Muhe, L.; Oljira, B.; Degefu, H.; Enquesellassie, F.; Weber, M.
OBJECTIVES—To assess the proportion of children with febrile disease who suffer from malaria and to identify clinical signs and symptoms that predict malaria during low and high transmission seasons. STUDY DESIGN—2490 children aged 2 to 59 months presenting to a health centre in rural Ethiopia with fever had their history documented and the following investigations: clinical examination, diagnosis, haemoglobin measurement, and a blood smear for malaria parasites. Clinical...
Finally, there was an indoor residual malaria transmission in a village of high coverage of bed nets and where the principal malaria vector is susceptibility to propoxur and bendiocarb; insecticides currently in use for indoor residual spraying. The continuing indoor transmission of malaria in such village implies the need for new tools to supplement the existing interventions and to reduce indoor malaria transmission.
Full Text Available Malariometric parameters are often primary endpoints of efficacy trials of malaria vaccine candidates. This study aims to describe the epidemiology of malaria prior to the conduct of a series of drug and vaccine trials in a rural area of Burkina Faso.Malaria incidence was prospectively evaluated over one year follow-up among two cohorts of children aged 0-5 years living in the Saponé health district. The parents of 1089 children comprising a passive case detection cohort were encouraged to seek care from the local health clinic at any time their child felt sick. Among this cohort, 555 children were randomly selected for inclusion in an active surveillance sub-cohort evaluated for clinical malaria during twice weekly home visits. Malaria prevalence was evaluated by cross-sectional survey during the low and high transmission seasons.Number of episodes per child ranged from 0 to 6 per year. Cumulative incidence was 67.4% in the passive and 86.2% in the active cohort and was highest among children 0-1 years. Clinical malaria prevalence was 9.8% in the low and 13.0% in the high season (p>0.05. Median days to first malaria episode ranged from 187 (95% CI 180-193 among children 0-1 years to 228 (95% CI 212, 242 among children 4-5 years. The alternative parasite thresholds for the malaria case definition that achieved optimal sensitivity and specificity (70-80% were 3150 parasites/µl in the high and 1350 parasites/µl in the low season.Clinical malaria burden was highest among the youngest age group children, who may represent the most appropriate target population for malaria vaccine candidate development. The pyrogenic threshold of parasitaemia varied markedly by season, suggesting a value for alternative parasitaemia levels in the malaria case defintion. Regional epidemiology of malaria described, Sapone area field centers are positioned for future conduct of malaria vaccine trials.
Biggs, Holly M; Lester, Rebecca; Nadjm, Behzad; Mtove, George; Todd, Jim E; Kinabo, Grace D; Philemon, Rune; Amos, Ben; Morrissey, Anne B; Reyburn, Hugh; Crump, John A
The epidemiology of Salmonella Typhi and invasive nontyphoidal Salmonella (NTS) differs, and prevalence of these pathogens among children in sub-Saharan Africa may vary in relation to malaria transmission intensity. We compared the prevalence of bacteremia among febrile pediatric inpatients aged 2 months to 13 years recruited at sites of high and low malaria endemicity in Tanzania. Enrollment at Teule Hospital, the high malaria transmission site, was from June 2006 through May 2007, and at Kilimanjaro Christian Medical Centre (KCMC), the low malaria transmission site, from September 2007 through August 2008. Automated blood culture, malaria microscopy with Giemsa-stained blood films, and human immunodeficiency virus testing were performed. At Teule, 3639 children were enrolled compared to 467 at KCMC. Smear-positive malaria was detected in 2195 of 3639 (60.3%) children at Teule and 11 of 460 (2.4%) at KCMC (P Salmonella Typhi was isolated from 11 (0.3%) children at Teule and 6 (1.3%) at KCMC (P = .008). With NTS excluded, the prevalence of bacteremia at Teule was 5.0% and at KCMC 4.1% (P = .391). Where malaria transmission was intense, invasive NTS was common and Salmonella Typhi was uncommon, whereas the inverse was observed at a low malaria transmission site. The relationship between these pathogens, the environment, and the host is a compelling area for further research.
the same area. Conclusion The burden of malaria in this birth cohort of HEU infants living in a high-transmission setting and taking daily TS prophylaxis was relatively low. Alternative etiologies of fever should be considered in HEU-infants taking daily TS prophylaxis who present with fever. Trial Registration NCT00993031, registered 8 October, 2009
Kakuru, Abel; Natureeba, Paul; Muhindo, Mary K; Clark, Tamara D; Havlir, Diane V; Cohan, Deborah; Dorsey, Grant; Kamya, Moses R; Ruel, Theodore
HIV-exposed, uninfected (HEU) infants suffer high morbidity and mortality in the first year of life compared to HIV-unexposed, uninfected (HUU) infants, but accurate data on the contribution of malaria are limited. The incidence of febrile illnesses and malaria were evaluated in a birth cohort of HEU infants. Infants were prescribed daily trimethoprim-sulfamethoxazole (TS) prophylaxis from 6 weeks of age until exclusion of HIV-infection after cessation of breastfeeding. Infants were followed for all illnesses using passive surveillance and routine blood smears were done monthly. Malaria was diagnosed as a positive blood smear plus fever. Placental malaria was determined by histopathology, placental blood smear and PCR. Risk factors for time to first episode of malaria were assessed using a Cox proportional hazards model. Malaria incidence among HEU infants aged 6-12 months was compared to that in other cohorts of HEU and HUU infants from the same region. Among 361 HEU infants enrolled, 248 completed 12 months of follow-up resulting in 1562 episodes of febrile illness and 253 episodes of malaria after 305 person-years of follow-up. The incidence of febrile illness was 5.12 episodes per person-year (PPY), ranging from 4.13 episodes PPY in the first 4 months of life to 5.71 episodes PPY between 5 and 12 months of age. The overall malaria incidence was 0.83 episodes per person-year (PPY), increasing from 0.03 episodes PPY in the first 2 months of life to 2.00 episodes PPY between 11 and 12 months of age. There were no episodes of complicated malaria. The prevalence of asymptomatic parasitaemia was 1.2 % (19 of 1568 routine smears positive). Infants born to mothers with parasites detected from placental blood smears were at higher risk of malaria (hazard ratio = 4.51, P malaria compared to HUU infants in other cohort studies from the same area. The burden of malaria in this birth cohort of HEU infants living in a high-transmission setting and taking daily TS
Barffour, Maxwell A; Schulze, Kerry J; Coles, Christian L; Chileshe, Justin; Kalungwana, Ng'andwe; Arguello, Margia; Siamusantu, Ward; Moss, William J; West, Keith P; Palmer, Amanda C
Background: Higher iron stores, defined by serum ferritin (SF) concentration, may increase malaria risk. Objective: We evaluated the association between SF assessed during low malaria season and the risk of malaria during high malaria season, controlling for inflammation. Methods: Data for this prospective study were collected from children aged 4-8 y ( n = 745) participating in a biofortified maize efficacy trial in rural Zambia. All malaria cases were treated at baseline (September 2012). We used baseline SF and malaria status indicated by positive microscopy at endline (March 2013) to define exposure and outcome, respectively. Iron status was defined as deficient (corrected or uncorrected SF malaria in the high transmission seasons (endline) as a function of iron status assessed in the low malaria seasons (baseline). Results: We observed an age-dependent, positive dose-response association between ferritin in the low malaria season and malaria incidence during the high malaria season in younger children. In children aged malaria risk in the moderate iron status [incidence rate ratio (IRR) with SF: 1.56; 95% CI: 0.64, 3.86; IRR with inflammation-corrected SF: 1.92; 95% CI: 0.75, 4.93] and high iron status (IRR with SF: 2.66; 95% CI: 1.10, 6.43; or IRR with corrected SF: 2.93; 95% CI: 1.17, 7.33) categories compared with the deficient iron status category. The relative increase in malaria risk for children with high iron status was statistically significant only among those with a concurrently normal serum soluble transferrin receptor concentration (malaria risk. Our findings underscore the need to integrate iron interventions with malaria control programs. This trial was registered at clinicaltrials.gov as NCT01695148. © 2017 American Society for Nutrition.
Full Text Available Malaria congenital infection constitutes a major risk in malaria endemic areas. In this study, we report the prevalence of transplacental malaria in Burkina Faso. In labour and delivery units, thick and thin blood films were made from maternal, placental, and umbilical cord blood to determine malaria infection. A total of 1,309 mother/baby pairs were recruited. Eighteen cord blood samples (1.4% contained malaria parasites (Plasmodium falciparum. Out of the 369 (28.2% women with peripheral positive parasitemia, 211 (57.2% had placental malaria and 14 (3.8% had malaria parasites in their umbilical cord blood. The umbilical cord parasitemia levels were statistically associated with the presence of maternal peripheral parasitemia (OR=9.24, ≪0.001, placental parasitemia (OR=10.74, ≪0.001, high-density peripheral parasitemia (OR=9.62, ≪0.001, and high-density placental parasitemia (OR=4.91, =0.03. In Burkina Faso, the mother-to-child transmission rate of malaria appears to be low.
Ouédraogo, Alphonse; Tiono, Alfred B.; Diarra, Amidou; Bougouma, Edith C. Christiane; Nébié, Issa; Konaté, Amadou T.; Sirima, Sodiomon B.
Malaria congenital infection constitutes a major risk in malaria endemic areas. In this study, we report the prevalence of transplacental malaria in Burkina Faso. In labour and delivery units, thick and thin blood films were made from maternal, placental, and umbilical cord blood to determine malaria infection. A total of 1,309 mother/baby pairs were recruited. Eighteen cord blood samples (1.4%) contained malaria parasites (Plasmodium falciparum). Out of the 369 (28.2%) women with peripheral positive parasitemia, 211 (57.2%) had placental malaria and 14 (3.8%) had malaria parasites in their umbilical cord blood. The umbilical cord parasitemia levels were statistically associated with the presence of maternal peripheral parasitemia (OR = 9.24, P ≪ 0.001), placental parasitemia (OR = 10.74, P ≪ 0.001), high-density peripheral parasitemia (OR = 9.62, P ≪ 0.001), and high-density placental parasitemia (OR = 4.91, P = 0.03). In Burkina Faso, the mother-to-child transmission rate of malaria appears to be low. PMID:22174725
Kigozi, Ruth; Baxi, Sanjiv M; Gasasira, Anne; Sserwanga, Asadu; Kakeeto, Stella; Nasr, Sussann; Rubahika, Denis; Dissanayake, Gunawardena; Kamya, Moses R; Filler, Scott; Dorsey, Grant
Recently the use of indoor residual spraying of insecticide (IRS) has greatly increased in Africa; however, limited data exist on the quantitative impacts of IRS on health outcomes in highly malaria endemic areas. Routine data were collected on more than 90,000 patient visits at a single health facility over a 56 month period covering five rounds of IRS using three different insecticides. Temporal associations between the timing of IRS and the probability of a patient referred for microscopy having laboratory confirmed malaria were estimated controlling for seasonality and age. Considering patients less than five years of age there was a modest decrease in the odds of malaria following the 1(st) round of IRS using DDT (OR = 0.76, p<0.001) and the 2(nd) round using alpha-cypermethrin (OR = 0.83, p = 0.002). Following rounds 3-5 using bendiocarb there was a much greater decrease in the odds of malaria (ORs 0.34, 0.16, 0.17 respectively, p<0.001 for all comparisons). Overall, the impact of IRS was less pronounced among patients 5 years or older. IRS was associated with a reduction in malaria morbidity in an area of high transmission intensity in Uganda and the benefits appeared to be greatest after switching to a carbamate class of insecticide.
Full Text Available Recently the use of indoor residual spraying of insecticide (IRS has greatly increased in Africa; however, limited data exist on the quantitative impacts of IRS on health outcomes in highly malaria endemic areas.Routine data were collected on more than 90,000 patient visits at a single health facility over a 56 month period covering five rounds of IRS using three different insecticides. Temporal associations between the timing of IRS and the probability of a patient referred for microscopy having laboratory confirmed malaria were estimated controlling for seasonality and age. Considering patients less than five years of age there was a modest decrease in the odds of malaria following the 1(st round of IRS using DDT (OR = 0.76, p<0.001 and the 2(nd round using alpha-cypermethrin (OR = 0.83, p = 0.002. Following rounds 3-5 using bendiocarb there was a much greater decrease in the odds of malaria (ORs 0.34, 0.16, 0.17 respectively, p<0.001 for all comparisons. Overall, the impact of IRS was less pronounced among patients 5 years or older.IRS was associated with a reduction in malaria morbidity in an area of high transmission intensity in Uganda and the benefits appeared to be greatest after switching to a carbamate class of insecticide.
Yamana, Teresa K.; Qiu, Xin; Eltahir, Elfatih A. B.
Malaria transmission is a complex system and in many parts of the world is closely related to climate conditions. However, studies on environmental determinants of malaria generally consider only concurrent climate conditions and ignore the historical or initial conditions of the system. Here, we demonstrate the concept of hysteresis in malaria transmission, defined as non-uniqueness of the relationship between malaria prevalence and concurrent climate conditions. We show the dependence of simulated malaria transmission on initial prevalence and the initial level of human immunity in the population. Using realistic time series of environmental variables, we quantify the effect of hysteresis in a modeled population. In a set of numerical experiments using HYDREMATS, a field-tested mechanistic model of malaria transmission, the simulated maximum malaria prevalence depends on both the initial prevalence and the initial level of human immunity in the population. We found the effects of initial conditions to be of comparable magnitude to the effects of interannual variability in environmental conditions in determining malaria prevalence. The memory associated with this hysteresis effect is longer in high transmission settings than in low transmission settings. Our results show that efforts to simulate and forecast malaria transmission must consider the exposure history of a location as well as the concurrent environmental drivers.
Poespoprodjo, J R; Fobia, W; Kenangalem, E; Hasanuddin, A; Sugiarto, P; Tjitra, E; Anstey, N M; Price, R N
The epidemiology of congenital malaria was investigated in a hospital-based malaria surveillance study in Papua, Indonesia. From April 2005 to January 2010, 4878 delivering women and their newborns underwent prospective clinical review and malaria screening by peripheral blood microscopy. Congenital malaria occurred in 8 per 1000 (38/4884) live births, with Plasmodium falciparum accounting for 76.3% (29) and P. vivax for 15.8% (6) of infections. Maternal malaria at delivery (adjusted odds ratio [AOR], 9.5; 95% confidence interval [CI], 4.2-21.5; P < .001), age ≤ 16 years (AOR, 4; 95% CI, 1.4-12.1; P = .011), and prior malaria during pregnancy (AOR, 2.2; 95% CI, 1.1-4.4, P = .022) were independent risk factors for vertical transmission. Of 29 mothers and neonates with contemporaneous peripheral parasitemia, 17% (5) had discordant parasite species, suggesting possible antenatal malaria transmission. Newborns with malaria were at significantly greater risk of low birth weight (AOR, 2.8; 95% CI, 1.2-6.6; P = .002). Following introduction of dihydroartemisinin-piperaquine for uncomplicated malaria in the second and third trimesters of pregnancy, congenital malaria incidence fell from 3.2% to 0.2% (odds ratio, 0.07; 95% CI, .03-.15; P < .001). Congenital malaria is an important cause of neonatal morbidity in this region co-endemic for P. falciparum and P. vivax malaria. The introduction of artemisinin-combination therapy was associated with a significant risk reduction in the vertical transmission of malaria.
Kesteman, Thomas; Rafalimanantsoa, Solofoniaina A; Razafimandimby, Harimahefa; Rasamimanana, Heriniaina H; Raharimanga, Vaomalala; Ramarosandratana, Benjamin; Ratsimbasoa, Arsene; Ratovonjato, Jocelyn; Elissa, Nohal; Randrianasolo, Laurence; Finlay, Alyssa; Rogier, Christophe; Randrianarivelojosia, Milijaona
pyrethroids. Two years after distribution, nearly all LLINs collected showed a loss of physical integrity and insecticide activity, Increased rainfall, decreasing use and reduced insecticide activity of long-lasting insecticide-treated nets, and drug shortages may have been responsible for, or contributed to, the outbreak observed in South-Eastern Madagascar in 2011-2012. Control interventions for malaria elimination must be sustained at the risk of triggering harmful epidemics, even in zones of high transmission.
Lal, Sham; Ndyomugenyi, Richard; Magnussen, Pascal; Hansen, Kristian S; Alexander, Neal D; Paintain, Lucy; Chandramohan, Daniel; Clarke, Siân E
Malaria-endemic countries have implemented community health worker (CHW) programs to provide malaria diagnosis and treatment to populations living beyond the reach of health systems. However, there is limited evidence describing the referral practices of CHWs. We examined the impact of malaria rapid diagnostic tests (mRDTs) on CHW referral in two cluster-randomized trials, one conducted in a moderate-to-high malaria transmission setting and one in a low-transmission setting in Uganda, between January 2010 and July 2012. All CHWs were trained to prescribe artemisinin-based combination therapy (ACT) for malaria and recognize signs and symptoms for referral to health centers. CHWs in the control arm used a presumptive diagnosis for malaria based on clinical symptoms, whereas intervention arm CHWs used mRDTs. CHWs recorded ACT prescriptions, mRDT results, and referral in patient registers. An intention-to-treat analysis was undertaken using multivariable logistic regression. Referral was more frequent in the intervention arm versus the control arm (moderate-to-high transmission, P < 0.001; low transmission, P < 0.001). Despite this increase, referral advice was not always given when ACTs or prereferral rectal artesunate were prescribed: 14% prescribed rectal artesunate in the moderate-to-high setting were not referred. In addition, CHWs considered factors alongside mRDTs when referring. Child visits during the weekends or the rainy season were less likely to be referred, whereas visits to CHWs more distant from health centers were more likely to be referred (low transmission only). CHWs using mRDTs and ACTs increased referral compared with CHWs using a presumptive diagnosis. To address these concerns, referral training should be emphasized in CHW programs as they are scaled-up. © The American Society of Tropical Medicine and Hygiene.
Abel Kakuru; Paul Natureeba; Muhindo, Mary K.; Clark, Tamara D.; Havlir, Diane V.; Deborah Cohan; Grant Dorsey; Kamya, Moses R; Theodore Ruel
Abstract Background HIV-exposed, uninfected (HEU) infants suffer high morbidity and mortality in the first year of life compared to HIV-unexposed, uninfected (HUU) infants, but accurate data on the contribution of malaria are limited. Methods The incidence of febrile illnesses and malaria were evaluated in a birth cohort of HEU infants. Infants were prescribed daily trimethoprim–sulfamethoxazole (TS) prophylaxis from 6 weeks of age until exclusion of HIV-infection after cessation of breastfee...
Full Text Available Abstract Malaria in pregnancy is one of the major causes of maternal morbidity and adverse birth outcomes. In high transmission areas, its prevention has recently changed, moving from a weekly or bimonthly chemoprophylaxis to intermittent preventive treatment (IPTp. IPTp consists in the administration of a single curative dose of an efficacious anti-malarial drug at least twice during pregnancy – regardless of whether the woman is infected or not. The drug is administered under supervision during antenatal care visits. Sulphadoxine-pyrimethamine (SP is the drug currently recommended by the WHO. While SP-IPTp seems an adequate strategy, there are many issues still to be explored to optimize it. This paper reviewed data on IPTp efficacy and discussed how to improve it. In particular, the determination of both the optimal number of doses and time of administration of the drug is essential, and this has not yet been done. As both foetal growth and deleterious effects of malaria are maximum in late pregnancy women should particularly be protected during this period. Monitoring of IPTp efficacy should be applied to all women, and not only to primi- and secondigravidae, as it has not been definitively established that multigravidae are not at risk for malaria morbidity and mortality. In HIV-positive women, there is an urgent need for specific information on drug administration patterns (need for higher doses, possible interference with sulpha-based prophylaxis of opportunistic infections. Because of the growing level of resistance of parasites to SP, alternative drugs for IPTp are urgently needed. Mefloquine is presently one of the most attractive options because of its long half life, high efficacy in sub-Saharan Africa and safety during pregnancy. Also, efforts should be made to increase IPTp coverage by improving the practices of health care workers, the motivation of women and their perception of malaria complications in pregnancy. Because IPTp
Full Text Available Abstract Background Malaria management policies currently recommend that the treatment should only be administered after laboratory confirmation. Where microscopy is not available, rapid diagnostic tests (RDTs are the usual alternative. Conclusive evidence is still lacking on the safety of a test-based strategy for children. Moreover, no formal attempt has been made to estimate RDTs accuracy on malaria-attributable fever. This study aims at estimating the accuracy of a RDT for the diagnosis of both malaria infection and malaria - attributable fever, in a region of Burkina Faso with a typically seasonal malaria transmission pattern. Methods Cross-sectional study. Subjects: all patients aged > 6 months consulting during the study periods. Gold standard for the diagnosis of malaria infection was microscopy. Gold standard for malaria-attributable fever was the number of fevers attributable to malaria, estimated by comparing parasite densities of febrile versus non-febrile subjects. Exclusion criteria: severe clinical condition needing urgent care. Results In the dry season, 186/852 patients with fever (22% and 213/1,382 patients without fever (15% had a Plasmodium falciparum infection. In the rainy season, this proportion was 841/1,317 (64% and 623/1,669 (37%, respectively. The attributable fraction of fever to malaria was 11% and 69%, respectively. The RDT was positive in 113/400 (28.3% fever cases in the dry season, and in 443/650 (68.2% in the rainy season. In the dry season, the RDT sensitivity and specificity for malaria infection were 86% and 90% respectively. In the rainy season they were 94% and 78% respectively. In the dry season, the RDT sensitivity and specificity for malaria-attributable fever were 94% and 75%, the positive predictive value (PPV was 9% and the negative predictive value (NPV was 99.8%. In the rainy season the test sensitivity for malaria-attributable fever was 97% and specificity was 55%. The PPV ranged from 38% for
Full Text Available Abstract Background HIV infection increases the risk of placental malaria, which is associated with poor maternal and infant outcomes. Recommendations in Uganda are for HIV-infected pregnant women to receive daily trimethoprim-sulphamethoxazole (TS and HIV-uninfected women to receive intermittent sulphadoxine-pyrimethamine (SP. TS decreases the risk of malaria in HIV-infected adults and children but has not been evaluated among pregnant women. Methods This was a cross sectional study comparing the prevalence of placental malaria between HIV-infected women prescribed TS and HIV-uninfected women prescribed intermittent preventive therapy with sulphadoxine-pyrimethamine (IPT-SP in a high malaria transmission area in Uganda. Placental blood was evaluated for malaria using smear and PCR. Results Placentas were obtained from 150 HIV-infected women on TS and 336 HIV-uninfected women on IPT-SP. The proportion of HIV-infected and HIV-uninfected women with placental malaria was 19% vs. 26% for those positive by PCR and 6% vs. 9% for those positive by smear, respectively. Among all infants, smear+ placental malaria was most predictive of low birth weight (LBW. Primigravidae were at higher risk than multigravidae of having placental malaria among HIV-uninfected, but not HIV-infected, women. Adjusting for gravidity, age, and season at the time of delivery, HIV-infected women on TS were not at increased risk for placental malaria compared to HIV-uninfected women on IPT-SP, regardless of the definition used. Conclusion Prevalence of placental malaria was similar in HIV-infected women on TS and HIV-uninfected women on IPT-SP. Nonetheless, while nearly all of the women in this study were prescribed anti-folates, the overall risk of placental malaria and LBW was unacceptably high. The population attributable risk of placental malaria on LBW was substantial, suggesting that future interventions that further diminish the risk of placental malaria may have a
Antonio-Nkondjio, Christophe; Defo-Talom, Blaise; Tagne-Fotso, Romuald; Tene-Fossog, Billy; Ndo, Cyrille; Lehman, Leopold Gustave; Tchuinkam, Timoléon; Kengne, Pierre; Awono-Ambene, Parfait
Rapid demographic growth in Douala city, Cameroon, has resulted in profound ecological and environmental changes. Although demographic changes can affect anopheline mosquito breeding sites, there is a lack of understanding about the epidemiological impact that such changes might have on vector ecology and malaria transmission. A 12-month entomological study was conducted in a highly populated district of Douala called Ndogpassi. Adult mosquitoes were collected using two methods: 1) human landing catches (HLC); and 2) Centers for Disease Control and Prevention (CDC) light traps; these methods were used twice monthly from January to December 2011. Mosquito genus and species were identified with morphological and molecular diagnostic tools. The sampling efficiency of the CDC light trap and HLC were compared. Anopheles gambiae infection with Plasmodium falciparum was detected using ELISA. Susceptibility to DDT, permethrin, and deltamethrin insecticides were also determined. A total of 6923 mosquitoes were collected by HLC (5198) and CDC light traps (1725). There was no equivalence in the sampling efficiency between light traps and human landing catches (P > 0.01). With 51% of the total, Culex was the most common, followed by Anopheles (26.14%), Mansonia (22.7%) and Aedes (0.1%). An. gambiae ss (M form) comprised ~98% of the total anophelines collected. An. gambiae had a biting rate of 0.25 to 49.25 bites per human per night, and was the only species found to be infected with P. falciparum. A P. falciparum infection rate of 0.5% was calculated (based on enzyme-linked immunosorbent assays using the circumsporozoite surface protein). The entomological inoculation rate was estimated at 31 infective bites per annum. Insecticide susceptibility tests on An. gambiae females revealed a mortality rate of 33%, 76% and 98% for DDT, permethrin and deltamethrin, respectively. The West African kdr allele (L1014F) was detected in 38 of the 61 An. gambiae analyzed (62.3%). The present
Full Text Available Abstract Background Rapid demographic growth in Douala city, Cameroon, has resulted in profound ecological and environmental changes. Although demographic changes can affect anopheline mosquito breeding sites, there is a lack of understanding about the epidemiological impact that such changes might have on vector ecology and malaria transmission. Methods A 12-month entomological study was conducted in a highly populated district of Douala called Ndogpassi. Adult mosquitoes were collected using two methods: 1 human landing catches (HLC; and 2 Centers for Disease Control and Prevention (CDC light traps; these methods were used twice monthly from January to December 2011. Mosquito genus and species were identified with morphological and molecular diagnostic tools. The sampling efficiency of the CDC light trap and HLC were compared. Anopheles gambiae infection with Plasmodium falciparum was detected using ELISA. Susceptibility to DDT, permethrin, and deltamethrin insecticides were also determined. Results A total of 6923 mosquitoes were collected by HLC (5198 and CDC light traps (1725. There was no equivalence in the sampling efficiency between light traps and human landing catches (P > 0.01. With 51% of the total, Culex was the most common, followed by Anopheles (26.14%, Mansonia (22.7% and Aedes (0.1%. An. gambiae ss (M form comprised ~98% of the total anophelines collected. An. gambiae had a biting rate of 0.25 to 49.25 bites per human per night, and was the only species found to be infected with P. falciparum. A P. falciparum infection rate of 0.5% was calculated (based on enzyme-linked immunosorbent assays using the circumsporozoite surface protein. The entomological inoculation rate was estimated at 31 infective bites per annum. Insecticide susceptibility tests on An. gambiae females revealed a mortality rate of 33%, 76% and 98% for DDT, permethrin and deltamethrin, respectively. The West African kdr allele (L1014F was detected in 38 of
Weiss, Daniel J; Bhatt, Samir; Mappin, Bonnie; Van Boeckel, Thomas P; Smith, David L; Hay, Simon I; Gething, Peter W
Temperature suitability for malaria transmission is a useful predictor variable for spatial models of malaria infection prevalence. Existing continental or global models, however, are synoptic in nature and so do not characterize inter-annual variability in seasonal patterns of temperature suitability, reducing their utility for predicting malaria risk. A malaria Temperature Suitability Index (TSI) was created by first modeling minimum and maximum air temperature with an eight-day temporal resolution from gap-filled MODerate Resolution Imaging Spectroradiometer (MODIS) daytime and night-time Land Surface Temperature (LST) datasets. An improved version of an existing biological model for malaria temperature suitability was then applied to the resulting temperature information for a 13-year data series. The mechanism underlying this biological model is simulation of emergent mosquito cohorts on a two-hour time-step and tracking of each cohort throughout its life to quantify the impact air temperature has on both mosquito survival and sporozoite development. The results of this research consist of 154 monthly raster surfaces that characterize spatiotemporal patterns in TSI across Africa from April 2000 through December 2012 at a 1 km spatial resolution. Generalized TSI patterns were as expected, with consistently high values in equatorial rain forests, seasonally variable values in tropical savannas (wet and dry) and montane areas, and low values in arid, subtropical regions. Comparisons with synoptic approaches demonstrated the additional information available within the dynamic TSI dataset that is lost in equivalent synoptic products derived from long-term monthly averages. The dynamic TSI dataset presented here provides a new product with far richer spatial and temporal information than any other presently available for Africa. As spatiotemporal malaria modeling endeavors evolve, dynamic predictor variables such as the malaria temperature suitability data developed
Michelle J. Boyle
Full Text Available Cytokine-producing CD4 T cells have important roles in immunity against Plasmodium falciparum (Pf malaria. However, the factors influencing functional differentiation of Pf-specific CD4 T cells in naturally exposed children are not well understood. Moreover, it is not known which CD4 T-cell cytokine-producing subsets are most critical for protection. We measured Pf-specific IFNγ-, IL10-, and TNFα-producing CD4 T-cell responses by multi-parametric flow cytometry in 265 children aged 6 months to 10 years enrolled in a longitudinal observational cohort in a high malaria transmission site in Uganda. We found that both age and parasite burden were independently associated with cytokine production by CD4 T cells. IL10 production by IFNγ+ CD4 T cells was higher in younger children and in those with high-parasite burden during recent infection. To investigate the role of CD4 T cells in immunity to malaria, we measured associations of Pf-specific CD4 cytokine-producing cells with the prospective risk of Pf infection and clinical malaria, adjusting for household exposure to Pf-infected mosquitos. Overall, the prospective risk of infection was not associated with the total frequency of Pf-specific CD4 T cells, nor of any cytokine-producing CD4 subset. However, the frequency of CD4 cells producing IL10 but not inflammatory cytokines (IFNγ and TNFα was associated with a decreased risk of clinical malaria once infected. These data suggest that functional polarization of the CD4 T-cell response may modulate the clinical manifestations of malaria and play a role in naturally acquired immunity.
Full Text Available The Kilombero Malaria Project (KMP attemps to define opperationally useful indicators of levels of transmission and disease and health system relevant monitoring indicators to evaluate the impact of disease control at the community or health facility level. The KMP is longitudinal community based study (N = 1024 in rural Southern Tanzania, investigating risk factors for malarial morbidity and developing household based malaria control strategies. Biweekly morbidity and bimonthly serological, parasitological and drug consumption surveys are carried out in all study households. Mosquito densities are measured biweekly in 50 sentinel houses by timed light traps. Determinants of transmission and indicators of exposure were not strongly aggregated within households. Subjective morbidity (recalled fever, objective morbidity (elevated body temperature and high parasitaemia and chloroquine consumption were strongly aggregated within a few households. Nested analysis of anti-NANP40 antibody suggest that only approximately 30% of the titer variance can explained by household clustering and that the largest proportion of antibody titer variability must be explained by non-measured behavioral determinants relating to an individual's level of exposure within a household. Indicators for evaluation and monitoring and outcome measures are described within the context of health service management to describe control measure output in terms of community effectiveness.
Teklemariam, Michael; Assefa, Ashenafi; Kassa, Moges; Mohammed, Hussien; Mamo, Hassen
Malaria, particularly due to Plasmodium falciparum, remains a major public health threat in Ethiopia. Artemether-lumefantine (AL) has been the first-line antimalarial drug against uncomplicated P. falciparum malaria in the country since 2004. Regular monitoring of antimalarial drugs is recommended by the World Health Organization (WHO) to help early detection of drug resistant strains of the parasite and contain their rapid spread. The objective of this study was to assess the therapeutic efficacy of AL in a high-transmission setting in Ethiopia. The study site was Setit Humera, northwest Ethiopia. Single-arm prospective study of a 28-day follow-up was conducted from October 2014 to January 2015 according to the revised WHO 2009 drug efficacy study protocol. Study end-points were classified into primary end-point and secondary end-point. While the primary end-point was the day-28 adequate clinical and parasitological response the secondary end-points were clinical and parasitological evaluations (parasite, fever and gametocyte clearance rate, incidence of drug adverse events) and the relative increment in hemoglobin (Hb) level from baseline to day (D) 14 and D28. A total of 92 patients were enrolled and 79 had completed the 28-day follow-up period. The overall cure rate was 98.8% with 95% confidence interval of 0.915-0.998 without polymerase chain reaction correction. The parasite clearance rate was high with fast resolution of clinical symptoms; 100% of the study participants cleared parasitaemia and fever on D3. Gametocyte carriage was reduced from 7% on D0 to 1% on D3 and complete clearance was achieved on D14. Mean Hb concentration significantly increased on D28 compared to that on D14. There was no serious adverse event. AL was efficacious and safe in a high-transmission setting for treatment of uncomplicated falciparum malaria.
Gemperli, Armin; Sogoba, Nafomon; Fondjo, Etienne; Mabaso, Musawenkosi; Bagayoko, Magaran; Briët, Olivier J T; Anderegg, Dan; Liebe, Jens; Smith, Tom; Vounatsou, Penelope
We have produced maps of Plasmodium falciparum malaria transmission in West and Central Africa using the Mapping Malaria Risk in Africa (MARA) database comprising all malaria prevalence surveys in these regions that could be geolocated. The 1846 malaria surveys analysed were carried out during different seasons, and were reported using different age groupings of the human population. To allow comparison between these, we used the Garki malaria transmission model to convert the malaria prevalence data at each of the 976 locations sampled to a single estimate of transmission intensity E, making use of a seasonality model based on Normalized Difference Vegetation Index (NDVI), temperature and rainfall data. We fitted a Bayesian geostatistical model to E using further environmental covariates and applied Bayesian kriging to obtain smooth maps of E and hence of age-specific prevalence. The product is the first detailed empirical map of variations in malaria transmission intensity that includes Central Africa. It has been validated by expert opinion and in general confirms known patterns of malaria transmission, providing a baseline against which interventions such as insecticide-treated nets programmes and trends in drug resistance can be evaluated. There is considerable geographical variation in the precision of the model estimates and, in some parts of West Africa, the predictions differ substantially from those of other risk maps. The consequent uncertainties indicate zones where further survey data are needed most urgently. Malaria risk maps based on compilations of heterogeneous survey data are highly sensitive to the analytical methodology.
Effectiveness of intermittent preventive treatment with sulfadoxine-pyrimethamine during pregnancy on placental malaria, maternal anaemia and birthweight in areas with high and low malaria transmission intensity in Tanzania.
Mosha, Dominic; Chilongola, Jaffu; Ndeserua, Rabi; Mwingira, Felista; Genton, Blaise
To assess the effectiveness of IPTp in two areas with different malaria transmission intensities. Prospective observational study recruiting pregnant women in two health facilities in areas with high and low malaria transmission intensities. A structured questionnaire was used for interview. Maternal clinic cards and medical logs were assessed to determine drug intake. Placental parasitaemia was screened using both light microscopy and real-time quantitative PCR. Of 350 pregnant women were recruited and screened for placental parasitaemia, 175 from each area. Prevalence of placental parasitaemia was 16.6% (CI 11.4-22.9) in the high transmission area and 2.3% (CI 0.6-5.7) in the low transmission area. Being primigravida and residing in a high transmission area were significant risk factors for placental malaria (OR 2.4; CI 1.1-5.0; P = 0.025) and (OR 9.4; CI 3.2-27.7; P < 0.001), respectively. IPTp was associated with a lower risk of placental malaria (OR 0.3; CI 0.1-1.0; P = 0.044); the effect was more pronounced in the high transmission area (OR 0.2; CI 0.06-0.7; P = 0.015) than in the low transmission area (OR 0.4; CI 0.04-4.5; P = 0.478). IPTp use was not associated with reduced risk of maternal anaemia or low birthweight, regardless of transmission intensity. The number needed to treat (NNT) was four (CI 2-6) women in the high transmission area and 33 (20-50) in the low transmission area to prevent one case of placental malaria. IPTp may have an effect on lowering the risk of placental malaria in areas of high transmission, but this effect did not translate into a benefit on risks of maternal anaemia or low birthweight. The NNT needs to be considered, and weighted against that of other protective measures, eventually targeting areas which are above a certain threshold of malaria transmission to maximise the benefit. © 2014 John Wiley & Sons Ltd.
Full Text Available Malaria is a vector-borne disease that is considered to be one of the most serious public health problems due to its high global mortality and morbidity rates. Although multiple strategies for controlling malaria have been used, many have had limited impact due to the appearance and rapid dissemination of mosquito resistance to insecticides, parasite resistance to multiple antimalarial drug, and the lack of sustainability. Individuals in endemic areas that have been permanently exposed to the parasite develop specific immune responses capable of diminishing parasite burden and the clinical manifestations of the disease, including blocking of parasite transmission to the mosquito vector. This is referred to as transmission blocking (TB immunity (TBI and is mediated by specific antibodies and other factors ingested during the blood meal that inhibit parasite development in the mosquito. These antibodies recognize proteins expressed on either gametocytes or parasite stages that develop in the mosquito midgut and are considered to be potential malaria vaccine candidates. Although these candidates, collectively called TB vaccines (TBV, would not directly stop malaria from infecting individuals, but would stop transmission from infected person to non-infected person. Here, we review the progress that has been achieved in TBI studies and the development of TBV and we highlight their potential usefulness in areas of low endemicity such as Latin America.
Arévalo-Herrera, Myriam; Solarte, Yezid; Marin, Catherin; Santos, Mariana; Castellanos, Jenniffer; Beier, John C; Valencia, Sócrates Herrera
Malaria is a vector-borne disease that is considered to be one of the most serious public health problems due to its high global mortality and morbidity rates. Although multiple strategies for controlling malaria have been used, many have had limited impact due to the appearance and rapid dissemination of mosquito resistance to insecticides, parasite resistance to multiple antimalarial drug, and the lack of sustainability. Individuals in endemic areas that have been permanently exposed to the parasite develop specific immune responses capable of diminishing parasite burden and the clinical manifestations of the disease, including blocking of parasite transmission to the mosquito vector. This is referred to as transmission blocking (TB) immunity (TBI) and is mediated by specific antibodies and other factors ingested during the blood meal that inhibit parasite development in the mosquito. These antibodies recognize proteins expressed on either gametocytes or parasite stages that develop in the mosquito midgut and are considered to be potential malaria vaccine candidates. Although these candidates, collectively called TB vaccines (TBV), would not directly stop malaria from infecting individuals, but would stop transmission from infected person to non-infected person. Here, we review the progress that has been achieved in TBI studies and the development of TBV and we highlight their potential usefulness in areas of low endemicity such as Latin America. PMID:21881775
Rossati, Antonella; Bargiacchi, Olivia; Kroumova, Vesselina; Zaramella, Marco; Caputo, Annamaria; Garavelli, Pietro Luigi
Malaria, the most common parasitic disease in the world, is transmitted to the human host by mosquitoes of the genus Anopheles. The transmission of malaria requires the interaction between the host, the vector and the parasite.The four species of parasites responsible for human malaria are Plasmodium falciparum, Plasmodium ovale, Plasmodium malariae and Plasmodium vivax. Occasionally humans can be infected by several simian species, like Plasmodium knowlesi, recognised as a major cause of human malaria in South-East Asia since 2004. While P. falciparum is responsible for most malaria cases, about 8% of estimated cases globally are caused by P. vivax. The different Plasmodia are not uniformly distributed although there are areas of species overlap. The life cycle of all species of human malaria parasites is characterised by an exogenous sexual phase in which multiplication occurs in several species of Anopheles mosquitoes, and an endogenous asexual phase in the vertebrate host. The time span required for mature oocyst development in the salivary glands is quite variable (7-30 days), characteristic of each species and influenced by ambient temperature. The vector Anopheles includes 465 formally recognised species. Approximately 70 of these species have the capacity to transmit Plasmodium spp. to humans and 41 are considered as dominant vector capable of transmitting malaria. The intensity of transmission is dependent on the vectorial capacity and competence of local mosquitoes. An efficient system for malaria transmission needs strong interaction between humans, the ecosystem and infected vectors. Global warming induced by human activities has increased the risk of vector-borne diseases such as malaria. Recent decades have witnessed changes in the ecosystem and climate without precedent in human history although the emphasis in the role of temperature on the epidemiology of malaria has given way to predisposing conditions such as ecosystem changes, political
Full Text Available The presumptive approach of confirming malaria in health facilities leads to over-diagnosis of malaria, over use of anti-malaria drugs and the risk of drug resistance development. WHO recommends parasitological confirmation before treatment with artemisinin-based combination therapy (ACT in all suspected malaria patients. The use of malaria rapid diagnostic tests (mRDTs would make it possible for prescribers to diagnose malaria at point-of-care and better target the use of antimalarials. Therefore, a cost-effectiveness analysis was performed on the introduction of mRDTs for management of malaria in under-five children in a high transmission area in Ghana where presumptive diagnosis was the norm in public health centres.A cluster-randomised controlled trial where thirty-two health centres were randomised into test-based diagnosis of malaria using mRDTs (intervention or clinical judgement (control was used to measure the effect of mRDTs on appropriate treatment: 'a child with a positive reference diagnosis prescribed a course of ACT or a child with a negative reference diagnosis not given an ACT'. Cost data was collected from five purposively selected health centres and used to estimate the health sector costs of performing an mRDT and treat children for malaria and other common febrile illnesses. Costs of training healthcare personnel and supervision in the study period were also collected. A sample of caregivers to children participating in the trial was interviewed about household cost incurred on transport, drugs, fees, and special food during a period of one week after the health centre visit as well as days unable to work. A decision model approach was used to calculate the incremental cost-effectiveness ratios (ICERs. Univariate and multivariate sensitivity analyses were applied to assess the robustness of ICERs.The availability of mRDTs for malaria diagnosis resulted in fewer ACT treatments compared to the clinical judgement approach (73
Appropriate targeting of artemisinin-based combination therapy by community health workers using malaria rapid diagnostic tests: findings from randomized trials in two contrasting areas of high and low malaria transmission in south-western Uganda.
Ndyomugyenyi, Richard; Magnussen, Pascal; Lal, Sham; Hansen, Kristian; Clarke, Siân E
To compare the impact of malaria rapid diagnostic tests (mRDTs), used by community health workers (CHWs), on the proportion of children decisions by CHWs were validated by microscopy on a reference blood slide collected at the time of consultation, to compare the proportion of children <5 years receiving appropriately targeted ACT treatment, defined as patients with microscopically-confirmed presence of parasites in a peripheral blood smear receiving artemether-lumefantrine or rectal artesunate, and patients with no malaria parasites not given ACT. In the moderate-to-high transmission area, ACT treatment was appropriately targeted in 79.3% (520/656) of children seen by CHWs using mRDTs to diagnose malaria, vs. 30.8% (215/699) of children seen by CHWs using presumptive diagnosis (P < 0.001). In the low transmission area, 90.1% (363/403) children seen by CHWs using mRDTs received appropriately targeted ACT treatment vs. 7.8% (64/817) seen by CHWs using presumptive diagnosis (P < 0.001). Low mRDT sensitivity in children with low-density parasitaemia (<200 parasites/μl) was identified as a potential concern. When equipped with mRDTs, ACT treatments delivered by CHWs are more accurately targeted to children with malaria parasites. mRDT use could play an important role in reducing overdiagnosis of malaria and improving fever case management within iCCM, in both moderate-to-high and low transmission areas. Nonetheless, missed treatments due to the low sensitivity of current mRDTs in patients with low parasite density are a concern. For community-based treatment in areas of low transmission and/or non-immune populations, presumptive treatment of all fevers as malaria may be advisable, until more sensitive diagnostic assays, suitable for routine use by CHWs in remote settings, become available. © 2016 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.
Bauch Julie A
Full Text Available Abstract Background Malaria transmission has declined dramatically in Zanzibar in recent years. Continuing use of preventive measures such as long-lasting insecticidal-treated nets (LLINs, and use of malaria rapid diagnostic tests (RDTs are essential to prevent malaria resurgence. This study employed qualitative methods to explore community perceptions of malaria risk and adherence to prevention measures in two districts in Zanzibar. Methods Key informant interviews with 24 primary health care providers and 24 focus group discussions with local residents in Zanzibar districts Wete and Central were conducted during April and May 2012 focusing on perception of malaria risk, current preventive practices used, reasons for using preventive practices and effective strategies for malaria control. Results Health care providers and residents appear to be aware of the decreasing incidence of malaria. Both groups continue the use of malaria preventive practices in this low and seasonal transmission setting. The most important preventive measures identified were LLINs, indoor residual spraying (IRS, and education. Barriers to malaria prevention include: lack of staff at clinics, insufficient number of LLINs distributed, and inadequate malaria education. Reasons for continued use of preventive practices include: fear of malaria returning to high levels, presence of mosquitoes during rainy seasons, and concern about local cases from other villages or imported cases from mainland Tanzania. Mosques, clinics, schools and community meetings were listed as most important sources of education. However, residents express the desire for more education. Conclusion Health care providers and residents generally reported consistent use of malaria preventive measures. However, maintaining and continuing to reduce malaria transmission will require ongoing education for both health care providers and residents to reinforce the importance of using preventive measures
Durnez, Lies; Mao, Sokny; Denis, Leen; Roelants, Patricia; Sochantha, Tho; Coosemans, Marc
...), targeting indoor- and late-biting malaria vectors only. The present study evaluated the vector density, early biting activity and malaria transmission of outdoor-biting malaria vectors in two forested regions in Cambodia...
George K. Christophides
Summary As the malaria burden persists in most parts of the developing world, the concept of implementation of new strategies such as the use of genetically modified mosquitoes to control the disease...
Smith, M. W.; Macklin, M. G.; Thomas, C. J.
Malaria risk is linked inextricably to the hydrological and geomorphological processes that form vector breeding sites. Yet environmental controls of malaria transmission are often represented by temperature and rainfall amounts, ignoring hydrological and geomorphological influences altogether. Continental-scale studies incorporate hydrology implicitly through simple minimum rainfall thresholds, while community-scale coupled hydrological and entomological models do not represent the actual diversity of the mosquito vector breeding sites. The greatest range of malaria transmission responses to environmental factors is observed at the catchment scale where seemingly contradictory associations between rainfall and malaria risk can be explained by hydrological and geomorphological processes that govern surface water body formation and persistence. This paper extends recent efforts to incorporate ecological factors into malaria-risk models, proposing that the same detailed representation be afforded to hydrological and, at longer timescales relevant for predictions of climate change impacts, geomorphological processes. We review existing representations of environmental controls of malaria and identify a range of hydrologically distinct vector breeding sites from existing literature. We illustrate the potential complexity of interactions among hydrology, geomorphology and vector breeding sites by classifying a range of water bodies observed in a catchment in East Africa. Crucially, the mechanisms driving surface water body formation and destruction must be considered explicitly if we are to produce dynamic spatial models of malaria risk at catchment scales.
Full Text Available Abstract Background Long-lasting insecticidal nets (LLINs are an important tool for controlling malaria. Much attention has been devoted to determine both the effect of LLINs on the reduction of Plasmodium infection rate and on clinically-confirmed malaria cases in sub-Saharan Africa. We carried out an epidemiological study to investigate whether LLINs impact on Plasmodium prevalence rate and the proportion of clinically-confirmed malaria cases, in five villages in the district of Toumodi, central Côte d'Ivoire. Methods From April 2007 to November 2008, a community-based malaria control programme was implemented in the study villages, which involved large-scale distribution of LLINs, and training and sensitization activities within the community. We determined the effect of this programme on Plasmodium prevalence rate, clinically-confirmed malaria cases and proportion of high parasitaemia rates in children aged 6-59 months through a series of cross-sectional surveys starting in April 2007 and repeated once every 6 months. Results We observed a significant decrease in the mean P. falciparum prevalence rate from April 2007 to April 2008 (p = 0.029. An opposite trend was observed from November 2007 to November 2008 when P. falciparum prevalence rate increased significantly (p = 0.003. Highly significant decreases in the proportions of clinical malaria cases were observed between April 2007 and April 2008 (p Conclusions Large-scale distribution of LLINs, accompanied by training and sensitization activities, significantly reduced Plasmodium prevalence rates among young children in the first year of the project, whereas overall clinical malaria rates dropped over the entire 18-month project period. A decrease in community motivation to sleep under bed nets, perhaps along with changing patterns of malaria transmission, might explain the observed increase in the Plasmodium prevalence rate between November 2007 and November 2008.
T-Regulatory Cells and Inflammatory and Inhibitory Cytokines in Malawian Children Residing in an Area of High and an Area of Low Malaria Transmission During Acute Uncomplicated Malaria and in Convalescence.
Nyirenda, Tonney S; Molyneux, Malcolm E; Kenefeck, Rupert; Walker, Lucy S K; MacLennan, Calman A; Heyderman, Robert S; Mandala, Wilson L
Malaria still infects many Malawian children, and it is a cause of death in some of them. Regulatory T cells (Tregs) help in negating immune-related pathology, it but can also favor multiplication of malaria parasites. The question remains whether children recovering from uncomplicated malaria (UCM) have higher Tregs and interleukin (IL)-10 levels in convalescence. We recruited children between the ages of 6 and 60 months presenting with acute UCM in Blantyre (low transmission area) and Chikwawa (high transmission area). We observed the children after 1 month and 3 months and analyzed their blood samples for parasitemia, lymphocyte subsets, and levels of the cytokines interferon (IFN)-γ, IL-10, and transforming growth factor (TGF)-β. Blood samples from age-matched controls were also analyzed for the same parameters. Compared with controls, acute UCM was associated with mild lymphopenia, splenomegaly, and high levels of IFN-γ, tumor necrosis factor-α, and IL-10, which normalized in convalescence. In Chikwawa, Treg counts were significantly (P < .0001) higher in convalescence compared with acute disease, whereas in Blantyre, these were as low as in healthy controls both during acute disease and in convalescence. Blantyre had a higher percentage of parasiteamic children (15% versus 12%) in convalescence compared with Chikwawa, but none of these developed symptomatic malaria during the study duration. Concentrations of TGF-β were higher at time points for the study participants and in controls from Blantyre compared with those recruited in Chikwawa. The high transmission area was associated with high Tregs counts and IL-10 concentrations in convalescence, which could have an effect on parasite clearance. We recommend that children recovering from UCM, especially those from high transmission area, should sleep under insecticide-treated nets, be screened for parasitemia, and a provision of antimalarial prophylaxis should be considered.
Parham, Paul E; Michael, Edwin
The impact of climate change on human health has received increasing attention in recent years, with potential impacts due to vector-borne diseases only now beginning to be understood. As the most severe vector-borne disease, with one million deaths globally in 2006, malaria is thought most likely to be affected by changes in climate variables due to the sensitivity of its transmission dynamics to environmental conditions. While considerable research has been carried out using statistical models to better assess the relationship between changes in environmental variables and malaria incidence, less progress has been made on developing process-based climate-driven mathematical models with greater explanatory power. Here, we develop a simple model of malaria transmission linked to climate which permits useful insights into the sensitivity of disease transmission to changes in rainfall and temperature variables. Both the impact of changes in the mean values of these key external variables and importantly temporal variation in these values are explored. We show that the development and analysis of such dynamic climate-driven transmission models will be crucial to understanding the rate at which P. falciparum and P. vivax may either infect, expand into or go extinct in populations as local environmental conditions change. Malaria becomes endemic in a population when the basic reproduction number R0 is greater than unity and we identify an optimum climate-driven transmission window for the disease, thus providing a useful indicator for determing how transmission risk may change as climate changes. Overall, our results indicate that considerable work is required to better understand ways in which global malaria incidence and distribution may alter with climate change. In particular, we show that the roles of seasonality, stochasticity and variability in environmental variables, as well as ultimately anthropogenic effects, require further study. The work presented here
Placental parasitemia is estimated to contribute up to 30% of preventable low birthweight (LBW), a leading cause of neonatal death in areas of stable malaria transmission. This review discusses the effects of plasmodium falciparum malaria (p.falciparum) in pregnancy in areas of stable malaria transmission and the effective ...
Samuels, Aaron M; Awino, Nobert; Odongo, Wycliffe; Abong'o, Benard; Gimnig, John; Otieno, Kephas; Shi, Ya Ping; Were, Vincent; Allen, Denise Roth; Were, Florence; Sang, Tony; Obor, David; Williamson, John; Hamel, Mary J; Patrick Kachur, S; Slutsker, Laurence; Lindblade, Kim A; Kariuki, Simon; Desai, Meghna
Most human Plasmodium infections in western Kenya are asymptomatic and are believed to contribute importantly to malaria transmission. Elimination of asymptomatic infections requires active treatment approaches, such as mass testing and treatment (MTaT) or mass drug administration (MDA), as infected persons do not seek care for their infection. Evaluations of community-based approaches that are designed to reduce malaria transmission require careful attention to study design to ensure that important effects can be measured accurately. This manuscript describes the study design and methodology of a cluster-randomized controlled trial to evaluate a MTaT approach for malaria transmission reduction in an area of high malaria transmission. Ten health facilities in western Kenya were purposively selected for inclusion. The communities within 3 km of each health facility were divided into three clusters of approximately equal population size. Two clusters around each health facility were randomly assigned to the control arm, and one to the intervention arm. Three times per year for 2 years, after the long and short rains, and again before the long rains, teams of community health volunteers visited every household within the intervention arm, tested all consenting individuals with malaria rapid diagnostic tests, and treated all positive individuals with an effective anti-malarial. The effect of mass testing and treatment on malaria transmission was measured through population-based longitudinal cohorts, outpatient visits for clinical malaria, periodic population-based cross-sectional surveys, and entomological indices.
Full Text Available Abstract Background Malaria transmission is highly heterogeneous, especially in low endemic countries, such as Cambodia. This results in geographical clusters of residual transmission in the dry, low transmission season, which can fuel the transmission to wider areas or populations during the wet season. A better understanding of spatial clustering of malaria can lead to a more efficient, targeted strategy to reduce malaria transmission. This study aims to evaluate the potential of the use of serological markers to define spatial patterns in malaria exposure. Methods Blood samples collected in a community-based randomized trial performed in 98 high endemic communities in Ratanakiri province, north-eastern Cambodia, were screened with a multiplex serological assay for five serological markers (three Plasmodium falciparum and two Plasmodium vivax. The antibody half-lives range from approximately six months until more than two years. Geographical heterogeneity in malaria transmission was examined using a spatial scan statistic on serology, PCR prevalence and malaria incidence rate data. Furthermore, to identify behavioural patterns or intrinsic factors associated with malaria exposure (antibody levels, risk factor analyses were performed by using multivariable random effect logistic regression models. The serological outcomes were then compared to PCR prevalence and malaria incidence data. Results A total of 6502 samples from two surveys were screened in an area where the average parasite prevalence estimated by PCR among the selected villages is 3.4 %. High-risk malaria pockets were observed adjacent to the ‘Tonle San River’ and neighbouring Vietnam for all three sets of data (serology, PCR prevalence and malaria incidence rates. The main risk factors for all P. falciparum antigens and P. vivax MSP1.19 are age, ethnicity and staying overnight at the plot hut. Conclusion It is possible to identify similar malaria pockets of higher malaria
Marc C. Tahita; Tinto, Halidou; Menten, Joris; Ouedraogo, Jean-Bosco; Guiguemde, Robert T.; van Geertruyden, Jean Pierre; Erhart, Annette; D’Alessandro, Umberto
Background Malaria in pregnancy is a major public health problem in endemic countries. Though the signs and symptoms of malaria among pregnant women have been already described, clinical presentation may vary according to intensity of transmission and local perceptions. Therefore, determining common signs and symptoms among pregnant women with a malaria infection may be extremely useful to identify those in need of further investigation by rapid diagnostic test or microscopy. Methods Six hund...
Sondo, Paul; Derra, Karim; Nakanabo, Seydou Diallo; Tarnagda, Zekiba; Kazienga, Adama; Valea, Innocent; Sorgho, Herman; Ouédraogo, Jean-Bosco; Guiguemdé, Tinga Robert; Tinto, Halidou
In Sahelian countries such as Burkina Faso, malaria transmission is seasonal with a high incidence of transmission during the rainy season. This study aimed to compare the effectiveness of the two recommended treatments (Artemether-Lumefantrine and Artesunate-Amodiaquine) for uncomplicated malaria in Burkina Faso regarding this seasonal variation of malaria transmission. This is part of a randomized open label trial comparing the effectiveness and safety of Artemether-Lumefantrine versus Artesunate-Amodiaquine according to routine practice in Nanoro. Patients with uncomplicated falciparum malaria were recruited all year round and followed-up for 28 days. To distinguish recrudescences from new infections, dried blood spots from day 0 and day of recurrent parasitaemia were used for nested-PCR genotyping of the polymorphic loci of the merozoite surface proteins 1 and 2. Seasonal influence was investigated by assessing the treatment outcomes according to the recruitment period of the patients. Two main groups (dry season versus rainy season) were defined following the seasonal characteristics of the study area. In Artemether-Lumefantrine group, the uncorrected cure rate was 76.5% in dry season versus 37.9% in rainy season. In Artesunate-Amodiaquine group, this was 93.3% and 57.1% during dry and rainy seasons, respectively. After PCR adjustment, the cure rate decreased from 85.9% in dry season to 75.0% in rainy season in Artemether-Lumefantrine group. InA rtesunate-Amodiaquine group, it was 93.3% in dry season and 80.7% during the rainy season. During the rainy season around 50% of patients had a new malaria episode by Day 28. The cure rate of both Artemether-Lumefantrine and Artesunate-Amodiaquine treatments was higher in dry season compared to rainy season due to high incidence of reinfections during the rainy season. For this reason, in addition to the curative effect, the post-treatment prophylactic effect should be taken into account in the choice of antimalarial
Bousema, T.; Drakeley, C.; Gesase, S.; Hashim, R.; Magesa, S.; Mosha, F.; Otieno, S.; Carneiro, I.; Cox, J.; Msuya, E.; Kleinschmidt, I.; Maxwell, C.; Greenwood, B.; Riley, E.; Sauerwein, R.W.; Chandramohan, D.; Gosling, R.
BACKGROUND: Variation in the risk of malaria within populations is a frequently described but poorly understood phenomenon. This heterogeneity creates opportunities for targeted interventions but only if hot spots of malaria transmission can be easily identified. METHODS: We determined spatial
Segeja, M D; Mmbando, Bruno Paul; Kamugisha, M L
Glucose-6-phosphate dehydrogenase (G6PD) deficiency and haemoglobin S (HbS) are very common genetic disorders in sub Saharan Africa, where malaria is endemic. These genetic disorders have been associated with protection against malaria and are therefore under strong selection pressure by the dise......Glucose-6-phosphate dehydrogenase (G6PD) deficiency and haemoglobin S (HbS) are very common genetic disorders in sub Saharan Africa, where malaria is endemic. These genetic disorders have been associated with protection against malaria and are therefore under strong selection pressure...... by the disease. In November-December 2003, we conducted a cross-sectional survey to determine the prevalence of G6PD deficiency and HbS in the population and relate these to malaria infection and haemoglobin levels in lowland and highland areas of differing malaria transmission patterns of Muheza, Tanzania...
Tahita, Marc C; Tinto, Halidou; Menten, Joris; Ouedraogo, Jean-Bosco; Guiguemde, Robert T; van Geertruyden, Jean Pierre; Erhart, Annette; D'Alessandro, Umberto
Malaria in pregnancy is a major public health problem in endemic countries. Though the signs and symptoms of malaria among pregnant women have been already described, clinical presentation may vary according to intensity of transmission and local perceptions. Therefore, determining common signs and symptoms among pregnant women with a malaria infection may be extremely useful to identify those in need of further investigation by rapid diagnostic test or microscopy. Six hundred pregnant women attending the maternity clinic of Nanoro District Hospital, Burkina Faso were recruited, 200 with suspected clinical malaria and 400 as controls. Cases were matched with controls by gestational age and parity. Signs and symptoms were collected and a blood sample taken for rapid diagnostic test, microscopy and haemoglobin measurement. A multivariate model was used to assess the predictive value of signs and symptoms for malaria infection. The overall prevalence of malaria was 42.6% (256/600) while anaemia was found in 60.8% (365/600) of the women. Nearly half (49%) of the cases and 39.5% of the controls had a malaria infection (p = 0.03). The most common signs and symptoms among the cases were fever (36%,72/200), history of fever (29%,58/200) and headache (52%,104/200). The positive predictive value for fever was 53% (95% CI:41-64), history of fever 58% (95% CI:37-63) and headache 51% (95% CI:41-61). Signs and symptoms suggestive of malaria are frequent among pregnant women living in areas of intense transmission. Common malaria symptoms are not strong predictors of infection. For a better management of malaria in pregnancy, active screening to detect and treat malaria infection early should be performed on all pregnant women attending a health facility.
Kapoor, Neeraj; Vanjak, Ivana; Rozzelle, James; Berges, Aym; Chan, Wei; Yin, Gang; Tran, Cuong; Sato, Aaron K; Steiner, Alexander R; Pham, Thao P; Birkett, Ashley J; Long, Carole A; Fairman, Jeff; Miura, Kazutoyo
Malaria, one of the most common vector borne human diseases, is a major world health issue. In 2015 alone, more than 200 million people were infected with malaria, out of which, 429 000 died. Even though artemisinin-based combination therapies (ACT) are highly effective at treating malaria infections, novel efforts toward development of vaccines to prevent transmission are still needed. Pfs25, a postfertilization stage parasite surface antigen, is a leading transmission-blocking vaccine (TBV) candidate. It is postulated that Pfs25 anchors to the cell membrane using a glycosylphosphatidylinositol (GPI) linker, which itself possesses pro-inflammatory properties. In this study, Escherichia coli derived extract (XtractCF+TM) was used in cell free protein synthesis [CFPS] to successfully express >200 mg/L of recombinant Pfs25 with a C-terminal non-natural amino acid (nnAA), namely, p-azidomethyl phenylalanine (pAMF), which possesses a reactive azide group. Thereafter, a unique conjugate vaccine (CV), namely, Pfs25-GPI was generated with dibenzocyclooctyne (DBCO) derivatized glycan core of malaria GPI using a simple but highly efficient copper free click chemistry reaction. In mice immunized with Pfs25 or Pfs25-GPI, the Pfs25-GPI group showed significantly higher titers compared to the Pfs25 group. Moreover, only purified IgGs from Pfs25-GPI group were able to significantly block transmission of parasites to mosquitoes, as judged by a standard membrane feeding assay [SMFA]. To our knowledge, this is the first report of the generation of a CV using Pfs25 and malaria specific GPI where the GPI is shown to enhance the ability of Pfs25 to elicit transmission blocking antibodies.
Mmbando, Bruno P; Lusingu, John P; Vestergaard, Lasse S
BACKGROUND: In Sub-Sahara Africa, malaria due to Plasmodium falciparum is the main cause of ill health. Evaluation of malaria interventions, such as drugs and vaccines depends on clinical definition of the disease, which is still a challenge due to lack of distinct malaria specific clinical...... features. Parasite threshold is used in definition of clinical malaria in evaluation of interventions. This however, is likely to be influenced by other factors such as transmission intensity as well as individual level of immunity against malaria. METHODS: This paper describes step function and dose...... response model with threshold parameter as a tool for estimation of parasite threshold for onset of malaria fever in highlands (low transmission) and lowlands (high transmission intensity) strata. These models were fitted using logistic regression stratified by strata and age groups (0-1, 2-3, 4-5, 6...
Full Text Available Abstract Background Cost-sharing schemes incorporating modest targeted subsidies have promoted insecticide-treated nets (ITNs for malaria prevention in the Kilombero Valley, southern Tanzania, since 1996. Here we evaluate resulting changes in bednet coverage and malaria transmission. Methods Bednets were sold through local agents at fixed prices representing a 34% subsidy relative to full delivery cost. A further targeted subsidy of 15% was provided to vulnerable groups through discount vouchers delivered through antenatal clinics and regular immunizations. Continuous entomological surveys (2,376 trap nights were conducted from October 2001 to September 2003 in 25 randomly-selected population clusters of a demographic surveillance system which monitored net coverage. Results Mean net usage of 75% (11,982/16,086 across all age groups was achieved but now-obsolete technologies available at the time resulted in low insecticide treatment rates. Malaria transmission remained intense but was substantially reduced: Compared with an exceptionally high historical mean EIR of 1481, even non-users of nets were protected (EIR [fold reduction] = 349 infectious bites per person per year [×4], while the average resident (244 [×6], users of typical nets (210 [×7] and users of insecticidal nets (105 [×14] enjoyed increasing benefits. Conclusion Despite low net treatment levels, community-level protection was equivalent to the personal protection of an ITN. Greater gains for net users and non-users are predicted if more expensive long-lasting ITN technologies can be similarly promoted with correspondingly augmented subsidies. Cost sharing strategies represent an important option for national programmes lacking adequate financing to fully subsidize comprehensive ITN coverage.
