Low-dose primaquine for falciparum malaria

Item does not contain fulltex

Estimating malaria transmission from humans to mosquitoes in a noisy landscape.

A basic quantitative understanding of malaria transmission requires measuring the probability a mosquito becomes infected after feeding on a human. Parasite prevalence in mosquitoes is highly age-dependent, and the unknown age-structure of fluctuating mosquito populations impedes estimation. Here, we simulate mosquito infection dynamics, where mosquito recruitment is modelled seasonally with fractional Brownian noise, and we develop methods for estimating mosquito infection rates. We find that noise introduces bias, but the magnitude of the bias depends on the 'colour' of the noise. Some of these problems can be overcome by increasing the sampling frequency, but estimates of transmission rates (and estimated reductions in transmission) are most accurate and precise if they combine parity, oocyst rates and sporozoite rates. These studies provide a basis for evaluating the adequacy of various entomological sampling procedures for measuring malaria parasite transmission from humans to mosquitoes and for evaluating the direct transmission-blocking effects of a vaccine

Human saliva as a source of anti-malarial antibodies to examine population exposure to Plasmodium falciparum

BACKGROUND: Antibody responses to malaria antigens reflect exposure to parasites, and seroprevalence correlates with malaria transmission intensity. Antibodies are routinely measured in sera or on dried blood spots but a non-invasive method would provide extra utility in sampling general populations. Saliva is already in use in the detection of plasma-derived IgM and IgG to viral infections. In this study, antibodies to Plasmodium falciparum merozoite antigens were compared between blood and saliva samples from the same individuals in unlinked surveys conducted in Tanzania and The Gambia. METHODS: In Tanzania, 53 individuals provided paired fingerprick blood and saliva sample using two commercially available sampling devices. In the Gambia, archived plasma and saliva samples collected from 200 children in the Farafenni area in a cross-sectional survey were analyzed.IgG antibodies against P. falciparum antigens, Merozoite Surface Protein-1 (MSP-119) and Apical membrane Antigen (AMA-1) were measured by ELISA in paired saliva and blood samples from both sites. Antibody levels were compared as continuous optical density (OD) values and by sero-positivity. RESULTS: Significant correlations between saliva and plasma antibody levels were seen in Tanzania for both antigens, AMA-1(r2 range 0.93 to 0.89, p < 0.001) and MSP-119 (r2 range 0.93 to 0.75, p < 0.001), with a weaker correlation for results from The Gambia (r2range 0.64 to 0.63, p < 0.01). When assessed as seropositivity and compared with plasma, sensitivity and specificity were good with saliva antibody levels to both AMA-1 and MSP-1(19) (sensitivity range 64-77% and specificity range 91-100% & 47-67% and 90-97% respectively) over the different sample sets. CONCLUSIONS: These data demonstrate anti-malarial antibodies can be detected in saliva and correlate strongly with levels in plasma. This non-invasive relatively simple collection method will be potentially useful for general population surveys, and particularly in migratory populations or those with infrequent contact with health services or opposed to blood withdrawal. Further studies will be needed to optimize collection methods, standardize volumes and content and develop controls

Reducing Plasmodium falciparum malaria transmission in Africa: a model-based evaluation of intervention strategies.

BACKGROUND: 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. METHODS AND FINDINGS: 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. CONCLUSIONS: 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 roll-out of interventions. In high-transmission settings and those in which vectors are mainly exophilic (outdoor-resting), additional new tools that target exophagic (outdoor-biting), exophilic, and partly zoophagic mosquitoes will be required

Dry season ecology of Anopheles gambiae complex mosquitoes in The Gambia

BACKGROUND: Malaria in The Gambia is highly seasonal, with transmission occurring as Anopheles gambiae s.l. populations expand during and immediately after a single annual rainy season that lasts from June to October. There has been very limited investigation of the ecology of vectors during the dry season, when numbers are very limited and distributions may be restricted. METHODS: Weekly adult mosquito collections (pyrethrum spray, light trap, and search collections from rooms, as well as light trap collections from animal shelters, abandoned wells and grain stores), and artificial sentinel breeding site surveys were performed in four villages near the upper tidal and partially saline part of the Gambia River in the last four months of an annual dry season (March to June). Mosquito species were identified by morphological and DNA analysis, and ELISA assays were performed to test for Plasmodium falciparum sporozoites and human blood meal components. RESULTS: Adults of An. gambiae s.l. were collected throughout the period, numbers increasing towards the end of the dry season when humidity was increasing. Adult collections were dominated by An. melas (86%), with An. gambiae s.s. (10%) and An. arabiensis (3%) also present throughout. Most females collected in room search and spray collections contained blood meals, but most from light traps were unfed. None of the females tested (n = 1709) contained sporozoites. Larvae (mostly An. gambiae s.s.) were recovered from artificial sentinel breeding sites in the two villages that had freshwater pools. These two villages had the highest proportions of An. gambiae s.s. adults, and experienced the most substantial increase in proportions of An. gambiae s.s. after the onset of rains. CONCLUSION: During the dry season population minimum, An. melas was the predominant vector species, but differences among villages in availability of fresh-water breeding sites correlate with egg laying activity and relative numbers of An. gambiae s.s. adults, and with the increase in this species immediately after the beginning of the rains. Local variation in dry season vector persistence is thus likely to influence spatial heterogeneity of transmission intensity in the early part of the rainy season

