The Johns Hopkins Malaria Research Institute

Baltimore, MD, United States

The Johns Hopkins Malaria Research Institute

Baltimore, MD, United States
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PubMed | The Johns Hopkins Malaria Research Institute, University of Witwatersrand, Ndola Central Hospital and Macha Research Trust
Type: Journal Article | Journal: Parasites & vectors | Year: 2016

Despite large reductions in malaria burden across Zambia, some regions continue to experience extremely high malaria transmission. In Nchelenge District, Luapula Province, northern Zambia, almost half the human population carries parasites. Intervention coverage has increased substantially over the past decade, but comprehensive district-wide entomological studies to guide delivery of vector control measures are lacking. This study describes the bionomics and spatio-temporal patterns of malaria vectors in Nchelenge over a two and a half year period, investigates what household factors are associated with high vector densities and determines why vector control may not have been effective in the past to better guide future control efforts.Between April 2012 and September 2014, twenty-seven households from across Nchelenge District were randomly selected for monthly light trap collections of mosquitoes. Anopheline mosquitoes were identified morphologically and molecularly to species. Foraging rates were estimated and sporozoite rates were determined by circumsporozoite ELISAs to calculate annual entomological inoculation rates. Blood feeding rates and host preference were determined by PCR. Zero-inflated negative binomial models measured environmental and household factors associated with mosquito abundance at study households such as season, proximity to the lake, and use of vector control measures.The dominant species in Nchelenge was An. funestus (s.s.) with An. gambiae (s.s.) as a secondary vector. Both vectors were found together in large numbers across the district and the combined EIRs of the two vectors exceeded 80 infectious bites per person per annum. An. funestus household densities increased in the dry season whilst An. gambiae surged during the rains. Presence of insecticide treated nets (ITNs) and closed eaves in the houses were found to be associated with fewer numbers of An. gambiae but not An. funestus. There was no association with indoor residual spraying (IRS).In Nchelenge, the co-existence of two highly anthropophagic vectors, present throughout the year, is likely to be driving the high malaria transmission evident in the district. The vectors here have been shown to be highly resistant to pyrethroids used for IRS during the study. Vector control interventions in this area would have to be multifaceted and district-wide for effective control of malaria.

Hughes G.L.,Johns Hopkins University | Hughes G.L.,The Johns Hopkins Malaria Research Institute | Ren X.,Johns Hopkins University | Ramirez J.L.,Johns Hopkins University | And 6 more authors.
PLoS Pathogens | Year: 2011

The endosymbiotic bacterium Wolbachia is being investigated as a potential control agent in several important vector insect species. Recent studies have shown that Wolbachia can protect the insect host against a wide variety of pathogens, resulting in reduced transmission of parasites and viruses. It has been proposed that compromised vector competence of Wolbachia-infected insects is due to up-regulation of the host innate immune system or metabolic competition. Anopheles mosquitoes, which transmit human malaria parasites, have never been found to harbor Wolbachia in nature. While transient somatic infections can be established in Anopheles, no stable artificially-transinfected Anopheles line has been developed despite numerous attempts. However, cultured Anopheles cells can be stably infected with multiple Wolbachia strains such as wAlbB from Aedes albopictus, wRi from Drosophila simulans and wMelPop from Drosophila melanogaster. Infected cell lines provide an amenable system to investigate Wolbachia-Anopheles interactions in the absence of an infected mosquito strain. We used Affymetrix GeneChip microarrays to investigate the effect of wAlbB and wRi infection on the transcriptome of cultured Anopheles Sua5B cells, and for a subset of genes used quantitative PCR to validate results in somatically-infected Anopheles mosquitoes. Wolbachia infection had a dramatic strain-specific effect on gene expression in this cell line, with almost 700 genes in total regulated representing a diverse array of functional classes. Very strikingly, infection resulted in a significant down-regulation of many immune, stress and detoxification-related transcripts. This is in stark contrast to the induction of immune genes observed in other insect hosts. We also identified genes that may be potentially involved in Wolbachia-induced reproductive and pathogenic phenotypes. Somatically-infected mosquitoes had similar responses to cultured cells. The data show that Wolbachia has a profound and unique effect on Anopheles gene expression in cultured cells, and has important implications for mechanistic understanding of Wolbachia-induced phenotypes and potential novel strategies to control malaria. © 2011 Hughes et al.