Petersen, E; Høgh, B; Dziegiel, M
, and a synthetic peptide (EENV)6 representing the C-terminal repeats from Pf155/RESA, were investigated longitudinally in 13 children and 7 adults living under conditions of continuous, intense malaria transmission. Some subjects did not recognize the antigens after malaria infection, and in subjects recognizing...... elicited by natural malaria infection in previously primed donors....
Background: Knowledge about the modes of transmission and preventive measures of malaria are important preceding factors for the acceptance and use of proven control tools by the community. Objective: To assess knowledge, attitude and practices (KAP) about modes of malaria transmission and preventive methods in ...
Rumisha, Susan Fred; Smith, Thomas; Abdulla, Salim; Masanja, Honorath; Vounatsou, Penelope
Malaria transmission is measured using entomological inoculation rate (EIR), number of infective mosquito bites/person/unit time. Understanding heterogeneity of malaria transmission has been difficult due to a lack of appropriate data. A comprehensive entomological database compiled by the Malaria Transmission Intensity and Mortality Burden across Africa (MTIMBA) project (2001-2004) at several sites is the most suitable dataset for studying malaria transmission-mortality relations. The data are sparse and large, with small-scale spatial-temporal variation. This work demonstrates a rigorous approach for analysing large and highly variable entomological data for the study of malaria transmission heterogeneity, measured by EIR, within the Rufiji Demographic Surveillance System (DSS), MTIMBA project site in Tanzania. Bayesian geostatistical binomial and negative binomial models with zero inflation were fitted for sporozoite rates (SRs) and mosquito density, respectively. The spatial process was approximated from a subset of locations. The models were adjusted for environmental effects, seasonality and temporal correlations and assessed based on their predictive ability. EIR was calculated using model-based predictions of SR and density. Malaria transmission was mostly influenced by rain and temperature, which significantly reduces the probability of observing zero mosquitoes. High transmission was observed at the onset of heavy rains. Transmission intensity reduced significantly during Year 2 and 3, contrary to the Year 1, pronouncing high seasonality and spatial variability. The southern part of the DSS showed high transmission throughout the years. A spatial shift of transmission intensity was observed where an increase in households with very low transmission intensity and significant reduction of locations with high transmission were observed over time. Over 68 and 85% of the locations selected for validation for SR and density, respectively, were correctly
Coulibaly, Drissa; Rebaudet, Stanislas; Travassos, Mark; Tolo, Youssouf; Laurens, Matthew; Kone, Abdoulaye K; Traore, Karim; Guindo, Ando; Diarra, Issa; Niangaly, Amadou; Daou, Modibo; Dembele, Ahmadou; Sissoko, Mody; Kouriba, Bourema; Dessay, Nadine; Gaudart, Jean; Piarroux, Renaud; Thera, Mahamadou A; Plowe, Christopher V; Doumbo, Ogobara K
Heterogeneous patterns of malaria transmission are thought to be driven by factors including host genetics, distance to mosquito breeding sites, housing construction, and socio-behavioural characteristics. Evaluation of local transmission epidemiology to characterize malaria risk is essential for planning malaria control and elimination programmes. The use of geographical information systems (GIS) techniques has been a major asset to this approach. To assess time and space distribution of malaria disease in Bandiagara, Mali, within a transmission season, data were used from an ongoing malaria incidence study that enrolled 300 participants aged under six years old". Children's households were georeferenced using a handheld global position system. Clinical malaria was defined as a positive blood slide for Plasmodium falciparum asexual stages associated with at least one of the following signs: headache, body aches, fever, chills and weakness. Daily rainfall was measured at the local weather station.Landscape features of Bandiagara were obtained from satellite images and field survey. QGIS™ software was used to map malaria cases, affected and non-affected children, and the number of malaria episodes per child in each block of Bandiagara. Clusters of high or low risk were identified under SaTScan(®) software according to a Bernoulli model. From June 2009 to May 2010, 296 clinical malaria cases were recorded. Though clearly temporally related to the rains, Plasmodium falciparum occurrence persisted late in the dry season. Two "hot spots" of malaria transmission also found, notably along the Yamé River, characterized by higher than expected numbers of malaria cases, and high numbers of clinical episodes per child. Conversely, the north-eastern sector of the town had fewer cases despite its proximity to a large body of standing water which was mosquito habitat. These results confirm the existence of a marked spatial heterogeneity of malaria transmission in Bandiagara
Stanisic, Danielle I; Moore, Kerryn A; Baiwog, Francesca; Ura, Alice; Clapham, Caroline; King, Christopher L; Siba, Peter M; Beeson, James G; Mueller, Ivo; Fowkes, Freya J; Rogerson, Stephen J
Low birth weight (LBW), anaemia and malaria are common in Papua New Guinean women. To identify risk factors for LBW, anaemia and preterm delivery (PTD), pregnant women recruited into a cohort study in Madang, Papua New Guinea, were followed to delivery. Of 470 women enrolled, delivery data were available for 328 (69.7%). By microscopy, 34.4% (113/328) of women had malaria parasitaemia at enrolment and 12.5% (41/328) at delivery; at each time point, PCR detected sub-microscopic parasitaemia in substantially more. Most infections were with Plasmodium falciparum; the remainder being predominantly P. vivax. Anaemia and smoking were associated with lower birth weight, and LBW (16.7%; 51/305) and PTD (21.8%; 63/290) were common. Histopathologically diagnosed chronic placental malaria was associated with LBW (adjusted odds ratio [aOR] 3.3; p=0.048) and PTD (aOR 4.2; p=0.01). Lack of maternal education predisposed to PTD. Sub-microscopic parasitaemia at delivery appeared to increase the risk of LBW. Of the genetic polymorphisms, Southeast Asian ovalocytosis, α(+)-thalassaemia and complement receptor 1 (CR1) deficiency, a CR1 heterozygous genotype was associated with decreased risk of anaemia and substantial but non-significant effects were noted in other comparisons. In coastal Papua New Guinea, malaria and anaemia are important causes of adverse pregnancy outcomes. © The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: firstname.lastname@example.org.
Ademolue, Temitope W; Aniweh, Yaw; Kusi, Kwadwo A; Awandare, Gordon A
In individuals living in malaria-endemic regions, parasitaemia thresholds for the onset of clinical symptoms vary with transmission intensity. The mechanisms that mediate this relationship are however, unclear. Since inflammatory responses to parasite infection contribute to the clinical manifestation of malaria, this study investigated inflammatory cytokine responses in children with malaria from areas of different transmission intensities (ranging from low to high). Blood samples were obtained from children confirmed with malaria at community hospitals in three areas with differing transmission intensities. Cytokine levels were assessed using the Luminex®-based magnetic bead array system, and levels were compared across sites using appropriate statistical tests. The relative contributions of age, gender, parasitaemia and transmission intensity on cytokine levels were investigated using multivariate regression analysis. Parasite density increased with increasing transmission intensity in children presenting to hospital with symptomatic malaria, indicating that the parasitaemia threshold for clinical malaria increases with increasing transmission intensity. Furthermore, levels of pro-inflammatory cytokines, including tumour necrosis factor alpha (TNF-α), interferon-gamma (IFN-γ), interleukin (IL)-1β, IL-2, IL-6, IL-8, and IL-12, decreased with increasing transmission intensity, and correlated significantly with parasitaemia levels in the low transmission area but not in high transmission areas. Similarly, levels of anti-inflammatory cytokines, including IL-4, IL-7, IL-10 and IL-13, decreased with increasing transmission intensity, with IL-10 showing strong correlation with parasitaemia levels in the low transmission area. Multiple linear regression analyses revealed that transmission intensity was a stronger predictor of cytokine levels than age, gender and parasitaemia. Taken together, the data demonstrate a strong relationship between the prevailing
T. A. Klein
Full Text Available World ecosystems differ significantly and a multidisciplinary malaria control approach must be adjusted to meet these requirements. These include a comprehensive understanding of the malaria vectors, their behavior, seasonal distribution and abundance, susceptibility to insecticides (physiological and behavioral, methods to reduce the numbers of human gametocyte carriers through effective health care systems and antimalarial drug treatment, urban malaria transmission versus rural or forest malaria transmission, and the impact of vaccine development. Many malaria vectors are members of species complexes and individual relationship to malaria transmission, seasonal distribution, bitting behavior, etc. is poorly understood. Additionaly, malaria patients are not examined for circulating gametocytes and both falciparum and vivax malaria patients may be highly infective to mosquitoes after treatment with currently used antimalarial drugs. Studies on the physiological and behavioral effects of DDT and other insecticides are inconclusive and need to be evalusted.
Yamana, Teresa K; Eltahir, Elfatih A B
Climate change is expected to affect the distribution of environmental suitability for malaria transmission by altering temperature and rainfall patterns; however, the local and global impacts of climate change on malaria transmission are uncertain. We assessed the effect of climate change on malaria transmission in West Africa. We coupled a detailed mechanistic hydrology and entomology model with climate projections from general circulation models (GCMs) to predict changes in vectorial capacity, an indication of the risk of human malaria infections, resulting from changes in the availability of mosquito breeding sites and temperature-dependent development rates. Because there is strong disagreement in climate predictions from different GCMs, we focused on the GCM projections that produced the best and worst conditions for malaria transmission in each zone of the study area. Simulation-based estimates suggest that in the desert fringes of the Sahara, vectorial capacity would increase under the worst-case scenario, but not enough to sustain transmission. In the transitional zone of the Sahel, climate change is predicted to decrease vectorial capacity. In the wetter regions to the south, our estimates suggest an increase in vectorial capacity under all scenarios. However, because malaria is already highly endemic among human populations in these regions, we expect that changes in malaria incidence would be small. Our findings highlight the importance of rainfall in shaping the impact of climate change on malaria transmission in future climates. Even under the GCM predictions most conducive to malaria transmission, we do not expect to see a significant increase in malaria prevalence in this region.
Murungi, Moses; Fulton, Travis; Reyes, Raquel; Matte, Michael; Ntaro, Moses; Mulogo, Edgar; Nyehangane, Dan; Juliano, Jonathan J; Siedner, Mark J; Boum, Yap; Boyce, Ross M
Poor specificity may negatively impact rapid diagnostic test (RDT)-based diagnostic strategies for malaria. We performed real-time PCR on a subset of subjects who had undergone diagnostic testing with a multiple-antigen (histidine-rich protein 2 and pan-lactate dehydrogenase pLDH [HRP2/pLDH]) RDT and microscopy. We determined the sensitivity and specificity of the RDT in comparison to results of PCR for the detection of Plasmodium falciparum malaria. We developed and evaluated a two-step algorithm utilizing the multiple-antigen RDT to screen patients, followed by confirmatory microscopy for those individuals with HRP2-positive (HRP2+)/pLDH-negative (pLDH-) results. In total, dried blood spots (DBS) were collected from 276 individuals. There were 124 (44.9%) individuals with an HRP2+/pLDH+ result, 94 (34.1%) with an HRP2+/pLDH- result, and 58 (21%) with a negative RDT result. The sensitivity and specificity of the RDT compared to results with real-time PCR were 99.4% (95% confidence interval [CI], 95.9 to 100.0%) and 46.7% (95% CI, 37.7 to 55.9%), respectively. Of the 94 HRP2+/pLDH- results, only 32 (34.0%) and 35 (37.2%) were positive by microscopy and PCR, respectively. The sensitivity and specificity of the two-step algorithm compared to results with real-time PCR were 95.5% (95% CI, 90.5 to 98.0%) and 91.0% (95% CI, 84.1 to 95.2), respectively. HRP2 antigen bands demonstrated poor specificity for the diagnosis of malaria compared to that of real-time PCR in a high-transmission setting. The most likely explanation for this finding is the persistence of HRP2 antigenemia following treatment of an acute infection. The two-step diagnostic algorithm utilizing microscopy as a confirmatory test for indeterminate HRP2+/pLDH- results showed significantly improved specificity with little loss of sensitivity in a high-transmission setting. Copyright © 2017 American Society for Microbiology.
Ruktanonchai, Nick W; DeLeenheer, Patrick; Tatem, Andrew J; Alegana, Victor A; Caughlin, T Trevor; Zu Erbach-Schoenberg, Elisabeth; Lourenço, Christopher; Ruktanonchai, Corrine W; Smith, David L
Humans move frequently and tend to carry parasites among areas with endemic malaria and into areas where local transmission is unsustainable. Human-mediated parasite mobility can thus sustain parasite populations in areas where they would otherwise be absent. Data describing human mobility and malaria epidemiology can help classify landscapes into parasite demographic sources and sinks, ecological concepts that have parallels in malaria control discussions of transmission foci. By linking transmission to parasite flow, it is possible to stratify landscapes for malaria control and elimination, as sources are disproportionately important to the regional persistence of malaria parasites. Here, we identify putative malaria sources and sinks for pre-elimination Namibia using malaria parasite rate (PR) maps and call data records from mobile phones, using a steady-state analysis of a malaria transmission model to infer where infections most likely occurred. We also examined how the landscape of transmission and burden changed from the pre-elimination setting by comparing the location and extent of predicted pre-elimination transmission foci with modeled incidence for 2009. This comparison suggests that while transmission was spatially focal pre-elimination, the spatial distribution of cases changed as burden declined. The changing spatial distribution of burden could be due to importation, with cases focused around importation hotspots, or due to heterogeneous application of elimination effort. While this framework is an important step towards understanding progressive changes in malaria distribution and the role of subnational transmission dynamics in a policy-relevant way, future work should account for international parasite movement, utilize real time surveillance data, and relax the steady state assumption required by the presented model.
Izabel Cristina Dos Reis
Full Text Available Fish farming in the Amazon has been stimulated as a solution to increase economic development. However, poorly managed fish ponds have been sometimes associated with the presence of Anopheles spp. and consequently, with malaria transmission. In this study, we analyzed the spatial and temporal dynamics of malaria in the state of Acre (and more closely within a single county to investigate the potential links between aquaculture and malaria transmission in this region. At the state level, we classified the 22 counties into three malaria endemicity patterns, based on the correlation between notification time series. Furthermore, the study period (2003-2013 was divided into two phases (epidemic and post-epidemic. Higher fish pond construction coincided both spatially and temporally with increased rate of malaria notification. Within one malaria endemic county, we investigated the relationship between the geolocation of malaria cases (2011-2012 and their distance to fish ponds. Entomological surveys carried out in these ponds provided measurements of anopheline abundance that were significantly associated with the abundance of malaria cases within 100 m of the ponds (P < 0.005; r = 0.39. These results taken together suggest that fish farming contributes to the maintenance of high transmission levels of malaria in this region.
Reis, Izabel Cristina Dos; Honório, Nildimar Alves; Barros, Fábio Saito Monteiro de; Barcellos, Christovam; Kitron, Uriel; Camara, Daniel Cardoso Portela; Pereira, Glaucio Rocha; Keppeler, Erlei Cassiano; da Silva-Nunes, Mônica; Codeço, Cláudia Torres
Fish farming in the Amazon has been stimulated as a solution to increase economic development. However, poorly managed fish ponds have been sometimes associated with the presence of Anopheles spp. and consequently, with malaria transmission. In this study, we analyzed the spatial and temporal dynamics of malaria in the state of Acre (and more closely within a single county) to investigate the potential links between aquaculture and malaria transmission in this region. At the state level, we classified the 22 counties into three malaria endemicity patterns, based on the correlation between notification time series. Furthermore, the study period (2003-2013) was divided into two phases (epidemic and post-epidemic). Higher fish pond construction coincided both spatially and temporally with increased rate of malaria notification. Within one malaria endemic county, we investigated the relationship between the geolocation of malaria cases (2011-2012) and their distance to fish ponds. Entomological surveys carried out in these ponds provided measurements of anopheline abundance that were significantly associated with the abundance of malaria cases within 100 m of the ponds (P < 0.005; r = 0.39). These results taken together suggest that fish farming contributes to the maintenance of high transmission levels of malaria in this region.
Yamana, T. K.; Eltahir, E. A.
Early warnings of malaria transmission allow health officials to better prepare for future epidemics. Monitoring rainfall is recognized as an important part of malaria early warning systems, as outlined by the Roll Back Malaria Initiative. The Hydrology, Entomology and Malaria Simulator (HYDREMATS) is a mechanistic model that relates rainfall to malaria transmission, and could be used to provide early warnings of malaria epidemics. HYDREMATS is used to make predictions of mosquito populations and vectorial capacity for 2005, 2006, and 2007 in Banizoumbou village in western Niger. HYDREMATS is forced by observed rainfall, followed by a rainfall prediction based on the seasonal mean rainfall for a period two or four weeks into the future. Predictions made using this method provided reasonable estimates of mosquito populations and vectorial capacity, two to four weeks in advance. The predictions were significantly improved compared to those made when HYDREMATS was forced with seasonal mean rainfall alone.
Ayisi, John G.; van Eijk, Anna M.; Newman, Robert D.; ter Kuile, Feiko O.; Shi, Ya Ping; Yang, Chunfu; Kolczak, Margarette S.; Otieno, Juliana A.; Misore, Ambrose O.; Kager, Piet A.; Lal, Renu B.; Steketee, Richard W.; Nahlen, Bernard L.
To determine whether maternal placental malaria is associated with an increased risk for perinatal mother-to-child HIV transmission (MTCT), we studied HIV-positive women in western Kenya. We enrolled 512 mother-infant pairs; 128 (25.0%) women had placental malaria, and 102 (19.9%) infants acquired
Malaria continues to be a major health problem in more than 100 endemic countries located primarily in tropical and sub-tropical regions around the world. Malaria transmission is a dynamic process and involves many interlinked factors, from uncontrollable natural environmental conditions to man-made disturbances to nature. Almost half of the population at risk of malaria lives in forest areas. Forests are hot beds of malaria transmission as they provide conditions such as vegetation cover, temperature, rainfall and humidity conditions that are conducive to distribution and survival of malaria vectors. Forests often lack infrastructure and harbor tribes with distinct genetic traits, socio-cultural beliefs and practices that greatly influence malaria transmission dynamics. Here we summarize the various topographical, entomological, parasitological, human ecological and socio-economic factors, which are crucial and shape malaria transmission in forested areas. An in-depth understanding and synthesis of the intricate relationship of these parameters in achieving better malaria control in various types of forest ecosystems is emphasized. PMID:24912923
Mordecai, Eerin A.; Paaijmans, Krijin P.; Johnson, Leah R.; Balzer, Christian; Ben-Horin, Tal; de Moor, Emily; McNally, Amy; Pawar, Samraat; Ryan, Sadie J.; Smith, Thomas C.; Lafferty, Kevin D.
The ecology of mosquito vectors and malaria parasites affect the incidence, seasonal transmission and geographical range of malaria. Most malaria models to date assume constant or linear responses of mosquito and parasite life-history traits to temperature, predicting optimal transmission at 31 °C. These models are at odds with field observations of transmission dating back nearly a century. We build a model with more realistic ecological assumptions about the thermal physiology of insects. Our model, which includes empirically derived nonlinear thermal responses, predicts optimal malaria transmission at 25 °C (6 °C lower than previous models). Moreover, the model predicts that transmission decreases dramatically at temperatures > 28 °C, altering predictions about how climate change will affect malaria. A large data set on malaria transmission risk in Africa validates both the 25 °C optimum and the decline above 28 °C. Using these more accurate nonlinear thermal-response models will aid in understanding the effects of current and future temperature regimes on disease transmission.
Martens, P; Hall, L
Reports of malaria are increasing in many countries and in areas thought free of the disease. One of the factors contributing to the reemergence of malaria is human migration. People move for a number of reasons, including environmental deterioration, economic necessity, conflicts, and natural disasters. These factors are most likely to affect the poor, many of whom live in or near malarious areas. Identifying and understanding the influence of these population movements can improve preventio...
Tanser, Frank C; Sharp, Brian; le Sueur, David
Climate change is likely to affect transmission of vector-borne diseases such as malaria. We quantitatively estimated current malaria exposure and assessed the potential effect of projected climate scenarios on malaria transmission. We produced a spatiotemporally validated (against 3791 parasite surveys) model of Plasmodium falciparum malaria transmission in Africa. Using different climate scenarios from the Hadley Centre global climate model (HAD CM3) climate experiments, we projected the potential effect of climate change on transmission patterns. Our model showed sensitivity and specificity of 63% and 96%, respectively (within 1 month temporal accuracy), when compared with the parasite surveys. We estimate that on average there are 3.1 billion person-months of exposure (445 million people exposed) in Africa per year. The projected scenarios would estimate a 5-7% potential increase (mainly altitudinal) in malaria distribution with surprisingly little increase in the latitudinal extents of the disease by 2100. Of the overall potential increase (although transmission will decrease in some countries) of 16-28% in person-months of exposure (assuming a constant population), a large proportion will be seen in areas of existing transmission. The effect of projected climate change indicates that a prolonged transmission season is as important as geographical expansion in correct assessment of the effect of changes in transmission patterns. Our model constitutes a valid baseline against which climate scenarios can be assessed and interventions planned.
Wanzira, Humphrey; Eganyu, Thomas; Mulebeke, Ronald; Bukenya, Fred; Echodu, Dorothy; Adoke, Yeka
Uganda is conducting a second mass LLIN distribution campaign and Katakwi district recently received LLINs as part of this activity. This study was conducted to measure the success of the campaign in this setting, an area of high transmission, with the objectives to estimate LLIN ownership, access and use pre and post campaign implementation. Two identical cross sectional surveys, based on the Malaria Indicator Survey methodology, were conducted in three sub-counties in this district (Kapujan, Magoro and Toroma), six months apart, one before and another after the mass distribution campaign. Data on three main LLIN indicators including; household LLIN ownership, population with access to an LLIN and use were collected using a household and a women's questionnaire identical to the Malaria Indicator Survey. A total of 601 and 607 households were randomly selected in survey one and two respectively. At baseline, 60.57% (56.53-64.50) of households owned at least one net for every two persons who stayed in the household the night before the survey which significantly increased to 70.35% (66.54-73.96) after the campaign (p = 0.001). Similarly, the percentage of the household population with access to an LLIN significantly increased from 84.76% (82.99-86.52) to 91.57% (90.33-92.81), p = 0.001 and the percentage of household population that slept under an LLIN the night before the survey also significantly increased from 56.85% (55.06-58.82) to 81.72% (76.75-83.21), p = 0.001. The LLIN mass campaign successfully achieved the national target of over eighty-five percent of the population with access to an LLIN in this setting, however, universal household coverage and use were fourteen and three percent points less than the national target respectively. This is useful for malaria programs to consider during the planning of future campaigns by tailoring efforts around deficient areas like mechanisms to increase universal coverage and behavior change communication.
Kamil A Braima
Full Text Available BACKGROUND: The suburban transmission of malaria in Selangor, Malaysia's most developed and populous state still remains a concern for public health in this region. Despite much successful control efforts directed at its reduction, sporadic cases, mostly brought in by foreigners have continued to occur. In addition, cases of simian malaria caused by Plasmodium knowlesi, some with fatal outcome have caused grave concern to health workers. The aim of this study was to investigate the possibility of local malaria transmission in suburban regions of Selangor, which are adjacent to secondary rainforests. FINDINGS: A malaria survey spanning 7 years (2006 - 2012 was conducted in Selangor. A total of 1623 laboratory confirmed malaria cases were reported from Selangor's nine districts. While 72.6% of these cases (1178/1623 were attributed to imported malaria (cases originating from other countries, 25.5% (414/1623 were local cases and 1.9% (31/1623 were considered as relapse and unclassified cases combined. In this study, the most prevalent infection was P. vivax (1239 cases, prevalence 76.3% followed by P. falciparum (211, 13.0%, P. knowlesi (75, 4.6%, P. malariae (71, 4.4% and P. ovale (1, 0.06%. Mixed infections comprising of P. vivax and P. falciparum were confirmed (26, 1.6%. Entomological surveys targeting the residences of malaria patients' showed that the most commonly trapped Anopheles species was An. maculatus. No oocysts or sporozoites were found in the An. maculatus collected. Nevertheless, the possibility of An. maculatus being the malaria vector in the investigated locations was high due to its persistent occurrence in these areas. CONCLUSIONS: Malaria cases reported in this study were mostly imported cases. However the co-existence of local cases and potential Plasmodium spp. vectors should be cause for concern. The results of this survey reflect the need of maintaining closely monitored malaria control programs and continuous extensive
Braima, Kamil A; Sum, Jia-Siang; Ghazali, Amir-Ridhwan M; Muslimin, Mustakiza; Jeffery, John; Lee, Wenn-Chyau; Shaker, Mohammed R; Elamin, Alaa-Eldeen M; Jamaiah, Ibrahim; Lau, Yee-Ling; Rohela, Mahmud; Kamarulzaman, Adeeba; Sitam, Frankie; Mohd-Noh, Rosnida; Abdul-Aziz, Noraishah M
The suburban transmission of malaria in Selangor, Malaysia's most developed and populous state still remains a concern for public health in this region. Despite much successful control efforts directed at its reduction, sporadic cases, mostly brought in by foreigners have continued to occur. In addition, cases of simian malaria caused by Plasmodium knowlesi, some with fatal outcome have caused grave concern to health workers. The aim of this study was to investigate the possibility of local malaria transmission in suburban regions of Selangor, which are adjacent to secondary rainforests. A malaria survey spanning 7 years (2006 - 2012) was conducted in Selangor. A total of 1623 laboratory confirmed malaria cases were reported from Selangor's nine districts. While 72.6% of these cases (1178/1623) were attributed to imported malaria (cases originating from other countries), 25.5% (414/1623) were local cases and 1.9% (31/1623) were considered as relapse and unclassified cases combined. In this study, the most prevalent infection was P. vivax (1239 cases, prevalence 76.3%) followed by P. falciparum (211, 13.0%), P. knowlesi (75, 4.6%), P. malariae (71, 4.4%) and P. ovale (1, 0.06%). Mixed infections comprising of P. vivax and P. falciparum were confirmed (26, 1.6%). Entomological surveys targeting the residences of malaria patients' showed that the most commonly trapped Anopheles species was An. maculatus. No oocysts or sporozoites were found in the An. maculatus collected. Nevertheless, the possibility of An. maculatus being the malaria vector in the investigated locations was high due to its persistent occurrence in these areas. Malaria cases reported in this study were mostly imported cases. However the co-existence of local cases and potential Plasmodium spp. vectors should be cause for concern. The results of this survey reflect the need of maintaining closely monitored malaria control programs and continuous extensive malaria surveillance in Peninsula Malaysia.
Braima, Kamil A.; Sum, Jia-Siang; Ghazali, Amir-Ridhwan M.; Muslimin, Mustakiza; Jeffery, John; Lee, Wenn-Chyau; Shaker, Mohammed R.; Elamin, Alaa-Eldeen M.; Jamaiah, Ibrahim; Lau, Yee-Ling; Rohela, Mahmud; Kamarulzaman, Adeeba; Sitam, Frankie; Mohd-Noh, Rosnida; Abdul-Aziz, Noraishah M.
Background The suburban transmission of malaria in Selangor, Malaysia’s most developed and populous state still remains a concern for public health in this region. Despite much successful control efforts directed at its reduction, sporadic cases, mostly brought in by foreigners have continued to occur. In addition, cases of simian malaria caused by Plasmodium knowlesi, some with fatal outcome have caused grave concern to health workers. The aim of this study was to investigate the possibility of local malaria transmission in suburban regions of Selangor, which are adjacent to secondary rainforests. Findings A malaria survey spanning 7 years (2006 - 2012) was conducted in Selangor. A total of 1623 laboratory confirmed malaria cases were reported from Selangor’s nine districts. While 72.6% of these cases (1178/1623) were attributed to imported malaria (cases originating from other countries), 25.5% (414/1623) were local cases and 1.9% (31/1623) were considered as relapse and unclassified cases combined. In this study, the most prevalent infection was P. vivax (1239 cases, prevalence 76.3%) followed by P. falciparum (211, 13.0%), P. knowlesi (75, 4.6%), P. malariae (71, 4.4%) and P. ovale (1, 0.06%). Mixed infections comprising of P. vivax and P. falciparum were confirmed (26, 1.6%). Entomological surveys targeting the residences of malaria patients’ showed that the most commonly trapped Anopheles species was An. maculatus. No oocysts or sporozoites were found in the An. maculatus collected. Nevertheless, the possibility of An. maculatus being the malaria vector in the investigated locations was high due to its persistent occurrence in these areas. Conclusions Malaria cases reported in this study were mostly imported cases. However the co-existence of local cases and potential Plasmodium spp. vectors should be cause for concern. The results of this survey reflect the need of maintaining closely monitored malaria control programs and continuous extensive malaria
Giha, H A; Elghazali, G; A-Elgadir, T M E
A hospital-based study was carried out in Gedarif town, eastern Sudan, an area of markedly unstable malaria transmission. Among the 2488 diagnosed malaria patients, 4.4% fulfilled the WHO criteria for severe malaria, and seven died of cerebral malaria. The predominant complication was severe...
Brady, Oliver J; Godfray, H Charles J; Tatem, Andrew J; Gething, Peter W; Cohen, Justin M; McKenzie, F Ellis; Alex Perkins, T; Reiner, Robert C; Tusting, Lucy S; Scott, Thomas W; Lindsay, Steven W; Hay, Simon I; Smith, David L
Standard advice regarding vector control is to prefer interventions that reduce the lifespan of adult mosquitoes. The basis for this advice is a decades-old sensitivity analysis of 'vectorial capacity', a concept relevant for most malaria transmission models and based solely on adult mosquito population dynamics. Recent advances in micro-simulation models offer an opportunity to expand the theory of vectorial capacity to include both adult and juvenile mosquito stages in the model. In this study we revisit arguments about transmission and its sensitivity to mosquito bionomic parameters using an elasticity analysis of developed formulations of vectorial capacity. We show that reducing adult survival has effects on both adult and juvenile population size, which are significant for transmission and not accounted for in traditional formulations of vectorial capacity. The elasticity of these effects is dependent on various mosquito population parameters, which we explore. Overall, control is most sensitive to methods that affect adult mosquito mortality rates, followed by blood feeding frequency, human blood feeding habit, and lastly, to adult mosquito population density. These results emphasise more strongly than ever the sensitivity of transmission to adult mosquito mortality, but also suggest the high potential of combinations of interventions including larval source management. This must be done with caution, however, as policy requires a more careful consideration of costs, operational difficulties and policy goals in relation to baseline transmission. © The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.
Biggs, Joseph; Raman, Jaishree; Cook, Jackie; Hlongwana, Khumbulani; Drakeley, Chris; Morris, Natashia; Serocharan, Ishen; Agubuzo, Eunice; Kruger, Philip; Mabuza, Aaron; Zitha, Alpheus; Machaba, Elliot; Coetzee, Maureen; Kleinschmidt, Immo
It is widely acknowledged that modifications to existing control interventions are required if South Africa is to achieve malaria elimination. Targeting indoor residual spraying (IRS) to areas where cases have been detected is one strategy currently under investigation in northeastern South Africa. This seroprevalence baseline study, nested within a targeted IRS trial, was undertaken to provide insights into malaria transmission dynamics in South Africa and evaluate whether sero-epidemiological practices have the potential to be routinely incorporated into elimination programmes. Filter-paper blood spots, demographic and household survey data were collected from 2710 randomly selected households in 56 study wards located in the municipalities of Ba-Phalaborwa and Bushbuckridge. Blood spots were assayed for Plasmodium falciparum apical membrane antigen-1 and merozoite surface protein-119 blood-stage antigens using an enzyme linked immunosorbent assay. Seroprevalence data were analysed using a reverse catalytic model to determine malaria seroconversion rates (SCR). Geospatial cluster analysis was used to investigate transmission heterogeneity while random effects logistic regression identified risk factors associated with malaria exposure. The overall SCR across the entire study site was 0.012 (95% CI 0.008-0.017) per year. Contrasting SCRs, corresponding to distinct geographical regions across the study site, ranging from transmission heterogeneity. Geospatial cluster analysis of household seroprevalence and age-adjusted antibody responses detected statistically significant (p transmission intensity and exposure to malaria was low across both study sites, malaria transmission intensity was highly heterogeneous and associated with low socio-economic status in the region. Findings suggest focal targeting of interventions has the potential to be an appropriate strategy to deploy in South Africa. Furthermore, routinely incorporating sero-epidemiological practices into
Mmbando, Bruno Paul; Cole-Lewis, H; Sembuche, S
Low birth weight (LBW) is a risk factor for infant mortality, morbidity, growth retardation, poor cognitive development, and chronic diseases. Maternal exposure to diseases such as malaria, HIV, and syphilis has been shown to have a significant impact on birth weight (BW). This study was aimed...... babies compared to first parity women (OR=0.44, 95% CI 0.19-0.98, P=0.045). Similarly, the risk of LBW was higher in women who had delayed MCH gestational booking and in women who conceived during high malaria transmission seasons. There was high degree of preference of digits ending with 0...
Kapwata, Thandi; Gebreslasie, Michael T
Malaria is an environmentally driven disease. In order to quantify the spatial variability of malaria transmission, it is imperative to understand the interactions between environmental variables and malaria epidemiology at a micro-geographic level using a novel statistical approach. The random forest (RF) statistical learning method, a relatively new variable-importance ranking method, measures the variable importance of potentially influential parameters through the percent increase of the mean squared error. As this value increases, so does the relative importance of the associated variable. The principal aim of this study was to create predictive malaria maps generated using the selected variables based on the RF algorithm in the Ehlanzeni District of Mpumalanga Province, South Africa. From the seven environmental variables used [temperature, lag temperature, rainfall, lag rainfall, humidity, altitude, and the normalized difference vegetation index (NDVI)], altitude was identified as the most influential predictor variable due its high selection frequency. It was selected as the top predictor for 4 out of 12 months of the year, followed by NDVI, temperature and lag rainfall, which were each selected twice. The combination of climatic variables that produced the highest prediction accuracy was altitude, NDVI, and temperature. This suggests that these three variables have high predictive capabilities in relation to malaria transmission. Furthermore, it is anticipated that the predictive maps generated from predictions made by the RF algorithm could be used to monitor the progression of malaria and assist in intervention and prevention efforts with respect to malaria.
Full Text Available Malaria is an environmentally driven disease. In order to quantify the spatial variability of malaria transmission, it is imperative to understand the interactions between environmental variables and malaria epidemiology at a micro-geographic level using a novel statistical approach. The random forest (RF statistical learning method, a relatively new variable-importance ranking method, measures the variable importance of potentially influential parameters through the percent increase of the mean squared error. As this value increases, so does the relative importance of the associated variable. The principal aim of this study was to create predictive malaria maps generated using the selected variables based on the RF algorithm in the Ehlanzeni District of Mpumalanga Province, South Africa. From the seven environmental variables used [temperature, lag temperature, rainfall, lag rainfall, humidity, altitude, and the normalized difference vegetation index (NDVI], altitude was identified as the most influential predictor variable due its high selection frequency. It was selected as the top predictor for 4 out of 12 months of the year, followed by NDVI, temperature and lag rainfall, which were each selected twice. The combination of climatic variables that produced the highest prediction accuracy was altitude, NDVI, and temperature. This suggests that these three variables have high predictive capabilities in relation to malaria transmission. Furthermore, it is anticipated that the predictive maps generated from predictions made by the RF algorithm could be used to monitor the progression of malaria and assist in intervention and prevention efforts with respect to malaria.
Full Text Available The association between P. falciparum eba-175, ama-1, and msp-3 polymorphism in the pathogenicity of malaria disease was investigated. We therefore compared the prevalence of different alleles between symptomatic and asymptomatic malarial children under five years of age living in Burkina Faso. Blood filter papers were collected during the 2008 malaria transmission season from 228 symptomatic and 199 asymptomatic children under five years of age. All patients were living in the rural area of Saponé at about 50 km from Ouagadougou, the capital city of Burkina Faso. P. falciparum parasite DNA was extracted using QIAGEN kits and the alleles diversity was assessed by a nested PCR. PCR products were then digested by restriction enzymes based on already described polymorphic regions of the eba-175, ama-1, and msp-3 genes. The individual alleles eba-175_FCR3 and msp-3_K1 frequencies were statistically higher (p0.05. The comparative analysis of P. falciparum genotypes indicated that the polymorphism in eba-175 and msp-3 genotypes varied between asymptomatic and symptomatic clinical groups and may contribute to the pathogenesis of malaria.
Lee, H I; Lee, J S; Shin, E H; Lee, W J; Kim, Y Y; Lee, K R
To evaluate the factors that determine the transmission level of vivax malaria using vectorial capacity, entomological surveys were conducted from June to August, 2000. From 6 nights of human-bait collection in Paju, the human biting rate (ma) was counted as 87.5 bites/man/night. The parity of Anopheles sinensis from human baiting collections fluctuated from 41% to 71% (average 48.8%) of which the rate gradually increased as time passed on: 35.2% in Jun.; 55.0% in July; 66.2% in Aug. From this proportion of parous, we could estimate the probability of daily survival rate of An. sinensis to be 0.79 assumed with 3 days gonotrophic cycle and the expectancy of infective life through 11 days could be defined as 0.073. Blood meal analysis was performed using ELISA to determine the blood meal source. Only 0.8% of blood meals were from human hosts. We could conclude that An. sinensis is highly zoophilic (cow 61.8%). Malaria is highly unstable (stability index malaria transmission potential is very low due to a low human blood index. Therefore, we could conclude that malaria transmission by An. sinensis is resulted by high population density, not by high transmission potential. For this reason, we need more effort to decrease vector population and vector-human contact to eradicate malaria in Korea.
its prevention methods, but are not well—intorrned ofthe beneﬁts of using l'ii'Ns. More education and advocacies on use of. lTNs to parents and children is needed. Key words: malaria. prevention, .... population were sleeping under mosquito nets in. Tanzania in 2003; while only 25% of the households had at least one ITN ...
Gerardin, Jaline; Bever, Caitlin A; Bridenbecker, Daniel; Hamainza, Busiku; Silumbe, Kafula; Miller, John M; Eisele, Thomas P; Eckhoff, Philip A; Wenger, Edward A
Reactive case detection could be a powerful tool in malaria elimination, as it selectively targets transmission pockets. However, field operations have yet to demonstrate under which conditions, if any, reactive case detection is best poised to push a region to elimination. This study uses mathematical modelling to assess how baseline transmission intensity and local interconnectedness affect the impact of reactive activities in the context of other possible intervention packages. Communities in Southern Province, Zambia, where elimination operations are currently underway, were used as representatives of three archetypes of malaria transmission: low-transmission, high household density; high-transmission, low household density; and high-transmission, high household density. Transmission at the spatially-connected household level was simulated with a dynamical model of malaria transmission, and local variation in vectorial capacity and intervention coverage were parameterized according to data collected from the area. Various potential intervention packages were imposed on each of the archetypical settings and the resulting likelihoods of elimination by the end of 2020 were compared. Simulations predict that success of elimination campaigns in both low- and high-transmission areas is strongly dependent on stemming the flow of imported infections, underscoring the need for regional-scale strategies capable of reducing transmission concurrently across many connected areas. In historically low-transmission areas, treatment of clinical malaria should form the cornerstone of elimination operations, as most malaria infections in these areas are symptomatic and onward transmission would be mitigated through health system strengthening; reactive case detection has minimal impact in these settings. In historically high-transmission areas, vector control and case management are crucial for limiting outbreak size, and the asymptomatic reservoir must be addressed through
Sepúlveda, Nuno; Manjurano, Alphaxard; Campino, Susana G; Lemnge, Martha; Lusingu, John; Olomi, Raimos; Rockett, Kirk A; Hubbart, Christina; Jeffreys, Anna; Rowlands, Kate; Clark, Taane G; Riley, Eleanor M; Drakeley, Chris J
Human malaria susceptibility is determined by multiple genetic factors. It is unclear, however, which genetic variants remain important over time. Genetic associations of 175 high-quality polymorphisms within several malaria candidate genes were examined in a sample of 8096 individuals from northeast Tanzania using altitude, seroconversion rates, and parasite rates as proxies of historical, recent, and current malaria transmission intensity. A principal component analysis was used to derive 2 alternative measures of overall malaria propensity of a location across different time scales. Common red blood cell polymorphisms (ie, hemoglobin S, glucose-6-phosphate dehydrogenase, and α-thalassemia) were the only ones to be associated with all 3 measures of transmission intensity and the first principal component. Moderate associations were found between some immune response genes (ie, IL3 and IL13) and parasite rates, but these could not be reproduced using the alternative measures of malaria propensity. We have demonstrated the potential of using altitude and seroconversion rate as measures of malaria transmission capturing medium- to long-term time scales to detect genetic associations that are likely to persist over time. These measures also have the advantage of minimizing the deleterious effects of random factors affecting parasite rates on the respective association signals.
, too much exposure to sunlight 25.3%, eating of oily foods 16.7%, cold weather 14.2% and witchcraft 1.2%. There was a statistical difference among the local beliefs on transmission. Local beliefs associated with malaria prevention in the ...
In this paper, we discuss an ordinary differential equation mathematical model for the spread of malaria in human and mosquito population. We suppose the human population to act as a reservoir. Both the species follow a logistic population model. The transmission coefficient or the interaction coefficient of humans is ...
Background: In recent years malaria is becoming endemic in highland areas beyond its previously known upper limit of transmission. Assessment of the situation of the disease in such areas is necessary in order to institute appropriate control activities. Objectives: The objectives of the study were to determine the ...
Sauerwein, R W; Bousema, T
Stimulated by recent advances in malaria control and increased funding, the elimination of malaria is now considered to be an attainable goal for an increasing number of malaria-endemic regions. This has boosted the interest in transmission-reducing interventions including vaccines that target sexual, sporogenic, and/or mosquito-stage antigens to interrupt malaria transmission (SSM-VIMT). SSM-VIMT aim to prevent human malaria infection in vaccinated communities by inhibiting parasite development within the mosquito after a blood meal taken from a gametocyte carrier. Only a handful of target antigens are in clinical development and progress has been slow over the years. Major stumbling blocks include (i) the expression of appropriately folded target proteins and their downstream purification, (ii) insufficient induction of sustained functional blocking antibody titers by candidate vaccines in humans, and (iii) validation of a number of (bio)-assays as correlate for blocking activity in the field. Here we discuss clinical manufacturing and testing of current SSM-VIMT candidates and the latest bio-assay development for clinical evaluation. New testing strategies are discussed that may accelerate the evaluation and application of SSM-VIMT. Copyright © 2015. Published by Elsevier Ltd.
Snow, R W; Omumbo, J A; Lowe, B; Molyneux, C S; Obiero, J O; Palmer, A; Weber, M W; Pinder, M; Nahlen, B; Obonyo, C; Newbold, C; Gupta, S; Marsh, K
highly endemic areas measures which reduce parasite transmission, and thus immunity, may lead to a change in both the clinical spectrum of severe disease and the overall burden of severe malaria morbidity.
Ebhuoma, Osadolor; Gebreslasie, Michael
Malaria is a serious public health threat in Sub-Saharan Africa (SSA), and its transmission risk varies geographically. Modelling its geographic characteristics is essential for identifying the spatial and temporal risk of malaria transmission. Remote sensing (RS) has been serving as an important tool in providing and assessing a variety of potential climatic/environmental malaria transmission variables in diverse areas. This review focuses on the utilization of RS-driven climatic/environmental variables in determining malaria transmission in SSA. A systematic search on Google Scholar and the Institute for Scientific Information (ISI) Web of Knowledge(SM) databases (PubMed, Web of Science and ScienceDirect) was carried out. We identified thirty-five peer-reviewed articles that studied the relationship between remotely-sensed climatic variable(s) and malaria epidemiological data in the SSA sub-regions. The relationship between malaria disease and different climatic/environmental proxies was examined using different statistical methods. Across the SSA sub-region, the normalized difference vegetation index (NDVI) derived from either the National Oceanic and Atmospheric Administration (NOAA) Advanced Very High Resolution Radiometer (AVHRR) or Moderate-resolution Imaging Spectrometer (MODIS) satellite sensors was most frequently returned as a statistically-significant variable to model both spatial and temporal malaria transmission. Furthermore, generalized linear models (linear regression, logistic regression and Poisson regression) were the most frequently-employed methods of statistical analysis in determining malaria transmission predictors in East, Southern and West Africa. By contrast, multivariate analysis was used in Central Africa. We stress that the utilization of RS in determining reliable malaria transmission predictors and climatic/environmental monitoring variables would require a tailored approach that will have cognizance of the geographical
Full Text Available Malaria is a serious public health threat in Sub-Saharan Africa (SSA, and its transmission risk varies geographically. Modelling its geographic characteristics is essential for identifying the spatial and temporal risk of malaria transmission. Remote sensing (RS has been serving as an important tool in providing and assessing a variety of potential climatic/environmental malaria transmission variables in diverse areas. This review focuses on the utilization of RS-driven climatic/environmental variables in determining malaria transmission in SSA. A systematic search on Google Scholar and the Institute for Scientific Information (ISI Web of KnowledgeSM databases (PubMed, Web of Science and ScienceDirect was carried out. We identified thirty-five peer-reviewed articles that studied the relationship between remotely-sensed climatic variable(s and malaria epidemiological data in the SSA sub-regions. The relationship between malaria disease and different climatic/environmental proxies was examined using different statistical methods. Across the SSA sub-region, the normalized difference vegetation index (NDVI derived from either the National Oceanic and Atmospheric Administration (NOAA Advanced Very High Resolution Radiometer (AVHRR or Moderate-resolution Imaging Spectrometer (MODIS satellite sensors was most frequently returned as a statistically-significant variable to model both spatial and temporal malaria transmission. Furthermore, generalized linear models (linear regression, logistic regression and Poisson regression were the most frequently-employed methods of statistical analysis in determining malaria transmission predictors in East, Southern and West Africa. By contrast, multivariate analysis was used in Central Africa. We stress that the utilization of RS in determining reliable malaria transmission predictors and climatic/environmental monitoring variables would require a tailored approach that will have cognizance of the geographical
Ebako N Takem
Full Text Available In areas of declining malaria transmission such as in The Gambia, the identification of malaria infected individuals becomes increasingly harder. School surveys may be used to identify foci of malaria transmission in the community.The survey was carried out in May-June 2011, before the beginning of the malaria transmission season. Thirty two schools in the Upper River Region of The Gambia were selected with probability proportional to size; in each school approximately 100 children were randomly chosen for inclusion in the study. Each child had a finger prick blood sample collected for the determination of antimalarial antibodies by ELISA, malaria infection by microscopy and PCR, and for haemoglobin measurement. In addition, a simple questionnaire on socio-demographic variables and the use of insecticide-treated bed nets was completed. The cut-off for positivity for antimalarial antibodies was obtained using finite mixture models. The clustered nature of the data was taken into account in the analyses.A total of 3,277 children were included in the survey. The mean age was 10 years (SD = 2.7 [range 4-21], with males and females evenly distributed. The prevalence of malaria infection as determined by PCR was 13.6% (426/3124 [95% CI = 12.2-16.3] with marked variation between schools (range 3-25%, p<0.001, while the seroprevalence was 7.8% (234/2994 [95%CI = 6.4-9.8] for MSP119, 11.6% (364/2997 [95%CI = 9.4-14.5] for MSP2, and 20.0% (593/2973 [95% CI = 16.5-23.2 for AMA1. The prevalence of all the three antimalarial antibodies positive was 2.7% (79/2920.This survey shows that malaria prevalence and seroprevalence before the transmission season were highly heterogeneous.
Takem, Ebako N; Affara, Muna; Amambua-Ngwa, Alfred; Okebe, Joseph; Ceesay, Serign J; Jawara, Musa; Oriero, Eniyou; Nwakanma, Davis; Pinder, Margaret; Clifford, Caitlin; Taal, Makie; Sowe, Momodou; Suso, Penda; Mendy, Alphonse; Mbaye, Amicoleh; Drakeley, Chris; D'Alessandro, Umberto
In areas of declining malaria transmission such as in The Gambia, the identification of malaria infected individuals becomes increasingly harder. School surveys may be used to identify foci of malaria transmission in the community. The survey was carried out in May-June 2011, before the beginning of the malaria transmission season. Thirty two schools in the Upper River Region of The Gambia were selected with probability proportional to size; in each school approximately 100 children were randomly chosen for inclusion in the study. Each child had a finger prick blood sample collected for the determination of antimalarial antibodies by ELISA, malaria infection by microscopy and PCR, and for haemoglobin measurement. In addition, a simple questionnaire on socio-demographic variables and the use of insecticide-treated bed nets was completed. The cut-off for positivity for antimalarial antibodies was obtained using finite mixture models. The clustered nature of the data was taken into account in the analyses. A total of 3,277 children were included in the survey. The mean age was 10 years (SD = 2.7) [range 4-21], with males and females evenly distributed. The prevalence of malaria infection as determined by PCR was 13.6% (426/3124) [95% CI = 12.2-16.3] with marked variation between schools (range 3-25%, p<0.001), while the seroprevalence was 7.8% (234/2994) [95%CI = 6.4-9.8] for MSP119, 11.6% (364/2997) [95%CI = 9.4-14.5] for MSP2, and 20.0% (593/2973) [95% CI = 16.5-23.2) for AMA1. The prevalence of all the three antimalarial antibodies positive was 2.7% (79/2920). This survey shows that malaria prevalence and seroprevalence before the transmission season were highly heterogeneous.
Samson S Kiware
Full Text Available BACKGROUND: High coverage of personal protection measures that kill mosquitoes dramatically reduce malaria transmission where vector populations depend upon human blood. However, most primary malaria vectors outside of sub-Saharan Africa can be classified as "very zoophagic," meaning they feed occasionally (<10% of blood meals upon humans, so personal protection interventions have negligible impact upon their survival. METHODS AND FINDINGS: We extended a published malaria transmission model to examine the relationship between transmission, control, and the baseline proportion of bloodmeals obtained from humans (human blood index. The lower limit of the human blood index enables derivation of simplified models for zoophagic vectors that (1 Rely on only three field-measurable parameters. (2 Predict immediate and delayed (with and without assuming reduced human infectivity, respectively impacts of personal protection measures upon transmission. (3 Illustrate how appreciable indirect communal-level protection for non-users can be accrued through direct personal protection of users. (4 Suggest the coverage and efficacy thresholds required to attain epidemiological impact. The findings suggest that immediate, indirect, community-wide protection of users and non-users alike may linearly relate to the efficacy of a user's direct personal protection, regardless of whether that is achieved by killing or repelling mosquitoes. High protective coverage and efficacy (≥80% are important to achieve epidemiologically meaningful impact. Non-users are indirectly protected because the two most common species of human malaria are strict anthroponoses. Therefore, the small proportion of mosquitoes that are killed or diverted while attacking humans can represent a large proportion of those actually transmitting malaria. CONCLUSIONS: Simplified models of malaria transmission by very zoophagic vectors may be used by control practitioners to predict intervention impact
Das, Manoj K; Prajapati, Brijesh K; Tiendrebeogo, Régis W
BACKGROUND: Malaria remains an important health problem in India with approximately 1 million cases in 2014. Of these, 7% occurred in the Jharkhand state mainly in the tribal population. METHODS: This study was conducted in Dumargarhi, a tribal village about 42 km east of Ranchi city, Jharkhand...... or complete out of phase pattern of the vector density peaks together with a high prevalence of parasite positive individuals in the study population explains the year-round malaria transmission in the study region. CONCLUSIONS: The collection of clinical data from a well-characterized tribal cohort from...... Jharkhand, India, has provided evidence for naturally acquired immunity against malaria in this hyperendemic region. The study also suggests that enforcement of existing control programmes can reduce the malaria burden further....
Chamchod, Farida; Britton, Nicholas F
We incorporate a vector-bias term into a malaria-transmission model to account for the greater attractiveness of infectious humans to mosquitoes in terms of differing probabilities that a mosquito arriving at a human at random picks that human depending on whether he is infectious or susceptible. We prove that transcritical bifurcation occurs at the basic reproductive ratio equalling 1 by projecting the flow onto the extended centre manifold. We next study the dynamics of the system when incubation time of malaria parasites in mosquitoes is included, and find that the longer incubation time reduces the prevalence of malaria. Also, we incorporate a random movement of mosquitoes as a diffusion term and a chemically directed movement of mosquitoes to humans expressed in terms of sweat and body odour as a chemotaxis term to study the propagation of infected population to uninfected population. We find that a travelling wave occurs; its speed is calculated numerically and estimated for the lower bound analytically.
Capinha, César; Rocha, Jorge; Sousa, Carla
Malaria is currently one of the world´s major health problems. About a half-million deaths are recorded every year. In Portugal, malaria cases were significantly high until the end of the 1950s but the disease was considered eliminated in 1973. In the past few years, endemic malaria cases have been recorded in some European countries. With the increasing human mobility from countries with endemic malaria to Portugal, there is concern about the resurgence of this disease in the country. Here, we model and map the risk of malaria transmission for mainland Portugal, considering 3 different scenarios of existing imported infections. This risk assessment resulted from entomological studies on An. atroparvus, the only known mosquito capable of transmitting malaria in the study area. We used the malariogenic potential (determined by receptivity, infectivity and vulnerability) applied over geospatial data sets to estimate spatial variation in malaria risk. The results suggest that the risk exists, and the hotspots are concentrated in the northeast region of the country and in the upper and lower Alentejo regions. PMID:27814371
Bomblies, A.; Eltahir, E.; Duchemin, J.
A coupled hydrology and entomology model for simulation of malaria transmission and malaria transmitting mosquito population dynamics is presented. Model development and validation is done using field data and observations collected at Banizoumbou and Zindarou, Niger spanning three wet seasons, from 2005 through 2007. The primary model objective is the accurate determination of climate variability effects on village scale malaria transmission. Malaria transmission dependence on climate variables is highly nonlinear and complex. Temperature and humidity affect mosquito longevity, temperature controls parasite development rates in the mosquito as well as subadult mosquito development rates, and precipitation determines the formation and persistence of adequate breeding pools. Moreover, unsaturated zone hydrology influences overland flow, and climate controlled evapotranspiration rates and root zone uptake therefore also influence breeding pool formation. High resolution distributed hydrologic simulation allows representation of the small-scale ephemeral pools that constitute the primary habitat of Anopheles gambiae mosquitoes, the dominant malaria vectors in the Niger Sahel. Remotely sensed soil type, vegetation type, and microtopography rasters are used to assign the distributed parameter fields for simulation of the land surface hydrologic response to precipitation and runoff generation. Predicted runoff from each cell flows overland and into topographic depressions, with explicit representation of infiltration and evapotranspiration. The model's entomology component interacts with simulated pools. Subadult (aquatic stage) mosquito breeding is simulated in the pools, and water temperature dependent stage advancement rates regulate adult mosquito emergence into the model domain. Once emerged, adult mosquitoes are tracked as independent individual agents that interact with their immediate environment. Attributes relevant to malaria transmission such as gonotrophic
Hendriksen, I.C.E.; White, L.J.; Veenemans, J.; Verhoef, J.C.M.
Background. In malaria-endemic settings, asymptomatic parasitemia complicates the diagnosis of malaria. Histidine-rich protein 2 (HRP2) is produced by Plasmodium falciparum, and its plasma concentration reflects the total body parasite burden. We aimed to define the malaria-attributable fraction of
Full Text Available Malaria transmission intensity is a crucial determinant of malarial disease burden and its measurement can help to define health priorities. Rapid, local estimates of transmission are required to focus resources better but current entomological and parasitological methods for estimating transmission intensity are limited in this respect. An alternative is determination of antimalarial antibody age-specific sero-prevalence to estimate sero-conversion rates (SCR, which have been shown to correlate with transmission intensity. This study evaluated SCR generated from samples collected from health facility attendees as a tool for a rapid assessment of malaria transmission intensity.The study was conducted in north east Tanzania. Antibodies to Plasmodium falciparum merozoite antigens MSP-1(19 and AMA-1 were measured by indirect ELISA. Age-specific antibody prevalence was analysed using a catalytic conversion model based on maximum likelihood to generate SCR. A pilot study, conducted near Moshi, found SCRs for AMA-1 were highly comparable between samples collected from individuals in a conventional cross-sectional survey and those collected from attendees at a local health facility. For the main study, 3885 individuals attending village health facilities in Korogwe and Same districts were recruited. Both malaria parasite prevalence and sero-positivity were higher in Korogwe than in Same. MSP-1(19 and AMA-1 SCR rates for Korogwe villages ranged from 0.03 to 0.06 and 0.07 to 0.21 respectively. In Same district there was evidence of a recent reduction in transmission, with SCR among those born since 1998 [MSP-1(19 0.002 to 0.008 and AMA-1 0.005 to 0.014 ] being 5 to 10 fold lower than among individuals born prior to 1998 [MSP-1(19 0.02 to 0.04 and AMA-1 0.04 to 0.13]. Current health facility specific estimates of SCR showed good correlations with malaria incidence rates in infants in a contemporaneous clinical trial (MSP-1(19 r(2 = 0.78, p<0.01 & AMA-1 r
Abdisalan M Noor
Full Text Available Historical evidence of the levels of intervention scale up and its relationships to changing malaria risks provides important contextual information for current ambitions to eliminate malaria in various regions of Africa today.Community-based Plasmodium falciparum prevalence data from 3,260 geo-coded time-space locations between 1969 and 1992 were assembled from archives covering an examination of 230,174 individuals located in northern Namibia. These data were standardized the age-range 2 to less than 10 years and used within a Bayesian model-based geo-statistical framework to examine the changes of malaria risk in the years 1969, 1974, 1979, 1984 and 1989 at 5×5 km spatial resolution. This changing risk was described against rainfall seasons and the wide-scale use of indoor-residual house-spraying and mass drug administration.Most areas of Northern Namibia experienced low intensity transmission during a ten-year period of wide-scale control activities between 1969 and 1979. As control efforts waned, flooding occurred, drug resistance emerged and the war for independence intensified the spatial extent of moderate-to-high malaria transmission expanded reaching a peak in the late 1980s.Targeting vectors and parasite in northern Namibia was likely to have successfully sustained a situation of low intensity transmission, but unraveled quickly to a peak of transmission intensity following a sequence of events by the early 1990s.
Brieger, W R; Sesay, H R; Adesina, H; Mosanya, M E; Ogunlade, P B; Ayodele, J O; Orisasona, S A
Urban malaria in West Africa is not well documented. While rapid urbanisation may create environmental conditions that favour mosquito breeding, urban pollution may inhibit the growth of Anopheles species. In 1996, the Basic Support for Institutionalizing Child Survival (BASICS) Project of the U.S. Agency for International Development (USAID) started building urban community health coalitions in Lagos, Nigeria, to empower communities to provide prompt treatment and appropriate prevention for major causes of childhood morbidity and mortality, including malaria, diarrhoeal disease, acute respiratory infections and vaccine preventable diseases. Intervention against malaria was predicated on national policies that assumed Nigeria was holo-endemic for malaria and that prompt treatment of febrile illness with anti-malarial drugs was an appropriate action. At the suggestion and with the assistance of another USAID programme, the Environmental Health Project (EHP), BASICS embarked on a rapid assessment of the epidemiological, entomological and sociological situation of malaria transmission and case management in three Lagos communities. During April and May 1998, blood film investigation of 916 children between the ages of 6 months and 5 years yielded a parasite prevalence rate of 0.9%. Night knockdown collections of mosquitoes in rooms yielded only C. quinquefasciatus and A. aegypti. The same results were obtained for night landing collections on human bait. Very low densities of A. gambiae larvae were found in breeding sites in Lagos Island (0.7) and Ajegunle (0.3). In contrast, community members, during focus group discussion identified malaria, in it various culturally defined forms, as a major health problem. Among the children examined clinically, 186 (20.3%) reported an illness, which they called "malaria" in the previous two weeks, and 180 had sought treatment for this illness. Data obtained from 303 shops in the area documented that a minimum of US dollars 4
Tawiah, Theresa; Hansen, Kristian Schultz; Baiden, Frank
(ACT) in all suspected malaria patients. The use of malaria rapid diagnostic tests (mRDTs) would make it possible for prescribers to diagnose malaria at point-of-care and better target the use of antimalarials. Therefore, a cost-effectiveness analysis was performed on the introduction of m...... analyses were applied to assess the robustness of ICERs. Results: The availability of mRDTs for malaria diagnosis resulted in fewer ACT treatments compared to the clinical judgement approach (73% versus 81%) and more children appropriately treated (70% versus 57%). The introduction of mRDT-based diagnosis......Background: The presumptive approach of confirming malaria in health facilities leads to over-diagnosis of malaria, over use of anti-malaria drugs and the risk of drug resistance development. WHO recommends parasitological confirmation before treatment with artemisinin-based combination therapy...
Chandler, Clare I R; Webb, Emily L; Maiteki-Sebuguzi, Catherine; Nayiga, Susan; Nabirye, Christine; DiLiberto, Deborah D; Ssemmondo, Emmanuel; Dorsey, Grant; Kamya, Moses R; Staedke, Sarah G
Rapid diagnostic tests for malaria (mRDTs) have been scaled-up widely across Africa. The PRIME study evaluated an intervention aiming to improve fever case management using mRDTs at public health centers in Uganda. A cluster-randomized trial was conducted from 2010-13 in Tororo, a high malaria transmission setting. Twenty public health centers were randomized in a 1:1 ratio to intervention or control. The intervention included training in health center management, fever case management with mRDTs, and patient-centered services; plus provision of mRDTs and artemether-lumefantrine (AL) when stocks ran low. Three rounds of Interviews were conducted with caregivers of children under five years of age as they exited health centers (N = 1400); reference mRDTs were done in children with fever (N = 1336). Health worker perspectives on mRDTs were elicited through semi-structured questionnaires (N = 49) and in-depth interviews (N = 10). The primary outcome was inappropriate treatment of malaria, defined as the proportion of febrile children who were not treated according to guidelines based on the reference mRDT. There was no difference in inappropriate treatment of malaria between the intervention and control arms (24.0% versus 29.7%, adjusted risk ratio 0.81 [95% CI: 0.56, 1.17] p = 0.24). Most children (76.0%) tested positive by reference mRDT, but many were not prescribed AL (22.5% intervention versus 25.9% control, p = 0.53). Inappropriate treatment of children testing negative by reference mRDT with AL was also common (31.3% invention vs 42.4% control, p = 0.29). Health workers appreciated mRDTs but felt that integrating testing into practice was challenging given constraints on time and infrastructure. The PRIME intervention did not have the desired impact on inappropriate treatment of malaria for children under five. In this high transmission setting, use of mRDTs did not lead to the reductions in antimalarial prescribing seen elsewhere. Broader investment in health
Viana, Mafalda; Hughes, Angela; Matthiopoulos, Jason; Ranson, Hilary; Ferguson, Heather M
Malaria transmission has been substantially reduced across Africa through the distribution of long-lasting insecticidal nets (LLINs). However, the emergence of insecticide resistance within mosquito vectors risks jeopardizing the future efficacy of this control strategy. The severity of this threat is uncertain because the consequences of resistance for mosquito fitness are poorly understood: while resistant mosquitoes are no longer immediately killed upon contact with LLINs, their transmission potential may be curtailed because of longer-term fitness costs that persist beyond the first 24 h after exposure. Here, we used a Bayesian state-space model to quantify the immediate (within 24 h of exposure) and delayed (>24 h after exposure) impact of insecticides on daily survival and malaria transmission potential of moderately and highly resistant laboratory populations of the major African malaria vector Anopheles gambiae Contact with LLINs reduced the immediate survival of moderately and highly resistant An. gambiae strains by 60-100% and 3-61%, respectively, and delayed mortality impacts occurring beyond the first 24 h after exposure further reduced their overall life spans by nearly one-half. In total, insecticide exposure was predicted to reduce the lifetime malaria transmission potential of insecticide-resistant vectors by two-thirds, with delayed effects accounting for at least one-half of this reduction. The existence of substantial, previously unreported, delayed mortality effects within highly resistant malaria vectors following exposure to insecticides does not diminish the threat of growing resistance, but posits an explanation for the apparent paradox of continued LLIN effectiveness in the presence of high insecticide resistance.
