoperative pain in adults.

Science.gov (United States)

Derry, Sheena; Cooper, Tess E; Phillips, Tudor

2016-09-22

Combining two different analgesics in fixed doses in a single tablet can provide better pain relief than either drug alone in acute pain. This appears to be broadly true across a range of different drug combinations, in postoperative pain and migraine headache. A new combination of dexketoprofen (a nonsteroidal anti-inflammatory drug) plus tramadol (an opioid) has been tested in acute postoperative pain conditions. It is not yet licensed for use. This review is one of a series on oral analgesics for acute postoperative pain. Individual reviews have been brought together in two overviews to provide information about the relative efficacy and harm of the different interventions. To assess the analgesic efficacy and adverse effects of a single fixed-dose of oral dexketoprofen plus tramadol, compared with placebo, for moderate to severe postoperative pain in adults, using methods that permit comparison with other analgesics evaluated in standardised trials using almost identical methods and outcomes. A secondary objective was to compare the combination with the individual analgesics alone. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) via CRSO, MEDLINE via Ovid, and Embase via Ovid from inception to 31 May 2016. We also searched the reference lists of retrieved studies and reviews, and two online clinical trial registries. Randomised, double-blind trials of oral dexketoprofen plus tramadol administered as a single oral dose, for the relief of acute postoperative pain in adults, and compared to placebo. Two review authors independently considered trials for inclusion in the review, examined issues of study quality and potential bias, and extracted data. For dichotomous outcomes, we calculated risk ratio (RR) and number needed to treat for an additional beneficial outcome (NNT) for dexketoprofen plus tramadol, compared with placebo with 95% confidence intervals (CI). We collected information on the number of participants with at least 50% of

Comparisons of predictors for typhoid and paratyphoid fever in Kolkata, India

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Deen Jacqueline L

2007-10-01

Full Text Available Abstract Background: Exposure of the individual to contaminated food or water correlates closely with the risk for enteric fever. Since public health interventions such as water improvement or vaccination campaigns are implemented for groups of individuals we were interested whether risk factors not only for the individual but for households, neighbourhoods and larger areas can be recognised? Methods: We conducted a large enteric fever surveillance study and analyzed factors which correlate with enteric fever on an individual level and factors associated with high and low risk areas with enteric fever incidence. Individual level data were linked to a population based geographic information systems. Individual and household level variables were fitted in Generalized Estimating Equations (GEE with the logit link function to take into account the likelihood that household factors correlated within household members. Results: Over a 12-month period 80 typhoid fever cases and 47 paratyphoid fever cases were detected among 56,946 residents in two bustees (slums of Kolkata, India. The incidence of paratyphoid fever was lower (0.8/1000/year, and the mean age of paratyphoid patients was older (17.1 years than for typhoid fever (incidence 1.4/1000/year, mean age 14.7 years. Residents in areas with a high risk for typhoid fever had lower literacy rates and economic status, bigger household size, and resided closer to waterbodies and study treatment centers than residents in low risk areas. Conclusion: There was a close correlation between the characteristics detected based on individual cases and characteristics associated with high incidence areas. Because the comparison of risk factors of populations living in high versus low risk areas is statistically very powerful this methodology holds promise to detect risk factors associated with diseases using geographic information systems.

Perturbation of cobalt 60 radiation doses by metal objects implanted during oral and maxillofacial surgery

International Nuclear Information System (INIS)

Tatcher, M.; Kuten, A.; Helman, J.; Laufer, D.

1984-01-01

The influence on cobalt 60 dose distributions of typical metal parts used in oral and maxillofacial surgery was studied. Relative doses were determined by exposing x-ray films in a polystyrene phantom set-up containing samples of vitallium, titanium, and stainless steel. Optical densities were converted to doses with the aid of sensitometric curves. The results show that for normal incidence there is a 25% to 40% increase in dose at the entrance side of the metal and a 20% to 25% decrease in dose at the exit side. The enhancement effect falls off rapidly and becomes negligible at about 1 mm from the interface. The reduction effect decreases more gradually and is still evident at distances of a few centimeters. These dose perturbations should be taken into account in the planning of radiation therapy for patients in whom metal objects have been implanted

Human kinetics of orally and intravenously administered low-dose 1,2-(13)C-dichloroacetate.

Science.gov (United States)

Jia, Minghong; Coats, Bonnie; Chadha, Monisha; Frentzen, Barbara; Perez-Rodriguez, Javier; Chadik, Paul A; Yost, Richard A; Henderson, George N; Stacpoole, Peter W

2006-12-01

Dichloroacetate (DCA) is a putative environmental hazard, owing to its ubiquitous presence in the biosphere and its association with animal and human toxicity. We sought to determine the kinetics of environmentally relevant concentrations of 1,2-(13)C-DCA administered to healthy adults. Subjects received an oral or intravenous dose of 2.5 microg/kg of 1,2-(13)C-DCA. Plasma and urine concentrations of 1,2-(13)C-DCA were measured by a modified gas chromatography-tandem mass spectrometry method. 1,2-(13)C-DCA kinetics was determined by modeling using WinNonlin 4.1 software. Plasma concentrations of 1,2-(13)C-DCA peaked 10 minutes and 30 minutes after intravenous or oral administration, respectively. Plasma kinetic parameters varied as a function of dose and duration. Very little unchanged 1,2-(13)C-DCA was excreted in urine. Trace amounts of DCA alter its own kinetics after short-term exposure. These findings have important implications for interpreting the impact of this xenobiotic on human health.

Effectiveness of one dose of oral cholera vaccine in response to an outbreak: a case-cohort study.

Science.gov (United States)

Azman, Andrew S; Parker, Lucy A; Rumunu, John; Tadesse, Fisseha; Grandesso, Francesco; Deng, Lul L; Lino, Richard Laku; Bior, Bior K; Lasuba, Michael; Page, Anne-Laure; Ontweka, Lameck; Llosa, Augusto E; Cohuet, Sandra; Pezzoli, Lorenzo; Sodjinou, Dossou Vincent; Abubakar, Abdinasir; Debes, Amanda K; Mpairwe, Allan M; Wamala, Joseph F; Jamet, Christine; Lessler, Justin; Sack, David A; Quilici, Marie-Laure; Ciglenecki, Iza; Luquero, Francisco J

2016-11-01

Oral cholera vaccines represent a new effective tool to fight cholera and are licensed as two-dose regimens with 2-4 weeks between doses. Evidence from previous studies suggests that a single dose of oral cholera vaccine might provide substantial direct protection against cholera. During a cholera outbreak in May, 2015, in Juba, South Sudan, the Ministry of Health, Médecins Sans Frontières, and partners engaged in the first field deployment of a single dose of oral cholera vaccine to enhance the outbreak response. We did a vaccine effectiveness study in conjunction with this large public health intervention. We did a case-cohort study, combining information on the vaccination status and disease outcomes from a random cohort recruited from throughout the city of Juba with that from all the cases detected. Eligible cases were those aged 1 year or older on the first day of the vaccination campaign who sought care for diarrhoea at all three cholera treatment centres and seven rehydration posts throughout Juba. Confirmed cases were suspected cases who tested positive to PCR for Vibrio cholerae O1. We estimated the short-term protection (direct and indirect) conferred by one dose of cholera vaccine (Shanchol, Shantha Biotechnics, Hyderabad, India). Between Aug 9, 2015, and Sept 29, 2015, we enrolled 87 individuals with suspected cholera, and an 898-person cohort from throughout Juba. Of the 87 individuals with suspected cholera, 34 were classified as cholera positive, 52 as cholera negative, and one had indeterminate results. Of the 858 cohort members who completed a follow-up visit, none developed clinical cholera during follow-up. The unadjusted single-dose vaccine effectiveness was 80·2% (95% CI 61·5-100·0) and after adjusting for potential confounders was 87·3% (70·2-100·0). One dose of Shanchol was effective in preventing medically attended cholera in this study. These results support the use of a single-dose strategy in outbreaks in similar epidemiological

A New Orally Active, Aminothiol Radioprotector-Free of Nausea and Hypotension Side Effects at Its Highest Radioprotective Doses

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Soref, Cheryl M. [ProCertus BioPharm, Inc., Madison, WI (United States); Hacker, Timothy A. [Department of Medicine, Cardiovascular Physiology Core, University of Wisconsin-Madison, Madison, WI (United States); Fahl, William E., E-mail: fahl@oncology.wisc.edu [ProCertus BioPharm, Inc., Madison, WI (United States); McArdle Laboratory for Cancer Research, University of Wisconsin Carbone Cancer Center, Madison, WI (United States)

2012-04-01

Purpose: A new aminothiol, PrC-210, was tested for orally conferred radioprotection (rats, mice; 9.0 Gy whole-body, which was otherwise lethal to 100% of the animals) and presence of the debilitating side effects (nausea/vomiting, hypotension/fainting) that restrict use of the current aminothiol, amifostine (Ethyol, WR-2721). Methods and Materials: PrC-210 in water was administered to rats and mice at times before irradiation, and percent-survival was recorded for 60 days. Subcutaneous (SC) amifostine (positive control) or SC PrC-210 was administered to ferrets (Mustela putorius furo) and retching/emesis responses were recorded. Intraperitoneal amifostine (positive control) or PrC-210 was administered to arterial cannulated rats to score drug-induced hypotension. Results: Oral PrC-210 conferred 100% survival in rat and mouse models against an otherwise 100% lethal whole-body radiation dose (9.0 Gy). Oral PrC-210, administered by gavage 30-90 min before irradiation, conferred a broad window of radioprotection. The comparison of PrC-210 and amifostine side effects was striking because there was no retching or emesis in 10 ferrets treated with PrC-210 and no induced hypotension in arterial cannulated rats treated with PrC-210. The tested PrC-210 doses were the ferret and rat equivalent doses of the 0.5 maximum tolerated dose (MTD) PrC-210 dose in mice. The human equivalent of this mouse 0.5 MTD PrC-210 dose would likely be the highest PrC-210 dose used in humans. By comparison, the mouse 0.5 MTD amifostine dose, 400 {mu}g/g body weight (equivalent to the human amifostine dose of 910 mg/m{sup 2}), when tested at equivalent ferret and rat doses in the above models produced 100% retching/vomiting in ferrets and 100% incidence of significant, progressive hypotension in rats. Conclusions: The PrC-210 aminothiol, with no detectable nausea/vomiting or hypotension side effects in these preclinical models, is a logical candidate for human drug development to use in healthy

Protective effects of orally applied fullerenol nano particles in rats after a single dose of doxorubicin

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Ičević Ivana Đ.

2011-01-01

Full Text Available Polyhydroxylated, water soluble, fullerenol C60(OH24 nano particles (FNP in vitro and in vivo models, showed an expressive biological activity. The goal of this work was to investigate the potential protective effects of orally applied FNP on rats after a single dose of doxorubicin (DOX (8 mg/kg (i.p. 6 h after the last application of FNP. After the last drug administration, the rats were sacrificed, and the blood and tissues were taken for the analysis. Biochemical and pathological results obtained in this study indicate that fullerenol (FNP, in H2O:DMSO (80:20, w/w solution given orally in final doses of 10, 14.4, and 21.2 mg/kg three days successively, has the protective (hepatoprotective and nephroprotective effect against doxorubicin-induced cytotoxicity via its antioxidant properties.

Typhoid fever and paratyphoid fever: Systematic review to estimate global morbidity and mortality for 2010

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Geoffrey C. Buckle

2012-06-01

Full Text Available Typhoid and paratyphoid fever remain important causes of morbidity worldwide. Accurate disease burden estimates are needed to guide policy decisions and prevention and control strategies.

Risk factors for typhoid outbreak in Sungai Congkak Recreational Park, Selangor 2009.

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Anita, S; Amir, K M; Fadzilah, K; Ahamad, J; Noorhaida, U; Marina, K; Paid, M Y; Hanif, Z

2012-02-01

Typhoid fever continues to pose public health problems in Selangor where cases are found sporadically with occasional outbreaks reported. In February 2009, Hospital Tengku Ampuan Rahimah (HTAR) reported a cluster of typhoid fever among four children in the pediatric ward. We investigated the source of the outbreak, risk factors for the infection to propose control measures. We conducted a case-control study to identify the risk factors for the outbreak. A case was defined as a person with S. typhi isolated from blood, urine or stool and had visited Sungai Congkak recreational park on 27th January 2010. Controls were healthy household members of cases who have similar exposure but no isolation of S. typhi in blood, urine or stool. Cases were identified from routine surveillance system, medical record searching from the nearest clinic and contact tracing other than family members including food handlers and construction workers in the recreational park. Immediate control measures were initiated and followed up. Twelve (12) cases were identified from routine surveillance with 75 household controls. The Case-control study showed cases were 17 times more likely to be 12 years or younger (95% CI: 2.10, 137.86) and 13 times more likely to have ingested river water accidentally during swimming (95% CI: 3.07, 58.71). River water was found contaminated with sewage disposal from two public toilets which effluent grew salmonella spp. The typhoid outbreak in Sungai Congkak recreational park resulted from contaminated river water due to poor sanitation. Children who accidentally ingested river water were highly susceptible. Immediate closure and upgrading of public toilet has stopped the outbreak.

Isavuconazole absorption following oral administration in healthy subjects is comparable to intravenous dosing, and is not affected by food, or drugs that alter stomach pH.

Science.gov (United States)

Schmitt-Hoffmann, Anne; Desai, Amit; Kowalski, Donna; Pearlman, Helene; Yamazaki, Takao; Townsend, Robert

2016-08-01

Two openlabel, single-dose, randomized crossover studies and one open-label, multiple-dose, parallel group study in healthy volunteers were conducted with the prodrug, isavuconazonium sulfate, to determine absolute bioavailability of the active triazole, isavuconazole (EudraCT 2007-004949-15; n = 14), and the effect of food (EudraCT 2007- 004940-63; n = 26), and pH (NCT02128893; n = 24) on the absorption of isavuconazole. Isavuconazonium sulfate 744 mg designed to deliver 400 mg of the active triazole isavuconazole was administered in the absolute bioavailability (oral or intravenous (IV) (2-hour infusion)) and food-effect studies (oral). In the pH-effect study, isavuconazonium sulfate 372 mg designed to deliver 200 mg of isavuconazole was administered orally three times daily (t.i.d.) for 2 days, followed by a single daily oral dose for 3 days, in the presence of steady state esomeprazole dosed orally at 40 mg/day. Isavuconazole was well tolerated in each study. Bioavailability: Geometric least squares mean ratios (GLSMR; oral/IV) for isavuconazole AUC∞, and Cmax were 98% (90% confidence interval (CI): 94, 101) and 78% (90% CI: 72, 85), respectively. Food-effect: GLSMR (fed/fasted) for AUC∞ and Cmax of isavuconazole in plasma were 110% (90% CI: 102, 118) and 92% (90% CI: 86, 98), respectively. Median tmax was 5 hours with food and 3 hours under fasted conditions. pH-effect: GLSMR for isavuconazole AUCtau and Cmax were 108% (90% CI: 89, 130) and 105% (90% CI: 89, 124), respectively. Orally administered isavuconazonium sulfate effectively delivers isavuconazole, as evidenced by the fact that oral isavuconazole is bioequivalent to the IV formulation. Dose adjustments are not required when switching between oral and IV formulations, regardless of food or drugs that increase gastric pH.

Typhoid fever complicated by intestinal perforation: a persisting fatal disease requiring surgical management

NARCIS (Netherlands)

Butler, T.; Knight, J.; Nath, S. K.; Speelman, P.; Roy, S. K.; Azad, M. A.

1985-01-01

In Bangladesh, clinical records of 323 patients with typhoid fever were reviewed to study the incidence, fatality, and optimal therapy of the complication of intestinal perforation. Fifteen patients (4.6%) developed intestinal perforation. Case-fatality rates were six of nine patients treated

Resolution of methylphenidate osmotic release oral system-induced hair loss in two siblings after dose escalation.

Science.gov (United States)

Ardic, Ulku Akyol; Ercan, Eyup Sabri

2017-11-01

This report describes the cases of two siblings who experienced hair loss after treatment with methylphenidate (MPH) osmotic release oral system (OROS). Hair loss was resolved after discontinuation of the drug, but the children re-initiated treatment, after which hair loss again occurred, but they continued the treatment. After dose escalation, the hair loss resolved. This is the first report to describe resolution of OROS-MPH-induced hair loss after dose escalation. © 2017 Japan Pediatric Society.

Patient doses during intra-oral radiography in dental offices

International Nuclear Information System (INIS)

Sakaino, Rie; Harata, Yasuo; Okano, Tomohiro; Sato, Kenji; Yosue, Takashi; Nishikawa, Keiichi; Sano, Tsukasa; Kobayashi, Ikuo

2011-01-01

Measurement of patient entrance dose (PED) and dose area product (DAP) at various dental offices in the Tokyo bay area and comparison of PEDs with the existing diagnostic reference levels recommended in the United Kingdom (UK). The survey included 28 dental clinics categorized by the type of intra-oral radiography used. PED was measured by placing an optically stimulated luminescence dosimeter (OSLD) at the tip of the cone. Exposure parameters were those used for the adult mandibular molar region in the respective clinics. The OSLD readings were calibrated using an ionizing chamber manufactured according to standards of the Japan Quality Assurance Organization. The area (A), of the X-ray beam, was calculated by exposing an X-ray film placed at the tip of the cone and measuring the exposed area. Then the DAP was calculated as the product of PED times A. The PED estimated at various dental clinics differed by a factor of 120. The mean, minimum, maximum, median and third quartile values of PEDs were 4.99, 0.18, 21.7, 3.60 and 5.76 mGy, respectively. At 60-70 kV, PEDs observed in clinics using digital imaging systems were below 2.1 mGy which was lower than that of clinics using films that were E-speed or faster. It was also observed that PEDs were directly proportional to the tube current and exposure time. The mean, minimum, maximum, median and third quartile of DAPs were 13.0, 0.45, 61.4, 9.34 and 13.4 cGy cm 2 , respectively. The DAP values showed a linear correlation coefficient of 0.99 with PED values. Measurement of PED and DAP using OSLD and X-ray film can play a useful role in optimization of radiation protection for patients during intra-oral radiography. This method can be conveniently applied to set up diagnostic reference levels by carrying out mass surveys in Japan. (author)

Safety, tolerability, and pharmacokinetics of single oral doses of tofacitinib, a Janus kinase inhibitor, in healthy volunteers.

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Krishnaswami, Sriram; Boy, Mary; Chow, Vincent; Chan, Gary

2015-03-01

Tofacitinib is an oral Janus kinase inhibitor. This randomized, double-blind, parallel-group, placebo-controlled study was the first evaluation of tofacitinib in humans. The objectives were to characterize the safety and tolerability, pharmacokinetics (PK), and pharmacodynamics of escalating single tofacitinib doses in healthy subjects. Tofacitinib (0.1, 0.3, 1, 3, 10, 30, 60, and 100 mg) or placebo was administered as oral powder for constitution. For each dose, 7-9 subjects were randomized to tofacitinib and 3-5 subjects to placebo. Ninety-five males and females (age range 19-45) completed the study. Forty-nine treatment-emergent all-causality adverse events (AEs) were observed; nausea and headache were the most frequently reported. Tofacitinib PK was characterized by rapid absorption (time to peak serum concentration [Tmax ] 0.5-1 hour), rapid elimination (mean terminal half-lives 2.3-3.1 hours), and dose-proportional systemic exposures (peak serum concentration [Cmax ] and area under the serum concentration-time curve from time zero to infinity [AUC0-∞ ]). No appreciable correlation was observed between tofacitinib dose and lymphocyte subset counts. Single-dose tofacitinib up to 100 mg in healthy subjects had a safety profile of mostly mild AEs, and no deaths, serious AEs, severe AEs or discontinuations due to AEs. © 2014, The American College of Clinical Pharmacology.

Placental transfer and pharmacokinetics of a single oral dose of [14C] p-nitrophenol in rats

International Nuclear Information System (INIS)

Abu-Qare, A.W.; Brownie, C.F.; Abou-Donia, M.B.

2000-01-01

The pharmacokinetics and placental transfer of a single oral dose of 100 mg/kg (10 μCi/kg, 16% of acute oral LD 50 ) of uniformly phenyl-labeled [ 14 C]p-nitrophenol were investigated in pregnant Sprague-Dawley rats at 14-18 days of gestation. Three animals were killed on gestation day 18, at 0.5, 1, 2, 4, 12, 24, and 48 h after dosing. Radioactivity was rapidly absorbed and distributed throughout the maternal and fetal tissues. The gastrointestinal tract contents retained 20% and 2% of the dose at 0.5 h and 4 h after dosing. The peak maternal plasma concentration of radioactivity (μg p-nitrophenol equivalent/ml) was 7.17 compared with 0.37 for fetal plasma at 0.5 h. Maximum concentration of radioactivity (μg p-nitrophenol equivalent/g fresh tissue) was detected in most tissues 0.5 h after dosing and was in descending order: kidney 23.27, liver 12.37, placenta 3.56, fetus 2.17, and brain 1.99. Radioactivity was eliminated from plasma and all tissues beiexponentially. The half-lives of elimination of 14 C were 34.65 h and 69.30 h for maternal and fetal plasma, respectively. p-Nitrophenol, detected by HPLC, was the major compound identified in plasma and tissues. While p-nitrophenol disappeared biphasically from maternal plasma and kidney, it was eliminated monophasically from brain, placenta, and liver. p-Nitrocatechol and p-aminophenol were detected in the liver with peak concentrations at 0.5 h of 1.13 and 1.00 μg/g fresh tissue, respectively. While the change in the concentration of p-nitrocatechol with time was monophasic, that of p-aminophenol showed a biphasic pattern with elimination half-lives of 1.93 h and 4.95 h, respectively. Radioactivity was rapidly excreted in the urine mostly as polar metabolites, while only 3% of the dose was recovered in the feces. Radioactive materials excreted in the urine comprised: glucuronides 4%, sulfates 8%, hot-acid hydrolysates 11%, nonconjugated compounds 16%, and water-soluble metabolites 61%. This study demonstrated

Shifts in geographic distribution and antimicrobial resistance during a prolonged typhoid fever outbreak--Bundibugyo and Kasese Districts, Uganda, 2009-2011.

