Plasmodium Transmission Research Articles

Protective efficacy of menthol propylene glycol carbonate compared to N, N-diethyl-methylbenzamide against mosquito bites in Northern Tanzania

BackgroundThe reduction of malaria parasite transmission by preventing human-vector contact is critical in lowering disease transmission and its outcomes. This underscores the need for effective and long lasting arthropod/insect repellents. Despite the reduction in malaria transmission and outcomes in Tanzania, personal protection against mosquito bites is still not well investigated. This study sought to determine the efficacy of menthol propylene glycol carbonate (MR08), Ocimum suave as compared to the gold standard repellent N, N-diethyl-methylbenzamide (DEET), either as a single dose or in combination (blend), both in the laboratory and in the field against Anopheles gambiae s.l and Culex quinquefasciatus.MethodsIn the laboratory evaluations, repellents were applied on one arm while the other arm of the same individual was treated with a base cream. Each arm was separately exposed in cages with unfed female mosquitoes. Repellents were evaluated either as a single dose or as a blend. Efficacy of each repellent was determined by the number of mosquitoes that landed and fed on treated arms as compared to the control or among them. In the field, evaluations were performed by human landing catches at hourly intervals from 18:00 hr to 01:00 hr.ResultsA total of 2,442 mosquitoes were collected during field evaluations, of which 2,376 (97.30%) were An. gambiae s.l while 66 (2.70%) were Cx. quinquefaciatus. MR08 and DEET had comparatively similar protective efficacy ranging from 92% to 100 for both single compound and blends. These findings indicate that MR08 has a similar protective efficacy as DEET for personal protection outside bed nets when used singly and in blends. Because of the personal protection provided by MR08, DEET and blends as topical applicants in laboratory and field situations, these findings suggest that, these repellents could be used efficiently in the community to complement existing tools. Overall, Cx. quinquefasciatus were significantly prevented from blood feeding compared to An. gambiae s.l.ConclusionThe incorporation of these topical repellents for protection against insect bites can be of additional value in the absence or presence of IRS and ITNs coverage. However, a combination of both the physical (bed nets) and the repellent should be used in an integrated manner for maximum protection, especially before going to bed. Additional research is needed to develop repellents with longer duration of protection.

Novel Vectors of Malaria Parasite in the Western Highlands of Kenya

To the Editor: The primary malaria control techniques, indoor application of residual insecticides and insecticide-treated bed nets, are used on the basis of previously assumed key characteristics of behaviors of vectors of malaria parasites, i.e., resting and feeding indoors (1). Any deviation from the typical activities of a species related to exophagy (feeding outdoors) and exophily (living and resting indoors) (2) or to population replacement, followed by increased outdoor biting or resting (3), may undermine malaria control efforts. Identification of mosquitoes that transmit malaria parasites has, for the most part, relied on the use of outdated morphologic keys (4,5) and, more recently, species-diagnostic PCR (6). Cryptic species or subpopulations that exhibit divergent behaviors (7) may be responsible for maintaining malaria parasite transmission, and without adequate discriminatory techniques, these vectors may be misidentified and their key behavioral differences overlooked.

Mosquito Feeding Assays to Determine the Infectiousness of Naturally Infected Plasmodium falciparum Gametocyte Carriers

IntroductionIn the era of malaria elimination and eradication, drug-based and vaccine-based approaches to reduce malaria transmission are receiving greater attention. Such interventions require assays that reliably measure the transmission of Plasmodium from humans to Anopheles mosquitoes.MethodsWe compared two commonly used mosquito feeding assay procedures: direct skin feeding assays and membrane feeding assays. Three conditions under which membrane feeding assays are performed were examined: assays with i) whole blood, ii) blood pellets resuspended with autologous plasma of the gametocyte carrier, and iii) blood pellets resuspended with heterologous control serum.Results930 transmission experiments from Cameroon, The Gambia, Mali and Senegal were included in the analyses. Direct skin feeding assays resulted in higher mosquito infection rates compared to membrane feeding assays (odds ratio 2.39, 95% confidence interval 1.94–2.95) with evident heterogeneity between studies. Mosquito infection rates in membrane feeding assays and direct skin feeding assays were strongly correlated (p<0.0001). Replacing the plasma of the gametocyte donor with malaria naïve control serum resulted in higher mosquito infection rates compared to own plasma (OR 1.92, 95% CI 1.68–2.19) while the infectiousness of gametocytes may be reduced during the replacement procedure (OR 0.60, 95% CI 0.52–0.70).ConclusionsDespite a higher efficiency of direct skin feeding assays, membrane feeding assays appear suitable tools to compare the infectiousness between individuals and to evaluate transmission-reducing interventions. Several aspects of membrane feeding procedures currently lack standardization; this variability makes comparisons between laboratories challenging and should be addressed to facilitate future testing of transmission-reducing interventions.