Rice, Benjamin L; Golden, Christopher D; Anjaranirina, Evelin Jean Gasta; Botelho, Carolina Mastella; Volkman, Sarah K; Hartl, Daniel L
Encouraging advances in the control of Plasmodium falciparum malaria have been observed across much of Africa in the past decade. However, regions of high relative prevalence and transmission that remain unaddressed or unrecognized provide a threat to this progress. Difficulties in identifying such localized hotspots include inadequate surveillance, especially in remote regions, and the cost and labor needed to produce direct estimates of transmission. Genetic data can provide a much-needed alternative to such empirical estimates, as the pattern of genetic variation within malaria parasite populations is indicative of the level of local transmission. Here, genetic data were used to provide the first empirical estimates of P. falciparum malaria prevalence and transmission dynamics for the rural, remote Makira region of northeastern Madagascar. Longitudinal surveys of a cohort of 698 total individuals (both sexes, 0-74 years of age) were performed in two communities bordering the Makira Natural Park protected area. Rapid diagnostic tests, with confirmation by molecular methods, were used to estimate P. falciparum prevalence at three seasonal time points separated by 4-month intervals. Genomic loci in a panel of polymorphic, putatively neutral markers were genotyped for 94 P. falciparum infections and used to characterize genetic parameters known to correlate with transmission levels. Overall, 27.8% of individuals tested positive for P. falciparum over the 10-month course of the study, a rate approximately sevenfold higher than the countrywide average for Madagascar. Among those P. falciparum infections, a high level of genotypic diversity and a high frequency of polygenomic infections (68.1%) were observed, providing a pattern consistent with high and stable transmission. Prevalence and genetic diversity data indicate that the Makira region is a hotspot of P. falciparum transmission in Madagascar. This suggests that the area should be highlighted for future
Garske, Tini; Ferguson, Neil M; Ghani, Azra C
Malaria transmission is strongly influenced by climatic conditions which determine the abundance and seasonal dynamics of the Anopheles vector. In particular, water temperature influences larval development rates whereas air temperature determines adult longevity as well as the rate of parasite development within the adult mosquito. Although data on land surface temperature exist at a spatial resolution of approximately 1 km globally with four time steps per day, comparable data are not currently available for air temperature. In order to address this gap and demonstrate the importance of using the right type of temperature data, we fitted simple models of the relationship between land-surface and air temperature at lower resolution to obtain a high resolution estimate of air temperature across Africa. We then used these estimates to calculate some crucial malaria transmission parameters that strongly depend on air temperatures. Our results demonstrate substantial differences between air and surface temperatures that impact temperature-based maps of areas suitable for transmission. We present high resolution maps of the malaria transmission parameters driven by air temperature and their seasonal variation. The fitted air temperature datasets are made publicly available alongside this publication.
Giha, H A; Rosthoj, S; Dodoo, D
This study investigated the epidemiology of uncomplicated falciparum malaria in an area of unstable and seasonal transmission in eastern Sudan. About 90% of malaria morbidity in this region occurs in the months of September to November, and very few malaria cases occur during the intensely arid...... Sudanese dry season and during years of drought. The malaria situation in the study site, the village of Daraweesh, was analysed during 3 consecutive malaria seasons in 1993-95 during which the 457 inhabitants suffered at total of 436 episodes of falciparum malaria. Using an Andersen-Gill proportional...
Knipes, Alaine Kathryn; Lemoine, Jean Frantz; Monestime, Franck; Fayette, Carl R; Direny, Abdel N; Desir, Luccene; Beau de Rochars, Valery E; Streit, Thomas G; Renneker, Kristen; Chu, Brian K; Chang, Michelle A; Mace, Kimberly E; Won, Kimberly Y; Lammie, Patrick J
Since 2001, Haiti's National Program for the Elimination of Lymphatic Filariasis (NPELF) has worked to reduce the transmission of lymphatic filariasis (LF) through annual mass drug administration (MDA) with diethylcarbamazine and albendazole. The NPELF reached full national coverage with MDA for LF in 2012, and by 2014, a total of 14 evaluation units (48 communes) had met WHO eligibility criteria to conduct LF transmission assessment surveys (TAS) to determine whether prevalence had been reduced to below a threshold, such that transmission is assumed to be no longer sustainable. Haiti is also endemic for malaria and many communities suffer a high burden of soil transmitted helminths (STH). Heeding the call from WHO for integration of neglected tropical diseases (NTD) activities, Haiti's NPELF worked with the national malaria control program (NMCP) and with partners to develop an integrated TAS (LF-STH-malaria) to include assessments for malaria and STH. The aim of this study was to evaluate the feasibility of using TAS surveys for LF as a platform to collect information about STH and malaria. Between November 2014 and June 2015, TAS were conducted in 14 evaluation units (EUs) including 1 TAS (LF-only), 1 TAS-STH-malaria, and 12 TAS-malaria, with a total of 16,655 children tested for LF, 14,795 tested for malaria, and 298 tested for STH. In all, 12 of the 14 EUs passed the LF TAS, allowing the program to stop MDA for LF in 44 communes. The EU where children were also tested for STH will require annual school-based treatment with albendazole to maintain reduced STH levels. Finally, only 12 of 14,795 children tested positive for malaria by RDT in 38 communes. Haiti's 2014-2015 Integrated TAS surveys provide evidence of the feasibility of using the LF TAS as a platform for integration of assessments for STH and or malaria.
Hisaeda, Hajime; Yasutomo, Koji
Malaria is still one of the infectious diseases urgently requiring control and causes socioeconomic burdens on people residing in developing countries. Malaria vaccines are expected to control the disease. However, there is no effective vaccine available despite the intense efforts of malaria scientists. One strategy for a malaria vaccine is to prevent parasite spread by means of interfering with parasite development in mosquito vectors, which is the so-called transmission-blocking vaccine (T...
Petersen, E; Høgh, B; Dziegiel, Morten Hanefeld
the antigens, the responses were often short-lived. In adults, the antibody responses to the GLURP489-1271 fusion protein and the (EENV)6 peptide peaked after 2 weeks, and not all individuals responded to all antigens. The antibody response, even against large fragments of conserved antigens, is not uniformly......The IgG and IgM antibody responses to the C-terminal 783 amino acids of the P. falciparum glutamate-rich protein, GLURP489-1271, expressed as an E. coli fusion protein, the IgG response to a 18-mer synthetic peptide EDKNEKGQHEIVEVEEIL (GLURP899-916) representing the C-terminal repeats of GLURP......, and a synthetic peptide (EENV)6 representing the C-terminal repeats from Pf155/RESA, were investigated longitudinally in 13 children and 7 adults living under conditions of continuous, intense malaria transmission. Some subjects did not recognize the antigens after malaria infection, and in subjects recognizing...
Zurovac, Dejan; Guintran, Jean-Olivier; Donald, Wesley; Naket, Esau; Malinga, Josephine; Taleo, George
Vanuatu, an archipelago country in Western Pacific harbouring low Plasmodium falciparum and Plasmodium vivax malaria transmission, has been implementing a malaria case management policy, recommending parasitological testing of patients with fever and anti-malarial treatment for test-positive only patients. A health facility survey to evaluate the health systems readiness to implement the policy and the quality of outpatient management for patients with fever was undertaken. A cross-sectional, cluster sample survey, using a range of quality-of-care methods, included all health centres and hospitals in Vanuatu. The main outcome measures were coverage of health facilities and health workers with commodities and support interventions, adherence to test and treatment recommendations, and factors influencing malaria testing. The survey was undertaken in 2014 during the low malaria season and included 41 health facilities, 67 health workers and 226 outpatient consultations for patients with fever. All facilities had capacity for parasitological diagnosis, 95.1 % stocked artemether-lumefantrine and 63.6 % primaquine. The coverage of health workers with support interventions ranged from 50 to 70 %. Health workers' knowledge was high only regarding treatment policy for uncomplicated P. falciparum malaria (83.4 %). History taking and clinical examination practices were sub-optimal. Some 35.0 % (95 % CI 23.4-48.6) of patients with fever were tested for malaria, of which all results were negative and only one patient received anti-malarial treatment. Testing was significantly higher for patients age 5 years and older (OR = 2.33; 95 % CI 1.48-5.02), seen by less qualified health workers (OR = 2.73; 95 % CI 1.48-5.02), health workers who received malaria case management training (OR = 2.39; 95 % CI 1.28-4.47) and patients with increased temperature (OR = 2.56; 95 % CI 1.17-5.57), main complaint of fever (OR = 5.82; 95 % CI 1.26-26.87) and without runny nose (OR = 3.75; 95 % CI 1
Full Text Available Rainfall and temperature are two of the major factors triggering malaria epidemics in warm semi-arid (desert-fringe and high altitude (highland-fringe epidemic risk areas. The ability of the mosquitoes to transmit Plasmodium spp. is dependent upon a series of biological features generally referred to as vectorial capacity. In this study, the vectorial capacity model (VCAP was expanded to include the influence of rainfall and temperature variables on malaria transmission potential. Data from two remote sensing products were used to monitor rainfall and temperature and were integrated into the VCAP model. The expanded model was tested in Eritrea and Madagascar to check the viability of the approach. The analysis of VCAP in relation to rainfall, temperature and malaria incidence data in these regions shows that the expanded VCAP correctly tracks the risk of malaria both in regions where rainfall is the limiting factor and in regions where temperature is the limiting factor. The VCAP maps are currently offered as an experimental resource for testing within Malaria Early Warning applications in epidemic prone regions of sub-Saharan Africa. User feedback is currently being collected in preparation for further evaluation and refinement of the VCAP model.
Rulisa, S.; Mens, P.F.; Karema, C.; Schallig, H.D.F.H.; Kaligirwa, N.; Vyankandondera, J.; de Vries, P.J.
Background: Malaria has a negative effect on pregnancy outcome, causing low birth weight, premature birth and stillbirths, particularly in areas with high malaria transmission. In Rwanda, malaria transmission intensity ranges from high to nil, probably associated with variable altitudes. Overall,
Chaccour, C.J.; Kobylinski, K.C.; Bassat, Q.; Bousema, T.; Drakeley, C.; Alonso, P.; Foy, B.D.
BACKGROUND: The heterogeneity of malaria transmission makes widespread elimination a difficult goal to achieve. Most of the current vector control measures insufficiently target outdoor transmission. Also, insecticide resistance threatens to diminish the efficacy of the most prevalent measures,
Lusingu, John P A; Vestergaard, Lasse S; Mmbando, Bruno P
and febrile malaria episodes was conducted among individuals aged below 20 years, residing in three villages of different altitude in areas of high, moderate and low malaria transmission intensity in North-Eastern Tanzania. RESULTS: The burden of anaemia and malarial fever fell mainly on the youngest children...... and was highest in the village with high transmission intensity. Although a considerable percentage of individuals in all villages carried intestinal worms, logistic regression models indicated that Plasmodium falciparum was the only significant parasitic determinant of anaemia. Interestingly, children who...... carried low-density parasitaemia at the start of the study had a lower risk of contracting a febrile malaria episode but a higher risk of anaemia during the study period, than children who were slide negative at this point in time. CONCLUSION: Young children living in the high transmission village carried...
Coulibaly, Drissa; Rebaudet, Stanislas; Travassos, Mark; Tolo, Youssouf; Laurens, Matthew; Kone, AK; Traore, Karim; Guindo, Ando; Diarra, Issa; Niangaly, Amadou; Daou, Modibo; Dembele, Ahmadou; Sissoko, Mody; Kouriba, Bourema; Dessay, Nadine
International audience; Background: Heterogeneous patterns of malaria transmission are thought to be driven by factors including host genetics, distance to mosquito breeding sites, housing construction, and socio-behavioural characteristics. Evaluation of local transmission epidemiology to characterize malaria risk is essential for planning malaria control and elimination programmes. The use of geographical information systems (GIS) techniques has been a major asset to this approach. To asses...
Das, Nani Gopal; Dhiman, Sunil; Talukdar, Pranab Kumar; Goswami, Diganta; Rabha, Bipul; Baruah, Indra; Veer, Vijay
Background Malaria transmission is perennial in the Assam–Arunachal Pradesh interstate border areas in the Sonitpur district of Assam, India. A yearlong study was carried out on the incidence of symptomatic and asymptomatic malaria and the role of asymptomatic malaria carriers in persistent transmission of the disease. The relationships between malaria incidence and weather parameters were also investigated. Methods Active and mass blood surveys were conducted on a monthly basis in Bengenajuli, Sapairaumari Pathar, and Nigam villages near the Assam–Arunachal Pradesh border. Epidemiological indices were estimated for malaria-positive cases. Multiple linear regression between monthly malaria incidence and monthly average temperature, and relative humidity along with monthly total rainfall was carried out. The known malaria vectors collected in CDC light traps were identified and recorded. Results Slide positivity rate (SPR) and Plasmodium falciparum percent (Pf%) for symptomatic malaria were 26.1 and 79.8, respectively. Prevalence of malaria vectors was observed throughout the year with varying density. Anopheles philippinensis/nivipes and A. annularis were predominant among the seven known vector species recorded currently. Asymptomatic parasitemia was detected throughout the year with SPR ranging from 4.8 to 5.3. Monthly rainfall with 1-month lag had the highest correlation (r=0.92) with SPR. The relationship between SPR and weather factors was established as SPR=−114.22+0.58 T min+1.38 RH+0.03 RF (R 2=0.89; p=0.00). Conclusion Low and relatively constant levels of asymptomatic parasitemia was present in the study area. High malaria vector density and presence of asymptomatic malaria parasite carriers were responsible for persistent malaria transmission in the region. This study concludes that passive detection and prompt treatment of asymptomatic carriers is essential for preventing persistent disease transmission. Rainfall along with some other weather
Nani Gopal Das
Full Text Available Background: Malaria transmission is perennial in the Assam–Arunachal Pradesh interstate border areas in the Sonitpur district of Assam, India. A yearlong study was carried out on the incidence of symptomatic and asymptomatic malaria and the role of asymptomatic malaria carriers in persistent transmission of the disease. The relationships between malaria incidence and weather parameters were also investigated. Methods: Active and mass blood surveys were conducted on a monthly basis in Bengenajuli, Sapairaumari Pathar, and Nigam villages near the Assam–Arunachal Pradesh border. Epidemiological indices were estimated for malaria-positive cases. Multiple linear regression between monthly malaria incidence and monthly average temperature, and relative humidity along with monthly total rainfall was carried out. The known malaria vectors collected in CDC light traps were identified and recorded. Results: Slide positivity rate (SPR and Plasmodium falciparum percent (Pf% for symptomatic malaria were 26.1 and 79.8, respectively. Prevalence of malaria vectors was observed throughout the year with varying density. Anopheles philippinensis/nivipes and A. annularis were predominant among the seven known vector species recorded currently. Asymptomatic parasitemia was detected throughout the year with SPR ranging from 4.8 to 5.3. Monthly rainfall with 1-month lag had the highest correlation (r=0.92 with SPR. The relationship between SPR and weather factors was established as SPR=−114.22+0.58 Tmin+1.38 RH+0.03 RF (R2=0.89; p=0.00. Conclusion: Low and relatively constant levels of asymptomatic parasitemia was present in the study area. High malaria vector density and presence of asymptomatic malaria parasite carriers were responsible for persistent malaria transmission in the region. This study concludes that passive detection and prompt treatment of asymptomatic carriers is essential for preventing persistent disease transmission. Rainfall along with some
Full Text Available Abstract Background Malaria transmission is highly heterogeneous in most settings, resulting in the formation of recognizable malaria hotspots. Targeting these hotspots might represent a highly efficacious way of controlling or eliminating malaria if the hotspots fuel malaria transmission to the wider community. Methods/design Hotspots of malaria will be determined based on spatial patterns in age-adjusted prevalence and density of antibodies against malaria antigens apical membrane antigen-1 and merozoite surface protein-1. The community effect of interventions targeted at these hotspots will be determined. The intervention will comprise larviciding, focal screening and treatment of the human population, distribution of long-lasting insecticide-treated nets and indoor residual spraying. The impact of the intervention will be determined inside and up to 500 m outside the targeted hotspots by PCR-based parasite prevalence in cross-sectional surveys, malaria morbidity by passive case detection in selected facilities and entomological monitoring of larval and adult Anopheles populations. Discussion This study aims to provide direct evidence for a community effect of hotspot-targeted interventions. The trial is powered to detect large effects on malaria transmission in the context of ongoing malaria interventions. Follow-up studies will be needed to determine the effect of individual components of the interventions and the cost-effectiveness of a hotspot-targeted approach, where savings made by reducing the number of compounds that need to receive interventions should outweigh the costs of hotspot-detection. Trial registration NCT01575613. The protocol was registered online on 20 March 2012; the first community was randomized on 26 March 2012.
Lynch Penelope A
Full Text Available Abstract Background Chemical insecticides against adult mosquitoes are a key element in most malaria management programmes, but their efficacy is threatened by the evolution of insecticide-resistant mosquitoes. By killing only older mosquitoes, entomopathogenic fungi can in principle significantly impact parasite transmission while imposing much less selection for resistance. Here an assessment is made as to which of the wide range of possible virulence characteristics for fungal biopesticides best realise this potential. Methods With mathematical models that capture relevant timings and survival probabilities within successive feeding cycles, transmission and resistance-management metrics are used to compare susceptible and resistant mosquitoes exposed to no intervention, to conventional instant-kill interventions, and to delayed-action biopesticides with a wide range of virulence characteristics. Results Fungal biopesticides that generate high rates of mortality at around the time mosquitoes first become able to transmit the malaria parasite offer potential for large reductions in transmission while imposing low fitness costs. The best combinations of control and resistance management are generally accessed at high levels of coverage. Strains which have high virulence in malaria-infected mosquitoes but lower virulence in malaria-free mosquitoes offer the ultimate benefit in terms of minimizing selection pressure whilst maximizing impact on transmission. Exploiting this phenotype should be a target for product development. For indoor residual spray programmes, biopesticides may offer substantial advantages over the widely used pyrethroid-based insecticides. Not only do fungal biopesticides provide substantial resistance management gains in the long term, they may also provide greater reductions in transmission before resistance has evolved. This is because fungal spores do not have contact irritancy, reducing the chances that a blood
Lynch, Penelope A; Grimm, Uwe; Thomas, Matthew B; Read, Andrew F
Chemical insecticides against adult mosquitoes are a key element in most malaria management programmes, but their efficacy is threatened by the evolution of insecticide-resistant mosquitoes. By killing only older mosquitoes, entomopathogenic fungi can in principle significantly impact parasite transmission while imposing much less selection for resistance. Here an assessment is made as to which of the wide range of possible virulence characteristics for fungal biopesticides best realise this potential. With mathematical models that capture relevant timings and survival probabilities within successive feeding cycles, transmission and resistance-management metrics are used to compare susceptible and resistant mosquitoes exposed to no intervention, to conventional instant-kill interventions, and to delayed-action biopesticides with a wide range of virulence characteristics. Fungal biopesticides that generate high rates of mortality at around the time mosquitoes first become able to transmit the malaria parasite offer potential for large reductions in transmission while imposing low fitness costs. The best combinations of control and resistance management are generally accessed at high levels of coverage. Strains which have high virulence in malaria-infected mosquitoes but lower virulence in malaria-free mosquitoes offer the ultimate benefit in terms of minimizing selection pressure whilst maximizing impact on transmission. Exploiting this phenotype should be a target for product development. For indoor residual spray programmes, biopesticides may offer substantial advantages over the widely used pyrethroid-based insecticides. Not only do fungal biopesticides provide substantial resistance management gains in the long term, they may also provide greater reductions in transmission before resistance has evolved. This is because fungal spores do not have contact irritancy, reducing the chances that a blood-fed mosquito can survive an encounter and thus live long enough to
Griffin, Jamie T; Hollingsworth, T Deirdre; Okell, Lucy C; Churcher, Thomas S; White, Michael; Hinsley, Wes; Bousema, Teun; Drakeley, Chris J; Ferguson, Neil M; Basáñez, María-Gloria; Ghani, Azra C
Over the past decade malaria intervention coverage has been scaled up across Africa. However, it remains unclear what overall reduction in transmission is achievable using currently available tools. We developed an individual-based simulation model for Plasmodium falciparum transmission in an African context incorporating the three major vector species (Anopheles gambiae s.s., An. arabiensis, and An. funestus) with parameters obtained by fitting to parasite prevalence data from 34 transmission settings across Africa. We incorporated the effect of the switch to artemisinin-combination therapy (ACT) and increasing coverage of long-lasting insecticide treated nets (LLINs) from the year 2000 onwards. We then explored the impact on transmission of continued roll-out of LLINs, additional rounds of indoor residual spraying (IRS), mass screening and treatment (MSAT), and a future RTS,S/AS01 vaccine in six representative settings with varying transmission intensity (as summarized by the annual entomological inoculation rate, EIR: 1 setting with low, 3 with moderate, and 2 with high EIRs), vector-species combinations, and patterns of seasonality. In all settings we considered a realistic target of 80% coverage of interventions. In the low-transmission setting (EIR approximately 3 ibppy [infectious bites per person per year]), LLINs have the potential to reduce malaria transmission to low levels (DDT coupled with MSAT could drive parasite prevalence below a 1% threshold. However, in the third (EIR = 46) with An. arabiensis prevailing, these interventions are insufficient to reach this threshold. In both high-transmission settings (EIR approximately 586 and 675 ibppy), either unrealistically high coverage levels (>90%) or novel tools and/or substantial social improvements will be required, although considerable reductions in prevalence can be achieved with existing tools and realistic coverage levels. Interventions using current tools can result in major reductions in P
Adam Mayyada B
Full Text Available Abstract Background Blood platelet levels are being evaluated as predictive and prognostic indicators of the severity of malaria infections in humans. However, there are few studies on platelets and Plasmodium falciparum malaria during pregnancy. Methods A case–control study was conducted at Gadarif Hospital in Eastern Sudan, an area characterized by unstable malaria transmission. The aim of the study was to investigate thrombocytopenia in pregnant women with P. falciparum malaria (cases and healthy pregnant women (controls. Results The median (interquartile platelet counts were significantly lower in patients with malaria (N = 60 than in the controls (N = 60, 61, 000 (43,000–85,000 vs. 249,000 (204,000–300,000/μL, respectively, p P. falciparum malaria (N = 12 compared with those patients with uncomplicated P. falciparum malaria (N = 48, 68, 000 (33,000-88,000/μL vs. 61, 000 (45,000–85,000/μL, respectively, p = 0.8. While none of the control group had thrombocytopenia (platelet count p P. falciparum malaria, compared with the pregnant healthy control group, were at higher risk (OR = 10.1, 95% CI = 4.1–25.18; p Conclusion P. falciparum malaria is associated with thrombocytopenia in pregnant women in this setting. More research is needed.
Eziefula Alice C
Full Text Available Abstract Following the recent successes of malaria control in sub-Saharan Africa, the gametocytocidal drug primaquine needs evaluation as a tool to further reduce the transmission of Plasmodium falciparum malaria. The drug has scarcely been used in Africa because of concerns about its safety in people with glucose-6-phosphate dehydrogenase (G6PD deficiency. The evidence base for the use of primaquine as a transmission blocker is limited by a lack of comparable clinical and parasitological endpoints between trials. In March 2012, a group of experts met in London to discuss the existing evidence on the ability of primaquine to block malaria transmission, to define the roadblocks to the use of primaquine in Africa and to develop a roadmap to enable its rapid, safe and effective deployment. The output of this meeting is a strategic plan to optimize trial design to reach desired goals efficiently. The roadmap includes suggestions for a series of phase 1, 2, 3 and 4 studies to address specific hurdles to primaquine’s deployment. These include ex-vivo studies on efficacy, primaquine pharmacokinetics and pharmacodynamics and dose escalation studies for safety in high-risk groups. Phase 3 community trials are proposed, along with Phase 4 studies to evaluate safety, particularly in pregnancy, through pharmacovigilance in areas where primaquine is already deployed. In parallel, efforts need to be made to address issues in drug supply and regulation, to map G6PD deficiency and to support the evaluation of alternative gametocytocidal compounds.
Gryseels, Charlotte; Durnez, Lies; Gerrets, René; Uk, Sambunny; Suon, Sokha; Set, Srun; Phoeuk, Pisen; Sluydts, Vincent; Heng, Somony; Sochantha, Tho; Coosemans, Marc; Peeters Grietens, Koen
In certain regions in Southeast Asia, where malaria is reduced to forested regions populated by ethnic minorities dependent on slash-and-burn agriculture, malaria vector populations have developed a propensity to feed early and outdoors, limiting the effectiveness of long-lasting insecticide-treated nets (LLIN) and indoor residual spraying (IRS). The interplay between heterogeneous human, as well as mosquito behaviour, radically challenges malaria control in such residual transmission contexts. This study examines human behavioural patterns in relation to the vector behaviour. The anthropological research used a sequential mixed-methods study design in which quantitative survey research methods were used to complement findings from qualitative ethnographic research. The qualitative research existed of in-depth interviews and participant observation. For the entomological research, indoor and outdoor human landing collections were performed. All research was conducted in selected villages in Ratanakiri province, Cambodia. Variability in human behaviour resulted in variable exposure to outdoor and early biting vectors: (i) indigenous people were found to commute between farms in the forest, where malaria exposure is higher, and village homes; (ii) the indoor/outdoor biting distinction was less clear in forest housing often completely or partly open to the outside; (iii) reported sleeping times varied according to the context of economic activities, impacting on the proportion of infections that could be accounted for by early or nighttime biting; (iv) protection by LLINs may not be as high as self-reported survey data indicate, as observations showed around 40% (non-treated) market net use while (v) unprotected evening resting and deep forest activities impacted further on the suboptimal use of LLINs. The heterogeneity of human behaviour and the variation of vector densities and biting behaviours may lead to a considerable proportion of exposure occurring during
Full Text Available Malaria resurgence risk in Morocco depends, among other factors, on environmental changes as well as the introduction of parasite carriers. The aim of this paper is to analyze the receptivity of the Loukkos area, large wetlands in Northern Morocco, to quantify and to map malaria transmission risk in this region using biological and environmental data. This risk was assessed on entomological risk basis and was mapped using environmental markers derived from satellite imagery. Maps showing spatial and temporal variations of entomological risk for Plasmodium vivax and P. falciparum were produced. Results showed this risk to be highly seasonal and much higher in rice fields than in swamps. This risk is lower for Afrotropical P. falciparum strains because of the low infectivity of Anopheles labranchiae, principal malaria vector in Morocco. However, it is very high for P. vivax mainly during summer corresponding to the rice cultivation period. Although the entomological risk is high in Loukkos region, malaria resurgence risk remains very low, because of the low vulnerability of the area.
Lopez-Perez, Mary; Pacheco, M Andreína; Buriticá, Lucía; Escalante, Ananias A; Herrera, Sócrates; Arévalo-Herrera, Myriam
Malaria causes a significant burden in highly endemic areas where children and pregnant women are more susceptible to severe disease and death, however, in low transmission settings malaria in pregnant women is less frequent. The aim of this study was to provide information of clinical profile, anti-parasite host immune responses and parasite genotyping of pregnant women with malaria in low endemic areas of Colombia. This was a descriptive study conducted through passive surveillance in 1328 individuals from three endemic areas of Córdoba, Nariño and Chocó departments between 2011 and 2013. Trained physicians confirmed the pregnancy status and recorded clinical and epidemiological information. Haematological parameters, as well as hepatic and renal function, anti-malarial antibodies and parasite genotypes were evaluated. A total of 582 women presented with malaria infection, 34 of whom were pregnant (5.8 %), and most were infected by Plasmodium falciparum (n = 24). In 44 % (n = 15) of the women, the infection occurred during the first half of pregnancy. Although uncomplicated disease and parasitaemia ≤20,000 parasites/µL were common (n = 31), three women (8.8 %) infected by P. falciparum were classified as severe cases. Mild to moderate anaemia (68 %) and mild thrombocytopaenia (41 %) were the most frequent blood alterations and in four women acute renal failure was observed. Six women presented a second malaria episode during pregnancy mainly caused by P. vivax (n = 5), although no direct evidence of relapse was found by genotyping. Two out of the six women presenting a second malaria episode had severe malaria. A low prevalence of specific anti-parasite antibodies was found. Microsatellites indicated that all P. vivax infections involved multiple lineages whereas all but one P. falciparum infections harboured single genotypes. Most malaria infected pregnant women displayed uncomplicated malaria, although a few of them with a second malaria episode presented
Full Text Available Abstract Background Previous studies in Dakar have highlighted the spatial and temporal heterogeneity of Anopheles gambiae s.l. biting rates. In order to improve the knowledge of the determinants of malaria transmission in this city, the present study reports the results of an extensive entomological survey that was conducted in 45 areas in Dakar from 2007 to 2010. Methods Water collections were monitored for the presence of anopheline larvae. Adult mosquitoes were sampled by human landing collection. Plasmodium falciparum circumsporozoïte (CSP protein indexes were measured by ELISA (enzyme-linked immunosorbent assay, and the entomological inoculation rates were calculated. Results The presence of anopheline larvae were recorded in 1,015 out of 2,683 observations made from 325 water collections. A water pH of equal to or above 8.0, a water temperature that was equal to or above 30°C, the absence of larvivorous fishes, the wet season, the presence of surface vegetation, the persistence of water and location in a slightly urbanised area were significantly associated with the presence of anopheline larvae and/or with a higher density of anopheline larvae. Most of the larval habitats were observed in public areas, i.e., freely accessible. A total of 496,310 adult mosquitoes were caught during 3096 person-nights, and 44967 of these specimens were identified as An.gambiae s.l. The mean An. gambiae s.l. human-biting rate ranged from 0.1 to 248.9 bites per person per night during the rainy season. Anopheles arabiensis (93.14%, Anopheles melas (6.83% and An. gambiae s.s. M form (0.03% were the three members of the An. gambiae complex. Fifty-two An. arabiensis and two An. melas specimens were CSP-positive, and the annual CSP index was 0.64% in 2007, 0.09% in 2008-2009 and 0.12% in 2009-2010. In the studied areas, the average EIR ranged from 0 to 17.6 infected bites per person during the entire transmission season. Conclusion The spatial and temporal
Hamad, A A; El Hassan, I M; El Khalifa, A A
Chronic Plasmodium falciparum malaria infections in a Sudanese village, in an area of seasonal and unstable malaria transmission, were monitored and genetically characterized to study the influence of persistent infection on the immunology and epidemiology of low endemicity malaria. During...... the October-December malaria season of 1996, 51 individuals out of a population of 420 had confirmed and treated P. falciparum malaria in the village of Daraweesh in eastern Sudan. In a cross-sectional survey carried out in December 1996, an additional 6 individuals were found to harbour a microscopically...
Lal, Sham; Ndyomugenyi, Richard; Paintain, Lucy; Alexander, Neal D; Hansen, Kristian S; Magnussen, Pascal; Chandramohan, Daniel; Clarke, Siân E
Many malaria-endemic countries have implemented national community health worker (CHW) programmes to serve remote populations that have poor access to malaria diagnosis and treatment. Despite mounting evidence of CHWs' ability to adhere to malaria rapid diagnostic tests (RDTs) and treatment guidelines, there is limited evidence whether CHWs adhere to the referral guidelines and refer severely ill children for further management. In southwest Uganda, this study examined whether CHWs referred children according to training guidelines and described factors associated with adherence to the referral guideline. A secondary analysis was undertaken of data collected during two cluster-randomized trials conducted between January 2010 and July 2011, one in a moderate-to-high malaria transmission setting and the other in a low malaria transmission setting. All CHWs were trained to prescribe artemisinin-based combination therapy (ACT) and recognize symptoms in children that required immediate referral to the nearest health centre. Intervention arm CHWs had additional training on how to conduct an RDT; CHWs in the control arm used a presumptive diagnosis for malaria using clinical signs and symptoms. CHW treatment registers were reviewed to identify children eligible for referral according to training guidelines (temperature of ≥38.5 °C), to assess whether CHWs adhered to the guidelines and referred them. Factors associated with adherence were examined with logistic regression models. CHWs failed to refer 58.8% of children eligible in the moderate-to-high transmission and 31.2% of children in the low transmission setting. CHWs using RDTs adhered to the referral guidelines more frequently than CHWs not using RDTs (moderate-to-high transmission: 50.1 vs 18.0%, p = 0.003; low transmission: 88.5 vs 44.1%, p sign and symptoms. As many countries scale up CHW programmes, routine monitoring of reported data should be examined carefully to assess whether CHWs adhere to referral
Gerardin, Jaline; Bever, Caitlin A.; Hamainza, Busiku; Miller, John M.; Eckhoff, Philip A.; Wenger, Edward A.
Mass campaigns with antimalarial drugs are potentially a powerful tool for local elimination of malaria, yet current diagnostic technologies are insufficiently sensitive to identify all individuals who harbor infections. At the same time, overtreatment of uninfected individuals increases the risk of accelerating emergence of drug resistance and losing community acceptance. Local heterogeneity in transmission intensity may allow campaign strategies that respond to index cases to successfully target subpatent infections while simultaneously limiting overtreatment. While selective targeting of hotspots of transmission has been proposed as a strategy for malaria control, such targeting has not been tested in the context of malaria elimination. Using household locations, demographics, and prevalence data from a survey of four health facility catchment areas in southern Zambia and an agent-based model of malaria transmission and immunity acquisition, a transmission intensity was fit to each household based on neighborhood age-dependent malaria prevalence. A set of individual infection trajectories was constructed for every household in each catchment area, accounting for heterogeneous exposure and immunity. Various campaign strategies—mass drug administration, mass screen and treat, focal mass drug administration, snowball reactive case detection, pooled sampling, and a hypothetical serological diagnostic—were simulated and evaluated for performance at finding infections, minimizing overtreatment, reducing clinical case counts, and interrupting transmission. For malaria control, presumptive treatment leads to substantial overtreatment without additional morbidity reduction under all but the highest transmission conditions. Compared with untargeted approaches, selective targeting of hotspots with drug campaigns is an ineffective tool for elimination due to limited sensitivity of available field diagnostics. Serological diagnosis is potentially an effective tool for
Cator, Lauren J; Thomas, Shalu; Paaijmans, Krijn P; Ravishankaran, Sangamithra; Justin, Johnson A; Mathai, Manu T; Read, Andrew F; Thomas, Matthew B; Eapen, Alex
Environmental temperature is an important driver of malaria transmission dynamics. Both the parasite and vector are sensitive to mean ambient temperatures and daily temperature variation. To understand transmission ecology, therefore, it is important to determine the range of microclimatic temperatures experienced by malaria vectors in the field. A pilot study was conducted in the Indian city of Chennai to determine the temperature variation in urban microclimates and characterize the thermal ecology of the local transmission setting. Temperatures were measured in a range of probable indoor and outdoor resting habitats of Anopheles stephensi in two urban slum malaria sites. Mean temperatures and daily temperature fluctuations in local transmission sites were compared with standard temperature measures from the local weather station. The biological implications of the different temperatures were explored using temperature-dependent parasite development models to provide estimates of the extrinsic incubation period (EIP) of Plasmodium vivax and Plasmodium falciparum. Mean daily temperatures within the urban transmission sites were generally warmer than those recorded at the local weather station. The main reason was that night-time temperatures were higher (and hence diurnal temperature ranges smaller) in the urban settings. Mean temperatures and temperature variation also differed between specific resting sites within the transmission environments. Most differences were of the order of 1-3°C but were sufficient to lead to important variation in predicted EIPs and hence, variation in estimates of transmission intensity. Standard estimates of environmental temperature derived from local weather stations do not necessarily provide realistic measures of temperatures within actual transmission environments. Even the small differences in mean temperatures or diurnal temperature ranges reported in this study can lead to large variations in key mosquito and/or parasite
Jamie T Griffin
Full Text Available Over the past decade malaria intervention coverage has been scaled up across Africa. However, it remains unclear what overall reduction in transmission is achievable using currently available tools.We developed an individual-based simulation model for Plasmodium falciparum transmission in an African context incorporating the three major vector species (Anopheles gambiae s.s., An. arabiensis, and An. funestus with parameters obtained by fitting to parasite prevalence data from 34 transmission settings across Africa. We incorporated the effect of the switch to artemisinin-combination therapy (ACT and increasing coverage of long-lasting insecticide treated nets (LLINs from the year 2000 onwards. We then explored the impact on transmission of continued roll-out of LLINs, additional rounds of indoor residual spraying (IRS, mass screening and treatment (MSAT, and a future RTS,S/AS01 vaccine in six representative settings with varying transmission intensity (as summarized by the annual entomological inoculation rate, EIR: 1 setting with low, 3 with moderate, and 2 with high EIRs, vector-species combinations, and patterns of seasonality. In all settings we considered a realistic target of 80% coverage of interventions. In the low-transmission setting (EIR approximately 3 ibppy [infectious bites per person per year], LLINs have the potential to reduce malaria transmission to low levels (90% or novel tools and/or substantial social improvements will be required, although considerable reductions in prevalence can be achieved with existing tools and realistic coverage levels.Interventions using current tools can result in major reductions in P. falciparum malaria transmission and the associated disease burden in Africa. Reduction to the 1% parasite prevalence threshold is possible in low- to moderate-transmission settings when vectors are primarily endophilic (indoor-resting, provided a comprehensive and sustained intervention program is achieved through
Qi, Qiuyin; Guerra, Carlos A; Moyes, Catherine L; Elyazar, Iqbal R F; Gething, Peter W; Hay, Simon I; Tatem, Andrew J
Many recent studies have examined the impact of urbanization on Plasmodium falciparum malaria endemicity and found a general trend of reduced transmission in urban areas. However, none has examined the effect of urbanization on Plasmodium vivax malaria, which is the most widely distributed malaria species and can also cause severe clinical syndromes in humans. In this study, a set of 10,003 community-based P. vivax parasite rate (PvPR) surveys are used to explore the relationships between PvPR in urban and rural settings. The PvPR surveys were overlaid onto a map of global urban extents to derive an urban/rural assignment. The differences in PvPR values between urban and rural areas were then examined. Groups of PvPR surveys inside individual city extents (urban) and surrounding areas (rural) were identified to examine the local variations in PvPR values. Finally, the relationships of PvPR between urban and rural areas within the ranges of 41 dominant Anopheles vectors were examined. Significantly higher PvPR values in rural areas were found globally. The relationship was consistent at continental scales when focusing on Africa and Asia only, but in the Americas, significantly lower values of PvPR in rural areas were found, though the numbers of surveys were small. Moreover, except for the countries in the Americas, the same trends were found at national scales in African and Asian countries, with significantly lower values of PvPR in urban areas. However, the patterns at city scales among 20 specific cities where sufficient data were available were less clear, with seven cities having significantly lower PvPR values in urban areas and two cities showing significantly lower PvPR in rural areas. The urban-rural PvPR differences within the ranges of the dominant Anopheles vectors were generally, in agreement with the regional patterns found. Except for the Americas, the patterns of significantly lower P. vivax transmission in urban areas have been found globally
Baidjoe, Amrish Y; Stevenson, Jennifer; Knight, Philip; Stone, William; Stresman, Gillian; Osoti, Victor; Makori, Euniah; Owaga, Chrispin; Odongo, Wycliffe; China, Pauline; Shagari, Shehu; Kariuki, Simon; Drakeley, Chris; Cox, Jonathan; Bousema, Teun
The East African highlands are fringe regions between stable and unstable malaria transmission. What factors contribute to the heterogeneity of malaria exposure on different spatial scales within larger foci has not been extensively studied. In a comprehensive, community-based cross-sectional survey an attempt was made to identify factors that drive the macro- and micro epidemiology of malaria in a fringe region using parasitological and serological outcomes. A large cross-sectional survey including 17,503 individuals was conducted across all age groups in a 100 km(2) area in the Western Kenyan highlands of Rachuonyo South district. Households were geo-located and prevalence of malaria parasites and malaria-specific antibodies were determined by PCR and ELISA. Household and individual risk-factors were recorded. Geographical characteristics of the study area were digitally derived using high-resolution satellite images. Malaria antibody prevalence strongly related to altitude (1350-1600 m, p malaria infections were apparently asymptomatic. Malaria parasite prevalence was associated with age, bed net use, house construction features, altitude and topographical wetness index. Antibody prevalence was associated with all these factors and distance to the nearest water body. Altitude was a major driver of malaria transmission in this study area, even across narrow altitude bands. The large proportion of asymptomatic parasite carriers at all altitudes and the age-dependent acquisition of malaria antibodies indicate stable malaria transmission; the strong correlation between current parasite carriage and serological markers of malaria exposure indicate temporal stability of spatially heterogeneous transmission.
Elhassan, I M; Hviid, L; Jakobsen, P H
In the present longitudinal study, a cohort (n = 98) of children and adults 5-30 years of age living in an area of highly seasonal and unstable malaria transmission were followed for malaria morbidity during several successive transmission seasons. Based on morbidity surveillance during 1993 and ...
Lucy C Okell
Full Text Available Artemisinin derivatives used in recently introduced combination therapies (ACTs for Plasmodium falciparum malaria significantly lower patient infectiousness and have the potential to reduce population-level transmission of the parasite. With the increased interest in malaria elimination, understanding the impact on transmission of ACT and other antimalarial drugs with different pharmacodynamics becomes a key issue. This study estimates the reduction in transmission that may be achieved by introducing different types of treatment for symptomatic P. falciparum malaria in endemic areas.We developed a mathematical model to predict the potential impact on transmission outcomes of introducing ACT as first-line treatment for uncomplicated malaria in six areas of varying transmission intensity in Tanzania. We also estimated the impact that could be achieved by antimalarials with different efficacy, prophylactic time, and gametocytocidal effects. Rates of treatment, asymptomatic infection, and symptomatic infection in the six study areas were estimated using the model together with data from a cross-sectional survey of 5,667 individuals conducted prior to policy change from sulfadoxine-pyrimethamine to ACT. The effects of ACT and other drug types on gametocytaemia and infectiousness to mosquitoes were independently estimated from clinical trial data. Predicted percentage reductions in prevalence of infection and incidence of clinical episodes achieved by ACT were highest in the areas with low initial transmission. A 53% reduction in prevalence of infection was seen if 100% of current treatment was switched to ACT in the area where baseline slide-prevalence of parasitaemia was lowest (3.7%, compared to an 11% reduction in the highest-transmission setting (baseline slide prevalence = 57.1%. Estimated percentage reductions in incidence of clinical episodes were similar. The absolute size of the public health impact, however, was greater in the highest-transmission
Theisen, Michael; Jore, Matthijs M; Sauerwein, Robert
Introduction: Malaria is a devastating vector-borne disease caused by the Plasmodium parasite, resulting in almost 0.5 million casualties per year. The parasite has a complex life-cycle that includes asexual replication in human red blood cells, causing symptomatic malaria, and sexual stages which...... are essential for the transmission to the mosquito vector. A vaccine targeting the sexual stages of the parasite and thus blocking transmission will be instrumental for the eradication of malaria. One of the leading transmission blocking vaccine candidates is the sexual stage antigen Pfs48/45. Areas covered...
Full Text Available Abstract Background In malaria endemic areas, individuals are frequently asymptomatic and may be undetected by conventional microscopy or newer, rapid diagnostic tests. Molecular techniques allow a more accurate assessment of this asymptomatic parasite burden, the extent of which is important for malaria control. This study examines the relative prevalence of sub-microscopic level parasite carriage and clonal complexity of infections (multiplicity of infection over a range of endemicities in a region of north-eastern Tanzania where altitude is an established proxy of malaria transmission. The PCR prevalence was then compared against other measures of transmission intensity collected in the same area. Methods This study used 1,121 blood samples collected from a previously conducted cross-sectional malario-metric survey during the short rainy season in 2001 from 13 villages (three at 1,200 m in altitude above sea level. Samples were analysed by PCR for carriage of parasites and multiplicity of infection. These data were compared with other measures of transmission intensity collected from the same area. Results Parasite prevalence was 34.7% by PCR and 13.6% by microscopy; a 2.5-fold difference in line with other recent observations. This fold difference was relatively consistent at the different altitude bands despite a marked decrease in parasite prevalence with altitude: vs 28.6, 600-1,200 m 35.5 vs 9.9, > 1,200 m 15.8 vs 5.9. The difference between parasite prevalence by PCR was 3.2 in individuals aged between 15 and 45 years (34.5 vs 10.9 compared with 2.5 in those aged 1-5 (34.0 vs 13.5 though this was not statistically significant. Multiplicity of infection (MOI ranged from 1.2 to 3.7 and was positively associated with parasite prevalence assessed by both PCR and microscopy. There was no association of MOI and age. Village level PCR parasite prevalence was strongly correlated with altitude, sero-conversion rate and predicted entomological
Full Text Available Abstract Background The presence of ongoing local malaria transmission, identified though local surveillance and reported to regional WHO offices, by S-E Asian countries, forms the basis of national and international chemoprophylaxis recommendations in western countries. The study was designed to examine whether the strategy of using malaria transmission in a local population was an accurate estimate of the malaria threat faced by travellers and a correlate of malaria in returning travellers. Methods Malaria endemicity was described from distribution and intensity in the local populations of ten S-E Asian destination countries over the period 2003-2008 from regionally reported cases to WHO offices. Travel acquired malaria was collated from malaria surveillance reports from the USA and 12 European countries over the same period. The numbers of travellers visiting the destination countries was based on immigration and tourism statistics collected on entry of tourists to the destination countries. Results In the destination countries, mean malaria rates in endemic countries ranged between 0.01 in Korea to 4:1000 population per year in Lao PDR, with higher regional rates in a number of countries. Malaria cases imported into the 13 countries declined by 47% from 140 cases in 2003 to 66 in 2008. A total of 608 cases (27.3% Plasmodium falciparum (Pf were reported over the six years, the largest number acquired in Indonesia, Thailand and Korea. Four countries had an incidence > 1 case per 100,000 traveller visits; Burma (Myanmar, Indonesia, Cambodia and Laos (range 1 to 11.8-case per 100,000 visits. The remaining six countries rates were Conclusion The intensity of malaria transmission particularly sub-national activity did not correlate with the risk of travellers acquiring malaria in the large numbers of arriving visitors. It is proposed to use a threshold incidence of > 1 case per 100,000 visits to consider targeted malaria prophylaxis
Full Text Available BACKGROUND: Towards the implementation of national malaria elimination programme in China since 2010, the epidemiology of malaria has changed dramatically, and the lowest malaria burden was achieved yearly. It is time to analyze the changes of malaria situation based on surveillance data from 2010 to 2012 to reconsider the strategies for malaria elimination. METHODS AND PRINCIPAL FINDINGS: Malaria epidemiological data was extracted from the provincial annual reports in China between 2010 and 2012. The trends of the general, autochthonous and imported malaria were analyzed, and epidemic areas were reclassified according to Action Plan of China Malaria Elimination (2010-2020. As a result, there reported 2743 malaria cases with a continued decline in 2012, and around 7% autochthonous malaria cases accounted. Three hundred and fifty-three individual counties from 19 provincial regions had autochthonous malaria between 2010 and 2012, and only one county was reclassified into Type I (local infections detected in 3 consecutive years and the annual incidences ≥ 1/10,000 again. However, the imported malaria cases reported of each year were widespread, and 598 counties in 29 provinces were suffered in 2012. CONCLUSIONS/SIGNIFICANCE: Malaria was reduced significantly from 2010 to 2012 in China, and malaria importation became an increasing challenge. It is necessary to adjust or update the interventions for subsequent malaria elimination planning and resource allocation.
Hyun M Yang
Full Text Available OBJECTIVE: Sensitivity analysis was applied to a mathematical model describing malaria transmission relating global warming and local socioeconomic conditions. METHODS: A previous compartment model was proposed to describe the overall transmission of malaria. This model was built up on several parameters and the prevalence of malaria in a community was characterized by the values assigned to them. To assess the control efforts, the model parameters can vary on broad intervals. RESULTS: By performing the sensitivity analysis on equilibrium points, which represent the level of malaria infection in a community, the different possible scenarios are obtained when the parameters are changed. CONCLUSIONS: Depending on malaria risk, the efforts to control its transmission can be guided by a subset of parameters used in the mathematical model.
Hundessa, Samuel; Li, Shanshan; Liu, De Li; Guo, Jinpeng; Guo, Yuming; Zhang, Wenyi; Williams, Gail
The proportion of imported malaria cases in China has increased over recent years, and has presented challenges for the malaria elimination program in China. However, little is known about the geographic distribution and environmental suitability for malaria transmission under projected climate change scenarios. Using the MaxEnt model based on malaria presence-only records, we produced environmental suitability maps and examined the relative contribution of topographic, demographic, and environmental risk factors for P. vivax and P. falciparum malaria in China. The MaxEnt model estimated that environmental suitability areas (ESAs) for malaria cover the central, south, southwest, east and northern regions, with a slightly wider range of ESAs extending to the northeast region for P. falciparum. There was spatial agreement between the location of imported cases and area environmentally suitable for malaria transmission. The ESAs of P. vivax and P. falciparum are projected to increase in some parts of southwest, south, central, north and northeast regions in the 2030s, 2050s, and 2080s, by a greater amount for P. falciparum under the RCP8.5 scenario. Temperature and NDVI values were the most influential in defining the ESAs for P. vivax, and temperature and precipitation the most influential for P. falciparum malaria. This study estimated that the ESA for malaria transmission in China will increase with climate change and highlights the potential establishment of further local transmission. This model should be used to support malaria control by targeting areas where interventions on malaria transmission need to be enhanced. Copyright © 2017 Elsevier Inc. All rights reserved.
Paulo FP Pimenta
Full Text Available In the Americas, areas with a high risk of malaria transmission are mainly located in the Amazon Forest, which extends across nine countries. One keystone step to understanding the Plasmodium life cycle in Anopheles species from the Amazon Region is to obtain experimentally infected mosquito vectors. Several attempts to colonise Ano- pheles species have been conducted, but with only short-lived success or no success at all. In this review, we review the literature on malaria transmission from the perspective of its Amazon vectors. Currently, it is possible to develop experimental Plasmodium vivax infection of the colonised and field-captured vectors in laboratories located close to Amazonian endemic areas. We are also reviewing studies related to the immune response to P. vivax infection of Anopheles aquasalis, a coastal mosquito species. Finally, we discuss the importance of the modulation of Plasmodium infection by the vector microbiota and also consider the anopheline genomes. The establishment of experimental mosquito infections with Plasmodium falciparum, Plasmodium yoelii and Plasmodium berghei parasites that could provide interesting models for studying malaria in the Amazonian scenario is important. Understanding the molecular mechanisms involved in the development of the parasites in New World vectors is crucial in order to better determine the interaction process and vectorial competence.
Arwati, Heny; Yotopranoto, Subagyo; Rohmah, Etik Ainun; Syafruddin, Din
Trenggalek district is a hypoendemic malaria area with mainly imported cases brought by migrant workers from islands outside Java. During malaria surveillance in 2015, no malaria cases were found microscopically, but some cases were positive by PCR. Therefore, a study was conducted to prove that local malaria transmission still occur. The adult villagers were invited to the house of the head of this village to be screened for malaria using aseptic venipuncture of 1 mL blood upon informed consent. Thin and thick blood films as well as blood spots on filter paper were made for each subject. The blood films were stained with Giemsa and the blood spots were used to extract DNA for polymerase chain reaction (PCR) amplification to determine the malaria infection. In addition, the history of malaria infection and travel to malaria endemic areas were recorded. Entomologic survey to detect the existence of anopheline vector was also conducted. Of the total 64 subjects that participated in the survey, no malaria parasites were found through microscopic examination of the blood films. The PCR analysis found six positive cases (two Plasmodium falciparum, one Plasmodium vivax and two mixed infection of both species), and two of them had no history of malaria and have never travelled to malaria endemic area. Entomologic survey using human bait trap detected the existence of Anopheles indefinitus that was found to be positive for P. vivax by PCR. The results indicated that although we did not find any microscopically slide positive cases, six PCR positive subjects were found. The fact that 2 of the 6 malaria positive subjects have never travelled to malaria endemic area together with the existence of the vector confirm the occurence of local transmission of malaria in the area.
Imbahale, S.S.; Mukabana, W.R.; Orindi, B.; Githeko, A.K.; Takken, W.
The main objective was to investigate malaria transmission dynamics in three different sites, two highland villages (Fort Ternan and Lunyerere) and a lowland peri-urban area (Nyalenda) of Kisumu city. Adult mosquitoes were collected using PSC and CDC light trap while malaria parasite incidence data
Eziefula, A.C.; Gosling, R.; Hwang, J.; Hsiang, M.S.; Bousema, J.T.; von Seidlein, L.; Drakeley, C.; on behalf of the Primaquine in Africa Discussion, G.
ABSTRACT: Following the recent successes of malaria control in sub-Saharan Africa, the gametocytocidal drug primaquine needs evaluation as a tool to further reduce the transmission of Plasmodium falciparum malaria. The drug has scarcely been used in Africa because of concerns about its safety in
Rosas-Aguirre, Angel; Llanos-Cuentas, Alejandro; Speybroeck, Niko
Where malaria endemicity is low, control programmes need increasingly sensitive tools for monitoring malaria transmission intensity (MTI) and to better define health priorities. A cross-sectional survey was conducted in a low endemicity area of the Peruvian north-western coast to assess the MTI u...
Waltmann, Andreea; Darcy, Andrew W; Harris, Ivor; Koepfli, Cristian; Lodo, John; Vahi, Ventis; Piziki, David; Shanks, G Dennis; Barry, Alyssa E; Whittaker, Maxine; Kazura, James W; Mueller, Ivo
Solomon Islands is intensifying national efforts to achieve malaria elimination. A long history of indoor spraying with residual insecticides, combined recently with distribution of long lasting insecticidal nets and artemether-lumefantrine therapy, has been implemented in Solomon Islands. The impact of these interventions on local endemicity of Plasmodium spp. is unknown. In 2012, a cross-sectional survey of 3501 residents of all ages was conducted in Ngella, Central Islands Province, Solomon Islands. Prevalence of Plasmodium falciparum, P. vivax, P. ovale and P. malariae was assessed by quantitative PCR (qPCR) and light microscopy (LM). Presence of gametocytes was determined by reverse transcription quantitative PCR (RT-qPCR). By qPCR, 468 Plasmodium spp. infections were detected (prevalence = 13.4%; 463 P. vivax, five mixed P. falciparum/P. vivax, no P. ovale or P. malariae) versus 130 by LM (prevalence = 3.7%; 126 P. vivax, three P. falciparum and one P. falciparum/P. vivax). The prevalence of P. vivax infection varied significantly among villages (range 3.0-38.5%, p<0.001) and across age groups (5.3-25.9%, p<0.001). Of 468 P. vivax infections, 72.9% were sub-microscopic, 84.5% afebrile and 60.0% were both sub-microscopic and afebrile. Local residency, low education level of the household head and living in a household with at least one other P. vivax infected individual increased the risk of P. vivax infection. Overall, 23.5% of P. vivax infections had concurrent gametocytaemia. Of all P. vivax positive samples, 29.2% were polyclonal by MS16 and msp1F3 genotyping. All five P. falciparum infections were detected in residents of the same village, carried the same msp2 allele and four were positive for P. falciparum gametocytes. P. vivax infection remains endemic in Ngella, with the majority of cases afebrile and below the detection limit of LM. P. falciparum has nearly disappeared, but the risk of re-introductions and outbreaks due to travel to nearby islands
Wort, Ulrika Uddenfeldt; Hastings, Ian; Mutabingwa, T. K.; Brabin, Bernard J.
BACKGROUND: The impact of malaria on the risk of stillbirth is still under debate. The aim of the present analysis was to determine comparative changes in stillbirth prevalence between two areas of Tanzania with different malaria transmission patterns in order to estimate the malaria attributable
James, S.; Takken, W.; Collins, F.H.; Gottlieb, M.
As global efforts to eliminate malaria intensify, accurate information on vector populations and transmission dynamics is critical for directing control efforts, developing new control tools, and predicting the effects of these interventions under various conditions. Currently, available sampling
Heinig, R L; Paaijmans, Krijn P; Hancock, Penelope A; Thomas, Matthew B
The effectiveness of conventional malaria vector control is being threatened by the spread of insecticide resistance. One promising alternative to chemicals is the use of naturally-occurring insect-killing fungi. Numerous laboratory studies have shown that isolates of fungal pathogens such as Beauveria bassiana can infect and kill adult mosquitoes, including those resistant to chemical insecticides.Unlike chemical insecticides, fungi may take up to a week or more to kill mosquitoes following exposure. This slow kill speed can still reduce malaria transmission because the malaria parasite itself takes at least eight days to complete its development within the mosquito. However, both fungal virulence and parasite development rate are strongly temperature-dependent, so it is possible that biopesticide efficacy could vary across different transmission environments.We examined the virulence of a candidate fungal isolate against two key malaria vectors at temperatures from 10-34 °C. Regardless of temperature, the fungus killed more than 90% of exposed mosquitoes within the predicted duration of the malarial extrinsic incubation period, a result that was robust to realistic diurnal temperature variation.We then incorporated temperature sensitivities of a suite of mosquito, parasite and fungus life-history traits that are important determinants of malaria transmission into a stage-structured malaria transmission model. The model predicted that, at achievable daily fungal infection rates, fungal biopesticides have the potential to deliver substantial reductions in the density of malaria-infectious mosquitoes across all temperatures representative of malaria transmission environments.Synthesis and applications. Our study combines empirical data and theoretical modelling to prospectively evaluate the potential of fungal biopesticides to control adult malaria vectors. Our results suggest that Beauveria bassiana could be a potent tool for malaria control and support further
Theisen, Michael; Roeffen, Will; Singh, Susheel K
Effective control and eventual eradication of malaria drives the imperative need for clinical development of a malaria vaccine. Asexual parasite forms are responsible for clinical disease and death while apathogenic gametocytes are responsible for transmission from man to mosquito. Vaccines...
Ndenga Bryson A
Full Text Available Abstract Background Recent resurgence of malaria in the highlands of Western Kenya has called for a more comprehensive understanding of the previously neglected complex highland vector ecology. Besides other drivers of malaria epidemiology, topography is likely to have a major effect on spatial vector and parasite distribution. The aim of this study was to determine the effects of topography on malaria spatial vector distribution and parasite prevalence. Methodology Indoor resting adult malaria vectors and blood parasites were collected in three villages along a 4 km transect originating from the valley bottom and ending at the hilltop for 13 months. Members of the Anopheles gambiae complex were identified by PCR. Blood parasites were collected from children 6–13 years old and densities categorized by site of home location and age of the children. Results Ninety eight percent (98% of An. gambiae s.s. and (99% Anopheles funestus were collected in houses located at the edge of the valley bottom, whereas 1% of An. gambiae s.s. were collected at mid hill and at the hilltop respectively. No An. funestus were collected at the hilltop. Malaria prevalence was 68% at the valley bottom, 40.2% at mid hill and 26.7% at the hilltop. Children aged six years and living at the edge of the valley bottom had an annual geometric mean number of 66.1 trophozoites for every 200 white blood cells, while those living at mid-hill had a mean of 84.8, and those living at hilltop had 199.5 trophozoites. Conclusion Malaria transmission in this area is mainly confined to the valley bottom. Effective vector control could be targeted at the foci. However, the few vectors observed at mid-hill maintained a relatively high prevalence rate. The higher variability in blood parasite densities and their low correlation with age in children living at the hilltop suggests a lower stability of transmission than at the mid-hill and valley bottom.
Wilson, Mark L; Krogstad, Donald J; Arinaitwe, Emmanuel; Arevalo-Herrera, Myriam; Chery, Laura; Ferreira, Marcelo U; Ndiaye, Daouda; Mathanga, Don P; Eapen, Alex
A major public health question is whether urbanization will transform malaria from a rural to an urban disease. However, differences about definitions of urban settings, urban malaria, and whether malaria control should differ between rural and urban areas complicate both the analysis of available data and the development of intervention strategies. This report examines the approach of the International Centers of Excellence for Malaria Research (ICEMR) to urban malaria in Brazil, Colombia, India (Chennai and Goa), Malawi, Senegal, and Uganda. Its major theme is the need to determine whether cases diagnosed in urban areas were imported from surrounding rural areas or resulted from transmission within the urban area. If infections are being acquired within urban areas, malaria control measures must be targeted within those urban areas to be effective. Conversely, if malaria cases are being imported from rural areas, control measures must be directed at vectors, breeding sites, and infected humans in those rural areas. Similar interventions must be directed differently if infections were acquired within urban areas. The hypothesis underlying the ICEMR approach to urban malaria is that optimal control of urban malaria depends on accurate epidemiologic and entomologic information about transmission. © The American Society of Tropical Medicine and Hygiene.
Ngarakana-Gwasira, E T; Bhunu, C P; Masocha, M; Mashonjowa, E
The sensitivity of vector borne diseases like malaria to climate continues to raise considerable concern over the implications of climate change on future disease dynamics. The problem of malaria vectors shifting from their traditional locations to invade new zones is of important concern. A mathematical model incorporating rainfall and temperature is constructed to study the transmission dynamics of malaria. The reproduction number obtained is applied to gridded temperature and rainfall datasets for baseline climate and future climate with aid of GIS. As a result of climate change, malaria burden is likely to increase in the tropics, the highland regions, and East Africa and along the northern limit of falciparum malaria. Falciparum malaria will spread into the African highlands; however it is likely to die out at the southern limit of the disease.
Dawes, Emma J; Churcher, Thomas S; Zhuang, Shijie; Sinden, Robert E; Basáñez, María-Gloria
Daily mortality is an important determinant of a vector's ability to transmit pathogens. Original simplifying assumptions in malaria transmission models presume vector mortality is independent of age, infection status and parasite load. Previous studies illustrate conflicting evidence as to the importance of Plasmodium-induced vector mortality, but very few studies to date have considered the effect of infection density on mosquito survival. A series of three experiments were conducted, each consisting of four cages of 400-1,000 Anopheles stephensi mosquitoes fed on blood infected with different Plasmodium berghei ookinete densities per microlitre of blood. Twice daily the numbers of dead mosquitoes in each group were recorded, and on alternate days a sample of live mosquitoes from each group were dissected to determine parasite density in both midgut and salivary glands. Survival analyses indicate that mosquito mortality is both age- and infection intensity-dependent. Mosquitoes experienced an initially high, partly feeding-associated, mortality rate, which declined to a minimum before increasing with mosquito age and parasite intake. As a result, the life expectancy of a mosquito is shown to be dependent on both insect age and the density of Plasmodium infection. These results contribute to understanding in greater detail the processes that influence sporogony in the mosquito, indicate the impact that parasite density could have on malaria transmission dynamics, and have implications for the design, development, and evaluation of transmission-blocking strategies.
Sinden Robert E
Full Text Available Abstract Background Daily mortality is an important determinant of a vector's ability to transmit pathogens. Original simplifying assumptions in malaria transmission models presume vector mortality is independent of age, infection status and parasite load. Previous studies illustrate conflicting evidence as to the importance of Plasmodium-induced vector mortality, but very few studies to date have considered the effect of infection density on mosquito survival. Methods A series of three experiments were conducted, each consisting of four cages of 400-1,000 Anopheles stephensi mosquitoes fed on blood infected with different Plasmodium berghei ookinete densities per microlitre of blood. Twice daily the numbers of dead mosquitoes in each group were recorded, and on alternate days a sample of live mosquitoes from each group were dissected to determine parasite density in both midgut and salivary glands. Results Survival analyses indicate that mosquito mortality is both age- and infection intensity-dependent. Mosquitoes experienced an initially high, partly feeding-associated, mortality rate, which declined to a minimum before increasing with mosquito age and parasite intake. As a result, the life expectancy of a mosquito is shown to be dependent on both insect age and the density of Plasmodium infection. Conclusion These results contribute to understanding in greater detail the processes that influence sporogony in the mosquito, indicate the impact that parasite density could have on malaria transmission dynamics, and have implications for the design, development, and evaluation of transmission-blocking strategies.
