Falciparum Malaria Transmission Research Articles

Climate Suitability for Stable Malaria Transmission in Zimbabwe Under Different Climate Change Scenarios

Climate is one factor that determines the potential range of malaria. As such, climate change may work with or against efforts to bring malaria under control. We developed a model of future climate suitability for stable Plasmodium falciparum malaria transmission in Zimbabwe. Current climate suitability for stable malaria transmission was based on the MARA/ARMA model of climatic constraints on the survival and development of the Anopheles vector and the Plasmodium falciparum malaria parasite. We explored potential future geographic distributions of malaria using 16 projections of climate in 2100. The results suggest that, assuming no future human-imposed constraints on malaria transmission, changes in temperature and precipitation could alter the geographic distribution of malaria in Zimbabwe, with previously unsuitable areas of dense human population becoming suitable for transmission. Among all scenarios, the highlands become more suitable for transmission, while the lowveld and areas with low precipitation show varying degrees of change, depending on climate sensitivity and greenhouse gas emission stabilization scenarios, and depending on the general circulation model used. The methods employed can be used within or across other African countries.

Potential effect of climate change on malaria transmission in Africa.

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.

An individual-based model of Plasmodium falciparum malaria transmission on the coast of Kenya

Individual-based models provide powerful tools to model complex interactions characterized by individual variability. This paper presents an object-oriented design for individual-based modelling of Plasmodium falciparum malaria transmission. Two kinds of objects, human and mosquito, that exhibit variability among individuals for parameters such as recovery and survival rates are defined. The model tracks the dynamics of human hosts and adult female mosquitoes individually. Immunity, modelled as a function of exposure history, is represented by reduced susceptibility and increased recovery rate. The model was calibrated using epidemiological data collected at 30 sites along the coast of Kenya. The sites were grouped into low, intermediate and high transmission based on mean daily human-biting rates. Simulation results show that malaria transmission was stable even in low transmission areas where the human-biting rate is approximately 0.5 bite per day. The model was used to examine the effect of infection control programmes that aim at interrupting transmission by reducing human-vector contact rates and implementing active case detection and drug treatment of infections. With this intervention, local elimination of malaria is likely with a probability of extinction of approximately 0.8 in low transmission areas. However, a small amount of immigration (> 0.3%) by infected people into the community could prevent local extinction of the parasite. In intermediate and high transmission areas, reduction in prevalence is short-lived and the probability of local elimination is low, even at high coverage levels of the intervention.

Relationship between parasite density and fever risk in a community exposed to a low level of malaria transmission in Madagascar highlands.

To establish a simple definition of a malaria attack based on blood parasite density and other explanatory covariates, a cohort study was conducted from 1993 to 1996 in the Madagascar highlands undergoing a low seasonal transmission of falciparum malaria. Using logistic regression, the explanatory variables found to be significantly related to the risk of fever are parasite density, age, season, and year. However, and in contrast with other studies, we found no evidence of a clear cutoff in parasite density values consistent with the concept of "pyrogenic threshold" despite a gradual increase of the risk of fever with increasing parasite density. Furthermore, the model evidenced an individual-dependent relationship at a given age. This point was in accordance with the immunological data recorded from the participants. The investigators conclude that the parasite density to distinguish malaria attacks from other causes of fever is not reliable in a context of low falciparum transmission.

What's buzzing? Mosquito genomics and transgenic mosquitoes.

Genome projects and associated technologies are now being established for mosquito species that are vectors of human disease. The recent announcement of an award by the National Institute of Allergy and Infectious Diseases (NIAID) to Celera Genomics to sequence the Anopheles gambiae genome will further accelerate the completion of the sequencing of this genome. Completion of the An. gambiae sequence will mean that the genomes of all three organisms involved in the transmission of falciparum malaria--the mosquito, the parasite, and the human--will have been sequenced. This will greatly facilitate the identification of genes and pathways involved in the transmission of malaria. The recent genetic transformation of An. gambiae with the piggyBac transposable element and the transformation of another important malarial vector, Anopheles stephensi using the Minos element, now provide researchers with powerful tools with which to genetically manipulate these medically important vector species. Here we review the recent progress made in the extension of contemporary tools of modern genetics and genomics into these medically important insects.

Climate suitability for stable malaria transmission in Zimbabwe under different climate change scenarios.