New Ultrastructural Analysis of the Invasive Apparatus of the Plasmodium Ookinete

Invasion of the mosquito midgut by the Plasmodium ookinete determines the success of transmission of malaria parasites from humans to mosquitoes and therefore, is a potential target for molecular intervention. Here, we show higher-resolution ultrastructural details of developing and mature P. gallinaceum ookinetes than previously available. Improved fixation and processing methods yielded substantially improved transmission electron micrographs of ookinetes, particularly with regard to visualization of subcellular secretory and other organelles. These new images provide new insights into the synthesis and function of vital invasive machinery focused on the following features: apical membrane protrusions presumptively used for attachment and protein secretion, dark spherical bodies at the apical end of the mature ookinete, and the presence of a dense array of micronemes apposed to microtubules at the apical end of the ookinete involved in constitutive secretion. This work advances understanding of the molecular and cellular details of the Plasmodium ookinete and provides the basis of future, more detailed mechanistic experimentation on the biology of the Plasmodium ookinete.

Polymerase chain reaction detection of human host preference and Plasmodium parasite infections in field collected potential malaria vectors

This study was carried out to determine the human host preference and presence of Plasmodium parasite in field collected Anopheles mosquitoes among four villages around a military cantonment located in malaria endemic Sonitpur district of Assam, India. Encountered malaria vector mosquitoes were identified and tested for host preference and Plasmodium presence using PCR method. Human host preference was detected using simple PCR, whereas vectorial status for Plasmodium parasite was confirmed using first round PCR with genus specific primers and thereafter nested PCR with three Plasmodium species specific primers. Out of 1874 blood fed vector mosquitoes collected, 187 (10%) were processed for PCR, which revealed that 40·6% had fed on human blood; 9·2% of human blood fed mosquito were harbouring Plasmodium parasites, 71·4% of which were confirmed to Plasmodium falciparum. In addition to An. minimus, An. annularis and An. culicifacies were also found positive for malaria parasites. The present study exhibits the human feeding tendency of Anopheles vectors highlighting their malaria parasite transmission potential. The present study may serve as a model for understanding the human host preference of malaria vectors and detection of malaria parasite inside the anopheline vector mosquitoes in order to update their vectorial status for estimating the possible role of these mosquitoes in malaria transmission. The study has used PCR method and suggests that PCR-based method should be used in this entire malarious region to correctly report the vectorial position of different malaria vectors.

Infection with Wolbachia protects mosquitoes against Plasmodium‐induced mortality in a natural system

In recent years, there has been a shift in the one host-one parasite paradigm with the realization that, in the field, most hosts are coinfected with multiple parasites. Coinfections are particularly relevant when the host is a vector of diseases, because multiple infections can have drastic consequences for parasite transmission at both the ecological and evolutionary timescales. Wolbachia pipientis is the most common parasitic microorganism in insects, and as such, it is of special interest for understanding the role of coinfections in the outcome of parasite infections. Here, we investigate whether Wolbachia can modulate the effect of Plasmodium on what is, arguably, the most important component of the vectorial capacity of mosquitoes: their longevity. For this purpose, and in contrast to recent studies that have focused on mosquito-Plasmodium and/or mosquito-Wolbachia combinations not found in nature, we work on a Wolbachia-mosquito-Plasmodium triad with a common evolutionary history. Our results show that Wolbachia protects mosquitoes from Plasmodium-induced mortality. The results are consistent across two different strains of Wolbachia and repeatable across two different experimental blocks. To our knowledge, this is the first time that such an effect has been shown for Plasmodium-infected mosquitoes and, in particular, in a natural Wolbachia-host combination. We discuss different mechanistic and evolutionary explanations for these results as well as their consequences for Plasmodium transmission.

The spiroindolone drug candidate NITD609 potently inhibits gametocytogenesis and blocks Plasmodium falciparum transmission to anopheles mosquito vector.