Relationship between child survival and malaria transmission: an analysis of the malaria transmission intensity and mortality burden across Africa (MTIMBA) project data in Rufiji demographic surveillance system, Tanzania.
Rumisha, Susan F; Smith, Thomas A; Masanja, Honorati; Abdulla, Salim; Vounatsou, Penelope
The precise nature of the relationship between malaria mortality and levels of transmission is unclear. Due to methodological limitations, earlier efforts to assess the linkage have lead to inconclusive results. The malaria transmission intensity and mortality burden across Africa (MTIMBA) project initiated by the INDEPTH Network collected longitudinally entomological data within a number of sites in sub-Saharan Africa to study this relationship. This work linked the MTIMBA entomology database with the routinely collected vital events within the Rufiji Demographic Surveillance System to analyse the transmission-mortality relation in the region. Bayesian Bernoulli spatio-temporal Cox proportional hazards models with village clustering, adjusted for age and insecticide-treated nets (ITNs), were fitted to assess the relation between mortality and malaria transmission measured by entomology inoculation rate (EIR). EIR was predicted at household locations using transmission models and it was incorporated in the model as a covariate with measure of uncertainty. Effects of covariates estimated by the model are reported as hazard ratios (HR) with 95% Bayesian confidence interval (BCI) and spatial and temporal parameters are presented. Separate analysis was carried out for neonates, infants and children 1-4 years of age. No significant relation between all-cause mortality and intensity of malaria transmission was indicated at any age in childhood. However, a strong age effect was shown. Comparing effects of ITN and EIR on mortality at different age categories, a decrease in protective efficacy of ITN was observed (i.e. neonates: HR = 0.65; 95% BCI:0.39-1.05; infants: HR = 0.72; 95% BCI:0.48-1.07; children 1-4 years: HR = 0.88; 95% BCI:0.62-1.23) and reduction on the effect of malaria transmission exposure was detected (i.e. neonates: HR = 1.15; 95% BCI:0.95-1.36; infants: HR = 1.13; 95% BCI:0.98-1.25; children 1-4 years: HR = 1.04; 95% BCI:0.89-1.18). A very strong spatial
Karen Molina Gómez
Full Text Available Reported urban malaria cases are increasing in Latin America, however, evidence of such trend remains insufficient. Here, we propose an integrated approach that allows characterizing malaria transmission at the rural-to-urban interface by combining epidemiological, entomological, and parasite genotyping methods.A descriptive study that combines active (ACD, passive (PCD, and reactive (RCD case detection was performed in urban and peri-urban neighborhoods of Quibdó, Colombia. Heads of households were interviewed and epidemiological surveys were conducted to assess malaria prevalence and identify potential risk factors. Sixteen primary cases, eight by ACD and eight by PCD were recruited for RCD. Using the RCD strategy, prevalence of 1% by microscopy (6/604 and 9% by quantitative polymerase chain reaction (qPCR (52/604 were found. A total of 73 houses and 289 volunteers were screened leading to 41 secondary cases, all of them in peri-urban settings (14% prevalence. Most secondary cases were genetically distinct from primary cases indicating that there were independent occurrences. Plasmodium vivax was the predominant species (76.3%, 71/93, most of them being asymptomatic (46/71. Urban and peri-urban neighborhoods had significant sociodemographic differences. Twenty-four potential breeding sites were identified, all in peri-urban areas. The predominant vectors for 1,305 adults were Anopheles nuneztovari (56,2% and An. Darlingi (42,5%. One An. nuneztovari specimen was confirmed naturally infected with P. falciparum by ELISA.This study found no evidence supporting the existence of urban malaria transmission in Quibdó. RCD strategy was more efficient for identifying malaria cases than ACD alone in areas where malaria transmission is variable and unstable. Incorporating parasite genotyping allows discovering hidden patterns of malaria transmission that cannot be detected otherwise. We propose to use the term "focal case" for those primary cases that
Molina Gómez, Karen; Caicedo, M Alejandra; Gaitán, Alexandra; Herrera-Varela, Manuela; Arce, María Isabel; Vallejo, Andrés F; Padilla, Julio; Chaparro, Pablo; Pacheco, M Andreína; Escalante, Ananias A; Arevalo-Herrera, Myriam; Herrera, Sócrates
Reported urban malaria cases are increasing in Latin America, however, evidence of such trend remains insufficient. Here, we propose an integrated approach that allows characterizing malaria transmission at the rural-to-urban interface by combining epidemiological, entomological, and parasite genotyping methods. A descriptive study that combines active (ACD), passive (PCD), and reactive (RCD) case detection was performed in urban and peri-urban neighborhoods of Quibdó, Colombia. Heads of households were interviewed and epidemiological surveys were conducted to assess malaria prevalence and identify potential risk factors. Sixteen primary cases, eight by ACD and eight by PCD were recruited for RCD. Using the RCD strategy, prevalence of 1% by microscopy (6/604) and 9% by quantitative polymerase chain reaction (qPCR) (52/604) were found. A total of 73 houses and 289 volunteers were screened leading to 41 secondary cases, all of them in peri-urban settings (14% prevalence). Most secondary cases were genetically distinct from primary cases indicating that there were independent occurrences. Plasmodium vivax was the predominant species (76.3%, 71/93), most of them being asymptomatic (46/71). Urban and peri-urban neighborhoods had significant sociodemographic differences. Twenty-four potential breeding sites were identified, all in peri-urban areas. The predominant vectors for 1,305 adults were Anopheles nuneztovari (56,2%) and An. Darlingi (42,5%). One An. nuneztovari specimen was confirmed naturally infected with P. falciparum by ELISA. This study found no evidence supporting the existence of urban malaria transmission in Quibdó. RCD strategy was more efficient for identifying malaria cases than ACD alone in areas where malaria transmission is variable and unstable. Incorporating parasite genotyping allows discovering hidden patterns of malaria transmission that cannot be detected otherwise. We propose to use the term "focal case" for those primary cases that lead to
von Fricken, Michael E; Weppelmann, Thomas A; Lam, Brandon; Eaton, Will T; Schick, Laura; Masse, Roseline; Beau De Rochars, Madsen V; Existe, Alexandre; Larkin, Joseph; Okech, Bernard A
Malaria transmission continues to occur in Haiti, with 25,423 confirmed cases of Plasmodium falciparum and 161,236 suspected infections reported in 2012. At low prevalence levels, passive surveillance measures, which rely primarily on reports from health systems, becomes less appropriate for capturing annual malaria incidence. To improve understanding of malaria transmission in Haiti, participants from the Ouest and Sud-Est departments were screened using a highly sensitive enzyme-linked immunosorbent assay (ELISA). Between February and May 2013, samples were collected from four different sites including a rural community, two schools, and a clinic located in the Ouest and Sud-Est departments of Haiti. A total of 815 serum samples were screened for malaria antibodies using an indirect ELISA coated with vaccine candidates apical membrane antigen (AMA-1) and merozoite surface protein-1 (MSP-119). The classification of previous exposure was established by using a threshold value that fell three standard deviations above the mean absorbance for suspected seronegative population members (OD of 0.32 and 0.26 for AMA-1 and MSP-1, respectively). The observed seroprevalence values were used to fit a modified reverse catalytic model to yield estimates of seroconversion rates. Of the samples screened, 172 of 815 (21.1%) were AMA-1 positive, 179 of 759 (23.6%) were MSP-119 positive, and 247 of 815 (30.3%) were positive for either AMA-1 or MSP-1; indicating rates of previous infections between 21.1% and 30.3%. Not surprisingly, age was highly associated with the likelihood of previous infection (p-value Haiti, transmission has remained relatively low over multiple decades. Elimination in Haiti appears to be feasible; however, surveillance must continue to be strengthened in order to respond to areas with high transmission and measure the impact of future interventions.
Full Text Available In many malarious regions malaria transmission roughly coincides with rainy seasons, which provide for more abundant larval habitats. In addition to precipitation, other meteorological and environmental factors may also influence malaria transmission. These factors can be remotely sensed using earth observing environmental satellites and estimated with seasonal climate forecasts. The use of remote sensing usage as an early warning tool for malaria epidemics have been broadly studied in recent years, especially for Africa, where the majority of the world’s malaria occurs. Although the Greater Mekong Subregion (GMS, which includes Thailand and the surrounding countries, is an epicenter of multidrug resistant falciparum malaria, the meteorological and environmental factors affecting malaria transmissions in the GMS have not been examined in detail. In this study, the parasitological data used consisted of the monthly malaria epidemiology data at the provincial level compiled by the Thai Ministry of Public Health. Precipitation, temperature, relative humidity, and vegetation index obtained from both climate time series and satellite measurements were used as independent variables to model malaria. We used neural network methods, an artificial-intelligence technique, to model the dependency of malaria transmission on these variables. The average training accuracy of the neural network analysis for three provinces (Kanchanaburi, Mae Hong Son, and Tak which are among the provinces most endemic for malaria, is 72.8% and the average testing accuracy is 62.9% based on the 1994-1999 data. A more complex neural network architecture resulted in higher training accuracy but also lower testing accuracy. Taking into account of the uncertainty regarding reported malaria cases, we divided the malaria cases into bands (classes to compute training accuracy. Using the same neural network architecture on the 19 most endemic provinces for years 1994 to 2000, the
Thick and thin blood smears stained with field stains A and B were made on grease-free slides and examined microscopically for the presence of malaria parasites. Structured questionnaires were used to gather socio-demographic data and knowledge, attitude and practices of the respondents regarding malaria. Out of the ...
Lusingu, John P A; Vestergaard, Lasse S; Alifrangis, Michael
of intense malaria transmission. METHODS: A six month longitudinal study was conducted in an area of holoendemic malaria transmission in north-eastern Tanzania, where the incidence of febrile malaria decreased sharply by the age of three years, and anaemia constituted a significant part of the malaria......BACKGROUND: Several studies conducted in areas of medium or low malaria transmission intensity have found associations between malaria immunity and plasma antibody levels to glutamate rich protein (GLURP). This study was conducted to analyse if a similar relationship could be documented in an area...... disease burden. Plasma antibodies to glutamate rich protein (GLURP) were analysed and related with protection against malaria morbidity in models correcting for the effect of age. RESULTS: The risk of febrile malaria episodes was reduced significantly in children with measurable anti-GLURP IgG1 antibodies...
Mutuku Francis M
Full Text Available Abstract Background Besides significantly reducing malaria vector densities, prolonged usage of bed nets has been linked to decline of Anopheles gambiae s.s. relative to Anopheles arabiensis, changes in host feeding preference of malaria vectors, and behavioural shifts to exophagy (outdoor biting for the two important malaria vectors in Africa, An. gambiae s.l. and Anopheles funestus. In southern coastal Kenya, bed net use was negligible in 1997-1998 when Anopheles funestus and An. gambiae s.s. were the primary malaria vectors, with An. arabiensis and Anopheles merus playing a secondary role. Since 2001, bed net use has increased progressively and reached high levels by 2009-2010 with corresponding decline in malaria transmission. Methods To evaluate the impact of the substantial increase in household bed net use within this area on vector density, vector composition, and human-vector contact, indoor and outdoor resting mosquitoes were collected in the same region during 2009-2010 using pyrethrum spray catches and clay pots for indoor and outdoor collections respectively. Information on bed net use per sleeping spaces and factors influencing mosquito density were determined in the same houses using Poisson regression analysis. Species distribution was determined, and number of mosquitoes per house, human-biting rates (HBR, and entomological inoculation rate (EIR were compared to those reported for the same area during 1997-1998, when bed net coverage had been minimal. Results Compared to 1997-1998, a significant decline in the relative proportion of An. gambiae s.s. among collected mosquitoes was noted, coupled with a proportionate increase of An. arabiensis. Following > 5 years of 60-86% coverage with bed nets, the density, human biting rate and EIR of indoor resting mosquitoes were reduced by more than 92% for An. funestus and by 75% for An. gambiae s.l. In addition, the host feeding choice of both vectors shifted more toward non
Mauro Shugiro Tada
Full Text Available Cross sectional studies on malaria prevalence was performed in 2001, 2002, and 2004 in Vila Candelária, an urban riverside area of Porto Velho, Rondônia, in the Brazilian Western Amazon, followed by longitudinal surveys on malaria incidence. Vila Candelária is a working class district, provided with electricity, water supply, and basic sanitation. Previous preliminary surveys indicated high malaria incidence in this community. At the end of year 2000 regular diagnostic and treatment measures for malaria were introduced, with active search of febrile cases among residents. Despite of both rapid treatment of cases and relative good sanitary and housing conditions, the malaria incidence persisted at high levels during the following years with an annual parasite index of 150 to 300/1000 inhabitants. Parasite surveys in 2001, 2002, and 2004 achieved through microscopy and polymerase chain reaction to diagnose malaria showed a constant high prevalence of asymptomatic carriers for both Plasmodium falciparum and P. vivax parasites. It was concluded that asymptomatic carriers represent an important reservoirs of parasites and that the carriers might contribute to maintaining the high level of transmission. Comparing our findings to similar geo-demographic situations found in other important urban communities of the Brazilian Amazon, we propose that asymptomatic carriers could explain malaria's outbreaks like the one recently observed in Manaus.
Idir G Akhouayri
Full Text Available The resident gut flora is known to have significant impacts on the life history of the host organism. Endosymbiotic bacterial species in the Anopheles mosquito gut are potent modulators of sexual development of the malaria parasite, Plasmodium, and thus proposed as potential control agents of malaria transmission.Here we report a melanotic pathology in the major African malaria vector Anopheles gambiae, caused by the dominant mosquito endosymbiont Elizabethkingiameningoseptica. Transfer of melanised tissues into the haemolymph of healthy adult mosquitoes or direct haemolymph inoculation with isolated E. meningoseptica bacteria were the only means for transmission and de novo formation of melanotic lesions, specifically in the fat body tissues of recipient individuals. We show that E. meningoseptica can be vertically transmitted from eggs to larvae and that E. meningoseptica-mono-associated mosquitoes display significant mortality, which is further enhanced upon Plasmodium infection, suggesting a synergistic impact of E. meningoseptica and Plasmodium on mosquito survival.The high pathogenicity and permanent association of E. meningoseptica with An. Gambiae through vertical transmission constitute attractive characteristics towards the potential design of novel mosquito/malaria biocontrol strategies.
Pothin, Emilie; Ferguson, Neil M; Drakeley, Chris J; Ghani, Azra C
Serological data are increasingly being used to monitor malaria transmission intensity and have been demonstrated to be particularly useful in areas of low transmission where traditional measures such as EIR and parasite prevalence are limited. The seroconversion rate (SCR) is usually estimated using catalytic models in which the measured antibody levels are used to categorize individuals as seropositive or seronegative. One limitation of this approach is the requirement to impose a fixed cut-off to distinguish seropositive and negative individuals. Furthermore, the continuous variation in antibody levels is ignored thereby potentially reducing the precision of the estimate. An age-specific density model which mimics antibody acquisition and loss was developed to make full use of the information provided by serological measures of antibody levels. This was fitted to blood-stage antibody density data from 12 villages at varying transmission intensity in Northern Tanzania to estimate the exposure rate as an alternative measure of transmission intensity. The results show a high correlation between the exposure rate estimates obtained and the estimated SCR obtained from a catalytic model (r = 0.95) and with two derived measures of EIR (r = 0.74 and r = 0.81). Estimates of exposure rate obtained with the density model were also more precise than those derived from catalytic models. This approach, if validated across different epidemiological settings, could be a useful alternative framework for quantifying transmission intensity, which makes more complete use of serological data.
Birhanu, Zewdie; Yihdego, Yemane Ye-Ebiyo; Emana, Daniel; Feyissa, Damtew; Kenate, Silashi; Kebede, Estifanos; Getahun, Kefelegn; Yewhalaw, Delenasaw
In the context of reduced transmission of malaria, it is essential to examine the association between exposure to malaria and haemoglobin level. This study measured the Haemoglobin level of children 2-9 years of age and examined its association with malariometric indices. A cross sectional study was conducted, during June 2016, on 763 children 2-9 years old, recruited from ten sites representing different malaria transmission settings in Ethiopia. Haemoglobin concentration was determined using HemoCue analyzer. Malariometric indices (splenomegaly rate, parasite rate and serological marker) were measured. The overall prevalence of anaemia was 17.3% (95% CI: 14.6-19.9) in the study population. Mild, moderate and severe anaemia accounted for 7.3%, 7.2% and 2.8% respectively. Of the children with anaemia (132), only 7 (5.3%) had malaria parasitaemia. The prevalence of malaria parasitaemia was 3.6% (2/56), 9.1% (5/55) and 0.0% (0/21) among children with mild, moderate and severe anaemia, respectively. Malaria reactive antibody and anaemia co-occurred in 3.13% (21/672) of the samples. Seroprevalence and parasitaemia did not have significant association with anaemia (p>0.05). However, splenomegaly was significantly associated with increased risk of anaemia (AOR=14.93; p=0.001). Anaemia was significantly higher among children 2-4 years old (22.2%), and children living in households without any insecticide treated bed net (34.0%). The prevalence of anaemia was lower by 55.0% among children living in households with at least one net (AOR=0.45, 95% CI: 0.21-0.96). Repeated exposure to malaria infections (seropositive) and parasitaemia was less likely to contribute to development of anaemia among children 2-9 years in this study setting. Thus, in low malaria endemic settings, anaemia prevention and control program required to reconsider the historical evidence that suggests malaria is one of the major risk factor for anaemia. Copyright © 2017. Published by Elsevier B.V.
Do Manh Cuong
Full Text Available Abstract Background Malaria is still prevalent in rural communities of central Vietnam even though, due to deforestation, the primary vector Anopheles dirus is uncommon. In these situations little is known about the secondary vectors which are responsible for maintaining transmission. Basic information on the identification of the species in these rural communities is required so that transmission parameters, such as ecology, behaviour and vectorial status can be assigned to the appropriate species. Methods In two rural villages - Khe Ngang and Hang Chuon - in Truong Xuan Commune, Quang Binh Province, north central Vietnam, a series of longitudinal entomological surveys were conducted during the wet and dry seasons from 2003 - 2007. In these surveys anopheline mosquitoes were collected in human landing catches, paired human and animal bait collections, and from larval surveys. Specimens belonging to species complexes were identified by PCR and sequence analysis, incrimination of vectors was by detection of circumsporozoite protein using an enzyme-linked immunosorbent assay. Results Over 80% of the anopheline fauna was made up of Anopheles sinensis, Anopheles aconitus, Anopheles harrisoni, Anopheles maculatus, Anopheles sawadwongporni, and Anopheles philippinensis. PCR and sequence analysis resolved identification issues in the Funestus Group, Maculatus Group, Hyrcanus Group and Dirus Complex. Most species were zoophilic and while all species could be collected biting humans significantly higher densities were attracted to cattle and buffalo. Anopheles dirus was the most anthropophilic species but was uncommon making up only 1.24% of all anophelines collected. Anopheles sinensis, An. aconitus, An. harrisoni, An. maculatus, An. sawadwongporni, Anopheles peditaeniatus and An. philippinensis were all found positive for circumsporozoite protein. Heterogeneity in oviposition site preference between species enabled vector densities to be high in both
Mogeni, Polycarp; Omedo, Irene; Nyundo, Christopher; Kamau, Alice; Noor, Abdisalan; Bejon, Philip
Malaria transmission intensity is heterogeneous, complicating the implementation of malaria control interventions. We provide a description of the spatial micro-epidemiology of symptomatic malaria and asymptomatic parasitaemia in multiple sites. We assembled data from 19 studies conducted between 1996 and 2015 in seven countries of sub-Saharan Africa with homestead-level geospatial data. Data from each site were used to quantify spatial autocorrelation and examine the temporal stability of hotspots. Parameters from these analyses were examined to identify trends over varying transmission intensity. Significant hotspots of malaria transmission were observed in most years and sites. The risk ratios of malaria within hotspots were highest at low malaria positive fractions (MPFs) and decreased with increasing MPF (p malaria across all sites, suggesting varying degrees of temporal stability. We observed geographical micro-variation in malaria transmission at sites with a variety of transmission intensities across sub-Saharan Africa. Hotspots are marked at lower transmission intensity, but it becomes difficult to show statistical significance when cases are sparse at very low transmission intensity. Given the predictability with which hotspots occur as transmission intensity falls, malaria control programmes should have a low threshold for responding to apparent clustering of cases.
Collins, Katharine A; Wang, Claire Yt; Adams, Matthew; Mitchell, Hayley; Rampton, Melanie; Elliott, Suzanne; Reuling, Isaie J; Bousema, Teun; Sauerwein, Robert; Chalon, Stephan; Möhrle, Jörg J; McCarthy, James S
Drugs and vaccines that can interrupt the transmission of Plasmodium falciparum will be important for malaria control and elimination. However, models for early clinical evaluation of candidate transmission-blocking interventions are currently unavailable. Here we describe a new model for evaluating malaria transmission from humans to Anopheles mosquitoes using controlled human malaria infection (CHMI). Seventeen healthy malaria-naïve volunteers underwent CHMI by intravenous inoculation of P. falciparum-infected erythrocytes to initiate blood-stage infection. Seven to eight days after inoculation participants received piperaquine (480 mg) to attenuate asexual parasite replication while allowing gametocytes to develop and mature. Primary endpoints were development of gametocytemia, the transmissibility of gametocytes from humans to mosquitoes, and the safety and tolerability of the CHMI transmission model. To investigate in-vivo gametocytocidal drug activity in this model, participants were either given an experimental antimalarial, artefenomel (500 mg), a known gametocytocidal drug, primaquine (15 mg), or remained untreated during the period of gametocyte carriage. Male and female gametocytes were detected in all participants, and transmission to mosquitoes was achieved from 8/11 (73%) participants evaluated. Compared to untreated controls (n = 7), primaquine (15 mg, n = 5) significantly reduced gametocyte burden (P = 0.01), while artefenomel (500 mg, n = 4) had no effect. Adverse events (AEs) were mostly mild or moderate. Three AEs were assessed as severe - fatigue, elevated alanine aminotransferase, and elevated aspartate aminotransferase - and were attributed to malaria infection. Transaminase elevations were transient, asymptomatic, and resolved without intervention. We report the safe and reproducible induction of P. falciparum gametocytes in healthy malaria-naïve volunteers at densities infectious to mosquitoes, thereby demonstrating the potential for
Fryauff, D J; Leksana, B; Masbar, S; Wiady, I; Sismadi, P; Susanti, A I; Nagesha, H S; Syafruddin; Atmosoedjono, S; Bangs, M J; Baird, J K
Nias Island, off the north-western coast of Sumatra, Indonesia, was one of the first locations in which chloroquine-resistant Plasmodium vivax malaria was reported. This resistance is of particular concern because its ancient megalithic culture and the outstanding surfing conditions make the island a popular tourist destination. International travel to and from the island could rapidly spread chloroquine-resistant strains of P. vivax across the planet. The threat posed by such strains, locally and internationally, has led to the routine and periodic re-assessment of the efficacy of antimalarial drugs and transmission potential on the island. Active case detection identified malaria in 124 (17%) of 710 local residents whereas passive case detection, at the central health clinic, confirmed malaria in 77 (44%) of 173 cases of presumed 'clinical malaria'. Informed consenting volunteers who had malarial parasitaemias were treated, according to the Indonesian Ministry of Health's recommendations, with sulfadoxine-pyrimethamine (SP) on day 0 (for P. falciparum) or with chloroquine (CQ) on days 0, 1 and 2 (for P. vivax). Each volunteer was then monitored for clinical and parasite response until day 28. Recurrent parasitaemia by day 28 treatment was seen in 29 (83%) of the 35 P. falciparum cases given SP (14, 11 and four cases showing RI, RII and RIII resistance, respectively). Recurrent parasitaemia was also observed, between day 11 and day 21, in six (21%) of the 28 P. vivax cases given CQ. Although the results of quantitative analysis confirmed only low prevalences of CQ-resistant P. vivax malaria, the prevalence of SP resistance among the P. falciparum cases was among the highest seen in Indonesia. When the parasites present in the volunteers with P. falciparum infections were genotyped, mutations associated with pyrimethamine resistance were found at high frequency in the dhfr gene but there was no evidence of selection for sulfadoxine resistance in the dhps gene
Full Text Available Abstract Background African malaria vectors bite predominantly indoors at night so sleeping under an Insecticide-Treated Net (ITN can greatly reduce malaria risk. Behavioural adaptation by mosquitoes to increasing ITN coverage could allow vector mosquitoes to bite outside of peak sleeping hours and undermine efficacy of this key malaria prevention measure. Methods High coverage with largely untreated nets has been achieved in the Kilombero Valley, southern Tanzania through social marketing programmes. Direct surveys of nightly biting activity by An. gambiae Giles were conducted in the area before (1997 and after (2004 implementation of ITN promotion. A novel analytical model was applied to estimate the effective protection provided by an ITN, based on published experimental hut trials combined with questionnaire surveys of human sleeping behaviour and recorded mosquito biting patterns. Results An. gambiae was predominantly endophagic and nocturnal in both surveys: Approximately 90% and 80% of exposure occurred indoors and during peak sleeping hours, respectively. ITNs consistently conferred >70% protection against exposure to malaria transmission for users relative to non-users. Conclusion As ITN coverage increases, behavioural adaptation by mosquitoes remains a future possibility. The approach described allows comparison of mosquito biting patterns and ITN efficacy at multiple study sites and times. Initial results indicate ITNs remain highly effective and should remain a top-priority intervention. Combined with recently developed transmission models, this approach allows rapid, informative and cost-effective preliminary comparison of diverse control strategies in terms of protection against exposure before more costly and intensive clinical trials.
Fletcher, Tom E; Beeching, N J
Malaria is a life-threatening disease, with its largest impact being due to Plasmodium falciparum infection in Africa. Military populations continue to be at a high risk of malaria and reported case series have frequently revealed poor compliance with preventative measures. The symptoms of malaria are non-specific and its management depends on awareness of the diagnosis and early recognition and treatment. This is aided by new and simple rapid diagnostic tests, but these should not replace the examination of blood films if these are available. Artemisinin combination therapy provides a more rapid and dependable cure of uncomplicated P falciparum infection, with artesunate now being the drug of choice in severe infection.
Gazzawi - Rogozinа L. V.
.5-4 months, and Preimaginal stages in reservoirs - about 4.5 months. The maximum number of species observed in mid-July. Due to the high number of attacks and activity in the summer , as well as the confinement of breeding sites to human settlements , An.maculipennis, An. messeae pose the greatest epidemiological risk. Conclusion. All of the above demonstrates the improvement of environmental conditions for the spread of malaria : growth of the transporter , the increase in precipitation , temperature longer transmission period of invasion .
C. T. Daniel-Ribeiro
Full Text Available The present paper reviews our recent data concerning the use of immunological methods employing monoclonal antibodies and synthetic peptides to study malaria transmission and immunity and to diagnose plasmodial infection. As concerns malaria transmission, we studied the main vectors of human malaria and the plasmodial species transmitted in endemic areas of Rondônia state, Brazil. The natural infection on anopheline was evaluated by immunoradiometric assay (IRMA using monoclonal antibodies to an immunodominant sporozoite surface antigen (CS protein demonstrated to be species specific. Our results showed that among six species of Anopheles found infected, An. darlingi was the main vector transmitting Plasmodium falciparum and P. vivax malaria in the immediate vicinity of houses. In order to assess the level of anti-CS antibodies we studied, by IRMA using the synthetic peptide corresponding to the repetitive epitope of the sporozoite CS protein, sera of individuals living in the same areas where the entomological survey has been performed. In this assay the prevalence of anti-CS antibodies was very low and did not reflect the malaria transmission rate in the studied areas. In relation to malaria diagnosis, a monoclonal antibody specific to an epitope of a 50 kDa exoantigen, the major component of supernatant collected at the time of schizont rupture, was used as a probe for the detection of P. falciparum antigens. This assay seemed to be more sensitive than parasitological examination for malaria diagnosis since it was able to detect plasmodial antigens in both symptomatic and asymtomatic individuals with negative thick blood smear at different intervals after a last parasitologically confirmed confirmed attack of malaria.
Jussara Rafael Angelo
Full Text Available This study aims to describe the role of mobility in malaria transmission by discussing recent changes in population movements in the Brazilian Amazon and developing a flow map of disease transmission in this region.This study presents a descriptive analysis using an ecological approach on regional and local scales. The study location was the municipality of Porto Velho, which is the capital of Rondônia state, Brazil. Our dataset was obtained from the official health database, the population census and an environmental database. During 2000-2007 and 2007-2010, the Porto Velho municipality had an annual population growth of 1.42% and 5.07%, respectively. This population growth can be attributed to migration, which was driven by the construction of the Madeira River hydroelectric complex. From 2010 to 2012, 63,899 malaria-positive slides were reported for residents of Porto Velho municipality; 92% of the identified samples were autochthonous, and 8% were allochthonous. The flow map of patients' movements between residential areas and areas of suspected infection showed two patterns of malaria transmission: 1 commuting between residential areas and the Jirau hydropower dam reservoir, and 2 movements between urban areas and farms and resorts in rural areas. It was also observed that areas with greater occurrences of malaria were characterized by a low rate of deforestation.The Porto Velho municipality exhibits high malaria endemicity and plays an important role in disseminating the parasite to other municipalities in the Amazon and even to non-endemic areas of the country. Migration remains an important factor for the occurrence of malaria. However, due to recent changes in human occupation of the Brazilian Amazon, characterized by intense expansion of transportation networks, commuting has also become an important factor in malaria transmission. The magnitude of this change necessitates a new model to explain malaria transmission in the Brazilian
Baidjoe, A.; Stone, W.; Ploemen, I.; Shagari, S.; Grignard, L.; Osoti, V.; Makori, E.; Stevenson, J.; Kariuki, S.; Sutherland, C.; Sauerwein, R.; Cox, J.; Drakeley, C.; Bousema, T.
BACKGROUND: Informing and evaluating malaria control efforts relies on knowledge of local transmission dynamics. Serological and molecular tools have demonstrated great sensitivity to quantify transmission intensity in low endemic settings where the sensitivity of traditional methods is limited.
Titanji Vincent PK
Full Text Available Abstract Background Malaria is a major public health problem in Cameroon. Unlike in the southern forested areas where the epidemiology of malaria has been better studied prior to the implementation of control activities, little is known about the distribution and role of anophelines in malaria transmission in the coastal areas. Methods A 12-month longitudinal entomological survey was conducted in Tiko, Limbe and Idenau from August 2001 to July 2002. Mosquitoes captured indoors on human volunteers were identified morphologically. Species of the Anopheles gambiae complex were identified using the polymerase chain reaction (PCR. Mosquito infectivity was detected by the enzyme-linked immunosorbent assay and PCR. Malariometric indices (plasmodic index, gametocytic index, parasite species prevalence were determined in three age groups (15 yrs and followed-up once every three months. Results In all, 2,773 malaria vectors comprising Anopheles gambiae (78.2%, Anopheles funestus (17.4% and Anopheles nili (7.4% were captured. Anopheles melas was not anthropophagic. Anopheles gambiae had the highest infection rates. There were 287, 160 and 149 infective bites/person/year in Tiko, Limbe and Idenau, respectively. Anopheles gambiae accounted for 72.7%, An. funestus for 23% and An. nili for 4.3% of the transmission. The prevalence of malaria parasitaemia was 41.5% in children 15 years, and Plasmodium falciparum was the predominant parasite species. Conclusion Malaria transmission is perennial, rainfall dependent and An. melas does not contribute to transmission. These findings are important in the planning and implementation of malaria control activities in coastal Cameroon and West Africa.
Onyango, Esther Achieng; Sahin, Oz; Awiti, Alex; Chu, Cordia; Mackey, Brendan
Malaria is one of the key research concerns in climate change-health relationships. Numerous risk assessments and modelling studies provide evidence that the transmission range of malaria will expand with rising temperatures, adversely impacting on vulnerable communities in the East African highlands. While there exist multiple lines of evidence for the influence of climate change on malaria transmission, there is insufficient understanding of the complex and interdependent factors that determine the risk and vulnerability of human populations at the community level. Moreover, existing studies have had limited focus on the nature of the impacts on vulnerable communities or how well they are prepared to cope. In order to address these gaps, a systems approach was used to present an integrated risk and vulnerability assessment framework for studies of community level risk and vulnerability to malaria due to climate change. Drawing upon published literature on existing frameworks, a systems approach was applied to characterize the factors influencing the interactions between climate change and malaria transmission. This involved structural analysis to determine influential, relay, dependent and autonomous variables in order to construct a detailed causal loop conceptual model that illustrates the relationships among key variables. An integrated assessment framework that considers indicators of both biophysical and social vulnerability was proposed based on the conceptual model. A major conclusion was that this integrated assessment framework can be implemented using Bayesian Belief Networks, and applied at a community level using both quantitative and qualitative methods with stakeholder engagement. The approach enables a robust assessment of community level risk and vulnerability to malaria, along with contextually relevant and targeted adaptation strategies for dealing with malaria transmission that incorporate both scientific and community perspectives.
ter Kuile, Feiko O.; Terlouw, Dianne J.; Phillips-Howard, Penelope A.; Hawley, William A.; Friedman, Jennifer F.; Kariuki, Simon K.; Shi, Ya Ping; Kolczak, Margarette S.; Lal, Altaf A.; Vulule, John M.; Nahlen, Bernard L.
The impact of insecticide (permethrin)-treated bed nets (ITNs) on malaria in pregnancy was studied in a rural area in western Kenya with intense perennial malaria transmission. All households in 40 of 79 villages were randomized to receive ITNs by January 1997. The ITNs were distributed in control
Kariuki, Simon K.; Lal, Altaf A.; Terlouw, Dianne J.; ter Kuile, Feiko O.; Ong'echa, John M. O.; Phillips-Howard, Penelope A.; Orago, Alloys S. S.; Kolczak, Margarette S.; Hawley, William A.; Nahlen, Bernard L.; Shi, Ya Ping
As part of a large community-based trial on the impact of insecticide (permethrin)-treated bed nets (ITNs) on childhood morbidity and mortality in an area of intense perennial malaria transmission in western Kenya, we assessed the effects of ITNs on malaria-specific humoral responses in young
S. S. Imbahale
Full Text Available The main objective was to investigate malaria transmission dynamics in three different sites, two highland villages (Fort Ternan and Lunyerere and a lowland peri-urban area (Nyalenda of Kisumu city. Adult mosquitoes were collected using PSC and CDC light trap while malaria parasite incidence data was collected from a cohort of children on monthly basis. Rainfall, humidity and temperature data were collected by automated weather stations. Negative binomial and Poisson generalized additive models were used to examine the risk of being infected, as well as the association with the weather variables. Anopheles gambiae s.s. was most abundant in Lunyerere, An. arabiensis in Nyalenda and An. funestus in Fort Ternan. The CDC light traps caught a higher proportion of mosquitoes (52.3% than PSC (47.7%, although not significantly different (P=0.689. The EIR’s were 0, 61.79 and 6.91 bites/person/year for Fort Ternan, Lunyerere and Nyalenda. Site, month and core body temperature were all associated with the risk of having malaria parasites (P<0.0001. Rainfall was found to be significantly associated with the occurrence of P. falciparum malaria parasites, but not relative humidity and air temperature. The presence of malaria parasite-infected children in all the study sites provides evidence of local malaria transmission.
Malaria is caused by four species of protozoa in the genus. Plasmodium. The parasites are transmitted to humans, only by female mosquitoes belong- ing to certain species of the genus anopheles, each time the infected insect takes a blood meal. Conversely, the female mosquito can pick up the infection when they bite ...
Baseline survey is an integral component of a malaria vector control programme, providing valuable information on mosquito behaviour that guide the suitability of chosen interventions. A need assessment of baseline entomological indices towards the future implementation of indoor residual spray (IRS) was conducted in ...
Out of 445 blood samples examined for malaria parasite 315 (70.80%) were positive while 130 (29.20%) were negative (p<0.05). This study provides useful baseline data for designing strategies for the control of mosquito-borne diseases in Minna and its environs. Keywords: pyrethroid, diversity, abundance, Anopheles sp., ...
economic activities include crop agriculture and livestock keeping. Adult mosquito collection and ... Based on the sequence of nucleotide amplified, An. arabiensis with 315bp, An. gambiae s.s with 390bp DNA fragments were .... for the design and implementation of malaria control strategies. Like in our study, studies.
Brock, P M; Fornace, K M; Parmiter, M; Cox, J; Drakeley, C J; Ferguson, H M; Kao, R R
The public health threat posed by zoonotic Plasmodium knowlesi appears to be growing: it is increasingly reported across South East Asia, and is the leading cause of malaria in Malaysian Borneo. Plasmodium knowlesi threatens progress towards malaria elimination as aspects of its transmission, such as spillover from wildlife reservoirs and reliance on outdoor-biting vectors, may limit the effectiveness of conventional methods of malaria control. The development of new quantitative approaches that address the ecological complexity of P. knowlesi, particularly through a focus on its primary reservoir hosts, will be required to control it. Here, we review what is known about P. knowlesi transmission, identify key knowledge gaps in the context of current approaches to transmission modelling, and discuss the integration of these approaches with clinical parasitology and geostatistical analysis. We highlight the need to incorporate the influences of fine-scale spatial variation, rapid changes to the landscape, and reservoir population and transmission dynamics. The proposed integrated approach would address the unique challenges posed by malaria as a zoonosis, aid the identification of transmission hotspots, provide insight into the mechanistic links between incidence and land use change and support the design of appropriate interventions.
Nunes, Julia K; Woods, Colleen; Carter, Terrell; Raphael, Theresa; Morin, Merribeth J; Diallo, Diadier; Leboulleux, Didier; Jain, Sanjay; Loucq, Christian; Kaslow, David C; Birkett, Ashley J
New interventions are needed to reduce morbidity and mortality associated with malaria, as well as to accelerate elimination and eventual eradication. Interventions that can break the cycle of parasite transmission, and prevent its reintroduction, will be of particular importance in achieving the eradication goal. In this regard, vaccines that interrupt malaria transmission (VIMT) have been highlighted as an important intervention, including transmission-blocking vaccines that prevent human-to-mosquito transmission by targeting the sexual, sporogonic, or mosquito stages of the parasite (SSM-VIMT). While the significant potential of this vaccine approach has been appreciated for decades, the development and licensure pathways for vaccines that target transmission and the incidence of infection, as opposed to prevention of clinical malaria disease, remain ill-defined. This article describes the progress made in critical areas since 2010, highlights key challenges that remain, and outlines important next steps to maximize the potential for SSM-VIMTs to contribute to the broader malaria elimination and eradication objectives. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.
Ghosh, Suma; Waite, Jessica L; Clayton, Dale H; Adler, Frederick R
Transmission of insect-borne diseases is shaped by the interactions among parasites, vectors, and hosts. Any factor that alters movement of infected vectors from infected to uninfeced hosts will in turn alter pathogen spread. In this paper, we study one such pathogen-vector-host system, avian malaria in pigeons transmitted by fly ectoparasites, where both two-way and three-way interactions play a key role in shaping disease spread. Bird immune defenses against flies can decrease malaria prevalence by reducing fly residence time on infected birds or increase disease prevalence by enhancing fly movement and thus infection transmission. We develop a mathematical model that illustrates how these changes in vector behavior influence pathogen transmission and show that malaria prevalence is maximized at an intermediate level of defense avoidance by the flies. Understanding how host immune defenses indirectly alter disease transmission by influencing vector behavior has implications for reducing the transmission of human malaria and other vectored pathogens. Published by Elsevier Ltd.
Tony Hiroshi Katsuragawa
Full Text Available UNLABELLED: The study area in Rondônia was the site of extensive malaria epidemic outbreaks in the 19(th and 20(th centuries related to environmental impacts, with large immigration flows. The present work analyzes the transmission dynamics of malaria in these areas to propose measures for avoiding epidemic outbreaks due to the construction of two Hydroelectric Power Plants. A population based baseline demographic census and a malaria prevalence follow up were performed in two river side localities in the suburbs of Porto Velho city and in its rural vicinity. The quantification and nature of malaria parasites in clinical patients and asymptomatic parasite carriers were performed using microscopic and Real Time PCR methodologies. Anopheles densities and their seasonal variation were done by monthly captures for defining HBR (hourly biting rate values. MAIN RESULTS: (i malaria among residents show the riverside profile, with population at risk represented by children and young adults; (ii asymptomatic vivax and falciparum malaria parasite carriers correspond to around 15% of adults living in the area; (iii vivax malaria relapses were responsible for 30% of clinical cases; (iv malaria risk for the residents was evaluated as 20-25% for vivax and 5-7% for falciparum malaria; (v anopheline densities shown outdoors HBR values 5 to 10 fold higher than indoors and reach 10.000 bites/person/year; (vi very high incidence observed in one of the surveyed localities was explained by a micro epidemic outbreak affecting visitors and temporary residents. Temporary residents living in tents or shacks are accessible to outdoors transmission. Seasonal fishermen were the main group at risk in the study and were responsible for a 2.6 fold increase in the malaria incidence in the locality. This situation illustrates the danger of extensive epidemic outbreaks when thousands of workers and secondary immigrant population will arrive attracted by opportunities opened by
Katsuragawa, Tony Hiroshi; Gil, Luiz Herman Soares; Tada, Mauro Shugiro; de Almeida e Silva, Alexandre; Costa, Joana D'Arc Neves; da Silva Araújo, Maisa; Escobar, Ana Lúcia; Pereira da Silva, Luiz Hildebrando
The study area in Rondônia was the site of extensive malaria epidemic outbreaks in the 19th and 20th centuries related to environmental impacts, with large immigration flows. The present work analyzes the transmission dynamics of malaria in these areas to propose measures for avoiding epidemic outbreaks due to the construction of two Hydroelectric Power Plants. A population based baseline demographic census and a malaria prevalence follow up were performed in two river side localities in the suburbs of Porto Velho city and in its rural vicinity. The quantification and nature of malaria parasites in clinical patients and asymptomatic parasite carriers were performed using microscopic and Real Time PCR methodologies. Anopheles densities and their seasonal variation were done by monthly captures for defining HBR (hourly biting rate) values. Main results: (i) malaria among residents show the riverside profile, with population at risk represented by children and young adults; (ii) asymptomatic vivax and falciparum malaria parasite carriers correspond to around 15% of adults living in the area; (iii) vivax malaria relapses were responsible for 30% of clinical cases; (iv) malaria risk for the residents was evaluated as 20–25% for vivax and 5–7% for falciparum malaria; (v) anopheline densities shown outdoors HBR values 5 to 10 fold higher than indoors and reach 10.000 bites/person/year; (vi) very high incidence observed in one of the surveyed localities was explained by a micro epidemic outbreak affecting visitors and temporary residents. Temporary residents living in tents or shacks are accessible to outdoors transmission. Seasonal fishermen were the main group at risk in the study and were responsible for a 2.6 fold increase in the malaria incidence in the locality. This situation illustrates the danger of extensive epidemic outbreaks when thousands of workers and secondary immigrant population will arrive attracted by opportunities opened by the Hydroelectric Power
Boyce, Ross; Reyes, Raquel; Matte, Michael; Ntaro, Moses; Mulogo, Edgar; Metlay, Joshua P; Band, Lawrence; Siedner, Mark J
There are several mechanisms by which global climate change may impact malaria transmission. We sought to assess how the increased frequency of extreme precipitation events associated with global climate change will influence malaria transmission in highland areas of East Africa. We used a differences-in-differences, quasi-experimental design to examine spatial variability in the incidence rate of laboratory-confirmed malaria cases and malaria-related hospitalizations between villages (1) at high versus low elevations, (2) with versus without rivers, and (3) upstream versus downstream before and after severe flooding that occurred in Kasese District, Western Region, Uganda, in May 2013. During the study period, 7596 diagnostic tests were performed, and 1285 patients were admitted with a diagnosis of malaria. We observed that extreme flooding resulted in an increase of approximately 30% in the risk of an individual having a positive result of a malaria diagnostic test in the postflood period in villages bordering a flood-affected river, compared with villages farther from a river, with a larger relative impact on upstream versus downstream villages (adjusted rate ratio, 1.91 vs 1.33). Extreme precipitation such as the flooding described here may pose significant challenges to malaria control programs and will demand timely responses to mitigate deleterious impacts on human health. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail email@example.com.
Full Text Available This systematic review elaborates the concepts and impacts of border malaria, particularly on the emergence and spread of Plasmodium falciparum and Plasmodium vivax multidrug resistance (MDR malaria on Thailand-Myanmar and Thailand-Cambodia borders. Border malaria encompasses any complex epidemiological settings of forest-related and forest fringe-related malaria, both regularly occurring in certain transmission areas and manifesting a trend of increased incidence in transmission prone areas along these borders, as the result of interconnections of human settlements and movement activities, cross-border population migrations, ecological changes, vector population dynamics, and multidrug resistance. For regional and global perspectives, this review analyzes and synthesizes the rationales pertaining to transmission dynamics and the vulnerabilities of border malaria that constrain surveillance and control of the world’s most MDR falciparum and vivax malaria on these chaotic borders.
Bhumiratana, Adisak; Intarapuk, Apiradee; Sorosjinda-Nunthawarasilp, Prapa; Maneekan, Pannamas; Koyadun, Surachart
This systematic review elaborates the concepts and impacts of border malaria, particularly on the emergence and spread of Plasmodium falciparum and Plasmodium vivax multidrug resistance (MDR) malaria on Thailand-Myanmar and Thailand-Cambodia borders. Border malaria encompasses any complex epidemiological settings of forest-related and forest fringe-related malaria, both regularly occurring in certain transmission areas and manifesting a trend of increased incidence in transmission prone areas along these borders, as the result of interconnections of human settlements and movement activities, cross-border population migrations, ecological changes, vector population dynamics, and multidrug resistance. For regional and global perspectives, this review analyzes and synthesizes the rationales pertaining to transmission dynamics and the vulnerabilities of border malaria that constrain surveillance and control of the world's most MDR falciparum and vivax malaria on these chaotic borders. PMID:23865048
Ya-Umphan, Phubeth; Cerqueira, Dominique; Parker, Daniel M; Cottrell, Gilles; Poinsignon, Anne; Remoue, Franck; Brengues, Cecile; Chareonviriyaphap, Theeraphap; Nosten, Francois; Corbel, Vincent
The modalities of malaria transmission along the Thailand-Myanmar border are poorly understood. Here we address the relevance of using a specific Anopheles salivary biomarker to measure the risk among humans of exposure to Anopheles bites. Serologic surveys were conducted from May 2013 to December 2014 in 4 sentinel villages. More than 9400 blood specimens were collected in filter papers from all inhabitants at baseline and then every 3 months thereafter, for up to 18 months, for analysis by enzyme-linked immunosorbent assay. The relationship between the intensity of the human antibody response and entomological indicators of transmission (human biting rates and entomological inoculation rates [EIRs]) was studied using a multivariate 3-level mixed model analysis. Heat maps for human immunoglobulin G (IgG) responses for each village and survey time point were created using QGIS 2.4. The levels of IgG response among participants varied significantly according to village, season, and age (P<.001) and were positively associated with the abundance of total Anopheles species and primary malaria vectors and the EIR (P<.001). Spatial clusters of high-IgG responders were identified across space and time within study villages. The gSG6-P1 biomarker has great potential to address the risk of transmission along the Thailand-Myanmar border and represents a promising tool to guide malaria interventions.
Wu, Yimin; Sinden, Robert E; Churcher, Thomas S; Tsuboi, Takafumi; Yusibov, Vidadi
Despite decades of effort battling against malaria, the disease is still a major cause of morbidity and mortality. Transmission-blocking vaccines (TBVs) that target sexual stage parasite development could be an integral part of measures for malaria elimination. In the 1950s, Huff et al. first demonstrated the induction of transmission-blocking immunity in chickens by repeated immunizations with Plasmodium gallinaceum-infected red blood cells. Since then, significant progress has been made in identification of parasite antigens responsible for transmission-blocking activity. Recombinant technologies accelerated evaluation of these antigens as vaccine candidates, and it is possible to induce effective transmission-blocking immunity in humans both by natural infection and now by immunization with recombinant vaccines. This chapter reviews the efforts to produce TBVs, summarizes the current status and advances and discusses the remaining challenges and approaches. Copyright © 2015 Elsevier Ltd. All rights reserved.
Cator, Lauren J; Pietri, Jose E; Murdock, Courtney C; Ohm, Johanna R; Lewis, Edwin E; Read, Andrew F; Luckhart, Shirley; Thomas, Matthew B
Malaria parasites alter mosquito feeding behaviour in a way that enhances parasite transmission. This is widely considered a prime example of manipulation of host behaviour to increase onward transmission, but transient immune challenge in the absence of parasites can induce the same behavioural phenotype. Here, we show that alterations in feeding behaviour depend on the timing and dose of immune challenge relative to blood ingestion and that these changes are functionally linked to changes in insulin signalling in the mosquito gut. These results suggest that altered phenotypes derive from insulin signalling-dependent host resource allocation among immunity, blood feeding, and reproduction in a manner that is not specific to malaria parasite infection. We measured large increases in mosquito survival and subsequent transmission potential when feeding patterns are altered. Leveraging these changes in physiology, behaviour and life history could promote effective and sustainable control of female mosquitoes responsible for transmission.
Komen, Kibii; Olwoch, Jane; Rautenbach, Hannes; Botai, Joel; Adebayo, Adetunji
Malaria in Limpopo Province of South Africa is shifting and now observed in originally non-malaria districts, and it is unclear whether climate change drives this shift. This study examines the distribution of malaria at district level in the province, determines direction and strength of the linear relationship and causality between malaria with the meteorological variables (rainfall and temperature) and ascertains their short- and long-run variations. Spatio-temporal method, Correlation analysis and econometric methods are applied. Time series monthly meteorological data (1998-2007) were obtained from South Africa Weather Services, while clinical malaria data came from Malaria Control Centre in Tzaneen (Limpopo Province) and South African Department of Health. We find that malaria changes and pressures vary in different districts with a strong positive correlation between temperature with malaria, r = 0.5212, and a weak positive relationship for rainfall, r = 0.2810. Strong unidirectional causality runs from rainfall and temperature to malaria cases (and not vice versa): F (1, 117) = 3.89, ρ = 0.0232 and F (1, 117) = 20.08, P < 0.001 and between rainfall and temperature, a bi-directional causality exists: F (1, 117) = 19.80; F (1,117) = 17.14, P < 0.001, respectively, meaning that rainfall affects temperature and vice versa. Results show evidence of strong existence of a long-run relationship between climate variables and malaria, with temperature maintaining very high level of significance than rainfall. Temperature, therefore, is more important in influencing malaria transmission in Limpopo Province.
these fly species could be involved in the transmission of cutaneous leishmaniasis caused by L. infantum and/or L. tropica. Conclusions: The isolation...of L. infantum from 1 of 6 giant rats (Cricetomys gambianus) captured at a case site of human cutaneous leishmaniasis in Kenya, provide insight on the...AD-A285 556 AD GRANT NOS: DAMD17-87-G-7016 and DAMD17-89-Z-9032 TITLE: MALARIA, LEISHMANIASIS & SHISTOSOMIASIS VECTOR ECOLOGY, TRANSMISSION
Gruell, Henning; Hamacher, Laura; Jennissen, Veronika; Tuchscherer, Armin; Ostendorf, Norbert; Löffler, Thorsten; Hallek, Michael; Kochanek, Matthias; Tannich, Egbert; Böll, Boris; Fätkenheuer, Gerd
Vector-borne diseases can be contracted by exposure to contaminated material. This mode of transmission is not geographically restricted to the presence of a vector. Unexpected infection in regions of low incidence potentially delays diagnosis. We report a case of severe falciparum malaria following nosocomial Plasmodium falciparum transmission in nonendemic Germany. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: firstname.lastname@example.org.
Full Text Available Abstract Background Following the success of the malaria control intervention on the island of Bioko, malaria control by the use of indoor residual spraying (IRS and long-lasting insecticide-treated nets (LLITN was extended to Rio Muni, on the mainland part of Equatorial Guinea. This manuscript reports on the malaria vectors present and the incidence of insecticide resistant alleles prior to the onset of the programme. Methods Anopheles mosquitoes were captured daily using window traps at 30 sentinel sites in Rio Muni, from December 2006 to July 2007. The mosquitoes were identified to species and their sporozoite rates, knockdown resistance (kdr and acetylcholinesterase (AChE sensitivity measured, to define the role of vector species in malaria transmission and their potential susceptibility to insecticides. Results A total of 6,162 Anopheles mosquitoes were collected of which 4,808 were morphologically identified as Anopheles gambiae s.l., 120 Anopheles funestus, 1,069 Anopheles moucheti, and 165 Anopheles nili s.l.. Both M and S molecular forms of Anopheles gambiae s.s. and Anopheles melas were identified. Anopheles ovengensis and Anopheles carnevalei were the only two members of the An. nili group to be identified. Using the species-specific sporozoite rates and the average number of mosquitoes per night, the number of infective mosquitoes per trap per 100 nights for each species complex was calculated as a measure of transmission risk. Both kdr-w and kdr-e alleles were present in the S-form of An. gambiae s.s. (59% and 19% respectively and at much lower frequencies in the M-form (9.7% and 1.8% respectively. The kdr-w and kdr-e alleles co-occurred in 103 S-form and 1 M-form specimens. No insensitive AChE was detected. Conclusion Anopheles gambiae s.s, a member of the Anopheles gambiae complex was shown to be the major vector in Rio Muni with the other three groups playing a relatively minor role in transmission. The demonstration of a high
Full Text Available Background & objectives: The influence of temperature on the life cycle of mosquitoes as well as on development of malaria parasite in mosquitoes is well studied. Most of the studies use outdoor temperature for understanding the transmission dynamics and providing projections of malaria. As the mosquitoes breed in water and rest usually indoors, it is logical to relate the transmission dynamics with temperature of micro-niche. The present study was, therefore, undertaken to understand the influence of different formats of temperature of different micro-niches on transmission of malaria for providing more realistic projections. Methods: The study was conducted in one village each of Assam and Uttarakhand s0 tates of India. Temperatures recorded from outdoor (air as well as indoor habitats (resting place of mosquito were averaged into daily, fortnightly and monthly and were used for determination of transmission windows (TWs for Plasmodium vivax (Pv and P. falciparum (Pf based on minimum temperature threshold required for transmission. Results: The daily temperature was found more useful for calculation of sporogony than fortnightly and monthly temperatures. Monthly TWs were further refined using fortnightly temperature, keeping in view the completion of more than one life cycle of malaria vectors and sporogony of malaria parasite in a month. A linear regression equation was generated to find out the relationship between outdoor and indoor temperatures and R  to predict the percentage of variation in indoor temperature as a function of outdoor temperature at both localities. Interpretation & conclusions: The study revealed that the indoor temperature was more than outdoors in stable malarious area (Assam but fluctuating in low endemic area like Uttarakhand. Transmission windows of malaria should be determined by transforming outdoor data to indoor and preferably at fortnightly interval. With daily recorded temperature, sporogonic and
Singh, Poonam; Yadav, Yogesh; Saraswat, Shweta; Dhiman, Ramesh C
The influence of temperature on the life cycle of mosquitoes as well as on development of malaria parasite in mosquitoes is well studied. Most of the studies use outdoor temperature for understanding the transmission dynamics and providing projections of malaria. As the mosquitoes breed in water and rest usually indoors, it is logical to relate the transmission dynamics with temperature of micro-niche. The present study was, therefore, undertaken to understand the influence of different formats of temperature of different micro-niches on transmission of malaria for providing more realistic projections. The study was conducted in one village each of Assam and Uttarakhand s0 tates of India. Temperatures recorded from outdoor (air) as well as indoor habitats (resting place of mosquito) were averaged into daily, fortnightly and monthly and were used for determination of transmission windows (TWs) for Plasmodium vivax (Pv) and P. falciparum (Pf) based on minimum temperature threshold required for transmission. The daily temperature was found more useful for calculation of sporogony than fortnightly and monthly temperatures. Monthly TWs were further refined using fortnightly temperature, keeping in view the completion of more than one life cycle of malaria vectors and sporogony of malaria parasite in a month. A linear regression equation was generated to find out the relationship between outdoor and indoor temperatures and R  to predict the percentage of variation in indoor temperature as a function of outdoor temperature at both localities. The study revealed that the indoor temperature was more than outdoors in stable malarious area (Assam) but fluctuating in low endemic area like Uttarakhand. Transmission windows of malaria should be determined by transforming outdoor data to indoor and preferably at fortnightly interval. With daily recorded temperature, sporogonic and gonotrophic cycles can also be calculated which is otherwise not possible with monthly data. The
Mizutani, Masanori; Iyori, Mitsuhiro; Blagborough, Andrew M; Fukumoto, Shinya; Funatsu, Tomohiro; Sinden, Robert E; Yoshida, Shigeto
A multistage malaria vaccine targeting the pre-erythrocytic and sexual stages of Plasmodium could effectively protect individuals against infection from mosquito bites and provide transmission-blocking (TB) activity against the sexual stages of the parasite, respectively. This strategy could help prevent malaria infections in individuals and, on a larger scale, prevent malaria transmission in communities of endemicity. Here, we describe the development of a multistage Plasmodium vivax vaccine which simultaneously expresses P. vivax circumsporozoite protein (PvCSP) and P25 (Pvs25) protein of this species as a fusion protein, thereby acting as a pre-erythrocytic vaccine and a TB vaccine, respectively. A new-concept vaccine platform based on the baculovirus dual-expression system (BDES) was evaluated. The BDES-Pvs25-PvCSP vaccine displayed correct folding of the Pvs25-PvCSP fusion protein on the viral envelope and was highly expressed upon transduction of mammalian cells in vitro. This vaccine induced high levels of antibodies to Pvs25 and PvCSP and elicited protective (43%) and TB (82%) efficacies against transgenic P. berghei parasites expressing the corresponding P. vivax antigens in mice. Our data indicate that our BDES, which functions as both a subunit and DNA vaccine, can offer a promising multistage vaccine capable of delivering a potent antimalarial pre-erythrocytic and TB response via a single immunization regimen. Copyright © 2014, American Society for Microbiology. All Rights Reserved.
Omumbo, J A; Hay, S I; Snow, R W; Tatem, A J; Rogers, D J
Malaria risk maps have re-emerged as an important tool for appropriately targeting the limited resources available for malaria control. In Sub-Saharan Africa empirically derived maps using standardized criteria are few and this paper considers the development of a model of malaria risk for East Africa. Statistical techniques were applied to high spatial resolution remotely sensed, human settlement and land-use data to predict the intensity of malaria transmission as defined according to the childhood parasite ratio (PR) in East Africa. Discriminant analysis was used to train environmental and human settlement predictor variables to distinguish between four classes of PR risk shown to relate to disease outcomes in the region. Independent empirical estimates of the PR were identified from Kenya, Tanzania and Uganda (n = 330). Surrogate markers of climate recorded on-board earth orbiting satellites, population settlement, elevation and water bodies all contributed significantly to the predictive models of malaria transmission intensity in the sub-region. The accuracy of the model was increased by stratifying East Africa into two ecological zones. In addition, the inclusion of urbanization as a predictor of malaria prevalence, whilst reducing formal accuracy statistics, nevertheless improved the consistency of the predictive map with expert opinion malaria maps. The overall accuracy achieved with ecological zone and urban stratification was 62% with surrogates of precipitation and temperature being among the most discriminating predictors of the PR. It is possible to achieve a high degree of predictive accuracy for Plasmodium falciparum parasite prevalence in East Africa using high-spatial resolution environmental data. However, discrepancies were evident from mapped outputs from the models which were largely due to poor coverage of malaria training data and the comparable spatial resolution of predictor data. These deficiencies will only be addressed by more random
Neal, Allison T; Taylor, Peter D
The local mate competition model from sex ratio theory predicts female-biased sex ratios in populations that are highly subdivided during mating, and is thought to accord well with the population structure of malaria parasites. However, the selective advantage of female-biased sex ratios comes from the resulting increase in total reproductive output, an advantage the transmission biology of malaria parasite likely reduces. We develop a mathematical model to determine how bottlenecks in transmission that cause diminishing fitness returns from female production affect sex ratio evolution. We develop four variations of this model that incorporate whether or not parasite clones have the ability to detect others that occupy the same host and whether or not the number of clones affects the total mating population size. Our model indicates that transmission bottlenecks favor less female-biased sex ratios than those predicted under LMC. This effect is particularly pronounced if clones have no information about the presence of coexisting clones and the number of mating individuals per patch is fixed. The model could extend our understanding of malaria parasite sex ratios in three main ways. First, it identifies inconsistencies between the theoretical predictions and the data presented in a previous study, and proposes revised predictions that are more consistent with underlying biology of the parasite. Second, it may account for the positive association between parasite density and sex ratio observed within and between some species. Third, it predicts a relationship between mortality rates in the vector and sex ratios, which appears to be supported by the little existing data we have. While the inspiration for this model came from malaria parasites, it should apply to any system in which per capita dispersal success diminishes with increasing numbers of females in a patch. Copyright © 2014 Elsevier Ltd. All rights reserved.
Full Text Available Abstract Background The impact of malaria on the risk of stillbirth is still under debate. The aim of the present analysis was to determine comparative changes in stillbirth prevalence between two areas of Tanzania with different malaria transmission patterns in order to estimate the malaria attributable component. Methods A retrospective analysis was completed of stillbirth differences between primigravidae and multigravidae in relation to malaria cases and transmission patterns for two different areas of Tanzania with a focus on the effects of the El Niño southern climatic oscillation (ENSO. One area, Kagera, experiences outbreaks of malaria, and the other area, Morogoro, is holoendemic. Delivery and malaria data were collected over a six year period from records of the two district hospitals in these locations. Results There was a significantly higher prevalence of low birthweight in primigravidae compared to multigravidae for both data sets. Low birthweight and stillbirth prevalence (17.5% and 4.8% were significantly higher in Kilosa compared to Ndolage (11.9% and 2.4%. There was a significant difference in stillbirth prevalence between Ndolage and Kilosa between malaria seasons (2.4% and 5.6% respectively, p Conclusion Malaria exposure during pregnancy has a delayed effect on birthweight outcomes, but a more acute effect on stillbirth risk.
Kabaria, Caroline W; Molteni, Fabrizio; Mandike, Renata; Chacky, Frank; Noor, Abdisalan M; Snow, Robert W; Linard, Catherine
With more than half of Africa's population expected to live in urban settlements by 2030, the burden of malaria among urban populations in Africa continues to rise with an increasing number of people at risk of infection. However, malaria intervention across Africa remains focused on rural, highly endemic communities with far fewer strategic policy directions for the control of malaria in rapidly growing African urban settlements. The complex and heterogeneous nature of urban malaria requires a better understanding of the spatial and temporal patterns of urban malaria risk in order to design effective urban malaria control programs. In this study, we use remotely sensed variables and other environmental covariates to examine the predictability of intra-urban variations of malaria infection risk across the rapidly growing city of Dar es Salaam, Tanzania between 2006 and 2014. High resolution SPOT satellite imagery was used to identify urban environmental factors associated malaria prevalence in Dar es Salaam. Supervised classification with a random forest classifier was used to develop high resolution land cover classes that were combined with malaria parasite prevalence data to identify environmental factors that influence localized heterogeneity of malaria transmission and develop a high resolution predictive malaria risk map of Dar es Salaam. Results indicate that the risk of malaria infection varied across the city. The risk of infection increased away from the city centre with lower parasite prevalence predicted in administrative units in the city centre compared to administrative units in the peri-urban suburbs. The variation in malaria risk within Dar es Salaam was shown to be influenced by varying environmental factors. Higher malaria risks were associated with proximity to dense vegetation, inland water and wet/swampy areas while lower risk of infection was predicted in densely built-up areas. The predictive maps produced can serve as valuable resources for
Theander, T G
Most studies of the natural history of Plasmodium falciparum infection have been performed in areas of stable malaria transmission and the acquisition of immunity to malaria in individuals who live in such areas is well documented. For the past 10 years, we have monitored host-parasite relationsh......Most studies of the natural history of Plasmodium falciparum infection have been performed in areas of stable malaria transmission and the acquisition of immunity to malaria in individuals who live in such areas is well documented. For the past 10 years, we have monitored host......-parasite relationships in an area characterized by unstable and seasonal malaria of low transmission intensity. The work was performed in the village Daraweesh located in north-eastern Sudan 16 km from Gedaref town. The climate of the region is characterized by well-defined wet and dry periods with a short rainy season...... followed by a long dry season. In some years the rains fail and there is little precipitation even during the wet season. Malaria cases are rare in the dry season and during droughts. In years with rains, falciparum malaria sweeps through Daraweesh during the wet season and 20-40% of the entire population...