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Walters, Maroya Spalding; Routh, Janell; Mikoleit, Matthew; Kadivane, Samuel; Ouma, Caroline; Mubiru, Denis; Mbusa, Ben; Murangi, Amos; Ejoku, Emmanuel; Rwantangle, Absalom; Kule, Uziah; Lule, John; Garrett, Nancy; Halpin, Jessica; Maxwell, Nikki; Kagirita, Atek; Mulabya, Fred; Makumbi, Issa; Freeman, Molly; Joyce, Kevin; Hill, Vince; Downing, Robert; Mintz, Eric

2014-03-01

Salmonella enterica serovar Typhi is transmitted by fecally contaminated food and water and causes approximately 22 million typhoid fever infections worldwide each year. Most cases occur in developing countries, where approximately 4% of patients develop intestinal perforation (IP). In Kasese District, Uganda, a typhoid fever outbreak notable for a high IP rate began in 2008. We report that this outbreak continued through 2011, when it spread to the neighboring district of Bundibugyo. A suspected typhoid fever case was defined as IP or symptoms of fever, abdominal pain, and ≥1 of the following: gastrointestinal disruptions, body weakness, joint pain, headache, clinically suspected IP, or non-responsiveness to antimalarial medications. Cases were identified retrospectively via medical record reviews and prospectively through laboratory-enhanced case finding. Among Kasese residents, 709 cases were identified from August 1, 2009-December 31, 2011; of these, 149 were identified during the prospective period beginning November 1, 2011. Among Bundibugyo residents, 333 cases were identified from January 1-December 31, 2011, including 128 cases identified during the prospective period beginning October 28, 2011. IP was reported for 507 (82%) and 59 (20%) of Kasese and Bundibugyo cases, respectively. Blood and stool cultures performed for 154 patients during the prospective period yielded isolates from 24 (16%) patients. Three pulsed-field gel electrophoresis pattern combinations, including one observed in a Kasese isolate in 2009, were shared among Kasese and Bundibugyo isolates. Antimicrobial susceptibility was assessed for 18 isolates; among these 15 (83%) were multidrug-resistant (MDR), compared to 5% of 2009 isolates. Molecular and epidemiological evidence suggest that during a prolonged outbreak, typhoid spread from Kasese to Bundibugyo. MDR strains became prevalent. Lasting interventions, such as typhoid vaccination and improvements in drinking water infrastructure

Effect of treatment with single total-dose intravenous iron versus daily oral iron(III-hydroxide polymaltose on moderate puerperal iron-deficiency anemia

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Iyoke CA

2017-05-01

Full Text Available Chukwuemeka Anthony Iyoke,1 Fausta Chioma Emegoakor,1 Euzebus Chinonye Ezugwu,1 Lucky Osaheni Lawani,2 Leonard Ogbonna Ajah,1 Jude Anazoeze Madu,3 Hyginus Uzo Ezegwui,1 Frank Okechukwu Ezugwu4 1Department of Obstetrics and Gynaecology, University of Nigeria, Enugu Campus, 2Department of Obstetrics and Gynaecology, Federal Teaching Hospital, Abakaliki, 3Department of Haematology, University of Nigeria, Nsukka, 4Department of Obstetrics and Gynaecology, College of Medicine, Enugu State University, Enugu, Nigeria Background: Iron-deficiency anemia is the most common nutritional cause of anemia in pregnancy and is often responsible for puerperal anemia. Puerperal anemia can impair postpartum maternal and neonatal well-being. Objective: To determine the effect of treatment of moderate puerperal iron-deficiency anemia using a single intravenous total-dose iron dextran versus daily single dose oral iron(III-hydroxide polymaltose. Methodology: A randomized controlled study in which postpartum women with moderate iron-deficiency anemia were randomized into treatment with either a single total-dose intravenous iron dextran or with daily single doses of oral iron(III-hydroxide polymaltose tablets for 6 weeks. Effects on hemoglobin concentration using either method were compared at 6 weeks postpartum. Analysis was per protocol using SPSS version 17 for windows. P-values ≤0.05 were considered significant. Results: Two hundred eighty-four women were recruited for the study: 142 women received single total dose intravenous infusion of iron dextran while 142 received daily oral iron(III-hydroxide polymaltose tablets. Approximately 84.0% (237/282 completed the study and were analyzed including 81% (115/142 of those randomized to injectable iron therapy compared to 85.9% (122/142 of those randomized to oral treatment. The proportions of women who had attained hemoglobin concentration of at least 10 g/dL by the 6 weeks postpartum visit did not differ

Health at the Sub-catchment Scale: Typhoid and Its Environmental Determinants in Central Division, Fiji.

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Jenkins, Aaron Peter; Jupiter, Stacy; Mueller, Ute; Jenney, Adam; Vosaki, Gandercillar; Rosa, Varanisese; Naucukidi, Alanieta; Mulholland, Kim; Strugnell, Richard; Kama, Mike; Horwitz, Pierre

2016-12-01

The impact of environmental change on transmission patterns of waterborne enteric diseases is a major public health concern. This study concerns the burden and spatial nature of enteric fever, attributable to Salmonella Typhi infection in the Central Division, Republic of Fiji at a sub-catchment scale over 30-months (2013-2015). Quantitative spatial analysis suggested relationships between environmental conditions of sub-catchments and incidence and recurrence of typhoid fever. Average incidence per inhabited sub-catchment for the Central Division was high at 205.9/100,000, with cases recurring in each calendar year in 26% of sub-catchments. Although the numbers of cases were highest within dense, urban coastal sub-catchments, the incidence was highest in low-density mountainous rural areas. Significant environmental determinants at this scale suggest increased risk of exposure where sediment yields increase following runoff. The study suggests that populations living on large systems that broaden into meandering mid-reaches and floodplains with alluvial deposition are at a greater risk compared to small populations living near small, erosional, high-energy headwaters and small streams unconnected to large hydrological networks. This study suggests that anthropogenic alteration of land cover and hydrology (particularly via fragmentation of riparian forest and connectivity between road and river networks) facilitates increased transmission of typhoid fever and that environmental transmission of typhoid fever is important in Fiji.

Comparative assessment of efficacy of two different pretreatment single oral doses of betamethasone on inter-appointment and postoperative discomfort: An in vivo clinical evaluation.

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Gyanani, Hitesh; Chhabra, Naveen; Parmar, Ghanshyam R

2016-01-01

Study aimed to evaluate the efficacy of two different pretreatment single oral doses of betamethasone on the incidence of inter-appointment flare up and postoperative discomfort. Fifty-four patients aged 18-59 years requiring endodontic treatment were selected and randomly assigned to three groups; single pretreatment oral dose of placebo or betamethasone in two different oral doses of 0.5 mg and 1 mg, respectively. Endodontic therapy was completed in two visits using triple antibiotic paste as intracanal medicament. Patients were given a questionnaire to record their pain at 1, 2, 3, and 7 days after treatment. In the second visit, obturation was done, and the patients were again instructed to record their pain scores after treatment and discharged. The verbal rating scale was used for recording the pain scores. Statistical analysis was done using ANOVA and the Friedman test. 0.5 mg betamethasone group showed least mean pain scores among all experimental groups; however, there was no statistically significant difference between any of the groups ( P > 0.05). Pretreatment single oral dose of betamethasone is an effective in managing endodontic flare-ups; however, the results were statistically insignificant.

Pulsed-dosing with oral sodium phenylbutyrate increases hemoglobin F in a patient with sickle cell anemia.

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Hines, Patrick; Dover, George J; Resar, Linda M S

2008-02-01

Increasing hemoglobin F (HbF) appears to be beneficial for patients with sickle cell anemia. We previously demonstrated that daily, oral sodium phenylbutyrate (OSPB) induces HbF synthesis in pediatric and adult patients with hemoglobin SS (HbSS). The high doses and need for daily therapy, however, have limited its use. Here, we report a patient treated with pulsed-dosing of OSPB for over 3 years. This patient developed a modest, but sustained elevation in HbF over the course of therapy without side effects. Although larger studies are needed, this case demonstrates that pulsed-dosing with OSPB enhances HbF synthesis. (c) 2007 Wiley-Liss, Inc.

A Study on the Single-dose Oral Toxicity of Super Key in Sprague-Dawley Rats

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Jinhee Kim

2015-09-01

Full Text Available Objectives: This study was performed to analyze the single-dose oral toxicity of the super key (processed sulfur. Methods: All experiments were conducted at Medvill, an institution authorized to perform non-clinical studies, under the Good Laboratory Practice (GLP regulations. In order to investigate the oral toxicity of super key We administered it orally to Sprague-Dawley (SD rats. The SD rats were divided into four groups of five male and five female animals per group: group 1 being the control group and groups 2, 3, and 4 being the experimental groups. Doses of super key 500 mg/kg, 1,000 mg/kg and 2,000 mg/kg were administered to the experimental groups, and a dose of normal saline solution, 10 mL/kg, was administered to the control group. We examined the survival rates, weights, clinical signs, gross findings and necropsy findings. This study was conducted under the approval of the Institutional Animal Ethics Committee. (Approval number: A01-14018. Results: No deaths or abnormalities occurred in any of the four groups. Although slight decreases in the weights of some female rats were noted, no significant changes in weights or differences in the gross findings between the control group and the experimental groups were observed. To check for abnormalities in organs, we used microscopy to examine representative histological sections of each specified organ; the results showed no significant differences in any of the organs. Conclusion: The results of this research showed that administration of 500 ─ 2,000 mg/kg of super key did not cause any changes in the weights or in the results of necropsy examinations. Neither did it result in any mortalities. The above findings suggest that treatment with super key is relatively safe. Further studies on this subject are needed to yield more concrete evidence.

Modelling and Optimal Control of Typhoid Fever Disease with Cost-Effective Strategies.

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Tilahun, Getachew Teshome; Makinde, Oluwole Daniel; Malonza, David

2017-01-01

We propose and analyze a compartmental nonlinear deterministic mathematical model for the typhoid fever outbreak and optimal control strategies in a community with varying population. The model is studied qualitatively using stability theory of differential equations and the basic reproductive number that represents the epidemic indicator is obtained from the largest eigenvalue of the next-generation matrix. Both local and global asymptotic stability conditions for disease-free and endemic equilibria are determined. The model exhibits a forward transcritical bifurcation and the sensitivity analysis is performed. The optimal control problem is designed by applying Pontryagin maximum principle with three control strategies, namely, the prevention strategy through sanitation, proper hygiene, and vaccination; the treatment strategy through application of appropriate medicine; and the screening of the carriers. The cost functional accounts for the cost involved in prevention, screening, and treatment together with the total number of the infected persons averted. Numerical results for the typhoid outbreak dynamics and its optimal control revealed that a combination of prevention and treatment is the best cost-effective strategy to eradicate the disease.

Pharmacokinetic interaction of enrofloxacin/trimethoprim combination following single-dose intraperitoneal and oral administration in rats.

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Choi, Myung-Jin; Yohannes, Sileshi Belew; Lee, Seung-Jin; Damte, Dereje; Kim, Jong-Choon; Suh, Joo-Won; Park, Seung-Chun

2014-03-01

The pharmacokinetic interaction of enrofloxacin and trimethoprim was evaluated after single-dose intraperitoneal or oral co-administration in rats. Plasma concentrations of the two drugs were determined by high-performance liquid chromatography. Following intraperitoneal combination, a significant (P trimethoprim, respectively. There was a significant (P trimethoprim. Further study is recommended in other species of animals.

Oral Cryotherapy for Preventing Oral Mucositis in Patients Receiving Cancer Treatment.

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Riley, Philip; McCabe, Martin G; Glenny, Anne-Marie

2016-10-01

In patients receiving treatment for cancer, does oral cryotherapy prevent oral mucositis? Oral cryotherapy is effective for the prevention of oral mucositis in adults receiving fluorouracil-based chemotherapy for solid cancers, and for the prevention of severe oral mucositis in adults receiving high-dose melphalan-based chemotherapy before hematopoietic stem cell transplantation (HSCT).

Influence of Vehicles Used for Oral Dosing of Test Molecules on the Progression of Mycobacterium tuberculosis Infection in Mice

OpenAIRE

Singh, Shubhra; Dwivedi, Richa; Chaturvedi, Vinita

2014-01-01

Preclinical evaluation of drug-like molecules requires their oral administration to experimental animals using suitable vehicles. We studied the effect of oral dosing with corn oil, carboxymethyl cellulose, dimethyl sulfoxide, and polysorbate-80 on the progression of Mycobacterium tuberculosis infection in mice. Infection was monitored by physical (survival time and body weight) and bacteriological (viable counts in lungs) parameters. Compared with water, corn oil significantly improved both ...

The effect of high-dose dronabinol (oral THC) maintenance on cannabis self-administration.

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Schlienz, Nicolas J; Lee, Dustin C; Stitzer, Maxine L; Vandrey, Ryan

2018-06-01

There is a clear need for advancing the treatment of cannabis use disorders. Prior research has demonstrated that dronabinol (oral THC) can dose-dependently suppress cannabis withdrawal and reduce the acute effects of smoked cannabis. The present study was conducted to evaluate whether high-dose dronabinol could reduce cannabis self-administration among daily users. Non-treatment seeking daily cannabis users (N = 13) completed a residential within-subjects crossover study and were administered placebo, low-dose dronabinol (120 mg/day; 40 mg tid), or high-dose dronabinol (180-240 mg/day; 60-80 mg tid) for 12 consecutive days (order counterbalanced). During each 12-day dronabinol maintenance phase, participants were allowed to self-administer smoked cannabis containing <1% THC (placebo) or 5.7% THC (active) under forced-choice (drug vs. money) or progressive ratio conditions. Participants self-administered significantly more active cannabis compared with placebo in all conditions. When active cannabis was available, self-administration was significantly reduced during periods of dronabinol maintenance compared with placebo maintenance. There was no difference in self-administration between the low- and high-dose dronabinol conditions. Chronic dronabinol dosing can reduce cannabis self-administration in daily cannabis users and suppress withdrawal symptoms. Cannabinoid agonist medications should continue to be explored for therapeutic utility in the treatment of cannabis use disorders. Copyright © 2018 Elsevier B.V. All rights reserved.

Environmental Survey of Drinking Water Sources in Kampala, Uganda, during a Typhoid Fever Outbreak.

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Murphy, J L; Kahler, A M; Nansubuga, I; Nanyunja, E M; Kaplan, B; Jothikumar, N; Routh, J; Gómez, G A; Mintz, E D; Hill, V R

2017-12-01

In 2015, a typhoid fever outbreak began in downtown Kampala, Uganda, and spread into adjacent districts. In response, an environmental survey of drinking water source types was conducted in areas of the city with high case numbers. A total of 122 samples was collected from 12 source types and tested for Escherichia coli , free chlorine, and conductivity. An additional 37 grab samples from seven source types and 16 paired large volume (20 liter) samples from wells and springs were also collected and tested for the presence of Salmonella enterica serovar Typhi. Escherichia coli was detected in 60% of kaveras (drinking water sold in plastic bags) and 80% of refilled water bottles; free chlorine was not detected in either source type. Most jerry cans (68%) contained E. coli and had free chlorine residuals below the WHO-recommended level of 0.5 mg/liter during outbreaks. Elevated conductivity readings for kaveras, refilled water bottles, and jerry cans (compared to treated surface water supplied by the water utility) suggested that they likely contained untreated groundwater. All unprotected springs and wells and more than 60% of protected springs contained E. coli Water samples collected from the water utility were found to have acceptable free chlorine levels and no detectable E. coli While S Typhi was not detected in water samples, Salmonella spp. were detected in samples from two unprotected springs, one protected spring, and one refilled water bottle. These data provided clear evidence that unregulated vended water and groundwater represented a risk for typhoid transmission. IMPORTANCE Despite the high incidence of typhoid fever globally, relatively few outbreak investigations incorporate drinking water testing. During waterborne disease outbreaks, measurement of physical-chemical parameters, such as free chlorine residual and electrical conductivity, and of microbiological parameters, such as the presence of E. coli or the implicated etiologic agent, in drinking

Evaluation of changes in serum chemistry in association with feed withdrawal or high dose oral gavage with Dextran Sodium Sulfate (DSS) induced gut leakage in broiler chickens

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Dextran sodium sulfate (DSS) has been shown to be effective at inducing enteric inflammation in broiler chickens, resulting in increased leakage of orally administered fluorescein isothiocyanate dextran to circulation. In a previous study, two doses of DSS (0.45g/dose) administered as oral gavage re...

Lung concentrations of telithromycin after oral dosing.

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Khair, O A; Andrews, J M; Honeybourne, D; Jevons, G; Vacheron, F; Wise, R

2001-06-01

Concentrations of telithromycin were measured in plasma, bronchial mucosa (BM), epithelial lining fluid (ELF) and alveolar macrophages (AM) following multiple oral doses. Concentrations were determined using a microbiological assay. There were 20 subjects in the study, allocated to three nominal time periods: 2, 12 and 24 h. Mean concentrations in plasma, BM, ELF and AM for 2, 12 and 24 h were as follows: 2 h, 1.86 mg/L, 3.88 mg/kg, 14.89 mg/L and 69.32 mg/L; 12 h, 0.23 mg/L, 1.41 mg/kg, 3.27 mg/L and 318.1 mg/L; and 24 h, 0.08 mg/L, 0.78 mg/kg, 0.97 mg/L and 161.57 mg/L. These concentrations of telithromycin in BM and ELF exceeded for 24 h the mean MIC90s of the common respiratory pathogens Streptococcus pneumoniae (0.12 mg/L) and Moraxella catarrhalis (0.03 mg/L), as well as the atypical microorganism Mycoplasma pneumoniae (0.001 mg/L), and suggest that telithromycin may be effective for the treatment of community-acquired pneumonia and chronic obstructive pulmonary disease.

Successful treatment for subinvolution of placental sites in the bitch with low oral doses of progestagen.

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Voorhorst, M J; van Brederode, J C; Albers-Wolthers, C H J; de Gier, J; Schaefers-Okkens, A C

2013-10-01

Subinvolution of placental sites (SIPS) is the major cause of persistent sanguineous vaginal discharge after parturition in the bitch. Spontaneous remission is common but may take several months, and hence, medical therapy to end the discharge is often requested. In this retrospective study, we evaluated the effect of treatment for SIPS with low oral doses of a progestagen. Nine bitches with SIPS, but otherwise clinically healthy, were found in the computer database of the Department of Clinical Sciences of Companion Animals. Seven of these bitches were treated with low oral doses of a progestagen (megestrol acetate, 0.1 mg/kg body weight (bw) once daily for the 1st week, then 0.05 mg/kg bw once daily for the 2nd week). The other two bitches were untreated. Treatment results were evaluated by a telephone questionnaire. Progestagen treatment was successful in all of the treated dogs; sanguineous vaginal discharge stopped within the treatment period. One of the two untreated dogs remained symptomatic until the next oestrus, approximately 120 days after parturition, and the other remained symptomatic until 6 weeks before the start of the next pro-oestrus, 270 days after parturition. No side effects of the progestagen treatment were observed. Subsequent gestations, parturitions and puerperal periods of 5 mated bitches were uneventful. One bitch did not become pregnant after mating. In conclusion, the results of this study indicate that oral administration of low doses of progestagen for 2 weeks is effective in stopping persistent sanguineous vaginal discharge in bitches with SIPS, with neither side effects nor reduced subsequent fertility. © 2013 Blackwell Verlag GmbH.

Ability of Saudi mothers to appropriately and accurately use dosing devices to administer oral liquid medications to their children

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Almazrou S

2014-12-01

Full Text Available Saja Almazrou, Hind Alsahly, Huda Alwattar, Lamya Alturki, Mona Alamri Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia Background: Most liquid medications are packaged with administration devices, which may be used inappropriately or inaccurately, and sometimes are not used at all. Because of the importance of their proper use for children's health, this study was designed to assess Saudi mothers' experiences with measuring cups, syringes, and droppers for oral liquid medications; to compare accuracy of dosing across these devices; and to determine the effects of mothers' education statuses and pharmacist counseling on dosing accuracy. Methods: This was a cross-sectional study in which mothers were observed as they used a set of commonly available dosing devices which are a dosing cup, syringe, and dropper. Interviews were conducted in the outpatient pharmacy waiting area in several tertiary hospitals and primary clinics in Riyadh, Saudi Arabia between March and April 2013. Saudi women who were mothers of children aged 12 years old or younger and who gave their consent were eligible. Caregivers other than mothers and subjects with vision problems or cognitive/physical disabilities were excluded. We gathered demographic information such as age, number of children, and education status. Subjects were asked if they had had counseling on how to use measuring devices and which device they preferred. Then, the mothers were required to demonstrate how to measure 5 mL of paracetamol (acetaminophen syrup using a cup and a syringe and 1 mL of paracetamol syrup using a dropper. Dosing errors were evaluated visually as overdosing, underdosing, or no error (if the dose was accurate. The data were entered into Microsoft Excel and evaluated using Stata 11.1. Logistic regression was employed to determine relationships. Results: The results revealed that 58% of participants measured an accurate dose of paracetamol

Dose and risk evaluation to the thyroid gland in intra-oral dental radiology

International Nuclear Information System (INIS)

Souza, Edmilson M.; Lima, Marco A.F.; Kelecom, Alphonse; Correa, Samanda C.A.; Silva, Ademir X.; Brito, Alan

2008-01-01

Intra-oral technique is one of the most frequently used procedures of dental radiology, allowing the detection of a variety of dental anomalies such as caries, dental trauma and periodontal lesions, while exposing patients to relatively low doses of radiation. However, although the adverse effects of doses generated by dental radiology are essentially stochastic, a number of epidemiological studies have provided evidence of an increased risk of thyroid tumors for dental radiography. Many studies have measured doses of radiation for dental radiography, but only a few have estimated thyroid dose. Furthermore, most of the studies on dose evaluation in dental radiology are based on standardized calculation phantoms, which neglect the variance of the patient size or even sex. The purpose of this study is to use the Monte Carlo code MCNPX and the FAX (Female Adult voXel) and MAX (Male Adult voXel) phantoms to investigate how absorbed doses to the thyroid gland in intraoral dental examinations vary in female and male patients. The lifetime cancer incidence attributable to dental examinations were estimated using the Biological Effects of Ionizing Radiations (BEIR) VII Committee Report. The phantoms study proved a useful trial for detecting the radiation dose to the thyroid gland and conclusively supported that the anatomy may be regarded as an influencing factor in radiation dose received during dental examination. Finally, the results have also confirmed that the association of the MCNPX code and the MAX and FAX phantoms is very useful in dosimetric studies on radiographic examinations of female and male patients. (author)

Prevalence of malaria, typhoid, toxoplasmosis and rubella among febrile children in Cameroon.

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Achonduh-Atijegbe, Olivia A; Mfuh, Kenji O; Mbange, Aristid H E; Chedjou, Jean P; Taylor, Diane W; Nerurkar, Vivek R; Mbacham, Wilfred F; Leke, Rose

2016-11-08

The current roll-out of rapid diagnostic tests (RDTs) in many endemic countries has resulted in the reporting of fewer cases of malaria-attributed illnesses. However, lack of knowledge of the prevalence of other febrile illnesses and affordable diagnostic tests means that febrile patients are not managed optimally. This study assessed the prevalence of commonly treatable or preventable febrile illnesses in children between 6 months and 15 years using rapid diagnostic tests at the point-of-care. Febrile children were enrolled between February-April 2014 at a health facility after obtaining informed consent from parent. Eligible participants were aged 6 months-15 years with a history of fever in the last 24 h or axillary temperature ≥38 °C at consultation. All participants were tested using RDTs for malaria, typhoid, toxoplasmosis and rubella. Malaria parasites were further identified by microscopy and PCR. Clinical and household characteristics were recorded and association with pathogens determined. Of the 315 children enrolled, the mean age was 5.8 ± 3.8 years. Stomach pain (41.2 %) was the most reported symptom. Prior to attending the health facility, 70.8 % had taken antipyretics, 27.9 % antimalarials, 11.4 % antibiotics and 13.3 % antifungal drugs. Among 315 children with fever, based on RDTs, 56.8 % were infected with malaria, 4.4 % with typhoid, 3.2 % with acute toxoplasmosis, and 1.3 % with rubella (all positive for rubella were in the same family and not vaccinated). All non-malarial infections were co-infections and approximately 30 % of the fever cases went un-diagnosed. Malaria prevalence by microscopy and PCR was 43.4 and 70.2 % respectively. The sensitivity and specificity of RDTs for the diagnosis of malaria were 75.98 and 100 % respectively, with 0.73 measurement agreement between RDTs and microscopy while that of RDT and PCR were 81 and 100 % respectively with a K value of 0.72. The use of Insecticide Treated Bednets was

Regulation of operant oral ethanol self-administration: a dose-response curve study in rats.