The global malaria agenda has undergone a reorientation from control of clinical cases to entirely eradicating malaria. For that purpose, a key objective is blocking transmission of malaria parasites from humans to mosquito vectors. The new antimalarial drug candidate NITD609 was evaluated for its transmission-reducing potential and compared to a few established antimalarials (lumefantrine, artemether, primaquine), using a suite of in vitro assays. By the use of a microscopic readout, NITD609 was found to inhibit the early and late development of Plasmodium falciparum gametocytes in vitro in a dose-dependent fashion over a range of 5 to 500 nM. In addition, using the standard membrane feeding assay, NITD609 was also found to be a very effective drug in reducing transmission to the Anopheles stephensi mosquito vector. Collectively, our data suggest a strong transmission-reducing effect of NITD609 acting against different P. falciparum transmission stages.

High Prevalence and Lineage Diversity of Avian Malaria in Wild Populations of Great Tits (Parus major) and Mosquitoes (Culex pipiens)

Avian malaria studies have taken a prominent place in different aspects of evolutionary ecology. Despite a recent interest in the role of vectors within the complex interaction system of the malaria parasite, they have largely been ignored in most epidemiological studies. Epidemiology of the disease is however strongly related to the vector's ecology and behaviour, and there is a need for basic investigations to obtain a better picture of the natural associations between Plasmodium lineages, vector species and bird hosts.The aim of the present study was to identify the mosquito species involved in the transmission of the haemosporidian parasites Plasmodium spp. in two wild populations of breeding great tits (Parus major) in western Switzerland. Additionally, we compared Plasmodium lineages, based on mitochondrial DNA cytochrome b sequences, between the vertebrate and dipteran hosts, and evaluated the prevalence of the parasite in the mosquito populations. Plasmodium spp. were detected in Culex pipiens only, with an overall 6.6% prevalence. Among the six cytochrome b lineages of Plasmodium identified in the mosquitoes, three were also present in great tits. The results provide evidence for the first time that C. pipiens can act as a natural vector of avian malaria in Europe and yield baseline data for future research on the epidemiology of avian malaria in European countries.

Selection of mosquito life-histories: a hidden weapon against malaria?

BackgroundThere has recently been a substantial decline in malaria incidence in much of Africa. While the decline can clearly be linked to increasing coverage of mosquito vector control interventions and effective drug treatment in most settings, the ubiquity of reduction raises the possibility that additional ecological and associated evolutionary changes may be reinforcing the effectiveness of current vector control strategies in previously unanticipated ways.Presentation of hypothesisHere it is hypothesized that the increasing coverage of insecticide-treated bed nets and other vector control methods may be driving selection for a shift in mosquito life history that reduces their ability to transmit malaria parasites. Specifically it is hypothesized that by substantially increasing the extrinsic rate of mortality experienced in vector populations, these interventions are creating a fitness incentive for mosquitoes to re-allocate their resources towards greater short-term reproduction at the expense of longer-term survival. As malaria transmission is fundamentally dependent on mosquito survival, a life history shift in this direction would greatly benefit control.Testing the hypothesisAt present, direct evaluation of this hypothesis within natural vector populations presents several logistical and methodological challenges. In the meantime, many insights can be gained from research previously conducted on wild Drosophila populations. Long-term selection experiments on these organisms suggest that increasing extrinsic mortality by a magnitude similar to that anticipated from the up-scaling of vector control measures generated an increase in their intrinsic mortality rate. Although this increase was small, a change of similar magnitude in Anopheles vector populations would be predicted to reduce malaria transmission by 80%.Implications of hypothesisThe hypothesis presented here provides a reminder that evolutionary processes induced by interventions against disease vectors may not always act to neutralize intervention effectiveness. In the search for new intervention strategies, consideration should be given to both the potential disadvantages and advantages of evolutionary processes resulting from their implementation, and attempts made to exploit those with greatest potential to enhance control.

Mosquito (Diptera: Culicidae) assemblages associated with Nidularium and Vriesea bromeliads in Serra do Mar, Atlantic Forest, Brazil.

