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1.
Trials ; 23(1): 578, 2022 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-35854371

RESUMO

BACKGROUND: Long-lasting insecticidal nets (LLINs) have contributed to the reduction of malaria in sub-Saharan Africa, including Tanzania. However, they rely on daily user behaviour and high coverage which is difficult to maintain. Also, insecticide resistance among malaria vector mosquitoes is contributing to reduced efficacy of control tools. To overcome these problems, we propose to evaluate a new tool for house modification, the insecticide-treated eave nets (ITENs) in combination with insecticide-treated window screens (ITWS) incorporated with dual active ingredient (dual AI) for the control of malaria. METHODS: Four hundred and fifty (450) households with intact walls, open eaves without screens or nets on the windows in Chalinze district will be eligible and recruited upon written informed consent. The households will be randomly allocated into two arms: one with ITENs and ITWS installed and the other without. Malaria parasite detection using a quantitative polymerase chain reaction (qPCR) will be conducted shortly after the long rain (June/July, 2022) as the primary outcome and shortly after the short rain (January/February, 2022) as the secondary outcome. Other secondary outcomes include clinical malaria cases, and density of malaria vectors and nuisance after the short rain and long rain. In addition, surveys will be conducted in households with ITENs and ITWS to estimate the intervention's cost during installation, adverse effects one month after installation, and presence, fabric integrity and user acceptance six and twelve months after installation. Bioefficacy and chemical content will be evaluated twelve months after installation. DISCUSSION: ITENs and ITWS have been shown in Kenya to reduce indoor mosquito density. However, it is not known if indoor mosquito density reduction translates into reduction of malaria cases. Data from the study will measure the potential public health value of an additional intervention for malaria control at the household level in areas of mosquito insecticide resistance that does not require daily adherence. TRIAL REGISTRATION: The study is registered on ClinicalTrials.gov .


Assuntos
Anopheles , Mosquiteiros Tratados com Inseticida , Inseticidas , Malária , Animais , Anopheles/parasitologia , Humanos , Inseticidas/farmacologia , Malária/prevenção & controle , Controle de Mosquitos/métodos , Mosquitos Vetores , Ensaios Clínicos Controlados Aleatórios como Assunto , Tanzânia
2.
Malar J ; 21(1): 211, 2022 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-35780113

RESUMO

BACKGROUND: Nchelenge District in northern Zambia suffers from holoendemic malaria transmission despite a decade of yearly indoor residual spraying (IRS) and insecticide-treated net (ITN) distributions. One hypothesis for this lack of impact is that some vectors in the area may forage in the early evening or outdoors. Anopheles gibbinsi specimens were identified in early evening mosquito collections performed in this study area, and further insight was gleaned into this taxon, including characterizing its genetic identity, feeding preferences, and potential role as a malaria vector. METHODS: Mosquitoes were collected in July and August 2019 by CDC light traps in Nchelenge District in indoor sitting rooms, outdoor gathering spaces, and animal pens from 16:00-22:00. Host detection by PCR, COI and ITS2 PCR, and circumsporozoite (CSP) ELISA were performed on all samples morphologically identified as An. gibbinsi, and a subset of specimens were selected for COI and ITS2 sequencing. To determine risk factors for increased abundance of An. gibbinsi, a negative binomial generalized linear mixed-effects model was performed with household-level variables of interest. RESULTS: Comparison of COI and ITS2 An. gibbinsi reference sequences to the NCBI database revealed > 99% identity to "Anopheles sp. 6" from Kenya. More than 97% of specimens were morphologically and molecularly consistent with An. gibbinsi. Specimens were primarily collected in animal pen traps (59.2%), followed by traps outdoors near where humans gather (24.3%), and traps set indoors (16.5%). Host DNA detection revealed a high propensity for goats, but 5% of specimens with detected host DNA had fed on humans. No specimens were positive for Plasmodium falciparum sporozoites. Animal pens and inland households > 3 km from Lake Mweru were both associated with increased An. gibbinsi abundance. CONCLUSIONS: This is the first report of An. gibbinsi in Nchelenge District, Zambia. This study provided a species identity for unknown "An. sp. 6" in the NCBI database, which has been implicated in malaria transmission in Kenya. Composite data suggest that this species is largely zoophilic and exophilic, but comes into contact with humans and the malaria parasites they carry. This species should continue to be monitored in Zambia and neighbouring countries as a potential malaria vector.