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Carnicella, Sebastien; Yowell, Quinn V; Ron, Dorit

2011-01-01

Oral ethanol self-administration procedures in rats are useful preclinical tools for the evaluation of potential new pharmacotherapies as well as for the investigation into the etiology of alcohol abuse disorders and addiction. Determination of the effects of a potential treatment on a full ethanol dose-response curve should be essential to predict its clinical efficacy. Unfortunately, this approach has not been fully explored because of the aversive taste reaction to moderate to high doses of ethanol, which may interfere with consumption. In this study, we set out to determine whether a meaningful dose-response curve for oral ethanol self-administration can be obtained in rats. Long-Evans rats were trained to self-administer a 20% ethanol solution in an operant procedure following a history of excessive voluntary ethanol intake. After stabilization of ethanol self-administration, the concentration of the solution was varied from 2.5 to 60% (v/v), and operant and drinking behaviors, as well as blood ethanol concentration (BEC), were evaluated following the self-administration of a 20, 40, and 60% ethanol solution. Varying the concentration of ethanol from 2.5 to 60% after the development of excessive ethanol consumption led to a typical inverted U-shaped dose-response curve. Importantly, rats adapted their level and pattern of responding to changes in ethanol concentration to obtain a constant level of intake and BEC, suggesting that their operant behavior is mainly driven by the motivation to obtain a specific pharmacological effect of ethanol. This procedure can be a useful and straightforward tool for the evaluation of the effects of new potential pharmacotherapies for the treatment of alcohol abuse disorders. Copyright © 2010 by the Research Society on Alcoholism.

A mass vaccination campaign targeting adults and children to prevent typhoid fever in Hechi; Expanding the use of Vi polysaccharide vaccine in Southeast China: A cluster-randomized trial

Directory of Open Access Journals (Sweden)

Yang Hong-hui

2005-05-01

Full Text Available Abstract Background One of the goals of this study was to learn the coverage, safety and logistics of a mass vaccination campaign against typhoid fever in children and adults using locally produced typhoid Vi polysaccharide (PS and group A meningococcal PS vaccines in southern China. Methods The vaccination campaign targeted 118,588 persons in Hechi, Guangxi Province, aged between 5 to 60 years, in 2003. The study area was divided into 107 geographic clusters, which were randomly allocated to receive one of the single-dose parenteral vaccines. All aspects regarding vaccination logistics, feasibility and safety were documented and systematically recorded. Results of the logistics, feasibility and safety are reported. Results The campaign lasted 5 weeks and the overall vaccination coverage was 78%. On average, the 30 vaccine teams gave immunizations on 23 days. Vaccine rates were higher in those aged ≤ 15 years (90% than in adolescents and young adults (70%. Planned mop-up activities increased the coverage by 17%. The overall vaccine wastage was 11%. The cold chain was maintained and documented. 66 individuals reported of adverse events out of all vaccinees, where fever (21%, malaise (19% and local redness (19% were the major symptoms; no life-threatening event occurred. Three needle-sharp events were reported. Conclusion The mass immunization proved feasible and safe, and vaccine coverage was high. Emphasis should be placed on: injection safety measures, community involvement and incorporation of mop-up strategies into any vaccination campaign. School-based and all-age Vi mass immunizations programs are potentially important public health strategies for prevention of typhoid fever in high-risk populations in southern China.

Localised transmission hotspots of a typhoid fever outbreak in the Democratic Republic of Congo.

Science.gov (United States)

Ali, Engy; Bergh, Rafael Van Den; D'hondt, Rob; Kuma-Kuma, Donat; Weggheleire, Anja De; Baudot, Yves; Lambert, Vincent; Hunter, Paul; Zachariah, Rony; Maes, Peter

2017-01-01

In a semi-urban setting in the Democratic Republic of Congo, this study aims to understand the dynamic of a typhoid fever (TF) outbreak and to assess: a) the existence of hot spots for TF transmission and b) the difference between typhoid cases identified within those hot spots and the general population in relation to socio-demographic characteristics, sanitation practice, and sources of drinking water. This was a retrospective analysis of TF outbreaks in 2011 in Kikwit, DRC using microbiological analysis of water sources and a structured interview questionnaire. There were a total of 1430 reported TF cases. The outbreak's epidemic curve shows earliest and highest peak attack rates (AR) in three military camps located in Kikwit (Ebeya 3.2%; Ngubu 3.0%; and Nsinga 2.2%) compared to an average peak AR of 0.6% in other affected areas. A total 320 cases from the military camps and the high burden health areas were interviewed. Typhoid cases in the military camps shared a latrine with more than one family (P<0.02). All tap water sources in both the military camps and general population were found to be highly contaminated with faecal coliforms. The role of military camps in Kikwit as early hotspots of TF transmission was likely associated with lower sanitary and hygiene conditions. The proximity of camps to the general population might have been responsible for disseminating TF to the general population. Mapping of cases during an outbreak could be crucial to identify hot spots for transmission and institute corrective measures.

Single- and Multiple-Dose Study To Determine the Safety, Tolerability, Pharmacokinetics, and Food Effect of Oral MRX-I versus Linezolid in Healthy Adult Subjects.

Science.gov (United States)

Eckburg, Paul B; Ge, Yigong; Hafkin, Barry

2017-04-01

A multipart phase 1 study was conducted to determine the safety, tolerability, pharmacokinetics, and food effect of the novel oral oxazolidinone, MRX-I, in healthy adults, as well as the tolerability of longer-term exposure of both oral MRX-I and linezolid. Thirty subjects in part 1 received single ascending doses of MRX-I or placebo under fasting or fed condition in a double-blind crossover design. Twelve subjects in part 2 received MRX-I at 800 mg every 12 h (q12h) for 14 days in a double-blind, placebo-controlled design. In part 3, 24 subjects were randomized to receive 28 days of MRX-I at 800 mg q12h or oral linezolid at 600 mg q12h for 28 days in a double-blind, double-dummy design. Oral MRX-I was associated with a greater bioavailability and exposure when administered with food, and minimal accumulation of MRX-I occurred after multiple-dose administration. Oral MRX-I was well tolerated at single doses of up to 1,200 and 800 mg q12h for up to 28 days; all adverse events were mild to moderate in severity, and there was no drug discontinuation due to adverse events. These data support further clinical development of oral MRX-I in the treatment of resistant Gram-positive bacterial infections. Copyright © 2017 American Society for Microbiology.

Evaluation of dipstick serologic tests for diagnosis of brucellosis and typhoid Fever in egypt

NARCIS (Netherlands)

Ismail, Tharwat F.; Smits, Henk; Wasfy, Momtaz O.; Malone, Joseph L.; Fadeel, Moustafa A.; Mahoney, Frank

2002-01-01

Two dipstick assays for the detection of Brucella- and typhoid-specific immunoglobulin M, recently developed by the Royal Tropical Institute of The Netherlands, were evaluated by use of 85 plasma samples from Egyptian patients. Both dipsticks were simple and accurate rapid diagnostic assays, and

A multiple-dose, double-blind comparison of intramuscularly and orally administered ketorolac tromethamine and Ketogan in patients with pain following orthopaedic surgery

DEFF Research Database (Denmark)

Gebuhr, Peter Henrik; Soelberg, M; Strauss, W

1994-01-01

combination product containing the narcotic analgesic, ketobemidone, plus a spasmolytic agent) by intramuscular injection every 1-6 h as needed for pain. When patients were able to tolerate an oral diet and were expected to respond to oral analgesic medication, based on overall pain sensitivity, they were...... and at the end of each day. Both treatments were effective immediately after the first dose and during the subsequent multiple-dose phase. There were no statistically significant differences between ketorolac and Ketogan. The results show that 10-mg doses of ketorolac in intramuscular injections followed by 10......In this multiple-dose, double-blind study 100 patients with moderate, severe or very severe pain following orthopaedic surgery were randomly assigned to receive ketorolac, a non-steroidal anti-inflammatory drug with potent analgesic properties (10 mg), or the standard regimen of Ketogan (a...

Peripheral arterial disease in a female using high-dose combined oral contraceptive pills.

Science.gov (United States)

Pallavee, P; Samal, Sunita; Samal, Rupal

2013-01-01

The association between oral contraceptive (OC) pills and vascular diseases is well-known, although, the present generation of pills is considered to be relatively safer in this regard. Hormonal treatment for severe abnormal uterine bleeding is usually considered after ruling out malignancy, when such bleeding is resistant to all other forms of treatment. We report a case of severe peripheral arterial disease in a female, who had been on high-dose OC pills for an extended period of time for severe uterine bleeding.

Safety and Efficacy of Low-Dose Oral Immunotherapy for Hen's Egg Allergy in Children.

Science.gov (United States)

Yanagida, Noriyuki; Sato, Sakura; Asaumi, Tomoyuki; Nagakura, Kenichi; Ogura, Kiyotake; Ebisawa, Motohiro

2016-01-01

The minimal dose for oral immunotherapy (OIT) tolerance is unknown. We investigated the efficacy and safety of low-dose OIT with 1/32 of the volume of a whole egg. Thirty-three children (aged ≥5 years) with egg allergies confirmed by oral food challenge against 1/32 of a heated whole egg (194 mg of egg protein) were enrolled. The OIT group ingested a scrambled egg once a day. The volume was gradually increased up to a maximum of 1/32 of a heated whole egg. Egg consumption was completely absent in the control group. There were no significant differences in background between the OIT and control groups. Respectively, 71% (15/21) and 0% (0/12) of the patients in the OIT and control groups exhibited sustained unresponsiveness to 1/32 of a whole egg 2 weeks after stopping OIT after 12 months (p egg. Egg white- or ovomucoid-specific IgE levels in the OIT group were significantly lower than at baseline after 12 months. Egg white- or ovomucoid-specific IgG as well as IgG4 levels in the OIT group were significantly higher than baseline levels after 1, 3, 6, and 12 months. Adverse allergic reactions were rare, and most symptoms were mild. Low-dose OIT induced sustained unresponsiveness to 1/32 and 1/2 of a whole egg, with no severe symptoms. To improve food allergies, continuous intake of small amounts of these foods may be as effective as the consumption of larger quantities. © 2017 The Author(s) Published by S. Karger AG, Basel.

Bioavailability and Pharmacokinetics of Oral Cocaine in Humans.

Science.gov (United States)

Coe, Marion A; Jufer Phipps, Rebecca A; Cone, Edward J; Walsh, Sharon L

2018-06-01

The pharmacokinetic profile of oral cocaine has not been fully characterized and prospective data on oral bioavailability are limited. A within-subject study was performed to characterize the bioavailability and pharmacokinetics of oral cocaine. Fourteen healthy inpatient participants (six males) with current histories of cocaine use were administered two oral doses (100 and 200 mg) and one intravenous (IV) dose (40 mg) of cocaine during three separate dosing sessions. Plasma samples were collected for up to 24 h after dosing and analyzed for cocaine and metabolites by gas chromatography-mass spectrometry. Pharmacokinetic parameters were calculated by non-compartmental analysis, and a two-factor model was used to assess for dose and sex differences. The mean ± SEM oral cocaine bioavailability was 0.32 ± 0.04 after 100 and 0.45 ± 0.06 after 200 mg oral cocaine. Volume of distribution (Vd) and clearance (CL) were both greatest after 100 mg oral (Vd = 4.2 L/kg; CL = 116.2 mL/[min kg]) compared to 200 mg oral (Vd = 2.9 L/kg; CL = 87.5 mL/[min kg]) and 40 mg IV (Vd = 1.3 L/kg; CL = 32.7 mL/[min kg]). Oral cocaine area-under-thecurve (AUC) and peak concentration increased in a dose-related manner. AUC metabolite-to-parent ratios of benzoylecgonine and ecgonine methyl ester were significantly higher after oral compared to IV administration and highest after the lower oral dose. In addition, minor metabolites were detected in higher concentrations after oral compared to IV cocaine. Oral cocaine produced a pharmacokinetic profile different from IV cocaine, which appears as a rightward and downward shift in the concentration-time profile. Cocaine bioavailability values were similar to previous estimates. Oral cocaine also produced a unique metabolic profile, with greater concentrations of major and minor metabolites.

Single Oral Dose Toxicity Test of Blue Honeysuckle Concentrate in Mice

Science.gov (United States)

Park, Sang-In; Choi, Seung-Hoon; Song, Chang-Hyun; Park, Soo-Jin; Shin, Yong-Kook; Han, Chang-Hyun; Lee, Young Joon; Ku, Sae-Kwang

2015-01-01

The objective of this study was to obtain single oral dose toxicity information for concentrated and lyophilized powder of blue honeysuckle (Lonicera caerulea L., Caprifoliaceae; BHcL) in female and male ICR mice to aid in the process of developing natural origin medicinal ingredients or foods following proximate analysis and phytochemical profile measurement. The proximate analysis revealed that BHcL had an energy value of 3.80 kcal/g and contained 0.93 g/g of carbohydrate, 0.41 g/g of sugar, 0.02 g/g of protein, and 0.20 mg/g of sodium. BHcL did not contain lipids, including saturated lipids, trans fats, or cholesterols. Further, BHcL contained 4.54% of betaine, 210.63 mg/g of total phenols, 159.30 mg/g of total flavonoids, and 133.57 mg/g of total anthocyanins. Following administration of a single oral BHcL treatment, there were no treatment-related mortalities, changes in body weight (bw) or organ weight, clinical signs, necropsy or histopathological findings up to 2,000 mg/kg bw, the limited dosage for rodents of both sexes. We concluded that BHcL is a practically non-toxic material in toxicity potency. PMID:25874034

The Impact of a One-Dose versus Two-Dose Oral Cholera Vaccine Regimen in Outbreak Settings: A Modeling Study

Science.gov (United States)

Azman, Andrew S.; Luquero, Francisco J.; Ciglenecki, Iza; Grais, Rebecca F.; Sack, David A.; Lessler, Justin

2015-01-01

Background In 2013, a stockpile of oral cholera vaccine (OCV) was created for use in outbreak response, but vaccine availability remains severely limited. Innovative strategies are needed to maximize the health impact and minimize the logistical barriers to using available vaccine. Here we ask under what conditions the use of one dose rather than the internationally licensed two-dose protocol may do both. Methods and Findings Using mathematical models we determined the minimum relative single-dose efficacy (MRSE) at which single-dose reactive campaigns are expected to be as or more effective than two-dose campaigns with the same amount of vaccine. Average one- and two-dose OCV effectiveness was estimated from published literature and compared to the MRSE. Results were applied to recent outbreaks in Haiti, Zimbabwe, and Guinea using stochastic simulations to illustrate the potential impact of one- and two-dose campaigns. At the start of an epidemic, a single dose must be 35%–56% as efficacious as two doses to avert the same number of cases with a fixed amount of vaccine (i.e., MRSE between 35% and 56%). This threshold decreases as vaccination is delayed. Short-term OCV effectiveness is estimated to be 77% (95% CI 57%–88%) for two doses and 44% (95% CI −27% to 76%) for one dose. This results in a one-dose relative efficacy estimate of 57% (interquartile range 13%–88%), which is above conservative MRSE estimates. Using our best estimates of one- and two-dose efficacy, we projected that a single-dose reactive campaign could have prevented 70,584 (95% prediction interval [PI] 55,943–86,205) cases in Zimbabwe, 78,317 (95% PI 57,435–100,150) in Port-au-Prince, Haiti, and 2,826 (95% PI 2,490–3,170) cases in Conakry, Guinea: 1.1 to 1.2 times as many as a two-dose campaign. While extensive sensitivity analyses were performed, our projections of cases averted in past epidemics are based on severely limited single-dose efficacy data and may not fully capture

The Impact of a One-Dose versus Two-Dose Oral Cholera Vaccine Regimen in Outbreak Settings: A Modeling Study.

Directory of Open Access Journals (Sweden)

Andrew S Azman

2015-08-01

Full Text Available In 2013, a stockpile of oral cholera vaccine (OCV was created for use in outbreak response, but vaccine availability remains severely limited. Innovative strategies are needed to maximize the health impact and minimize the logistical barriers to using available vaccine. Here we ask under what conditions the use of one dose rather than the internationally licensed two-dose protocol may do both.Using mathematical models we determined the minimum relative single-dose efficacy (MRSE at which single-dose reactive campaigns are expected to be as or more effective than two-dose campaigns with the same amount of vaccine. Average one- and two-dose OCV effectiveness was estimated from published literature and compared to the MRSE. Results were applied to recent outbreaks in Haiti, Zimbabwe, and Guinea using stochastic simulations to illustrate the potential impact of one- and two-dose campaigns. At the start of an epidemic, a single dose must be 35%-56% as efficacious as two doses to avert the same number of cases with a fixed amount of vaccine (i.e., MRSE between 35% and 56%. This threshold decreases as vaccination is delayed. Short-term OCV effectiveness is estimated to be 77% (95% CI 57%-88% for two doses and 44% (95% CI -27% to 76% for one dose. This results in a one-dose relative efficacy estimate of 57% (interquartile range 13%-88%, which is above conservative MRSE estimates. Using our best estimates of one- and two-dose efficacy, we projected that a single-dose reactive campaign could have prevented 70,584 (95% prediction interval [PI] 55,943-86,205 cases in Zimbabwe, 78,317 (95% PI 57,435-100,150 in Port-au-Prince, Haiti, and 2,826 (95% PI 2,490-3,170 cases in Conakry, Guinea: 1.1 to 1.2 times as many as a two-dose campaign. While extensive sensitivity analyses were performed, our projections of cases averted in past epidemics are based on severely limited single-dose efficacy data and may not fully capture uncertainty due to imperfect

Pharmacokinetics of meloxicam after intravenous, intramuscular, and oral administration of a single dose to Hispaniolan Amazon parrots (Amazona ventralis).

Science.gov (United States)

Molter, Christine M; Court, Michael H; Cole, Gretchen A; Gagnon, David J; Hazarika, Suwagmani; Paul-Murphy, Joanne R

2013-03-01

To compare pharmacokinetics after IV, IM, and oral administration of a single dose of meloxicam to Hispaniolan Amazon parrots (Amazona ventralis). 11 healthy parrots. Cohorts of 8 of the 11 birds comprised 3 experimental groups for a crossover study. Pharmacokinetics were determined from plasma concentrations measured via high-performance liquid chromatography after IV, IM, and oral administration of meloxicam at a dose of 1 mg/kg. Initial mean ± SD plasma concentration of 17.3 ± 9.0 μg/mL was measured 5 minutes after IV administration, whereas peak mean concentration was 9.3 ± 1.8 μg/mL 15 minutes after IM administration. At 12 hours after administration, mean plasma concentrations for IV (3.7 ± 2.5 μg/mL) and IM (3.5 ± 2.2 μg/mL) administration were similar. Peak mean plasma concentration (3.5 ± 1.2 μg/mL) was detected 6 hours after oral administration. Absolute systemic bioavailability of meloxicam after IM administration was 100% but was lower after oral administration (range, 49% to 75%). Elimination half-lives after IV, IM, and oral administration were similar (15.9 ± 4.4 hours, 15.1 ± 7.7 hours, and 15.8 ± 8.6 hours, respectively). Pharmacokinetic data may provide useful information for use of meloxicam in Hispaniolan Amazon parrots. A mean plasma concentration of 3.5 μg/mL would be expected to provide analgesia in Hispaniolan Amazon parrots; however, individual variation may result in some birds having low plasma meloxicam concentrations after IV, IM, or oral administration. After oral administration, meloxicam concentration slowly reached the target plasma concentration, but that concentration was not sustained in most birds.

Study on Feasibility and Logistics of Vaccination with Typhoid Vi-vaccine on School Children in North Jakarta Indonesia: Analysis of the Vaccination Cost

OpenAIRE

Massie, Roy G.A

2011-01-01

Background: In recent years, Indonesia government has become increasingly concerned with the issues of financing childhood vaccines and immunization programs including vaccine for typhoid fever. The objective of the analysis is to provide alternative resources and to provide understandable data generated from the Study on Feasibility and Logistics of Vaccination School Age Children With Typhoid Vi-Vaccine in North Jakarta Indonesia. Methods: The analysis was focus on measurement of the cost ...

A multiple-dose, double-blind comparison of intramuscularly and orally administered ketorolac tromethamine and Ketogan in patients with pain following orthopaedic surgery

DEFF Research Database (Denmark)

Gebuhr, Peter Henrik; Soelberg, M; Strauss, W

1994-01-01

In this multiple-dose, double-blind study 100 patients with moderate, severe or very severe pain following orthopaedic surgery were randomly assigned to receive ketorolac, a non-steroidal anti-inflammatory drug with potent analgesic properties (10 mg), or the standard regimen of Ketogan (a combin......-mg doses of oral ketorolac are as effective as Ketogan for the treatment of pain following orthopaedic surgery. Ketorolac appears to be better tolerated than Ketogan since significantly fewer patients reported adverse events (P = 0.004) when taking ketorolac.......In this multiple-dose, double-blind study 100 patients with moderate, severe or very severe pain following orthopaedic surgery were randomly assigned to receive ketorolac, a non-steroidal anti-inflammatory drug with potent analgesic properties (10 mg), or the standard regimen of Ketogan (a...... combination product containing the narcotic analgesic, ketobemidone, plus a spasmolytic agent) by intramuscular injection every 1-6 h as needed for pain. When patients were able to tolerate an oral diet and were expected to respond to oral analgesic medication, based on overall pain sensitivity, they were...

Evaluation of Genotoxicity and 28-day Oral Dose Toxicity on Freeze-dried Powder of Tenebrio molitor Larvae (Yellow Mealworm).

Science.gov (United States)

Han, So-Ri; Yun, Eun-Young; Kim, Ji-Young; Hwang, Jae Sam; Jeong, Eun Ju; Moon, Kyoung-Sik

2014-06-01

The larval form of Tenebrio molitor (T. molitor) has been eaten in many countries and provides benefits as a new food source of protein for humans. However, no information exists regarding its safety for humans. The objective of the present study was to evaluate the genotoxicity and repeated dose oral toxicity of the freeze-dried powder of T. molitor larvae. The genotoxic potential was evaluated by a standard battery testing: bacterial reverse mutation test, in vitro chromosome aberration test, and in vivo micronucleus test. To assess the repeated dose toxicity, the powder was administered once daily by oral gavage to Sprague-Dawley (SD) rats at dose levels of 0, 300, 1000 and 3000 mg/kg/day for 28 days. The parameters which were applied to the study were mortality, clinical signs, body and organ weights, food consumption, ophthalmology, urinalysis, hematology, serum chemistry, gross findings and histopathologic examination. The freezedried powder of T. molitor larvae was not mutagenic or clastogenic based on results of in vitro and in vivo genotoxicity assays. Furthermore, no treatment-related changes or findings were observed in any parameters in rats after 28 days oral administration. In conclusion, the freeze-dried powder of T. molitor larvae was considered to be non-genotoxic and the NOAEL (No Observed Adverse Effect Level) was determined to be 3000 mg/kg/day in both sexes of SD rats under our experimental conditions.

Gonad doses for male patients from stomach examination and oral cholegraphy using the X-ray image intensifying technique and television fluoroscopy

International Nuclear Information System (INIS)

Steinbach, W.; Richter, K.; Koenig, W.; Menzel, B.; Reisinger, W.; Uhlich, F.

1979-01-01

The gonad dose was measured for male patients undergoing stomach examinations and oral cholegraphy by means of a diagnostic twelve pulse generator (TuR D 1500) and an X-ray apparatus 'Diagnost 100' (Philips-Mueller). In a small group of patients the gonad dose was ascertained per exposure to a 70 mm single spot film, to a 24 cm x 30 cm full size radiograph, and per minute of exposure to image intensifier fluoroscopy. The total gonad dose in both the diagnostic techniques was determined seperately in larger groups of patients. In stomach examination large size radiography led to a gonad dose 20 times higher than that obtained with the spot film technique, while exposure from cholegraphy was 10 times higher. The gonad dose per exposure of a single spot film was about 0.5 mrad. In examinations of the stomach the gonad dose from one minute fluroscopy was 18 times higher than the doses determined for a single spot film, and in cholegraphy it was 10 times higher. Supposing mean values of the number of radiographs and of the fluoroscopy time according to the conditions applied, the gonad dose in stomach examination from the film-screen technique is about twice that from the television image-intensifying technique. By comparison, oral cholegraphy exclusively performed by large-size radiography yielded about the same gonad dose as the spot film television technique. Total dose values determined separately confirmed these evaluations. (author)

Placental and milk transfer, disposition and elimination of a single oral dose of [14C acetyl] acephate in Sprague Dawley rats

International Nuclear Information System (INIS)

Bakry, N.M.; Salama, A.K.; Abou-Donia, M.B.