BackgroundThe most substantial and best preserved area of Atlantic Forest is within the biogeographical sub-region of Serra do Mar. The topographic complexity of the region creates a diverse array of microclimates, which can affect species distribution and diversity inside the forest. Given that Atlantic Forest includes highly heterogeneous environments, a diverse and medically important Culicidae assemblage, and possible species co-occurrence, we evaluated mosquito assemblages from bromeliad phytotelmata in Serra do Mar (southeastern Brazil).MethodsLarvae and pupae were collected monthly from Nidularium and Vriesea bromeliads between July 2008 and June 2009. Collection sites were divided into landscape categories (lowland, hillslope and hilltop) based on elevation and slope. Correlations between bromeliad mosquito assemblage and environmental variables were assessed using multivariate redundancy analysis. Differences in species diversity between bromeliads within each category of elevation were explored using the Renyi diversity index. Univariate binary logistic regression analyses were used to assess species co-occurrence. ResultsA total of 2,024 mosquitoes belonging to 22 species were collected. Landscape categories (pseudo-F value = 1.89, p = 0.04), bromeliad water volume (pseudo-F = 2.99, p = 0.03) and bromeliad fullness (Pseudo-F = 4.47, p < 0.01) influenced mosquito assemblage structure. Renyi diversity index show that lowland possesses the highest diversity indices. The presence of An. homunculus was associated with Cx. ocellatus and the presence of An. cruzii was associated with Cx. neglectus, Cx. inimitabilis fuscatus and Cx. worontzowi. Anopheles cruzii and An. homunculus were taken from the same bromeliad, however, the co-occurrence between those two species was not statistically significant.ConclusionsOne of the main findings of our study was that differences in species among mosquito assemblages were influenced by landscape characteristics. The bromeliad factor that influenced mosquito abundance and assemblage structure was fullness. The findings of the current study raise important questions about the role of An. homunculus in the transmission of Plasmodium in Serra do Mar, southeastern Atlantic Forest.

Malaria Prevalence in Forest and Nonforest Areas of Kokrajhar District of Assam

An analysis of malaria prevalence and its trends in Kokrajhar district of Assam over the last ten years starting from 2001 to 2010 shows that the occurrence of malaria in the forest area is significantly higher than in the nonforest area (). The transmission of malaria parasite takes place through only two Plasmodium species of P. falciparum (PF) and P. vivax (PV) in both the forest and nonforest areas of the district, and the prevalence of P. falciparum has been found higher. The annual blood examination rate (ABER) is relatively lower in forest area than the nonforest area while annual parasite incidence (API) of the former was much higher. Nearly one-third of the population of the district is under high risk of being affected. The malaria API and forest cover of the district during the period are negatively correlated with a coefficient of −0.57. Special measures are necessary to contain the transmission of malaria in forest area.

Asymptomatic Malaria Correlates with Anaemia in Pregnant Women at Ouagadougou, Burkina Faso

Sub-Saharan Africa records each year about thirty-two million pregnant women living in areas of high transmission of Plasmodium falciparum causing malaria. The aim of this study was to carve out the prevalence of asymptomatic malaria among pregnant women and to emphasize its influence on haematological markers. The prevalence of Plasmodium falciparum asymptomatic infection among pregnant women was 30% and 24% with rapid detection test (RDT) and microscopy, respectively. The prevalence of P. falciparum asymptomatic malaria was reduced among pregnant women using sulfadoxine-pyrimethamine's intermittent preventive treatment and 61% of them were anaemic. Anaemia was significantly more common in women infected with P. falciparum compared with the uninfected pregnant women. Most of the women had normal levels of homocysteine and low levels of folate, respectively. Therefore, the systematic diagnosis of malaria should be introduced to pregnant women as a part of the antenatal care.

Mosquitoes as potential bridge vectors of malaria parasites from non-human primates to humans.

Malaria is caused by Plasmodium parasites which are transmitted by mosquitoes. Until recently, human malaria was considered to be caused by human-specific Plasmodium species. Studies on Plasmodium parasites in non-human primates (NHPs), however, have identified parasite species in gorillas and chimpanzees that are closely related to human Plasmodium species. Moreover, P. knowlesi, long known as a parasite of monkeys, frequently infects humans. The requirements for such a cross-species exchange and especially the role of mosquitoes in this process are discussed, as the latter may act as bridge vectors of Plasmodium species between different primates. Little is known about the mosquito species that would bite both humans and NHPs and if so, whether humans and NHPs share the same Plasmodium vectors. To understand the vector-host interactions that can lead to an increased Plasmodium transmission between species, studies are required that reveal the nature of these interactions. Studying the potential role of NHPs as a Plasmodium reservoir for humans will contribute to the ongoing efforts of human malaria elimination, and will help to focus on critical areas that should be considered in achieving this goal.