Assuntos
Anopheles , Malária , Animais , Anopheles/parasitologia , DNA , Malária/epidemiologia , Mosquitos Vetores/parasitologia , Zâmbia/epidemiologia
3.
Nat Commun ; 13(1): 4123, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35840625

RESUMO

Plasmodium vivax is the most widespread human malaria parasite. Due to the presence of extravascular reservoirs and relapsing infections from dormant liver stages, P. vivax is particularly difficult to control and eliminate. Experimental research is hampered by the inability to maintain P. vivax cultures in vitro, due to its tropism for immature red blood cells (RBCs). Here, we describe a new humanized mice model that can support efficient human erythropoiesis and maintain long-lasting multiplication of inoculated cryopreserved P. vivax parasites and their sexual differentiation, including in bone marrow. Mature gametocytes were transmitted to Anopheles mosquitoes, which led to the formation of salivary gland sporozoites. Importantly, blood-stage P. vivax parasites were maintained after the secondary transfer of fresh or frozen infected bone marrow cells to naïve chimeras. This model provides a unique tool for investigating, in vivo, the biology of intraerythrocytic P. vivax.


Assuntos
Anopheles , Malária Vivax , Animais , Anopheles/parasitologia , Humanos , Malária Vivax/parasitologia , Camundongos , Recidiva Local de Neoplasia , Plasmodium vivax , Esporozoítos
4.
Am J Trop Med Hyg ; 107(1): 154-161, 2022 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-35895359

RESUMO

Understanding the reservoir and infectivity of Plasmodium gametocytes to vector mosquitoes is crucial to align strategies aimed at malaria transmission elimination. Yet, experimental information is scarce regarding the infectivity of Plasmodium vivax for mosquitoes in diverse epidemiological settings where the proportion of asymptomatically infected individuals varies at a microgeographic scale. We measured the transmissibility of clinical and subclinical P. vivax malaria parasite carriers to the major mosquito vector in the Amazon Basin, Nyssorhynchus darlingi (formerly Anopheles). A total of 105 participants with natural P. vivax malaria infection were recruited from a cohort study in Loreto Department, Peruvian Amazon. Four of 18 asymptomatic individuals with P. vivax positivity by blood smear infected colony-grown Ny. darlingi (22%), with 2.6% (19 of 728) mosquitoes infected. In contrast, 77% (44/57) of symptomatic participants were infectious to mosquitoes with 51% (890 of 1,753) mosquitoes infected. Infection intensity was greater in symptomatic infections (mean, 17.8 oocysts/mosquito) compared with asymptomatic infections (mean, 0.28 oocysts/mosquito), attributed to parasitemia/gametocytemia level. Paired experiments (N = 27) using direct skin-feeding assays and direct membrane mosquito-feeding assays showed that infectivity to mosquitoes was similar for both methods. Longitudinal studies with longer follow-up of symptomatic and asymptomatic parasite infections are needed to determine the natural variations of disease transmissibility.


Assuntos
Anopheles , Malária Vivax , Malária , Animais , Anopheles/parasitologia , Infecções Assintomáticas/epidemiologia , Estudos de Coortes , Humanos , Malária Vivax/parasitologia , Mosquitos Vetores/parasitologia , Plasmodium vivax
5.
PLoS Pathog ; 18(6): e1010609, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35687594

RESUMO

The spread of insecticide resistance in Anopheles mosquitoes and drug resistance in Plasmodium parasites is contributing to a global resurgence of malaria, making the generation of control tools that can overcome these roadblocks an urgent public health priority. We recently showed that the transmission of Plasmodium falciparum parasites can be efficiently blocked when exposing Anopheles gambiae females to antimalarials deposited on a treated surface, with no negative consequences on major components of mosquito fitness. Here, we demonstrate this approach can overcome the hurdles of insecticide resistance in mosquitoes and drug resistant in parasites. We show that the transmission-blocking efficacy of mosquito-targeted antimalarials is maintained when field-derived, insecticide resistant Anopheles are exposed to the potent cytochrome b inhibitor atovaquone, demonstrating that this drug escapes insecticide resistance mechanisms that could potentially interfere with its function. Moreover, this approach prevents transmission of field-derived, artemisinin resistant P. falciparum parasites (Kelch13 C580Y mutant), proving that this strategy could be used to prevent the spread of parasite mutations that induce resistance to front-line antimalarials. Atovaquone is also highly effective at limiting parasite development when ingested by mosquitoes in sugar solutions, including in ongoing infections. These data support the use of mosquito-targeted antimalarials as a promising tool to complement and extend the efficacy of current malaria control interventions.