Milligan Paul J
Full Text Available Abstract Background Mosquito-proofing homes was one of the principal methods of environmental management in the early 1900s. House screening provides protection against malaria by reducing exposure to malaria parasites and has the added benefit of protecting everyone sleeping in the house, avoiding issues of inequity within the household. The aim of this study is to determine whether house screening protects people against malaria in Africa. It is hoped that this study will mark the beginning of a series of trials assessing a range of environmental interventions for malaria control in Africa. Design A 3-armed randomised-controlled trial will be conducted in and around Farafenni town in The Gambia, West Africa, to assess whether screening windows, doors and closing eaves or installing netting ceilings in local houses can substantially reduce malaria transmission and anaemia compared to homes with no screening. Eligible houses will be sorted and stratified by location and the number of children in each house, then randomly allocated to the interventions in blocks of 5 houses (2 with full screening, 2 with screened ceilings and 1 control house without screening. Risk of malaria transmission will be assessed in each house by routine collections of mosquitoes using light traps and an anaemia prevalence study in children at the end of the main transmission period. Discussion Practical issues concerning intervention implementation, as well as the potential benefits and risks of the study, are discussed. Trial Registration ISRCTN51184253 – Screening-homes to prevent malaria
van Eijk, Anna M; Hill, Jenny; Noor, Abdisalan M; Snow, Robert W; ter Kuile, Feiko O
In malarious areas, pregnant women are more likely to have detectable malaria than are their non-pregnant peers, and the excess risk of infection varies with gravidity. Pregnant women attending antenatal clinic for their first visit are a potential pragmatic sentinel group to track the intensity of malaria transmission; however, the relation between malaria prevalence in children, a standard measure to estimate malaria endemicity, and pregnant women has never been compared. We obtained data on malaria prevalence in pregnancy from the Malaria in Pregnancy Library (January, 2015) and data for children (0-59 months) were obtained from recently published work on parasite prevalence in Africa and the Malaria in Pregnancy Library. We used random effects meta-analysis to obtain a pooled prevalence ratio (PPR) of malaria in children versus pregnant women (during pregnancy, not at delivery) and by gravidity, and we used meta-regression to assess factors affecting the prevalence ratio. We used data from 18 sources that included 57 data points. There was a strong linear relation between the prevalence of malaria infection in pregnant women and children (r=0·87, ppregnant women is strongly correlated with prevalence data in children obtained from household surveys, and could provide a pragmatic adjunct to survey strategies to track trends in malaria transmission in Africa. The Malaria in Pregnancy Consortium, which is funded through a grant from the Bill & Melinda Gates Foundation to the Liverpool School of Tropical Medicine, UK; US Centers for Disease Control and Prevention; and Wellcome Trust, UK. Copyright © 2015 van Eijk et al. Open access article published under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.
Okuneye, Kamaldeen; Gumel, Abba B
A new non-autonomous model is designed and used to assess the impact of variability in temperature and rainfall on the transmission dynamics of malaria in a population. In addition to adding age-structure in the host population and the dynamics of immature malaria mosquitoes, a notable feature of the new model is that recovered individuals do not revert to wholly-susceptible class (that is, recovered individuals enjoy reduced susceptibility to new malaria infection). In the absence of disease-induced mortality, the disease-free solution of the model is shown to be globally-asymptotically stable when the associated reproduction ratio is less than unity. The model has at least one positive periodic solution when the reproduction ratio exceeds unity (and the disease persists in the community in this case). Detailed uncertainty and sensitivity analysis, using mean monthly temperature and rainfall data from KwaZulu-Natal province of South Africa, shows that the top three parameters of the model that have the most influence on the disease transmission dynamics are the mosquito carrying capacity, transmission probability per contact for susceptible mosquitoes and human recovery rate. Numerical simulations of the model show that, for the KwaZulu-Natal province, malaria burden increases with increasing mean monthly temperature and rainfall in the ranges ([17-25]°C and [32-110] mm), respectively (and decreases with decreasing mean monthly temperature and rainfall values). In particular, transmission is maximized for mean monthly temperature and rainfall in the ranges [21-25]°C and [95-125] mm. This occurs for a six-month period in KwaZulu-Natal (hence, this study suggests that anti-malaria control efforts should be intensified during this period). It is shown, for the fixed mean monthly temperature of KwaZulu-Natal, that malaria burden decreases whenever the amount of rainfall exceeds a certain threshold value. It is further shown (through sensitivity analysis and
Andrew S Bell
Full Text Available The evolution of drug resistant Plasmodium parasites is a major challenge to effective malaria control. In theory, competitive interactions between sensitive parasites and resistant parasites within infections are a major determinant of the rate at which parasite evolution undermines drug efficacy. Competitive suppression of resistant parasites in untreated hosts slows the spread of resistance; competitive release following treatment enhances it. Here we report that for the murine model Plasmodium chabaudi, co-infection with drug-sensitive parasites can prevent the transmission of initially rare resistant parasites to mosquitoes. Removal of drug-sensitive parasites following chemotherapy enabled resistant parasites to transmit to mosquitoes as successfully as sensitive parasites in the absence of treatment. We also show that the genetic composition of gametocyte populations in host venous blood accurately reflects the genetic composition of gametocytes taken up by mosquitoes. Our data demonstrate that, at least for this mouse model, aggressive chemotherapy leads to very effective transmission of highly resistant parasites that are present in an infection, the very parasites which undermine the long term efficacy of front-line drugs.
Makanga, Boris; Yangari, Patrick; Rahola, Nil; Rougeron, Virginie; Elguero, Eric; Boundenga, Larson; Moukodoum, Nancy Diamella; Okouga, Alain Prince; Arnathau, Céline; Durand, Patrick; Willaume, Eric; Ayala, Diego; Fontenille, Didier; Ayala, Francisco J; Renaud, François; Ollomo, Benjamin; Prugnolle, Franck; Paupy, Christophe
Recent studies have highlighted the large diversity of malaria parasites infecting African great apes (subgenus Laverania) and their strong host specificity. Although the existence of genetic incompatibilities preventing the cross-species transfer may explain host specificity, the existence of vectors with a high preference for a determined host represents another possibility. To test this hypothesis, we undertook a 15-mo-long longitudinal entomological survey in two forest regions of Gabon, where wild apes live, at different heights under the canopy. More than 2,400 anopheline mosquitoes belonging to 18 species were collected. Among them, only three species of Anopheles were found infected with ape Plasmodium: Anopheles vinckei, Anopheles moucheti, and Anopheles marshallii Their role in transmission was confirmed by the detection of the parasites in their salivary glands. Among these species, An. vinckei showed significantly the highest prevalence of infection and was shown to be able to transmit parasites of both chimpanzees and gorillas. Transmission was also shown to be conditioned by seasonal factors and by the heights of capture under the canopy. Moreover, human landing catches of sylvan Anopheles demonstrated the propensity of these three vector species to feed on humans when available. Our results suggest therefore that the strong host specificity observed in the Laveranias is not linked to a specific association between the vertebrate host and the vector species and highlight the potential role of these vectors as bridge between apes and humans.
Full Text Available BACKGROUND: An epidemiological and entomological study was carried out in Balaghat district, Madhya Pradesh, India to understand the dynamics of forest malaria transmission in a difficult and hard to reach area where indoor residual spray and insecticide treated nets were used for vector control. METHODS: This community based cross-sectional study was undertaken from January 2010 to December 2012 in Baihar and Birsa Community Health Centres of district Balaghat for screening malaria cases. Entomological surveillance included indoor resting collections, pyrethrum spray catches and light trap catches. Anophelines were assayed by ELISA for detection of Plasmodium circumsporozoite protein. FINDINGS: Plasmodium falciparum infection accounted for >80% of all infections. P. vivax 16.5%, P. malariae 0.75% and remaining were mixed infections of P. falciparum, P. vivax and P. malariae. More than, 30% infections were found in infants under 6 months of age. Overall, an increasing trend in malaria positivity was observed from 2010 to 2012 (chi-square for trend = 663.55; P<0.0001. Twenty five Anopheles culicifacies (sibling species C, D and E were positive for circumsporozoite protein of P. falciparum (44% and P. vivax (56%. Additionally, 2 An. fluviatilis, were found positive for P. falciparum and 1 for P. vivax (sibling species S and T. An. fluviatilis sibling species T was found as vector in forest villages for the first time in India. CONCLUSION: These results showed that the study villages are experiencing almost perennial malaria transmission inspite of indoor residual spray and insecticide treated nets. Therefore, there is a need for new indoor residual insecticides which has longer residual life or complete coverage of population with long lasting insecticide treated nets or both indoor residual spray and long lasting bed nets for effective vector control. There is a need to undertake a well designed case control study to evaluate the efficacy
Miura, K.; Stone, W.J.R.; Koolen, K.M.; Deng, B.; Zhou, L; Gemert, G.J.A. van; Locke, E.; Morin, M.; Bousema, T.; Sauerwein, R.W.; Long, C.A.; Dechering, K.J.
BACKGROUND: An effective malaria transmission-blocking vaccine may play an important role in malaria elimination efforts, and a robust biological assay is essential for its development. The standard membrane-feeding assay (SMFA) for Plasmodium falciparum infection of mosquitoes is considered a "gold
Theisen, Michael; Jore, Matthijs M; Sauerwein, Robert
Malaria is a devastating vector-borne disease caused by the Plasmodium parasite, resulting in almost 0.5 million casualties per year. The parasite has a complex life-cycle that includes asexual replication in human red blood cells, causing symptomatic malaria, and sexual stages which are essential for the transmission to the mosquito vector. A vaccine targeting the sexual stages of the parasite and thus blocking transmission will be instrumental for the eradication of malaria. One of the leading transmission blocking vaccine candidates is the sexual stage antigen Pfs48/45. Areas covered: PubMed was searched to review the progress and future prospects for clinical development of a Pfs48/45-based subunit vaccine. We will focus on biological function, naturally acquired immunity, functional activity of specific antibodies, sequence diversity, production of recombinant protein and preclinical studies. Expert commentary: Pfs48/45 is one of the lead-candidates for a transmission blocking vaccine and should be further explored in clinical trials.
Sovi, Arthur; Govoétchan, Renaud; Tokponnon, Filémon; Hounkonnou, Hermine; Aïkpon, Rock; Agossa, Fiacre; Gnanguenon, Virgile; Salako, Albert S; Agossou, Christian; Ossè, Razaki; Okè, Mariam; Gbénou, Dina; Massougbodji, Achille; Akogbéto, Martin
The goal of the study is to investigate if local agricultural practices have an impact on malaria transmission in four villages located in the same geographical area within a radius of 15 kilometers. Among the villages, one (Itassoumba) is characterized by the presence of a large market garden and fishpond basins, the three others (Itakpako, Djohounkollé and Ko-koumolou) are characterized by traditional food-producing agriculture. Malaria transmission was evaluated using human-landing catches, both indoors and outdoors, two nights per month for 12 months. Field collected females An. gambiae s.l. were exposed for 1 hour to 0.75% permethrin and 0.05% deltamethrin using WHO insecticide susceptibility test kits and procedures. The presence of the kdr mutation was analyzed by PCR. Anopheles gambiae s.s form M (93.65%), was identified as the main malaria vector. Its susceptibility level to pyrethroids was the same (p > 0.05) in all villages. kdr mutation frequencies are 81.08 in Itakpako, 85 in Itassoumba, 79.73 in Djohounkollé and 86.84 in Ko-Koumolou (p = 0.63). The entomological inoculation rate ranged from 9.62 to 21.65 infected bites of An. gambiae per human per year in Djohounkollé, Itakpako and Ko-Koumolou against 1159.62 in Itassoumba (p < 0.0001). The level of resistance of An. gambiae to pyrethroids was the same in the four villages. The heterogeneous character of malaria epidemiology was confirmed. The creation of fishponds basins and the development of market-gardening activities increased drastically the malaria transmission in Itassoumba.
Full Text Available Abstract Background Knowledge of the local pattern of malaria transmission and the effect of season on transmission is essential for the planning and evaluation of malaria interventions. Therefore, entomological surveys were carried out in the forest-savannah transitional belt of Ghana (Kintampo from November 2003 to November 2005 in preparation for drug and vaccine trials. Results A total of 23,406 mosquitoes were caught from 919 traps over the two-year period (November 2003 to November 2005: 54.3% were Culicines, 36.2% Anopheles funestus, and 9.4% Anopheles gambiae. Infection rates with Plasmodium falciparum were 4.7% and 1.5% for Anopheles gambiae and Anopheles funestus, respectively. Entomological inoculation rates (EIRs were 269 infective bites per person per year in the first year (November 2003-October 2004 and 231 the following year (November 2004-November 2005. Polymerase Chain Reaction (PCR analysis detected only Anopheles gambiae s.s. Nineteen mosquitoes were tested by PCR in the wet season; 16 were S-molecular form, 2 M-molecular form and 1 hybrid (S/M. In the dry season, sixteen mosquitoes were tested; 11 S-molecular form, 2 M-molecular form and 3 S/M hybrids. The frequency of knock down resistance (kdr genotypes F(R was 0.60. Conclusion The dynamics and seasonal abundance of malaria vectors in the Kintampo area was influenced by micro-ecology, rainfall and temperature patterns. Transmission patterns did not differ significantly between the two years (2004 and 2005 and both Anopheles gambiae and Anopheles funestus were identified as effective vectors. EIR estimates in 2004/2005 were between 231 and 269 infective bites per person per year. The information provided by the study will help in planning intensified malaria control activities as well as evaluating the impact of malaria interventions in the middle belt of Ghana.
Baidjoe, Amrish; Stone, Will; Ploemen, Ivo; Shagari, Shehu; Grignard, Lynn; Osoti, Victor; Makori, Euniah; Stevenson, Jennifer; Kariuki, Simon; Sutherland, Colin; Sauerwein, Robert; Cox, Jonathan; Drakeley, Chris; Bousema, Teun
Informing and evaluating malaria control efforts relies on knowledge of local transmission dynamics. Serological and molecular tools have demonstrated great sensitivity to quantify transmission intensity in low endemic settings where the sensitivity of traditional methods is limited. Filter paper blood spots are commonly used a source of both DNA and antibodies. To enhance the operational practicability of malaria surveys, a method is presented for combined DNA extraction and antibody elution. Filter paper blood spots were collected as part of a large cross-sectional survey in the Kenyan highlands. DNA was extracted using a saponin/chelex method. The eluate of the first wash during the DNA extraction process was used for antibody detection and compared with previously validated antibody elution procedures. Antibody elution efficiency was assessed by total IgG ELISA for malaria antigens apical membrane antigen-1 (AMA-1) and merozoite-surface protein-1 (MSP-142). The sensitivity of nested 18S rRNA and cytochrome b PCR assays and the impact of doubling filter paper material for PCR sensitivity were determined. The distribution of cell material and antibodies throughout filter paper blood spots were examined using luminescent and fluorescent reporter assays. Antibody levels measured after the combined antibody/DNA extraction technique were strongly correlated to those measured after standard antibody elution (p DNA extraction increased sensitivity. The concentration of cell and antibody material was not homogenously distributed throughout blood spots. Combined DNA extraction and antibody elution is an operationally attractive approach for high throughput assessment of cumulative malaria exposure and current infection prevalence in endemic settings. Estimates of antibody prevalence are unaffected by the combined extraction and elution procedure. The choice of target gene and the amount and source of filter paper material for DNA extraction can have a marked impact on
Nikolaeva, Daria; Draper, Simon J; Biswas, Sumi
The continued global burden of malaria can in part be attributed to a complex lifecycle, with both human hosts and mosquito vectors serving as transmission reservoirs. In preclinical models of vaccine-induced immunity, antibodies to parasite sexual-stage antigens, ingested in the mosquito blood meal, can inhibit parasite survival in the insect midgut as judged by ex vivo functional studies such as the membrane feeding assay. In an era of renewed political momentum for malaria elimination and eradication campaigns, such observations have fueled support for the development and implementation of so-called transmission-blocking vaccines. While leading candidates are being evaluated using a variety of promising vaccine platforms, the field is also beginning to capitalize on global '-omics' data for the rational genome-based selection and unbiased characterization of parasite and mosquito proteins to expand the candidate list. This review covers the progress and prospects of these recent developments.
Athina, D.; Bakhtiar, T.; Jaharuddin
In this paper, we consider a model of the transmission of malaria which was developed by Silva and Torres equipped with two control variables, namely the use of insecticide treated nets (ITN) to reduce the number of human beings infected and spraying to reduce the number of mosquitoes. Pontryagin maximum principle was applied to derive the differential equation system as optimality conditions which must be satisfied by optimal control variables. The Mangasarian sufficiency theorem shows that Pontryagin maximum principle is necessary as well as sufficient conditions for optimization problem. The 4th-order Runge Kutta method was then performed to solve the differential equations system. The numerical results show that both controls given at once can reduce the number of infected individuals as well as the number of mosquitoes which reduce the impact of malaria transmission.
Quiñones Martha L
Full Text Available Abstract Background Malaria has recently re-emerged as a public health burden in Colombia. Although the problem seems to be climate-driven, there remain significant gaps of knowledge in the understanding of the complexity of malaria transmission, which have motivated attempts to develop a comprehensive model. Methods The mathematical tool was applied to represent Plasmodium falciparum malaria transmission in two endemic-areas. Entomological exogenous variables were estimated through field campaigns and laboratory experiments. Availability of breeding places was included towards representing fluctuations in vector densities. Diverse scenarios, sensitivity analyses and instabilities cases were considered during experimentation-validation process. Results Correlation coefficients and mean square errors between observed and modelled incidences reached 0.897–0.668 (P > 0.95 and 0.0002–0.0005, respectively. Temperature became the most relevant climatic parameter driving the final incidence. Accordingly, malaria outbreaks are possible during the favourable epochs following the onset of El Niño warm events. Sporogonic and gonotrophic cycles showed to be the entomological key-variables controlling the transmission potential of mosquitoes' population. Simulation results also showed that seasonality of vector density becomes an important factor towards understanding disease transmission. Conclusion The model constitutes a promising tool to deepen the understanding of the multiple interactions related to malaria transmission conducive to outbreaks. In the foreseeable future it could be implemented as a tool to diagnose possible dynamical patterns of malaria incidence under several scenarios, as well as a decision-making tool for the early detection and control of outbreaks. The model will be also able to be merged with forecasts of El Niño events to provide a National Malaria Early Warning System.
Malaria, the greatest pandemia in the world, claims an estimated one million lives each year in Africa alone. While it may still be said that for the most part malaria is found in what is known as the world's poverty belt, cases are now frequently diagnosed in western countries. Due to resistant strains of malaria which have developed because of…
Debabani Roy Chowdhury
Full Text Available Malaria caused by Plasmodium falciparum is responsible for nearly 1 million deaths annually. Although much progress has been made in the recent past, the development of a safe, effective and affordable malaria vaccine has remained a challenge. A vaccine targeting sexual stages of the parasite will not only reduce malaria transmission by female Anopheles mosquitoes, but also reduce the spread of parasites able to evade immunity elicited by vaccines targeting pre-erythrocytic and erythrocytic asexual stages. We focused our studies on Pfs48/45, a protein expressed in the sexual stages developing within an infected person and one of the most promising transmission-blocking vaccine targets. Functional immunogenicity of Pfs48/45 protein requires proper disulfide bond formation, consequently evaluation of the immunogenicity of recombinant full-length Pfs48/45 has been hampered by difficulties in expressing properly folded protein to date. Here we present a strategy involving harmonization of codons for successful recombinant expression of full length Pfs48/45 in Escherichia coli. The purified protein, designated CH-rPfs48/45, was recognized by monoclonal antibodies directed against reduction-sensitive conformational epitopes in the native protein. Immunogenicity evaluation in mice revealed potent transmission blocking activity in membrane feeding assays of antisera elicited by CH-rPfs48/45 formulated in three different adjuvants, i.e. Alum, Montanide ISA-51 and complete Freund's adjuvant. More importantly, CH-rPfs48/45 formulated with Montanide ISA-51 when administered to nonhuman primates (Olive baboons, Papio anubis resulted in uniformly high antibody responses (ELISA titers >2 million in all five animals. Sera from these animals displayed greater than 93% blocking activity in membrane feeding assays after a single immunization, reaching nearly complete blocking after a booster dose of the vaccine. The relative ease of expression and induction of
Sheldrake, L.; Mitchell, D.; Allen, M. R.
Temperature and precipitation limit areas of stable malaria transmission, but the effects of climate change on the disease remain controversial. Previously, studies have not separated the influence of anthropogenic climate change and natural variability, despite being an essential step in the attribution of climate change impacts. Ensembles of 2900 simulations of regional climate in sub-Saharan Africa for the year 2013, one representing realistic conditions and the other how climate might have been in the absence of human influence, were used to force a P.falciparium climate suitability model developed by the Mapping Malaria Risk in Africa project. Strongest signals were detected in areas of unstable transmission, indicating their heightened sensitivity to climatic factors. Evidently, impacts of human-induced climate change were unevenly distributed: the probability of conditions being suitable for stable malaria transmission were substantially reduced (increased) in the Sahel (Greater Horn of Africa (GHOA), particularly in the Ethiopian and Kenyan highlands). The length of the transmission season was correspondingly shortened in the Sahel and extended in the GHOA, by 1 to 2 months, including in Kericho (Kenya), where the role of climate change in driving recent malaria occurrence is hotly contested. Human-induced warming was primarily responsible for positive anomalies in the GHOA, while reduced rainfall caused negative anomalies in the Sahel. The latter was associated with anthropogenic impacts on the West African Monsoon, but uncertainty in the RCM's ability to reproduce precipitation trends in the region weakens confidence in the result. That said, outputs correspond well with broad-scale changes in observed endemicity, implying a potentially important contribution of anthropogenic climate change to the malaria burden during the past century. Results support the health-framing of climate risk and help indicate hotspots of climate vulnerability, providing
Pullan Rachel L
Full Text Available Abstract Background In Ethiopia, malaria transmission is seasonal and unstable, with both Plasmodium falciparum and Plasmodium vivax endemic. Such spatial and temporal clustering of malaria only serves to underscore the importance of regularly collecting up-to-date malaria surveillance data to inform decision-making in malaria control. Cross-sectional school-based malaria surveys were conducted across Oromia Regional State to generate up-to-date data for planning malaria control interventions, as well as monitoring and evaluation of operational programme implementation. Methods Two hundred primary schools were randomly selected using a stratified and weighted sampling frame; 100 children aged five to 18 years were then randomly chosen within each school. Surveys were carried out in May 2009 and from October to December 2009, to coincide with the peak of malaria transmission in different parts of Oromia. Each child was tested for malaria by expert microscopy, their haemoglobin measured and a simple questionnaire completed. Satellite-derived environmental data were used to assess ecological correlates of Plasmodium infection; Bayesian geostatistical methods and Kulldorff's spatial scan statistic were employed to investigate spatial heterogeneity. Results A total 20,899 children from 197 schools provided blood samples, two selected schools were inaccessible and one school refused to participate. The overall prevalence of Plasmodium infection was found to be 0.56% (95% CI: 0.46-0.67%, with 53% of infections due to P. falciparum and 47% due to P. vivax. Of children surveyed, 17.6% (95% CI: 17.0-18.1% were anaemic, while 46% reported sleeping under a mosquito net the previous night. Malaria was found at 30 (15% schools to a maximum elevation of 2,187 metres, with school-level Plasmodium prevalence ranging between 0% and 14.5%. Although environmental variables were only weakly associated with P. falciparum and P. vivax infection, clusters of infection
Israel Kayode Olayemi
Full Text Available For the first time in Africa, an entomological study went beyond the conventional practice of determining parity and survival rates of field-collected adult anopheline mosquitoes but also related these variables to duration of Plasmodium sporogony and estimated the expectation of infective life. Blood-seeking female mosquitoes were collected in Ilorin, Nigeria, from January 2005 to December 2006, and dissected for ovarian tracheations following WHO recommended techniques. The results indicated an annual mean parous rate of 70.92%, and significantly higher parous rates in the rainy than dry season, which also had very low densities. Mean probability of daily survival of the mosquitoes was 0.80, with annual mean life expectancy of 12.24 days. The probability of surviving the sporogonic cycle was low (< 0.4 but the expectation of infective life was long, especially in the rainy season (mean = 8.31 days. The epidemiological implications of these results were discussed. The An. gambiae population in Ilorin is dominated by older mosquitoes with high survival rates thus, suggesting a high vector potential for the species in the area. These information on the survival rates of An. gambiae in relation to malaria transmission would enhance the development of a more focused and informed vector control interventions
Tutterrow, Yeung L; Avril, Marion; Singh, Kavita
Placental malaria, caused by sequestration of Plasmodium falciparum-infected erythrocytes in the placenta, is associated with increased risk of maternal morbidity and poor birth outcomes. The parasite antigen VAR2CSA (variant surface antigen 2-chondroitin sulfate A) is expressed on infected...... erythrocytes and mediates binding to chondroitin sulfate A, initiating inflammation and disrupting homeostasis at the maternal-fetal interface. Although antibodies can prevent sequestration, it is unclear whether parasite clearance is due to antibodies to a single Duffy binding-like (DBL) domain...
Full Text Available BACKGROUND: Malaria is endemic in 13 of 64 districts of Bangladesh, representing a population at risk of about 27 million people. The highest rates of malaria in Bangladesh occur in the Chittagong Hill Districts, and Plasmodium falciparum (predominately chloroquine resistant is the most prevalent species. METHODS: The objective of this research was to describe the epidemiology of symptomatic P. falciparum malaria in an area of Bangladesh following the introduction of a national malaria control program. We carried out surveillance for symptomatic malaria due to P. falciparum in two demographically defined unions of the Chittagong Hill Districts in Bangladesh, bordering western Myanmar, between October 2009 and May 2012. The association between sociodemographics and temporal and climate factors with symptomatic P. falciparum infection over two years of surveillance data was assessed. Risk factors for infection were determined using a multivariate regression model. RESULTS: 472 cases of symptomatic P. falciparum malaria cases were identified among 23,372 residents during the study period. Greater than 85% of cases occurred during the rainy season from May to October, and cases were highly clustered geographically within these two unions with more than 80% of infections occurring in areas that contain approximately one-third of the total population. Risk factors statistically associated with infection in a multivariate logistic regression model were living in the areas of high incidence, young age, and having an occupation including jhum cultivation and/or daily labor. Use of long lasting insecticide-treated bed nets was high (89.3%, but its use was not associated with decreased incidence of infection. CONCLUSION: Here we show that P. falciparum malaria continues to be hypoendemic in the Chittagong Hill Districts of Bangladesh, is highly seasonal, and is much more common in certain geographically limited hot spots and among certain occupations.
Niu, Guodong; Franc A, Caio; Zhang, Genwei; Roobsoong, Wanlapa; Nguitragool, Wang; Wang, Xiaohong; Prachumsri, Jetsumon; Butler, Noah S; Li, Jun
FREP1 in mosquito midguts facilitates Plasmodium falciparum parasite transmission. The fibrinogen-like (FBG) domain of FREP1 is highly conserved (>90% identical) among Anopheles species from different continents, suggesting that anti-FBG antibodies may block malaria transmission to all anopheline mosquitoes. Using standard membrane-feeding assays, anti-FREP1 polyclonal antibodies significantly blocked transmission of Plasmodium berghei and Plasmodium vivax to Anopheles gambiae and Anopheles dirus , respectively. Furthermore, in vivo studies of mice immunized with FBG achieved >75% blocking efficacy of P. berghei to A. gambiae without triggering immunopathology. Anti-FBG serum also reduced >81% of P. falciparum infection to A. gambiae Finally, we showed that FBG interacts with Plasmodium gametocytes and ookinetes, revealing the molecular mechanism of its antibody transmission-blocking activity. Collectively, our data support that FREP1-mediated Plasmodium transmission to mosquitoes is a conserved pathway and that targeting the FBG domain of FREP1 will limit the transmission of multiple Plasmodium species to multiple Anopheles species. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.
Full Text Available Since the territory is divided with the province of Banten, in West Java there are five regencies that defined as malaria endemic area, there are Ciamis, Tasikmalaya, Garut, Cianjur and Sukabumi. Sufferer, concentrated in southern coastal areas (Indonesian Ocean starting from the beach of Kalipucang at Ciamis up to coast of Cikakak at Sukabumi which borders the province of Banten and also mountain and plantations areas. Malaria morbidity incidence risk factors is differ in each of these endemic areas. In general is the presence of malaria patients without symptoms who can be a source of infection that so difficult to know its existence. Still the number of standing water that can become mosqui-to breeding places of Anopheles spp, such as fish pond, small puddle on the riverside, shrimp pond, mangrove forests that potentially at the beginning of the rainy season, the fields during rice that potential when the rice growing and the river that potential in the dry season. The existence of high population mobility and also the number of vegetation in the surrounding residential population and the existence of cattle are placed close to settle-ments.
Full Text Available Anopheles mosquitoes transmit at least 200 million annual malaria infections worldwide. Despite considerable genomic resources, mechanistic understanding of biological processes in Anopheles has been hampered by a lack of tools for reverse genetics. Here, we report successful application of the CRISPR/Cas9 system for highly efficient, site-specific mutagenesis in the diverse malaria vectors Anopheles albimanus, A. coluzzii, and A. funestus. When guide RNAs (gRNAs and Cas9 protein are injected at high concentration, germline mutations are common and usually biallelic, allowing for the rapid creation of stable mutant lines for reverse genetic analysis. Our protocol should enable researchers to dissect the molecular and cellular basis of anopheline traits critical to successful disease transmission, potentially exposing new targets for malaria control.
Jäckle, Mario J; Blumentrath, Christian G; Zoleko, Rella M; Akerey-Diop, Daisy; Mackanga, Jean-Rodolphe; Adegnika, Ayôla A; Lell, Bertrand; Matsiegui, Pierre-Blaise; Kremsner, Peter G; Mombo-Ngoma, Ghyslain; Ramharter, Michael
Malaria remains one of the most important infectious diseases in pregnancy in sub-Saharan Africa. Whereas seasonal malaria chemoprevention is advocated as public health intervention for children in certain areas of highly seasonal malaria transmission, the impact of seasonality on malaria in pregnancy has not yet been investigated for stable, hyper-endemic transmission settings of Equatorial Africa. The aim of this study was to investigate the influence of seasonality on the prevalence of malaria in pregnancy in Gabon. The study was conducted at a rural district hospital in Gabon between January 2008 and December 2011. At first antenatal care visits demographic data, parity, age, and gestational age of pregnant women were documented and thick blood smears were performed for the diagnosis of malaria. Seasonality and established risk factors were evaluated in univariate and multivariate analysis for their association with Plasmodium falciparum infection. 1,661 pregnant women were enrolled in this study. Participants presenting during high transmission seasons were at significantly higher risk for P. falciparum infection compared to low transmission seasons (adjusted odds ratio [AOR] 1.91, 95% confidence interval [CI] 1.39-2.63, p risk factors including parity (AOR 0.45, CI 0.30-0.69, p risk factors for P. falciparum infection. High-risk groups including nulli- and primipara and younger women aged 13-17 years showed a disproportionately increased risk for malaria in high transmission seasons from 17% to 64% prevalence in low and high transmission periods, respectively. Seasonal variations lead to important differences in the risk for P. falciparum infection in pregnancy in the setting of central African regions with stable and hyper-endemic malaria transmission. The seasonal increase in malaria in pregnancy is most pronounced in high-risk groups constituted by young and pauciparous women. The evaluation of tailored seasonal prevention strategies for these high
Full Text Available Abstract Background Highland areas of Africa are mostly malaria hypoendemic, due to climate which is not appropriate for anophelines development and their reproductive fitness. In view of designing a malaria control strategy in Western Cameroon highlands, baseline data on anopheline species bionomics were collected. Methods Longitudinal entomological surveys were conducted in three localities at different altitudinal levels. Mosquitoes were captured when landing on human volunteers and by pyrethrum spray catches. Sampled Anopheles were tested for the presence of Plasmodium circumsporozoite proteins and their blood meal origin with ELISA. Entomological parameters of malaria epidemiology were assessed using Mac Donald's formula. Results Anopheline species diversity and density decreased globally from lowland to highland. The most aggressive species along the altitudinal transect was Anopheles gambiae s.s. of S molecular form, followed in the lowland and on the plateau by An. funestus, but uphill by An. hancocki. An. gambiae and An. ziemanni exhibited similar seasonal biting patterns at the different levels, whereas different features were observed for An. funestus. Only indoor resting species could be captured uphill; it is therefore likely that endophilic behaviour is necessary for anophelines to climb above a certain threshold. Of the ten species collected along the transect, only An. gambiae and An. funestus were responsible for malaria transmission, with entomological inoculation rates (EIR of 90.5, 62.8 and zero infective bites/human/year in the lowland, on the plateau and uphill respectively. The duration of gonotrophic cycle was consistently one day shorter for An. gambiae as compared to An. funestus at equal altitude. Altitudinal climate variations had no effect on the survivorship and the subsequent life expectancy of the adult stage of these malaria vectors, but most probably on aquatic stages. On the contrary increasing altitude
Hardy, Andrew; Mageni, Zawadi; Dongus, Stefan; Killeen, Gerry; Macklin, Mark G; Majambare, Silas; Ali, Abdullah; Msellem, Mwinyi; Al-Mafazy, Abdul-Wahiyd; Smith, Mark; Thomas, Chris
Larval source management strategies can play an important role in malaria elimination programmes, especially for tackling outdoor biting species and for eliminating parasite and vector populations when they are most vulnerable during the dry season. Effective larval source management requires tools for identifying geographic foci of vector proliferation and malaria transmission where these efforts may be concentrated. Previous studies have relied on surface topographic wetness to indicate hydrological potential for vector breeding sites, but this is unsuitable for karst (limestone) landscapes such as Zanzibar where water flow, especially in the dry season, is subterranean and not controlled by surface topography. We examine the relationship between dry and wet season spatial patterns of diagnostic positivity rates of malaria infection amongst patients reporting to health facilities on Unguja, Zanzibar, with the physical geography of the island, including land cover, elevation, slope angle, hydrology, geology and geomorphology in order to identify transmission hot spots using Boosted Regression Trees (BRT) analysis. The distribution of both wet and dry season malaria infection rates can be predicted using freely available static data, such as elevation and geology. Specifically, high infection rates in the central and southeast regions of the island coincide with outcrops of hard dense limestone which cause locally elevated water tables and the location of dolines (shallow depressions plugged with fine-grained material promoting the persistence of shallow water bodies). This analysis provides a tractable tool for the identification of malaria hotspots which incorporates subterranean hydrology, which can be used to target larval source management strategies.
The Effect of Indoor Residual Spraying on the Prevalence of Malaria Parasite Infection, Clinical Malaria and Anemia in an Area of Perennial Transmission and Moderate Coverage of Insecticide Treated Nets in Western Kenya.
John E Gimnig
Full Text Available Insecticide treated nets (ITNs and indoor residual spraying (IRS have been scaled up for malaria prevention in sub-Saharan Africa. However, there are few studies on the benefit of implementing IRS in areas with moderate to high coverage of ITNs. We evaluated the impact of an IRS program on malaria related outcomes in western Kenya, an area of intense perennial malaria transmission and moderate ITN coverage (55-65% use of any net the previous night.The Kenya Division of Malaria Control, with support from the US President's Malaria Initiative, conducted IRS in one lowland endemic district with moderate coverage of ITNs. Surveys were conducted in the IRS district and a neighboring district before IRS, after one round of IRS in July-Sept 2008 and after a second round of IRS in April-May 2009. IRS was conducted with pyrethroid insecticides. At each survey, 30 clusters were selected for sampling and within each cluster, 12 compounds were randomly selected. The primary outcomes measured in all residents of selected compounds included malaria parasitemia, clinical malaria (P. falciparum infection plus history of fever and anemia (Hb<8 of all residents in randomly selected compounds. At each survey round, individuals from the IRS district were matched to those from the non-IRS district using propensity scores and multivariate logistic regression models were constructed based on the matched dataset.At baseline and after one round of IRS, there were no differences between the two districts in the prevalence of malaria parasitemia, clinical malaria or anemia. After two rounds of IRS, the prevalence of malaria parasitemia was 6.4% in the IRS district compared to 16.7% in the comparison district (OR = 0.36, 95% CI = 0.22-0.59, p<0.001. The prevalence of clinical malaria was also lower in the IRS district (1.8% vs. 4.9%, OR = 0.37, 95% CI = 0.20-0.68, p = 0.001. The prevalence of anemia was lower in the IRS district but only in children under 5 years of age (2
Vardo, A M; Schall, J J
Within the vertebrate host, infections of a malaria parasite (Plasmodium) could include a single genotype of cells (single-clone infections) or two to several genotypes (multiclone infections). Clonal diversity of infection plays an important role in the biology of the parasite, including its life history, virulence, and transmission. We determined the clonal diversity of Plasmodium mexicanum, a lizard malaria parasite at a study region in northern California, using variable microsatellite markers, the first such study for any malaria parasite of lizards or birds (the most common hosts for Plasmodium species). Multiclonal infections are common (50-88% of infections among samples), and measures of genetic diversity for the metapopulation (expected heterozygosity, number of alleles per locus, allele length variation, and effective population size) all indicated a substantial overall genetic diversity. Comparing years with high prevalence (1996-1998 = 25-32% lizards infected), and years with low prevalence (2001-2005 = 6-12%) found fewer alleles in samples taken from the low-prevalence years, but no reduction in overall diversity (H = 0.64-0.90 among loci). In most cases, rare alleles appeared to be lost as prevalence declined. For sites chronically experiencing low transmission intensity (prevalence approximately 1%), overall diversity was also high (H = 0.79-0.91), but there were fewer multiclonal infections. Theory predicts an apparent excess in expected heterozygosity follows a genetic bottleneck. Evidence for such a distortion in genetic diversity was observed after the drop in parasite prevalence under the infinite alleles mutation model but not for the stepwise mutation model. The results are similar to those reported for the human malaria parasite, Plasmodium falciparum, worldwide, and support the conclusion that malaria parasites maintain high genetic diversity in host populations despite the potential for loss in alleles during the transmission cycle or
Full Text Available Blocking Plasmodium falciparum transmission to mosquitoes has been designated a strategic objective in the global agenda of malaria elimination. Transmission is ensured by gametocyte-infected erythrocytes (GIE that sequester in the bone marrow and at maturation are released into peripheral blood from where they are taken up during a mosquito blood meal. Release into the blood circulation is accompanied by an increase in GIE deformability that allows them to pass through the spleen. Here, we used a microsphere matrix to mimic splenic filtration and investigated the role of cAMP-signalling in regulating GIE deformability. We demonstrated that mature GIE deformability is dependent on reduced cAMP-signalling and on increased phosphodiesterase expression in stage V gametocytes, and that parasite cAMP-dependent kinase activity contributes to the stiffness of immature gametocytes. Importantly, pharmacological agents that raise cAMP levels in transmissible stage V gametocytes render them less deformable and hence less likely to circulate through the spleen. Therefore, phosphodiesterase inhibitors that raise cAMP levels in P. falciparum infected erythrocytes, such as sildenafil, represent new candidate drugs to block transmission of malaria parasites.
Vestergaard, Lasse S; Lusingu, John P; Nielsen, Morten A
at population level, we conducted an immunoepidemiological study in nearby communities in northeastern Tanzania, situated at different altitudes and therefore exposed to different levels of P. falciparum transmission intensity. Samples of plasma and infected red blood cells (IRBC) were collected from 759......-VSA IgG response developed dramatically in individuals at 1 to 2 years of age in the high-transmission area, reaching a maximum level at around 10 years of age; only a modest further increase was observed among older children and adults. In contrast, at lower levels of malaria transmission, anti-VSA Ig...... and functional characteristics of the variant-specific antibody response, which is likely to be important for protection against malaria....
Gregory, James A.; Li, Fengwu; Tomosada, Lauren M.; Cox, Chesa J.; Topol, Aaron B.; Vinetz, Joseph M.; Mayfield, Stephen
Subunit vaccines are significantly more expensive to produce than traditional vaccines because they are based primarily on recombinant proteins that must be purified from the expression system. Despite the increased cost, subunit vaccines are being developed because they are safe, effective, and can elicit antibodies that confer protection against diseases that are not currently vaccine-preventable. Algae are an attractive platform for producing subunit vaccines because they are relatively inexpensive to grow, genetically tractable, easily scaled to large volumes, have a short generation time, and are devoid of inflammatory, viral, or prion contaminants often present in other systems. We tested whether algal chloroplasts can produce malaria transmission blocking vaccine candidates, Plasmodium falciparum surface protein 25 (Pfs25) and 28 (Pfs28). Antibodies that recognize Pfs25 and Pfs28 disrupt the sexual development of parasites within the mosquito midgut, thus preventing transmission of malaria from one human host to the next. These proteins have been difficult to produce in traditional recombinant systems because they contain tandem repeats of structurally complex epidermal growth factor-like domains, which cannot be produced in bacterial systems, and because they are not glycosylated, so they must be modified for production in eukaryotic systems. Production in algal chloroplasts avoids these issues because chloroplasts can fold complex eukaryotic proteins and do not glycosylate proteins. Here we demonstrate that algae are the first recombinant system to successfully produce an unmodified and aglycosylated version of Pfs25 or Pfs28. These antigens are structurally similar to the native proteins and antibodies raised to these recombinant proteins recognize Pfs25 and Pfs28 from P. falciparum. Furthermore, antibodies to algae-produced Pfs25 bind the surface of in-vitro cultured P. falciparum sexual stage parasites and exhibit transmission blocking activity. Thus
... a CDC Malaria Branch clinician. email@example.com Malaria and Travelers Recommend on Facebook Tweet Share Compartir ... may be at risk for infection. Determine if malaria transmission occurs at the destinations Obtain a detailed ...
Kaindoa, Emmanuel W; Matowo, Nancy S; Ngowo, Halfan S; Mkandawile, Gustav; Mmbando, Arnold; Finda, Marcelina; Okumu, Fredros O
An. arabiensis (44.1%). Though An. arabiensis is still the most abundant vector species here, the remaining malaria transmission is predominantly mediated by An. funestus, possibly due to high insecticide resistance and high survival probabilities. Interventions that effectively target An. funestus mosquitoes could therefore significantly improve control of persistent malaria transmission in south-eastern Tanzania.
Emmanuel W Kaindoa
.8% than An. arabiensis (44.1%. Though An. arabiensis is still the most abundant vector species here, the remaining malaria transmission is predominantly mediated by An. funestus, possibly due to high insecticide resistance and high survival probabilities. Interventions that effectively target An. funestus mosquitoes could therefore significantly improve control of persistent malaria transmission in south-eastern Tanzania.
Bayesian variable selection in modelling geographical heterogeneity in malaria transmission from sparse data: an application to Nouna Health and Demographic Surveillance System (HDSS) data, Burkina Faso.
Diboulo, Eric; Sié, Ali; Diadier, Diallo A; Karagiannis Voules, Dimitrios A; Yé, Yazoume; Vounatsou, Penelope
the relatively small geographical extend of the study area. Malaria transmission is very heterogeneous over the study area. The EIR maps clearly depict a strong spatial and temporal heterogeneity despite the relatively small geographical extend of the study area. Model based estimates of transmission can be used to identify high transmission areas in order to prioritise interventions and support research in malaria epidemiology.
Tompkins, Adrian M; Ermert, Volker
The relative roles of climate variability and population related effects in malaria transmission could be better understood if regional-scale dynamical malaria models could account for these factors. A new dynamical community malaria model is introduced that accounts for the temperature and rainfall influences on the parasite and vector life cycles which are finely resolved in order to correctly represent the delay between the rains and the malaria season. The rainfall drives a simple but physically based representation of the surface hydrology. The model accounts for the population density in the calculation of daily biting rates. Model simulations of entomological inoculation rate and circumsporozoite protein rate compare well to data from field studies from a wide range of locations in West Africa that encompass both seasonal endemic and epidemic fringe areas. A focus on Bobo-Dioulasso shows the ability of the model to represent the differences in transmission rates between rural and peri-urban areas in addition to the seasonality of malaria. Fine spatial resolution regional integrations for Eastern Africa reproduce the malaria atlas project (MAP) spatial distribution of the parasite ratio, and integrations for West and Eastern Africa show that the model grossly reproduces the reduction in parasite ratio as a function of population density observed in a large number of field surveys, although it underestimates malaria prevalence at high densities probably due to the neglect of population migration. A new dynamical community malaria model is publicly available that accounts for climate and population density to simulate malaria transmission on a regional scale. The model structure facilitates future development to incorporate migration, immunity and interventions.
Tompkins, Adrian M; Caporaso, Luca
Using mathematical modelling tools, we assessed the potential for land use change (LUC) associated with the Intergovernmental Panel on Climate Change low- and high-end emission scenarios (RCP2.6 and RCP8.5) to impact malaria transmission in Africa. To drive a spatially explicit, dynamical malaria model, data from the four available earth system models (ESMs) that contributed to the LUC experiment of the Fifth Climate Model Intercomparison Project are used. Despite the limited size of the ESM ensemble, stark differences in the assessment of how LUC can impact climate are revealed. In three out of four ESMs, the impact of LUC on precipitation and temperature over the next century is limited, resulting in no significant change in malaria transmission. However, in one ESM, LUC leads to increases in precipitation under scenario RCP2.6, and increases in temperature in areas of land use conversion to farmland under both scenarios. The result is a more intense transmission and longer transmission seasons in the southeast of the continent, most notably in Mozambique and southern Tanzania. In contrast, warming associated with LUC in the Sahel region reduces risk in this model, as temperatures are already above the 25-30°C threshold at which transmission peaks. The differences between the ESMs emphasise the uncertainty in such assessments. It is also recalled that the modelling framework is unable to adequately represent local-scale changes in climate due to LUC, which some field studies indicate could be significant.
ter Kuile, Feiko O.; Terlouw, Dianne J.; Kariuki, Simon K.; Phillips-Howard, Penelope A.; Mirel, Lisa B.; Hawley, William A.; Friedman, Jennifer F.; Shi, Ya Ping; Kolczak, Margarette S.; Lal, Altaf A.; Vulule, John M.; Nahlen, Bernard L.
As part of a community-based, group-randomized, controlled trial of insecticide-treated bed nets (ITNs) in an area with intense malaria transmission in western Kenya, a birth cohort (n = 833) was followed monthly until the age of 24 months to determine the potential beneficial and adverse effects of
Ndyomugyenyi, Richard; Magnussen, Pascal; Clarke, Siân
Knowledge of malaria and treatment-seeking behaviour was investigated in an area of low transmission in Uganda to help health services to plan for appropriate interventions to control malaria. Although knowledge of malaria symptoms, preventive methods and malaria risks was widespread, few were...... actually using insecticide-treated nets. Many patients (25%) had received treatment prior to visiting a health facility, with drug shops and general stores being the main sources of treatment. Some shops dispensed quinine, a second-line drug recommended for complicated malaria. Prescription practices...... of health staff often did not comply with guidelines. Only 30% of patients received treatment at a health facility within 24h of onset of symptoms. Findings indicate a need for community-level information campaigns on prompt treatment and introduction of home-based management of fever. Measures are needed...
Diuk Wasser, Maria Ana
The explosive population growth and widespread urbanization in Africa requires a significant increase in food production. Crop irrigation is therefore expected to increase in the future, although it is often blamed for aggravating the health risk of local communities---by providing habitats suitable for mosquitoes vectors of malaria (Anopheles gambiae s.l. and An. funestus in our study area) and other diseases. An epidemiological paradox sometimes occurs, however, when an increase in vector numbers is accompanied by a reduction of the risk of infection, due to a reduction in mosquito longevity and of their tendency to bite human (vs. animals). The objective of this dissertation was to determine how agricultural patterns mapped using satellite data affected vector densities and malaria transmission parameters in 18 rice-cropping villages in Mali. I used a combination of optical (Landsat ETM+) and synthetic aperture radar (ERS-2 SAR). Using Landsat data, rice was distinguished from other land uses with 98% accuracy and rice cohorts were discriminated with 84% accuracy (three classes) or 94% (two classes). ERS-2 SAR backscatter was correlated with the height and biomass of rice plants and was therefore useful to distinguish among rice growth stages. As in previous studies, the early vegetative stage was associated with higher larval production. SAR was further able to distinguish between agronomic practices linked to high and low-production within those early stages. The landcover maps were integrated with archived data on adult and larval anopheline densities and malaria transmission parameters. The area of several landcovers explained up to 89% of the variability in mosquito numbers. The maximum correlation was obtained when landcover was measured in a 1-km buffer area. Vector density was negatively associated to parity and anthropophilic rates. An. gambiae showed higher vectorial capacity (VC) than An. funestus , with seasonal variations. Peak VC for both species
Rulisa, Stephen; Mens, Pètra F.; Karema, Corine; Schallig, Henk D. F. H.; Kaligirwa, Nadine; Vyankandondera, Joseph; de Vries, Peter J.
Malaria has a negative effect on pregnancy outcome, causing low birth weight, premature birth and stillbirths, particularly in areas with high malaria transmission. In Rwanda, malaria transmission intensity ranges from high to nil, probably associated with variable altitudes. Overall, the incidence
... deadly type occurs in Africa south of the Sahara Desert. Malaria symptoms include chills, flu-like symptoms, fever, vomiting, diarrhea, and jaundice. A blood test can diagnose it. It can be life-threatening. However, you can treat malaria with drugs. ...
Full Text Available Malaria is an infectious disease caused by Plasmodium spp, are naturally transmitted by the mosquito Anopheles spp. Malaria transmission occurs because of interaction between the agent, the definitive host and intermediate hosts (humans. Therefore, the transmission of malaria is injluenced by the presence and fluctuations in vector populations (i.e transmitting mosquito Anopheles spp.Malaria diagnosis consists of clinical diagnosis and diagnosis based on laboratory examination. Clinical diagnosis or clinical malaria diagnosis was presumptive diagnosis of malaria based on clinical examination of patients with symptoms include fever (periodical, heat, level of consciousness, dizziness, etc. as well as specific local typical symptoms. Experiences of medical personnel who perform precise diagnosis will determine whether or not the diagnosis, so that clinical diagnosis cannot be the main reference in the treatment of malaria because of high error rates.
Pastrana-Mena, Rebecca; Mathias, Derrick K; Delves, Michael; Rajaram, Krithika; King, Jonas G; Yee, Rebecca; Trucchi, Beatrice; Verotta, Luisella; Dinglasan, Rhoel R
The evolution of drug resistance is a recurrent problem that has plagued efforts to treat and control malaria. Recent emergence of artemisinin resistance in Southeast Asia underscores the need to develop novel antimalarials and identify new targetable pathways in Plasmodium parasites. Transmission-blocking approaches, which typically target gametocytes in the host bloodstream or parasite stages in the mosquito gut, are recognized collectively as a strategy that when used in combination with antimalarials that target erythrocytic stages will not only cure malaria but will also prevent subsequent transmission. We tested four derivatives of (+)-usnic acid, a metabolite isolated from lichens, for transmission-blocking activity against Plasmodium falciparum using the standard membrane feeding assay. For two of the derivatives, BT37 and BT122, we observed a consistent dose-response relationship between concentration in the blood meal and oocyst intensity in the midgut. To explore their mechanism of action, we used the murine model Plasmodium berghei and found that both derivatives prevent ookinete maturation. Using fluorescence microscopy, we demonstrated that in the presence of each compound zygote vitality was severely affected, and those that did survive failed to elongate and mature into ookinetes. The observed phenotypes were similar to those described for mutants of specific kinases (NEK2/NEK4) and of inner membrane complex 1 (IMC1) proteins, which are all vital to the zygote-to-ookinete transition. We discuss the implications of our findings and our high-throughput screening approach to identifying next generation, transmission-blocking antimalarials based on the scaffolds of these (+)-usnic acid derivatives.
Background The WHO has reported that RDT and microscopy-confirmed malaria cases have declined in recent years. However, it is still unclear if this reflects a real decrease in incidence in Bangladesh, as particularly the hilly and forested areas of the Chittagong Hill Tract (CHT) Districts report more than 80% of all cases and deaths. surveillance and epidemiological data on malaria from the CHT are limited; existing data report Plasmodium falciparum and Plasmodium vivax as the dominant species. Methods A cross-sectional survey was conducted in the District of Bandarban, the southernmost of the three Hill Tracts Districts, to collect district-wide malaria prevalence data from one of the regions with the highest malaria endemicity in Bangladesh. A multistage cluster sampling technique was used to collect blood samples from febrile and afebrile participants and malaria microscopy and standardized nested PCR for diagnosis were performed. Demographic data, vital signs and splenomegaly were recorded. Results Malaria prevalence across all subdistricts in the monsoon season was 30.7% (95% CI: 28.3-33.2) and 14.2% (95% CI: 12.5-16.2) by PCR and microscopy, respectively. Plasmodium falciparum mono-infections accounted for 58.9%, P. vivax mono-infections for 13.6%, Plasmodium malariae for 1.8%, and Plasmodium ovale for 1.4% of all positive cases. In 24.4% of all cases mixed infections were identified by PCR. The proportion of asymptomatic infections among PCR-confirmed cases was 77.0%, oligosymptomatic and symptomatic cases accounted for only 19.8 and 3.2%, respectively. Significantly (p malaria prevalence in two to nine year olds were 18.6 and 34.6%, respectively. No significant difference in malaria prevalence and parasite density was observed between dry and rainy season. Conclusions A large proportion of asymptomatic plasmodial infections was found which likely act as a reservoir of transmission. This has major implications for ongoing malaria control programmes that
Morahan, Belinda; Garcia-Bustos, Jose
The symptoms of malaria, one of the infectious diseases with the highest mortality and morbidity world-wide, are caused by asexual parasites replicating inside red blood cells. Disease transmission, however, is effected by non-replicating cells which have differentiated into male or female gametocytes. These are the forms infectious to mosquito vectors and the insects are the only hosts where parasite sexual reproduction can take place. Malaria is thus a complex infection in which pharmacological treatment of symptoms may still allow transmission for long periods, while pharmacological blockage of infectivity may not cure symptoms. The process of parasite sexual differentiation and development is still being revealed but it is clear that kinase-mediated signalling mechanisms play a significant role. This review attempts to summarise our limited current knowledge on the signalling mechanisms involved in the transition from asexual replication to sexual differentiation and reproduction, with a brief mention to the effects of current treatments on the sexual stages and to some of the difficulties inherent in developing pharmacological interventions to curtail disease transmission. Copyright © 2014 Elsevier B.V. All rights reserved.
Shimp, Richard L; Rowe, Christopher; Reiter, Karine; Chen, Beth; Nguyen, Vu; Aebig, Joan; Rausch, Kelly M; Kumar, Krishan; Wu, Yimin; Jin, Albert J; Jones, David S; Narum, David L
Successful efforts to control infectious diseases have often required the use of effective vaccines. The current global strategy for control of malaria, including elimination and eradication will also benefit from the development of an effective vaccine that interrupts malaria transmission. To this end, a vaccine that disrupts malaria transmission within the mosquito host has been investigated for several decades targeting a 25 kDa ookinete specific surface protein, identified as Pfs25. Phase 1 human trial results using a recombinant Pfs25H/Montanide ISA51 formulation demonstrated that human Pfs25 specific antibodies block parasite infectivity to mosquitoes; however, the extent of blocking was likely insufficient for an effective transmission blocking vaccine. To overcome the poor immunogenicity, processes to produce and characterize recombinant Pfs25H conjugated to a detoxified form of Pseudomonas aeruginosa exoprotein A (EPA) have been developed and used to manufacture a cGMP pilot lot for use in human clinical trials. The Pfs25-EPA conjugate appears as a nanoparticle with an average molar mass in solution of approximately 600 kDa by static light scattering with an average diameter 20 nm (range 10-40 nm) by dynamic light scattering. The molar ratio of Pfs25H to EPA is about 3 to 1 by amino acid analysis, respectively. Outbred mice immunized with the Pfs25-EPA conjugated nanoparticle formulated on Alhydrogel(®) had a 75-110 fold increase in Pfs25H specific antibodies when compared to an unconjugated Pfs25H/Alhydrogel(®) formulation. A phase 1 human trial using the Pfs25-EPA/Alhydrogel(®) formulation is ongoing in the United States. Published by Elsevier Ltd.
Full Text Available Abstract Background Knowledge of some baseline entomological data such as Entomological Inoculation Rates (EIR is crucially needed to assess the epidemiological impact of malaria control activities directed either against parasites or vectors. In Chad, most published surveys date back to the 1960's. In this study, anopheline species composition and their relation to malaria transmission were investigated in a dry Sudanian savannas area of Chad. Methods A 12-month longitudinal survey was conducted in the irrigated rice-fields area of Goulmoun in south western Chad. Human landing catches were performed each month from July 2006 to June 2007 in three compounds (indoors and outdoors and pyrethrum spray collections were conducted in July, August and October 2006 in 10 randomly selected rooms. Mosquitoes belonging to the Anopheles gambiae complex and to the An. funestus group were identified by molecular diagnostic tools. Plasmodium falciparum infection and blood meal sources were detected by ELISA. Results Nine anopheline species were collected by the two sampling methods. The most aggressive species were An. arabiensis (51 bites/human/night, An. pharoensis (12.5 b/h/n, An. funestus (1.5 b/h/n and An. ziemanni (1.3 b/h/n. The circumsporozoite protein rate was 1.4% for An. arabiensis, 1.4% for An. funestus, 0.8% for An. pharoensis and 0.5% for An. ziemanni. Malaria transmission is seasonal, lasting from April to December. However, more than 80% of the total EIR was concentrated in the period from August to October. The overall annual EIR was estimated at 311 bites of infected anophelines/human/year, contributed mostly by An. arabiensis (84.5% and An. pharoensis (12.2%. Anopheles funestus and An. ziemanni played a minor role. Parasite inoculation occurred mostly after 22:00 hours but around 20% of bites of infected anophelines were distributed earlier in the evening. Conclusion The present study revealed the implication of An. pharoensis in malaria
Kwadwo A Kusi
Full Text Available As an increasing number of malaria-endemic countries approach the disease elimination phase, sustenance of control efforts and effective monitoring are necessary to ensure success. Mathematical models that estimate anti-parasite antibody seroconversion rates are gaining relevance as more sensitive transmission intensity estimation tools. Models however estimate yearly seroconversion and seroreversion rates and usually predict long term changes in transmission, occurring years before the time of sampling. Another challenge is the identification of appropriate antigen targets since specific antibody levels must directly reflect changes in transmission patterns. We therefore investigated the potential of antibodies to sporozoite and blood stage antigens for detecting short term differences in malaria transmission in two communities in Northern Ghana with marked, seasonal transmission.Cross-sectional surveys were conducted during the rainy and dry seasons in two communities, one in close proximity to an irrigation dam and the other at least 20 Km away from the dam. Antibodies against the sporozoite-specific antigens circumsporozoite protein (CSP and Cell traversal for ookinetes and sporozoites (CelTOS and the classical blood stage antigen apical membrane antigen 1 (AMA1 were measured by indirect ELISA. Antibody levels and seroprevalence were compared between surveys and between study communities. Antibody seroprevalence data were fitted to a modified reversible catalytic model to estimate the seroconversion and seroreversion rates.Changes in sporozoite-specific antibody levels and seroprevalence directly reflected differences in parasite prevalence between the rainy and dry seasons and hence the extent of malaria transmission. Seroconversion rate estimates from modelled seroprevalence data did not however support the above observation.The data confirms the potential utility of sporozoite-specific antigens as useful markers for monitoring short term
Tanga, M C; Ngundu, W I; Judith, N; Mbuh, J; Tendongfor, N; Simard, Frédéric; Wanji, S
An entomological survey was conducted in Cameroon between October 2004 and September 2005, in nine localities targeted for malaria vector control based on adult productivity and variability. Mosquitoes were collected by human-landing catches (HLCs) and pyrethrum spray catches. A total of 12 500 anophelines were collected and dissected: Anopheles gambiae s.l. (56.86%), An. funestus s.l. (32.57%), An. hancocki (9.38%), and An. nili (1.18%). Applying PCR revealed that specimens of the An. funestus group were An. funestus s.s. and An. gambiae complex were mostly An. melas and An. gambiae s.s. of the M and S molecular forms with the M forms being the most predominant. The natural distribution patterns of Anopheles species were largely determined by altitude with some species having unique environmental tolerance limits. A human blood index (HBI) of 99.05% was recorded. Mean probability of daily survival of the malaria vectors was 0.92, with annual mean life expectancy of 21.9 days and the expectation of infective life was long with a mean of 7.4 days. The high survival rates suggest a high vector potential for the species. This information enhances the development of a more focused and informed vector control intervention. Copyright 2010 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.
Full Text Available Abstract Background Malaria during first few months of life may be due to transplacental transfer of parasitized maternal erythrocytes. Although IgG and IgM antimalarial antibodies can be detected in maternal blood, only IgG antibodies are present in the infant's blood. These antibodies can delay and modify the onset of clinical manifestations. Case Presentation An infant is described who presented with irritability and feeding problems. Clinical examination and investigations revealed that the infant was afebrile, had jaundice, hepatosplenomegaly and haemolytic anaemia. Peripheral smear demonstrated Plasmodium vivax. While the mother had significant levels of immunoglobulin G (IgG, the infant was found negative for IgG and had low immunoglobulin M (IgM levels. The mother had a history of febrile illness during pregnancy and her peripheral smear was also positive for P. vivax. Both were successfully treated with chloroquine in the dose of 25 mg/kg/day over three days. Conclusion The case emphasizes the importance of considering the diagnosis of malaria even in infants in low transmission area, who may not present with typical symptoms of malaria, such as fever, but have other clinical manifestations like jaundice and haemolytic anaemia.
Full Text Available Abstract Background Malaria is an important public-health problem in the archipelago of Vanuatu and climate has been hypothesized as important influence on transmission risk. Beginning in 1988, a major intervention using insecticide-treated bed nets (ITNs was implemented in the country in an attempt to reduce Plasmodium transmission. To date, no study has addressed the impact of ITN intervention in Vanuatu, how it may have modified the burden of disease, and whether there were any changes in malaria incidence that might be related to climatic drivers. Methods and findings Monthly time series (January 1983 through December 1999 of confirmed Plasmodium falciparum and Plasmodium vivax infections in the archipelago were analysed. During this 17 year period, malaria dynamics underwent a major regime shift around May 1991, following the introduction of bed nets as a control strategy in the country. By February of 1994 disease incidence from both parasites was reduced by at least 50%, when at most 20% of the population at risk was covered by ITNs. Seasonal cycles, as expected, were strongly correlated with temperature patterns, while inter-annual cycles were associated with changes in precipitation. Following the bed net intervention, the influence of environmental drivers of malaria dynamics was reduced by 30–80% for climatic forces, and 33–54% for other factors. A time lag of about five months was observed for the qualitative change ("regime shift" between the two parasites, the change occurring first for P. falciparum. The latter might be explained by interspecific interactions between the two parasites within the human hosts and their distinct biology, since P. vivax can relapse after a primary infection. Conclusion The Vanuatu ITN programme represents an excellent example of implementing an infectious disease control programme. The distribution was undertaken to cover a large, local proportion (~80% of people in villages where malaria was
Full Text Available Abstract Background Adequate malaria diagnosis and treatment remain major difficulties in rural sub-Saharan Africa. These issues deserve renewed attention in the light of first-line treatment with expensive artemisinin-combination therapy (ACT and changing patterns of transmission intensity. This study describes diagnostic and treatment practices in Mto wa Mbu, an area that used to be hyperendemic for malaria, but where no recent assessments of transmission intensity have been conducted. Methods Retrospective and prospective data were collected from the two major village health clinics. The diagnosis in prospectively collected data was confirmed by microscopy. The level of transmission intensity was determined by entomological assessment and by estimating sero-conversion rates using anti-malarial antibody responses. Results Malaria transmission intensity by serological assessment was equivalent to 40% of outpatients attending the clinics in 2006–2007 were diagnosed with malaria. Prospective data demonstrated a very high overdiagnosis of malaria. Microscopy was unreliable with Conclusion Transmission intensity has dropped considerably in the area of Mto wa Mbu. Despite this, most fevers are still regarded and treated as malaria, thereby ignoring true causes of febrile illness and over-prescribing ACT. The discrepancy between the perceived and actual level of transmission intensity may be present in many areas in sub-Saharan Africa and calls for greater efforts in defining levels of transmission on a local scale to help rational drug-prescribing behaviour.