As climate is one factor determining the potential range of malaria, climate change may work with or against efforts to bring malaria under control. We developed a model of future climate suitability for stable Plasmodium falciparum malaria transmission in Zimbabwe. Current climate suitability for stable malaria transmission is based on the MARA/ARMA model of climatic constraints on the survival and development of the Anopheles vector and the Plasmodium falciparum malaria parasite. We explored potential future geographic distributions of malaria using sixteen projections of climate in 2100. The results suggest that, assuming no future human-imposed constraints on malaria transmission, changes in temperature and precipitation could alter the geographic distribution of malaria in Zimbabwe, with previously unsuitable areas of dense human population becoming suitable for transmission. Among all scenarios, the highlands become more suitable for transmission, while the lowveld and areas currently limited by precipitation show varying degrees of change, depending on climate sensitivity and greenhouse gas emission stabilization scenarios, and depending on the general circulation model used. The methods employed can be used within or across other African countries.

SEASONALITY, PARASITE DIVERSITY, AND LOCAL EXTINCTIONS INPLASMODIUM FALCIPARUMMALARIA

We incorporate stochastic, density-dependent seasonal recruitment in adult Anopheles mosquito populations in a discrete-event model of Plasmodium falciparum malaria transmission and find the probabilities of parasite extinction higher than with perennial transmission. Seasonal fluctuations in vector populations act to synchronize the dynamics of infection and immunity in host populations, leading to fluctuations in parasite prevalence greater than expected solely on the basis of high- and low-season vector densities. This synchronization also biases frequencies of infection with multiple parasite phenotypes or genotypes.

Validity of Lot Quality Assurance Sampling to optimize falciparum malaria surveys in low-transmission areas

To control the reappearance of malaria in the Madagascan highlands, indoor house-spraying of DDT was conducted from 1993 until 1998. Before the end of the insecticide-spraying programme, a surveillance system was set up to allow rapid identification of new malaria epidemics. When the number of suspected clinical malaria cases notified to the surveillance system exceeds a predetermined threshold, a parasitological survey is carried out in the community to confirm whether or not transmission of falciparum malaria is increasing. Owing to the low specificity of the surveillance system, this confirmation stage is essential to guide the activities of the control programme. For this purpose, Lot Quality Assurance Sampling (LQAS), which usually requires smaller sample sizes, seemed to be a valuable alternative to conventional survey methods. In parallel to a conventional study of Plasmodium falciparum prevalence carried out in 1998, we investigated the ability of LQAS to rapidly classify zones according to a predetermined prevalence level. Two prevalence thresholds (5% and 15%) were tested using various sampling plans. A plan (36, 2), meaning that at least 2 individuals found to be positive among a random sample of 36, enabled us to classify a community correctly with a sensitivity of 100% and a specificity of 94%. LQAS is an effective tool for rapid assessment of falciparum malaria prevalence when monitoring malaria transmission.

Malaria and pregnancy: placental cytokine expression and its relationship to intrauterine growth retardation.

Malaria infections during pregnancy can lead to the delivery of low-birth-weight infants. In this study, cytokine mRNA was measured in placentas from 23 malaria-infected and 21 uninfected primigravid women who had delivered in Mangochi, Malawi, a region with a high rate of transmission of falciparum malaria. Significantly increased expression of interleukin (IL)-1beta, IL-8, and tumor necrosis factor (TNF)-alpha and decreased expression of IL-6 and transforming growth factor-beta1 were found in malaria-infected compared with uninfected placentas. TNF-alpha and IL-8 were produced by maternally derived hemozoin-laden placental macrophages. Increased TNF-alpha expression was associated with increased placental hemozoin concentrations. Increased TNF-alpha or IL-8 expression in the placenta was associated with intrauterine growth retardation but not with preterm delivery. The results suggest that malaria infections induce a potentially harmful proinflammatory response in the placenta.

Effect of chemotherapy on malaria transmission among Yanomami Amerindians: simulated consequences of placebo treatment.

To determine whether chemotherapy effectively reduces Plasmodium falciparum malaria transmission in isolated human populations, we followed two abrupt sequential outbreaks of malaria infection among Yanomami Amerindians and modeled the effect of chemotherapy and the consequences if no drug was available. A Macdonald-type mathematical model demonstrated that both outbreaks comprised a single epidemic event linked by an invisible outbreak in vector mosquitoes. The basic reproductive number, R0, from fitted values based on the treated epidemic was 2 during the initial phase of the epidemic, and waned as vector density decreased with the onset of the dry season. In the observed epidemic, 60 (45%) of 132 village residents were affected, and the treated outbreak ended after two months. Although the initial chemotherapy regimen was only marginally effective, the duration of human infectivity was reduced from an expected nine months to two weeks. In the absence of this intervention, the initial R0 value would have been 40, more than 60% of the population would have been infected, and more than 30% would have remained parasitemic until the next rainy season (about six months later). Another outbreak would then have ensued, and malaria probably would have remained endemic in this village. Our simulated placebo treatment permits us to conclude that even partially effective chemotherapeutic interventions, such as those in our study, interrupt serial transmission of P. falciparum among isolated human populations that are exposed to infection seasonally.