Assuntos
Anopheles , Antimaláricos , Malária Falciparum , Malária , Plasmodium , Animais , Anopheles/parasitologia , Antimaláricos/farmacologia , Atovaquona/farmacologia , Feminino , Malária/parasitologia , Malária/prevenção & controle , Malária Falciparum/tratamento farmacológico , Malária Falciparum/parasitologia , Malária Falciparum/prevenção & controle , Plasmodium falciparum/genética
6.
Malar J ; 21(1): 188, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35705981

RESUMO

BACKGROUND: A study was conducted prior to implementing a cluster-randomized controlled trial (CRT) of a lethal house lure strategy in central Côte d'Ivoire to provide baseline information on malaria indicators in 40 villages across five health districts. METHODS: Human landing catches (HLC) were performed between November and December 2016, capturing mosquitoes indoors and outdoors between 18.00 and 08.00 h. Mosquitoes were processed for entomological indicators of malaria transmission (human biting, parity, sporozoite, and entomological inoculation rates (EIR)). Species composition and allelic frequencies of kdr-w and ace-1R mutations were also investigated within the Anopheles gambiae complex. RESULTS: Overall, 15,632 mosquitoes were captured. Anopheles gambiae sensu lato (s.l.) and Anopheles funestus were the two malaria vectors found during the survey period, with predominance for An. gambiae (66.2%) compared to An. funestus (10.3%). The mean biting rate for An. gambiae was almost five times higher than that for An. funestus (19.8 bites per person per night for An. gambiae vs 4.3 bites per person per night for An. funestus) and this was evident indoors and outdoors. Anopheles funestus was more competent to transmit malaria parasites in the study area, despite relatively lower number tested for sporozoite index (4.14% (63/1521) for An. gambiae vs 8.01% (59/736) for An. funestus; χ2 = 12.216; P < 0.0001). There were no significant differences between the proportions infected outdoors and indoors for An. gambiae (4.03 vs 4.13%; χ2 = 0.011; P = 0.9197) and for An. funestus (7.89 vs 8.16%; χ2 = 2.58e-29; P = 1). The majority of both infected vectors with malaria parasites harboured Plasmodium falciparum (93.65% for An. gambiae and 98. 31% for An. funestus). Overall, the EIR range for both species in the different districts appeared to be high (0.35-2.20 infected bites per human per night) with the highest value observed in the district of North-Eastern-Bouaké. There were no significant differences between transmission occurring outdoor and indoor for both species. Of the An. gambiae s.l. analysed, only An. gambiae sensu stricto (14.1%) and Anopheles coluzzii (85.9%) were found. The allelic frequencies of kdr and ace-1R were higher in An. gambiae (0.97 for kdr and 0.19 for ace-1R) than in An. coluzzii (0.86 for kdr and 0.10 for ace-1R) (P < 0.001). CONCLUSION: Despite universal coverage with long-lasting insecticidal nets (LLINs) in the area, there was an abundance of the malaria vectors (An. gambiae and An. funestus) in the study area in central Côte d'Ivoire. Consistent with high insecticide resistance intensity previously detected in these districts, the current study detected high kdr frequency (> 85%), coupled with high malaria transmission pattern, which could guide the use of Eave tubes in the study areas.