Hughes G.L.,Johns Hopkins University | Hughes G.L.,The Johns Hopkins Malaria Research Institute | Koga R.,Japan National Institute of Advanced Industrial Science and Technology | Xue P.,Johns Hopkins University | And 4 more authors.
PLoS Pathogens | Year: 2011

Endosymbiotic Wolbachia bacteria are potent modulators of pathogen infection and transmission in multiple naturally and artificially infected insect species, including important vectors of human pathogens. Anopheles mosquitoes are naturally uninfected with Wolbachia, and stable artificial infections have not yet succeeded in this genus. Recent techniques have enabled establishment of somatic Wolbachia infections in Anopheles. Here, we characterize somatic infections of two diverse Wolbachia strains (wMelPop and wAlbB) in Anopheles gambiae, the major vector of human malaria. After infection, wMelPop disseminates widely in the mosquito, infecting the fat body, head, sensory organs and other tissues but is notably absent from the midgut and ovaries. Wolbachia initially induces the mosquito immune system, coincident with initial clearing of the infection, but then suppresses expression of immune genes, coincident with Wolbachia replication in the mosquito. Both wMelPop and wAlbB significantly inhibit Plasmodium falciparum oocyst levels in the mosquito midgut. Although not virulent in non-bloodfed mosquitoes, wMelPop exhibits a novel phenotype and is extremely virulent for approximately 12-24 hours post-bloodmeal, after which surviving mosquitoes exhibit similar mortality trajectories to control mosquitoes. The data suggest that if stable transinfections act in a similar manner to somatic infections, Wolbachia could potentially be used as part of a strategy to control the Anopheles mosquitoes that transmit malaria. © 2011 Hughes et al.

Hughes G.L.,Pennsylvania State University | Vega-Rodriguez J.,Johns Hopkins University | Vega-Rodriguez J.,The Johns Hopkins Malaria Research Institute | Xue P.,Johns Hopkins University | Rasgon J.L.,Pennsylvania State University
Applied and Environmental Microbiology | Year: 2012

Wolbachia, a common bacterial endosymbiont of insects, has been shown to protect its hosts against a wide range of pathogens. However, not all strains exert a protective effect on their host. Here we assess the effects of two divergent Wolbachia strains, wAlbB from Aedes albopictus and wMelPop from Drosophila melanogaster, on the vector competence of Anopheles gambiae challenged with Plasmodium berghei. We show that the wAlbB strain significantly increases P. berghei oocyst levels in the mosquito midgut while wMelPop modestly suppresses oocyst levels. The wAlbB strain is avirulent to mosquitoes while wMelPop is moderately virulent to mosquitoes pre-blood meal and highly virulent after mosquitoes have fed on mice. These various effects on P. berghei levels suggest that Wolbachia strains differ in their interactions with the host and/or pathogen, and these differences could be used to dissect the molecular mechanisms that cause interference of pathogen development in mosquitoes. © 2012, American Society for Microbiology.

Foy B.D.,Colorado State University | Kobylinski K.C.,Colorado State University | Silva I.M.D.,Colorado State University | Rasgon J.L.,Johns Hopkins University | And 2 more authors.
Trends in Parasitology | Year: 2011

Systemic endectocidal drugs, used to control nematodes in humans and other vertebrates, can be toxic to Anopheles spp. mosquitoes when they take a blood meal from a host that has recently received one of these drugs. Recent laboratory and field studies have highlighted the potential of ivermectin to control malaria parasite transmission if this drug is distributed strategically and more often. There are important theoretical benefits to this strategy, as well as caveats. A better understanding of drug effects against vectors and malaria ecologies are needed. In the near future, ivermectin and other endectocides could serve as potent and novel malaria transmission control tools that are directly linked to the control of neglected tropical diseases in the same communities. © 2011 Elsevier Ltd.

Zhang X.,Johns Hopkins University | Norris D.E.,Johns Hopkins University | Norris D.E.,The Johns Hopkins Malaria Research Institute | Rasgon J.L.,Johns Hopkins University | Rasgon J.L.,The Johns Hopkins Malaria Research Institute
FEMS Microbiology Ecology | Year: 2011

The lone star tick Amblyomma americanum is host to a wide diversity of endosymbiotic bacteria. We identified a novel Wolbachia symbiont infecting A. americanum. Multilocus sequence typing phylogenetically placed the endosymbiont in the increasingly diverse F supergroup. We assayed a total of 1031 ticks (119 females, 78 males and 834 nymphs in 89 pools) from 16 Maryland populations for infection. Infection frequencies in the natural populations were approximately 5% in females and o2% (minimum infection rate) in nymphs; infection was not detected in males. Infected populations were only observed in southern Maryland, suggesting the possibility that Wolbachia is currently invading Maryland A. americanum populations. Because F supergroup Wolbachia have been detected previously in filarial nematodes, tick samples were assayed for nematodes by PCR. Filarial nematodes were detected in 70% and 9% of Wolbachia-positive and Wolbachia-negative tick samples, respectively. While nematodes were more common in Wolbachia-positive tick samples, the lack of a strict infection concordance (Wolbachia-positive, nematode-negative and Wolbachia-negative, nematode-positive ticks) suggests that Wolbachia prevalence in ticks is not due to nematode infection. Supporting this hypothesis, phylogenetic analysis indicated that the nematodes were likely a novel species within the genus Acanthocheilonema, which has been previously shown to be Wolbachia-free. © 2011 Federation of European Microbiological Societies.

