Heritability of P. falciparum and P. vivax Malaria in a Karen Population in Thailand

The majority of studies concerning malaria host genetics have focused on individual genes that confer protection against rather than susceptibility to malaria. Establishing the relative impact of genetic versus non-genetic factors on malaria infection and disease is essential to focus effort on key determinant factors. This relative contribution has rarely been evaluated for Plasmodium falciparum and almost never for Plasmodium vivax. We conducted a longitudinal cohort study in a Karen population of 3,484 individuals in a region of mesoendemic malaria, Thailand from 1998 to 2005. The number of P. falciparum and P. vivax clinical cases and the parasite density per person were determined. Statistical analyses were performed to account for the influence of environmental factors and the genetic heritability of the phenotypes was calculated using the pedigree-based variance components model. The genetic contribution to the number of clinical episodes resulting from P. falciparum and P. vivax were 10% and 19% respectively. There was also moderate genetic contribution to the maximum and overall parasite trophozoite density phenotypes for both P. falciparum (16%&16%) and P. vivax (15%&13%). These values, for P. falciparum, were similar to those previously observed in a region of much higher transmission intensity in Senegal, West Africa. Although environmental factors play an important role in acquiring an infection, genetics plays a determinant role in the outcome of an infection with either malaria parasite species prior to the development of immunity

Longitudinal study of Plasmodium falciparum and Plasmodium vivax in a Karen population in Thailand

<p>Abstract</p> <p>Background</p> <p>Clinical case treatment of malaria infections where <it>Plasmodium falciparum </it>and <it>Plasmodium vivax </it>are sympatric has achieved effective reductions in <it>P. falciparum </it>prevalence and incidence rates, but has been less successful for <it>P. vivax</it>. The high transmissibility of <it>P. vivax </it>and its capacity to relapse have been suggested to make it a harder parasite species to control.</p> <p>Methods</p> <p>A clinical malaria case treatment programme was carried out over a decade in a Karen community composed of seven hamlets on the Thai-Myanmar border.</p> <p>Results</p> <p>From 1994 to 2004, prevalence rates of both <it>P. falciparum </it>and <it>P. vivax </it>decreased by 70–90% in six of the seven study hamlets, but were unchanged in one hamlet. Overall, incidence rates decreased by 72% and 76% for <it>P. falciparum </it>and <it>P. vivax </it>respectively over the period 1999–2004. The age-incidence and prevalence curves suggested that <it>P. vivax </it>was more transmissible than <it>P. falciparum </it>despite a greater overall burden of infection with <it>P. falciparum</it>. Male gender was associated with increased risk of clinical presentation with either parasite species. Children (< 15 years old) had an increased risk of presenting with <it>P. vivax </it>but not <it>P. falciparum</it>.</p> <p>Conclusion</p> <p>There was a considerable reduction in incidence rates of both <it>P. vivax </it>and <it>P. falciparum </it>over a decade following implementation of a case treatment programme. The concern that intervention methods would inadvertently favour one species over another, or even lead to an increase in one parasite species, does not appear to be fulfilled in this case.</p

Malaria Incidence and Prevalence Among Children Living in a Peri-Urban Area on the Coast of Benin, West Africa: A Longitudinal Study

Clinical malaria incidence was determined over 18 months in a cohort of 553 children living in a peri-urban area near Cotonou. Three cross-sectional surveys were also carried out. Malaria incidence showed a marked seasonal distribution with two peaks: the first corresponding to the long rainy season, and the second corresponding to the overflowing of Lake Nokoue. The overall Plasmodium falciparum incidence rate was estimated at 84/1,000 person-months, and its prevalence was estimated at over 40% in the two first surveys and 68.9% in the third survey. Multivariate analysis showed that girls and people living in closed houses had a lower risk of clinical malaria. Bed net use was associated with a lower risk of malaria infection. Conversely, children of families owing a pirogue were at higher risk of clinical malaria. Considering the high pyrethroids resistance, indoor residual spraying with either a carbamate or an organophospate insecticide may have a major impact on the malaria burden

Optimally timing primaquine treatment to reduce Plasmodium falciparum transmission in low endemicity Thai-Myanmar border populations