Assuntos
Anopheles , Mordeduras e Picadas , Malária , Animais , Anopheles/parasitologia , Costa do Marfim/epidemiologia , Humanos , Resistência a Inseticidas/genética , Malária/prevenção & controle , Mosquitos Vetores/parasitologia , Esporozoítos
7.
PLoS Pathog ; 18(6): e1010643, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35731833

RESUMO

Plasmodium sporozoites that are transmitted by blood-feeding female Anopheles mosquitoes invade hepatocytes for an initial round of intracellular replication, leading to the release of merozoites that invade and multiply within red blood cells. Sporozoites and merozoites share a number of proteins that are expressed by both stages, including the Apical Membrane Antigen 1 (AMA1) and the Rhoptry Neck Proteins (RONs). Although AMA1 and RONs are essential for merozoite invasion of erythrocytes during asexual blood stage replication of the parasite, their function in sporozoites was still unclear. Here we show that AMA1 interacts with RONs in mature sporozoites. By using DiCre-mediated conditional gene deletion in P. berghei, we demonstrate that loss of AMA1, RON2 or RON4 in sporozoites impairs colonization of the mosquito salivary glands and invasion of mammalian hepatocytes, without affecting transcellular parasite migration. Three-dimensional electron microscopy data showed that sporozoites enter salivary gland cells through a ring-like structure and by forming a transient vacuole. The absence of a functional AMA1-RON complex led to an altered morphology of the entry junction, associated with epithelial cell damage. Our data establish that AMA1 and RONs facilitate host cell invasion across Plasmodium invasive stages, and suggest that sporozoites use the AMA1-RON complex to efficiently and safely enter the mosquito salivary glands to ensure successful parasite transmission. These results open up the possibility of targeting the AMA1-RON complex for transmission-blocking antimalarial strategies.


Assuntos
Anopheles , Plasmodium , Animais , Anopheles/parasitologia , Feminino , Glucanos , Mamíferos , Merozoítos/metabolismo , Plasmodium/metabolismo , Plasmodium berghei/genética , Proteínas de Protozoários/metabolismo , Esporozoítos/metabolismo
8.
Malar J ; 21(1): 172, 2022 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-35672768

RESUMO

BACKGROUND: Low-level of malaria transmission persist in Zanzibar despite high coverage of core vector control interventions. This study was carried out in hot-spot sites to better understand entomological factors that may contribute to residual malaria transmission in Zanzibar. METHODS: A total of 135 households were randomly selected from six sites and consented to participate with 20-25 households per site. Mosquito vector surveillance was carried out indoors and outdoors from 6:00 pm-7:00 am using miniaturized double net trap (DN-Mini™). Additional collections were done indoors using mouth aspirators to retrieve resting mosquitoes from wall and ceiling surfaces, and outdoors using resting bucket and pit traps. All collected mosquitoes were morphologically and genetically (PCR) analysed in the laboratory. All collected anopheline and blood-fed mosquitoes were analysed for sporozoite infection and blood meal host preferences by Circumsporozoite Protein ELISA and blood meal ELISA, respectively. The differences between indoor and outdoor mosquito biting rates were analysed using generalized linear mixed models. Levels of resistance to commonly used insecticides were quantified by WHO susceptibility tests. RESULTS: Out of 704 malaria vectors collected across 135 households, PCR analysis shows that 98.60% were Anopheles arabiensis, 0.6% Anopheles merus and 0.6% Anopheles gambiae sensu stricto. Sporozoite ELISA analysis indicates that all mosquitoes were negative for the malaria parasite. The results show that more An. arabiensis were collected outdoor (~ 85%) compared to indoor (~ 15%). Furthermore, large numbers of An. arabiensis were caught in outdoor resting sites, where the pit trap (67.2%) collected more mosquitoes compared to the outdoor DN-Mini trap (32.8%). Nearly two-thirds (60.7%) of blood-fed mosquitoes had obtained blood meals from non-human hosts. Mosquitoes displayed non-uniform susceptibility status and resistance intensity among the tested insecticides across the study sites to all WHO recommended insecticides across the study sites. CONCLUSION: This study suggests that in contexts such as Zanzibar, testing of novel techniques to complement indoor protection and targeting outdoor biting and/or resting mosquitoes, may be warranted to complement existing interventions and contribute to malaria elimination efforts. The study highlights the need to implement novel interventions and/or adaptations of strategies that can target outdoors biting mosquitoes.