Efficacy of sulfadoxine-pyrimethamine for prevention of placental malaria in an area of Kenya with a high prevalence of malaria and human immunodeficiency virus infection.

A fever case management (CM) approach using sulfadoxine-pyrimethamine (SP) was compared with two presumptive intertmittent SP treatment regimens in the second and third trimesters in pregnant primigravidae and secundigravidae in an area of intense Plasmodium falciparum malaria transmission in western Kenya. The investigation evaluated efficacy of the antimalarial regimens for prevention of placental malaria and examined the effect of human immunodeficiency virus (HIV) infection on antimalarial drug efficacy and adverse drug reactions. Twenty-seven percent (93 of 343) of pregnant women in the CM group had placental malaria compared with 12% (38 of 330; P < 0.001) of women who received two doses of SP and compared with 9% (28 of 316; P < 0.001) of women who received monthly SP. Fourteen percent (49 of 341) of women in the CM group delivered low birth weight (LBW) infants compared with 8% (27 of 325; P=0.118) of women who received two doses of SP and compared with 8% (26 of 331; P=0.078) of women who received monthly SP. Seven percent (7 of 99) of the HIV-negative women on the two-dose SP regimen had placental malaria compared with 25% (10 of 39; P=0.007) of HIV-positive women on the same regimen; the rate of placental malaria in HIV-positive women was reduced to 7% (2 of 28; P=-0.051) for women on the monthly SP regimen. Less than 2% of women reported adverse drug reactions, with no statistically significant differences between HIV-positive and HIV-negative women. Intermittent treatment with SP is safe and efficacious for the prevention of placental malaria in pregnant primigravidae and secundigravidae in sub-Saharan Africa. While a two-dose SP regimen may be effective in areas with low HIV seroprevalence, administration of SP monthly during the second and third trimesters of pregnancy should be considered in areas of high HIV seroprevalence to prevent the effects of maternal malaria on the newborn.

Mechanisms that reduce transmission of Plasmodium falciparum malaria in semiimmune and nonimmune persons.

Transmission of Plasmodium falciparum can be reduced by immune factors present in the mosquito blood meal. Specific antibodies and white blood cells (WBCs) can interact with the sexual stages of the parasite inside the mosquito midgut. The relative contribution of serum factors and WBCs on transmission reduction in gametocyte carriers from an endemic area in Cameroon and in travelers with a first malaria experience was studied. Blood from these gametocyte carriers was fed to mosquitoes through membrane feeders after serum replacement, WBC depletion, or both. In most imported malaria cases, serum factors, WBCs, or both showed a significant effect on transmission reduction, while infectiousness of gametocyte carriers from Cameroon was reduced by humoral plasma factors only. In addition, the infectivity of gametocytes from semiimmune carriers was significantly lower compared with that of nonimmune carriers, and infectivity was independent of gametocyte density and the presence of WBCs or plasma factors (or both) in the blood meal.

The role of aspecific immunity in transmission of Plasmodium falciparum malaria to mosquitoes

The role of aspecific immunity in transmission of Plasmodium falciparum malaria to mosquitoes

The role of aspecific immunity in transmission of Plasmodium falciparum malaria to mosquitoes

The role of aspecific immunity in transmission of Plasmodium falciparum malaria to mosquitoes

Artemisinin derivatives may interfere with falciparum malaria transmission

Artemisinin derivatives may interfere with falciparum malaria transmission

Randomised trial of pyronaridine versus chloroquine for acute uncomplicated falciparum malaria in Africa

SummaryBackground The spread of chloroquine resistance poses a serious problem in Africa, where falciparum malaria transmission is the highest in the world. Pyronaridine, an acridine derivative, has been used successfully to treat malaria in China for over 20 years. We compared the efficacy of pyronaridine and chloroquine in African adult patients with acute uncomplicated falciparum malaria in Yaoundé, Cameroon, where chloroquine resistance is well established.Methods 96 patients were randomly assigned treatment with chloroquine 25 mg/kg or pyronaridine 32 mg/kg, both orally and divided over 3 days. Patients were followed up for at least 14 days on an outpatient basis. Analysis was by on-active-treatment.Findings After losses from follow-up (11) or because of self-medication with quinine (four), 41 patients treated with chloroquine and 40 treated with pyronaridine were analysed. Parasite clearance during the 14-day follow-up with chloroquine and pyronaridine was 44% and 100%, respectively. All patients treated with pyronaridine were afebrile by day 3, and parasitaemia cleared by day 4. No serious drug-related side-effects were noted in pyronaridine-treated patients.Interpretation Pyronaridine was rapidly effective and well-tolerated in African patients with acute, uncomplicated falciparum malaria and may represent an alternative drug against chloroquine-resistant malaria.