Manana, Pinky N; Kuonza, Lazarus; Musekiwa, Alfred; Mpangane, Hluphi D; Koekemoer, Lizette L
In South Africa malaria is endemic in Mpumalanga, Limpopo and the north-eastern areas of KwaZulu-Natal provinces. South Africa has set targets to eliminate malaria by 2018 and research into complementary vector control tools such as the Sterile Insect Technique (SIT) is ongoing. It is important to understand community perceptions regarding malaria transmission and control interventions to enable development of community awareness campaign messages appropriate to the needs of the community. We aimed to assess knowledge, attitudes, and practices regarding malaria transmission to inform a public awareness campaign for SIT in Jozini Local Municipality, Mamfene in KwaZulu-Natal province. We conducted a cross-sectional survey in three communities in Mamfene, KwaZulu-Natal during 2015. A structured field piloted questionnaire was administered to 400 randomly selected heads of households. Descriptive statistics were used to summarize data. Of the 400 participants interviewed, 99% had heard about malaria and correctly associated it with mosquito bites. The sources of malaria information were the local health facility (53%), radio (16%) and community meetings (7%). Approximately 63% of the participants were able to identify three or four symptoms of malaria. The majority (76%) were confident that indoor residual spraying (IRS) kills mosquitoes and prevents infection. Bed nets were used by 2% of the participants. SIT knowledge was poor (9%), however 63% of the participants were supportive of mosquito releases for research purposes. The remaining 37% raised concerns and fears, including fear of the unknown and lack of information on the SIT. Appropriate knowledge, positive attitude and acceptable treatment-seeking behaviour for malaria were demonstrated by members of the community. Community involvement will be crucial in achieving success of the SIT and future studies should further investigate concerns raised by the community. The existing communication channels used by the
Ernst, Kacey C; Hayden, Mary H; Olsen, Heather; Cavanaugh, Jamie L; Ruberto, Irene; Agawo, Maurice; Munga, Stephen
Challenges persist in ensuring access to and optimal use of long-lasting, insecticidal bed nets (LLINs). Factors associated with ownership and use may differ depending on the history of malaria and prevention control efforts in a specific region. Understanding how the cultural and social-environmental context of bed net use may differ between high- and low-risk regions is important when identifying solutions to improve uptake and appropriate use. Community forums and a household, cross-sectional survey were used to collect information on factors related to bed net ownership and use in western Kenya. Sites with disparate levels of transmission were selected, including an endemic lowland area, Miwani, and a highland epidemic-prone area, Kapkangani. Analysis of ownership was stratified by site. A combined site analysis was conducted to examine factors associated with use of all available bed nets. Logistic regression modelling was used to determine factors associated with ownership and use of owned bed nets. Access to bed nets as the leading barrier to their use was identified in community forums and cross-sectional surveys. While disuse of available bed nets was discussed in the forums, it was a relatively rare occurrence in both sites. Factors associated with ownership varied by site. Education, perceived risk of malaria and knowledge of individuals who had died of malaria were associated with higher bed net ownership in the highlands, while in the lowlands individuals reporting it was easy to get a bed net were more likely to own one. A combined site analysis indicated that not using an available bed net was associated with the attitudes that taking malaria drugs is easier than using a bed net and that use of a bed net will not prevent malaria. In addition, individuals with an unused bed net in the household were more likely to indicate that bed nets are difficult to use, that purchased bed nets are better than freely distributed ones, and that bed nets should only
Angélica Domingues Hristov
Full Text Available Studies on autochthonous malaria in low-transmission areas in Brazil have acquired epidemiological relevance because they suggest continued transmission in what remains of the Atlantic Forest. In the southeastern portion of the state of São Paulo, outbreaks in the municipality of Juquitiba have been the focus of studies on the prevalence of Plasmodium, including asymptomatic cases. Data on the occurrence of the disease or the presence of antiplasmodial antibodies in pregnant women from this region have not previously been described. Although Plasmodium falciparum in pregnant women has been widely addressed in the literature, the interaction of Plasmodium vivax and Plasmodium malariae with this cohort has been poorly explored to date. We monitored the circulation of Plasmodium in pregnant women in health facilities located in Juquitiba using thick blood film and molecular protocols, as well as immunological assays, to evaluate humoural immune parameters. Through real-time and nested polymerase chain reaction, P. vivax and P. malariae were detected for the first time in pregnant women, with a positivity of 5.6%. Immunoassays revealed the presence of IgG antibodies: 44% for ELISA-Pv, 38.4% for SD-Bioline-Pv and 18.4% for indirect immunofluorescence assay-Pm. The high prevalence of antibodies showed significant exposure of this population to Plasmodium. In regions with similar profiles, testing for a malaria diagnosis might be indicated in prenatal care.
Korean vivax malaria had been prevalent for longtime throughout the country with low endemicity. As a result of the Korean war (1950-1953), malaria became epidemic. In 1959-1969 when the National Malaria Eradication Service (NMES) was implemented, malaria rates declined, with low endemicity in the south-west and south plain areas and high endemic foci in north Kyongsangbuk-do (province) and north and east Kyonggi-do. NMES activities greatly contributed in accelerating the control and later eradication of malaria. The Republic of Korea (South Korea) was designated malaria free in 1979. However, malaria re-emerged in 1993 and an outbreak occurred in north Kyonggi-do and north-west Kangwon-do (in and/or near the Demilitarized Zone, DMZ), bordering North Korea. It has been postulated that most of the malaria cases resulted from bites of sporozoite-infected females of An. sinensis dispersed from North Korea across the DMZ. Judging from epidemiological and socio-ecological factors, vivax malaria would not be possible to be endemic in South Korea. Historical data show that vivax malaria in Korea is a typical unstable malaria. Epidemics may occur when environmental, socio-economical, and/or political factors change in favor to malaria transmission, and when such factors change to normal conditions malaria rates become low and may disappear. Passive case detection is a most feasible and recommendable control measure against the unstable vivax malaria in Korea in cost-effect point of view. PMID:11002647
Ree, H I
Korean vivax malaria had been prevalent for longtime throughout the country with low endemicity. As a result of the Korean war (1950-1953), malaria became epidemic. In 1959-1969 when the National Malaria Eradication Service (NMES) was implemented, malaria rates declined, with low endemicity in the south-west and south plain areas and high endemic foci in north Kyongsangbuk-do (province) and north and east Kyonggi-do. NMES activities greatly contributed in accelerating the control and later eradication of malaria. The Republic of Korea (South Korea) was designated malaria free in 1979. However, malaria re-emerged in 1993 and an outbreak occurred in north Kyonggi-do and north-west Kangwon-do (in and/or near the Demilitarized Zone, DMZ), bordering North Korea. It has been postulated that most of the malaria cases resulted from bites of sporozoite-infected females of An. sinensis dispersed from North Korea across the DMZ. Judging from epidemiological and socio-ecological factors, vivax malaria would not be possible to be endemic in South Korea. Historical data show that vivax malaria in Korea is a typical unstable malaria. Epidemics may occur when environmental, socio-economical, and/or political factors change in favor to malaria transmission, and when such factors change to normal conditions malaria rates become low and may disappear. Passive case detection is a most feasible and recommendable control measure against the unstable vivax malaria in Korea in cost-effect point of view.
Grass, David; Jasinski, Michael F.; Govere, John
There has been increasing effort in recent years to employ satellite remotely sensed data to identify and map vector habitat and malaria transmission risk in data sparse environments. In the current investigation, available satellite and other land surface climatology data products are employed in short-term forecasting of infection rates in the Mpumalanga Province of South Africa, using a multivariate autoregressive approach. The climatology variables include precipitation, air temperature and other land surface states computed by the Off-line Land-Surface Global Assimilation System (OLGA) including soil moisture and surface evaporation. Satellite data products include the Normalized Difference Vegetation Index (NDVI) and other forcing data used in the Goddard Earth Observing System (GEOS-1) model. Predictions are compared to long- term monthly records of clinical and microscopic diagnoses. The approach addresses the high degree of short-term autocorrelation in the disease and weather time series. The resulting model is able to predict 11 of the 13 months that were classified as high risk during the validation period, indicating the utility of applying antecedent climatic variables to the prediction of malaria incidence for the Mpumalanga Province.
Yadouléton, Anges; N'guessan, Raphael; Allagbé, Hyacinthe; Asidi, Alex; Boko, Michel; Osse, Razack; Padonou, Gil; Kindé, Gazard; Akogbéto, Martin
Urban agricultural practices are expanding in several cities of the Republic of Benin. This study aims to assess the impact of such practices on transmission of the malaria parasite in major cities of Benin. A cross sectional entomological study was carried out from January to December 2009 in two vegetable farming sites in southern Benin (Houeyiho and Acron) and one in the northern area (Azèrèkè). The study was based on sampling of mosquitoes by Human Landing Catches (HLC) in households close to the vegetable farms and in others located far from the farms. During the year of study, 71,678 female mosquitoes were caught by HLC of which 25% (17,920/71,678) were Anopheles species. In the areas surveyed, the main malaria parasite, Plasmodium falciparum was transmitted in the south by Anopheles gambiae s.s. Transmission was high during the two rainy seasons (April to July and October to November) but declined in the two dry seasons (December to March and August to September). In the north, transmission occurred from June to October during the rainy season and was vehicled by two members of the An. gambiae complex: Anopheles gambiae s.s. (98%) and Anopheles arabiensis (2%).At Houeyiho, Acron and Azèrèkè, the Entomological Inoculation Rates (EIRs) and the Human Biting Rates (HBRs) were significantly higher during the dry season in Households Close to Vegetable Farms (HCVF) than in those located far from the vegetable areas (HFVF) (p 0.05).The knock-down resistance (kdr) mutation was the main resistance mechanism detected at high frequency (0.86 to 0.91) in An. gambiae s.l. at all sites. The ace-1R mutation was also found but at a very low frequency (< 0.1). These findings showed that communities living close to vegetable farms are permanently exposed to malaria throughout the year, whereas the risk in those living far from such agricultural practices is limited and only critical during the rainy seasons. Measures must be taken by African governments to create
Full Text Available Abstract Background Urban agricultural practices are expanding in several cities of the Republic of Benin. This study aims to assess the impact of such practices on transmission of the malaria parasite in major cities of Benin. Method A cross sectional entomological study was carried out from January to December 2009 in two vegetable farming sites in southern Benin (Houeyiho and Acron and one in the northern area (Azèrèkè. The study was based on sampling of mosquitoes by Human Landing Catches (HLC in households close to the vegetable farms and in others located far from the farms. Results During the year of study, 71,678 female mosquitoes were caught by HLC of which 25% (17,920/71,678 were Anopheles species. In the areas surveyed, the main malaria parasite, Plasmodium falciparum was transmitted in the south by Anopheles gambiae s.s. Transmission was high during the two rainy seasons (April to July and October to November but declined in the two dry seasons (December to March and August to September. In the north, transmission occurred from June to October during the rainy season and was vehicled by two members of the An. gambiae complex: Anopheles gambiae s.s. (98% and Anopheles arabiensis (2%. At Houeyiho, Acron and Azèrèkè, the Entomological Inoculation Rates (EIRs and the Human Biting Rates (HBRs were significantly higher during the dry season in Households Close to Vegetable Farms (HCVF than in those located far from the vegetable areas (HFVF (p 0.05. The knock-down resistance (kdr mutation was the main resistance mechanism detected at high frequency (0.86 to 0.91 in An. gambiae s.l. at all sites. The ace-1R mutation was also found but at a very low frequency ( Conclusion These findings showed that communities living close to vegetable farms are permanently exposed to malaria throughout the year, whereas the risk in those living far from such agricultural practices is limited and only critical during the rainy seasons. Measures must be
Fernando, Sumadhya Deepika; Rodrigo, Chaturaka; de Silva, Nipun; Semege, Saveen; Rajapakse, Senaka; Samaranayake, Nilakashi; Senenayake, Sanath; Premaratne, Risintha Gayan
The security forces are a high risk group for malaria transmission in Sri Lanka. Interrupting transmission and maintaining surveillance in this group is an important component of elimination efforts. The objective of the study was to develop a prototype educational programme on malaria for security forces serving in endemic areas. An interactive seminar was designed to deliver the required knowledge. The content was on current status, transmission, signs and symptoms and the role of security personnel in identification and prevention of malaria. Each seminar was preceded by a pre-test and followed by a post test to assess the improvement of knowledge. Fifty seminars were held in eight districts over 2 months with 2301 security forces personnel participating. Pre seminar knowledge on malaria was significantly better in the medical corps, those who had completed secondary education and in the Army compared to other security forces (pmalaria amongst security forces personnel who are a high risk group for re-introduction of malaria into the country. © The Author 2014. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: firstname.lastname@example.org.
Full Text Available Abstract Background Suriname was a high malaria risk country before the introduction of a new five-year malaria control program in 2005, the Medical Mission Malaria Programme (MM-MP. Malaria was endemic in the forested interior, where especially the stabile village communities were affected. Case description The interventions of the MM-MP included new strategies for prevention, vector control, case management, behavioral change communication (BCC/information, education and communication (IEC, and strengthening of the health system (surveillance, monitoring and evaluation and epidemic detection system. After a slow first year with non-satisfying scores for the performance indicators, the MM-MP truly engaged in its intervention activities in 2006 and kept its performance up until the end of 2009. A total of 69,994 long-lasting insecticide-treated nets were distributed and more than 15,000 nets re-impregnated. In high-risk areas, this was complemented with residual spraying of insecticides. Over 10,000 people were screened with active case detection in outbreak and high-risk areas. Additional notification points were established and the national health system was strengthened. Discussion and evaluation In the current paper, the MM-MP is evaluated both on account of the targets established within the programme and on account of its impact on the malaria situation in Suriname. Malaria vector populations, monitored in sentinel sites, collapsed after 2006 and concurrently the number of national malaria cases decreased from 8,618 in 2005 to 1,509 in 2009. Malaria transmission risk shifted from the stabile village communities to the mobile gold mining communities, especially those along the French Guiana border. Conclusions The novel strategies for malaria control introduced in Suriname within the MM-MP have led to a significant decrease in the national malaria burden. The challenge is to further reduce malaria using the available strategies as
Dewasurendra Rajika L
Full Text Available Abstract Background The incidence of malaria in Sri Lanka has significantly declined in recent years. Similar trends were seen in Kataragama, a known malaria endemic location within the southern province of the country, over the past five years. This is a descriptive study of anti-malarial antibody levels and selected host genetic mutations in residents of Kataragama, under low malaria transmission conditions. Methods Sera were collected from 1,011 individuals residing in Kataragama and anti-malarial antibodies and total IgE levels were measured by a standardized ELISA technique. Host DNA was extracted and used for genotyping of selected SNPs in known genes associated with malaria. The antibody levels were analysed in relation to the past history of malaria (during past 10 years, age, sex, the location of residence within Kataragama and selected host genetic markers. Results A significant increase in antibodies against Plasmodium falciparum antigens AMA1, MSP2, NANP and Plasmodium vivax antigen MSP1 in individuals with past history of malaria were observed when compared to those who did not. A marked increase of anti-MSP1(Pf and anti-AMA1(Pv was also evident in individuals between 45–59 years (when compared to other age groups. Allele frequencies for two SNPs in genes that code for IL-13 and TRIM-5 were found to be significantly different between those who have experienced one or more malaria attacks within past 10 years and those who did not. When antibody levels were classified into a low-high binary trait, significant associations were found with four SNPs for anti-AMA1(Pf; two SNPs for anti-MSP1(Pf; eight SNPs for anti-NANP(Pf; three SNPs for anti-AMA1(Pv; seven SNPs for anti-MSP1(Pv; and nine SNPs for total IgE. Eleven of these SNPs with significant associations with anti-malarial antibody levels were found to be non–synonymous. Conclusions Evidence is suggestive of an age–acquired immunity in this study population in spite of
Gryseels, C.; Durnez, L.; Gerrets, R.; Uk, S.; Suon, S.; Set, S.; Phoeuk, P.; Sluydts, V.; Heng, S.; Sochantha, T.; Coosemans, M.; Peeters Grietens, K.
Background: In certain regions in Southeast Asia, where malaria is reduced to forested regions populated by ethnic minorities dependent on slash-and-burn agriculture, malaria vector populations have developed a propensity to feed early and outdoors, limiting the effectiveness of long-lasting
Rosas-Aguirre, Angel; Llanos-Cuentas, Alejandro; Speybroeck, Niko; Cook, Jackie; Contreras-Mancilla, Juan; Soto, Veronica; Gamboa, Dionicia; Pozo, Edwar; Ponce, Oscar J; Pereira, Mayne O; Soares, Irene S; Theisen, Michael; D'Alessandro, Umberto; Erhart, Annette
Where malaria endemicity is low, control programmes need increasingly sensitive tools for monitoring malaria transmission intensity (MTI) and to better define health priorities. A cross-sectional survey was conducted in a low endemicity area of the Peruvian north-western coast to assess the MTI using both molecular and serological tools. Epidemiological, parasitological and serological data were collected from 2,667 individuals in three settlements of Bellavista district, in May 2010. Parasite infection was detected using microscopy and polymerase chain reaction (PCR). Antibodies to Plasmodium vivax merozoite surface protein-119 (PvMSP1₁₉) and to Plasmodium falciparum glutamate-rich protein (PfGLURP) were detected by ELISA. Risk factors for exposure to malaria (seropositivity) were assessed by multivariate survey logistic regression models. Age-specific antibody prevalence of both P. falciparum and P. vivax were analysed using a previously published catalytic conversion model based on maximum likelihood for generating seroconversion rates (SCR). The overall parasite prevalence by microscopy and PCR were extremely low: 0.3 and 0.9%, respectively for P. vivax, and 0 and 0.04%, respectively for P. falciparum, while seroprevalence was much higher, 13.6% for P. vivax and 9.8% for P. falciparum. Settlement, age and occupation as moto-taxi driver during previous year were significantly associated with P. falciparum exposure, while age and distance to the water drain were associated with P. vivax exposure. Likelihood ratio tests supported age seroprevalence curves with two SCR for both P. vivax and P. falciparum indicating significant changes in the MTI over time. The SCR for PfGLURP was 19-fold lower after 2002 as compared to before (λ1 = 0.022 versus λ2 = 0.431), and the SCR for PvMSP1₁₉ was four-fold higher after 2006 as compared to before (λ1 = 0.024 versus λ2 = 0.006). Combining molecular and serological tools considerably enhanced the capacity of
Sanchez, Juan F; Carnero, Andres M; Rivera, Esteban; Rosales, Luis A; Baldeviano, G Christian; Asencios, Jorge L; Edgel, Kimberly A; Vinetz, Joseph M; Lescano, Andres G
The reemergence of malaria in the last decade in Madre de Dios, southern Peruvian Amazon basin, was accompanied by ecological, political, and socioeconomic changes related to the proliferation of illegal gold mining. We conducted a secondary analysis of passive malaria surveillance data reported by the health networks in Madre de Dios between 2001 and 2012. We calculated the number of cases of malaria by year, geographic location, intensity of illegal mining activities, and proximity of health facilities to the Peru-Brazil Interoceanic Highway. During 2001-2012, 203,773 febrile cases were identified in Madre de Dios, of which 30,811 (15.1%) were confirmed cases of malaria; all but 10 cases were due to Plasmodium vivax Cases of malaria rose rapidly between 2004 and 2007, reached 4,469 cases in 2005, and then declined after 2010 to pre-2004 levels. Health facilities located in areas of intense illegal gold mining reported 30-fold more cases than those in non-mining areas (ratio = 31.54, 95% confidence interval [CI] = 19.28, 51.60). Finally, health facilities located > 1 km from the Interoceanic Highway reported significantly more cases than health facilities within this distance (ratio = 16.20, 95% CI = 8.25, 31.80). Transmission of malaria in Madre de Dios is unstable, geographically heterogeneous, and strongly associated with illegal gold mining. These findings highlight the importance of spatially oriented interventions to control malaria in Madre de Dios, as well as the need for research on malaria transmission in illegal gold mining camps. © The American Society of Tropical Medicine and Hygiene.
Makanga, B; Yangari, P.; Rahola, N; Rougeron, V.; Elguero, E; Boundenga, L; Moukodoum, ND; Okouga, AP; Arnathau, C; Durand, P; Willaume, E.; Ayala, D; D. Fontenille; Ayala, FJ; Renaud, F.
Recent studies have highlighted the large diversity of malaria parasites infecting African great apes (subgenus Laverania) and their strong host specificity. Although the existence of genetic incompatibilities preventing the cross-species transfer may explain host specificity, the existence of vectors with a high preference for a determined host represents another possibility. To test this hypothesis, we undertook a 15-mo-long longitudinal entomological survey in two forest regions of Gabon, ...
Full Text Available IV/AIDS is a global problem involving industrialized and developing country including Indonesia. Malaria has killed millions ofhuman beings almost 3 million people each year, whereas since 1999, nearly 36 million people in the world infected with HIV and 3 million more have died (Kakilaya, 2006. HIV infection increases the risk and aggravate malaria. In Africa in the area of malaria transmission intensities high and low, HIVaggravate malaria and improve case fatality at any age (Eline 2006. HIVis an RNA viruses whose hallmark is the reverse transcriptation ofits genomic. Malaria is a protozoan disease transmitted by the bite ofinfected anopheles mosquito. Infection malaria can stimulate HIV replication and may cause faster progression ofHIV disease.
Jacobson, Jerry O; Cueto, Carmen; Smith, Jennifer L; Hwang, Jimee; Gosling, Roly; Bennett, Adam
To eliminate malaria, malaria programmes need to develop new strategies for surveillance and response appropriate for the changing epidemiology that accompanies transmission decline, in which transmission is increasingly driven by population subgroups whose behaviours place them at increased exposure. Conventional tools of malaria surveillance and response are likely not sufficient in many elimination settings for accessing high-risk population subgroups, such as mobile and migrant populations (MMPs), given their greater likelihood of asymptomatic infections, illegal risk behaviours, limited access to public health facilities, and high mobility including extended periods travelling away from home. More adaptive, targeted strategies are needed to monitor transmission and intervention coverage effectively in these groups. Much can be learned from HIV programmes' experience with "second generation surveillance", including how to rapidly adapt surveillance and response strategies to changing transmission patterns, biological and behavioural surveys that utilize targeted sampling methods for specific behavioural subgroups, and methods for population size estimation. This paper reviews the strategies employed effectively for HIV programmes and offers considerations and recommendations for adapting them to the malaria elimination context.
Outchkourov, N.S.; Roeffen, W.; Kaan, A.; Jansen, Josephine; Luty, A.; Schuiffel, D.; Gemert, G.J.A. van; Vegte-Bolmer, M van de; Sauerwein, R.W.; Stunnenberg, H.G.
Malaria kills >1 million people each year, in particular in sub-Saharan Africa. Although asexual forms are directly responsible for disease and death, sexual stages account for the transmission of Plasmodium parasites from human to the mosquito vector and therefore the spread of the parasite in the
Wiseman, Virginia; Hawley, William A.; ter Kuile, Feiko O.; Phillips-Howard, Penelope A.; Vulule, John M.; Nahlen, Bernard L.; Mills, Anne J.
This study compared the costs and effects of insecticide (permethrin)-treated bed net (ITN) use in children less than five years of age in an area of intense, perennial malaria transmission in western Kenya. The data were derived from a group-randomized controlled trial of ITNs conducted between
PETERSON, N.E. 7 PINHEIRO, F.P. - Programa multidisciplinario de vigilancia de las enfermedades infecciosas en zonas colindantes con la carretera...identificada por teste imunoenzimatico. In: CONGRESSO DA SOCIEDADE BRASILEIRA DE MEDICINA TROPICAL. Dynamics of malaria transmission in Rond6nia and
Breeveld, Florence J. V.; Vreden, Stephen G. S.; Grobusch, Martin P.
Suriname has cleared malaria from its capital city and coastal areas mainly through the successful use of chloroquine and DDT (dichloro-diphenyl-trichloroethane) during the Global Malaria Eradication programme that started in 1955. Nonetheless, malaria transmission rates remained high in the
Dynamics of malaria transmission and susceptibility to clinical malaria episodes following treatment of Plasmodium falciparum asymptomatic carriers: results of a cluster-randomized study of community-wide screening and treatment, and a parallel entomology study.
Tiono, Alfred B; Guelbeogo, Moussa W; Sagnon, N Falé; Nébié, Issa; Sirima, Sodiomon B; Mukhopadhyay, Amitava; Hamed, Kamal
In malaria-endemic countries, large proportions of individuals infected with Plasmodium falciparum are asymptomatic and constitute a reservoir of parasites for infection of newly hatched mosquitoes. Two studies were run in parallel in Burkina Faso to evaluate the impact of systematic identification and treatment of asymptomatic carriers of P. falciparum, detected by rapid diagnostic test, on disease transmission and susceptibility to clinical malaria episodes. A clinical study assessed the incidence of symptomatic malaria episodes with a parasite density >5,000/μL after three screening and treatment campaigns ~1 month apart before the rainy season; and an entomological study determined the effect of these campaigns on malaria transmission as measured by entomological inoculation rate. The intervention arm had lower prevalence of asymptomatic carriers of asexual parasites and lower prevalence of gametocyte carriers during campaigns 2 and 3 as compared to the control arm. During the entire follow-up period, out of 13,767 at-risk subjects, 2,516 subjects (intervention arm 1,332; control arm 1,184) had symptomatic malaria. Kaplan-Meier analysis of the incidence of first symptomatic malaria episode with a parasite density >5,000/μL showed that, in the total population, the two treatment arms were similar until Week 11-12 after campaign 3, corresponding with the beginning of the malaria transmission season, after which the probability of being free of symptomatic malaria was lower in the intervention arm (logrank p entomological inoculation rate was comparable in both arms, with September peaks in both indices. Community screening and targeted treatment of asymptomatic carriers of P. falciparum had no effect on the dynamics of malaria transmission, but seemed to be associated with an increase in the treated community's susceptibility to symptomatic malaria episodes after the screening campaigns had finished. These results highlight the importance of further
Hyun M Yang
Full Text Available OBJECTIVE: Describe the overall transmission of malaria through a compartmental model, considering the human host and mosquito vector. METHODS: A mathematical model was developed based on the following parameters: human host immunity, assuming the existence of acquired immunity and immunological memory, which boosts the protective response upon reinfection; mosquito vector, taking into account that the average period of development from egg to adult mosquito and the extrinsic incubation period of parasites (transformation of infected but non-infectious mosquitoes into infectious mosquitoes are dependent on the ambient temperature. RESULTS: The steady state equilibrium values obtained with the model allowed the calculation of the basic reproduction ratio in terms of the model's parameters. CONCLUSIONS: The model allowed the calculation of the basic reproduction ratio, one of the most important epidemiological variables.
Yang Hyun M
Full Text Available OBJECTIVE: Describe the overall transmission of malaria through a compartmental model, considering the human host and mosquito vector. METHODS: A mathematical model was developed based on the following parameters: human host immunity, assuming the existence of acquired immunity and immunological memory, which boosts the protective response upon reinfection; mosquito vector, taking into account that the average period of development from egg to adult mosquito and the extrinsic incubation period of parasites (transformation of infected but non-infectious mosquitoes into infectious mosquitoes are dependent on the ambient temperature. RESULTS: The steady state equilibrium values obtained with the model allowed the calculation of the basic reproduction ratio in terms of the model's parameters. CONCLUSIONS: The model allowed the calculation of the basic reproduction ratio, one of the most important epidemiological variables.
. Malaria is a disease that could reemerge depending on the development of risk factors for transmission. So, although now the number of cases of malaria in Pamotan village Pangandaran district has decreased, but will back to increase due to have a history as high malaria endemic areas. To anticipate, the further analysis of research data has been carried out with the aim to identify the transmission risk factors as well as to estimate the emergence of malaria cases. Results of data analysis ...
Semakula, Henry M; Song, Guobao; Zhang, Shushen; Achuu, Simon P
The increasing protection gaps of insecticide-treated nets and indoor-residual spraying methods against malaria have led to an emergence of residual transmission in sub-Saharan Africa and thus, supplementary strategies to control mosquitoes are urgently required. To assess household environmental resources and practices that increase or reduce malaria risk among children under-five years of age in order to identify those aspects that can be adopted to control residual transmission. Household environmental resources, practices and malaria test results were extracted from Malaria Indicators Survey datasets for Tanzania, Burundi, Malawi and Liberia with 16,747 children from 11,469 households utilised in the analysis. Logistic regressions were performed to quantify the contribution of each factor to malaria occurrence. Cattle rearing reduced malaria risk between 26%-49% while rearing goats increased the risk between 26%-32%. All piped-water systems reduced malaria risk between 30%-87% (Tanzania), 48%-95% (Burundi), 67%-77% (Malawi) and 58%-73 (Liberia). Flush toilets reduced malaria risk between 47%-96%. Protected-wells increased malaria risk between 19%-44%. Interestingly, boreholes increased malaria risk between 19%-75%. Charcoal use reduced malaria risk between 11%-49%. Vector control options for tackling mosquitoes were revealed based on their risk levels. These included cattle rearing, installation of piped-water systems and flush toilets as well as use of smokeless fuels.
Lillian L M Shapiro
Full Text Available Malaria transmission is known to be strongly impacted by temperature. The current understanding of how temperature affects mosquito and parasite life history traits derives from a limited number of empirical studies. These studies, some dating back to the early part of last century, are often poorly controlled, have limited replication, explore a narrow range of temperatures, and use a mixture of parasite and mosquito species. Here, we use a single pairing of the Asian mosquito vector, An. stephensi and the human malaria parasite, P. falciparum to conduct a comprehensive evaluation of the thermal performance curves of a range of mosquito and parasite traits relevant to transmission. We show that biting rate, adult mortality rate, parasite development rate, and vector competence are temperature sensitive. Importantly, we find qualitative and quantitative differences to the assumed temperature-dependent relationships. To explore the overall implications of temperature for transmission, we first use a standard model of relative vectorial capacity. This approach suggests a temperature optimum for transmission of 29°C, with minimum and maximum temperatures of 12°C and 38°C, respectively. However, the robustness of the vectorial capacity approach is challenged by the fact that the empirical data violate several of the model's simplifying assumptions. Accordingly, we present an alternative model of relative force of infection that better captures the observed biology of the vector-parasite interaction. This model suggests a temperature optimum for transmission of 26°C, with a minimum and maximum of 17°C and 35°C, respectively. The differences between the models lead to potentially divergent predictions for the potential impacts of current and future climate change on malaria transmission. The study provides a framework for more detailed, system-specific studies that are essential to develop an improved understanding on the effects of temperature
Baidjoe, A.Y.; Stevenson, J.; Knight, P; Stone, W.J.R.; Stresman, G.; Osoti, V; Makori, E; OWAGA, C.; Odongo, W; China, P; Shagari, S; Kariuki, S; Drakeley, C; Cox, J; Bousema, T.
Background The East African highlands are fringe regions between stable and unstable malaria transmission. What factors contribute to the heterogeneity of malaria exposure on different spatial scales within larger foci has not been extensively studied. In a comprehensive, community-based cross-sectional survey an attempt was made to identify factors that drive the macro- and micro epidemiology of malaria in a fringe region using parasitological and serological outcomes. Methods A large cross-...
Rupashree Singh; Igboanua Ifeanyic Godson; Sanjay Singh; Rajendra Bahadur Singh; Nike Tawakaltu Isyaku; Ukatu Victoria Ebere
Background & objectives: In malaria endemic areas, continuous exposure to Plasmodium parasites leads to asymptomatic carriers that provide a reservoir, contributing to the persistence of malaria transmission. Thus, a study of the degree of prevalence of asymptomatic parasitaemias will help in assessing the level of reservoir of infection. Methods: All the consented participants without any signs and symptoms, suggestive of malaria were interviewed and thick blood smears were made to detect...
Ursing, Johan; Rombo, Lars; Rodrigues, Amabelia
per 2 people and 97% usage. All-cause mortality decreased from post-war peaks in 1999 until 2012 in all age groups and was not negatively affected by malaria resurgence. CONCLUSION: The cause of decreasing malaria incidence (1995-2007) was probably multifactorial and coincident with the use...... curtailed malaria epidemics. All-cause mortality was not negatively affected by malaria resurgence.......INTRODUCTION: As Plasmodium falciparum prevalence decreases in many parts of Sub-Saharan Africa, so does immunity resulting in larger at risk populations and increased risk of malaria resurgence. In Bissau, malaria prevalence decreased from ∼50% to 3% between 1995 and 2003. The epidemiological...
Delrieu, Isabelle; Leboulleux, Didier; Ivinson, Karen; Gessner, Bradford D
Vaccines interrupting Plasmodium falciparum malaria transmission targeting sexual, sporogonic, or mosquito-stage antigens (SSM-VIMT) are currently under development to reduce malaria transmission. An international group of malaria experts was established to evaluate the feasibility and optimal design of a Phase III cluster randomized trial (CRT) that could support regulatory review and approval of an SSM-VIMT. The consensus design is a CRT with a sentinel population randomly selected from defined inner and buffer zones in each cluster, a cluster size sufficient to assess true vaccine efficacy in the inner zone, and inclusion of ongoing assessment of vaccine impact stratified by distance of residence from the cluster edge. Trials should be conducted first in areas of moderate transmission, where SSM-VIMT impact should be greatest. Sample size estimates suggest that such a trial is feasible, and within the range of previously supported trials of malaria interventions, although substantial issues to implementation exist. Copyright © 2015 Elsevier Ltd. All rights reserved.
Niang, Makhtar; Thiam, Laty Gaye; Sane, Rokhaya; Diagne, Nafissatou; Talla, Cheikh; Doucoure, Souleymane; Faye, Joseph; Diop, Fode; Badiane, Abdoulaye; Diouf, Babacar; Camara, Diogop; Diene-Sarr, Fatoumata; Sokhna, Cheikh; Richard, Vincent; Toure-Balde, Aissatou
In the progress towards malaria elimination, the accurate diagnosis of low-density asymptomatic infections is critical. Low-density asymptomatic submicroscopic malaria infections may act as silent reservoirs that maintain low-level residual malaria transmission in the community. Light microscopy, the gold standard in malaria diagnosis lacks the sensitivity to detect low-level parasitaemia. In this study, the presence and prevalence of submicroscopic Plasmodium carriage were investigated to estimate the parasites reservoir among asymptomatic individuals living in low transmission areas in Dielmo and Ndiop, Senegal during the dry season. A total of 2,037 blood samples were collected during cross-sectional surveys prior the malaria transmission season in July 2013 (N = 612), June 2014 (N = 723) and June 2015 (N = 702) from asymptomatic individuals living in Dielmo and Ndiop, Senegal. Samples were used to determine the prevalence of submicroscopic Plasmodium carriage by real time PCR (qPCR) in comparison to microscopy considered as gold standard. The prevalence of submicroscopic Plasmodium carriage was 3.75% (23/612), 12.44% (90/723) and 6.41% (45/702) in 2013, 2014 and 2015, respectively. No Plasmodium carriage was detected by microscopy in 2013 while microscopy-based prevalence of Plasmodium carriage accounted for only 0.27% (2/723) and 0.14% (1/702) in 2014 and 2015, respectively. Plasmodium falciparum accounted for the majority of submicroscopic infections and represented 86.95% (20/23), 81.11% (73/90) and 95.55 (43/45) of infections in 2013, 2014 and 2015 respectively. Low-density submicroscopic asymptomatic Plasmodium carriage is common in the study areas during the dry season indicating that traditional measures are insufficient to assess the scale of parasite reservoir when transmission reaches very low level. Control and elimination strategies may wish to consider using molecular methods to identify parasites carriers to guide Mass screening and Treatment
Depinay, J.M.O.; Mbogo, C.M.; Killeen, G.; Knols, B.G.J.; Beier, J.; Carlson, J.; Dushoff, J.; Billingsley, P.; Mwambi, H.; Githure, J.; Toure, A.M.; McKenzie, F.E.
Background: Malaria is one of the oldest and deadliest infectious diseases in humans. Many mathematical models of malaria have been developed during the past century, and applied to potential interventions. However, malaria remains uncontrolled and is increasing in many areas, as are vector and
Full Text Available Abstract Background Evolutionary theory suggests that the selection pressure on parasites to maximize their transmission determines their optimal host exploitation strategies and thus their virulence. Establishing the adaptive basis to parasite life history traits has important consequences for predicting parasite responses to public health interventions. In this study we examine the extent to which malaria parasites conform to the predicted adaptive trade-off between transmission and virulence, as defined by mortality. The majority of natural infections, however, result in sub-lethal virulent effects (e.g. anaemia and are often composed of many strains. Both sub-lethal effects and pathogen population structure have been theoretically shown to have important consequences for virulence evolution. Thus, we additionally examine the relationship between anaemia and transmission in single and mixed clone infections. Results Whereas there was a trade-off between transmission success and virulence as defined by host mortality, contradictory clone-specific patterns occurred when defining virulence by anaemia. A negative relationship between anaemia and transmission success was found for one of the parasite clones, whereas there was no relationship for the other. Notably the two parasite clones also differed in a transmission phenotype (gametocyte sex ratio that has previously been shown to respond adaptively to a changing blood environment. In addition, as predicted by evolutionary theory, mixed infections resulted in increased anaemia. The increased anaemia was, however, not correlated with any discernable parasite trait (e.g. parasite density or with increased transmission. Conclusions We found some evidence supporting the hypothesis that there is an adaptive basis correlating virulence (as defined by host mortality and transmission success in malaria parasites. This confirms the validity of applying evolutionary virulence theory to biomedical
McKenzie F Ellis
Full Text Available Abstract Background Prior studies have shown that annual entomological inoculation rates (EIRs must be reduced to less than one to substantially reduce the prevalence of malaria infection. In this study, EIR values were used to quantify the impact of insecticide-treated bed nets (ITNs, indoor residual spraying (IRS, and source reduction (SR on malaria transmission. The analysis of EIR was extended through determining whether available vector control tools can ultimately eradicate malaria. Method The analysis is based primarily on a review of all controlled studies that used ITN, IRS, and/or SR and reported their effects on the EIR. To compare EIRs between studies, the percent difference in EIR between the intervention and control groups was calculated. Results Eight vector control intervention studies that measured EIR were found: four ITN studies, one IRS study, one SR study, and two studies with separate ITN and IRS intervention groups. In both the Tanzania study and the Solomon Islands study, one community received ITNs and one received IRS. In the second year of the Tanzania study, EIR was 90% lower in the ITN community and 93% lower in the IRS community, relative to the community without intervention; the ITN and IRS effects were not significantly different. In contrast, in the Solomon Islands study, EIR was 94% lower in the ITN community and 56% lower in the IRS community. The one SR study, in Dar es Salaam, reported a lower EIR reduction (47% than the ITN and IRS studies. All of these vector control interventions reduced EIR, but none reduced it to zero. Conclusion These studies indicate that current vector control methods alone cannot ultimately eradicate malaria because no intervention sustained an annual EIR less than one. While researchers develop new tools, integrated vector management may make the greatest impact on malaria transmission. There are many gaps in the entomological malaria literature and recommendations for future
Tagbor, Harry; Antwi, Gifty Dufie; Acheampong, Princess Ruhama; Bart Plange, Constance; Chandramohan, Daniel; Cairns, Matthew
To investigate the effectiveness of seasonal malaria chemoprevention (SMC) and community case management with long-acting artemisinin-based combination therapies (ACTs) for the control of malaria in areas of extended seasonal malaria transmission. Individually randomised, placebo-controlled trial in the Ashanti Region of Ghana. A total of 2400 children aged 3-59 months received either: (i) a short-acting ACT for case management of malaria (artemether-lumefantrine, AL) plus placebo SMC, or (ii) a long-acting ACT (dihydroartemisinin-piperaquine, DP) for case management plus placebo SMC or (iii) AL for case management plus active SMC with sulphadoxine-pyrimethamine and amodiaquine. SMC or placebo was delivered on five occasions during the rainy season. Malaria cases were managed by community health workers, who used rapid diagnostic tests to confirm infection prior to treatment. The incidence of malaria was lower in children given SMC during the rainy season. Compared to those given placebo SMC and AL for case management, the adjusted hazard ratio (aHR) was 0.62 (95% CI: 0.41, 0.93), P = 0.020 by intention to treat and 0.53 (95% CI: 0.29, 0.95), P = 0.033 among children given five SMC courses. There were no major differences between groups given different ACTs for case management (aHR DP vs. AL 1.18 (95% CI 0.83, 1.67), P = 0.356). SMC may have an important public health impact in areas with a longer transmission season, but further optimisation of SMC schedules is needed to maximise its impact in such settings. © 2015 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.
Bastiaens, G.J.H.; Schaftenaar, E.; Ndaro, A.; Keuter, M.; Bousema, T.; Shekalaghe, S.
BACKGROUND: Patterns of decreasing malaria transmission intensity make presumptive treatment of malaria an unjustifiable approach in many African settings. The controlled use of anti-malarials after laboratory confirmed diagnosis is preferable in low endemic areas. Diagnosis may be facilitated by
Full Text Available Abstract Background With an Annual Parasite Incidence (API of 132.1, in the high and moderate risks zones, the Maroni area of French Guiana has the second highest malaria incidence of South-America after Guyana (API = 183.54 and far above Brazil (API = 28.25. Malaria transmission is occurring despite strong medical assistance and active vector control, based on general WHO recommendations. This situation is generated by two main factors that are the social and cultural characteristics of this border area, where several ethnic groups are living, and the lack of understanding of transmission dynamics of the main mosquito vector, Anopheles darlingi. In this context, entomological data collected in two villages belonging to two different ethnic groups of the French border of the Maroni River, were retrospectively analysed to find out how the mosquito bionomics are related to the malaria transmission patterns. Methods Data were provided by human landing catches of mosquitoes carried out each month for two years in two villages belonging to two ethnic groups, the Amerindians Wayanas and the Aloukous of African origin. The mosquitoes were sorted by species, sex, date, hour and place of collection and processed for Plasmodium sp. parasite detection. The data were compiled to provide the following variables: human biting rates (HBR, parity rates (PR, numbers of infective bites (IB, entomological inoculation rates (EIR and numbers of infected mosquitoes surviving enough to transmit (IMT. Spatial and temporal differences of variables between locations and during the night were tested by the Kruskall-Wallis analysis of variance to find out significant variations. Results The populations of the main mosquito vector An. darlingi showed significant variations in the spatial and temporal HBR/person/night and HBR/person/hour, IB/person/month and IB/person/hour, and IMT/village/night and IMT/village/hour. In the village of Loca (Aloukous, the IMT peaked from June
Full Text Available Transmission of malaria parasites from humans to Anopheles mosquitoes can be inhibited by specific antibodies elicited during malaria infection, which target surface Plasmodium gametocyte/gamete proteins. Some of these proteins may have potential for vaccine development. Pvs48/45 is a P. vivax gametocyte surface antigen orthologous to Pfs48/45, which may play a role during parasite fertilization and thus has potential for transmission blocking (TB activity. Here we describe the expression of a recombinant Pvs48/45 protein expressed in Escherichia coli as a ∼60kDa construct which we tested for antigenicity using human sera and for its immunogenicity and transmission blocking activity of specific anti-mouse and anti-monkey Pvs48/45 antibodies. The protein reacted with sera of individuals from malaria-endemic areas and in addition induced specific IgG antibody responses in BALB/c mice and Aotus l. griseimembra monkeys. Sera from both immunized animal species recognized native P. vivax protein in Western blot (WB and immunofluorescence assays. Moreover, sera from immunized mice and monkeys produced significant inhibition of parasite transmission to An. Albimanus mosquitoes as shown by membrane feeding assays. Results indicate the presence of reactive epitopes in the Pvs48/45 recombinant product that induce antibodies with TB activity. Further testing of this protein is ongoing to determine its vaccine potential.
Maxwell, Caroline A; Chambo, William; Mwaimu, Mathew; Magogo, Frank; Carneiro, Ilona A; Curtis, Christopher F
Background Highland areas with naturally less intense malaria transmission may provide models of how lowland areas might become if transmission was permanently reduced by sustained vector control. It has been argued that vector control should not be attempted in areas of intense transmission. Methods Mosquitoes were sampled with light traps, pyrethrum spray and window exit traps. They were tested by ELISA for sporozoites. Incidence of malaria infection was measured by clearing existing infections from children with chlorproguanil-dapsone and then taking weekly blood samples. Prevalence of malaria infection and fever, anaemia and splenomegaly were measured in children of different age groups. All these measurements were made in highland and lowland areas of Tanzania before and after provision of bednets treated with alphacypermethrin. Results Entomological inoculation rates (EIR) were about 17 times greater in a lowland than a highland area, but incidence of infection only differed by about 2.5 times. Malaria morbidity was significantly less prevalent in the highlands than the lowlands. Treated nets in the highlands and lowlands led to 69–75% reduction in EIR. Malaria morbidity showed significant decline in younger children at both altitudes after introduction of treated nets. In children aged 6–12 the decline was only significant in the highlands Conclusions There was no evidence that the health benefits to young children due to the nets in the lowlands were "paid for" by poorer health later in life. Our data support the idea of universal provision of treated nets, not a focus on areas of natural hypo-endemicity. PMID:14585106
Full Text Available Abstract Background Highland areas with naturally less intense malaria transmission may provide models of how lowland areas might become if transmission was permanently reduced by sustained vector control. It has been argued that vector control should not be attempted in areas of intense transmission. Methods Mosquitoes were sampled with light traps, pyrethrum spray and window exit traps. They were tested by ELISA for sporozoites. Incidence of malaria infection was measured by clearing existing infections from children with chlorproguanil-dapsone and then taking weekly blood samples. Prevalence of malaria infection and fever, anaemia and splenomegaly were measured in children of different age groups. All these measurements were made in highland and lowland areas of Tanzania before and after provision of bednets treated with alphacypermethrin. Results Entomological inoculation rates (EIR were about 17 times greater in a lowland than a highland area, but incidence of infection only differed by about 2.5 times. Malaria morbidity was significantly less prevalent in the highlands than the lowlands. Treated nets in the highlands and lowlands led to 69–75% reduction in EIR. Malaria morbidity showed significant decline in younger children at both altitudes after introduction of treated nets. In children aged 6–12 the decline was only significant in the highlands Conclusions There was no evidence that the health benefits to young children due to the nets in the lowlands were "paid for" by poorer health later in life. Our data support the idea of universal provision of treated nets, not a focus on areas of natural hypo-endemicity.
This podcast is an overview of the Clinician Outreach and Communication Activity (COCA) Call: Malaria Cases in the U.S. Reach 40-Year High: Information and Guidance for Clinicians. The number of malaria cases reported in the United States in 2011 was the largest since 1971, representing a 14 percent increase from 2010 and a 48 percent increase from 2008. A CDC subject matter expert describes malaria prevention strategies aimed at reducing the risk of malaria in travelers, discusses the diagnosis of malaria in patients with suspect malaria, and explains the treatment options for confirmed malaria cases. Created: 2/26/2014 by Center for Global Health (CGH); Malaria Branch; Emergency Risk Communication Branch (ERCB); Office of Public Health Preparedness and Response (OPHPR). Date Released: 2/26/2014.
Ouattara, Amed; Laurens, Matthew B
Despite global efforts to control malaria, the illness remains a significant public health threat. Currently, there is no licensed vaccine against malaria, but an efficacious vaccine would represent an important public health tool for successful malaria elimination. Malaria vaccine development continues to be hindered by a poor understanding of antimalarial immunity, a lack of an immune correlate of protection, and the genetic diversity of malaria parasites. Current vaccine development efforts largely target Plasmodium falciparum parasites in the pre-erythrocytic and erythrocytic stages, with some research on transmission-blocking vaccines against asexual stages and vaccines against pregnancy-associated malaria. The leading pre-erythrocytic vaccine candidate is RTS,S, and early results of ongoing Phase 3 testing show overall efficacy of 46% against clinical malaria. The next steps for malaria vaccine development will focus on the design of a product that is efficacious against the highly diverse strains of malaria and the identification of a correlate of protection against disease. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: email@example.com.
Gryseels, C.; Peeters Grietens, K.; Dierickx, S.; Nguyen Xuan, X.; Uk, S.; Bannister-Tyrrell, M.; Trienekens, S.; Muela Ribera, J.; Hausmann-Muela, S.; Gerrets, R.; D'Alessandro, U.; Sochantha, T.; Coosemans, M.; Erhart, A.
Malaria control along the Vietnam-Cambodia border presents a challenge for both countries' malaria elimination targets as the region is forested, inhabited by ethnic minority populations, and potentially characterized by early and outdoor malaria transmission. A mixed methods study assessed the
Anna L Goodman
Full Text Available The ookinete surface protein Pfs25 is a macrogamete-to-ookinete/ookinete stage antigen of Plasmodium falciparum, capable of exerting high-level anti-malarial transmission-blocking activity following immunization with recombinant protein-in-adjuvant formulations. Here, this antigen was expressed in recombinant chimpanzee adenovirus 63 (ChAd63, human adenovirus serotype 5 (AdHu5 and modified vaccinia virus Ankara (MVA viral vectored vaccines. Two immunizations were administered to mice in a heterologous prime-boost regime. Immunization of mice with AdHu5 Pfs25 at week 0 and MVA Pfs25 at week 10 (Ad-MVA Pfs25 resulted in high anti-Pfs25 IgG titers, consisting of predominantly isotypes IgG1 and IgG2a. A single priming immunization with ChAd63 Pfs25 was as effective as AdHu5 Pfs25 with respect to ELISA titers at 8 weeks post-immunization. Sera from Ad-MVA Pfs25 immunized mice inhibited the transmission of P. falciparum to the mosquito both ex vivo and in vivo. In a standard membrane-feeding assay using NF54 strain P. falciparum, oocyst intensity in Anopheles stephensi mosquitoes was significantly reduced in an IgG concentration-dependent manner when compared to control feeds (96% reduction of intensity, 78% reduction in prevalence at a 1 in 5 dilution of sera. In addition, an in vivo transmission-blocking effect was also demonstrated by direct feeding of immunized mice infected with Pfs25DR3, a chimeric P. berghei line expressing Pfs25 in place of endogenous Pbs25. In this assay the density of Pfs25DR3 oocysts was significantly reduced when mosquitoes were fed on vaccinated as compared to control mice (67% reduction of intensity, 28% reduction in prevalence and specific IgG titer correlated with efficacy. These data confirm the utility of the adenovirus-MVA vaccine platform for the induction of antibodies with transmission-blocking activity, and support the continued development of this alternative approach to transmission-blocking malaria subunit
Wong, Jacklyn; Bayoh, Nabie; Olang, George; Killeen, Gerry; Hamel, Mary J; Vulule, John M.; Gimnig, John E.
Background\\ud Operational vector sampling methods lack standardization, making quantitative comparisons of malaria transmission across different settings difficult. Human landing catch (HLC) is considered the research gold standard for measuring human-mosquito contact, but is unsuitable for large-scale sampling. This study assessed mosquito catch rates of CDC light trap (CDC-LT), Ifakara tent trap (ITT), window exit trap (WET), pot resting trap (PRT), and box resting trap (BRT) relative to HL...
Wanja, Elizabeth; Achilla, Rachel; Obare, Peter; Adeny, Rose; Moseti, Caroline; Otieno, Victor; Morang'a, Collins; Murigi, Ephantus; Nyamuni, John; Monthei, Derek R; Ogutu, Bernhards; Buff, Ann M
One objective of the Kenya National Malaria Strategy 2009-2017 is scaling access to prompt diagnosis and effective treatment. In 2013, a quality assurance (QA) pilot was implemented to improve accuracy of malaria diagnostics at selected health facilities in low-transmission counties of Kenya. Trends in malaria diagnostic and QA indicator performance during the pilot are described. From June to December 2013, 28 QA officers provided on-the-job training and mentoring for malaria microscopy, malaria rapid diagnostic tests and laboratory QA/quality control (QC) practices over four 1-day visits at 83 health facilities. QA officers observed and recorded laboratory conditions and practices and cross-checked blood slides for malaria parasite presence, and a portion of cross-checked slides were confirmed by reference laboratories. Eighty (96%) facilities completed the pilot. Among 315 personnel at pilot initiation, 13% (n = 40) reported malaria diagnostics training within the previous 12 months. Slide positivity ranged from 3 to 7%. Compared to the reference laboratory, microscopy sensitivity ranged from 53 to 96% and positive predictive value from 39 to 53% for facility staff and from 60 to 96% and 52 to 80%, respectively, for QA officers. Compared to reference, specificity ranged from 88 to 98% and negative predictive value from 98 to 99% for health-facility personnel and from 93 to 99% and 99%, respectively, for QA officers. The kappa value ranged from 0.48-0.66 for facility staff and 0.57-0.84 for QA officers compared to reference. The only significant test performance improvement observed for facility staff was for specificity from 88% (95% CI 85-90%) to 98% (95% CI 97-99%). QA/QC practices, including use of positive-control slides, internal and external slide cross-checking and recording of QA/QC activities, all increased significantly across the pilot (p malaria QA/QC practices over the pilot. However, these advances did not translate into improved accuracy of
Pedro, R S; Brasil, P; Pina-Costa, A; Machado, C R; Damasceno, L S; Daniel-Ribeiro, C T; Guaraldo, L
Malaria is a potentially severe disease, widespread in tropical and subtropical areas. Apart from parasite drug resistance, which receives the largest share of attention, several factors directly influence the response to antimalarial treatment such as incorrect doses, adverse drug events, lack of adherence to treatment, drug quality and drug-drug interactions. Pharmacotherapy follow-up can be used to monitor and improve the effectiveness of treatment, prevent drug-related problems and ensure patient safety. The aim of this study was to describe the results of the implementation of pharmacotherapy follow-up of patients with malaria seen at a reference centre for malaria diagnosis and treatment (CPD-Mal) located in the city of Rio de Janeiro, an area without malaria transmission. A descriptive study was conducted from January 2009 to September 2013 at the Instituto Nacional de Infectologia Evandro Chagas (INI) of the Fundação Oswaldo Cruz (Fiocruz). All malaria patients enrolled in the study were treated according to the Brazilian Malaria Therapy Guidelines. Data collected during pharmacotherapy follow-up were recorded in a standardized form. The variables included were age, gender, comorbidities, antimalarials and concomitant medications used, adverse drug reactions (ADR), clinical and parasitological cure times, and treatment outcomes classified as success, recurrence (recrudescence or relapse); and lost to follow-up. The ADR were classified by severity (DAIDS-NIH), organ system affected (WHO-ART) and likelihood to be caused by drugs (Naranjo scale). One hundred thirteen cases of malaria were included. Patients were aged between 13 and 66 years and the majority of them (75.2%) were male. Ninety-four ADR were observed, most classified as mild (85.1%), related to disorders of the gastrointestinal system (63.8%), such as nausea and vomiting, and assessed as "possibly" caused by the antimalarial drugs (91.5%). The majority of clinical (90.9%) and parasitological
Killeen, Gerry F; Govella, Nicodem J; Lwetoijera, Dickson W; Okumu, Fredros O
Anopheles arabiensis is stereotypical of diverse vectors that mediate residual malaria transmission globally, because it can feed outdoors upon humans or cattle, or enter but then rapidly exit houses without fatal exposure to insecticidal nets or sprays. Life histories of a well-characterized An. arabiensis population were simulated with a simple but process-explicit deterministic model and relevance to other vectors examined through sensitivity analysis. Where most humans use bed nets, two thirds of An. arabiensis blood feeds and half of malaria transmission events were estimated to occur outdoors. However, it was also estimated that most successful feeds and almost all (>98 %) transmission events are preceded by unsuccessful attempts to attack humans indoors. The estimated proportion of vector blood meals ultimately obtained from humans indoors is dramatically attenuated by availability of alternative hosts, or partial ability to attack humans outdoors. However, the estimated proportion of mosquitoes old enough to transmit malaria, and which have previously entered a house at least once, is far less sensitive to both variables. For vectors with similarly modest preference for cattle over humans and similar ability to evade fatal indoor insecticide exposure once indoors, >80 % of predicted feeding events by mosquitoes old enough to transmit malaria are preceded by at least one house entry event, so long as ≥40 % of attempts to attack humans occur indoors and humans outnumber cattle ≥4-fold. While the exact numerical results predicted by such a simple deterministic model should be considered only approximate and illustrative, the derived conclusions are remarkably insensitive to substantive deviations from the input parameter values measured for this particular An. arabiensis population. This life-history analysis, therefore, identifies a clear, broadly-important opportunity for more effective suppression of residual malaria transmission by An. arabiensis
Flahault Antoine; McKenzie F Ellis; Menach Arnaud; Smith David L
Abstract Background Mosquitoes commute between blood-meal hosts and water. Thus, heterogeneity in human biting reflects underlying spatial heterogeneity in the distribution and suitability of larval habitat as well as inherent differences in the attractiveness, suitability and distribution of blood-meal hosts. One of the possible strategies of malaria control is to identify local vector species and then attack water bodies that contain their larvae. Methods Biting and host seeking, not ovipos...
Goggins William B
Full Text Available Abstract Background Malaria is a major public health burden in the tropics with the potential to significantly increase in response to climate change. Analyses of data from the recent past can elucidate how short-term variations in weather factors affect malaria transmission. This study explored the impact of climate variability on the transmission of malaria in the tropical rain forest area of Mengla County, south-west China. Methods Ecological time-series analysis was performed on data collected between 1971 and 1999. Auto-regressive integrated moving average (ARIMA models were used to evaluate the relationship between weather factors and malaria incidence. Results At the time scale of months, the predictors for malaria incidence included: minimum temperature, maximum temperature, and fog day frequency. The effect of minimum temperature on malaria incidence was greater in the cool months than in the hot months. The fog day frequency in October had a positive effect on malaria incidence in May of the following year. At the time scale of years, the annual fog day frequency was the only weather predictor of the annual incidence of malaria. Conclusion Fog day frequency was for the first time found to be a predictor of malaria incidence in a rain forest area. The one-year delayed effect of fog on malaria transmission may involve providing water input and maintaining aquatic breeding sites for mosquitoes in vulnerable times when there is little rainfall in the 6-month dry seasons. These findings should be considered in the prediction of future patterns of malaria for similar tropical rain forest areas worldwide.
81. INTRODUCTION. Malaria transmission occurs in all six WHO regions. Globally, an estimated 3.3 billion people are at risk of being infected with malaria and developing disease, and 1.2 billion are at high risk1. According to the latest estimates, 214 million new cases of malaria occurred globally in 2015, leading to 438.
Yusof, Ruhani; Lau, Yee Ling; Mahmud, Rohela; Fong, Mun Yik; Jelip, Jenarun; Ngian, Hie Ung; Mustakim, Sahlawati; Hussin, Hani Mat; Marzuki, Noradilah; Mohd Ali, Marlindawati
Plasmodium knowlesi is a simian parasite that has been recognized as the fifth species causing human malaria. Naturally-acquired P. knowlesi infection is widespread among human populations in Southeast Asia. The aim of this epidemiological study was to determine the incidence and distribution of malaria parasites, with a particular focus on human P. knowlesi infection in Malaysia. A total of 457 microscopically confirmed, malaria-positive blood samples were collected from 22 state and main district hospitals in Malaysia between September 2012 and December 2013. Nested PCR assay targeting the 18S rRNA gene was used to determine the infecting Plasmodium species. A total of 453 samples were positive for Plasmodium species by using nested PCR assay. Plasmodium knowlesi was identified in 256 (56.5%) samples, followed by 133 (29.4%) cases of Plasmodium vivax, 49 (10.8%) cases of Plasmodium falciparum, two (0.4%) cases of Plasmodium ovale and one (0.2%) case of Plasmodium malariae. Twelve mixed infections were detected, including P. knowlesi/P. vivax (n = 10), P. knowlesi/P. falciparum (n = 1), and P. falciparum/P. vivax (n = 1). Notably, P. knowlesi (Included mixed infections involving P. knowlesi (P. knowlesi/P. vivax and P. knowlesi /P. falciparum)) showed the highest proportion in Sabah (84/115 cases, prevalence of 73.0%), Sarawak (83/120, 69.2%), Kelantan (42/56, 75.0%), Pahang (24/25, 96.0%), Johor (7/9, 77.8%), and Terengganu (4/5, 80.0%,). In contrast, the rates of P. knowlesi infection in Selangor and Negeri Sembilan were found to be 16.2% (18/111 cases) and 50.0% (5/10 cases), respectively. Sample of P. knowlesi was not obtained from Kuala Lumpur, Melaka, Perak, Pulau Pinang, and Perlis during the study period, while a microscopically-positive sample from Kedah was negative by PCR. In addition to Sabah and Sarawak, which have been known for high prevalence of P. knowlesi infection, the findings from this study highlight the widespread distribution of P
Liu, Xue; Culleton, Richard; Tao, Li; Xia, Hui; Gao, Qi
Abstract Background Congenital malaria, in which infants are directly infected with malaria parasites from their mother prior to or during birth, is a potentially life-threatening condition that occurs at relatively low rates in malaria-endemic regions. It is recognized as a serious problem in Plasmodium falciparum–endemic sub-Saharan Africa, where recent data suggests that it is more common than previously believed. In such regions where malaria transmission is high, neonates may be protected from disease caused by congenital malaria through the transfer of maternal antibodies against the parasite. However, in low P. vivax–endemic regions, immunity to vivax malaria is low; thus, there is the likelihood that congenital vivax malaria poses a more significant threat to newborn health. Malaria had previously been a major parasitic disease in China, and congenital malaria case reports in Chinese offer valuable information for understanding the risks posed by congenital malaria to neonatal health. As most of the literature documenting congenital malaria cases in China are written in Chinese and therefore are not easily accessible to the global malaria research community, we have undertaken an extensive review of the Chinese literature on this subject. Methods/Principal Findings Here, we reviewed congenital malaria cases from three major searchable Chinese journal databases, concentrating on data from 1915 through 2011. Following extensive screening, a total of 104 cases of congenital malaria were identified. These cases were distributed mainly in the eastern, central, and southern regions of China, as well as in the low-lying region of southwest China. The dominant species was P. vivax (92.50%), reflecting the malaria parasite species distribution in China. The leading clinical presentation was fever, and other clinical presentations were anaemia, jaundice, paleness, diarrhoea, vomiting, and general weakness. With the exception of two cases, all patients were cured
Tompkins, Adrian M; Ermert, Volker
Background The relative roles of climate variability and population related effects in malaria transmission could be better understood if regional-scale dynamical malaria models could account for these factors. Methods A new dynamical community malaria model is introduced that accounts for the temperature and rainfall influences on the parasite and vector life cycles which are finely resolved in order to correctly represent the delay between the rains and the malaria season. The rainfall driv...
Aline Correa de Carvalho
Full Text Available Purpose: To investigate changes in multifocal electroretinography (mfERG parameters associated with high dose chloroquine therapy for treatment of malaria in the Amazonia region of Brazil. Methods: Forty-eight subjects who had received chloroquine treatment for single or multiple malaria infections with a cumulative dose ranging from 1,050 to 27,000mg were included. The control group consisted of 37 healthy aged-matched subjects. Data was collected on amplitude and implicit time of the N1, P1 and N2 waves in the central macular hexagon (R1 and in five concentric rings at different retinal eccentricities (R2-R6. Results: No significant difference was observed in any mfERG parameter between chloroquine treated patients and control subjects. A comparison with previous data obtained from patients with rheumatologic disorders in the same region of Brazil who had received larger cumulative doses of chloroquine and had displayed mfERG changes, indicated that retinal toxicity seems to be dependent on cumulative dose. Conclusion: Lack of mfERG changes in the current study suggests that intensive high dose chloroquine therapy for treatment of malaria is not associated with retinal toxicity.