Assuntos
Anopheles , Inseticidas , Malária , Piretrinas , Animais , Anopheles/parasitologia , Comportamento Alimentar , Malária/prevenção & controle , Controle de Mosquitos/métodos , Mosquitos Vetores/parasitologia , Esporozoítos , Tanzânia
9.
Trends Parasitol ; 38(8): 610-613, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35715304

RESUMO

One hundred and twenty five years ago, in August 1897, Ronald Ross discovered forms of the malaria parasite in the gut of two mosquitoes. Shortly afterwards, Giovanni Battista Grassi established how the transmissive forms of the parasite, sporozoites, develop in these Plasmodium oocysts. Today, we still understand surprisingly little about the molecular processes governing oocyst biology.


Assuntos
Anopheles , Plasmodium , Animais , Anopheles/parasitologia , Oocistos , Esporozoítos
10.
Acta Trop ; 233: 106567, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35714924

RESUMO

Malaria is an important public health problem, caused by Plasmodium parasites which are transmitted by female Anopheles mosquitoes that bite humans to obtain blood. The aim of this work was to identify the blood feeding sources of Anopheles female mosquitoes and calculate their entomological indices in relation to Plasmodium transmission. Mosquitoes were collected in malaria endemic localities of the Bajo Cauca and Pacific regions of Colombia using human landing catch and barrier screens, from 18:00 to 24:00 hr, in 2018-2021. Animal censuses within a radius of ∼250 m were carried out at each sampling site. A total of 2018 Anopheles specimens were collected and the most abundant species were Anopheles (Nys.) darlingi and Anopheles (Nys.) nuneztovari. The highest human biting rate was 77.5 bites per person per night (b/p/n) for An. nuneztovari in Córdoba-Pacific and 17.5 b/p/n for An. darlingi in Villa Grande-Bajo Cauca. Both species were active mainly in indoor unwalled rooms of the houses. Only An. nuneztovari from Córdoba-Pacific was infected with Plasmodium, with an entomological inoculation rate of 91.25 infective bites per year. Detection of blood feeding sources demonstrate that humans were the most common host, however, An. nuneztovari showed a preference for feeding on dogs and An. darlingi on pigs, dogs and Galliformes, rather than humans. These results contribute to entomological surveillance information and provide valuable data that can be used to tailor effective control interventions to minimize human-vector contact in these malaria endemic regions.


Assuntos
Anopheles , Doenças Endêmicas , Malária , Mosquitos Vetores , Animais , Anopheles/parasitologia , Colômbia/epidemiologia , Cães , Feminino , Galliformes , Humanos , Malária/epidemiologia , Mosquitos Vetores/parasitologia , Plasmodium , Suínos
11.
J Vis Exp ; (183)2022 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-35635457

RESUMO

Malaria remains one of the most devastating diseases worldwide and, to date, the African region is still responsible for 94% of all cases worldwide. This parasitic disease requires a protozoan parasite, an Anopheles mosquito vector, and a vertebrate host. The Anopheles genus comprises more than 500 species, of which 60 are known as vectors of the parasite. The Plasmodium parasite genus consists of 250 species, and 48 of these are involved in disease transmission. Furthermore, the Plasmodium falciparum parasite has contributed toward an estimated 99.7% of malaria cases in sub-Saharan Africa in recent years. Gametocytes form part of the sexual stage of the parasite and are ingested by the female mosquito upon feeding on an infected human host. Further development of the parasite within the mosquito is enhanced by favorable environmental conditions in the midgut of the mosquito. Here, the fusion of the female and male gametes takes place, and the motile ookinetes originate. The ookinetes enter the midgut epithelium of the mosquito, and mature ookinetes form oocysts, which, in turn, produce motile sporozoites. These sporozoites migrate to the mosquito's salivary glands and are injected as a mosquito takes a blood meal. For drug discovery purposes, mosquitoes were artificially infected with gametocyte-infected blood in the standard membrane feeding assay (SMFA). To detect infection within the mosquito and/or to assess the efficacy of antimalarial compounds, the midguts of the female mosquitoes were removed post infection and were stained with mercurochrome. This method was used to enhance the visual detection of oocysts under the microscope for the accurate determination of oocyst prevalence and intensity.