Computer Simulation of a Malaria Control Trial in Vanuatu using a Mathematical Model with Variable Vectorial Capacity.

We have developed a mathematical model to estimate the degree of transmission of Plasmodium falciparum malaria, that is adjusted to an endemic region in Vanuatu, eastern Melanesia, incorporating the factor concerning the loss of immunity in human hosts. Applying this model, we have carried out simulations for more than fifty situations. Our model is based on Dietz et al. (DMT) model which contains epidemiological factors related to malaria transmission. By using field data from an epidemiological study in Vanuatu, we have determined epidemiological parameters and improved the model. Also our model can treat situations with variable vectorial capacity value. The simulations carried out show that it is important to decrease vectorial capacity by taking anti-malarial measures in order to reduce the prevalence of malaria. One or two operations of mass drug administration will reduce Plasmodium falciparum prevalence drastically, but intense reinfection will raise infection rate again within a few years. However, the resurgence of malaria will not occur for a long time if mass drug administration accompanied with possible reduction of vectorial capacity by vector control such as insecticide impregnated bed nets and others.

Mapping the densities of malaria vectors within a single village

Small scale spatial variation and temporal heterogeneity in mosquito densities can have important consequences for disease transmission, but the extreme variation which is observed in populations of malaria vectors makes it difficult to obtain good predictions of densities for short time periods over limited areas. We have applied Bayesian techniques derived for use in cancer epidemiology in order to map densities of Anopheles gambiae s.l. and A. funestus in a Tanzanian village where there is intense transmission of Plasmodium falciparum malaria. Estimates derived in this way should prove useful in vector population biology and in improving estimates of exposure-response relationships of the human host to malaria. The same methods can be applied in other fields of animal ecology.

Malaria Vaccine Study Site in Irian Jaya, Indonesia: Plasmodium falciparum Incidence Measurements and Epidemiologic Considerations in Sample Size Estimation

Malaria epidemiologic and entomologic studies were performed during both the high transmission and low transmission seasons to characterize the Plasmodium falciparum malaria transmission at a proposed malaria vaccine trial site in Irian Jaya, Indonesia. The study population consisted of two subsets: native Irianese men with lifelong exposure to malaria and transmigrants who arrived from a nonmalarious area 2.5 years before the start of the study. All subjects received a radical cure for malaria and were then monitored weekly by blood film. Both P. falciparum malaria attack rates and incidence densities were calculated; transmigrants had a significantly higher rate (P = 0.003) than the Irianese during the low transmission season study (20-weeks long) but not during the high transmission season study (12-weeks long). Lack of exposure-induced immunity left the transmigrants at a minimum 17-25% greater relative risk of becoming parasitemic compared with the Irianese during the low transmission season study. During the high transmission season study, 50% of the transmigrants were P. falciparum positive by week 6 and 50% of the Irianese by week 9. During the low transmission season, 50% of the transmigrants were positive by week 10 and 43% of the Irianese were positive by week 17. Entomologic studies showed that Anopheles koliensis was the predominant vector (> 98% of anopheline catch). Entomologic inoculation rates for P. falciparum were 0.018 and 0.39 infective bites/person/night for the low and high transmission seasons, respectively. New P. vivax cases represented between 16% and 42% of all initial malaria cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Sporozoite rate and malaria prevalence

In a recently published paper, Tom Burkot and colleagues in Papua New Guinea provide an important set of data for vivax and falciparum malaria transmission. Using on enzyme-linked immunosorbent assay (ELISA) technique they measured sporozoite rates in mosquitoes from human bait collections from eight villages and related these to parasite prevalence in 1–9-year-old children. Because the ELISA technique has allowed the data to be obtained with an accuracy which has hitherto been unavailable, the results provide a unique opportunity to compare sporozoite rate, biting density and prevalence. These seminal data will fuel debates about the epidemiology of malaria which may provide insights into potential control strategies. The following commentary focuses on falciparum malaria and explores a more detailed analysis of the data.