1991-01-01

A single oral dose of 40 mg/kg (6.4 μCi/kg) of [ 14 C acetyl]acephate was administered on day 18 of gestation to pregnant Sprague Dawley rats. Eight groups of three rats were killed after 10 min and 0.5, 1, 3, 6, 12, 24, and 48 hr. At the end of the 48 hr experimental period, a total of 22.38% of the dose was exhaled as carbon dioxide, while only 1.25% and 0.60% of the dose were eliminated in the urine and feces, respectively. Trace amount (0.03% of the dose) was recovered in expired air as volatile materials. Radioactive acephate was rapidly absorbed and distributed in the tissues, with levels in most tissues reaching a peak concentration within 1 to 3 hr. The highest concentration of radioactivity was present in the maternal stomach followed by the liver. A total of 0.72% of the dose was recovered in the fetus. In another study, a single oral dose of 40 mg/kg [ 14 C acetyl]acephate was administered to the dams right after delivery. Nursing and suckling groups were killed at intervals of 1, 3, 6, 12, 24, 36, and 48 hr after dosing. Generally, the highest concentrations of radioactivity were present in the stomach, small intestine, liver, lung, and kidneys. A total of 0.96% of the dose was recovered in the sucklings

Monte Carlo method for dose calculation due to oral X-rays

International Nuclear Information System (INIS)

Loureiro, Eduardo Cesar de Miranda

1998-06-01

The increasing utilization of oral X-rays, especially in youngsters and children, calls for the assessment of equivalent doses in their organs and tissues. With this purpose, a Monte Carlo code was adapted to simulate an X-ray source irradiating phantoms of the MIRD-5 type with different ages (10, 15 and 40 years old) to calculate the conversion coefficients which transform the exposure at skin to equivalent doses at several organs and tissues of interest. In order to check the computer program, simulations were performed for adult patients using the original code (ADAM.FOR developed at the GSF-Germany) and the adapted program (MCDRO.PAS). Good agreement between results obtained with both codes was observed. Irradiations of the incisive, canine and molar teeth were simulated. The conversion factors were calculated for the following organs and tissues: thyroid, active bone narrow (head and whole body), bone (facial skeleton, cranium and whole body), skin (head and whole body) and crystalline. Based on the obtained results, it follows that the younger the patient and the larger the field area, the higher the dose in assessed organs and tissues. The variation of the source-skin distance does not change the conversion coefficients. On the other hand, the increase in the voltage applied to the X-ray tube causes an increase in the calculated conversion coefficients. (author)

Phase I-II study of everolimus and low-dose oral cyclophosphamide in patients with metastatic renal cell cancer

International Nuclear Information System (INIS)

Huijts, Charlotte M; Santegoets, Saskia J; Eertwegh, Alfons J van den; Pijpers, Laura S; Haanen, John B; Gruijl, Tanja D de; Verheul, Henk M; Vliet, Hans J van der

2011-01-01

For patients with metastatic renal cell cancer (mRCC) who progressed on vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor therapy, the orally administered mammalian target of rapamycin (mTOR) inhibitor everolimus has been shown to prolong progression free survival. Intriguingly, inhibition of mTOR also promotes expansion of immunosuppressive regulatory T cells (Tregs) that can inhibit anti-tumor immune responses in a clinically relevant way in various tumor types including RCC. This study intends to investigate whether the antitumor efficacy of everolimus can be increased by preventing the detrimental everolimus induced expansion of Tregs using a metronomic schedule of cyclophosphamide. This phase I-II trial is a national multi-center study of different doses and schedules of low-dose oral cyclophosphamide in combination with a fixed dose of everolimus in patients with mRCC not amenable to or progressive after a VEGF-receptor tyrosine kinase inhibitor containing treatment regimen. In the phase I part of the study the optimal Treg-depleting dose and schedule of metronomic oral cyclophosphamide when given in combination with everolimus will be determined. In the phase II part of the study we will evaluate whether the percentage of patients progression free at 4 months of everolimus treatment can be increased from 50% to 70% by adding metronomic cyclophosphamide (in the dose and schedule determined in the phase I part). In addition to efficacy, we will perform extensive immune monitoring with a focus on the number, phenotype and function of Tregs, evaluate the safety and feasibility of the combination of everolimus and cyclophosphamide, perform monitoring of selected angiogenesis parameters and analyze everolimus and cyclophosphamide drug levels. This phase I-II study is designed to determine whether metronomic cyclophosphamide can be used to counter the mTOR inhibitor everolimus induced Treg expansion in patients with metastatic renal cell

Phase I-II study of everolimus and low-dose oral cyclophosphamide in patients with metastatic renal cell cancer

Directory of Open Access Journals (Sweden)

Huijts Charlotte M

2011-11-01

Full Text Available Abstract Background For patients with metastatic renal cell cancer (mRCC who progressed on vascular endothelial growth factor (VEGF receptor tyrosine kinase inhibitor therapy, the orally administered mammalian target of rapamycin (mTOR inhibitor everolimus has been shown to prolong progression free survival. Intriguingly, inhibition of mTOR also promotes expansion of immunosuppressive regulatory T cells (Tregs that can inhibit anti-tumor immune responses in a clinically relevant way in various tumor types including RCC. This study intends to investigate whether the antitumor efficacy of everolimus can be increased by preventing the detrimental everolimus induced expansion of Tregs using a metronomic schedule of cyclophosphamide. Methods/design This phase I-II trial is a national multi-center study of different doses and schedules of low-dose oral cyclophosphamide in combination with a fixed dose of everolimus in patients with mRCC not amenable to or progressive after a VEGF-receptor tyrosine kinase inhibitor containing treatment regimen. In the phase I part of the study the optimal Treg-depleting dose and schedule of metronomic oral cyclophosphamide when given in combination with everolimus will be determined. In the phase II part of the study we will evaluate whether the percentage of patients progression free at 4 months of everolimus treatment can be increased from 50% to 70% by adding metronomic cyclophosphamide (in the dose and schedule determined in the phase I part. In addition to efficacy, we will perform extensive immune monitoring with a focus on the number, phenotype and function of Tregs, evaluate the safety and feasibility of the combination of everolimus and cyclophosphamide, perform monitoring of selected angiogenesis parameters and analyze everolimus and cyclophosphamide drug levels. Discussion This phase I-II study is designed to determine whether metronomic cyclophosphamide can be used to counter the mTOR inhibitor everolimus

Effect of repeated oral therapeutic doses of methylphenidate on food intake and growth rate in rats.

Science.gov (United States)

Alam, Nausheen; Najam, Rahila

2015-01-01

Central nervous system stimulants are known to produce anorexia. Previous data suggest that methylphenidate can have variable effects on caloric intake and growth rate. A dose-response study was performed to monitor caloric intake, liquid intake and growth rate in rats following repeated administration of human oral therapeutic doses 2 mg/kg/day, 5mg/kg/day and 8mg/kg/day of methylphenidate. We found that food intake and water intake, increased in all weeks and at all doses used in the study. Growth rate increased more at higher dose (8mg/kg/day) and at low dose (2mg/kg/day) of methylphenidate in 1(st) and 2(nd) week whereas more decreased by the above doses in 3(rd) week, suggesting that food stimulation leads to initial increase in growth rate but long term administration of methylphenidate attenuate growth rate that is not due to modulation of appetite but may be due to anxiety and increased activity produce by stimulants. A possible role of DA, 5HT receptors in modulation of appetite and anxiety is discussed.

Simulated rat intestinal fluid improves oral exposure prediction for poorly soluble compounds over a wide dose range

Directory of Open Access Journals (Sweden)

Joerg Berghausen

2016-03-01

Full Text Available Solubility can be the absorption limiting factor for drug candidates and is therefore a very important input parameter for oral exposure prediction of compounds with limited solubility. Biorelevant media of the fasted and fed state have been published for humans, as well as for dogs in the fasted state. In a drug discovery environment, rodents are the most common animal model to assess the oral exposure of drug candidates. In this study a rat simulated intestinal fluid (rSIF is proposed as a more physiologically relevant media to describe drug solubility in rats. Equilibrium solubility in this medium was tested as input parameter for physiologically-based pharmacokinetics (PBPK simulations of oral pharmacokinetics in the rat. Simulations were compared to those obtained using other solubility values as input parameters, like buffer at pH 6.8, human simulated intestinal fluid and a comprehensive dissolution assay based on rSIF. Our study on nine different compounds demonstrates that the incorporation of rSIF equilibrium solubility values into PBPK models of oral drug exposure can significantly improve the reliability of simulations in rats for doses up to 300 mg/kg compared to other media. The comprehensive dissolution assay may help to improve further simulation outcome, but the greater experimental effort as compared to equilibrium solubility may limit its use in a drug discovery environment. Overall, PBPK simulations based on solubility in the proposed rSIF medium can improve prioritizing compounds in drug discovery as well as planning dose escalation studies, e.g. during toxicological investigations.

A imunidade na febre tifóide I. A vacinação anti-tifoídica de Wright, 1896 a 1979 Immunity in typhoid fever. I. The anti-typhoid vaccine of Wristh, 1896 to 1979

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Arlete Moreira Milhomem

1982-03-01

período, enquanto duas doses (intervalo de 4 semanas dão maior proteção e por tempo mais longo; g a proteção oferecida pela vacinação é maior nos jovens que nos adultos; h a vacina oral inativada (Typhoral não oferece proteção mesmo em doses elevadas. Algumas experiências com animais (camundongos, chimpanzés e voluntários humanos indicaram que uma melhor proteção foi obtida com vacinas vivas atenuadas. Contudo em tais experiências houve persistência tanto da amostra vacinante como da amostra desafio e ainda uma relação significante entre a amostra da vacina rugosa utilizada para imunização e lesões renais abacterianas de natureza desconhecida.The present comprehensive review deals with the available literature on anti-typhoid vaccines. Among the biological products, no other has raised as much controversy regarding efficacy as this commom preventive, since its early introduction by Wright, Pfeiffer & Kole. From the beginning the lack of an adequate experimental procedure for testing the vaccine potency was felt, and only poor and partial data were gathered, both from human and animal models, in relation to the basic immunological mechanism of the response to vaccination. For this reason a number of different methods have been proposed and used leading to variations in such aspects as: a the nature of bacterial strains for preparing the vaccine; b the handling of vaccine strains-killed by heat, various chemicals (alcohol, ether acetone or lysed, or employing avirulent strains; c the addition of different components (preservatives and related microrganisms; d the route of application (subcutaneous, intradermal, oral, etc; e the dose (number of organisms; f the time schedule for application. Many field trials failed to be conclusive. It is considered that the early field trials lacked proper controls, which were introduced later, in the well planned investigations sponsored by World Health Organization, in several parts of the World (Yugoslavia

Encephalitis in a traveller with typhoid fever: efficacy of corticosteroids.

Science.gov (United States)

Mellon, Guillaume; Eme, Anne-Line; Rohaut, Benjamin; Brossier, Florence; Epelboin, Loïc; Caumes, Eric

2017-09-01

Typhoid fever is a bacterial infection caused by Salmonella typhi or S. paratyphi, recognized as a classical cause of fever in returning travellers. However, neuropsychiatric presentations are rarely reported in travellers diagnosed in western countries, whereas they are more commonly described in patients treated in endemic areas. We describe such a case and discuss the pathophysiologic mechanisms of this complication. © International Society of Travel Medicine, 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Antimalarial iron chelator, FBS0701, shows asexual and gametocyte Plasmodium falciparum activity and single oral dose cure in a murine malaria model.

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Patricia Ferrer

Full Text Available Iron chelators for the treatment of malaria have proven therapeutic activity in vitro and in vivo in both humans and mice, but their clinical use is limited by the unsuitable absorption and pharmacokinetic properties of the few available iron chelators. FBS0701, (S3"-(HO-desazadesferrithiocin-polyether [DADFT-PE], is an oral iron chelator currently in Phase 2 human studies for the treatment of transfusional iron overload. The drug has very favorable absorption and pharmacokinetic properties allowing for once-daily use to deplete circulating free iron with human plasma concentrations in the high µM range. Here we show that FBS0701 has inhibition concentration 50% (IC(50 of 6 µM for Plasmodium falciparum in contrast to the IC(50 for deferiprone and deferoxamine at 15 and 30 µM respectively. In combination, FBS0701 interfered with artemisinin parasite inhibition and was additive with chloroquine or quinine parasite inhibition. FBS0701 killed early stage P. falciparum gametocytes. In the P. berghei Thompson suppression test, a single dose of 100 mg/kg reduced day three parasitemia and prolonged survival, but did not cure mice. Treatment with a single oral dose of 100 mg/kg one day after infection with 10 million lethal P. yoelii 17XL cured all the mice. Pretreatment of mice with a single oral dose of FBS0701 seven days or one day before resulted in the cure of some mice. Plasma exposures and other pharmacokinetics parameters in mice of the 100 mg/kg dose are similar to a 3 mg/kg dose in humans. In conclusion, FBS0701 demonstrates a single oral dose cure of the lethal P. yoelii model. Significantly, this effect persists after the chelator has cleared from plasma. FBS0701 was demonstrated to remove labile iron from erythrocytes as well as enter erythrocytes to chelate iron. FBS0701 may find clinically utility as monotherapy, a malarial prophylactic or, more likely, in combination with other antimalarials.

High-throughput bacterial SNP typing identifies distinct clusters of Salmonella Typhi causing typhoid in Nepalese children

LENUS (Irish Health Repository)

Holt, Kathryn E

2010-05-31

Abstract Background Salmonella Typhi (S. Typhi) causes typhoid fever, which remains an important public health issue in many developing countries. Kathmandu, the capital of Nepal, is an area of high incidence and the pediatric population appears to be at high risk of exposure and infection. Methods We recently defined the population structure of S. Typhi, using new sequencing technologies to identify nearly 2,000 single nucleotide polymorphisms (SNPs) that can be used as unequivocal phylogenetic markers. Here we have used the GoldenGate (Illumina) platform to simultaneously type 1,500 of these SNPs in 62 S. Typhi isolates causing severe typhoid in children admitted to Patan Hospital in Kathmandu. Results Eight distinct S. Typhi haplotypes were identified during the 20-month study period, with 68% of isolates belonging to a subclone of the previously defined H58 S. Typhi. This subclone was closely associated with resistance to nalidixic acid, with all isolates from this group demonstrating a resistant phenotype and harbouring the same resistance-associated SNP in GyrA (Phe83). A secondary clone, comprising 19% of isolates, was observed only during the second half of the study. Conclusions Our data demonstrate the utility of SNP typing for monitoring bacterial populations over a defined period in a single endemic setting. We provide evidence for genotype introduction and define a nalidixic acid resistant subclone of S. Typhi, which appears to be the dominant cause of severe pediatric typhoid in Kathmandu during the study period.

Evaluation of Genotoxicity and 28-day Oral Dose Toxicity on Freeze-dried Powder of Tenebrio molitor Larvae (Yellow Mealworm)

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Han, So-Ri; Yun, Eun-Young; Kim, Ji-Young; Hwang, Jae Sam; Jeong, Eun Ju

2014-01-01

The larval form of Tenebrio molitor (T. molitor) has been eaten in many countries and provides benefits as a new food source of protein for humans. However, no information exists regarding its safety for humans. The objective of the present study was to evaluate the genotoxicity and repeated dose oral toxicity of the freeze-dried powder of T. molitor larvae. The genotoxic potential was evaluated by a standard battery testing: bacterial reverse mutation test, in vitro chromosome aberration test, and in vivo micronucleus test. To assess the repeated dose toxicity, the powder was administered once daily by oral gavage to Sprague-Dawley (SD) rats at dose levels of 0, 300, 1000 and 3000 mg/kg/day for 28 days. The parameters which were applied to the study were mortality, clinical signs, body and organ weights, food consumption, ophthalmology, urinalysis, hematology, serum chemistry, gross findings and histopathologic examination. The freezedried powder of T. molitor larvae was not mutagenic or clastogenic based on results of in vitro and in vivo genotoxicity assays. Furthermore, no treatment-related changes or findings were observed in any parameters in rats after 28 days oral administration. In conclusion, the freeze-dried powder of T. molitor larvae was considered to be non-genotoxic and the NOAEL (No Observed Adverse Effect Level) was determined to be 3000 mg/kg/day in both sexes of SD rats under our experimental conditions. PMID:25071922

An evaluation of the applicability of gamma radiation for preparing typhoid fever vaccine

International Nuclear Information System (INIS)

Malafiej, E.; Lachmanowa, S.; Horoszewicz-Malafiej, A.; Politechnika Lodzka

1974-01-01

Using mouse protection test, two typhoid fever vaccines were comparatively tested for efficacy: that prepared by thermal inactivation and that treated with ionizing radiation. The experiments were performed with white mice BALB/c. Co 60 was used as the radiation source. Vaccine prepared by the thermal inactivation showed higher protective activity than the vaccine prepared by treatment with ionizing radiation. (author)

Treatment failure in a typhoid patient infected with nalidixic acid resistant S. enterica serovar Typhi with reduced susceptibility to Ciprofloxacin: a case report from Cameroon

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Asonganyi Etienne DN

2005-06-01

Full Text Available Abstract Background Fluoroquinolones or third generation cephalosporins are the drugs of choice for the treatment of typhoid fever. Treatment failure with fluoroquinolones has been reported in Asia and Europe. We report a case of ciprofloxacin treatment failure in typhoid fever in Cameroon. Case presentation A 29-year-old female patient with suspected typhoid fever from Kumba, Cameroon, yielded growth of Salmonella enterica serovar Typhi in blood culture. The isolate was resistant to nalidixic acid but sensitive to ciprofloxacin by disc diffusion test. However, the patient did not respond to treatment with ciprofloxacin, although the isolate was apparently susceptible to ciprofloxacin. Conclusion Treatment failure with ciprofloxacin in our case indicates the presence of nalidixic acid resistant S. enterica serovar Typhi (NARST with reduced susceptibility to ciprofloxacin in Cameroon (Central Africa.

Bilateral femoral head avascular necrosis with a very low dose of oral corticosteroid used for panhypopituitarism.

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Dharmshaktu, Pramila; Aggarwal, Anshita; Dutta, Deep; Kulshreshtha, Bindu

2016-01-13

Avascular necrosis (AVN) of the femoral head is a rare complication related to glucocorticoid administration and traditionally has been associated with high doses and/or prolonged therapy. Occurrence of osteonecrosis with a physiological replacement dose of glucocorticoids has not been reported previously. We report a 38-year-old man with non-secreting pituitary adenoma who developed bilateral AVN while on a very small dose of oral prednisolone for secondary adrenal insufficiency after surgery for pituitary adenoma. The patient was switched to hydrocortisone. Zolindronic acid was administered and the patient underwent bilateral core decompressive surgery resulting in a reduction of hip pain and improvement. When last evaluated, 2 years after diagnosis of AVN, the patient was functionally independent, and was able to do his routine activities with mild pain. The report intends to highlight the occurrence of AVN of the femur even with a very small dose of prednisolone used for treatment of panhypopituitarism. Glucocorticoids may have to be continued in the lowest possible dose using the most physiological preparation such as hydrocortisone when stoppage is not possible. 2016 BMJ Publishing Group Ltd.

Bilateral femoral head avascular necrosis with a very low dose of oral corticosteroid used for panhypopituitarism

Science.gov (United States)

Dharmshaktu, Pramila; Aggarwal, Anshita; Dutta, Deep; Kulshreshtha, Bindu

2016-01-01

Avascular necrosis (AVN) of the femoral head is a rare complication related to glucocorticoid administration and traditionally has been associated with high doses and/or prolonged therapy. Occurrence of osteonecrosis with a physiological replacement dose of glucocorticoids has not been reported previously. We report a 38-year-old man with non-secreting pituitary adenoma who developed bilateral AVN while on a very small dose of oral prednisolone for secondary adrenal insufficiency after surgery for pituitary adenoma. The patient was switched to hydrocortisone. Zolindronic acid was administered and the patient underwent bilateral core decompressive surgery resulting in a reduction of hip pain and improvement. When last evaluated, 2 years after diagnosis of AVN, the patient was functionally independent, and was able to do his routine activities with mild pain. The report intends to highlight the occurrence of AVN of the femur even with a very small dose of prednisolone used for treatment of panhypopituitarism. Glucocorticoids may have to be continued in the lowest possible dose using the most physiological preparation such as hydrocortisone when stoppage is not possible. PMID:26762348

Typhoid intestinal perforations at a University teaching hospital in Northwestern Tanzania: A surgical experience of 104 cases in a resource-limited setting

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Chalya Phillipo L

2012-03-01

Full Text Available Abstract Background Typhoid intestinal perforation is still prevalent in many developing countries. Despite the advances in the management, the outcome in these patients in resource limited countries is still very poor. This study was to review our experiences on the surgical management of typhoid intestinal perforation and to determine the prognostic factors for mortality in our local setting. Methods This was a combined retrospective and prospective study of patients who were operated for typhoid intestinal perforation at Bugando Medical Centre between August 2006 and September 2011. Data collected were analyzed using SPSS computer software version 15. Results A total of 104 patients were studied representing 8.7% of typhoid fever cases. Males were affected twice more than the females (2.6:1. Their ages ranged from 8 to 76 years with a median age of 18.5 years. The peak age incidence was in the 11-20 years age group. Fever and abdominal pain were the most common presenting symptoms and majority of the patients (80.8% perforated between within 14 days of illness. Chest and abdominal radiographs revealed pneumoperitonium in 74.7% of cases. Ultrasound showed free peritoneal collection in 85.7% of cases. Nine (10.2% patients were HIV positive with a median CD4+ count of 261 cells/μl. The perforation-surgery interval was more than 72 hours in 90(86.5% patients. The majority of patients (84.6% had single perforations and ileum was the most common part of the bowel affected occurring in 86.2% of cases. Simple closure of the perforations was the most commonly performed procedure accounting for 78.8% of cases. Postoperative complication rate was 39.4% and surgical site infection was the most frequent complication in 55.5% of cases. Mortality rate was 23.1% and it was statistically significantly associated with delayed presentation, inadequate antibiotic treatment prior to admission, shock on admission, HIV positivity, low CD4 count (P Conclusion

Low energy helium-neon laser prevents oral mucositis after high-dose chemo-radiotherapy: results of a double-blind randomized trial

International Nuclear Information System (INIS)

Cowen, Didier; Tardieu, Corinne; Resbeut, Michel; Hannoun-Levi, Jean-Michel; Alzieu, Claude; Schubert, Marc; Franquin, Jean-Claude

1996-01-01

Purpose: To evaluate the efficiency of Helium-Neon (He-Ne) laser in the prevention of oral mucositis (OM) induced by high dose chemoradiotherapy before bone marrow transplantation (BMT). Methods and materials: Between 1993 and 1995, 30 consecutive patients (pts) receiving an autologous peripheral stem-cell or bone marrow transplant (BMT) after high dose chemoradiotherapy were randomized to receive or not prophylactic laser applications to the oral mucosa. Chemotherapy consisted of cyclophosphamide, 60 mg/kg intravenously (IV) on day (d)-5 and d-4 in 27 cases, or melphalan 140 mg/kg IV on d-4 in 3 cases. Total body irradiation consisted of 12 Gy midplane dose in six fractions and 3 days. He-Ne laser (632.8 nm wavelength, power 60 mW) applications were performed daily from d-5 to d-1 on 5 anatomic sites of the oral mucosa. Oral examination was performed daily from d0 to d+20. Mucositis was scored according to an oral exam guide with a 16 items scale of which 4 were assessed by the pts themselves. Mean daily scores of pain, ability to swallow and saliva production were measured. A daily mucositis index (DMI) and a cumulative score of oral mucositis (CSOM) were established. Requirement for narcotics and parenteral nutrition were measured. Validation of the grading scale was carried out using the Cronbach alpha coefficient for the internal validation and the test-retest correlation coefficient for the reproducibility analysis. The U Mann Whitney test was used to test for differences among groups. Patients were assigned to either laser treatment (L+) or sham-treatment (L-) by computer blocked randomization. Results: No pt was excluded for failure to complete the laser application protocol. Laser applications were well tolerated and no side effects were reported. The items were highly interrelated as well as the index considered as a whole: over 21 days, α = 0.97. Reproducibility analysis between the nurses in charge with the oral examination showed a significant

Evaluation of the Widal tube agglutination test for the diagnosis of typhoid fever among children admitted to a rural hdospital in Tanzania and a comparison with previous studies

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Malahiyo Rajabu

2010-06-01

Full Text Available Abstract Background The diagnosis of typhoid fever is confirmed by culture of Salmonella enterica serotype Typhi (S. typhi. However, a more rapid, simpler, and cheaper diagnostic method would be very useful especially in developing countries. The Widal test is widely used in Africa but little information exists about its reliability. Methods We assessed the performance of the Widal tube agglutination test among febrile hospitalized Tanzanian children. We calculated the sensitivity, specificity, positive predictive value (PPV, and negative predictive value (NPV of various anti-TH and -TO titers using culture-confirmed typhoid fever cases as the "true positives" and all other febrile children with blood culture negative for S. typhi as the "true negatives." Results We found that 16 (1% of 1,680 children had culture-proven typhoid fever. A single anti-TH titer of 1:80 and higher was the optimal indicator of typhoid fever. This had a sensitivity of 75%, specificity of 98%, NPV of 100%, but PPV was only 26%. We compared our main findings with those from previous studies. Conclusion Among febrile hospitalized Tanzanian children with a low prevalence of typhoid fever, a Widal titer of ≥ 1:80 performed well in terms of sensitivity, specificity, and NPV. However a test with improved PPV that is similarly easy to apply and cost-efficient is desirable.