Rapid screening for glucose-6-phosphate dehydrogenase deficiency and haemoglobin polymorphisms in Africa by a simple high-throughput SSOP-ELISA method

BACKGROUND: Mutations in the haemoglobin beta-globin (HbB) and glucose-6-phosphate dehydrogenase (G6PD) genes cause widespread human genetic disorders such as sickle cell diseases and G6PD deficiency. In sub-Saharan Africa, a few predominant polymorphic variants of each gene account for a majority of these deficiencies. Examining at a larger scale the clinical importance of these independent genetic disorders, their possible association with malaria pathogenesis and innate resistance, and their relevance for antimalarial drug treatment, would be easier if an accurate screening method with limited costs was available. METHODS: A simple and rapid technique was developed to detect the most prominent single nucleotide polymorphisms (SNPs) in the HbB and G6PD genes. The method is able to detect the different haemoglobin polymorphisms A, S, C and E, as well as G6PD polymorphisms B, A and A- based on PCR-amplification followed by a hybridization step using sequence-specific oligonucleotide probes (SSOPs) specific for the SNP variants and quantified by ELISA. RESULTS: The SSOP-ELISA method was found to be specific, and compared well to the commonly used PCR-RFLP technique. Identical results were obtained in 98% (haemoglobin) and 95% (G6PD) of the tested 90 field samples from a high-transmission area in Tanzania, which were used to validate the new technique. CONCLUSION: The simplicity and accuracy of the new methodology makes it suitable for application in settings where resources are limited. It would serve as a valuable tool for research purposes by monitoring genotype frequencies in relation to disease epidemiology

Glucose-6-phosphate dehydrogenase status and risk of hemolysis in Plasmodium falciparum-infected African children receiving single-dose primaquine.

Glucose-6-phosphate dehydrogenase (G6PD) enzyme function and genotype were determined in Ugandan children with uncomplicated falciparum malaria enrolled in a primaquine trial after exclusion of severe G6PD deficiency by fluorescent spot test. G6PD A- heterozygotes and hemizygotes/homozygotes experienced dose-dependent lower hemoglobin concentrations after treatment. No severe anemia was observed

Loss of Population Levels of Immunity to Malaria as a Result of Exposure-Reducing Interventions: Consequences for Interpretation of Disease Trends

BACKGROUND: The persistence of malaria as an endemic infection and one of the major causes of childhood death in most parts of Africa has lead to a radical new call for a global effort towards eradication. With the deployment of a highly effective vaccine still some years away, there has been an increased focus on interventions which reduce exposure to infection in the individual and -by reducing onward transmission-at the population level. The development of appropriate monitoring of these interventions requires an understanding of the timescales of their effect. METHODS & FINDINGS: Using a mathematical model for malaria transmission which incorporates the acquisition and loss of both clinical and parasite immunity, we explore the impact of the trade-off between reduction in exposure and decreased development of immunity on the dynamics of disease following a transmission-reducing intervention such as insecticide-treated nets. Our model predicts that initially rapid reductions in clinical disease incidence will be observed as transmission is reduced in a highly immune population. However, these benefits in the first 5-10 years after the intervention may be offset by a greater burden of disease decades later as immunity at the population level is gradually lost. The negative impact of having fewer immune individuals in the population can be counterbalanced either by the implementation of highly-effective transmission-reducing interventions (such as the combined use of insecticide-treated nets and insecticide residual sprays) for an indefinite period or the concurrent use of a pre-erythrocytic stage vaccine or prophylactic therapy in children to protect those at risk from disease as immunity is lost in the population. CONCLUSIONS: Effective interventions will result in rapid decreases in clinical disease across all transmission settings while population-level immunity is maintained but may subsequently result in increases in clinical disease many years later as population-level immunity is lost. A dynamic, evolving intervention programme will therefore be necessary to secure substantial, stable reductions in malaria transmission

Plasmodium falciparum gametocyte carriage in asymptomatic children in western Kenya

BACKGROUND: Studies on Plasmodium falciparum gametocyte development and dynamics have almost exclusively focused on patients treated with antimalarial drugs, while the majority of parasite carriers in endemic areas are asymptomatic. This study identified factors that influence gametocytaemia in asymptomatic children in the absence and presence of pyrimethamine-sulphadoxine (SP) antimalarial treatment. METHODS: A cohort of 526 children (6 months – 16 years) from western Kenya was screened for asexual parasites and gametocytes and followed weekly up to four weeks. Children with an estimated parasitaemia of ≥1,000 parasites/μl were treated with SP according to national guidelines. Factors associated with gametocyte development and persistence were determined in untreated and SP-treated children with P. falciparum mono-infection. RESULTS: Gametocyte prevalence at enrolment was 33.8% in children below five years of age and decreased with age. In the absence of treatment 18.6% of the children developed gametocytaemia during follow-up; in SP-treated children this proportion was 29.8%. Age, high asexual parasite density and gametocyte presence at enrolment were predictive factors for gametocytaemia. The estimated mean duration of gametocytaemia for children below five, children from five to nine and children ten years and above was 9.4, 7.8 and 4.1 days, respectively. CONCLUSION: This study shows that a large proportion of asymptomatic untreated children develop gametocytaemia. Gametocytaemia was particularly common in children below five years who harbor gametocytes for a longer period of time. The age-dependent duration of gametocytaemia has not been previously shown and could increase the importance of this age group for the infectious reservoir