Taxonomía y distribución de los anofelinos en el estado de Veracruz, México (Diptera: Culicidae, Anophelinae)

La malaria o paludismo es una enfermedad humana causada por protozoarios del género Plasmodium y es transmitida por hembras de mosquito de ciertas especies de Anopheles. Se estima queen México el 33.1% de la población vive en áreas donde puede ocurrir la transmisión de la malaria. Veracruz es un estado donde la enfermedad es endémica debido a diversos factores que lo hacen una zona de riesgo para la transmisión, entre ellos las condiciones climáticas y la migración humana. Por lo anterior, en este trabajo se presentan las bases para la reactivación de la vigilancia entomológica del paludismo en el estado de Veracruz, para lo cual se provee la diagnosis ilustrada de la larva, la pupa y los adultos de ambos sexos de las especies de anofelinos del estado, así como las claves taxonómicas que permiten su reconocimiento, con base en el examen de ejemplares recolectados o depositados en coleccionesentomológicas de referencia. También se obtuvieron mapas de distribución conocida y potencial de las especies por medio de GARP. Se mencionan además algunos datos bionómicos y la importanciamédica de cada especie. Se conocen en Veracruz 18 especies de anofelinos, agrupadas en dos géneros, Chagasia con una especie y Anopheles con 17 pertenecientes a los subgéneros An. (Anopheles), An. (Kerteszia) y An. (Nyssorhynchus). Se reconocen cuatro grupos de especies de acuerdo a su capacidad de transmisión de plasmodios y por su amplitud de distribución: el grupo de alto riesgo constituido por 2 especies; el grupo de riesgo moderado o regional, con 8 especies; el de escaso riesgo, con 3 especies y el de riesgo nulo con 5 especies. Prácticamente todo el estado posee vectores potenciales por lo que debe reestablecerse la vigilancia permanente de sus poblaciones. Este trabajo aporta elementos de juicio para que el estado pueda ser, en un futuro cercano, certificado como área libre de paludismo.

Malaria elimination in Malawi: Research needs in highly endemic, poverty-stricken contexts

Malaria control in the impoverished, highly endemic settings of sub-Saharan Africa remains a major public health challenge. Successes have been achieved only where sustained, concerted, multi-pronged interventions have been instituted. As one of the world‘s poorest countries, Malawi experiences malaria incidence rates that have remained high despite a decade of gradually expanding and more intensive prevention efforts. The Malawi International Center for Excellence in Malaria Research (ICEMR) is beginning work to augment the knowledge base for reducing Plasmodium transmission and malaria morbidity and mortality. Among ICEMR goals, we intend to better assess patterns of infection and disease, and analyze transmission by Anopheles vector species in both urban and rural ecological settings. We will evaluate parasite population genetics and dynamics, transmission intensities and vector ecologies, social and environmental determinants of disease patterns and risk, and human–vector–parasite dynamics. Such context-specific information will help to focus appropriate prevention and treatment activities on efforts to control malaria in Malawi. In zones of intense and stable transmission, like Malawi, elimination poses particularly thorny challenges – and these challengers are different from those of traditional control and prevention activities. Working toward elimination will require knowledge of how various interventions impact on transmission as it approaches very low levels. At present, Malawi is faced with immediate, context-specific problems of scaling-up prevention and control activities simply to begin reducing infection and disease to tolerable levels. The research required to support these objectives is critically evaluated here.

Quantitative assessment of Plasmodium falciparum sexual development reveals potent transmission-blocking activity by methylene blue

Clinical studies and mathematical models predict that, to achieve malaria elimination, combination therapies will need to incorporate drugs that block the transmission of Plasmodium falciparum sexual stage parasites to mosquito vectors. Efforts to measure the activity of existing antimalarials on intraerythrocytic sexual stage gametocytes and identify transmission-blocking agents have, until now, been hindered by a lack of quantitative assays. Here, we report an experimental system using P. falciparum lines that stably express gametocyte-specific GFP-luciferase reporters, which enable the assessment of dose- and time-dependent drug action on gametocyte maturation and transmission. These studies reveal activity of the first-line antimalarial dihydroartemisinin and the partner drugs lumefantrine and pyronaridine against early gametocyte stages, along with moderate inhibition of mature gametocyte transmission to Anopheles mosquitoes. The other partner agents monodesethyl-amodiaquine and piperaquine showed activity only against immature gametocytes. Our data also identify methylene blue as a potent inhibitor of gametocyte development across all stages. This thiazine dye almost fully abolishes P. falciparum transmission to mosquitoes at concentrations readily achievable in humans, highlighting the potential of this chemical class to reduce the spread of malaria.