Challenges and Opportunities for Typhoid Fever Control: A Call for Coordinated Action.

Science.gov (United States)

Steele, A Duncan; Hay Burgess, Deborah C; Diaz, Zoey; Carey, Megan E; Zaidi, Anita K M

2016-03-15

The burden of enteric fever caused by Salmonella enterica serovars Typhi and Paratyphi is substantial and has high impact in toddlers and young children. This burden is relatively well documented in Asia, and this supplement provides new data on the substantial burden in several sub-Saharan African countries. Challenges in standardized surveillance and imperfect diagnostic tools have resulted in patchy local disease data, which are not well acknowledged or integrated into local country evidence and health awareness for decision making. There is a need to strengthen diagnostics for the generation of burden data in country. Furthermore, the guidelines and training for treatment of enteric fever cases in Africa are sorely needed to help mitigate the inappropriate use of antimicrobial treatment. Classic water safety and access to sanitation development remain powerful tools for the control of typhoid fever, yet the huge economic costs and long timelines are unlikely to provide a short- to middle-term solution. Emerging threats, including multidrug resistance and increasing urbanization in regions such as sub-Saharan Africa, warrant focused attention to shorter-term interventions including immunization, and must include vaccine strategies with the new typhoid conjugate vaccines. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

The dose effects of short-term dronabinol (oral THC) maintenance in daily cannabis users.

Science.gov (United States)

Vandrey, Ryan; Stitzer, Maxine L; Mintzer, Miriam Z; Huestis, Marilyn A; Murray, Jeannie A; Lee, Dayong

2013-02-01

Prior studies have separately examined the effects of dronabinol (oral THC) on cannabis withdrawal, cognitive performance, and the acute effects of smoked cannabis. A single study examining these clinically relevant domains would benefit the continued evaluation of dronabinol as a potential medication for the treatment of cannabis use disorders. Thirteen daily cannabis smokers completed a within-subject crossover study and received 0, 30, 60 and 120mg dronabinol per day for 5 consecutive days. Vital signs and subjective ratings of cannabis withdrawal, craving and sleep were obtained daily; outcomes under active dose conditions were compared to those obtained under placebo dosing. On the 5th day of medication maintenance, participants completed a comprehensive cognitive performance battery and then smoked five puffs of cannabis for subjective effects evaluation. Each dronabinol maintenance period occurred in a counterbalanced order and was separated by 9 days of ad libitum cannabis use. Dronabinol dose-dependently attenuated cannabis withdrawal and resulted in few adverse side effects or decrements in cognitive performance. Surprisingly, dronabinol did not alter the subjective effects of smoked cannabis, but cannabis-induced increases in heart rate were attenuated by the 60 and 120mg doses. Dronabinol's ability to dose-dependently suppress cannabis withdrawal may be therapeutically beneficial to individuals trying to stop cannabis use. The absence of gross cognitive impairment or side effects in this study supports safety of doses up to 120mg/day. Continued evaluation of dronabinol in targeted clinical studies of cannabis treatment, using an expanded range of doses, is warranted. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Reproductive toxicity in rats after chronic oral exposure to low dose of depleted uranium

International Nuclear Information System (INIS)

Li Rong; Ai Guoping; Xu Hui; Su Yongping; Cheng Tianmin; Leng Yanbing

2007-01-01

Objective: To study the reproductive toxicity in rats induced by low dose of depleted uranium (DU). Methods: Male and female rats(F 0 generation) were exposed to DU in food at doses of 0, 0.4, 4 and 40 mg·kg -1 ·d -1 for 160 days, respectively. Then the activities of enzymes in testis and sexual hormone contents in serum were detected. Mature male rats were mated with female rats exposed to the same doses for 14 days. Pregnant rate and normal labor rate in F 0 rats were detected, as well as the survival rate and weight of F 1 rats within 21 d after birth. Results: No adverse effects of DU on fertility were evident at any dose in F 0 rats. Compared with control group, the rate of pregnancy, normal labor, survival of offspring birth and offspring nurture in F 1 generation of high-dose group reduced to 40.0%, 33.3%, 33.3%, and 33.3%, respectively. The sexual hormone contents in F 0 generation exposed increased, but those in Fl rats decreased significantly. The activities of lactate dehydrogenase-X (LDH-X) decreased in F 1 rats exposed to high-dose of DU, and those of sorbitol dehydrogenase (SDH), LDH and Na + -K + -ATPase decreased in F 1 rats exposed to DU. Conclusions: Reproduction function, growth and development of F 0 rats are not obviously affected after chronic oral exposure to DU, while the toxicity effects in F 1 generation was observed at any dose. (authors)

Antibiotic resistance, integrons and Salmonella genomic island 1 among non-typhoidal Salmonella serovars in The Netherlands.

NARCIS (Netherlands)

Vo, An T T; Duijkeren, Engeline van; Fluit, Ad C; Wannet, Wim J B; Verbruggen, Anjo J; Maas, Henny M E; Gaastra, Wim

2006-01-01

The objective of this study was to investigate the antimicrobial resistance patterns, integron characteristics and gene cassettes as well as the presence of Salmonella genomic island 1 (SGI1) in non-typhoidal Salmonella (NTS) isolates from human and animal origin. Epidemiologically unrelated Dutch

Rhabdomyolysis Complicating Typhoid Fever in A Child and Review of the Literature.

Science.gov (United States)

Snelling, Peter James; Moriarty, Paul; Vaska, Vikram L; Levitt, David; Nourse, Clare

2017-09-01

Typhoid fever is an important cause of morbidity and mortality in the developing world, particularly in children, but is infrequently observed in the developed world and can occur in patients without a significant travel history. Rhabdomyolysis as a complication has rarely been reported, and never in a child. A child with Salmonella enterica serovar Typhi septicemia, complicated by rhabdomyolysis, encephalopathy and pancreatitis is described and all 15 reported cases to date are summarized.

Effect of combined oral doses of Δ(9)-tetrahydrocannabinol (THC) and cannabidiolic acid (CBDA) on acute and anticipatory nausea in rat models.

Science.gov (United States)

Rock, Erin M; Connolly, Cassidy; Limebeer, Cheryl L; Parker, Linda A

2016-09-01

The purpose of this study was to evaluate the potential of oral combined cannabis constituents to reduce nausea. The objective of this study was to determine the effect of combining subthreshold oral doses of Δ(9)-tetrahydrocannabinol (THC) and cannabidiolic acid (CBDA) on acute and anticipatory nausea in rat models of conditioned gaping. The potential of intragastric (i.g.) administration of THC, CBDA, or combined doses, to interfere with acute nausea-induced conditioned gaping (acute nausea) or the expression of contextually elicited conditioned gaping (anticipatory nausea), was evaluated. For acute nausea, i.g. administration of subthreshold doses of THC (0.5 and 1 mg/kg) or CBDA (0.5 and 1 μg/kg) significantly suppressed acute nausea-induced gaping, whereas higher individual doses of both THC and CBDA were maximally effective. Combined i.g. administration of higher doses of THC and CBDA (2.5 mg/kg THC-2.5 μg/kg CBDA; 10 mg/kg THC-10 μg/kg CBDA; 20 mg/kg THC-20 μg/kg CBDA) also enhanced positive hedonic reactions elicited by saccharin solution during conditioning. For anticipatory nausea, combined subthreshold i.g. doses of THC (0.1 mg/kg) and CBDA (0.1 μg/kg) suppressed contextually elicited conditioned gaping. When administered i.g., THC was effective on its own at doses ranging from 1 to 10 mg/kg, but CBDA was only effective at 10 μg/kg. THC alone was equally effective by intraperitoneal (i.p.) and i.g. administration, whereas CBDA alone was more effective by i.p. administration (Rock et al. in Psychopharmacol (Berl) 232:4445-4454, 2015) than by i.g. administration. Oral administration of subthreshold doses of THC and CBDA may be an effective new treatment for acute nausea and anticipatory nausea and appetite enhancement in chemotherapy patients.

Orbital cellulitis in course of typhoid fever; Zapalenie tkanki oczodolowej w przebiegu duru brzusznego

Energy Technology Data Exchange (ETDEWEB)

Nowacka, K; Szreter, M; Mikolajewicz, J [Centrum Zdrwowia Dziecka, Warsaw (Poland)

1994-12-31

In 18 months girl with exophthalmus of the left eye and extensive swelling of the soft tissues in both orbits during continued fever was observed. Typhoid fever with a non-typical course and ophthalmic complications were diagnosed on the basis of serological tests. Complete cure after treatment with augmenting was obtained. (author) 10 refs, 2 figs

Orbital cellulitis in course of typhoid fever; Zapalenie tkanki oczodolowej w przebiegu duru brzusznego

Energy Technology Data Exchange (ETDEWEB)

Nowacka, K.; Szreter, M.; Mikolajewicz, J. [Centrum Zdrwowia Dziecka, Warsaw (Poland)

1993-12-31

In 18 months girl with exophthalmus of the left eye and extensive swelling of the soft tissues in both orbits during continued fever was observed. Typhoid fever with a non-typical course and ophthalmic complications were diagnosed on the basis of serological tests. Complete cure after treatment with augmenting was obtained. (author) 10 refs, 2 figs

Sevoflurane-emergence agitation: Effect of supplementary low-dose oral ketamine premedication in preschool children undergoing dental surgery

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Khattab Ahmed

2009-01-01

Full Text Available Background and Objectives: The use of sevoflurane in pediatric anesthesia, which could enable a more rapid emergence and recovery, is complicated by the frequent occurrence of post-anesthesia agitation. This study aims to test the efficacy of adding a low dose of ketamine orally, as a supplement to the midazolam-based oral premedication for reducing sevoflurane-related emergence agitation. Materials and Methods: Ninety-two preschool children, aged between two and six years, with an American Society of Anesthesiologists physical status I or II, scheduled for elective dental filling and extractions under general anesthesia were included. The patients were allocated into two groups: Group M (46 patients received oral midazolam 0.5 mg/kg, mixed with ibuprofen 10 mg/kg, while group KM (46 patients received a similar premedication mixture, in addition to ketamine 2 mg/kg. The acceptance of the drug mixture, the onset of action, and the occurrence of vomiting were monitored over the next 30 minutes. Induction of anesthesia was carried out using sevoflurane 8 Vol% in 100% oxygen via face mask. Anesthesia was maintained with sevoflurane 1.5-2 Vol% in an oxygen-nitrous oxide mixture. After extubation, the standard scoring scale was used for assessing the quality of emergence. Agitation parameters were measured using a five-point scale. Agitated children were managed by giving intravenous increments of fentanyl 1 μg/ kg. The time of hospital discharge allowance was recorded. Results: Drug palatability, vomiting, and onset of action of premedication; showed no significant differences between both groups. Time of eye opening after discontinuation of sevoflurane showed no significant differences between both groups. Postoperative agitation score and rescue fentanyl consumption were higher in group M than in group KM on admission to the PACU ( P < 0.01. The time of hospital discharge allowance in group M was longer than in group KM ( P< 0.05. Conclusion

Effervescent N-Acetylcysteine Tablets versus Oral Solution N-Acetylcysteine in Fasting Healthy Adults: An Open-Label, Randomized, Single-Dose, Crossover, Relative Bioavailability Study

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Spencer C. Greene, MD, FACEP, FACMT

2016-01-01

Conclusions: Data from this study of a single dose of 11 g oral NAC demonstrated that effervescent NAC tablets and oral solution NAC met the regulatory criteria for bioequivalence in fasting healthy adult subjects. Effervescent NAC tablets appear to be a more palatable alternative for treatment of acetaminophen overdose. ClinicalTrials.gov identifier: NCT02723669.

Combined rapid (TUBEX test for typhoid-paratyphoid A fever based on strong anti-O12 response: design and critical assessment of sensitivity.

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Meiying Yan

Full Text Available Rapid diagnostics can be accurate but, often, those based on antibody detection for infectious diseases are unwittingly underrated for various reasons. Herein, we described the development of a combined rapid test for two clinically-indistinguishable bacterial diseases, typhoid and paratyphoid A fever, the latter fast emerging as a global threat. By using monoclonal antibodies (mAbs to bacterial antigens of known chemical structures as probes, we were able to dissect the antibody response in patients at the level of monosaccharides. Thus, a mAb specific for a common lipopolysaccharide antigen (O12 found in both the causative organisms was employed to semi-quantify the amounts of anti-O12 antibodies present in both types of patients in an epitope-inhibition particle-based (TUBEX immunoassay. This colorimetric assay detected not only anti-O12 antibodies that were abundantly produced, but also, by steric hindrance, antibodies to an adjoining epitope (O9 or O2 in the typhoid or paratyphoid bacillus, respectively. Sensitivity and, particularly, reaction intensities, were significantly better than those obtained using an anti-O9 or anti-O2 mAb-probe in the examination of paired sera from 22 culture-confirmed typhoid patients (sensitivity, 81.8% vs 75.0% or single sera from 36 culture-confirmed paratyphoid patients (52.8% vs 28.6, respectively. Importantly, sensitivity was better (97.1% for typhoid, 75.0% for paratyphoid if allowance was made for the absence of relevant antibodies in certain specimens as determined by an independent, objective assay (ELISA--such specimens might have been storage-denatured (especially the older paratyphoid samples or procured from non-responders. Benchmarking against ELISA, which revealed high concordance between the two tests, was useful and more appropriate than comparing with culture methods as traditionally done, since antibody tests and culture target slightly different stages of these diseases. Paired sera

Serum bactericidal assay for the evaluation of typhoid vaccine using a semi-automated colony-counting method.

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Jang, Mi Seon; Sahastrabuddhe, Sushant; Yun, Cheol-Heui; Han, Seung Hyun; Yang, Jae Seung

2016-08-01

Typhoid fever, mainly caused by Salmonella enterica serovar Typhi (S. Typhi), is a life-threatening disease, mostly in developing countries. Enzyme-linked immunosorbent assay (ELISA) is widely used to quantify antibodies against S. Typhi in serum but does not provide information about functional antibody titers. Although the serum bactericidal assay (SBA) using an agar plate is often used to measure functional antibody titers against various bacterial pathogens in clinical specimens, it has rarely been used for typhoid vaccines because it is time-consuming and labor-intensive. In the present study, we established an improved SBA against S. Typhi using a semi-automated colony-counting system with a square agar plate harboring 24 samples. The semi-automated SBA efficiently measured bactericidal titers of sera from individuals immunized with S. Typhi Vi polysaccharide vaccines. The assay specifically responded to S. Typhi Ty2 but not to other irrelevant enteric bacteria including Vibrio cholerae and Shigella flexneri. Baby rabbit complement was more appropriate source for the SBA against S. Typhi than complements from adult rabbit, guinea pig, and human. We also examined the correlation between SBA and ELISA for measuring antibody responses against S. Typhi using pre- and post-vaccination sera from 18 human volunteers. The SBA titer showed a good correlation with anti-Vi IgG quantity in the serum as determined by Spearman correlation coefficient of 0.737 (P measure functional antibody titers against S. Typhi in sera from human subjects immunized with typhoid vaccines. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Development of a Biomarker for Penconazole: A Human Oral Dosing Study and a Survey of UK Residents’ Exposure

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Craig Sams

2016-05-01

Full Text Available Penconazole is a widely used fungicide in the UK; however, to date, there have been no peer-reviewed publications reporting human metabolism, excretion or biological monitoring data. The objectives of this study were to i develop a robust analytical method, ii determine biomarker levels in volunteers exposed to penconazole, and, finally, to iii measure the metabolites in samples collected as part of a large investigation of rural residents’ exposure. An LC-MS/MS method was developed for penconazole and two oxidative metabolites. Three volunteers received a single oral dose of 0.03 mg/kg body weight and timed urine samples were collected and analysed. The volunteer study demonstrated that both penconazole-OH and penconazole-COOH are excreted in humans following an oral dose and are viable biomarkers. Excretion is rapid with a half-life of less than four hours. Mean recovery of the administered dose was 47% (range 33%–54% in urine treated with glucuronidase to hydrolyse any conjugates. The results from the residents’ study showed that levels of penconazole-COOH in this population were low with >80% below the limit of detection. Future sampling strategies that include both end of exposure and next day urine samples, as well as contextual data about the route and time of exposure, are recommended.

Nonrandomized study comparing the effects of preoperative radiotherapy and daily administration of low-dose cisplatin with those radiotherapy alone for oral cancer

International Nuclear Information System (INIS)

Kurita, Hiroshi; Azegami, Takuya; Kobayashi, Hirokazu; Kurashina, Kenji; Tanaka, Kouichi; Kotani, Akira; Oguchi, Masahiko; Tamura, Minoru.

1997-01-01

The purpose of this study was to compare the effect of preoperative radiotherapy and daily administration of low-dose cisplatin with those of radiotherapy alone for oral cancer. Ten patients underwent preoperative radiotherapy of 30 to 40 Gy with concomitant daily administration of low-dose cisplatin (5 mg/body or 5 mg/m 2 ). Ten patients received external radiotherapy alone. The locoregional response rates (complete response and partial response) did not differ significantly between the two groups (80% for combined therapy and 60% for radiotherapy alone). On histopathologic evaluation of surgical specimens, however, the combined-therapy group (80%) had a higher response rate than did the radiotherapy-alone group (10%; p<0.01). We conclude that daily administration of low-dose cisplatin enhances the efficacy of radiotherapy against primary tumors. We also suggested that combined therapy may be beneficial as an initial treatment for oral cancer before a planned operation. (author)

Successful comeback of the single-dose live oral cholera vaccine CVD 103-HgR.

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Herzog, Christian

2016-01-01

Effective and easy to administer cholera vaccines are in need more than ever, for at risk populations and travellers alike. In many parts of the world cholera is still endemic, causing outbreaks and constituting repeatedly serious public health problems. The oral live cholera vaccine CVD 103-HgR (Orochol, Mutachol), the first genetically modified organism (GMO) used as vaccine, was in its time (launched 1993, Switzerland) the ideal cholera vaccine: single-dose, protective efficacy of 80-100% against moderate to severe cholera, acting within 8 days and exhibiting excellent safety, indiscernible from placebo. However, there were strong headwinds: In the 1990s the indication for cholera vaccines was generally downplayed by experts and in 1997 the European Commission called for a moratorium of GMOs which blocked the registration in the European Union. Thus, demand for this vaccine remained low and in 2003 it was taken off the market for economic reasons. After a decade in obscurity it (Vaxchora) has resurfaced again, now produced in the U.S. and equipped with a U.S. FDA license (June 10, 2016). What had happened? This commentary gives a critical account of an almost unbelievable string of misadventures, emerging adverse circumstances and man-made failures which nearly killed this single-dose live oral cholera vaccine. The good news is that patience and persistence lead to success in the end, allowing good science to prevail for the benefit of those in need. Copyright © 2016 Elsevier Ltd. All rights reserved.

Single dose oral ibuprofen plus paracetamol (acetaminophen) for acute postoperative pain.

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Derry, Christopher J; Derry, Sheena; Moore, R Andrew

2013-06-24

Combining two different analgesics in fixed doses in a single tablet can provide better pain relief than either drug alone in acute pain. This appears to be broadly true across a range of different drug combinations, in postoperative pain and migraine headache. Some combinations of ibuprofen and paracetamol are available for use without prescription in some acute pain situations. To assess the efficacy and adverse effects of single dose oral ibuprofen plus paracetamol for acute postoperative pain using methods that permit comparison with other analgesics evaluated in standardised trials using almost identical methods and outcomes. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library (Issue 4 of 12, 2013), MEDLINE (1950 to May 21st 2013), EMBASE (1974 to May 21st 2013), the Oxford Pain Database, ClinicalTrials.gov, and reference lists of articles. Randomised, double-blind clinical trials of single dose, oral ibuprofen plus paracetamol compared with placebo or the same dose of ibuprofen alone for acute postoperative pain in adults. Two review authors independently considered trials for inclusion in the review, assessed quality, and extracted data. We used validated equations to calculate the area under the pain relief versus time curve and derive the proportion of participants with at least 50% of maximum pain relief over six hours. We calculated relative risk (RR) and number needed to treat to benefit (NNT) for ibuprofen plus paracetamol, ibuprofen alone, or placebo. We used information on use of rescue medication to calculate the proportion of participants requiring rescue medication and the weighted mean of the median time to use. We also collected information on adverse events. Searches identified three studies involving 1647 participants. Each of them examined several dose combinations. Included studies provided data from 508 participants for the comparison of ibuprofen 200 mg + paracetamol 500 mg with placebo, 543

A comparison of the effect of two doses of oral melatonin with oral midazolam and placebo on pre-operative anxiety, cognition and psychomotor function in children: A randomised double-blind study

Directory of Open Access Journals (Sweden)

Madhuri S Kurdi

2016-01-01

Full Text Available Background and Aims: Melatonin (MT, a naturally occurring pituitary hormone has a sleep promoting effect. There are very few studies on pre-operative oral MT (0.2-0.5 mg/kg in children. We planned a study to assess the efficacy of oral MT in two doses and compare it with oral midazolam and placebo for pre-operative anxiolysis, sedation, maintenance of cognition and psychomotor skills, parental separation behaviour and venepuncture compliance. Methods: This prospective double-blind randomised study was conducted after ethical committee approval on 100 children aged 5-15 years, American Society of Anaesthesiologists physical status I and II undergoing elective surgery at our hospital from January 1, 2014, to December 31, 2014. Mentally disordered children were excluded from the study. They were randomised into four groups of 25 each (A, B, C, D to receive either oral MT 0.5 mg/kg or 0.75 mg/kg or oral midazolam 0.5 mg/kg or placebo 45-60 min, respectively, before induction. The child′s anxiety, cognition and psychomotor function before and after pre-medication, behaviour during the parental separation and venepuncture were appropriately scored. Kruskal-Wallis analysis of variance for intergroup and Wilcoxon matched pairs tests for intragroup comparisons of data were applied. Results: The four groups were comparable regarding mean age, weight and sex. The anxiety score reductions in the three groups when compared to placebo were statistically significant. Children receiving MT 0.75 mg/kg had maximum anxiolysis and venepuncture compliance (P < 0.05. Cognition was decreased with maximum sedation, successful parental separation and psychomotor impairment in the midazolam group (P < 0.05. Conclusion: Oral MT (0.5 mg/kg and 0.75 mg/kg in children decreases pre-operative anxiety without impairing cognitive and psychomotor functions, the 0.75 mg/kg dose being most effective.