Zhang X.,Johns Hopkins University | Ren X.,Johns Hopkins University | Ren X.,The Johns Hopkins Malaria Research Institute | Norris D.E.,Johns Hopkins University | And 2 more authors.
Ticks and Tick-borne Diseases | Year: 2012

Amblyomma americanum (the lone star tick) is a broadly distributed tick that transmits multiple pathogens of humans and domestic animals. 'Candidatus Rickettsia amblyommii' is a spotted-fever group rickettsial species that is potentially associated with human disease. In 2008 and 2009, we assayed over 500 unfed adult ticks from 19 Maryland populations for the presence of 'Candidatus R. amblyommii'. Infection frequencies ranged from 33% to 100%, with an average infection rate of 60% in 2008 and 69% in 2009. Infection frequencies did not differ statistically between sexes. To develop a system in which to study 'Candidatus R. amblyommii' in the laboratory, we used a cell line developed from Anopheles gambiae mosquitoes (Sua5B) to isolate and culture 'Candidatus R. amblyommii' from field-collected A. americanum ticks from 2 localities in Maryland. After infection, Sua5B cells were infected for more than 40 passages. Infection was confirmed by Rickettsia-specific PCR, gene sequencing, and Rickettsia-specific fluorescence in situ hybridization (FISH). These data show that 'Candidatus R. amblyommii' is widespread in Maryland A. americanum populations and that Sua5B cells are a useful tool for culturing Rickettsia infections from wild ticks. © 2011 Elsevier GmbH.

Oluwagbemi O.O.,The Johns Hopkins Malaria Research Institute | Oluwagbemi O.O.,Covenant University | Fornadel C.M.,The Johns Hopkins Malaria Research Institute | Adebiyi E.F.,Covenant University | And 2 more authors.
PLoS ONE | Year: 2013

Anopheles mosquitoes transmit malaria, a major public health problem among many African countries. One of the most effective methods to control malaria is by controlling the Anopheles mosquito vectors that transmit the parasites. Mathematical models have both predictive and explorative utility to investigate the pros and cons of different malaria control strategies. We have developed a C++ based, stochastic spatially explicit model (ANOSPEX; Anopheles Spatially-Explicit) to simulate Anopheles metapopulation dynamics. The model is biologically rich, parameterized by field data, and driven by field-collected weather data from Macha, Zambia. To preliminarily validate ANOSPEX, simulation results were compared to field mosquito collection data from Macha; simulated and observed dynamics were similar. The ANOSPEX model will be useful in a predictive and exploratory manner to develop, evaluate and implement traditional and novel strategies to control malaria, and for understanding the environmental forces driving Anopheles population dynamics. © 2013 Oluwagbemi et al.

PubMed | The Johns Hopkins Malaria Research Institute
Type: Review | Journal: Insects | Year: 2016

Entomological indices and bionomic descriptions of malaria vectors are essential to accurately describe and understand malaria transmission and for the design and evaluation of appropriate control interventions. In order to correctly assign spatio-temporal distributions, behaviors and responses to interventions to particular anopheline species, identification of mosquitoes must be accurately made. This paper reviews the current methods and their limitations in correctly identifying anopheline mosquitoes in sub-Saharan Africa, and highlights the importance of molecular methods to discriminate cryptic species and identify lesser known anophelines. The increasing number of reports of

PubMed | The Johns Hopkins Malaria Research Institute and Macha Research Trust
Type: Journal Article | Journal: Journal of medical entomology | Year: 2016

Southern Zambia is the focus of strategies to create malaria-free zones. Interventions being rolled out include test and treat strategies and distribution of insecticide-treated bed nets that target vectors that host-seek indoors and late at night. In Macha, Choma District, collections of mosquitoes were made outdoors using barrier screens within homesteads or UV bulb light traps set next to goats, cattle, or chickens during the rainy season of 2015. Anopheline mosquitoes were identified to species using molecular methods and Plasmodium falciparum infectivity was determined by ELISA and real-time qPCR methods. More than 40% of specimens caught were identified as Anopheles squamosus Theobald, 1901 of which six were found harboring malaria parasites. A single sample, morphologically identified as Anopheles coustani Laveran, 1900, was also found to be infectious. All seven specimens were caught outdoors next to goat pens. Parasite-positive specimens as well as a subset of An. squamosus specimens from either the same study or archive collections from the same area underwent sequencing of the mitochondrial cytochrome oxidase subunit I gene. Maximum parsimony trees constructed from the aligned sequences indicated presence of at least two clades of An. squamosus with infectious specimens falling in each clade. The single infectious specimen identified morphologically as An. coustani could not be matched to reference sequences. This is the first report from Zambia of infections in An. squamosus, a species which is described in literature to display exophagic traits. The bionomic characteristics of this species needs to be studied further to fully evaluate the implications for indoor-targeted vector control.

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