<p>Abstract</p> <p>Background</p> <p>Effective malaria control has successfully reduced the malaria burden in many countries, but to eliminate malaria, these countries will need to further improve their control efforts. Here, a malaria control programme was critically evaluated in a very low-endemicity Thai-Myanmar border population, where early detection and prompt treatment have substantially reduced, though not ended, <it>Plasmodium falciparum </it>transmission, in part due to carriage of late-maturing gametocytes that remain post-treatment. To counter this effect, the WHO recommends the use of a single oral dose of primaquine along with an effective blood schizonticide. However, while the effectiveness of primaquine as a gametocidal agent is widely documented, the mismatch between primaquine's short half-life, the long-delay for gametocyte maturation and the proper timing of primaquine administration have not been studied.</p> <p>Methods</p> <p>Mathematical models were constructed to simulate 8-year surveillance data, between 1999 and 2006, of seven villages along the Thai-Myanmar border. A simple model was developed to consider primaquine pharmacokinetics and pharmacodynamics, gametocyte carriage, and infectivity.</p> <p>Results</p> <p>In these populations, transmission intensity is very low, so the <it>P. falciparum </it>parasite rate is strongly linked to imported malaria and to the fraction of cases not treated. Given a 3.6-day half-life of gametocyte, the estimated duration of infectiousness would be reduced by 10 days for every 10-fold reduction in initial gametocyte densities. Infectiousness from mature gametocytes would last two to four weeks and sustain some transmission, depending on the initial parasite densities, but the residual mature gametocytes could be eliminated by primaquine. Because of the short half-life of primaquine (approximately eight hours), it was immediately obvious that with early administration (within three days after an acute attack), primaquine would not be present when mature gametocytes emerged eight days after the appearance of asexual blood-stage parasites. A model of optimal timing suggests that primaquine follow-up approximately eight days after a clinical episode could further reduce the duration of infectiousness from two to four weeks down to a few days. The prospects of malaria elimination would be substantially improved by changing the timing of primaquine administration and combining this with effective detection and management of imported malaria cases. The value of using primaquine to reduce residual gametocyte densities and to reduce malaria transmission was considered in the context of a malaria transmission model; the added benefit of the primaquine follow-up treatment would be relatively large only if a high fraction of patients (>95%) are initially treated with schizonticidal agents.</p> <p>Conclusion</p> <p>Mathematical models have previously identified the long duration of <it>P. falciparum </it>asexual blood-stage infections as a critical point in maintaining malaria transmission, but infectiousness can persist for two to four weeks because of residual populations of mature gametocytes. Simulations from new models suggest that, in areas where a large fraction of malaria cases are treated, curing the asexual parasitaemia in a primary infection, and curing mature gametocyte infections with an eight-day follow-up treatment with primaquine have approximately the same proportional effects on reducing the infectious period. Changing the timing of primaquine administration would, in all likelihood, interrupt transmission in this area with very good health systems and with very low endemicity.</p

Genetic Determination and Linkage Mapping of Plasmodium falciparum Malaria Related Traits in Senegal

Plasmodium falciparum malaria episodes may vary considerably in their severity and clinical manifestations. There is good evidence that host genetic factors contribute to this variability. To date, most genetic studies aiming at the identification of these genes have used a case/control study design for severe malaria, exploring specific candidate genes. Here, we performed a family-based genetic study of falciparum malaria related phenotypes in two independent longitudinal survey cohorts, as a first step towards the identification of genes and mechanisms involved in the outcome of infection. We studied two Senegalese villages, Dielmo and Ndiop that differ in ethnicity, malaria transmission and endemicity. We performed genome-scan linkage analysis of several malaria-related phenotypes both during clinical attacks and asymptomatic infection. We show evidence for a strong genetic contribution to both the number of clinical falciparum malaria attacks and the asymptomatic parasite density. The asymptomatic parasite density showed linkage to chromosome 5q31 (LOD = 2.26, empirical p = 0.0014, Dielmo), confirming previous findings in other studies. Suggestive linkage values were also obtained at three additional chromosome regions: the number of clinical malaria attacks on chromosome 5p15 (LOD = 2.57, empirical p = 0.001, Dielmo) and 13q13 (LOD = 2.37, empirical p = 0.0014 Dielmo), and the maximum parasite density during asymptomatic infection on chromosome 12q21 (LOD = 3.1, empirical p<10−4, Ndiop). While regions of linkage show little overlap with genes known to be involved in severe malaria, the four regions appear to overlap with regions linked to asthma or atopy related traits, suggesting that common immune related pathways may be involved