Evaluation of a simple and rapid dipstick assay for the diagnosis of typhoid fever in Indonesia

NARCIS (Netherlands)

Gasem, M. Hussein; Smits, Henk L.; Goris, Marga G. A.; Dolmans, Wil M. V.

2002-01-01

To support the clinical diagnosis of typhoid fever in Indonesia, where most hospitals and health centres have no facilities for culture, a rapid dipstick assay for the detection of Salmonella typhi-specific IgM antibodies was evaluated on serum samples from 127 patients clinically suspected of

Human genetic variation in VAC14 regulates Salmonella invasion and typhoid fever through modulation of cholesterol.

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Alvarez, Monica I; Glover, Luke C; Luo, Peter; Wang, Liuyang; Theusch, Elizabeth; Oehlers, Stefan H; Walton, Eric M; Tram, Trinh Thi Bich; Kuang, Yu-Lin; Rotter, Jerome I; McClean, Colleen M; Chinh, Nguyen Tran; Medina, Marisa W; Tobin, David M; Dunstan, Sarah J; Ko, Dennis C

2017-09-12

Risk, severity, and outcome of infection depend on the interplay of pathogen virulence and host susceptibility. Systematic identification of genetic susceptibility to infection is being undertaken through genome-wide association studies, but how to expeditiously move from genetic differences to functional mechanisms is unclear. Here, we use genetic association of molecular, cellular, and human disease traits and experimental validation to demonstrate that genetic variation affects expression of VAC14, a phosphoinositide-regulating protein, to influence susceptibility to Salmonella enterica serovar Typhi ( S Typhi) infection. Decreased VAC14 expression increased plasma membrane cholesterol, facilitating Salmonella docking and invasion. This increased susceptibility at the cellular level manifests as increased susceptibility to typhoid fever in a Vietnamese population. Furthermore, treating zebrafish with a cholesterol-lowering agent, ezetimibe, reduced susceptibility to S Typhi. Thus, coupling multiple genetic association studies with mechanistic dissection revealed how VAC14 regulates Salmonella invasion and typhoid fever susceptibility and may open doors to new prophylactic/therapeutic approaches.

Distribution of chloramphenicol to tissues, plasma and urine in pigs after oral intake of low doses.

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Aspenström-Fagerlund, Bitte; Nordkvist, Erik; Törnkvist, Anna; Wallgren, Per; Hoogenboom, Ron; Berendsen, Bjorn; Granelli, Kristina

2016-09-01

Toxic effects of chloramphenicol in humans caused the ban for its use in food-producing animals in the EU. A minimum required performance level (MRPL) was specified for chloramphenicol at 0.3 μg kg(-1) for various matrices, including urine. In 2012, residues of chloramphenicol were found in pig urine and muscle without signs of illegal use. Regarding its natural occurrence in straw, it was hypothesised that this might be the source, straw being compulsory for use as bedding material for pigs in Sweden. Therefore, we investigated if low daily doses of chloramphenicol (4, 40 and 400 μg/pig) given orally during 14 days could result in residues in pig tissues and urine. A dose-related increase of residues was found in muscle, plasma, kidney and urine (showing the highest levels), but no chloramphenicol was found in the liver. At the lowest dose, residues were below the MRPL in all tissues except in the urine. However, in the middle dose, residues were above the MRPL in all tissues except muscle, and at the highest dose in all matrices. This study proves that exposure of pigs to chloramphenicol in doses occurring naturally in straw could result in residues above the MRPL in plasma, kidney and especially urine.

Single-dose Live Oral Cholera Vaccine CVD 103-HgR Protects Against Human Experimental Infection With Vibrio cholerae O1 El Tor.

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Chen, Wilbur H; Cohen, Mitchell B; Kirkpatrick, Beth D; Brady, Rebecca C; Galloway, David; Gurwith, Marc; Hall, Robert H; Kessler, Robert A; Lock, Michael; Haney, Douglas; Lyon, Caroline E; Pasetti, Marcela F; Simon, Jakub K; Szabo, Flora; Tennant, Sharon; Levine, Myron M

2016-06-01

No licensed cholera vaccine is presently available in the United States. Cholera vaccines available in other countries require 2 spaced doses. A single-dose cholera vaccine that can rapidly protect short-notice travelers to high-risk areas and help control explosive outbreaks where logistics render 2-dose immunization regimens impractical would be a major advance.PXVX0200, based on live attenuated Vibrio cholerae O1 classical Inaba vaccine strain CVD 103-HgR, elicits seroconversion of vibriocidal antibodies (a correlate of protection) within 10 days of a single oral dose. We investigated the protection conferred by this vaccine in a human cholera challenge model. Consenting healthy adult volunteers, 18-45 years old, were randomly allocated 1:1 to receive 1 oral dose of vaccine (approximately 5 × 10(8) colony-forming units [CFU]) or placebo in double-blind fashion. Volunteers ingested approximately 1 × 10(5) CFU of wild-type V. cholerae O1 El Tor Inaba strain N16961 10 days or 3 months after vaccination and were observed on an inpatient research ward for stool output measurement and management of hydration. The vaccine was well tolerated, with no difference in adverse event frequency among 95 vaccinees vs 102 placebo recipients. The primary endpoint, moderate (≥3.0 L) to severe (≥5.0 L) diarrheal purge, occurred in 39 of 66 (59.1%) placebo controls but only 2 of 35 (5.7%) vaccinees at 10 days (vaccine efficacy, 90.3%; P < .0001) and 4 of 33 (12.1%) vaccinees at 3 months (vaccine efficacy, 79.5%; P < .0001). The significant vaccine efficacy documented 10 days and 3 months after 1 oral dose of PXVX0200 supports further development as a single-dose cholera vaccine. NCT01895855. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Single-dose pharmacokinetics and tolerability of oral delta-9- tetrahydrocannabinol in patients with amyotrophic lateral sclerosis.

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Joerger, Markus; Wilkins, Justin; Fagagnini, Stefania; Baldinger, Reto; Brenneisen, Rudolf; Schneider, Ursula; Goldman, Bea; Weber, Markus

2012-06-01

Cannabinoids exert neuroprotective and symptomatic effects in amyotrophic lateral sclerosis (ALS). We assessed the pharmacokinetics (PK) and tolerability of delta-9-tetrahydrocannabinol (THC) in ALS patients. Nine patients received THC single oral doses of 5mg and 10mg, separated by a wash-out period of two weeks. Blood samples for the determination of THC, 11-nor-9-carboxy-THC (THC-COOH) and hydroxy-THC (THC-OH) were taken up to 8 hours after intake. Adverse events were assessed by visual analogue scales (VAS). Plasma concentrations of the active metabolite THC-OH were submitted to sequential pharmacokinetic-pharmacodynamic population modeling on individual heart rate as a proxy for THC's cardiovasculatory effects. Drowsiness, euphoria, orthostasis, sleepiness, vertigo and weakness were significantly more frequent in patients receiving 10mg compared to 5 mg THC. A marked interindividual variability was found for the absorption of oral THC (84%) and elimination of THC-COOH (45%). PK data did not support any clinically relevant deviation from linear PK in the investigated range of concentrations. Plasma concentrations of THC-OH were positively correlated with the individual heart rate. An E(max-model) was successfully fitted to individual heart rate, with a THC-OH plasma concentration of 3.2 x 10(-4) μmol/L for EC(50) and an E(max) of 93 bpm for heart rate. The higher 10mg dose of THC was dose-limiting in patients with ALS. High interindividual PK variability requires individuell titration of THC for potential therapeutic use in patients with ALS.

Plasma concentrations of fenbendazole (FBZ and oxfendazole in alpacas (Lama pacos after single intravenous and oral dosing of FBZ

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Lakritz J

2015-02-01

Full Text Available Jeffrey Lakritz,1 Daniel Linden,2 David E Anderson,3 Terri A Specht4 1Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA; 2Department of Agriculture and Engineering Technologies, College of Food, Agriculture and Environmental Sciences, The Ohio State University, Wooster, OH, USA; 3Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN, USA; 4Four Star Veterinary Service, Chickasaw, OH, USA Abstract: The objective of this study was to determine plasma pharmacokinetics and bioavailability of fenbendazole (FBZ and oxfendazole (OFZ after intravenous (iv and oral administrations of FBZ (5 mg/kg to alpacas. Plasma concentrations of FBZ and OFZ after administration of FBZ iv and orally (5 mg/kg were determined by high-performance liquid chromatography with ultraviolet detection. Total clearance (CL of FBZ was 16.5±4 mL/kg/min (range: 4–31 mL/kg/min, and steady-state volume of distribution (Vdss was 3.3±1 L/kg (range: 1.7–7.4 L/kg. The terminal phase half-life of FBZ after iv administration was 5.9±3.8 hours (range: 0.8–20 hours. After oral administration, the FBZ terminal phase half-life was 23±5 hours (range: 9–37 hours and the systemic bioavailability of FBZ was 16%±6% (range: 1%–41%. Peak FBZ concentrations after oral administration were 0.13±0.05 µg/mL (range: 0.05–0.28 µg/mL at 10 hours (range: 8–12 hours. Peak plasma OFZ concentrations after oral dosing with FBZ (5 mg/kg were 0.14±0.05 µg/mL (0.05–0.3 µg/mL at 24±7 hours (range: 12–48 hours. FBZ clearance is lower in comparison to that of other species. Systemic availability of FBZ after oral administration is low after oral dosing. Metabolites of FBZ produced by alpacas are similar to those observed in other species. Keywords: bioavailability, benzimidazoles, camelid, pharmacokinetics

Pharmacokinetics of Levetiracetam in Healthy Hispaniolan Amazon Parrots ( Amazona ventralis ) After Oral Administration of a Single Dose.

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Schnellbacher, Rodney; Beaufrère, Hugues; Vet, Dr Med; Arnold, Robert D; Tully, Thomas N; Mayer, Joerg; Divers, Stephen J

2014-09-01

Long-term anticonvulsive treatments have been poorly described in birds, and few pharmacokinetic studies have been performed, with mixed results. Levetiracetam, a new anticonvulsive drug, has shown good efficacy for monotherapy or adjunctive treatment of seizures in both human and veterinary medicine. To determine pharmacokinetics of levetiracetam in Hispaniolan Amazon parrots ( Amazona ventralis ), 20 healthy birds were randomly divided into 2 groups and administered either a 50 mg/kg (n = 10) or a 100 mg/kg (n = 10) oral dose of levetiracetam with no observable adverse effects. Blood samples were collected at baseline and at 12 time intervals (6 per group) for 16 hours. The concentration-time profiles resembled characteristic absorption, with maximum plasma concentrations of 61.0 μg/mL and 95.1 μg/mL at 60 minutes; terminal half-lives at 2.38 and 2.37 hours; volumes of distribution of 0.807 and 0.773 L/kg, with an area under the curve at 14 100 and 28 820 mg × min/L; and clearance rates of 3.65 and 3.60 mL/min per kg, respectively. Plasma concentrations were greater than 5.5 mg/L for up to 9.4 and 12 hours, suggesting an 8- and 12-hour oral dosing at 50 and 100 mg/kg, respectively, would be sufficient to maintain targeted values. Clinically, doses and frequencies may need escalation based on differences in species and individuals, and drug levels should be monitored.

Oral sodium phenylbutyrate in patients with recurrent malignant gliomas: a dose escalation and pharmacologic study.

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Phuphanich, Surasak; Baker, Sharyn D; Grossman, Stuart A; Carson, Kathryn A; Gilbert, Mark R; Fisher, Joy D; Carducci, Michael A

2005-04-01

We determined the maximum tolerated dose (MTD), toxicity profile, pharmacokinetic parameters, and preliminary efficacy data of oral sodium phenylbutyrate (PB) in patients with recurrent malignant gliomas. Twenty-three patients with supratentorial recurrent malignant gliomas were enrolled on this dose escalation trial. Four dose levels of PB were studied: 9, 18, 27, and 36 g/day. Data were collected to assess toxicity, response, survival, and pharmacokinetics. All PB doses of 9, 18, and 27 g/day were well tolerated. At 36 g/day, two of four patients developed dose-limiting grade 3 fatigue and somnolence. At the MTD of 27 g/day, one of seven patients developed reversible grade 3 somnolence. Median survival from time of study entry was 5.4 months. One patient had a complete response for five years, and no partial responses were noted, which yielded an overall response rate of 5%. Plasma concentrations of 706, 818, 1225, and 1605 muM were achieved with doses of 9, 18, 27, and 36 g/day, respectively. The mean value for PB clearance in this patient population was 22 liters/h, which is significantly higher than the 16 liters/h reported in patients with other malignancies who were not receiving P450 enzyme-inducing anticonvulsant drugs (P = 0.038). This study defines the MTD and recommended phase 2 dose of PB at 27 g/day for heavily pretreated patients with recurrent gliomas. The pharmacology of PB appears to be affected by concomitant administration of P450-inducing anticonvulsants.

Evaluation of fleroxacin (RO 23-6240) as single-oral-dose therapy of culture-proven chancroid in Nairobi, Kenya.

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MacDonald, K S; Cameron, D W; D'Costa, L; Ndinya-Achola, J O; Plummer, F A; Ronald, A R

1989-01-01

Chancroid is gaining importance as a sexually transmitted disease because of its association with transmission of human immunodeficiency virus type 1 (HIV-1). Effective, simply administered therapy for chancroid is necessary. Fleroxacin is effective against Haemophilus ducreyi in vitro. We performed an initial randomized clinical trial to assess the efficacy of fleroxacin for treatment of chancroid in Nairobi, Kenya. Fifty-three men with culture-positive chancroid were randomly assigned to receive either 200 mg (group 1) or 400 mg (group 2) of fleroxacin as a single oral dose. Groups 1 and 2 were similar with regard to severity of disease, bubo formation, and HIV-1 status. A satisfactory clinical response to therapy was noted in 23 of 26 patients (88%) in group 1 and 18 of 23 patients (78%) in group 2. Bacteriological failure occurred in 1 of 26 evaluable patients (4%) in group 1 and 4 of 23 evaluable patients (17%) in group 2. Two of 37 HIV-1-seronegative men (5%) and 3 of 11 HIV-1-infected men (27%) were bacteriological failures. Fleroxacin, 200 or 400 mg as a single oral dose, is efficacious therapy for microbiologically proven chancroid in patients who do not have concurrent HIV-1 infection. Among HIV-1-infected men, a single dose of 200 or 400 mg of fleroxacin is inadequate therapy for chancroid. PMID:2502065

Formative research and development of an evidence-based communication strategy: the introduction of Vi typhoid fever vaccine among school-aged children in Karachi, Pakistan.

Science.gov (United States)

Pach, Alfred; Tabbusam, Ghurnata; Khan, M Imran; Suhag, Zamir; Hussain, Imtiaz; Hussain, Ejaz; Mumtaz, Uzma; Haq, Inam Ul; Tahir, Rehman; Mirani, Amjad; Yousafzai, Aisha; Sahastrabuddhe, Sushant; Ochiai, R Leon; Soofi, Sajid; Clemens, John D; Favorov, Michael O; Bhutta, Zulfiqar A

2013-01-01

The authors conducted formative research (a) to identify stakeholders' concerns related to typhoid fever and the need for disease information and (b) to develop a communication strategy to inform stakeholders and address their concerns and motivate for support of a school-based vaccination program in Pakistan. Data were collected during interactive and semi-structured focus group discussions and interviews, followed by a qualitative analysis and multidisciplinary consultative process to identify an effective social mobilization strategy comprised of relevant media channels and messages. The authors conducted 14 focus group discussions with the parents of school-aged children and their teachers, and 13 individual interviews with school, religious, and political leaders. Parents thought that typhoid fever was a dangerous disease, but were unsure of their children's risk. They were interested in vaccination and were comfortable with a school-based vaccination if conducted under the supervision of trained and qualified staff. Teachers and leaders needed information on typhoid fever, the vaccine, procedures, and sponsors of the vaccination program. Meetings were considered the best form of information dissemination, followed by printed materials and mass media. This study shows how qualitative research findings can be translated into an effective social mobilization and communication approach. The findings of the research indicated the importance of increasing awareness of typhoid fever and the benefits of vaccination against the disease. Identification and dissemination of relevant, community-based disease and vaccination information will increase demand and use of vaccination.

A study of acute phase and transport protein synthesis in undernourished men using simulated infection and uniformly 15N-labelled Spirulina Platenses

International Nuclear Information System (INIS)

Kurpad, A.V.; Soares, M.J.; Sekhar, R.V.; Reeds, P.J.; Fjeld, C.R.

1994-01-01

This study was conducted to test the hypothesis that acute phase protein synthesis is accelerated and transport protein synthesis is decelerated in adult men in whom the stress of infection is superimposed upon undernutrition. As a pilot study, four chronically undernourished men and two well-nourished controls were studied on two occasions separated by four days; the second session was conducted 24 hours after the administration of typhoid vaccine. Basal urine and blood samples were collected and then subjects were given priming oral doses of 15 N-Spirulina (13.5mg/kg body weight) and oral doses (3.5mg/kg body weight) every 30 min for the next six hours. Meals were aliquoted during the dosing period. Blood samples were collected at four, five and six hours. 15 N enrichment in different fractions of plasma i.e., albumin, non-albumin and amino acids, was measured by combustion GC-IRMS. Total urinary nitrogen was measured by Kjeldahl. 5 refs, 2 figs, 3 tabs

Identification of carriers among individuals recruited in the typhoid registry in Malaysia using stool culture, polymerase chain reaction, and dot enzyme immunoassay as detection tools.

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Chua, Ang Lim; Aziah, Ismail; Balaram, Prabha; Bhuvanendran, Saatheeyavaane; Anthony, Amy Amilda; Mohmad, Siti Norazura; Nasir, Norhafiza M; Hassan, Haslizai; Naim, Rochman; Meran, Lila P; Hussin, Hani M; Ismail, Asma

2015-03-01

Chronic carriers of Salmonella Typhi act as reservoirs for the organism and become the agents of typhoid outbreaks in a community. In this study, chronic carriers in Kelantan, Malaysia were first identified using the culture and polymerase chain reaction method. Then, a novel serological tool, designated Typhidot-C, was evaluated in retrospect using the detected individuals as control positives. Chronic carriage positive by the culture and polymerase chain reaction method was recorded at 3.6% (4 out of 110) among individuals who previously had acute typhoid fever and a 9.4% (10 out of 106) carriage rate was observed among food handlers screened during outbreaks. The Typhidot-C assay was able to detect all these positive carriers showing its potential as a viable carrier screening tool and can be used for efficient detection of typhoid carriers in an endemic area. These findings were used to establish the first carrier registry for S Typhi carriers in Malaysia. © 2012 APJPH.

Evaluation of the Risk of Grade 3 Oral and Pharyngeal Dysphagia Using Atlas-Based Method and Multivariate Analyses of Individual Patient Dose Distributions

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Otter, Sophie [Department of Clinical Oncology, Royal Marsden Hospital, Sutton and London (United Kingdom); Schick, Ulrike; Gulliford, Sarah [Department of Clinical Oncology, Royal Marsden Hospital, Sutton and London (United Kingdom); The Institute of Cancer Research, London (United Kingdom); Lal, Punita [Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow India (India); Franceschini, Davide [Department of Radiotherapy and Radiosurgery, Humanitas Research Hospital, Milan (Italy); Newbold, Katie; Nutting, Christopher; Harrington, Kevin [Department of Clinical Oncology, Royal Marsden Hospital, Sutton and London (United Kingdom); The Institute of Cancer Research, London (United Kingdom); Bhide, Shreerang, E-mail: shreerang.bhide@icr.ac.uk [Department of Clinical Oncology, Royal Marsden Hospital, Sutton and London (United Kingdom); The Institute of Cancer Research, London (United Kingdom); Department of Radiotherapy and Radiosurgery, Humanitas Research Hospital, Milan (Italy)

2015-11-01

Purpose: The study aimed to apply the atlas of complication incidence (ACI) method to patients receiving radical treatment for head and neck squamous cell carcinomas (HNSCC), to generate constraints based on dose-volume histograms (DVHs), and to identify clinical and dosimetric parameters that predict the risk of grade 3 oral mucositis (g3OM) and pharyngeal dysphagia (g3PD). Methods and Materials: Oral and pharyngeal mucosal DVHs were generated for 253 patients who received radiation (RT) or chemoradiation (CRT). They were used to produce ACI for g3OM and g3PD. Multivariate analysis (MVA) of the effect of dosimetry, clinical, and patient-related variables was performed using logistic regression and bootstrapping. Receiver operating curve (ROC) analysis was also performed, and the Youden index was used to find volume constraints that discriminated between volumes that predicted for toxicity. Results: We derived statistically significant dose-volume constraints for g3OM over the range v28 to v70. Only 3 statistically significant constraints were derived for g3PD v67, v68, and v69. On MVA, mean dose to the oral mucosa predicted for g3OM and concomitant chemotherapy and mean dose to the inferior constrictor (IC) predicted for g3PD. Conclusions: We have used the ACI method to evaluate incidences of g3OM and g3PD and ROC analysis to generate constraints to predict g3OM and g3PD derived from entire individual patient DVHs. On MVA, the strongest predictors were radiation dose (for g3OM) and concomitant chemotherapy (for g3PD).

Epidemiology, clinical manifestations, and molecular typing of salmonella typhi isolated from patients with typhoid fever in Lebanon.

Science.gov (United States)

Kanj, Souha S; Kanafani, Zeina A; Shehab, Marwa; Sidani, Nisreen; Baban, Tania; Baltajian, Kedak; Dakdouki, Ghenwa K; Zaatari, Mohamad; Araj, George F; Wakim, Rima Hanna; Dbaibo, Ghassan; Matar, Ghassan M

2015-06-01

The objective of this study was to examine the epidemiology and the clinical manifestations of typhoid fever as well as the susceptibility and strain relatedness of Salmonella typhi isolates in Lebanon from 2006 to 2007. A total of 120 patients with typhoid fever were initially identified from various areas of the country based on positive culture results for S. typhi from blood, urine, stools, bone marrow and/or positive serology. Clinical, microbiological and molecular analysis was performed on cases with complete data available. These results indicated that drinking water was an unlikely mode of transmission of the infection. Despite increasing reports of antimicrobial resistance among S. typhi isolates, the vast majority of these isolates were susceptible to various antibiotic agents, including ampicillin, cephalosporins, quinolones, and trimethoprim/sulfamethoxazole. Molecular analysis of the isolates revealed a predominance of one single genotype with no variation in distribution across the geographical regions. Copyright © 2014 Ministry of Health, Saudi Arabia. Published by Elsevier Ltd. All rights reserved.