Full Text Available Abstract Background The elimination of malaria in Zanzibar is highly dependent on sustained effective coverage of bed-nets to avoid malaria resurgence. The Health Belief Model (HBM framework was used to explore the perceptions of malaria and bed-net use after a noticeable reduction in malaria incidence. Methods Nineteen in-depth interviews were conducted with female and male caretakers of children under five in North A district, Zanzibar. Deductive content analysis was used to identify meaning units that were condensed, coded and assigned to pre-determined elements of the HBM. Results Awareness of malaria among caretakers was high but the illness was now seen as easily curable and uncommon. In addition to the perceived advantage of providing protection against malaria, bed-nets were also thought to be useful for avoiding mosquito nuisance, especially during the rainy season when the malaria and mosquito burden is high. The discomfort of sleeping under a net during the hot season was the main barrier that interrupted consistent bed-net usage. The main cue to using a bed-net was high mosquito density, and children were prioritized when it came to bed-net usage. Caretakers had high perceived self-efficacy and did not find it difficult to use bed-nets. Indoor Residual Spraying (IRS, which was recognized as an additional means of mosquito prevention, was not identified as an alternative for bed-nets. A barrier to net ownership was the increasingly high cost of bed-nets. Conclusions Despite the reduction in malaria incidence and the resulting low malaria risk perceptions among caretakers, the benefit of bed-nets as the most proficient protection against mosquito bites upholds their use. This, in combination with the perceived high self-efficacy of caretakers, supports bed-net usage, while seasonality interrupts consistent use. High effective coverage of bed-nets could be further improved by reinforcing the benefits of bed-nets, addressing the seasonal
Background Current malaria vector control programmes rely on insecticides with rapid contact toxicity. However, spatial repellents can also be applied to reduce man-vector contact, which might ultimately impact malaria transmission. The aim of this study was to quantify effects of airborne pyrethroids from coils and DDT used an indoor residual spray (IRS) on entomological parameters that influence malaria transmission. Methods The effect of Transfluthrin and Metofluthrin coils compared to DDT on house entry, exit and indoor feeding behaviour of Anopheles gambiae sensu lato were measured in experimental huts in the field and in the semi-field. Outcomes were deterrence - reduction in house entry of mosquitoes; irritancy or excito-repellency – induced premature exit of mosquitoes; blood feeding inhibition and effect on mosquito fecundity. Results Transfluthrin coils, Metofluthrin coils and DDT reduced human vector contact through deterrence by 38%, 30% and 8%, respectively and induced half of the mosquitoes to leave huts before feeding (56%, 55% and 48%, respectively). Almost all mosquitoes inside huts with Metofluthrin and Transfluthrin coils and more than three quarters of mosquitoes in the DDT hut did not feed, almost none laid eggs and 67%, 72% and 70% of all mosquitoes collected from Transfluthrin, Metofluthrin and DDT huts, respectively had died after 24 hours. Conclusion This study highlights that airborne pyrethroids and DDT affect a range of anopheline mosquito behaviours that are important parameters in malaria transmission, namely deterrence, irritancy/excito-repellency and blood-feeding inhibition. These effects are in addition to significant toxicity and reduced mosquito fecundity that affect mosquito densities and, therefore, provide community protection against diseases for both users and non-users. Airborne insecticides and freshly applied DDT had similar effects on deterrence, irritancy and feeding inhibition. Therefore, it is suggested that
Gryseels, Charlotte; Peeters Grietens, Koen; Dierickx, Susan; Xuan, Xa Nguyen; Uk, Sambunny; Bannister-Tyrrell, Melanie; Trienekens, Suzan; Ribera, Joan Muela; Hausmann-Muela, Susanna; Gerrets, René; D'Alessandro, Umberto; Sochantha, Tho; Coosemans, Marc; Erhart, Annette
Malaria control along the Vietnam–Cambodia border presents a challenge for both countries' malaria elimination targets as the region is forested, inhabited by ethnic minority populations, and potentially characterized by early and outdoor malaria transmission. A mixed methods study assessed the vulnerability to malaria among the Jarai population living on both sides of the border in the provinces of Ratanakiri (Cambodia) and Gia Lai (Vietnam). A qualitative study generated preliminary hypotheses that were quantified in two surveys, one targeting youth (N = 498) and the other household leaders (N = 449). Jarai male youth, especially in Cambodia, had lower uptake of preventive measures (57.4%) and more often stayed overnight in the deep forest (35.8%) compared with the female youth and the adult population. Among male youth, a high-risk subgroup was identified that regularly slept at friends' homes or outdoors, who had fewer bed nets (32.5%) that were torn more often (77.8%). The vulnerability of Jarai youth to malaria could be attributed to the transitional character of youth itself, implying less fixed sleeping arrangements in nonpermanent spaces or non-bed sites. Additional tools such as long-lasting hammock nets could be suitable as they are in line with current practices. PMID:26283747
Suswardany, Dwi Linna; Sibbritt, David W; Supardi, Sudibyo; Pardosi, Jerico F; Chang, Sungwon; Adams, Jon
The level of traditional medicine use, particularly Jamu use, in Indonesia is substantial. Indonesians do not always seek timely treatment for malaria and may seek self-medication via traditional medicine. This paper reports findings from the first focused analyses of traditional medicine use for malaria in Indonesia and the first such analyses worldwide to draw upon a large sample of respondents across high-risk malaria endemic areas. A sub-study of the Indonesia Basic Health Research/Riskesdas Study 2010 focused on 12,226 adults aged 15 years and above residing in high-risk malaria-endemic provinces. Logistic regression was undertaken to determine the significant associations for traditional medicine use for malaria symptoms. Approximately one in five respondents use traditional medicine for malaria symptoms and the vast majority experiencing multiple episodes of malaria use traditional medicine alongside free antimalarial drug treatments. Respondents consuming traditional medicine for general health/common illness purposes every day (odds ratio: 3.75, 95% Confidence Interval: 2.93 4.79), those without a hospital in local vicinity (odds ratio: 1.31, 95% Confidence Interval: 1.10 1.57), and those living in poorer quality housing, were more likely to use traditional medicine for malaria symptoms. A substantial percentage of those with malaria symptoms utilize traditional medicine for treating their malaria symptoms. In order to promote safe and effective malaria treatment, all providing malaria care in Indonesia need to enquire with their patients about possible traditional medicine use.
Theisen, M.; Jore, M.M.; Sauerwein, R.
INTRODUCTION: Malaria is a devastating vector-borne disease caused by the Plasmodium parasite, resulting in almost 0.5 million casualties per year. The parasite has a complex life-cycle that includes asexual replication in human red blood cells, causing symptomatic malaria, and sexual stages which
Full Text Available Abstract Background Early recognition of symptoms and signs perceived as malaria are important for effective case management, as few laboratories are available at peripheral health facilities. The validity and reliability of clinical signs and symptoms used by health workers to diagnose malaria were assessed in an area of low transmission in south-western Uganda. Methods The study had two components: 1 passive case detection where all patients attending the out patient clininc with a febrile illness were included and 2 a longitudinal active malaria case detection survey was conducted in selected villages. A malaria case was defined as any slide-confirmed parasitaemia in a person with an axillary temperature ≥ 37.5°C or a history of fever within the last 24 hrs and no signs suggestive of other diseases. Results Cases of malaria were significantly more likely to report joint pains, headache, vomiting and abdominal pains. However, due to the low prevalence of malaria, the predictive values of these individual signs alone, or in combination, were poor. Only 24.8% of 1627 patients had malaria according to case definition and > 75% of patients were unnecessarily treated for malaria and few slide negative cases received alternative treatment. Conclusion In low-transmission areas, more attention needs to be paid to differential diagnosis of febrile illnesses In view of suggested changes in anti-malarial drug policy, introducing costly artemisinin combination therapy accurate, rapid diagnostic tools are necessary to target treatment to people in need.
Hiwat, H.; Hardjopawiro, L.S.; Takken, W.; Villegas, L.
Background Suriname was a high malaria risk country before the introduction of a new five-year malaria control program in 2005, the Medical Mission Malaria Programme (MM-MP). Malaria was endemic in the forested interior, where especially the stabile village communities were affected. Case
Marques, Sara R; Ramakrishnan, Chandra; Carzaniga, Raffaella; Blagborough, Andrew M; Delves, Michael J; Talman, Arthur M; Sinden, Robert E
Gametocytes are the sole Plasmodium parasite stages that infect mosquitoes; therefore development of functional gametes is required for malaria transmission. Flagellum assembly of the Plasmodium male gamete differs from that of most other eukaryotes in that it is intracytoplasmic but retains a key conserved feature: axonemes assemble from basal bodies. The centriole/basal body protein SAS-6 normally regulates assembly and duplication of these organelles and its depletion causes severe flagellar/ciliary abnormalities in a diverse array of eukaryotes. Since basal body and flagellum assembly are intimately coupled to male gamete development in Plasmodium, we hypothesized that SAS-6 disruption may cause gametogenesis defects and perturb transmission. We show that Plasmodium berghei sas6 knockouts display severely abnormal male gametogenesis presenting reduced basal body numbers, axonemal assembly defects and abnormal nuclear allocation. The defects in gametogenesis reduce fertilization and render Pbsas6 knockouts less infectious to mosquitoes. Additionally, we show that lack of Pbsas6 blocks transmission from mosquito to vertebrate host, revealing an additional yet undefined role in ookinete to sporulating oocysts transition. These findings underscore the vulnerability of the basal body/SAS-6 to malaria transmission blocking interventions. © 2014 The Authors. Cellular Microbiology published by John Wiley & Sons Ltd.
R Mark Jones
Full Text Available Malaria transmission blocking vaccines (TBVs are considered an effective means to control and eventually eliminate malaria. The Pfs25 protein, expressed predominantly on the surface of the sexual and sporogonic stages of Plasmodium falciparum including gametes, zygotes and ookinetes, is one of the primary targets for TBV. It has been demonstrated that plants are an effective, highly scalable system for the production of recombinant proteins, including virus-like particles (VLPs. We engineered VLPs (Pfs25-CP VLP comprising Pfs25 fused to the Alfalfa mosaic virus coat protein (CP and produced these non-enveloped hybrid VLPs in Nicotiana benthamiana plants using a Tobacco mosaic virus-based 'launch' vector. Purified Pfs25-CP VLPs were highly consistent in size (19.3±2.4 nm in diameter with an estimated 20-30% incorporation of Pfs25 onto the VLP surface. Immunization of mice with one or two doses of Pfs25-CP VLPs plus Alhydrogel® induced serum antibodies with complete transmission blocking activity through the 6 month study period. These results support the evaluation of Pfs25-CP VLP as a potential TBV candidate and the feasibility of the 'launch' vector technology for the production of VLP-based recombinant vaccines against infectious diseases.
Significance of circumsporozoite-specific antibody in the natural transmission of Plasmodium falciparum, Plasmodium vivax, and Plasmodium malariae in an aboriginal (Orang Asli) population of central peninsula Malaysia.
Gordon, D M; Davis, D R; Lee, M; Lambros, C; Harrison, B A; Samuel, R; Campbell, G H; Jegathesan, M; Selvarajan, K; Lewis, G E
Two hundred and seventy-five Orang Asli volunteers living in nine villages in the Pos Legap Valley of Perak State, peninsular Malaysia, participated in a prospective study designed to characterize the epidemiological, parasitological, and entomological characteristics of Plasmodium falciparum, P. vivax, and P. malariae malaria transmission. Prevalence rates for the three plasmodial species at initiation of the study ranged from 56% in the 0-4-year-old age group to 0% in individuals over the age of 40. Entomological surveys were conducted, enabling us to determine mosquito salivary gland-positive rates and entomological inoculation rates of 1.2 infectious mosquito bites per person per month for P. falciparum, 2.4 for P. vivax, and 0.3 for P. malariae. Cumulative incidence rates over the 16 weeks of the study, following radical cure of all volunteers, were 22.5% for P. falciparum, 12.7% for P. vivax, and 1.5% for P. malariae. The median baseline antibody titer against the immunodominant repetitive B cell epitope of P. falciparum or P. vivax circumsporozoite protein was significantly higher for volunteers who did not become parasitemic. Volunteers were selected for further study if they had evidence of being challenged with P. falciparum sporozoites during the study, based on a two-fold or greater increase in antibody titer against the immunodominant repetitive B cell epitope of the circumsporozoite protein. Resistance to infection was seen in six of 10 individuals who had high (greater than 25 OD units) baseline ELISA titers, compared with only three of 24 individuals who had low baseline ELISA titers (chi 2 P less than 0.02). A similar analysis for P. vivax did not show a significant correlation.
Full Text Available Identifying and assessing the relative effects of the numerous determinants of malaria transmission, at different spatial scales and resolutions, is of primary importance in defining control strategies and reaching the goal of the elimination of malaria. In this context, based on a knowledge-based model, a normalized landscape-based hazard index (NLHI was established at a local scale, using a 10 m spatial resolution forest vs. non-forest map, landscape metrics and a spatial moving window. Such an index evaluates the contribution of landscape to the probability of human-malaria vector encounters, and thus to malaria transmission risk. Since the knowledge-based model is tailored to the entire Amazon region, such an index might be generalized at large scales for establishing a regional view of the landscape contribution to malaria transmission. Thus, this study uses an open large-scale land use and land cover dataset (i.e., the 30 m TerraClass maps and proposes an automatic data-processing chain for implementing NLHI at large-scale. First, the impact of coarser spatial resolution (i.e., 30 m on NLHI values was studied. Second, the data-processing chain was established using R language for customizing the spatial moving window and computing the landscape metrics and NLHI at large scale. This paper presents the results in the State of Amapá, Brazil. It offers the possibility of monitoring a significant determinant of malaria transmission at regional scale.
Garcia-Longoria, Luz; Hellgren, Olof; Bensch, Staffan; de Lope, Florentino; Marzal, Alfonso
The identification of the regions where vector-borne diseases are transmitted is essential to study transmission patterns and to recognize future changes in environmental conditions that may potentially influence the transmission areas. SGS1, one of the lineages of Plasmodium relictum, is known to have active transmission in tropical Africa and temperate regions of Europe. Nuclear sequence data from isolates infected with SGS1 (based on merozoite surface protein 1 (MSP1) allelic diversity) have provided new insights on the distribution and transmission areas of these allelic variants. For example, MSP1 alleles transmitted in Africa differ from those transmitted in Europe, suggesting the existence of two populations of SGS1 lineages. However, no study has analysed the distribution of African and European transmitted alleles in Afro-Palearctic migratory birds. With this aim, we used a highly variable molecular marker to investigate whether juvenile house martins become infected in Europe before their first migration to Africa. We explored the MSP1 allelic diversity of P. relictum in adult and juvenile house martins. We found that juveniles were infected with SGS1 during their first weeks of life, confirming active transmission of SGS1 to house martins in Europe. Moreover, we found that all the juveniles and most of adults were infected with one European transmitted MSP1 allele, whereas two adult birds were infected with two African transmitted MSP1 alleles. These findings suggest that house martins are exposed to different strains of P. relictum in their winter and breeding quarters.
A large proportion of asymptomatic Plasmodium infections with low and sub-microscopic parasite densities in the low transmission setting of Temotu Province, Solomon Islands: challenges for malaria diagnostics in an elimination setting
PCR positive P. falciparum, but failed to detect 12/13 microscopy and PCR positive P. vivax infections. Conclusion Asymptomatic malaria infections and infections with low and sub-microscopic parasite densities are highly prevalent in Temotu province where malaria transmission is low. This presents a challenge for elimination since the large proportion of the parasite reservoir will not be detected by standard active and passive case detection. Therefore effective mass screening and treatment campaigns will most likely need more sensitive assays such as a field deployable molecular based assay.
Bi, Yan; Yu, Weiwei; Hu, Wenbiao; Lin, Hualiang; Guo, Yuming; Zhou, Xiao-Nong; Tong, Shilu
Background Malaria remains a public health problem in the remote and poor area of Yunnan Province, China. Yunnan faces an increasing risk of imported malaria infections from Mekong river neighboring countries. This study aimed to identify the high risk area of malaria transmission in Yunnan Province, and to estimate the effects of climatic variability on the transmission of Plasmodium vivax and Plasmodium falciparum in the identified area. Methods We identified spatial clusters of malaria cas...
An Economic Evaluation of the Posttreatment Prophylactic Effect of Dihydroartemisinin-Piperaquine Versus Artemether-Lumefantrine for First-Line Treatment of Plasmodium falciparum Malaria Across Different Transmission Settings in Africa.
Pfeil, Johannes; Borrmann, Steffen; Bassat, Quique; Mulenga, Modest; Talisuna, Ambrose; Tozan, Yesim
Malaria disproportionately affects young children. Clinical trials in African children showed that dihydroartemisinin-piperaquine (DP) is an effective antimalarial and has a longer posttreatment prophylactic (PTP) effect against reinfections than other artemisinin-based combination therapies, including artemether-lumefantrine (AL). Using a previously developed Markov model and individual patient data from a multicenter African drug efficacy trial, we assessed the economic value of the PTP effect of DP versus AL in pediatric malaria patients from health-care provider's perspective in low-to-moderate and moderate-to-high transmission settings under different drug co-payment scenarios. In low-to-moderate transmission settings, first-line treatment with DP was highly cost-effective with an incremental cost-effectiveness ratio of US$5 (95% confidence interval [CI] = -76 to 196) per disability-adjusted life year (DALY) averted. In moderate-to-high transmission settings, DP first-line treatment led to a mean cost saving of US$1.09 (95% CI = -0.88 to 3.85) and averted 0.05 (95% CI = -0.08 to 0.22) DALYs per child per year. Our results suggested that DP might be superior to AL for first-line treatment of uncomplicated childhood malaria across a range of transmission settings in Africa. © The American Society of Tropical Medicine and Hygiene.
Alareqi, Lina M Q; Mahdy, Mohammed A K; Lau, Yee-Ling; Fong, Mun-Yik; Abdul-Ghani, Rashad; Ali, Arwa A; Cheong, Fei-Wen; Tawfek, Rehab; Mahmud, Rohela
Malaria is a public health threat in Yemen, with 149,451 cases being reported in 2013. Of these, Plasmodium falciparum represents 99%. Prompt diagnosis by light microscopy (LM) and rapid diagnostic tests (RTDs) is a key element in the national strategy of malaria control. The heterogeneous epidemiology of malaria in the country necessitates the field evaluation of the current diagnostic strategies, especially RDTs. Thus, the present study aimed to evaluate LM and an RDT, combining both P. falciparum histidine-rich protein-2 (PfHRP-2) and Plasmodium lactate dehydrogenase (pLDH), for falciparum malaria diagnosis and survey in a malaria-endemic area during the transmission season against nested polymerase chain reaction (PCR) as the reference method. A household-based, cross-sectional malaria survey was conducted in Mawza District, a malaria-endemic area in Taiz governorate. A total of 488 participants were screened using LM and PfHRP-2/pLDH RDT. Positive samples (160) and randomly selected negative samples (52) by both RDT and LM were further analysed using 18S rRNA-based nested PCR. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the RDT were 96.0% (95% confidence interval (CI): 90.9-98.3), 56.0% (95% CI: 44.7-66.8), 76.3% (95% CI: 69.0-82.3), and 90.4% (95% CI: 78.8-96.8), respectively. On the other hand, LM showed sensitivity of 37.6% (95% CI: 29.6-46.3), specificity of 97.6% (95% CI: 91.7-99.7), PPV of 95.9% (95% CI: 86.3-98.9), and NPV of 51.3% (95% CI: 43.2-59.2). The sensitivity of LM dropped to 8.5% for detecting asymptomatic malaria. Malaria prevalence was 32.8% (32.1 and 37.5% for ≥10 and <10 years, respectively) with the RDT compared with 10.7% (10.8 and 9.4% for age groups of ≥10 and <10 years, respectively) with LM. Among asymptomatic malaria individuals, LM and RDT-based prevalence rates were 1.6 and 25.6%, respectively. However, rates of 88.2 and 94.1% of infection with P. falciparum were found
Kouassi, Bernard L; de Souza, Dziedzom K; Goepogui, Andre; Balde, Siradiou M; Diakité, Lamia; Sagno, Arsène; Djameh, Georgina I; Chammartin, Frédérique; Vounatsou, Penelope; Bockarie, Moses J; Utzinger, Jürg; Koudou, Benjamin G
.... in the city of Conakry, Guinea, and discusses the prospect for malaria elimination. Water bodies were prospected to identify potential mosquito breeding sites for 6 days each in the dry season (January 2013...
Yeung Lo Tutterrow
Full Text Available VAR2CSA mediates sequestration of Plasmodium falciparum-infected erythrocytes in the placenta, increasing the risk of poor pregnancy outcomes. Naturally acquired antibodies (Ab to placental parasites at delivery have been associated with improved pregnancy outcomes, but Ab levels and how early in pregnancy Ab must be present in order to eliminate placental parasites before delivery remains unknown. Antibodies to individual Duffy-binding like domains of VAR2CSA have been studied, but the domains lack many of the conformational epitopes present in full-length VAR2CSA (FV2. Thus, the purpose of this study was to describe the acquisition of Ab to FV2 in women residing in high and low transmission areas and determine how Ab levels during pregnancy correlate with clearance of placental parasites. Plasma samples collected monthly throughout pregnancy from pregnant women living in high and low transmission areas in Cameroon were evaluated for Ab to FV2 and the proportion of high avidity Ab (i.e., Ab that remain bound in the presence of 3M NH(4SCN was assessed. Ab levels and proportion of high avidity Ab were compared between women with placental malaria (PM(+ and those without (PM(- at delivery. Results showed that PM(- women had significantly higher Ab levels (p = 0.0047 and proportion of high avidity Ab (p = 0.0009 than PM(+ women throughout pregnancy. Specifically, women with moderate to high Ab levels (>5,000 MFI and those with ≥ 35% high avidity Ab at 5-6 months were found to have 2.3 (95% CI, 1.0-4.9 and 7.6-fold (p = 0.0013, 95% CI: 1.2-50.0 reduced risk of placental malaria, respectively. These data show that high levels of Ab to FV2, particularly those with high avidity for FV2, produced by mid-pregnancy are important in clearing parasites from the placenta. Both high Ab levels and proportion of high avidity Ab to FV2 may serve as correlates of protection for assessing immunity against placental malaria.
Full Text Available Using parasite genotyping tools, we screened patients with mild uncomplicated malaria seeking treatment at a clinic in Thiès, Senegal, from 2006 to 2011. We identified a growing frequency of infections caused by genetically identical parasite strains, coincident with increased deployment of malaria control interventions and decreased malaria deaths. Parasite genotypes in some cases persisted clonally across dry seasons. The increase in frequency of genetically identical parasite strains corresponded with decrease in the probability of multiple infections. Further, these observations support evidence of both clonal and epidemic population structures. These data provide the first evidence of a temporal correlation between the appearance of identical parasite types and increased malaria control efforts in Africa, which here included distribution of insecticide treated nets (ITNs, use of rapid diagnostic tests (RDTs for malaria detection, and deployment of artemisinin combination therapy (ACT. Our results imply that genetic surveillance can be used to evaluate the effectiveness of disease control strategies and assist a rational global malaria eradication campaign.
van Gool, Tom; van Wolfswinkel, Marlies E; Koelewijn, Rob; van Thiel, Pieter P A M; Jacobs, Jan; van Hellemond, Jaap J; van Genderen, Perry J J
Counts of malaria parasites in peripheral blood are important to assess severity of Plasmodium falciparum malaria. Thin and thick smears are routinely used for this purpose. In this study the Binax NOW Malaria Test, an easy-to-perform rapid diagnostic test, with Histidine Rich Protein-2 (HRP-2) and aldolase as diagnostic markers, was used for semi-quantitative assessment of parasitaemia of P. falciparum. In 257 patients with imported P. falciparum malaria, reactivity of aldolase increased with higher parasitaemia. In all patients with a parasitaemia above 50,000 asexual parasites/μl (> 1%) co-reactivity of HRP-2 and aldolase was observed. Absence of aldolase reactivity in the presence of HRP-2 was a reliable predictive marker to exclude high (> 1%) parasitaemia in P. falciparum malaria. Assessment of HRP-2 and aldolase co-reactivity can be of help in clinical decision making in the acute care setting of returning travellers suspected of having malaria.
Caballero Jambrina, Antonio
confirmed that this configuration provides high linear end-to-end transmission links and is capable of transparent transport of high spectral efficient modulation formats. Furthermore, this thesis introduces a novel approach for the generation and detection of high speed wireless signals in mm-wave......This thesis expands the state-of-the-art on the detection of high speed wireless signals using optics. Signal detection at speeds over 1 Gbps at carrier Radio Frequency (RF) ranging from 5 GHz to 100 GHz have been achieved by applying novel concepts on optical digital coherent receivers....... This achievement has satisfied the requirements on transmission robustness and high capacity of next generation hybrid optical fibre-wireless networks. One important contribution of this thesis is the novel concept of photonic downconversion with free-running pulsed laser source for phase modulated Radio...
Yusof, Ruhani; Lau, Yee Ling; Mahmud, Rohela; Fong, Mun Yik; Jelip, Jenarun; Ngian, Hie Ung; Mustakim, Sahlawati; Hussin, Hani Mat; Marzuki, Noradilah; Mohd Ali, Marlindawati
.... knowlesi infection in Malaysia. A total of 457 microscopically confirmed, malaria-positive blood samples were collected from 22 state and main district hospitals in Malaysia between September 2012 and December 2013...
Heikenfeld, J.; Steckl, A. J.
High-efficiency spatial light modulation has been demonstrated for transmissive electrowetting (EW) light valves (ELVs). The ELV structure consists of a competitive oil/water-on-dielectric EW cell fabricated on an optically transparent substrate. ELVs are configured as display devices by attaching a diffuse backlight powered by white converted InGaN light emitting diodes. The oil film contains ˜1wt.% nonpolar organic chromophores which absorb with near-neutral optical density across the visible light spectrum. Using the EW effect, spatial light modulation is achieved as the water layer locally displaces the oil film. The transmissivity of the cell can be modulated from ˜5% (zero bias) to >80% (˜30V). ELV switching speed depends on cell size, typically ˜10-100ms for 1 and 3mm2 cells. Additional optical enhancement can decrease the off-state ELV transmissivity to <1%.
Malarial paroxysms are usually sudden, with 3 discernible stages: chills, fever, and sweating. After the paroxysm , the exhausted patient usually sleeps...jaundice Very rare Same as P. vivax Other features Late-day paroxysms , high fever, nausea, vomiting High fever, nausea, vomiting, diarrhea Peripheral
Akogbéto, Martin C; Aïkpon, Rock Y; Azondékon, Roseric; Padonou, Gil G; Ossè, Razaki A; Agossa, Fiacre R; Beach, Raymond; Sèzonlin, Michel
From 2008 to 2013, a prevention intervention against malaria based on indoor residual spraying (IRS) was implemented in Benin. From 2008 to 2012, Ficam M(®), a bendiocarb-containing product was used for house spraying, in association with pirimiphos methyl EC (Actellic EC) in 2013. This operation aimed to strengthen the effectiveness of treated nets so as to expedite the achievement of Millennium Development Goals (MDGs): the reduction of morbidity and mortality due to malaria by 75 % from 2000 to 2015. Monitoring and evaluation (M&E) was implemented in order to evaluate the impact of IRS intervention on malaria transmission. Anopheles gambiae s.l. populations were sampled by human landing catch. In addition, window exit traps and pyrethrum spray catches were performed to assess exophagic behaviour of Anopheles vectors the main malaria vector in the treated areas. The residual activity of insecticide in the treated walls was also assessed using WHO bioassay test. The purpose of this project was to draw attention to new challenges and future prospects for the success of IRS in Benin. The main strength of the intervention was a large-scale operation in which more than 80 % of the houses were treated due to the strong adhesion of population. In addition, a significant reduction of the EIR in areas under IRS were observed. However, there were many challenges including the high cost of IRS implementation and the identification of suitable areas to implement IRS. This was because of the low and short residual effect of the insecticides recommended for IRS and the management strategy for vector resistance to insecticides. This indicated that challenges are accompanied by suggested solutions. For the cost of IRS to be accessible to states, then local organizations need to be created in partnership with the National Malaria Control Programme (NMCP) in order to ensure relevant planning and implementation of IRS. As an anticipatory measure against vector resistance, this
Mohamed, Abdelrahim O; Abdel Hamid, Muzamil M; Mohamed, Omer S; Elkando, Nuha S; Suliman, Abdelmaroof; Adam, Mariam A; Elnour, Fahad Awad Ali; Malik, Elfatih M
Artemisinin-based combination therapy (ACT), together with other control measures, have reduced the burden of falciparum malaria in sub-Saharan countries, including Sudan. Sudan adopted ACT in 2004 with a remarkable reduction in mortality due to falciparum malaria. However, emergence of resistance to the first-line treatment artesunate and sulfadoxine/pyrimethamine (AS/SP) has created new challenges to the control of malaria in Sudan. A search for an alternative drug of choice for treating uncomplicated malaria has become inevitable. The objective of this study was to evaluate the therapeutic efficacies of dihydroartemisinin/piperaquine (DHA-PPQ) and AS/SP in an area of unstable transmission in Blue Nile State, Sudan in 2015-16. A total of 148 patients with uncomplicated malaria were recruited in the study from November 2015 to end of January 2016. Seventy-five patients received DHA-PPQ while 73 received AS/SP. Patients were monitored for clinical and parasitological outcomes following the standard WHO protocol for a period of 42 days for DHA-PPQ and 28 days for AS/SP; nested PCR (nPCR) was performed to confirm parasite re-appearance from day 7 onwards. Fifty-five patients completed the DHA-PPQ arm protocol with success cure rate of 98.2% (95% CI 90.3-100%) and one late clinical failure 1.8% (95% CI 0.0-9.7%). The AS/SP showed adequate clinical and parasitological response (ACPR) of 83.6% (95% CI 71.9-91.8%), early treatment failure was 1.6% (95% CI 0.0-8.8%) and late parasitological failure (LPF) was 14.8% (95% CI 7-26.2%). The respective PCR uncorrected LPF was 20%. DHA-PPQ is an efficacious ACT and candidate for replacement of first-line treatment in Sudan while AS/SP showed high treatment failure rate and must be replaced.
Delil, Romedan Kedir; Dileba, Temesgen Kale; Habtu, Yitagesu Aweke; Gone, Terefe Fuge; Leta, Taye Janfa
Despite a remarkable decline in morbidity and mortality since the era of malaria roll back strategy, it still poses a huge challenge in Ethiopia in general and in Hadiya Zone in particular. Although, there are data from routine health management information on few indicators, there is scarcity of data showing magnitude of malaria and associated factors including knowledge and practice in the study area. Therefore, the aim of this study was to assess magnitude and factors affecting malaria in low transmission areas among febrile cases attending public health facilities in Hadiya Zone, Ethiopia. A facility based cross-sectional study was conducted in Hadiya Zone from May 15 to June 15, 2014. Simple random sampling was used to select the health facility while systematic random sampling technique was used to reach febrile patients attending public health facilities. Data were collected by a pre-tested structured questionnaire containing sections of socio demographic risk factors and knowledge and prevention practices of malaria. Data were entered to Epi-Info software version 3.5.4 and exported to SPSS version 16 for descriptive and logistic regression analysis. One hundred six (25.8%) of participating febrile patients attending at sampled health facilities were found to have malaria by microscopy. Of which, P.vivax, P.falciparum and mixed infection accounted for 76(71. 7%), 27 (25.5%) and 3 (2.8%), respectively. History of travel to malaria endemic area, [AOR: 2.59, 95% CI: (1.24, 5.38)], not using bed net, [AOR: 4.67, 95%CI:, (2.11, 10.37)], poor practice related to malaria prevention and control, [AOR: 2.28, (95%CI: (1.10, 4.74)], poor knowledge about malaria, [AOR: 5.09,95%CI: (2.26,11.50)] and estimated distance of stagnant water near to the residence, [AOR: 3.32, (95%CI: (1.13, 9.76)] were significantly associated factors of malaria positivity in the study. The present study revealed that malaria is still a major source of morbidity in the study area among febrile
Romedan Kedir Delil
Full Text Available Despite a remarkable decline in morbidity and mortality since the era of malaria roll back strategy, it still poses a huge challenge in Ethiopia in general and in Hadiya Zone in particular. Although, there are data from routine health management information on few indicators, there is scarcity of data showing magnitude of malaria and associated factors including knowledge and practice in the study area. Therefore, the aim of this study was to assess magnitude and factors affecting malaria in low transmission areas among febrile cases attending public health facilities in Hadiya Zone, Ethiopia.A facility based cross-sectional study was conducted in Hadiya Zone from May 15 to June 15, 2014. Simple random sampling was used to select the health facility while systematic random sampling technique was used to reach febrile patients attending public health facilities. Data were collected by a pre-tested structured questionnaire containing sections of socio demographic risk factors and knowledge and prevention practices of malaria. Data were entered to Epi-Info software version 3.5.4 and exported to SPSS version 16 for descriptive and logistic regression analysis.One hundred six (25.8% of participating febrile patients attending at sampled health facilities were found to have malaria by microscopy. Of which, P.vivax, P.falciparum and mixed infection accounted for 76(71. 7%, 27 (25.5% and 3 (2.8%, respectively. History of travel to malaria endemic area, [AOR: 2.59, 95% CI: (1.24, 5.38], not using bed net, [AOR: 4.67, 95%CI:, (2.11, 10.37], poor practice related to malaria prevention and control, [AOR: 2.28, (95%CI: (1.10, 4.74], poor knowledge about malaria, [AOR: 5.09,95%CI: (2.26,11.50] and estimated distance of stagnant water near to the residence, [AOR: 3.32, (95%CI: (1.13, 9.76] were significantly associated factors of malaria positivity in the study.The present study revealed that malaria is still a major source of morbidity in the study area among
3D7-derived Plasmodium falciparum erythrocyte membrane protein 1 is a frequent target of naturally acquired antibodies recognizing protein domains in a particular pattern independent of malaria transmission intensity
Joergensen, Louise; Vestergaard, Lasse S; Turner, Louise
in individuals living in the high transmission village and by the age of 2-4 years most individuals had Abs against most constructs. This level of reactivity was found at the age of 10-20 years in the medium transmission village and was never reached by individuals living under low transmission. Nevertheless...... derived from 3D7 in individuals living under markedly different malaria transmission intensity and were unable to find differences in the Ab acquisition rate to PfEMP1 of different groupings (A, B, or C) or domain type (alpha, beta, gamma, delta, epsilon, or x). Abs were acquired early in life......-parasite relationship factors operating at all transmission intensities....
Andréoletti, Olivier; Litaise, Claire; Simmons, Hugh; Corbière, Fabien; Lugan, Séverine; Costes, Pierrette; Schelcher, François; Vilette, Didier; Grassi, Jacques; Lacroux, Caroline
It is now clearly established that the transfusion of blood from variant CJD (v-CJD) infected individuals can transmit the disease. Since the number of asymptomatic infected donors remains unresolved, inter-individual v-CJD transmission through blood and blood derived products is a major public health concern. Current risk assessments for transmission of v-CJD by blood and blood derived products by transfusion rely on infectious titers measured in rodent models of Transmissible Spongiform Encephalopathies (TSE) using intra-cerebral (IC) inoculation of blood components. To address the biological relevance of this approach, we compared the efficiency of TSE transmission by blood and blood components when administrated either through transfusion in sheep or by intra-cerebral inoculation (IC) in transgenic mice (tg338) over-expressing ovine PrP. Transfusion of 200 µL of blood from asymptomatic infected donor sheep transmitted prion disease with 100% efficiency thereby displaying greater virulence than the transfusion of 200 mL of normal blood spiked with brain homogenate material containing 103ID50 as measured by intracerebral inoculation of tg338 mice (ID50 IC in tg338). This was consistent with a whole blood titer greater than 103.6 ID50 IC in tg338 per mL. However, when the same blood samples were assayed by IC inoculation into tg338 the infectious titers were less than 32 ID per mL. Whereas the transfusion of crude plasma to sheep transmitted the disease with limited efficacy, White Blood Cells (WBC) displayed a similar ability to whole blood to infect recipients. Strikingly, fixation of WBC with paraformaldehyde did not affect the infectivity titer as measured in tg338 but dramatically impaired disease transmission by transfusion in sheep. These results demonstrate that TSE transmission by blood transfusion can be highly efficient and that this efficiency is more dependent on the viability of transfused cells than the level of infectivity measured by IC
Knols Bart GJ
Full Text Available Abstract Background Based on sensitivity analysis of the MacDonald-Ross model, it has long been argued that the best way to reduce malaria transmission is to target adult female mosquitoes with insecticides that can reduce the longevity and human-feeding frequency of vectors. However, these analyses have ignored a fundamental biological difference between mosquito adults and the immature stages that precede them: adults are highly mobile flying insects that can readily detect and avoid many intervention measures whereas mosquito eggs, larvae and pupae are confined within relatively small aquatic habitats and cannot readily escape control measures. Presentation of the hypothesis We hypothesize that the control of adult but not immature mosquitoes is compromised by their ability to avoid interventions such as excito-repellant insecticides. Testing the hypothesis We apply a simple model of intervention avoidance by mosquitoes and demonstrate that this can substantially reduce effective coverage, in terms of the proportion of the vector population that is covered, and overall impact on malaria transmission. We review historical evidence that larval control of African malaria vectors can be effective and conclude that the only limitations to the effective coverage of larval control are practical rather than fundamental. Implications of the hypothesis Larval control strategies against the vectors of malaria in sub-Saharan Africa could be highly effective, complementary to adult control interventions, and should be prioritized for further development, evaluation and implementation as an integral part of Rolling Back Malaria.
ter Kuile, Feiko O.; Terlouw, Dianne J.; Phillips-Howard, Penelope A.; Hawley, William A.; Friedman, Jennifer F.; Kolczak, Margarette S.; Kariuki, Simon K.; Shi, Ya Ping; Kwena, Arthur M.; Vulule, John M.; Nahlen, Bernard L.
Information on the impact of insecticide (permethrin)-treated bed nets (ITNs) from randomized controlled trials in areas of intense perennial malaria transmission is limited. As part of a large-scale, community-based, group-randomized controlled trial of the effect of ITNs on childhood mortality in
Chourasia, Mehul Kumar; Raghavendra, Kamaraju; Bhatt, Rajendra M; Swain, Dipak Kumar; Meshram, Hemraj M; Meshram, Jayant K; Suman, Shrity; Dubey, Vinita; Singh, Gyanendra; Prasad, Kona Madhavinadha; Kleinschmidt, Immo
The burden of sub-patent malaria is difficult to recognize in low endemic areas due to limitation of diagnostic tools, and techniques. Polymerase chain reaction (PCR), a molecular based technique, is one of the key methods for detection of low parasite density infections. The study objective was to assess the additional burden of asymptomatic and sub-patent malaria infection among tribal populations inhabiting three endemic villages in Keshkal sub-district, Chhattisgarh, India. A cross-sectional survey was conducted in March-June 2016, during the low transmission season, to measure and compare prevalence of malaria infection using three diagnostics: rapid diagnostic test, microscopy and nested-PCR. Out of 437 individuals enrolled in the study, 103 (23.6%) were malaria positive by PCR and/or microscopy of whom 89.3% were Plasmodium falciparum cases, 77.7% were afebrile and 35.9% had sub-patent infections. A substantial number of asymptomatic and sub-patent malaria infections were identified in the survey. Hence, strategies for identifying and reducing the hidden burden of asymptomatic and sub-patent infections should focus on forest rural tribal areas using more sensitive molecular diagnostic methods to curtail malaria transmission.
Wahid, Sobia; Stresman, Gillian H; Kamal, Syed Sajid; Sepulveda, Nuno; Kleinschmidt, Immo; Bousema, Teun; Drakeley, Chris
Afghan refugees in northern Pakistan have been resident for over 30 years and current information on malaria in this population is sparse. Understanding malaria risk and distribution in refugee camps is important for effective management both in camps and on return to Afghanistan. Cross-sectional malariometric surveys were conducted in five Afghan refugee camps to determine infection and exposure to both Plasmodium falciparum and Plasmodium vivax. Factors associated with malaria infection and exposure were analysed using logistic regression, and spatial heterogeneity within camps was investigated with SatScan. In this low-transmission setting, prevalence of infection in the five camps ranged from 0-0.2 to 0.4-9 % by rapid diagnostic test and 0-1.39 and 5-15 % by polymerase chain reaction for P. falciparum and P. vivax, respectively. Prevalence of anti-malarial antibodies to P. falciparum antigens was 3-11 and 17-45 % for P. vivax antigens. Significant foci of P. vivax infection and exposure were detected in three of the five camps. Hotspots of P. falciparum were also detected in three camps, only one of which also showed evidence of P. vivax hotspots. There is low and spatially heterogeneous malaria transmission in the refugee camps in northern Pakistan. Understanding malaria risk in refugee camps is important so the malaria risk faced by these populations in the camps and upon their return to Afghanistan can be effectively managed.
Background Plasmodium falciparum is the major cause of malaria infection in the island of São Tomé, in the Republic of São Tomé and Príncipe (STP), with an incidence of 40 - 50% before 2004. Since 2004, through the coordination of the Ministry of Health of STP and their Centro Nacional de Endemias (CNE), an integrated malaria control programme has been intensively deployed on the island of São Tomé. Malaria morbidity and mortality decreased by 95% after three years of effective intervention. In the low transmission settings, however, malaria seasonal fluctuation can be a potential problem directly related to epidemics if ongoing control measures are interrupted. Studies on a number of associated factors with malaria epidemics and the measures taken to respond to outbreaks are presented. Methods The integrated malaria control programme included indoor residual spraying (IRS), long-lasting insecticidal nets (LLINs), intermittent preventive therapy for pregnant women, as well as early diagnosis and prompt treatment with artemisinin-based combination therapy (ACT). Regular implementation of an island-wide IRS programme was carried out yearly in 2004-2007, and enhanced throughout the island in 2009. Malaria incidence and prevalence were estimated based on passive case detection and mass screening, respectively. Slide positivity rates were used for monitoring the beginning of a malaria epidemic or a seasonal peak. Results A steep decline of ca. 95% of malaria morbidity and mortality was observed between 2004 and 2008 with use of the combined control methods. Malaria incidence was 2.0%, 1.5%, and 3.0% for 2007, 2008, and 2009, respectively. In April 2008, a cross-sectional country-wide surveillance showed malaria prevalence of 3.5%, of which 95% cases were asymptomatic carriers. Only 50% of asymptomatic carriers were cured with ACT treatment, while 90% of the symptomatic patients were cured by ACT treatment as confirmed with a follow up study. Malaria morbidity
Greenwood, Brian; Dicko, Alassane; Sagara, Issaka; Zongo, Issaka; Tinto, Halidou; Cairns, Matthew; Kuepfer, Irene; Milligan, Paul; Ouedraogo, Jean-Bosco; Doumbo, Ogobara; Chandramohan, Daniel
In many parts of the African Sahel and sub-Sahel, where malaria remains a major cause of mortality and morbidity, transmission of the infection is highly seasonal. Seasonal malaria chemoprevention (SMC), which involves administration of a full course of malaria treatment to young children at monthly intervals during the high transmission season, is proving to be an effective malaria control measure in these areas. However, SMC does not provide complete protection and it is demanding to deliver for both families and healthcare givers. Furthermore, there is a risk of the emergence in the future of resistance to the drugs, sulfadoxine-pyrimethamine and amodiaquine, that are currently being used for SMC. Substantial progress has been made in the development of malaria vaccines during the past decade and one malaria vaccine, RTS,S/AS01, has received a positive opinion from the European Medicines Authority and will soon be deployed in large-scale, pilot implementation projects in sub-Saharan Africa. A characteristic feature of this vaccine, and potentially of some of the other malaria vaccines under development, is that they provide a high level of efficacy during the period immediately after vaccination, but that this wanes rapidly, perhaps because it is difficult to develop effective immunological memory to malaria antigens in subjects exposed previously to malaria infection. A potentially effective way of using malaria vaccines with high initial efficacy but which provide only a short period of protection could be annual, mass vaccination campaigns shortly before each malaria transmission season in areas where malaria transmission is confined largely to a few months of the year.
Rek, J.; Katrak, S.; Obasi, H.; Nayebare, P.; Katureebe, A.; Kakande, E.; Arinaitwe, E.; Nankabirwa, J.I.; Jagannathan, P.; Drakeley, C.; Staedke, S.G.; Smith, D.L.; Bousema, T.; Kamya, M.; Rosenthal, P.J.; Dorsey, G.; Greenhouse, B.
BACKGROUND: Parasite prevalence is a key metric used to quantify the burden of malaria and assess the impact of control strategies. Most published estimates of parasite prevalence are based on microscopy and likely underestimate true prevalence. METHODS: Thick smear microscopy was performed in
Ndyomugyenyi, Richard; Clarke, Siân E; Hutchison, Coll L.
-randomised placebo-controlled trial involving 5775 women of all parities examined the effect of IPTp, ITNs alone, or ITNs used in combination with IPTp on maternal anaemia and low birth weight (LBW) in a highland area of southwestern Uganda. The overall prevalence of malaria infection, maternal anaemia and LBW...
Robert, Leon L; Santos-Ciminera, Patricia D; Andre, Richard G; Schultz, George W; Lawyer, Phillip G; Nigro, Joseph; Masuoka, Penny; Wirtz, Robert A; Neely, John; Gaines, David; Cannon, Charles E; Pettit, Denise; Garvey, Carol W; Goodfriend, David; Roberts, Donald R
Two recent outbreaks of locally acquired, mosquito-transmitted malaria in Virginia in 1998 and 2002 demonstrate the continued risk of endemic mosquito-transmitted malaria in heavily populated areas of the eastern United States. Increasing immigration, growth in global travel, and the presence of competent anopheline vectors throughout the eastern United States contribute to the increasing risk of malaria importation and transmission. On August 23 and 25, 2002, Plasmodium vivax malaria was diagnosed in 2 teenagers in Loudoun County, Virginia. The Centers for Disease Control and Prevention (CDC) deemed these cases to be locally acquired because of the lack of risk factors for malaria, such as international travel, blood transfusion, organ transplantation, or needle sharing. The patients lived approximately 0.5 mi apart; however, 1 patient reported numerous visits to friends who lived directly across the street from the other patient. Two Anopheles quadrimaculatus s.l. female pools collected in Loudoun County, Virginia, and 1 An. punctipennis female pool collected in Fairfax County, Virginia, tested positive for P. vivax 210 with the VecTest panel assay and enzyme-linked immunosorbent assay (ELISA). In addition, 2 An. quadrimaculatus s.l. female pools collected in Montgomery, Maryland, tested positive for P. vivax 210. The CDC confirmed these initial results with the circumsporozoite ELISA. The authors believe that this is the 1st demonstration of Plasmodium-infected mosquitoes collected in association with locally acquired human malaria in the United States since the current national malaria surveillance system began in 1957.
Plasmodium falciparum, anaemia and cognitive and educational performance among school children in an area of moderate malaria transmission: baseline results of a cluster randomized trial on the coast of Kenya.
Halliday, Katherine E; Karanja, Peris; Turner, Elizabeth L; Okello, George; Njagi, Kiambo; Dubeck, Margaret M; Allen, Elizabeth; Jukes, Matthew C H; Brooker, Simon J
Studies have typically investigated health and educational consequences of malaria among school-aged children in areas of high malaria transmission, but few have investigated these issues in moderate transmission settings. This study investigates the patterns of and risks for Plasmodium falciparum and anaemia and their association with cognitive and education outcomes on the Kenyan coast, an area of moderate malaria transmission. As part of a cluster randomised trial, a baseline cross-sectional survey assessed the prevalence of and risk factors for P. falciparum infection and anaemia and the associations between health status and measures of cognition and educational achievement. Results are presented for 2400 randomly selected children who were enrolled in the 51 intervention schools. The overall prevalence of P. falciparum infection and anaemia was 13.0% and 45.5%, respectively. There was marked heterogeneity in the prevalence of P. falciparum infection by school. In multivariable analysis, being male, younger age, not sleeping under a mosquito net and household crowding were adjusted risk factors for P. falciparum infection, whilst P. falciparum infection, being male and indicators of poor nutritional intake were risk factors for anaemia. No association was observed between either P. falciparum or anaemia and performance on tests of sustained attention, cognition, literacy or numeracy. The results indicate that in this moderate malaria transmission setting, P. falciparum is strongly associated with anaemia, but there is no clear association between health status and education. Intervention studies are underway to investigate whether removing the burden of chronic asymptomatic P. falciparum and related anaemia can improve education outcomes. © 2012 Blackwell Publishing Ltd.
Ingabire, Chantal Marie; Alaii, Jane; Hakizimana, Emmanuel; Kateera, Fredrick; Muhimuzi, Daniel; Nieuwold, Ingmar; Bezooijen, Karsten; Rulisa, Stephen; Kaligirwa, Nadine; Muvunyi, Claude; Koenraadt, Constantianus J. M.; Mutesa, Leon; van Vugt, Michele; van den Borne, Bart
Despite the significant reduction of malaria transmission in Rwanda, Ruhuha sector is still a highly endemic area for malaria. The objective of this activity was to explore and brainstorm the potential roles of various community stakeholders in malaria elimination. Horizontal participatory
Ingabire, C.M.; Alaii, J.; Hakizimana, E.; Kateera, F.; Muhimuzi, D.; Nieuwold, I.; Bezooijen, K.; Rulisa, S.; Kaligirwa, N.; Muvunyi, C.; Koenraadt, C.J.M.; Mutesa, L.; Vugt, van M.; Borne, van den B.
Background Despite the significant reduction of malaria transmission in Rwanda, Ruhuha sector is still a highly endemic area for malaria. The objective of this activity was to explore and brainstorm the potential roles of various community stakeholders in malaria elimination. Methods Horizontal
da Silveira Bressan Clarisse
Full Text Available Abstract Background In 2010, Brazil recorded 3343,599 cases of malaria, with 99.6% of them concentrated in the Amazon region. Plasmodium vivax accounts for 86% of the cases circulating in the country. The extra-Amazonian region, where transmission does not occur, recorded about 566 cases imported from the Amazonian area in Brazil and South America, from Central America, Asia and African countries. Prolonged incubation periods have been described for P. vivax malaria in temperate climates. The diversity in essential biological characteristics is traditionally considered as one possible explanation to the emergence of relapse in malaria and to the differences in the duration of the incubation period, which can also be explained by the use of chemoprophylaxis. Studying the reported cases of P. vivax malaria in Rio de Janeiro, where there is no vector transmission, has made it possible to evaluate the extension of the incubation period and to notice that it may be extended in some cases. Methods Descriptive study of every malaria patients who visited the clinic in the last five years. The mean, standard deviation, median, minimum and maximum of all incubation periods were analysed. Results From the total of 80 patients seen in the clinic during the study time, with confirmed diagnosis of malaria, 49 (63% were infected with P. vivax. Between those, seven had an estimated incubation period varying from three to 12 months and were returned travellers from Brazilian Amazonian states (6 and Indonesia (1. None of them had taken malarial chemoprophylaxis. Conclusions The authors emphasize that considering malaria as a possible cause of febrile syndrome should be a post-travel routine, independent of the time elapsed after exposure in the transmission area, even in the absence of malaria chemoprophylaxis. They speculate that, since there is no current and detailed information about the biological cycle of human malaria plasmodia's in Brazil, it is possible
Heinig, Rebecca L.; Paaijmans, Krijn P.; Hancock, Penelope A.; Thomas, Matthew B
Summary The effectiveness of conventional malaria vector control is being threatened by the spread of insecticide resistance. One promising alternative to chemicals is the use of naturally occurring insect?killing fungi. Numerous laboratory studies have shown that isolates of fungal pathogens such as Beauveria bassiana can infect and kill adult mosquitoes, including those resistant to chemical insecticides. Unlike chemical insecticides, fungi may take up to a week or more to kill mosquitoes f...
Nias Island, off the north-western coast of Sumatra, Indonesia, was one of the first locations in which chloroquine-resistant Plasmodium vivax malaria was reported. This resistance is of particular concern because its ancient megalithic culture and the outstanding surfing conditions make the island a popular tourist destination. International travel to and from the island could rapidly spread chloroquine-resistant strains of P. vivax across the planet. The threat posed by such strains, locall...
Singh, Susheel K; Thrane, Susan; Janitzek, Christoph M
Malaria is a devastating disease caused by Plasmodium parasites, resulting in almost 0.5 million deaths per year. The Pfs48/45 protein exposed on the P. falciparum sexual stages is one of the most advanced antigen candidates for a transmission-blocking (TB) vaccine in the clinical pipeline. However...
Okumu Fredros O
Full Text Available Abstract Background Indoor residual insecticide spraying (IRS and long-lasting insecticide treated nets (LLINs are commonly used together even though evidence that such combinations confer greater protection against malaria than either method alone is inconsistent. Methods A deterministic model of mosquito life cycle processes was adapted to allow parameterization with results from experimental hut trials of various combinations of untreated nets or LLINs (Olyset®, PermaNet 2.0®, Icon Life® nets with IRS (pirimiphos methyl, lambda cyhalothrin, DDT, in a setting where vector populations are dominated by Anopheles arabiensis, so that community level impact upon malaria transmission at high coverage could be predicted. Results Intact untreated nets alone provide equivalent personal protection to all three LLINs. Relative to IRS plus untreated nets, community level protection is slightly higher when Olyset® or PermaNet 2.0® nets are added onto IRS with pirimiphos methyl or lambda cyhalothrin but not DDT, and when Icon Life® nets supplement any of the IRS insecticides. Adding IRS onto any net modestly enhances communal protection when pirimiphos methyl is sprayed, while spraying lambda cyhalothrin enhances protection for untreated nets but not LLINs. Addition of DDT reduces communal protection when added to LLINs. Conclusions Where transmission is mediated primarily by An. arabiensis, adding IRS to high LLIN coverage provides only modest incremental benefit (e.g. when an organophosphate like pirimiphos methyl is used, but can be redundant (e.g. when a pyrethroid like lambda cyhalothin is used or even regressive (e.g. when DDT is used for the IRS. Relative to IRS plus untreated nets, supplementing IRS with LLINs will only modestly improve community protection. Beyond the physical protection that intact nets provide, additional protection against transmission by An. arabiensis conferred by insecticides will be remarkably small, regardless of
Lal, Sham; Ndyomugenyi, Richard; Magnussen, Pascal
Malaria-endemic countries have implemented community health worker (CHW) programs to provide malaria diagnosis and treatment to populations living beyond the reach of health systems. However, there is limited evidence describing the referral practices of CHWs. We examined the impact of malaria...... rapid diagnostic tests (mRDTs) on CHW referral in two cluster-randomized trials, one conducted in a moderate-to-high malaria transmission setting and one in a low-transmission setting in Uganda, between January 2010 and July 2012. All CHWs were trained to prescribe artemisinin-based combination therapy...
Wong, Jacklyn; Bayoh, Nabie; Olang, George; Killeen, Gerry F; Hamel, Mary J; Vulule, John M; Gimnig, John E
Operational vector sampling methods lack standardization, making quantitative comparisons of malaria transmission across different settings difficult. Human landing catch (HLC) is considered the research gold standard for measuring human-mosquito contact, but is unsuitable for large-scale sampling. This study assessed mosquito catch rates of CDC light trap (CDC-LT), Ifakara tent trap (ITT), window exit trap (WET), pot resting trap (PRT), and box resting trap (BRT) relative to HLC in western Kenya to 1) identify appropriate methods for operational sampling in this region, and 2) contribute to a larger, overarching project comparing standardized evaluations of vector trapping methods across multiple countries. Mosquitoes were collected from June to July 2009 in four districts: Rarieda, Kisumu West, Nyando, and Rachuonyo. In each district, all trapping methods were rotated 10 times through three houses in a 3 × 3 Latin Square design. Anophelines were identified by morphology and females classified as fed or non-fed. Anopheles gambiae s.l. were further identified as Anopheles gambiae s.s. or Anopheles arabiensis by PCR. Relative catch rates were estimated by negative binomial regression. When data were pooled across all four districts, catch rates (relative to HLC indoor) for An. gambiae s.l (95.6% An. arabiensis, 4.4% An. gambiae s.s) were high for HLC outdoor (RR = 1.01), CDC-LT (RR = 1.18), and ITT (RR = 1.39); moderate for WET (RR = 0.52) and PRT outdoor (RR = 0.32); and low for all remaining types of resting traps (PRT indoor, BRT indoor, and BRT outdoor; RR type varied from district to district. ITT, CDC-LT, and WET appear to be effective methods for large-scale vector sampling in western Kenya. Ultimately, choice of collection method for operational surveillance should be driven by trap efficacy and scalability, rather than fine-scale precision with respect to HLC. When compared with recent, similar trap evaluations in Tanzania and Zambia, these data suggest
A technology characterization for high Btu gas transmission was prepared. The scope of work was confined to a literature review. The work was divided into four specific areas as follows: (1) a summary of pertinent information from the environmental report of the Great Lakes Gas Company for a 365-mile high pressure pipeline serving American Natural Gas Company's proposed lignite gasification plant in North Dakota; (2) statistical information concerning the operation of the existing United States natural gas transmission pipeline network; (3) a summary of pertinent information from the environmental impact statement of the United States Department of Interior for the proposed 1,619-mile Northern Border Pipeline from Morgan, Montana to Delmont, Pennsylvania; and (4) a summary of pertinent information from the environmental impact statement of the Federal Power Commission for a proposed El Paso Natural Gas Company 418-mile pipeline within the State of Texas which was to be constructed in response to the displacement of natural gas by Liquefied Natural Gas (LNG) importation on the East Coast.
Rossi, Gabriele; Van den Bergh, Rafael; Nguon, Chea; Debackere, Mark; Vernaeve, Lieven; Khim, Nimol; Kim, Saorin; Menard, Didier; De Smet, Martin; Kindermans, Jean-Marie
Reactive case detection (RACD) around falciparum malaria cases in Cambodia is performed as rapid diagnostic test-based household screening around index cases, typically with a low detection rate. We improved RACD by including individuals occupationally co-exposed with index cases and PCR-based diagnosis. The positivity rate increased 20-fold, from 0.16% to 3.9%. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: firstname.lastname@example.org.
A-Elgadir, T M E; Theander, T G; Elghazali, G
The variant surface antigens (VSA) of infected erythrocytes are important pathogenic markers, a set of variants (VSA(SM)), were assumed to be associated with severe malaria (SM), while SM constitutes clinically diverse forms, such as, severe malarial anemia (SMA) and cerebral malaria (CM). This s......The variant surface antigens (VSA) of infected erythrocytes are important pathogenic markers, a set of variants (VSA(SM)), were assumed to be associated with severe malaria (SM), while SM constitutes clinically diverse forms, such as, severe malarial anemia (SMA) and cerebral malaria (CM...... range of isolates had a higher level of VSA Ab against the recognized isolates (correlation coefficient, 0.727, PSMA (P....001). Parasites obtained from patients with SMA or from children were better recognized than isolates obtained from patients with uncomplicated malaria or from adults, P
Kalifa A Bojang
Full Text Available The Expanded Programme on Immunisation (EPI provides an effective way of delivering intermittent preventive treatment for malaria (IPT to infants. However, it is uncertain how IPT can be delivered most effectively to older children. Therefore, we have compared two approaches to the delivery of IPT to Gambian children: distribution by village health workers (VHWs or through reproductive and child health (RCH trekking teams. In rural areas, RCH trekking teams provide most of the health care to children under the age of 5 years in the Infant Welfare Clinic, and provide antenatal care for pregnant women.During the 2006 malaria transmission season, the catchment populations of 26 RCH trekking clinics in The Gambia, each with 400-500 children 6 years of age and under, were randomly allocated to receive IPT from an RCH trekking team or from a VHW. Treatment with a single dose of sulfadoxine pyrimethamine (SP plus three doses of amodiaquine (AQ were given at monthly intervals during the malaria transmission season. Morbidity from malaria was monitored passively throughout the malaria transmission season in all children, and a random sample of study children from each cluster was examined at the end of the malaria transmission season. The primary study endpoint was the incidence of malaria. Secondary endpoints included coverage of IPTc, mean haemoglobin (Hb concentration, and the prevalence of asexual malaria parasitaemia at the end of malaria transmission period. Financial and economic costs associated with the two delivery strategies were collected and incremental cost and effects were compared. A nested case-control study was used to estimate efficacy of IPT treatment courses. Treatment with SP plus AQ was safe and well tolerated. There were 49 cases of malaria with parasitaemia above 5,000/µl in the areas where IPT was delivered through RCH clinics and 21 cases in the areas where IPT was delivered by VHWs, (incidence rates 2.8 and 1.2 per 1
Coulibaly, Drissa; Travassos, Mark A; Tolo, Youssouf; Laurens, Matthew B; Kone, Abdoulaye K; Traore, Karim; Sissoko, Mody; Niangaly, Amadou; Diarra, Issa; Daou, Modibo; Guindo, Boureima; Rebaudet, Stanislas; Kouriba, Bourema; Dessay, Nadine; Piarroux, Renaud; Plowe, Christopher V; Doumbo, Ogobara K; Thera, Mahamadou A; Gaudart, Jean
In areas of seasonal malaria transmission, the incidence rate of malaria infection is presumed to be near zero at the end of the dry season. Asymptomatic individuals may constitute a major parasite reservoir during this time. We conducted a longitudinal analysis of the spatio-temporal distribution of clinical malaria and asymptomatic parasitemia over time in a Malian town to highlight these malaria transmission dynamics. For a cohort of 300 rural children followed over 2009-2014, periodicity and phase shift between malaria and rainfall were determined by spectral analysis. Spatial risk clusters of clinical episodes or carriage were identified. A nested-case-control study was conducted to assess the parasite carriage factors. Malaria infection persisted over the entire year with seasonal peaks. High transmission periods began 2-3 months after the rains began. A cluster with a low risk of clinical malaria in the town center persisted in high and low transmission periods. Throughout 2009-2014, cluster locations did not vary from year to year. Asymptomatic and gametocyte carriage were persistent, even during low transmission periods. For high transmission periods, the ratio of asymptomatic to clinical cases was approximately 0.5, but was five times higher during low transmission periods. Clinical episodes at previous high transmission periods were a protective factor for asymptomatic carriage, but carrying parasites without symptoms at a previous high transmission period was a risk factor for asymptomatic carriage. Stable malaria transmission was associated with sustained asymptomatic carriage during dry seasons. Control strategies should target persistent low-level parasitemia clusters to interrupt transmission.
Koita, Kadiatou; Novotny, Joseph; Kunene, Simon; Zulu, Zulizile; Ntshalintshali, Nyasatu; Gandhi, Monica; Gosling, Roland
Swaziland has made great progress towards its goal of malaria elimination by 2015. However, malaria importation from neighbouring high-endemic Mozambique through Swaziland's eastern border remains a major factor that could prevent elimination from being achieved. In order to reach elimination, Swaziland must rapidly identify and treat imported malaria cases before onward transmission occurs. A nationwide formative assessment was conducted over eight weeks to determine if the imported cases of malaria identified by the Swaziland National Malaria Control Programme could be linked to broader social networks and to explore methods to access these networks. Using a structured format, interviews were carried out with malaria surveillance agents (6), health providers (10), previously identified imported malaria cases (19) and people belonging to the networks identified through these interviews (25). Most imported malaria cases were Mozambicans (63%, 12/19) making a living in Swaziland and sustaining their families in Mozambique. The majority of imported cases (73%, 14/19) were labourers and self-employed contractors who travelled frequently to Mozambique to visit their families and conduct business. Social networks of imported cases with similar travel patterns were identified through these interviews. Nearly all imported cases (89%, 17/19) were willing to share contact information to enable network members to be interviewed. Interviews of network members and key informants revealed common congregation points, such as the urban market places in Manzini and Malkerns, as well as certain bus stations, where people with similar travel patterns and malaria risk behaviours could be located and tested for malaria. This study demonstrated that imported cases of malaria belonged to networks of people with similar travel patterns. This study may provide novel methods for screening high-risk groups of travellers using both snowball sampling and time-location sampling of networks to
Antimalarial drugs will be essential tools at all stages of malaria elimination along the path towards eradication, including the early control or "attack" phase to drive down transmission and the later stages of maintaining interruption of transmission, preventing reintroduction of malaria, and eliminating the last residual foci of infection. Drugs will continue to be used to treat acute malaria illness and prevent complications in vulnerable groups, but better drugs are needed for elimination-specific indications such as mass treatment, curing asymptomatic infections, curing relapsing liver stages, and preventing transmission. The ideal malaria eradication drug is a coformulated drug combination suitable for mass administration that can be administered in a single encounter at infrequent intervals and that results in radical cure of all life cycle stages of all five malaria species infecting humans. Short of this optimal goal, highly desirable drugs might have limitations such as targeting only one or two parasite species, the priorities being Plasmodium falciparum and Plasmodium vivax. The malaria research agenda for eradication should include research aimed at developing such drugs and research to develop situation-specific strategies for using both current and future drugs to interrupt malaria transmission.