Comparative evaluation of systemic drugs for their effects against Anopheles gambiae

Laboratory and field studies have shown that ivermectin, a drug that targets invertebrate ligand-gated ion channels (LGICs), is potently active against Anopheles spp. mosquitoes at concentrations present in human blood after standard drug administrations; thus ivermectin holds promise as a mass human-administered endectocide that could help suppress malaria parasite transmission. We evaluated other systemic LGIC-targeting drugs for their activities against the African malaria vector Anopheles gambiae using in vitro blood feeding assays. Eprinomectin, selamectin, moxidectin, and N-tert-butyl nodulisporamide were evaluated as potentially systemic drugs having similar modes of action to ivermectin; all primarily are agonists of invertebrate glutamate-gated chloride ion channels. Additionally, nitenpyram and spinosad were evaluated as systemic drugs that primarily work as agonists of nicotinic acetylcholine receptor channels. Only eprinomectin killed An. gambiae at concentrations that were comparable to ivermectin. At sub-lethal doses, nitenpyram and moxidectin marginally affected mosquito re-blood feeding ability. The macrocyclic lactones, particularly eprinomectin, caused significantly increased knockdown and significantly inhibited recovery in blood fed females. These data are a first step in evaluating drugs that might be eventually combined with, or substituted for ivermectin for future malaria parasite transmission control.

Species-Specific Features of DARC, the Primate Receptor for Plasmodium vivax and Plasmodium knowlesi

The DARC (Duffy antigen/receptor for chemokines) gene, also called Duffy or FY, encodes a membrane-bound chemokine receptor. Two malaria parasites, Plasmodium vivax and Plasmodium knowlesi, use DARC to trigger internalization into red blood cells. Although much has been reported on the evolution of DARC null alleles, little is known about the evolution of the coding portion of this gene or the role that protein sequence divergence in this receptor may play in disease susceptibility or zoonosis. Here, we show that the Plasmodium interaction domain of DARC is nearly invariant in the human population, suggesting that coding polymorphism there is unlikely to play a role in differential susceptibility to infection. However, an analysis of DARC orthologs from 35 simian primate species reveals high levels of sequence divergence in the Plasmodium interaction domain. Signatures of positive selection in this domain indicate that species-specific mutations in the protein sequence of DARC could serve as barriers to the transmission of Plasmodium between primate species.

Rational deployment of antimalarial drugs in Africa: should first-line combination drugs be reserved for paediatric malaria cases?

Artemisinin-based combination therapy is exerting novel selective pressure upon populations of Plasmodium falciparum across Africa. Levels of resistance to non-artemisinin partner drugs differ among parasite populations, and so the artemisinins are not uniformly protected from developing resistance, already present in South East Asia. Here, we consider strategies for prolonging the period of high level efficacy of combination therapy for two particular endemicities common in Africa. Under high intensity transmission, two alternating first-line combinations, ideally with antagonistic selective effects on the parasite genome, are advocated for paediatric malaria cases. This leaves second-line and other therapies for adult cases, and for intermittent preventive therapy. The drug portfolio would be selected to protect the 'premier' combination regimen from selection for resistance, while maximising impact on severe disease and mortality in children. In endemic areas subject to low, seasonal transmission of Plasmodium falciparum, such a strategy may deliver little benefit, as children represent a minority of cases. Nevertheless, the deployment of other drug-based interventions in low transmission and highly seasonal areas, such as mass drug administration aimed to interrupt malaria transmission, or intermittent preventive therapy, does provide an opportunity to diversify drug pressure. We thus propose an integrated approach to drug deployment, which minimises direct selective pressure on parasite populations from any one drug component. This approach is suitable for qualitatively and quantitatively different burdens of malaria, and should be supported by a programme of routine surveillance for emerging resistance.

Infecting Mosquitoes Hampers Parasites, as Might a Malaria Vaccine

Infecting Anopheles gambiae mosquitoes with Wolbachia bacteria significantly lowers levels of the malaria parasite Plasmodium falciparum in those insects and thus interferes with their capacity to transmit malaria parasites to humans, according to Jason Rasgon at Johns Hopkins University in Baltimore, Md., and his collaborators. “This is the first time that anyone has shown that Wolbachia infections can reduce levels of the human malaria parasite in Anopheles,” he says. Whether this approach proves practical depends in part on learning how to transmit Wolbachia efficiently between generations of mosquitoes—and, ultimately, on combining this approach with others, including development and use of vaccines.