Dose selection trial of metronomic oral vinorelbine monotherapy in patients with metastatic cancer: a hellenic cooperative oncology group clinical translational study

International Nuclear Information System (INIS)

Briasoulis, Evangelos; Vassias, Antonios; Klouvas, George; Boukovinas, Ioannis; Fountzilas, George; Syrigos, Kostantinos N; Kalofonos, Haralambos; Samantas, Epaminontas; Aravantinos, Gerasimos; Kouvatseas, George; Pappas, Periklis; Biziota, Eirini; Sainis, Ioannis; Makatsoris, Thomas; Varthalitis, Ioannis; Xanthakis, Ioannis

2013-01-01

Metronomic chemotherapy is considered an anti-angiogenic therapy that involves chronic administration of low-dose chemotherapy at regular short intervals. We investigated the optimal metronomic dose of oral vinorelbine when given as monotherapy in patients with metastatic cancer. Patients with recurrent metastatic breast (BC), prostate (PC) or non-small cell lung cancer (NSCLC) and adequate organ functions were randomly assigned to 30, 40 or 50 mg vinorelbine, taken orally three times a week. Treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or maximum 24 months. Primary endpoint was time-to-treatment failure (TTF) and secondary were progression-free survival (PFS), toxicity, changes in blood concentrations of angiogenesis-associated biomarkers and pharmacokinetics. Seventy-three patients were enrolled. Four-month TTF rate did not differ between the three arms: 25.9% (11.1%-46.2% 95% Confidence Interval), 33.3% (15.6%-55.3%) and 18.2% (5.2%-40.3%) for the 30 mg, 40 mg and 50 mg arms (p-value = 0.56). Objective response was seen in 2 patients with NSCLC (treated at 30 and 50 mg respectively), one with BC (at 40 m g) and one with PC (at 50 mg) and lasted from 4 to 100 weeks, with maximum response duration achieved at 50 mg. Adverse events were mild and negligible and did not differ between the three arms. Blood levels of vinorelbine reached steady state from the second week of treatment and mean values for the 30, 40 and 50 mg were respectively 1.8 ng/ml (SD 1.10), 2.2 ng/ml (SD 1.87) and 2.6 ng/ml (SD 0.69). Low pre-treatment blood concentrations of FGF2 and IL8 predicted favorable response to therapy (p values 0.02 and 0.006, respectively), while high levels of TEK gene transcript predicted treatment resistance. Considering the antitumor activity and response duration, the negligible toxicity of the highest dose investigated and the lack of drug accumulation over time, we suggest that 50 mg given three times a week is the

[Directions for use of corticosteroids and calcineurin inhibitors against generalized myasthenia gravis: therapeutic strategies that can lead to early improvements and veer away from high-dose oral corticosteroids].

Science.gov (United States)

Utsugisawa, Kimiaki; Nagane, Yuriko; Suzuki, Shigeaki; Suzuki, Norihiro

2012-01-01

The advent of effective immune treatment has meant that myasthenia gravis (MG) is most often not lethal. However, many MG patients still find it difficult to maintain daily activities due to chronic residual fatigability and long-term side effects of medication, since full remission without immune treatment is not common. Our analysis demonstrated that disease severity, dose of oral corticosteroids, and depressive state are the major independent factors negatively associated with self-reported QOL (MG-QOL15-J score). It is noteworthy that oral corticosteroid, the first-line agent for MG, is negatively associated with patients' QOL. When the analysis took into account MGFA postintervention status and dose of oral prednisolne (PSL), the MG-QOL15-J score of MM status patients taking ≤ 5 mg PSL per day is identically low (i.e., just as good QOL) as that seen in CSR and is a target of treatment. In order to veer away from high-dose oral corticosteroids and to achieve early MM or better status with PSL ≤ 5 mg/day, we advocate the early aggressive treatment strategy that can achieve early improvement by performing an aggressive therapy using combined treatment with plasmapheresis and high-dose intravenous methylprednisolone and then maintain an improved clinical status using low-dose oral corticosteroids and calcineurin inhibitors (cyclosporine microemulsion and tacrolimus). The early stages of MG are susceptible to treatment with calcineurin inhibitors. When using cyclosporine microemulsion for MG, blood concentrations 2 h after administration (C2) correlate with clinical improvement and immediately before administration (C0) with side effects (increased serum creatinine and/or hypertension). Monitoring of C2 and C0 levels is useful to estimate efficacy and safety of the drug.

Dgroup: DG01689 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available e oral polimyelitis vaccine (JP17) ... D06261 ... Typhoid vaccine ... D10193 ... Live attenuated human rota virus vaccine, oral ... D10211 ... Rotav...irus vaccine, live, oral, pentavalent ... Antiviral ATC code: J07 Vaccine ...

Superantigen-Induced Cytokine Release from Whole-Blood Cell Culture as a Functional Measure of Drug Efficacy after Oral Dosing in Nonhuman Primates

National Research Council Canada - National Science Library

Krakauer, Teresa; Stephens, Julie; Buckley, Marilyn; Tate, Mallory

2007-01-01

...) closely resemble humans. We examined the ex vivo cytokine response of superantigen-stimulated whole-blood cells as a first step to therapeutic efficacy testing for bacterial superantigen-induced shock in NHP after oral dosing of pentoxifylline...

Single oral dose toxicity test of polycalcium, a mixed composition of polycan and calcium lactate-gluconate 1:9 (G/G) in SD rat.

Science.gov (United States)

Kim, Joo-Wan; Choi, Jae-Suk; Ha, Yu-Mi; Choi, In Soon; Kim, Ki-Young; Cho, Hyung-rae; Rha, Chae-hun; Ku, Sae-Kwang

2013-11-01

The object of this study was to obtain acute oral toxicity information of Polycalcium, a mixed composition of Polycan and Calcium lactate-gluconate 1:9 (g/g), in Sprague-Dawely (SD) rats. In order to investigate the toxicity and identify target organs, Polycalcium were once orally administered to female and male SD rats at dose levels of 2000, 1000, 500 and 0 (control) mg/kg body weights. The mortality, changes on body weight and clinical signs were monitored during 14 days after treatment with gross observation, changes on the organ weights and histopathology of principle organs and treatment sites based on the recommendation of KFDA Guidelines [2009-116, 2009]. As the results of single oral treatment of Polycalcium, no treatment related mortalities were observed within 14 days after end of treatment up to 2000 mg/kg, the limited dosage of rodents in the both genders. In addition, no Polycalcium treatment related changes on the body and organ weights, clinical signs, necropsy and histopathological findings were detected. The results obtained in this study suggest that the Polycalcium is non-toxic in rats. The LD50 and approximate LD in rats after single oral dose of Polycalcium were considered over 2000 mg/kg in both female and male, respectively.

Plasma methylphenidate concentrations in youths treated with high-dose osmotic release oral system formulation.

Science.gov (United States)

Stevens, Jonathan R; George, Robert A; Fusillo, Steven; Stern, Theodore A; Wilens, Timothy E

2010-02-01

Children and adolescents are being treated increasingly for attention-deficit/hyperactivity disorder (ADHD) with a variety of stimulants in higher than Food and Drug Administration (FDA)-approved doses and in combination with other medications. We sought to determine methylphenidate (MPH) concentrations in children and adolescents treated with high-dose, extended-release osmotic release oral system (OROS) MPH plus concomitant medications, and to examine MPH concentrations with respect to the safety and tolerability of treatment. Plasma MPH concentrations were measured by liquid chromatography-mass spectrometry 4-5 hours after administration of medication in a sample of youths diagnosed with ADHD. These youths were treated naturalistically with higher than FDA-approved doses of OROS MPH in addition to their concomitant medications. Markers of safety and tolerability (e.g., measures of blood pressure and heart rate) were also examined. Among the 17 patients (with a mean age of 16.2 +/- 2 years and a mean number of concurrent medications of 2.23 +/- 0.94), the mean plasma MPH concentration was 28 +/- 9.1 ng/mL, despite a mean daily dose of OROS MPH of 169 +/- 5 mg (3.0 +/- 0.8 mg/kg per day). No patient had a plasma MPH level >or=50 ng/mL or clinical signs of stimulant toxicity. No correlation was found between plasma MPH concentrations and OROS MPH dose or changes in vital signs. High-dose OROS MPH, used in combination with other medications, was not associated with either unusually elevated plasma MPH concentrations or with clinically meaningful changes in vital signs. Study limitations include a single time-point sampling of MPH concentrations, a small sample size, and a lack of outcome measures to address treatment effectiveness.

Single dose oral ranitidine improves MRCP image quality: a double-blind study

International Nuclear Information System (INIS)

Bowes, M.T.; Martin, D.F.; Melling, A.; Roberts, D.; Laasch, H.-U.; Sukumar, S.; Morris, J.

2007-01-01

Aim: To investigate the possibility of whether a single 300 mg dose of ranitidine given orally 2-3 h before magnetic resonance cholangiopancreatography (MRCP) could reduce the signal from the stomach and duodenum, and thus increase the conspicuousness of the biliary tree. Materials and methods: Thirty-five volunteers (22 female, 13 male), (age range 21-50) were underwent MRCP in a double-blind, placebo-controlled, randomized, crossover trial on a Philips Intera 1.5 T machine using a phased array surface coil. Imaging was carried out in the coronal oblique plane. Six 40 mm sections were acquired at varying angles to delineate the biliary tree and pancreatic duct. The 70 examinations were blindly scored by three consultants experienced in cholangiography. Results: After ranitidine administration there was a significant decrease in signal from the stomach (mean = 17.7, p = 0.0005, CI 10, 25.3) and duodenum (mean = 18.4, p = 0.0005, 95%CI 9.6, 27.1) with a significant increase in conspicuousness of the distal common duct (mean = 7.7, p = 0.033, 95%CI 0.7, 14.7) and proximal common duct (mean = 8.7, p = 0.010 CI 2.2, 15.2). There were no adverse effects. Conclusion: Oral ranitidine is a cheap and effective agent to decrease signal from the upper gastrointestinal tract and to improve visibility of the biliary tree

Intra-oral cone radiation therapy for selected carcinomas of the oral cavity

International Nuclear Information System (INIS)

Wang, C.C.; Doppke, K.P.; Biggs, P.J.

1983-01-01

A study of 101 patients with early carcinomas of the oral cavity, T1 and T2, treated by external cobalt 60 beam and/or intra-oral cone (IOC) radiation therapy between 1964 through 1980 was made. The two year disease-free survival rate, including surgical salvage, was 88% and the local control rate was 85%. The incidence of radiation complications, i.e., soft tissue ulceration and/or osteoradionecrosis, was 14% and varied with various tumor sites and radiation doses delivered. The present review shows that local control and radiation complications are closely related to radiation doses and varies with different tumor sites of the oral cavity. Radiation therapy dosages expressed in terms of TDF values for these lesions are herein recommended. With proper selections of lesions arising from the oral cavity, combined external beam and IOC radiation therapy has been found extremely efficacious in achieving good local tumor control and high survival rates with excellent cosmetic and functional results and minimum radiation sequalae

Oral Tolerance: Therapeutic Implications for Autoimmune Diseases

Directory of Open Access Journals (Sweden)

Ana M. C. Faria

2006-01-01

Full Text Available Oral tolerance is classically defined as the suppression of immune responses to antigens (Ag that have been administered previously by the oral route. Multiple mechanisms of tolerance are induced by oral Ag. Low doses favor active suppression, whereas higher doses favor clonal anergy/deletion. Oral Ag induces Th2 (IL-4/IL-10 and Th3 (TGF-β regulatory T cells (Tregs plus CD4+CD25+ regulatory cells and LAP+T cells. Induction of oral tolerance is enhanced by IL-4, IL-10, anti-IL-12, TGF-β, cholera toxin B subunit (CTB, Flt-3 ligand, anti-CD40 ligand and continuous feeding of Ag. In addition to oral tolerance, nasal tolerance has also been shown to be effective in suppressing inflammatory conditions with the advantage of a lower dose requirement. Oral and nasal tolerance suppress several animal models of autoimmune diseases including experimental allergic encephalomyelitis (EAE, uveitis, thyroiditis, myasthenia, arthritis and diabetes in the nonobese diabetic (NOD mouse, plus non-autoimmune diseases such as asthma, atherosclerosis, colitis and stroke. Oral tolerance has been tested in human autoimmune diseases including MS, arthritis, uveitis and diabetes and in allergy, contact sensitivity to DNCB, nickel allergy. Positive results have been observed in phase II trials and new trials for arthritis, MS and diabetes are underway. Mucosal tolerance is an attractive approach for treatment of autoimmune and inflammatory diseases because of lack of toxicity, ease of administration over time and Ag-specific mechanism of action. The successful application of oral tolerance for the treatment of human diseases will depend on dose, developing immune markers to assess immunologic effects, route (nasal versus oral, formulation, mucosal adjuvants, combination therapy and early therapy.

An international point source outbreak of typhoid fever: a European collaborative investigation*

Science.gov (United States)

Stanwell-Smith, R. E.; Ward, L. R.

1986-01-01

A point source outbreak of Salmonella typhi, degraded Vi-strain 22, affecting 32 British visitors to Kos, Greece, in 1983 was attributed by a case—control study to the consumption of a salad at one hotel. This represents the first major outbreak of typhoid fever in which a salad has been identified as the vehicle. The source of the infection was probably a carrier in the hotel staff. The investigation demonstrates the importance of national surveillance, international cooperation, and epidemiological methods in the investigation and control of major outbreaks of infection. PMID:3488842

Does radiation dose to the salivary glands and oral cavity predict patient-rated xerostomia and sticky saliva in head and neck cancer patients treated with curative radiotherapy?

International Nuclear Information System (INIS)

Jellema, Anke Petra; Doornaert, Patricia; Slotman, Ben J.; Rene Leemans, C.; Langendijk, Johannes A.

2005-01-01

Background and Purpose: To investigate the association between the mean salivary gland and oral cavity dose, with patient-rated moderate and severe xerostomia and sticky saliva. Patients and methods: One hundred and fifty-seven patients treated with bilateral irradiation for head and neck cancer were included. The parotid and submandibular glands and the oral cavity were delineated on plannings-CT scans. At baseline and 6 and 12 months self-reported xerostomia and sticky saliva were assessed using the EORTC QLQ-H and N35 questionnaire. Results: At 6 months a significant association between the mean parotid (MD par ) and mean submandibular dose (MD subm ) and xerostomia was observed (OR-MD par : 1.17; P=0.002 and OR-MD subm : 1.08; P=0.02). Between MD par and MD subm , a significant interaction term was present. No significant association was found with the oral cavity dose. Xerostomia was reversible depending on MD par and MD subm . Considering Sticky saliva, a significant association was found at 6 and 12 months with MD subm (OR: 1.03; P par and MD subm influence the risk of xerostomia in irradiated patients at 6 months. This probability as a function of the mean parotid dose significantly depended on the mean dose in the submandibular glands. Sticky saliva mainly depends on MD subm

Oral exposure to low-dose of nonylphenol impairs memory performance in Sprague-Dawley rats.

Science.gov (United States)

Kawaguchi, Shinichiro; Kuwahara, Rika; Kohara, Yumi; Uchida, Yutaro; Oku, Yushi; Yamashita, Kimihiro

2015-02-01

Nonylphenol ethoxylate (NPE) is a non-ionic surfactant, that is degraded to short-chain NPE and 4-nonylphenol (NP) by bacteria in the environment. NP, one of the most common environmental endocrine disruptors, exhibits weak estrogen-like activity. In this study, we investigated whether oral administration of NP (at 0.5 and 5 mg/kg doses) affects spatial learning and memory, general activity, emotionality, and fear-motivated learning and memory in male and female Sprague-Dawley (SD) rats. SD rats of both sexes were evaluated using a battery of behavioral tests, including an appetite-motivated maze test (MAZE test) that was used to assess spatial learning and memory. In the MAZE test, the time required to reach the reward in male rats treated with 0.5 mg/kg NP group and female rats administered 5 mg/kg NP was significantly longer than that for control animals of the corresponding sex. In other behavioral tests, no significant differences were observed between the control group and either of the NP-treated groups of male rats. In female rats, inner and ambulation values for animals administered 0.5 mg/kg NP were significantly higher than those measured in control animals in open-field test, while the latency in the group treated with 5 mg/kg NP was significantly shorter compared to the control group in step-through passive avoidance test. This study indicates that oral administration of a low-dose of NP slightly impairs spatial learning and memory performance in male and female rats, and alters emotionality and fear-motivated learning and memory in female rats only.

Effect of single oral doses of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on incretin and plasma glucose levels after an oral glucose tolerance test in patients with type 2 diabetes

DEFF Research Database (Denmark)

Herman, Gary A; Bergman, Arthur; Stevens, Catherine

2006-01-01

CONTEXT: In response to a meal, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are released and modulate glycemic control. Normally these incretins are rapidly degraded by dipeptidyl peptidase-4 (DPP-4). DPP-4 inhibitors are a novel class of oral antihyperglyce......CONTEXT: In response to a meal, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are released and modulate glycemic control. Normally these incretins are rapidly degraded by dipeptidyl peptidase-4 (DPP-4). DPP-4 inhibitors are a novel class of oral...... antihyperglycemic agents in development for the treatment of type 2 diabetes. The degree of DPP-4 inhibition and the level of active incretin augmentation required for glucose lowering efficacy after an oral glucose tolerance test (OGTT) were evaluated. OBJECTIVE: The objective of the study was to examine...... concentrations; and sitagliptin pharmacokinetics. RESULTS: Sitagliptin dose-dependently inhibited plasma DPP-4 activity over 24 h, enhanced active GLP-1 and GIP levels, increased insulin/C-peptide, decreased glucagon, and reduced glycemic excursion after OGTTs administered at 2 and 24 h after single oral 25...

Pharmacokinetic/pharmacodynamic modeling of benazepril and benazeprilat after administration of intravenous and oral doses of benazepril in healthy horses.

Science.gov (United States)

Serrano-Rodríguez, Juan Manuel; Gómez-Díez, Manuel; Esgueva, María; Castejón-Riber, Cristina; Mena-Bravo, Antonio; Priego-Capote, Feliciano; Ayala, Nahúm; Caballero, Juan Manuel Serrano; Muñoz, Ana

2017-10-01

Pharmacokinetic and pharmacodynamic (PK/PD) properties of the angiotensin-converting enzyme inhibitor (ACEI) benazeprilat have not been evaluated in horses. This study was designed to establish PK profiles for benazepril and benazeprilat after intravenous (IV) and oral (PO) administration of benazepril using a PK/PD model. This study also aims to determine the effects of benazeprilat on serum angiotensin converting enzyme (ACE), selecting the most appropriate dose that suppresses ACE activity. Six healthy horses in a crossover design received IV benazepril at 0.50mg/kg and PO at doses 0 (placebo), 0.25, 0.50 and 1.00mg/kg. Blood pressures (BP) were measured and blood samples were obtained at different times in order to measure serum drug concentrations and serum ACE activity, using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and spectrophotometry, respectively. Systemic bioavailability of benazeprilat after PO benazepril was 3-4%. Maximum ACE inhibitions from baseline were 99.63% (IV benazepril), 6.77% (placebo) and 78.91%, 85.74% and 89.51% (for the three PO benazepril doses). Significant differences in BP were not found. Although oral availability was low, benazeprilat 1.00mg/kg, reached sufficient serum concentrations to induce long lasting serum ACE inhibitions (between 88 and 50%) for the first 48h. Additional research on benazepril administration in equine patients is indicated. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pharmacokinetic Evaluation of a Single Intramuscular High Dose versus an Oral Long-Term Supplementation of Cholecalciferol.

Directory of Open Access Journals (Sweden)

Katharina Wylon

Full Text Available Vitamin D deficiency is frequent during the winter and occurs throughout the year in the elderly or patients suffering from autoimmune diseases. The objective of this study was to evaluate the pharmacokinetic properties of oral supplementation versus a single intramuscular injection of cholecalciferol in healthy individuals.Up to 8,000 I.U. oral cholecalciferol was administered daily for 84 days in a 4 week dose-escalation setting to vitamin D deficient individuals. In another cohort, a single intramuscular injection of 100,000 I.U. cholecalciferol was given. In both cohorts, individuals without vitamin D intake served as the comparison group. 25-hydroxyvitamin D (25(OHD concentrations were measured in all individuals at defined time points throughout the studies.The mean 25(OHD serum concentration increased significantly after oral cholecalciferol intake compared to the control group (day 28: 83.4 nmol/l and 42.5 nmol/l; day 56: 127.4 nmol/l and 37.3 nmol/l; day 84: 159.7 nmol/l and 30.0 nmol/l. In individuals receiving 100,000 I.U. cholecalciferol intramuscular, the mean 25(OHD serum concentration peaked after 4 weeks measuring 70.9 nmol/l compared to 32.7 nmol/l in the placebo group (p = 0.002. The increase of 25(OHD serum concentrations after 28 days was comparable between both routes of administration (p = 0.264.Oral and intramuscular cholecalciferol supplementation effectively increased serum 25(OHD concentrations.

Pharmacokinetic Profile of Oral Cannabis in Humans: Blood and Oral Fluid Disposition and Relation to Pharmacodynamic Outcomes.

Science.gov (United States)

Vandrey, Ryan; Herrmann, Evan S; Mitchell, John M; Bigelow, George E; Flegel, Ronald; LoDico, Charles; Cone, Edward J

2017-03-01

Most research on cannabis pharmacokinetics has evaluated inhaled cannabis, but oral ("edible") preparations comprise an increasing segment of the cannabis market. To assess oral cannabis pharmacokinetics and pharmacodynamics, healthy adults (N = 6 per dose) were administered cannabis brownies containing 10, 25 or 50 mg 9-tetrahydrocannabinol (THC). Whole blood and oral fluid specimens were obtained at baseline and then for 9 days post-exposure; 6 days in a residential research setting and 3 days as outpatients. Measures of subjective, cardiovascular and performance effects were obtained at baseline and for 8 h post-ingestion. The mean Cmax for THC in whole blood was 1, 3.5 and 3.3 ng/mL for the 10, 25 and 50 mg THC doses, respectively. The mean maximum concentration (Cmax) and mean time to maximum concentration (Tmax) of 11-OH-THC in whole blood were similar to THC. Cmax blood concentrations of THCCOOH were generally higher than THC and had longer Tmax values. The mean Tmax for THC in oral fluid occurred immediately following oral dose administration, and appear to reflect local topical residue rather than systemic bioavailbility. Mean Cmax oral fluid concentrations of THCCOOH were lower than THC, erratic over time and mean Tmax occurred at longer times than THC. The window of THC detection ranged from 0 to 22 h for whole blood (limit of quantitation (LOQ) = 0.5 ng/mL) and 1.9 to 22 h for oral fluid (LOQ = 1.0 ng/mL). Subjective drug and cognitive performance effects were generally dose dependent, peaked at 1.5-3 h post-administration, and lasted 6-8 h. Whole blood cannabinoid concentrations were significantly correlated with subjective drug effects. Correlations between blood cannabinoids and cognitive performance measures, and between oral fluid and all pharmacodynamic outcomes were either non-significant or not orderly by dose. Quantitative levels of cannabinoids in whole blood and oral fluid were low compared with levels observed following inhalation of

Oral sodium phenylbutyrate in patients with recurrent malignant gliomas: A dose escalation and pharmacologic study1

Science.gov (United States)

Phuphanich, Surasak; Baker, Sharyn D.; Grossman, Stuart A.; Carson, Kathryn A.; Gilbert, Mark R.; Fisher, Joy D.; Carducci, Michael A.

2005-01-01

We determined the maximum tolerated dose (MTD), toxicity profile, pharmacokinetic parameters, and preliminary efficacy data of oral sodium phenylbutyrate (PB) in patients with recurrent malignant gliomas. Twenty-three patients with supratentorial recurrent malignant gliomas were enrolled on this dose escalation trial. Four dose levels of PB were studied: 9, 18, 27, and 36 g/day. Data were collected to assess toxicity, response, survival, and pharmacokinetics. All PB doses of 9, 18, and 27 g/day were well tolerated. At 36 g/day, two of four patients developed dose-limiting grade 3 fatigue and somnolence. At the MTD of 27 g/day, one of seven patients developed reversible grade 3 somnolence. Median survival from time of study entry was 5.4 months. One patient had a complete response for five years, and no partial responses were noted, which yielded an overall response rate of 5%. Plasma concentrations of 706, 818, 1225, and 1605 μM were achieved with doses of 9, 18, 27, and 36 g/day, respectively. The mean value for PB clearance in this patient population was 22 liters/h, which is significantly higher than the 16 liters/h reported in patients with other malignancies who were not receiving P450 enzyme–inducing anticonvulsant drugs (P = 0.038). This study defines the MTD and recommended phase 2 dose of PB at 27 g/day for heavily pretreated patients with recurrent gliomas. The pharmacology of PB appears to be affected by concomitant administration of P450-inducing anticonvulsants. PMID:15831235

Effects of a single, oral 60 mg caffeine dose on attention in healthy adult subjects.