Hydrogen recycling during RF plasma heating in the U-3M torsatron

The hydrogen recycling behavior has been studied during the plasma experiments in torsatron U-3M. For this purpose, the time dependence of the molecular hydrogen pressure in the U-3M torsatron vacuum chamber in the modes of RF wall conditioning and RF plasma heating has been measured. The experimental results show that the hydrogen pumping from the vacuum chamber runs at constant rate during the RF discharge for each mode. After RF power switching-off the inverse desorption of hydrogen, accumulated during the RF discharge in the vacuum chamber walls and helical coil surfaces, is observed. When the antenna anode voltages and the RF pulse duration in both modes are increasing, the character of the time dependences of hydrogen pressure does not change significantly.Изучено поведение рециклинга водорода во время плазменных экспериментов на торсатроне У-3М. Для этой цели было проведено измерение временных зависимостей давления водорода в вакуумной камере торсатрона У-3М в режимах ВЧ-чистки стенок камеры и ВЧ-нагрева плазмы. Экспериментальные результаты показали, что в обоих режимах во время ВЧ-разряда скорость откачки водорода из вакуумной камеры остается постоянной для каждого из режимов. После выключения ВЧ-мощности наблюдается обратная десорбция водорода, накопленного во время ВЧ-разряда в стенках вакуумной камеры и винтовых катушек. Повышение анодных напряжений на ВЧ-антеннах и увеличение длительности ВЧ-импульса существенно не влияют на характер временных зависимостей давления водорода.Вивчено поведінку рециклінгу водню під час плазмових експериментів на торсатроні У-3М. Для цієї мети було проведено вимірювання часових залежностей тиску водню у вакуумній камері торсатрона У-3М в режимах ВЧ-чистки стінок камери і ВЧ-нагріву плазми. Експериментальні результати показали, що в обох режимах під час ВЧ-розряду швидкість відкачування водню з вакуумної камери залишається постійною для кожного з режимів. Після виключення ВЧ-потужності спостерігається зворотна десорбція водню, накопиченого під час ВЧ-розряду в стінках вакуумної камери і гвинтових котушок. Підвищення анодних напруг на ВЧ-антенах і збільшення тривалості ВЧ-імпульсу істотно не впливають на характер тимчасових залежностей тиску водню

A high force of Plasmodium vivax blood-stage infection drives the rapid acquisition of immunity in Papua New Guinean children

When both parasite species are co-endemic, Plasmodium vivax incidence peaks in younger children compared to P. falciparum. To identify differences in the number of blood stage infections of these species and its potential link to acquisition of immunity, we have estimated the molecular force of blood-stage infection of P. vivax (molFOB, i.e. the number of genetically distinct blood-stage infections over time), and compared it to previously reported values for P. falciparum.; P. vivax molFOB was estimated by high resolution genotyping parasites in samples collected over 16 months in a cohort of 264 Papua New Guinean children living in an area highly endemic for P. falciparum and P. vivax. In this cohort, P. vivax episodes decreased three-fold over the age range of 1-4.5 years.; On average, children acquired 14.0 new P. vivax blood-stage clones/child/year-at-risk. While the incidence of clinical P. vivax illness was strongly associated with mol FOB (incidence rate ratio (IRR) = 1.99, 95% confidence interval (CI95) [1.80, 2.19]), molFOB did not change with age. The incidence of P. vivax showed a faster decrease with age in children with high (IRR = 0.49, CI95 [0.38, 0.64] p>0.001) compared to those with low exposure (IRR = 0.63, CI95[0.43, 0.93] p = 0.02).; P. vivax molFOB is considerably higher than P. falciparum molFOB (5.5 clones/child/year-at-risk). The high number of P. vivax clones that infect children in early childhood contribute to the rapid acquisition of immunity against clinical P. vivax malaria

Assessment of rodent communities in two provinces of Cambodia

Rodents play an important role in regulating ecosystems, in particular through seed dispersion and predation, and constitute a prey for mesopredators. However, rodents are considered pests in rural areas because they can cause significant damage to crops, especially during episodes of sudden population growth (Singleton, 2003). Rodents are also carriers or reservoirs for numerous zoonotic diseases that represent a serious threat to human health (Meerburg et al., 2009; Luis et al., 2013; Olival et al., 2017). Multi-site assessments of rodent communities are consequently needed to understand the implications of various spatio-temporal factors on these ecosystem services, the epidemiology of rodent-borne diseases, and other interactions with humans