Daniel B Larremore
Full Text Available The var genes of the human malaria parasite Plasmodium falciparum present a challenge to population geneticists due to their extreme diversity, which is generated by high rates of recombination. These genes encode a primary antigen protein called PfEMP1, which is expressed on the surface of infected red blood cells and elicits protective immune responses. Var gene sequences are characterized by pronounced mosaicism, precluding the use of traditional phylogenetic tools that require bifurcating tree-like evolutionary relationships. We present a new method that identifies highly variable regions (HVRs, and then maps each HVR to a complex network in which each sequence is a node and two nodes are linked if they share an exact match of significant length. Here, networks of var genes that recombine freely are expected to have a uniformly random structure, but constraints on recombination will produce network communities that we identify using a stochastic block model. We validate this method on synthetic data, showing that it correctly recovers populations of constrained recombination, before applying it to the Duffy Binding Like-α (DBLα domain of var genes. We find nine HVRs whose network communities map in distinctive ways to known DBLα classifications and clinical phenotypes. We show that the recombinational constraints of some HVRs are correlated, while others are independent. These findings suggest that this micromodular structuring facilitates independent evolutionary trajectories of neighboring mosaic regions, allowing the parasite to retain protein function while generating enormous sequence diversity. Our approach therefore offers a rigorous method for analyzing evolutionary constraints in var genes, and is also flexible enough to be easily applied more generally to any highly recombinant sequences.
Size of adult mosquitoes is known to affect both population dynamics as well as disease transmission. Studies devoted to this topic have given different results for different species. For example in some mosquito species, large size was found to be associated with high fecundity and longer
Cui, Liwang; Yan, Guiyun; Sattabongkot, Jetsumon; Cao, Yaming; Chen, Bin; Chen, Xiaoguang; Fan, Qi; Fang, Qiang; Jongwutiwes, Somchai; Parker, Daniel; Sirichaisinthop, Jeeraphat; Kyaw, Myat Phone; Su, Xin-zhuan; Yang, Henglin; Yang, Zhaoqing; Wang, Baomin; Xu, Jianwei; Zheng, Bin; Zhong, Daibin; Zhou, Guofa
The Greater Mekong Subregion (GMS), comprised of six countries including Cambodia, China's Yunnan Province, Lao PDR, Myanmar (Burma), Thailand and Vietnam, is one of the most threatening foci of malaria. Since the initiation of the WHO's Mekong Malaria Program a decade ago, malaria situation in the GMS has greatly improved, reflected in the continuous decline in annual malaria incidence and deaths. However, as many nations are moving towards malaria elimination, the GMS nations still face great challenges. Malaria epidemiology in this region exhibits enormous geographical heterogeneity with Myanmar and Cambodia remaining high-burden countries. Within each country, malaria distribution is also patchy, exemplified by 'border malaria' and 'forest malaria' with high transmission occurring along international borders and in forests or forest fringes, respectively. 'Border malaria' is extremely difficult to monitor, and frequent malaria introductions by migratory human populations constitute a major threat to neighboring, malaria-eliminating countries. Therefore, coordination between neighboring countries is essential for malaria elimination from the entire region. In addition to these operational difficulties, malaria control in the GMS also encounters several technological challenges. Contemporary malaria control measures rely heavily on effective chemotherapy and insecticide control of vector mosquitoes. However, the spread of multidrug resistance and potential emergence of artemisinin resistance in Plasmodium falciparum make resistance management a high priority in the GMS. This situation is further worsened by the circulation of counterfeit and substandard artemisinin-related drugs. In most endemic areas of the GMS, P. falciparum and Plasmodium vivax coexist, and in recent malaria control history, P. vivax has demonstrated remarkable resilience to control measures. Deployment of the only registered drug (primaquine) for the radical cure of vivax malaria is severely
Nielsen, Morten A; Resende, Mafalda; Alifrangis, Michael
In areas of high Plasmodium falciparum transmission, immunity to malaria is acquired during childhood, so that adults in general are clinically immune. One exception is that first-time pregnant women are susceptible to pregnancy-associated malaria caused by accumulation of parasites in the placenta...... mediates the adhesive and antigenic phenotypes shown by parasites causing placental malaria....
Snow, Robert W.; Amratia, Punam; Zamani, Ghasem; Mundia, Clara W.; Noor, Abdisalan M.; Memish, Ziad A.; Al Zahrani, Mohammad H.; Al Jasari, Adel; Fikri, Mahmoud; Atta, Hoda
The transmission of malaria across the Arabian Peninsula is governed by the diversity of dominant vectors and extreme aridity. It is likely that where malaria transmission was historically possible it was intense and led to a high disease burden. Here, we review the speed of elimination, approaches taken, define the shrinking map of risk since 1960 and discuss the threats posed to a malaria-free Arabian Peninsula using the archive material, case data and published works. From as early as the 1940s, attempts were made to eliminate malaria on the peninsula but were met with varying degrees of success through to the 1970s; however, these did result in a shrinking of the margins of malaria transmission across the peninsula. Epidemics in the 1990s galvanised national malaria control programmes to reinvigorate control efforts. Before the launch of the recent global ambition for malaria eradication, countries on the Arabian Peninsula launched a collaborative malaria-free initiative in 2005. This initiative led a further shrinking of the malaria risk map and today locally acquired clinical cases of malaria are reported only in Saudi Arabia and Yemen, with the latter contributing to over 98% of the clinical burden. PMID:23548086
Butykai, A; Kocsis, V; Szaller, D; Bordacs, S; Tatrai-Szekeres, E; Kiss, L F; Bota, A; Vertessy, B G; Zelles, T; Kezsmarki, I
The need to develop new methods for the high-sensitivity diagnosis of malaria has initiated a global activity in medical and interdisciplinary sciences. Most of the diverse variety of emerging techniques are based on research-grade instruments, sophisticated reagent-based assays or rely on expertise. Here, we suggest an alternative optical methodology with an easy-to-use and cost-effective instrumentation, which takes advantage of the unique properties of malaria pigment revealed in the present study. Malaria pigment, also called hemozoin, is an insoluble microcrystalline form of heme. We found that these crystallites show remarkable magnetic and optical anisotropy distinctly from any other components of blood. In suspensions they can simultaneously act as magnetically driven micro-rotors and spinning polarizers. These properties can gain fundamental importance not only in the diagnosis of malaria and in therapies, where hemozoin is considered as drug target or immune modulator, but generally in the magnetic ...
Anna M van Eijk, PhD
Funding: The Malaria in Pregnancy Consortium, which is funded through a grant from the Bill & Melinda Gates Foundation to the Liverpool School of Tropical Medicine, UK; US Centers for Disease Control and Prevention; and Wellcome Trust, UK.
Enweronu-Laryea Christabel C
Full Text Available Abstract Background Congenital malaria is defined as malaria parasitaemia in the first week of life. The reported prevalence of congenital malaria in sub-Saharan Africa is variable (0 - 46%. Even though the clinical significance of congenital malaria parasitaemia is uncertain, anti-malarial drugs are empirically prescribed for sick newborns by frontline health care workers. Data on prevalence of congenital malaria in high-risk newborns will inform appropriate drug use and timely referral of sick newborns. Methods Blood samples of untreated newborns less than 1 week of age at the time of referral to Korle Bu Teaching hospital in Accra, Ghana during the peak malaria seasons (April to July of 2008 and 2010 were examined for malaria parasites by, i Giemsa-stained thick and thin blood smears for parasite count and species identification, ii histidine-rich protein- and lactic dehydrogenase-based rapid diagnosis tests, or iii polymerase chain reaction amplification of the merozoite surface protein 2 gene, for identification of sub-microscopic parasitaemia. Other investigations were also done as clinically indicated. Results In 2008, nine cases of Plasmodium falciparum parasitaemia were diagnosed by microscopy in 405 (2.2% newborns. All the nine newborns had low parasite densities (≤50 per microlitre. In 2010, there was no case of parasitaemia by either microscopy or rapid diagnosis tests in 522 newborns; however, 56/467 (12% cases of P. falciparum were detected by polymerase chain reaction. Conclusion Congenital malaria is an uncommon cause of clinical illness in high-risk untreated newborns referred to a tertiary hospital in the first week of life. Empirical anti-malarial drug treatment for sick newborns without laboratory confirmation of parasitaemia is imprudent. Early referral of sick newborns to hospitals with resources and skills for appropriate care is recommended.
Neafsey, D. E.; Waterhouse, R. M.; Abai, M. R.; Aganezov, S. S.; Alekseyev, M. A.; Allen, J. E.; Amon, J.; Arca, B.; Arensburger, P.; Artemov, G.; Assour, L. A.; Basseri, H.; Berlin, A.; Birren, B. W.; Blandin, S. A.; Brockman, A. I.; Burkot, T. R.; Burt, A.; Chan, C. S.; Chauve, C.; Chiu, J. C.; Christensen, M.; Costantini, C.; Davidson, V. L. M.; Deligianni, E.; Dottorini, T.; Dritsou, V.; Gabriel, S. B.; Guelbeogo, W. M.; Hall, A. B.; Han, M. V.; Hlaing, T.; Hughes, D. S. T.; Jenkins, A. M.; Jiang, X.; Jungreis, I.; Kakani, E. G.; Kamali, M.; Kemppainen, P.; Kennedy, R. C.; Kirmitzoglou, I. K.; Koekemoer, L. L.; Laban, N.; Langridge, N.; Lawniczak, M. K. N.; Lirakis, M.; Lobo, N. F.; Lowy, E.; Maccallum, R. M.; Mao, C.; Maslen, G.; Mbogo, C.; Mccarthy, J.; Michel, K.; Mitchell, S. N.; Moore, W.; Murphy, K. A.; Naumenko, A. N.; Nolan, T.; Novoa, E. M.; O'loughlin, S.; Oringanje, C.; Oshaghi, M. A.; Pakpour, N.; Papathanos, P. A.; Peery, A. N.; Povelones, M.; Prakash, A.; Price, D. P.; Rajaraman, A.; Reimer, L. J.; Rinker, D. C.; Rokas, A.; Russell, T. L.; Sagnon, N.; Sharakhova, M. V.; Shea, T.; Simao, F. A.; Simard, F.; Slotman, M. A.; Somboon, P.; Stegniy, V.; Struchiner, C. J.; Thomas, G. W. C.; Tojo, M.; Topalis, P.; Tubio, J. M. C.; Unger, M. F.; Vontas, J.; Walton, C.; Wilding, C. S.; Willis, J. H.; Wu, Y.-c.; Yan, G.; Zdobnov, E. M.; Zhou, X.; Catteruccia, F.; Christophides, G. K.; Collins, F. H.; Cornman, R. S.; Crisanti, A.; Donnelly, M. J.; Emrich, S. J.; Fontaine, M. C.; Gelbart, W.; Hahn, M. W.; Hansen, I. A.; Howell, P. I.; Kafatos, F. C.; Kellis, M.; Lawson, D.; Louis, C.; Luckhart, S.; Muskavitch, M. A. T.; Ribeiro, J. M.; Riehle, M. A.; Sharakhov, I. V.; Tu, Z.; Zwiebel, L. J.; Besansky, N. J.
Variation in vectorial capacity for human malaria among Anopheles mosquito species is determined by many factors, including behavior, immunity, and life history. To investigate the genomic basis of vectorial capacity and explore new avenues for vector control, we sequenced the genomes of 16
Malaria-associated anaemia is a potentially preventable cause of severe morbidity and mortality in children < 5years of age, in areas of high malaria transmission in sub-Saharan Africa. In a cross-sectional study of 3586 children, 80% were anaemic (haemoglobin [Hb]<11g/dL) and 3% had severe anaemia
Full Text Available Background: The pathogenesis of malaria during pregnancy is not fully understood. A proinflammatory cytokine, macrophage migration inhibitory factor (MIF is suggested as a factor involved in the pathogenesis of malaria during pregnancy. Methods: A cross-sectional study was conducted in Medani Hospital, Sudan to investigate MIF levels in placental malaria. Obstetrical and medical characteristics were gathered from each parturient woman using questionnaires. All women (151 were investigated for malaria using blood film and placental histology. MIF levels were measured using ELISA in paired maternal and cord blood samples. Results: There were no P. falciparum-positive blood films obtained from maternal peripheral blood, placenta or cord samples. Out of 151 placentae, four (2.6%, one (0.7%, 32 (21.2% showed acute, chronic and past infection on histopathology examinations respectively, while the rest (114; 75.5% of them showed no signs of infection.There was no significant difference in the median (interquartile of maternal [5.0 (3.7─8.8 vs 6.2(3.5─12.0 ng/ml, P=0.643] and cord [8.1(3.3─16.9 vs 8.3(4.2─16.9, ng/ml, P= 0.601] MIF levels between women with a positive result for placental malaria infection (n=37 and women with a negative result for placental malaria infection (n=114. In regression models placental malaria was not associated with maternal MIF, hemoglobin or birth weight. MIF was not associated with hemoglobin or birth weight. Conclusion: There was no association between maternal and cord MIF levels, placental malaria, maternal hemoglobin and birth weight.
Ashton, Ruth A; Bennett, Adam; Yukich, Joshua; Bhattarai, Achuyt; Keating, Joseph; Eisele, Thomas P
Coverage of malaria control interventions is increasing dramatically across endemic countries. Evaluating the impact of malaria control programs and specific interventions on health indicators is essential to enable countries to select the most effective and appropriate combination of tools to accelerate progress or proceed toward malaria elimination. When key malaria interventions have been proven effective under controlled settings, further evaluations of the impact of the intervention using randomized approaches may not be appropriate or ethical. Alternatives to randomized controlled trials are therefore required for rigorous evaluation under conditions of routine program delivery. Routine health management information system (HMIS) data are a potentially rich source of data for impact evaluation, but have been underused in impact evaluation due to concerns over internal validity, completeness, and potential bias in estimates of program or intervention impact. A range of methodologies were identified that have been used for impact evaluations with malaria outcome indicators generated from HMIS data. Methods used to maximize internal validity of HMIS data are presented, together with recommendations on reducing bias in impact estimates. Interrupted time series and dose-response analyses are proposed as the strongest quasi-experimental impact evaluation designs for analysis of malaria outcome indicators from routine HMIS data. Interrupted time series analysis compares the outcome trend and level before and after the introduction of an intervention, set of interventions or program. The dose-response national platform approach explores associations between intervention coverage or program intensity and the outcome at a subnational (district or health facility catchment) level.
Bødker, Rene; Akida, J.; Shayo, D.
in the Usambara Mountains, Tanzania, from 300 m to 1700 m. Routine entomological collections were made using spray catches and light traps for 15 mo. Direct estimates of entomological inoculation rates and indirect estimates of vectorial capacity suggested a >1000-fold reduction in transmission intensity between...
Valerian L Kiggundu
Full Text Available There is a paucity of data on malaria among hospitalized children in malaria endemic areas. We determined the prevalence, presentation and treatment outcomes of malaria and anemia among children in two hospitals in Rakai, Uganda.Children under five years hospitalized in Kalisizo hospital or Bikira health center in Rakai district, Uganda between May 2011 and May 2012 were enrolled and followed-up until discharge, death or referral. Data were collected on social-demographic characteristics, current and past illnesses and clinical signs and symptoms. Blood smears, hemoglobin (Hgb levels and HIV testing were performed from finger/heel prick blood. The associations between malaria infection and other factors were estimated using log-binomial regression to estimate adjusted prevalence risk ratios (aPRR and 95% confidence intervals (CIs, controlling for clustering at health facilities.2471 children were enrolled. The most common medical presentations were fever (96.2%, cough (61.7%, vomiting (44.2%, diarrhea (20.8%, and seizures (16.0%. The prevalence of malaria parasitemia was 54.6%. Children with malaria were more likely to present with a history of fever (aPRR 2.23; CI 1.18-4.24 and seizures (aPRR 1.12; CI 1.09-1.16. Confirmed malaria was significantly lower among girls than boys (aPRR 0.92; CI 0.91-0.93, HIV infected children (aPRR 0.60 CI 0.52-0.71, and children with diarrhea (aPRR 0.76; CI 0.65-0.90. The overall prevalence of anemia (Hgb<10 g/dl was 56.3% and severe anemia (Hgb<6 g/dL was 17.8%. Among children with severe anemia 76.8% had malaria parasitemia, of whom 93.1% received blood transfusion. Malaria associated mortality was 0.6%.There was a high prevalence of malaria parasitemia and anemia among inpatient children under five years. Malaria prevention is a priority in this population.
Full Text Available Abstract Background Counts of malaria parasites in peripheral blood are important to assess severity of Plasmodium falciparum malaria. Thin and thick smears are routinely used for this purpose. Methods In this study the Binax NOW® Malaria Test, an easy-to-perform rapid diagnostic test, with Histidine Rich Protein-2 (HRP-2 and aldolase as diagnostic markers, was used for semi-quantitative assessment of parasitaemia of P. faciparum. Results In 257 patients with imported P. falciparum malaria, reactivity of aldolase increased with higher parasitaemia. In all patients with a parasitaemia above 50,000 asexual parasites/μl (> 1% co-reactivity of HRP-2 and aldolase was observed. Absence of aldolase reactivity in the presence of HRP-2 was a reliable predictive marker to exclude high (> 1% parasitaemia in P. falciparum malaria. Conclusions Assessment of HRP-2 and aldolase co-reactivity can be of help in clinical decision making in the acute care setting of returning travellers suspected of having malaria.
Ebako Ndip Takem
Full Text Available Pregnant women have a higher risk of malaria compared to non-pregnant women. This review provides an update on knowledge acquired in the past decade on P. falciparum and P.vivax infections in pregnancy. Maternal risk factors for malaria in pregnancy (MiP include low maternal age, low gravidity, and low gestational age. The effects of MIP include maternal anaemia, low birth weight (LBW, preterm delivery and increased infant mortality. P. falciparum infected erythrocytes sequester in the placenta by expressing surface antigens, mainly variant surface antigen (VAR2CSA, that bind to specific receptors, mainly chondroitin sulphate A. In stable transmission settings, the higher malaria risk in primigravidae can be explained by the non recognition of these surface antigens by the immune system. Recently, placental sequestration has been described also for P.vivax infections. The mechanism of preterm delivery and intrauterine growth retardation is not completely understood, but fever (preterm delivery, anaemia, and high cytokines levels have been implicated. Clinical suspicion of MiP should be confirmed by parasitological diagnosis. The sensitivity of microscopy, with placenta histology as the gold standard, is 60% and 45% for peripheral and placental falciparum infections, respectively. Compared to microscopy, RDTs have a lower sensitivity. Insecticide treated nets (ITN and intermittent preventive treatment in pregnancy (IPTp are recommended for the prevention of MiP in stable transmission settings. ITNs have been shown to reduce malaria infection and adverse pregnancy outcomes by 28-47%. Although resistance is a concern, SP has been shown to be equivalent to MQ and AQ for IPTp. For the treatment of uncomplicated malaria, a combination of quinine + clyndamycin is recommended in all trimesters, while artesunate+ clindamycin or any other ACT known to be effective in the region are recommended in the second and third trimesters. For severe
Leang, Rithea; Khu, Naw Htee; Mukaka, Mavuto; Debackere, Mark; Tripura, Rupam; Kheang, Soy Ty; Chy, Say; Kak, Neeraj; Buchy, Philippe; Tarantola, Arnaud; Menard, Didier; Roca-Felterer, Arantxa; Fairhurst, Rick M; Kheng, Sim; Muth, Sinoun; Ngak, Song; Dondorp, Arjen M; White, Nicholas J; Taylor, Walter Robert John
In 2012, the World Health Organization recommended the addition of single low-dose primaquine (SLDPQ, 0.25 mg base/kg body weight) to artemisinin combination therapies to block the transmission of Plasmodium falciparum without testing for glucose-6-phosphate dehydrogenase deficiency. The targeted group was non-pregnant patients aged ≥ 1 year (later changed to ≥ 6 months) with acute uncomplicated falciparum malaria, primarily in countries with artemisinin-resistant P. falciparum (ARPf). No dosing regimen was suggested, leaving malaria control programmes and clinicians in limbo. Therefore, we designed a user-friendly, age-based SLDPQ regimen for Cambodia, the country most affected by ARPf. By reviewing primaquine's pharmacology, we defined a therapeutic dose range of 0.15-0.38 mg base/kg (9-22.5 mg in a 60-kg adult) for a therapeutic index of 2.5. Primaquine doses (1-20 mg) were tested using a modelled, anthropometric database of 28,138 Cambodian individuals (22,772 healthy, 4119 with malaria and 1247 with other infections); age distributions were: 0.5-4 years (20.0 %, n = 5640), 5-12 years (9.1 %, n = 2559), 13-17 years (9.1 %, n = 2550), and ≥ 18 years (61.8 %, n = 17,389). Optimal age-dosing groups were selected according to calculated mg base/kg doses and proportions of individuals receiving a therapeutic dose. Four age-dosing bands were defined: (1) 0.5-4 years, (2) 5-9 years, (3) 10-14 years, and (4) ≥15 years to receive 2.5, 5, 7.5, and 15 mg of primaquine base, resulting in therapeutic doses in 97.4 % (5494/5640), 90.5 % (1511/1669), 97.7 % (1473/1508), and 95.7 % (18,489/19,321) of individuals, respectively. Corresponding median (1st-99th centiles) mg base/kg doses of primaquine were (1) 0.23 (0.15-0.38), (2) 0.29 (0.18-0.45), (3) 0.27 (0.15-0.39), and (4) 0.29 (0.20-0.42). This age-based SLDPQ regimen could contribute substantially to malaria elimination and requires urgent evaluation in Cambodia and
Philippa A West
Full Text Available Insecticide treated nets (ITNs and indoor residual spraying (IRS are effective vector control tools that protect against malaria. There is conflicting evidence regarding whether using ITNs and IRS in combination provides additional benefit over using either of these methods alone. This study investigated factors that may modify the effect of the combined use of IRS and ITNs compared to using ITNs alone on malaria infection prevalence.Secondary analysis was carried out on data from a cluster randomised trial in north-west Tanzania. 50 clusters received ITNs from a universal coverage campaign; of these 25 were randomly allocated to additionally receive two rounds of IRS in 2012. In cross-sectional household surveys children 0.5-14 years old were tested for Plasmodium falciparum infections (PfPR two, six and ten months after the first IRS round.IRS protected those sleeping under nets (OR = 0.38, 95%CI 0.26-0.57 and those who did not (OR = 0.43, 95%CI 0.29-0.63. The protective effect of IRS was not modified by community level ITN use (ITN use = 50%, OR = 0.46, 95%CI 0.28-0.74. The additional protection from IRS was similar in low (<10% PfPR, OR = 0.38, 95%CI 0.19-0.75 and high transmission areas (≥10% PfPR, OR = 0.34, 95%CI 0.18-0.67. ITN use was protective at the individual-level regardless of whether the village had been sprayed (OR = 0.83, 95%CI 0.70-0.98. Living in a sprayed village was protective regardless of whether the individual slept under an ITN last night (OR = 0.41, 95%CI 0.29-0.58.Implementing IRS in addition to ITNs was beneficial for individuals from villages with a wide range of transmission intensities and net utilisation levels. Net users received additional protection from IRS. ITNs were providing some individual protection, even in this area with high levels of pyrethroid insecticide resistance. These results demonstrate that there is a supplementary benefit of IRS even when ITNs are effective.ClinicalTrials.gov NCT01697852.
Full Text Available Abstract Background Malaria has a negative effect on pregnancy outcome, causing low birth weight, premature birth and stillbirths, particularly in areas with high malaria transmission. In Rwanda, malaria transmission intensity ranges from high to nil, probably associated with variable altitudes. Overall, the incidence decreased over the last six years (2002–2007. Therefore, the impact of malaria on birth outcomes is also expected to vary over time and space. Methods Obstetric indicators (birth weight and pregnancy outcome and malaria incidence were compared and analyzed to their association over time (2002–2007 and space. Birth data from 12,526 deliveries were collected from maternity registers of 11 different primary health centers located in different malaria endemic areas. Malaria data for the same communities were collected from the National Malaria Control Programme. Associations were sought with mixed effects models and logistic regression. Results In all health centres, a significant increase of birth weight over the years was observed (p Conclusion In Rwanda, birth weight and pregnancy outcome are not directly influenced by malaria, which is in contrast to many other studied areas. Although malaria incidence overall has declined and mean birth weight increased over the studied period, no direct association was found between the two. Socio-economic factors and improved nutrition could be responsible for birth weight changes in recent years.
Smithuis, Frank M; Kyaw, Moe Kyaw; Phe, U Ohn; van der Broek, Ingrid; Katterman, Nina; Rogers, Colin; Almeida, Patrick; Kager, Piet A; Stepniewska, Kasia; Lubell, Yoel; Simpson, Julie A; White, Nicholas J
Insecticide-treated bed nets (ITN) reduce malaria morbidity and mortality consistently in Africa, but their benefits have been less consistent in Asia. This study's objective was to evaluate the malaria protective efficacy of village-wide usage of ITN in Western Myanmar and estimate the cost-effectiveness of ITN compared with extending early diagnosis and treatment services. A cluster-randomized controlled trial was conducted in Rakhine State to assess the efficacy of ITNs in preventing malaria and anaemia in children and their secondary effects on nutrition and development. The data were aggregated for each village to obtain cluster-level infection rates. In total 8,175 children under 10 years of age were followed up for 10 months, which included the main malaria transmission period. The incidence and prevalence of Plasmodium falciparum and Plasmodium vivax infections, and the biting behaviour of Anopheles mosquitoes in the area were studied concurrently. The trial data along with costs for current recommended treatment practices were modelled to estimate the cost-effectiveness of ITNs compared with, or in addition to extending the coverage of early diagnosis and treatment services. In aggregate, malaria infections, spleen rates, haemoglobin concentrations, and weight for height, did not differ significantly during the study period between villages with and without ITNs, with a weighted mean difference of -2.6 P. falciparum episodes per 1,000 weeks at risk (95% Confidence Interval -7 to 1.8). In areas with a higher incidence of malaria there was some evidence ITN protective efficacy. The economic analysis indicated that, despite the uncertainty and variability in their protective efficacy in the different study sites, ITN could still be cost-effective, but not if they displaced funding for early diagnosis and effective treatment which is substantially more cost-effective. In Western Myanmar deployment of ITNs did not provide consistent protection against malaria
Greenwood Brian M
Full Text Available Abstract Research on malaria vaccines is currently directed primarily towards the development of vaccines that prevent clinical malaria. Malaria elimination, now being considered seriously in some epidemiological situations, requires a different vaccine strategy, since success will depend on killing all parasites in the community in order to stop transmission completely. The feature of the life-cycles of human malarias that presents the greatest challenge to an elimination programme is the persistence of parasites as asymptomatic infections. These are an important source from which transmission to mosquitoes can occur. Consequently, an elimination strategy requires a community-based approach covering all individuals and not just those who are susceptible to clinical malaria. The progress that has been made in development of candidate malaria vaccines is reviewed. It is unlikely that many of these will have the efficacy required for complete elimination of parasites, though they may have an important role to play as part of future integrated control programmes. Vaccines for elimination must have a high level of efficacy in order to stop transmission to mosquitoes. This might be achieved with some pre-erythrocytic stage candidate vaccines or by targeting the sexual stages directly with transmission-blocking vaccines. An expanded malaria vaccine programme with such objectives is now a priority.
Litzenberger, Wayne; Lava, Val
References are contained for HVDC systems, converter stations and components, overhead transmission lines, cable transmission, system design and operations, simulation of high voltage direct current systems, high-voltage direct current installations, and flexible AC transmission system (FACTS).
Reader, Janette; Botha, Mariëtte; Theron, Anjo; Lauterbach, Sonja B; Rossouw, Claire; Engelbrecht, Dewaldt; Wepener, Melanie; Smit, Annél; Leroy, Didier; Mancama, Dalu; Coetzer, Theresa L; Birkholtz, Lyn-Marie
The discovery of malaria transmission-blocking compounds is seen as key to malaria elimination strategies and gametocyte-screening platforms are critical filters to identify active molecules. However, unlike asexual parasite assays measuring parasite proliferation, greater variability in end-point readout exists between different gametocytocidal assays. This is compounded by difficulties in routinely producing viable, functional and stage-specific gametocyte populations. Here, a parallel evaluation of four assay platforms on the same gametocyte populations was performed for the first time. This allowed the direct comparison of the ability of different assay platforms to detect compounds with gametocytocidal activity and revealed caveats in some assay readouts that interrogate different parasite biological functions. Gametocytogenesis from Plasmodium falciparum (NF54) was optimized with a robust and standardized protocol. ATP, pLDH, luciferase reporter and PrestoBlue® assays were compared in context of a set of 10 reference compounds. The assays were performed in parallel on the same gametocyte preparation (except for luciferase reporter lines) using the same drug preparations (48 h). The remaining parameters for each assay were all comparable. A highly robust method for generating viable and functional gametocytes was developed and comprehensively validated resulting in an average gametocytaemia of 4%. Subsequent parallel assays for gametocytocidal activity indicated that different assay platforms were not able to screen compounds with variant chemical scaffolds similarly. Luciferase reporter assays revealed that synchronized stage-specific gametocyte production is essential for drug discovery, as differential susceptibility in various gametocyte developmental populations is evident. With this study, the key parameters for assays aiming at testing the gametocytocidal activity of potential transmission blocking molecules against Plasmodium gametocytes were
Malaria transmission rates and risks can be greatly reduced by vector control, mitigating high malaria incidence and prevalence rates. Methods and strategies for malaria vector control (MVC) have been well documented by WHO, although its implementation varies widely. Technical guidelines for MVC strategies and materials are readily available, but the status and role of MVC have not been reviewed and redefined in terms of programme management and resource allocation. There are huge changes since November 1993 when the last WHO Study Group reviewed vector control for malaria and other mosquito-borne diseases, following the 1992 adoption of the Global Malaria Control Strategy. Operationally, with reform of the health sector in many countries, the centrally managed and vertically structured malaria control programme (MCP) has been superseded by a community-based and decentralized one. This poses challenges for effective implementation of MVC strategies. Therefore it became evident that the role of vector control in malaria control needs to be reconsidered to develop a strategic framework for MVC implementation by national malaria control programmes and other partners. This report of a WHO Study Group on Malaria Vector Control and Personal Protection reviewed the current vector control strategies and their effectiveness in various operational and eco-epidemiological settings, and identified challenges for implementation in different health systems. An outline strategic framework for strengthening malaria vector control implementation was developed. The process of deciding about which mosquito control method is appropriate in a given situation should be guided by an analysis of the level of malaria endemicity and vector bionomics, the eco-epidemiological setting, the health management system and an estimate of the programme sustainability. This report also provides a basis for the development of a strategic framework for strengthening malaria vector control
Mota Maria M
Full Text Available Abstract Background The Plasmodium Cysteine Repeat Modular Proteins (PCRMP are a family of four conserved proteins of malaria parasites, that contain a number of motifs implicated in host-parasite interactions. Analysis of mutants of the rodent parasite Plasmodium berghei lacking expression of PCRMP1 or 2 showed that these proteins are essential for targeting of P. berghei sporozoites to the mosquito salivary gland and, hence, for transmission from the mosquito to the mouse. Methods In this work, the role of the remaining PCRMP family members, PCRMP3 and 4, has been investigated throughout the Plasmodium life cycle by generation and analysis of P. berghei gene deletion mutants, Δpcrmp3 and Δpcrmp4. The role of PCRMP members during the transmission and hepatic stages of the Plasmodium lifecycle has been evaluated by light- and electron microscopy and by analysis of liver stage development in HEPG2 cells in vitro and by infecting mice with mutant sporozoites. In addition, mice were immunized with live Δpcrmp3 and Δpcrmp4 sporozoites to evaluate their immunization potential as a genetically-attenuated parasite-based vaccine. Results Disruption of pcrmp3 and pcrmp4 in P. berghei revealed that they are also essential for transmission of the parasite through the mosquito vector, although acting in a distinct way to pbcrmp1 and 2. Mutants lacking expression of PCRMP3 or PCRMP4 show normal blood stage development and oocyst formation in the mosquito and develop into morphologically normal sporozoites, but these have a defect in egress from oocysts and do not enter the salivary glands. Sporozoites extracted from oocysts perform gliding motility and invade and infect hepatocytes but do not undergo further development and proliferation. Furthermore, the study shows that immunization with Δcrmp3 and Δcrmp4 sporozoites does not confer protective immunity upon subsequent challenge. Conclusions PCRMP3 and 4 play multiple roles during the Plasmodium life
Huho, Bernadette J.; Killeen, Gerard F.; Ferguson, Heather M.; Tami, Adriana; Lengeler, Christian; Charlwood, J. Derek; Kihonda, Aniset; Kihonda, Japhet; Kachur, S. Patrick; Smith, Thomas A.; Abdulla, Salim M. K.
Background: Artemisinin-based combination therapy (ACT) for treating malaria has activity against immature gametocytes. In theory, this property may complement the effect of terminating otherwise lengthy malaria infections and reducing the parasite reservoir in the human population that can infect
van Eijk, Anna M.; Hill, Jenny; Noor, Abdisalan M.; Snow, Robert W.; ter Kuile, Feiko O.
Background In malarious areas, pregnant women are more likely to have detectable malaria than are their nonpregnant peers, and the excess risk of infection varies with gravidity. Pregnant women attending antenatal clinic for their first visit are a potential pragmatic sentinel group to track the
de Oliveira, Elaine Cristina; dos Santos, Emerson Soares; Zeilhofer, Peter; Souza-Santos, Reinaldo; Atanaka-Santos, Marina
In Brazil, 99% of the cases of malaria are concentrated in the Amazon region, with high level of transmission. The objectives of the study were to use geographic information systems (GIS) analysis and logistic regression as a tool to identify and analyse the relative likelihood and its socio-environmental determinants of malaria infection in the Vale do Amanhecer rural settlement, Brazil. A GIS database of georeferenced malaria cases, recorded in 2005, and multiple explanatory data layers was built, based on a multispectral Landsat 5 TM image, digital map of the settlement blocks and a SRTM digital elevation model. Satellite imagery was used to map the spatial patterns of land use and cover (LUC) and to derive spectral indices of vegetation density (NDVI) and soil/vegetation humidity (VSHI). An Euclidian distance operator was applied to measure proximity of domiciles to potential mosquito breeding habitats and gold mining areas. The malaria risk model was generated by multiple logistic regression, in which environmental factors were considered as independent variables and the number of cases, binarized by a threshold value was the dependent variable. Out of a total of 336 cases of malaria, 133 positive slides were from inhabitants at Road 08, which corresponds to 37.60% of the notifications. The southern region of the settlement presented 276 cases and a greater number of domiciles in which more than ten cases/home were notified. From these, 102 (30.36%) cases were caused by Plasmodium falciparum and 174 (51.79%) cases by Plasmodium vivax. Malaria risk is the highest in the south of the settlement, associated with proximity to gold mining sites, intense land use, high levels of soil/vegetation humidity and low vegetation density. Mid-resolution, remote sensing data and GIS-derived distance measures can be successfully combined with digital maps of the housing location of (non-) infected inhabitants to predict relative likelihood of disease infection through the
Levine, Rebecca S; Peterson, A Townsend; Benedict, Mark Q
The Anopheles quadrimaculatus s.l. (Say) complex consists of at least five species distinguished by distribution, genetic incompatibility, and allele frequencies. However, the distributions of the members have only been described by collection locations. Building on this information and environmental data, preliminary predictions of their distribution were produced using a genetic algorithm and point occurrence data. Based on resulting predicted border areas and undersampled regions, we obtained and analyzed additional geo-referenced specimens and compared their distribution with our preliminary predictions. We found good agreement between the preliminary predictions and the subsequent collections, regardless of the fact that additional specimens were deliberately sought from areas most likely to reveal inconsistencies. Final predicted distributions describe widespread distribution of A.quadrimaculatus throughout the eastern United States. A. maverlius and A. smaragdinus have similar predicted ranges limited to the southeastern United States. The predicted ranges of the sister taxa A. diluvialis and A. inundatus were similar to one another along the southeastern coast even though they seem to be allopatric. The historical role of A. quadrimaculatus s.l. in transmission of malaria was also examined. We conclude that A. quadrimaculatus s.s. was the only species of the complex capable of vectoring malaria in the United States throughout the area in which malaria occurred. However, any or all the members of the complex may have been regionally important, particularly in areas of most intense transmission.
Assessing the effects of global warming and local social and economic conditions on the malaria transmission Quantificando os efeitos do aquecimento global e das condições socioeconômicas locais na transmissão de malária
Hyun M Yang
Full Text Available OBJECTIVE: To show how a mathematical model can be used to describe and to understand the malaria transmission. METHODS: The effects on malaria transmission due to the impact of the global temperature changes and prevailing social and economic conditions in a community were assessed based on a previously presented compartmental model, which describes the overall transmission of malaria. RESULTS/CONCLUSIONS: The assessments were made from the scenarios produced by the model both in steady state and dynamic analyses. Depending on the risk level of malaria, the effects on malaria transmission can be predicted by the temperature ambient or local social and-economic conditions.OBJETIVO: Apresenta-se um modelo matemático mostrando como esse instrumento pode ser importante para descrever a transmissão de malária. MÉTODOS: Baseado no modelo proposto previamente, foram quantificados os efeitos de dois fatores que podem afetar a transmissão da malaria: a temperatura ambiente e as condições socioeconômicas locais. RESULTADOS/CONCLUSÕES: A quantificação foi feita estudando o modelo proposto no estado estacionário e na sua dinâmica. Dependendo do nível de risco de malária, os principais efeitos na transmissão de malária são devidos à temperatura ambiente ou às condições socioeconômicas.
with other vectors playing a secondary role in malaria transmission. Malaria interventions need to be strengthened to reduce even further the malaria transmission in the area. Keywords: malaria, mosquito, composition, larval habitats, Rwanda. Introduction. Malaria remains a leading cause of mortality and morbidity ...
Keïta, M; Baber, I; Sogoba, N; Maïga, H M; Diallo, M'b; Doumbia, S; Traoré, S F
A better understanding of malaria transmission dynamics is an essential element in the development of any targeted vector control strategy. The objective of this study was to better understand malaria transmission dynamics along the Niger River in Sudan savanna zone of Mali. Trough cross-sectional surveys, Anopheline larvae were collected by WHO standard dipping technique, and vector adults by Human Landing and pyrethrum spray catches methods. The vector population was composed of An. gambiae s.l. (> 99%) and An. funestus (hamlet Fourda) compared to farther inland Kéniéroba. The average infection rate of An. gambiae s.l. was 3.63% and 4.06% in Kéniéroba and Fourda respectively. The average entomological inoculation rate (EIR) during the study period was almost similar in Kéniéroba (0.70 infective bites/person/month) and Fourda (0.69 infective bites/person/month). The means EIRs over each of the rainy season 2006 and 2007 were always higher than the one of the dry season 2007 in both localities, with much smaller amplitude in Fourda than in Kéniéroba. However, the level of the transmission was 2.31 (0.37/0.16) times higher in Fourda than in Kéniéroba during the dry season.We conclude that in Sudan savanna zone of Mali, malaria transmission along the river is continuous throughout the year, but it is more intense in the immediate vicinity of the river during the dry season than during the rainy season in opposition to more distant localities to the river and vector control should not be focused only on the rainy in such setting.
Cui, Liwang; Yan, Guiyun; Sattabongkot, Jetsumon; Cao, Yaming; Chen, Bin; Chen, Xiaoguang; Fan, Qi; Fang, Qiang; Jongwutiwes, Somchai; Parker, Daniel; Sirichaisinthop, Jeeraphat; Kyaw, Myat Phone; Su, Xin-zhuan; Yang, Henglin; Yang, Zhaoqing; Wang, Baomin; Xu, Jianwei; Zheng, Bin; Zhong, Daibin; Zhou, Guofa
The Greater Mekong Subregion (GMS), comprised of six countries including Cambodia, China's Yunnan Province, Lao PDR, Myanmar (Burma), Thailand and Vietnam, is one of the most threatening foci of malaria. Since the initiation of the WHO's Mekong Malaria Program a decade ago, malaria situation in the GMS has greatly improved, reflected in the continuous decline in annual malaria incidence and deaths. However, as many nations are moving towards malaria elimination, the GMS nations still face great challenges. Malaria epidemiology in this region exhibits enormous geographical heterogeneity with Myanmar and Cambodia remaining high-burden countries. Within each country, malaria distribution is also patchy, exemplified by ‘border malaria’ and ‘forest malaria’ with high transmission occurring along international borders and in forests or forest fringes, respectively. ‘Border malaria’ is extremely difficult to monitor, and frequent malaria introductions by migratory human populations constitute a major threat to neighboring, malaria-eliminating countries. Therefore, coordination between neighboring countries is essential for malaria elimination from the entire region. In addition to these operational difficulties, malaria control in the GMS also encounters several technological challenges. Contemporary malaria control measures rely heavily on effective chemotherapy and insecticide control of vector mosquitoes. However, the spread of multidrug resistance and potential emergence of artemisinin resistance in Plasmodium falciparum make resistance management a high priority in the GMS. This situation is further worsened by the circulation of counterfeit and substandard artemisinin-related drugs. In most endemic areas of the GMS, P. falciparum and P. vivax coexist, and in recent malaria control history, P. vivax has demonstrated remarkable resilience to control measures. Deployment of the only registered drug (primaquine) for the radical cure of vivax malaria is
Okami, Suguru; Kohtake, Naohiko
The disease burden of malaria has decreased as malaria elimination efforts progress. The mapping approach that uses spatial risk distribution modeling needs some adjustment and reinvestigation in accordance with situational changes. Here we applied a mathematical modeling approach for standardized morbidity ratio (SMR) calculated by annual parasite incidence using routinely aggregated surveillance reports, environmental data such as remote sensing data, and non-environmental anthropogenic data to create fine-scale spatial risk distribution maps of western Cambodia. Furthermore, we incorporated a combination of containment status indicators into the model to demonstrate spatial heterogeneities of the relationship between containment status and risks. The explanatory model was fitted to estimate the SMR of each area (adjusted Pearson correlation coefficient R2 = 0.774; Akaike information criterion AIC = 149.423). A Bayesian modeling framework was applied to estimate the uncertainty of the model and cross-scale predictions. Fine-scale maps were created by the spatial interpolation of estimated SMRs at each village. Compared with geocoded case data, corresponding predicted values showed conformity [Spearman's rank correlation r = 0.662 in the inverse distance weighed interpolation and 0.645 in ordinal kriging (95% confidence intervals of 0.414-0.827 and 0.368-0.813, respectively), Welch's t-test; Not significant]. The proposed approach successfully explained regional malaria risks and fine-scale risk maps were created under low-to-moderate malaria transmission settings where reinvestigations of existing risk modeling approaches were needed. Moreover, different representations of simulated outcomes of containment status indicators for respective areas provided useful insights for tailored interventional planning, considering regional malaria endemicity.
Full Text Available The disease burden of malaria has decreased as malaria elimination efforts progress. The mapping approach that uses spatial risk distribution modeling needs some adjustment and reinvestigation in accordance with situational changes. Here we applied a mathematical modeling approach for standardized morbidity ratio (SMR calculated by annual parasite incidence using routinely aggregated surveillance reports, environmental data such as remote sensing data, and non-environmental anthropogenic data to create fine-scale spatial risk distribution maps of western Cambodia. Furthermore, we incorporated a combination of containment status indicators into the model to demonstrate spatial heterogeneities of the relationship between containment status and risks. The explanatory model was fitted to estimate the SMR of each area (adjusted Pearson correlation coefficient R2 = 0.774; Akaike information criterion AIC = 149.423. A Bayesian modeling framework was applied to estimate the uncertainty of the model and cross-scale predictions. Fine-scale maps were created by the spatial interpolation of estimated SMRs at each village. Compared with geocoded case data, corresponding predicted values showed conformity [Spearman's rank correlation r = 0.662 in the inverse distance weighed interpolation and 0.645 in ordinal kriging (95% confidence intervals of 0.414-0.827 and 0.368-0.813, respectively, Welch's t-test; Not significant]. The proposed approach successfully explained regional malaria risks and fine-scale risk maps were created under low-to-moderate malaria transmission settings where reinvestigations of existing risk modeling approaches were needed. Moreover, different representations of simulated outcomes of containment status indicators for respective areas provided useful insights for tailored interventional planning, considering regional malaria endemicity.
Full Text Available Malaria is one of the most widespread parasitic infection in Asian countries affecting the poor of the poor. In an effort to develop an effective vaccine for the treatment of malaria, various attempts are being made worldwide. If successful, such a vaccine can be effective for treatment of both Plasmodium vivax and Plasmodium falciparum. This would also be able to avoid complications such as drug resistance, resistance to insecticides, nonadherence to the treatment schedule, and eventually high cost of treatment in the resource-limited settings. In the current compilation, the details from the literature were collected by using PubMed and Medline as search engines and searched for terms such as malaria, vaccine, and malaria treatment. This review collates and provides glimpses of the information on the recent malaria vaccine development. The reader will be taken through the historical perspective followed by the approaches to the malaria vaccine development from pre-erythrocytic stage vaccines, asexual stage vaccines, transmission blocking vaccines, etc. Looking at the current scenario of the malaria and treatment strategies, it is an absolute need of an hour that an effective malaria vaccine should be developed. This would bring a revolutionary breakthrough in the treatment modalities especially when there is increasing emergence of resistance to existing drug therapy. It would be of great purpose to serve those living in malaria endemic region and also for travelers which are nonimmune and coming to malaria endemic region. As infection by P. vivax is more prevalent in India and other Asian subcontinent and is often prominent in areas where elimination is being attempted, special consideration is required of the role of vaccines in blocking transmission, regardless of the stages being targeted. Development of vaccines is feasible but with the support of private sector and government organization in terms of regulatory and most importantly
Althouse, B M; Hammitt, L L; Grant, L; Wagner, B G; Reid, R; Larzelere-Hinton, F; Weatherholtz, R; Klugman, K P; Rodgers, G L; O'Brien, K L; Hu, H
Identifying the transmission sources and reservoirs of Streptococcus pneumoniae (SP) is a long-standing question for pneumococcal epidemiology, transmission dynamics, and vaccine policy. Here we use serotype to identify SP transmission and examine acquisitions (in the same household, local community, and county, or of unidentified origin) in a longitudinal cohort of children and adults from the Navajo Nation and the White Mountain Apache American Indian Tribes. We found that adults acquire SP relatively more in the household than other age groups, and children 2-8 years old typically acquire in their own or surrounding communities. Age-specific transmission probability matrices show that transmissions within household were mostly seen from older to younger siblings. Outside the household, children most often transmit to other children in the same age group, showing age-assortative mixing behavior. We find toddlers and older children to be most involved in SP transmission and acquisition, indicating their role as key drivers of SP epidemiology. Although infants have high carriage prevalence, they do not play a central role in transmission of SP compared with toddlers and older children. Our results are relevant to inform alternative pneumococcal conjugate vaccine dosing strategies and analytic efforts to inform optimization of vaccine programs, as well as assessing the transmission dynamics of pathogens transmitted by close contact in general.
Assessment of the effect of larval source management and house improvement on malaria transmission when added to standard malaria control strategies in southern Malawi: study protocol for a cluster-randomised controlled trial.
McCann, Robert S; van den Berg, Henk; Diggle, Peter J; van Vugt, Michèle; Terlouw, Dianne J; Phiri, Kamija S; Di Pasquale, Aurelio; Maire, Nicolas; Gowelo, Steven; Mburu, Monicah M; Kabaghe, Alinune N; Mzilahowa, Themba; Chipeta, Michael G; Takken, Willem
Due to outdoor and residual transmission and insecticide resistance, long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) will be insufficient as stand-alone malaria vector control interventions in many settings as programmes shift toward malaria elimination. Combining additional vector control interventions as part of an integrated strategy would potentially overcome these challenges. Larval source management (LSM) and structural house improvements (HI) are appealing as additional components of an integrated vector management plan because of their long histories of use, evidence on effectiveness in appropriate settings, and unique modes of action compared to LLINs and IRS. Implementation of LSM and HI through a community-based approach could provide a path for rolling-out these interventions sustainably and on a large scale. We will implement community-based LSM and HI, as additional interventions to the current national malaria control strategies, using a randomised block, 2 × 2 factorial, cluster-randomised design in rural, southern Malawi. These interventions will be continued for two years. The trial catchment area covers about 25,000 people living in 65 villages. Community participation is encouraged by training community volunteers as health animators, and supporting the organisation of village-level committees in collaboration with The Hunger Project, a non-governmental organisation. Household-level cross-sectional surveys, including parasitological and entomological sampling, will be conducted on a rolling, 2-monthly schedule to measure outcomes over two years (2016 to 2018). Coverage of LSM and HI will also be assessed throughout the trial area. Combining LSM and/or HI together with the interventions currently implemented by the Malawi National Malaria Control Programme is anticipated to reduce malaria transmission below the level reached by current interventions alone. Implementation of LSM and HI through a community
Wangdi, Kinley; Kaewkungwal, Jaranit; Singhasivanon, Pratap; Silawan, Tassanee; Lawpoolsri, Saranath; White, Nicholas J
At the verge of elimination of malaria in Bhutan, this study was carried out to analyse the trend of malaria in the endemic districts of Bhutan and to identify malaria clusters at the sub-districts. The findings would aid in implementing the control activities. Poisson regression was performed to study the trend of malaria incidences at district level from 1994 to 2008. Spatial Empirical Bayesian smoothing was deployed to identify clusters of malaria at the sub-district level from 2004 to 2008. Trend of the overall districts and most of the endemic districts have decreased except Pemagatshel, which has an increase in the trend. Spatial cluster-outlier analysis showed that malaria clusters were mostly concentrated in the central and eastern Bhutan in three districts of Dagana, Samdrup Jongkhar and Sarpang. The disease clusters were reported throughout the year. Clusters extended to the non-transmission areas in the eastern Bhutan. There is significant decrease in the trend of malaria with the elimination at the sight. The decrease in the trend can be attributed to the success of the control and preventive measures. In order to realize the target of elimination of malaria, the control measure needs to be prioritized in these high-risk clusters of malaria.
Full Text Available Abstract Background At the verge of elimination of malaria in Bhutan, this study was carried out to analyse the trend of malaria in the endemic districts of Bhutan and to identify malaria clusters at the sub-districts. The findings would aid in implementing the control activities. Poisson regression was performed to study the trend of malaria incidences at district level from 1994 to 2008. Spatial Empirical Bayesian smoothing was deployed to identify clusters of malaria at the sub-district level from 2004 to 2008. Results Trend of the overall districts and most of the endemic districts have decreased except Pemagatshel, which has an increase in the trend. Spatial cluster-outlier analysis showed that malaria clusters were mostly concentrated in the central and eastern Bhutan in three districts of Dagana, Samdrup Jongkhar and Sarpang. The disease clusters were reported throughout the year. Clusters extended to the non-transmission areas in the eastern Bhutan. Conclusions There is significant decrease in the trend of malaria with the elimination at the sight. The decrease in the trend can be attributed to the success of the control and preventive measures. In order to realize the target of elimination of malaria, the control measure needs to be prioritized in these high-risk clusters of malaria.
Malaria is a serious parasitic disease in the developing world, causing high morbidity and mortality. The pathogenesis of malaria is complex, and the clinical presentation of disease ranges from severe and complicated, to mild and uncomplicated, to asymptomatic malaria. Despite a wealth of studies on the clinical severity of disease, asymptomatic malaria infections are still poorly understood. Asymptomatic malaria remains a challenge for malaria control programs as it significantly influences transmission dynamics. A thorough understanding of the interaction between hosts and parasites in the development of different clinical outcomes is required. In this review, the problems and obstacles to the study and control of asymptomatic malaria are discussed. The human and parasite factors associated with differential clinical outcomes are described and the management and treatment strategies for the control of the disease are outlined. Further, the crucial gaps in the knowledge of asymptomatic malaria that should be the focus of future research towards development of more effective malaria control strategies are highlighted. PMID:22289302
Full Text Available Dari tahun 1979 sampai dengan 1981 dilaksanakan penelitian epidemiologi malaria disuatu daerah hypo-endemis di Kalimantan Selatan. Sebagian dari penelitian yang dilaporkan di sini, menilai hasil penyemprotan rumah dengan DDT yang dilaksanakan secara rutin oleh Dinas Kesehatan Propinsi serta menilai intervensi yang diadakan atas dasar epidemiologi setempat. Daerah transmigrasi Batutungku disemprot secara rutin dan hasilnya dibandingkan dengan Panyipatan, suatu desa yang tidak disemprot. Hasil surveillance menunjukkan bahwa incidence rate tiap tahun selama tiga tahun penelitian di kedua daerah turunnya sama : di Batutungku dari 10,20/00 menjadi 8,70/00 pada tahun 1980 dan 5,30/00 pada tahun 1981, dan di Panyipatan dari 16,60/00 menjadi 14,60/00 pada tahun 1980 dan 7,70/00 pada tahun 1981. Fluktuasi kepadatan An. nigerrimus dan An. peditaeniatus, dua species anopheles yang paling banyak tertangkap di daerah penelitian, juga tidak menunjukkan adanya perbedaan di kedua daerah. Dengan incidence rate dan data entomologis ini, dibuktikan bahwa penyemprotan rumah-rumah di Batutungku tidak efektif. Bahwa di kedua daerah incidence rate tiap tahun menurun, disebabkan oleh ''radical treatment' yang dimulai di kedua daerah sejak Oktober 1979. ''Mass treatment "di dua R W di Batutungku di mana incidence malaria per bulan lebih tinggi daripada lain-lain R W, dapat menekan malaria transmisi.
Verhave, Jan Peter
When Plasmodium vivax tertian malaria was prevalent in The Netherlands, the use of therapeutic malaria for the treatment of neurosyphilis patients presented an opportunity for biological studies of the parasite's behaviour, in healthy volunteers. One unexplained phenomenon was the long latency between natural exposure to a single infected mosquito and the appearance of clinical signs (average 8 months). Dutch studies with volunteers and syphilis patients, suggested that hundreds of sporozoites transmitted by several mosquito bites were enough to provoke an early attack, known from tropical vivax-malaria. Sporozoites appeared to be programmed either to delay their pre-erythrocytic development or to proceed to an early attack within three weeks. The number of infectious bites also determined the relapse rate and the number of relapses after a primary attack. Analyses of primary cases and relapses from the previous year were used to predict the incidence for the next year. These historic findings fit well with recent studies on genotyping of blood stages during primary attacks and relapses. External factors (i.e. the milieu inside the human host) may trigger hypnozoites to reactivate, but predetermined periods of latency should also be considered.
Verhave Jan Peter
Full Text Available Abstract When Plasmodium vivax tertian malaria was prevalent in The Netherlands, the use of therapeutic malaria for the treatment of neurosyphilis patients presented an opportunity for biological studies of the parasite’s behaviour, in healthy volunteers. One unexplained phenomenon was the long latency between natural exposure to a single infected mosquito and the appearance of clinical signs (average 8 months. Dutch studies with volunteers and syphilis patients, suggested that hundreds of sporozoites transmitted by several mosquito bites were enough to provoke an early attack, known from tropical vivax-malaria. Sporozoites appeared to be programmed either to delay their pre-erythrocytic development or to proceed to an early attack within three weeks. The number of infectious bites also determined the relapse rate and the number of relapses after a primary attack. Analyses of primary cases and relapses from the previous year were used to predict the incidence for the next year. These historic findings fit well with recent studies on genotyping of blood stages during primary attacks and relapses. External factors (i.e. the milieu inside the human host may trigger hypnozoites to reactivate, but predetermined periods of latency should also be considered.
Laneri, Karina; Paul, Richard E; Tall, Adama; Faye, Joseph; Diene-Sarr, Fatoumata; Sokhna, Cheikh; Trape, Jean-François; Rodó, Xavier
Assessing the influence of climate on the incidence of Plasmodium falciparum malaria worldwide and how it might impact local malaria dynamics is complex and extrapolation to other settings or future times is controversial. This is especially true in the light of the particularities of the short- and long-term immune responses to infection. In sites of epidemic malaria transmission, it is widely accepted that climate plays an important role in driving malaria outbreaks. However, little is known about the role of climate in endemic settings where clinical immunity develops early in life. To disentangle these differences among high- and low-transmission settings we applied a dynamical model to two unique adjacent cohorts of mesoendemic seasonal and holoendemic perennial malaria transmission in Senegal followed for two decades, recording daily P. falciparum cases. As both cohorts are subject to similar meteorological conditions, we were able to analyze the relevance of different immunological mechanisms compared with climatic forcing in malaria transmission. Transmission was first modeled by using similarly unique datasets of entomological inoculation rate. A stochastic nonlinear human-mosquito model that includes rainfall and temperature covariates, drug treatment periods, and population variability is capable of simulating the complete dynamics of reported malaria cases for both villages. We found that under moderate transmission intensity climate is crucial; however, under high endemicity the development of clinical immunity buffers any effect of climate. Our models open the possibility of forecasting malaria from climate in endemic regions but only after accounting for the interaction between climate and immunity.
West, Philippa A; Protopopoff, Natacha; Wright, Alexandra; Kivaju, Zuhura; Tigererwa, Robinson; Mosha, Franklin W; Kisinza, William; Rowland, Mark; Kleinschmidt, Immo
Insecticide treated nets (ITNs) and indoor residual spraying (IRS) are effective vector control tools that protect against malaria. There is conflicting evidence regarding whether using ITNs and IRS in combination provides additional benefit over using either of these methods alone. This study investigated factors that may modify the effect of the combined use of IRS and ITNs compared to using ITNs alone on malaria infection prevalence. Secondary analysis was carried out on data from a cluster randomised trial in north-west Tanzania. 50 clusters received ITNs from a universal coverage campaign; of these 25 were randomly allocated to additionally receive two rounds of IRS in 2012. In cross-sectional household surveys children 0.5-14 years old were tested for Plasmodium falciparum infections (PfPR) two, six and ten months after the first IRS round. IRS protected those sleeping under nets (OR = 0.38, 95%CI 0.26-0.57) and those who did not (OR = 0.43, 95%CI 0.29-0.63). The protective effect of IRS was not modified by community level ITN use (ITN use = 50%, OR = 0.46, 95%CI 0.28-0.74). The additional protection from IRS was similar in low (areas (≥10% PfPR, OR = 0.34, 95%CI 0.18-0.67). ITN use was protective at the individual-level regardless of whether the village had been sprayed (OR = 0.83, 95%CI 0.70-0.98). Living in a sprayed village was protective regardless of whether the individual slept under an ITN last night (OR = 0.41, 95%CI 0.29-0.58). Implementing IRS in addition to ITNs was beneficial for individuals from villages with a wide range of transmission intensities and net utilisation levels. Net users received additional protection from IRS. ITNs were providing some individual protection, even in this area with high levels of pyrethroid insecticide resistance. These results demonstrate that there is a supplementary benefit of IRS even when ITNs are effective. ClinicalTrials.gov NCT01697852.
Baidjoe, Amrish; Stone, Will; Ploemen, Ivo; Shagari, Shehu; Grignard, Lynn; Osoti, Victor; Makori, Euniah; Stevenson, Jennifer; Kariuki, Simon; Sutherland, Colin; Sauerwein, Robert; Cox, Jonathan; Drakeley, Chris; Bousema, Teun
.... Filter paper blood spots are commonly used a source of both DNA and antibodies. To enhance the operational practicability of malaria surveys, a method is presented for combined DNA extraction and antibody elution...
Glaubitt, W.; Sporn, D.; Hussmann, E. [Fraunhofer-Institut fuer Silicatforschung (ISC), Wuerzburg (Germany); Gombert, A.; Wittwer, V. [Fraunhofer-Institut fuer Solare Energiesysteme (ISE), Freiburg im Breisgau (Germany)
Antireflective quarter-wave single layers with an improved abrasion resistance were prepared from sols by dip coating of float glasses, which can be used for covering solar cells and collectors. The coating sols are based on tetraalkoxysilane hydrolyzed in the presence of different organic additives, eg. polymers. This kind of sols lead to a stable pore structure in the pre-annealed film, which allows to treat it even at temperatures neccessary for glass strengthening. A heat treatment above 600 C improved the abrasion resistance, but was not accompanied by a reduction of the pore volume as would commonly be expected. The resulting porous film therefore showed the required effective refractive index of <1.3, and increased the transmission of such coated low-iron glass up to 99.6% in the visible spectral range and 97.0% in the solar spectral range. (orig.)
Arruda, Eder Ferreira de; Araujo, Felipe Monteiro de; Guimarães, Maria Gabriela da Silva; Nogueira, Rudi; Ramalho, Alanderson Alves; Silva-Nunes, Monica da
The aim of this study was to analyze the prevalence of malaria-attributable anemia in the urban population of Mâncio Lima, Acre State, Brazil. This was a non-concurrent cohort study of 1,167 persons followed for the three months prior to the interview using data from the SIVEP-Malaria database. Anemia frequency and prevalence rates were calculated in patients with and without a recent history of malaria, according to target variables. 50.2% of the individuals were males, and 67.96% were 15 years or older. Overall anemia prevalence was 7.1%, higher in the 6 months to 5 years age bracket. Some 8.3% of men with a recent history of malaria presented anemia. Overall, prevalence of malaria-attributable anemia was negligible, except in men (2.4%) and the Cobal neighborhood (51.4%). The results showed that anemia prevalence was low and that malaria's contribution to anemia only existed in men and in specific geographic areas.
The WADAPT group (Wireless Allowing Data and Power Transmission has been formed to study the feasibility of wireless data transmission for future tracking detectors. These proceedings cover current developments focused on communication in the 60 GHz band. This frequency band offers a high bandwidth, a small form factor and an already mature technology. Motivation for wireless data transmission for high energy physics application and the developments towards a demonstrator prototype are summarized. Feasibility studies concerning the construction and operation of a wireless transceiver system have been performed. Data transmission tests with a transceiver prototype operating at even higher frequencies in the 240 GHz band are described. Data transmission at rates up to 10 Gb/s have been obtained successfully using binary phase shift keying.
Adrienne M. Lucas
The malaria eradication campaign that started in Sri Lanka in the late 1940s virtually eliminated malaria transmission on the island. I use the pre-eradication differences in malaria endemicity within Sri Lanka to identify the effect of malaria eradication on fertility and child survival. Malaria eradication increased the number of live births through increasing age specific fertility and causing an earlier first birth. The effect of malaria on the transition time to higher order births is in...
Ekonomou, L.; Kontargyri, V. T.; Kourtesi, St.; Maris, T. I.; Stathopulos, I. A.
According to the literature high voltage transmission line problems are faced using conventional analytical methods, which include in most cases empirical and/or approximating equations. Artificial intelligence and more specifically artificial neural networks (ANN) are addressed in this work, in order to give accurate solutions to high voltage transmission line problems using in the calculations only actual field data. Two different case studies are studied, i.e., the estimation of critical flashover voltage on polluted insulators and the estimation of lightning performance of high voltage transmission lines. ANN models are developed and are tested on operating high voltage transmission lines and polluted insulators, producing very satisfactory results. These two ANN models can be used in electrical engineers' studies aiming at the more effective protection of high voltage equipment.
Determinant factors for malaria transmission on the coast of Oaxaca State, the main residual transmission focus in Mexico Factores determinantes de la transmisión de paludismo en la costa del estado de Oaxaca, el principal foco residual de transmisión en México
Juan E Hernández-Avila
Full Text Available OBJECTIVE: The purpose of this study was to investigate the influence of demographic, socioeconomic and ecological factors in malaria transmission in the most important residual transmission focus in Mexico, located in the state of Oaxaca. MATERIAL AND METHODS: The extension of the focus was determined by a spatial and time analysis of the distribution of malaria cases in the state between 1998 and 1999 using a Geographical Information System. A malaria transmission intensity index (MTII was constructed based on the total number of cases during the study period and the duration and frequency of transmission