Science.gov (United States)

Wilhelmus, Micha Mm; Hay, Justin L; Zuiker, Rob Gja; Okkerse, Pieter; Perdrieu, Christelle; Sauser, Julien; Beaumont, Maurice; Schmitt, Jeroen; van Gerven, Joop Ma; Silber, Beata Y

2017-02-01

Caffeine induces positive effects on sustained attention, although studies assessing the acute effects of low caffeine dose (caffeine on sustained attention in tests lasting up to 45 minutes using 82 low or non-caffeine-consuming healthy male ( n=41) and female ( n=41) adults aged between 40 and 60 years. Vigilance was measured using Mackworth Clock test, Rapid Visual Information Processing Test, adaptive tracking test, saccadic eye movement and attention switch test. Effects on mood and fatigue were analysed using Bond and Lader and Caffeine Research visual analogue scales, and Samn-Perelli questionnaire. Saliva sampling was performed for both compliance and caffeine pharmacokinetic analysis. Administration of a 60 mg caffeine dose resulted in a significant improvement in sustained attention compared with the placebo. Also a significantly improved peak saccadic velocity and reaction time performance was found, and decreased error rate. Significantly increased feelings of alertness, contentment and overall mood after caffeine treatment compared with placebo were observed. This study demonstrated that in healthy adult subjects oral administration of a single 60 mg caffeine dose elicited a clear enhancement of sustained attention and alertness, measured both in multiple objective performances and in subjective scales.

Typhoid fever in young children in Bangladesh: clinical findings, antibiotic susceptibility pattern and immune responses.

Directory of Open Access Journals (Sweden)

Farhana Khanam

2015-04-01

Full Text Available Children bear a large burden of typhoid fever caused by Salmonella enterica serotype Typhi (S. Typhi in endemic areas. However, immune responses and clinical findings in children are not well defined. Here, we describe clinical and immunological characteristics of young children with S. Typhi bacteremia, and antimicrobial susceptibility patterns of isolated strains.As a marker of recent infection, we have previously characterized antibody-in-lymphocyte secretion (TPTest during acute typhoid fever in adults. We similarly assessed membrane preparation (MP IgA responses in young children at clinical presentation, and then 7-10 days and 21-28 days later. We also assessed plasma IgA, IgG and IgM responses and T cell proliferation responses to MP at these time points. We compared responses in young children (1-5 years with those seen in older children (6-17 years, adults (18-59 years, and age-matched healthy controls.We found that, compared to age-matched controls patients in all age cohorts had significantly more MP-IgA responses in lymphocyte secretion at clinical presentation, and the values fell in all groups by late convalescence. Similarly, plasma IgA responses in patients were elevated at presentation compared to controls, with acute and convalescent IgA and IgG responses being highest in adults. T cell proliferative responses increased in all age cohorts by late convalescence. Clinical characteristics were similar in all age cohorts, although younger children were more likely to present with loss of appetite, less likely to complain of headache compared to older cohorts, and adults were more likely to have ingested antibiotics. Multi-drug resistant strains were present in approximately 15% of each age cohort, and 97% strains had resistance to nalidixic acid.This study demonstrates that S. Typhi bacteremia is associated with comparable clinical courses, immunologic responses in various age cohorts, including in young children, and that TPTest

Effect of high-dose oral multivitamins and minerals in participants not treated with statins in the randomized Trial to Assess Chelation Therapy (TACT).

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Issa, Omar M; Roberts, Rhonda; Mark, Daniel B; Boineau, Robin; Goertz, Christine; Rosenberg, Yves; Lewis, Eldrin F; Guarneri, Erminia; Drisko, Jeanne; Magaziner, Allan; Lee, Kerry L; Lamas, Gervasio A

2018-01-01

In a prespecified subgroup analysis of participants not on statin therapy at baseline in the TACT, a high-dose complex oral multivitamins and multimineral regimen was found to have a large unexpected benefit compared with placebo. The regimen tested was substantially different from any vitamin regimen tested in prior clinical trials. To explore these results, we performed detailed additional analyses of participants not on statins at enrollment in TACT. TACT was a factorial trial testing chelation treatments and a 28-component high-dose oral multivitamins and multiminerals regimen versus placebo in post-myocardial infarction (MI) patients 50 years or older. There were 460 (27%) of 1,708 TACT participants not taking statins at baseline, 224 (49%) were in the active vitamin group and 236 (51%) were in the placebo group. Patients were enrolled at 134 sites around the United States and Canada. Daily high-dose oral multivitamins and multiminerals (6 tablets, active or placebo). The primary end point of TACT was time to the first occurrence of any component of the composite end point: all-cause mortality, MI, stroke, coronary revascularization, or hospitalization for angina. The primary end point occurred in 137 nonstatin participants (30%), of which 51 (23%) of 224 were in the active group and 86 (36%) of 236 were taking placebo (hazard ratio, 0.62; 95% confidence interval, 0.44-0.87; P=.006). Results in the key TACT secondary end point, a combination of cardiovascular mortality, stroke, or recurrent MI, was consistent in favoring the active vitamin group (hazard ratio, 0.46; 95% confidence interval, 0.28-0.75; P=.002). Multiple end point analyses were consistent with these results. High-dose oral multivitamin and multimineral supplementation seem to decrease combined cardiac events in a stable, post-MI population not taking statin therapy at baseline. These unexpected findings are being retested in the ongoing TACT2. Copyright © 2017 The Authors. Published by Elsevier

Alteration of the systemic and microcirculation by a single oral dose of flavan-3-ols.

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Kodai Ingawa

Full Text Available Several systematic reviews have reported that flow mediated dilatation (FMD was significantly increased in subjects after ingestion of chocolate that contains flavan-3-ols; however, the mechanisms responsible for this effect are not clear. In this study, we evaluated the effects of a single oral dose of flavan-3-ols on the systemic circulation and microcirculation in the cremaster muscle using intravital video microscopy in vivo. The cremaster muscle in rats was spread over a plastic chamber and a gastric tube was placed into the stomach. Blood flow in the cremasteric artery was determined using a laser Doppler flowmeter, while blood pressure and heart rate were measured by the tail-cuff method. Red blood cell velocity in arterioles and blood flow in the artery were significantly increased 5 min after the administration of 10 mg/kg flavan-3-ols compared with distilled water treatment. The number of capillaries recruited in the cremaster muscle was also significantly increased 15 min after treatment. Microscopic observation confirmed that increased shear stress on endothelial cells was maintained during the measurement period. The mean arterial blood pressure and heart rate were also significantly elevated soon after administration and returned to baseline before the end of the observation period. Plasma nitrate and nitrite levels, and NO phosphorylation of aortic tissue were significantly increased at 60 min after administration of flavan-3-ols. According to these results, a single oral dose of flavan-3-ols elevates blood pressure and flow transiently, and these effects induce NO production through increased shear stress on endothelial cells.

Combined oral contraceptives: venous thrombosis.

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de Bastos, Marcos; Stegeman, Bernardine H; Rosendaal, Frits R; Van Hylckama Vlieg, Astrid; Helmerhorst, Frans M; Stijnen, Theo; Dekkers, Olaf M

2014-03-03

Combined oral contraceptive (COC) use has been associated with venous thrombosis (VT) (i.e., deep venous thrombosis and pulmonary embolism). The VT risk has been evaluated for many estrogen doses and progestagen types contained in COC but no comprehensive comparison involving commonly used COC is available. To provide a comprehensive overview of the risk of venous thrombosis in women using different combined oral contraceptives. Electronic databases (Pubmed, Embase, Web of Science, Cochrane, CINAHL, Academic Search Premier and ScienceDirect) were searched in 22 April 2013 for eligible studies, without language restrictions. We selected studies including healthy women taking COC with VT as outcome. The primary outcome of interest was a fatal or non-fatal first event of venous thrombosis with the main focus on deep venous thrombosis or pulmonary embolism. Publications with at least 10 events in total were eligible. The network meta-analysis was performed using an extension of frequentist random effects models for mixed multiple treatment comparisons. Unadjusted relative risks with 95% confidence intervals were reported.Two independent reviewers extracted data from selected studies. 3110 publications were retrieved through a search strategy; 25 publications reporting on 26 studies were included. Incidence of venous thrombosis in non-users from two included cohorts was 0.19 and 0.37 per 1 000 person years, in line with previously reported incidences of 0,16 per 1 000 person years. Use of combined oral contraceptives increased the risk of venous thrombosis compared with non-use (relative risk 3.5, 95% confidence interval 2.9 to 4.3). The relative risk of venous thrombosis for combined oral contraceptives with 30-35 μg ethinylestradiol and gestodene, desogestrel, cyproterone acetate, or drospirenone were similar and about 50-80% higher than for combined oral contraceptives with levonorgestrel. A dose related effect of ethinylestradiol was observed for gestodene

Clinical Parameters following Multiple Oral Dose Administration of a Standardized Andrographis paniculata Capsule in Healthy Thai Subjects.

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Suriyo, Tawit; Pholphana, Nanthanit; Ungtrakul, Teerapat; Rangkadilok, Nuchanart; Panomvana, Duangchit; Thiantanawat, Apinya; Pongpun, Wanwisa; Satayavivad, Jutamaad

2017-06-01

Andrographis paniculata has been widely used in Scandinavian and Asian counties for the treatment of the common cold, fever, and noninfectious diarrhea. The present study was carried out to investigate the physiological effects of short-term multiple dose administration of a standardized A. paniculata capsule used for treatment of the common cold and uncomplicated upper respiratory tract infections, including blood pressure, electrocardiogram, blood chemistry, hematological profiles, urinalysis, and blood coagulation in healthy Thai subjects. Twenty healthy subjects (10 males and 10 females) received 12 capsules per day orally of 4.2 g of a standardized A. paniculata crude powder (4 capsules of 1.4 g of A. paniculata , 3 times per day, 8 h intervals) for 3 consecutive days. The results showed that all of the measured clinical parameters were found to be within normal ranges for a healthy person. However, modulation of some parameters was observed after the third day of treatment, for example, inductions of white blood cells and absolute neutrophil count in the blood, a reduction of plasma alkaline phosphatase, and an induction of urine pH. A rapid and transient reduction in blood pressure was observed at 30 min after capsule administration, resulting in a significant reduction of mean systolic blood pressure. There were no serious adverse events observed in the subjects during the treatment period. In conclusion, this study suggests that multiple oral dosing of A. paniculata at the normal therapeutic dose for the common cold and uncomplicated upper respiratory tract infections modulates various clinical parameters within normal ranges for a healthy person. Georg Thieme Verlag KG Stuttgart · New York.

Emerging nalidixic acid and ciprofloxacin resistance in non-typhoidal Salmonella isolated from patients having acute diarrhoeal disease

International Nuclear Information System (INIS)

Panhotra, B.R.; Saxena, A.K.; Al-Arabi, Ali M.

2004-01-01

Non-typhoidal Salmonella are one of the key etiological agents of diarrhoeal disease. The appearence of multiple drung resistance along with resistance to quinolones in this bacterium poses a serious therapeutic problem. We determined the prevalence of nalidixic acid and ciprofloxacin resistance in non-typhodial Salmonella isolated from faecal samples of patients with acute diarroheal disease attending the outpatient and inpatient department of a hospital in Saudi Arabia during the years 1999 to 2002. Non-typhodial Salmonella were isolated from faecal samples. Antimicrobial susceptibility was tested by the disc diffusion test. MICs to nalidixic acid and ciprofloxacinwere determined by the agar dilution method. During the study period , 524 strains of non-typhoidal Salmonella were isolated. Strains belonging to serogroup C1were the commonest (41.4%) followed by serogroups B and D (15.6% and 14.5%, respectively). Resistance to ampicillin was observed in 22.9% and to trimethoprim/sulphamethoxazole in 18.5%of the strains. Nalidixic acid resistance was encounterd in 9.9% and ciprofloxacin esistance in 2.3% of the strains. Resistance to nalidixic acid significantly increased from 0.1% in 1999 to 5.51% in 2002 ( p=0.0007)and ciprofloxacin resistance increased significantly from 0.1% in 1999 to 0.9% in 2002( p=0.0001). MICs to nalidixic acid and ciprofloxacin were determined among 29 nalidixic acid-resistant strains of non-typhoidal salmonella isolated during 2002. The MIC was >256 ug /ml to nalidixic acid and 8 to 16 ug/ml to ciprofloxacin. The increasing rate of antimicrobial resistance encountered among non-tyophoidal Salmonella necessiate the judicious use of these drugs in humans. Moreover, these findings support the concern that the use of quinolones in animal feed may lead to an increasein resistance and should should be restricted. (author)

Evaluation of the Diagnostic Accuracy of a Typhoid IgM Flow Assay for the Diagnosis of Typhoid Fever in Cambodian Children Using a Bayesian Latent Class Model Assuming an Imperfect Gold Standard

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Moore, Catrin E.; Pan-Ngum, Wirichada; Wijedoru, Lalith P. M.; Sona, Soeng; Nga, Tran Vu Thieu; Duy, Pham Thanh; Vinh, Phat Voong; Chheng, Kheng; Kumar, Varun; Emary, Kate; Carter, Michael; White, Lisa; Baker, Stephen; Day, Nicholas P. J.; Parry, Christopher M.

2014-01-01

Rapid diagnostic tests are needed for typhoid fever (TF) diagnosis in febrile children in endemic areas. Five hundred children admitted to the hospital in Cambodia between 2009 and 2010 with documented fever (≥ 38°C) were investigated using blood cultures (BCs), Salmonella Typhi/Paratyphi A real-time polymerase chain reactions (PCRs), and a Typhoid immunoglobulin M flow assay (IgMFA). Test performance was determined by conventional methods and Bayesian latent class modeling. There were 32 cases of TF (10 BC- and PCR-positive cases, 14 BC-positive and PCR-negative cases, and 8 BC-negative and PCR-positive cases). IgMFA sensitivity was 59.4% (95% confidence interval = 41–76), and specificity was 97.8% (95% confidence interval = 96–99). The model estimate sensitivity for BC was 81.0% (95% credible interval = 54–99). The model estimate sensitivity for PCR was 37.8% (95% credible interval = 26–55), with a specificity of 98.2% (95% credible interval = 97–99). The model estimate sensitivity for IgMFA (≥ 2+) was 77.9% (95% credible interval = 58–90), with a specificity of 97.5% (95% credible interval = 95–100). The model estimates of IgMFA sensitivity and specificity were comparable with BCs and better than estimates using conventional analysis. PMID:24218407

SU-F-P-29: Impact of Oral Contrast Agent for Assisting in Outlining Small Intestine On Pelvic IMAT Dose in Patients with Cervical Cancer

Energy Technology Data Exchange (ETDEWEB)

Zhang, R; Bai, W; Fan, X [The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei (China)

2016-06-15

Purpose: As the advanced intensity modulated arc therapy(IMAT) delivery systems becoming a main role of treatment ways, which places even greater demands on delivering accuracy. The impact of oral contrast agent (meglumine diatrizoate) for assisting in outlining the small intestine on pelvic IMAT dose in patients with cervical cancer was investigated. Methods: Ten cervical cancer patients for postoperative radiotherapy underwent CT scans, and the planning target volumes (PTV) and organs at risk (including the small intestine, rectum, bladder, colon and the left and right femoral head) were contoured. The IMAT plans were generated on Oncentra v4.1 planning system for each case, PTV was prescribed to 50.4 Gy in 28 fractions. Then another plan was generated by re-calculating the radiation dose after changing the electron density of the small bowel. The first plan (plan A) was the conventional IMAT plan (with oral contrast agent), and the second one (plan B) specified the electron density of the small bowel (without oral contrast agent). Paired t-test was used to compare the dose distribution between the two plans. Results: The PTV’s D2, D50, D95, V110, conformity index, and homogeneity index of plans A and B were 5610.5 vs. 5611.4 cGy (P=0.175), 5348.5 vs. 5348.0 cGy (P=0.869), 5039 vs. 5042.3 (P=0.518), 6.0% vs. 6.1 %( P=0.886), 0.1269 vs. 0.1271 (P=0.34) and 0.8421 vs. 0.8416 (P=0.598), respectively. The volumes of the small bowel receiving at least 30 Gy (V30) and the minimum dose of 2% volume accepted (D2) for plans A and B were 31.6% vs. 31.9% (P=0.371) and 5067.8 vs. 5085.4 cGy (P=0.377), while rectum V50 of the two plans was 12.4% vs. 12.1% (P=0.489). Conclusion: The oral contrast agent (meglumine diatrizoate) filling the small intestine does not lead to a significant increase in the pelvic IMAT dose in patients with cervical cancer.

Acute Oral Toxicity of Tetrodotoxin in Mice: Determination of Lethal Dose 50 (LD50 and No Observed Adverse Effect Level (NOAEL

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Paula Abal

2017-02-01

Full Text Available Tetrodotoxin (TTX is starting to appear in molluscs from the European waters and is a hazard to seafood consumers. This toxin blocks sodium channels resulting in neuromuscular paralysis and even death. As a part of the risk assessment process leading to a safe seafood level for TTX, oral toxicity data are required. In this study, a 4-level Up and Down Procedure was designed in order to determine for the first time the oral lethal dose 50 (LD50 and the No Observed Adverse Effect Level (NOAEL in mice by using an accurate well-characterized TTX standard.

Macroscopic, pathologic and immunologic investigations of ten patients with carcinoma of oral cavity treated by a single large dose irradiation

International Nuclear Information System (INIS)

Mikuriya, Shuichi; Saito, Tsutomu; Konoeda, Koichi; Igarashi, Seishi; Hirohashi, Hitoshi

1979-01-01

The immunosuppressive effect of radiation has been emphasized. Although the irradiated cancer cells die gradually during the treatment, it is understood that they keep cancer specific antigenecity in that process. Another words, we assume that the immunologic capacity participates in the dying process of cancer cells by radiotherapy. We have been preferring to treat carcinoma by a single large dose irradiation method because this method does not impair the patient's immunologic capacity. On this time, we treated ten patients with carcinoma of oral cavity by this method and could obtain favorable results. 1) Ten patients with carcinoma of oral cavity classified in T1N0M0-T3N0M0 were irradiated by 4 - 10 MeV betatron electron. In seven patients, 2,500 - 3,000 rads were given at once and other three patients were irradiated with fractionated dose of 1,000 rads three times within two weeks (total 3,000 rads per two weeks). 2) Effects of a single large dose irradiation were remarkable and almost all cancer cells in these patients disappeared both macroscopically and pathologically. 3) According to the results of cellular immunity tests, numbers of peripheral lymphocytes, absolute numbers of fractionated T and B cells, and blastoid formation rate of lymphocytes stimulated by PHA in vitro were all increased and values obtained by four kinds of skin tests were also elevated after the radiations. These results indicate that the single large dose irradiation for these patients does not impair the immunologic capacity of the patients. (author)

"In the Fall of the Year We Were Troubled with Some Sickness": Typhoid Fever Deaths, Sherman Institute, 1904.

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Keller, Jean A.

1999-01-01

Driven by his vision of the ideal American Indian vocational boarding school, Harwood Hall, an experienced administrator of Indian boarding schools, lobbied Congress to build Sherman Institute, which opened in Riverside, California, in 1902. A master of public relations, Hall downplayed the illness and deaths of students when typhoid fever swept…

Forecasting typhoid fever incidence in the Cordillera administrative region in the Philippines using seasonal ARIMA models

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Cawiding, Olive R.; Natividad, Gina May R.; Bato, Crisostomo V.; Addawe, Rizavel C.

2017-11-01

The prevalence of typhoid fever in developing countries such as the Philippines calls for a need for accurate forecasting of the disease. This will be of great assistance in strategic disease prevention. This paper presents a development of useful models that predict the behavior of typhoid fever incidence based on the monthly incidence in the provinces of the Cordillera Administrative Region from 2010 to 2015 using univariate time series analysis. The data used was obtained from the Cordillera Office of the Department of Health (DOH-CAR). Seasonal autoregressive moving average (SARIMA) models were used to incorporate the seasonality of the data. A comparison of the results of the obtained models revealed that the SARIMA (1,1,7)(0,0,1)12 with a fixed coefficient at the seventh lag produces the smallest root mean square error (RMSE), mean absolute error (MAE), Akaike Information Criterion (AIC), and Bayesian Information Criterion (BIC). The model suggested that for the year 2016, the number of cases would increase from the months of July to September and have a drop in December. This was then validated using the data collected from January 2016 to December 2016.

Antipyretic efficacy and tolerability of oral ibuprofen, oral dipyrone and intramuscular dipyrone in children: a randomized controlled trial

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Judith Prado

Full Text Available CONTEXT AND OBJECTIVE: Dipyrone is a widely used over-the-counter antipyretic in Latin America, and elsewhere among Latin immigrants. Despite limited evidence, physicians often prescribe oral ibuprofen or intramuscular dipyrone as the most effective antipyretics. Our aim was to compare the antipyretic efficacy and tolerability of a single dose of oral ibuprofen, oral dipyrone or intramuscular dipyrone in febrile children. DESIGN AND SETTING: Randomized, single-blind clinical trial, at San Bartolomé Mother-Child National Teaching Hospital, Lima, Peru. METHODS: Children from six months to six years old with fever (rectal temperature: 38.3 to 39.8° C in the emergency ward between February and June 2003 were eligible. Seventy-five children were randomly assigned to receive a single dose of oral ibuprofen (10 mg/kg, oral dipyrone (15 mg/kg or intramuscular dipyrone (15 mg/kg. The primary outcome was mean temperature reduction after 30, 45, 60, 90 and 120 minutes. Secondary outcomes were fever-associated symptoms and clinical adverse events. RESULTS: Fever decreased by about 0.5° C after 45 minutes and by about 1.0° C after 120 minutes in all three groups. Mean temperatures were similar for the three groups at all times. There was a significant decrease in fever-associated symptoms for all groups. Six patients (four receiving oral dipyrone and two receiving ibuprofen were withdrawn because of vomiting within 20 minutes after first dose of study medication. One patient assigned to oral ibuprofen presented transient urticaria. CONCLUSIONS: Antipyretic efficacy and tolerability were similar for oral ibuprofen, oral dipyrone and intramuscular dipyrone. Oral antipyretics seem more appropriate for feverish children.

Absolute Oral Bioavailability of Creatine Monohydrate in Rats: Debunking a Myth.

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Alraddadi, Eman A; Lillico, Ryan; Vennerstrom, Jonathan L; Lakowski, Ted M; Miller, Donald W

2018-03-08

Creatine is an ergogenic compound used by athletes to enhance performance. Supplementation with creatine monohydrate (CM) has been suggested for musculoskeletal and neurological disorders. Until now, little is known about its pharmacokinetic profile. Our objective was to determine the oral bioavailability of CM and the influence of dose on oral absorption. Rats were dosed orally with low dose (10 mg/kg) or high dose (70 mg/kg) 13 C-labeled CM. Blood samples were removed at various time points. Muscle and brain tissue were collected at the conclusion of the study. Plasma and tissue levels of 13 C-labeled creatine were determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Physiologically based pharmacokinetic (PBPK) models of CM were built using GastroPlus™. These models were used to predict the plasma concentration-time profiles of creatine hydrochloride (CHCL), which has improved aqueous solubility compared to CM. Absolute oral bioavailability for low dose CM was 53% while high dose CM was only 16%. The simulated C max of 70 mg/kg CHCL was around 35 μg/mL compared to 14 μg/mL for CM with a predicted oral bioavailability of 66% with CHCL compared to 17% with CM. Our results suggest that the oral bioavailability of CM is less than complete and subject to dose and that further examination of improved dosage formulations of creatine is warranted.

Oral and transdermal DL-methylphenidate-ethanol interactions in C57BL/6J mice: potentiation of locomotor activity with oral delivery.