Assuntos
Anopheles , Malária Falciparum , Malária , Plasmodium , Animais , Anopheles/parasitologia , Feminino , Humanos , Malária/parasitologia , Malária Falciparum/parasitologia , Masculino , Mosquitos Vetores , Plasmodium falciparum , Esporozoítos
12.
Proc Natl Acad Sci U S A ; 119(21): e2104282119, 2022 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-35576470

RESUMO

Malaria control interventions target nocturnal feeding of the Anopheles vectors indoors to reduce parasite transmission. Mass deployment of insecticidal bed nets and indoor residual spraying with insecticides, however, may induce mosquitoes to blood-feed at places and at times when humans are not protected. These changes can set a ceiling to the efficacy of these control interventions, resulting in residual malaria transmission. Despite its relevance for disease transmission, the daily rhythmicity of Anopheles biting behavior is poorly documented, most investigations focusing on crepuscular hours and nighttime. By performing mosquito collections 48-h around the clock, both indoors and outdoors, and by modeling biting events using circular statistics, we evaluated the full daily rhythmicity of biting in urban Bangui, Central African Republic. While the bulk of biting by Anopheles gambiae, Anopheles coluzzii, Anopheles funestus, and Anopheles pharoensis occurred from sunset to sunrise outdoors, unexpectedly ∼20 to 30% of indoor biting occurred during daytime. As biting events did not fully conform to any family of circular distributions, we fitted mixtures of von Mises distributions and found that observations were consistent with three compartments, corresponding indoors to populations of early-night, late-night, and daytime-biting events. It is not known whether these populations of biting events correspond to spatiotemporal heterogeneities or also to distinct mosquito genotypes/phenotypes belonging consistently to each compartment. Prevalence of Plasmodium falciparum in nighttime- and daytime-biting mosquitoes was the same. As >50% of biting occurs in Bangui when people are unprotected, malaria control interventions outside the domiciliary environment should be envisaged.


Assuntos
Anopheles , Ritmo Circadiano , Comportamento Alimentar , Mordeduras e Picadas de Insetos , Malária , Controle de Mosquitos , Animais , Anopheles/parasitologia , Anopheles/fisiologia , República Centro-Africana , Humanos , Mordeduras e Picadas de Insetos/parasitologia , Malária/prevenção & controle , Malária/transmissão , Controle de Mosquitos/métodos , Mosquitos Vetores , Plasmodium falciparum/isolamento & purificação
13.
Sci Rep ; 12(1): 7674, 2022 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-35538208

RESUMO

Members of the Anopheles gambiae complex and Anopheles funestus group are significant vectors of the malaria parasite Plasmodium species in the Afro-tropical region of the world. Molecular identification and variation in the wing were studied among female An. Gambiae complex and An. funestus group, to investigate morphological variations in the wing of local vectors populations of adult female mosquitoes found in five different locations in Akure North Local Government Area of Ondo State (Oba-Ile, Igoba, Isinigbo, Ita-Ogbolu and Iju). The variations in the wing character were found in the 3rd main dark spot area (Pre-apical dark spot-character 8) on the coastal region (Vein region I) of Anopheles gambiae complex wing; with two types (A and B) of wings identified with An. gambiae complex in the study area. Molecular study shows that all the wing type A are Anopheles gambiae s.s., they represent 53.39% of the total An. gambiae complex in the study area. Some of the Anopheles gambiae s.s. (28.30%) and all An. arabiensis (18.30%) were found with wing type B. Among 750 individual Anopheles mosquito species identified using Polymerase Chain Reaction (PCR method), 433 samples representing 57.73% were An. gambiae s.s. while 97 (12.93%) samples were An. arabiensis. Anopheles leesoni was the only member of the An. funestus group identified in the study area. Anopheles leesoni mosquitoes identified in the study location were 182, representing 24.27% of the total Anopheles mosquito species identified using the molecular method. Anopheles gambiae s.s., An. arabiensis, and An. leesoni are only Anopheles mosquito species responsible for malaria transmission in the study area. Anopheles leesoni was the only member of the An. funestus group identified in the study area.


Assuntos
Anopheles , Malária , Animais , Anopheles/genética , Anopheles/parasitologia , Feminino , Governo Local , Masculino , Mosquitos Vetores/genética , Mosquitos Vetores/parasitologia , Nigéria
14.
mBio ; 13(3): e0057822, 2022 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-35638735

RESUMO

Sexual reproduction of Plasmodium falciparum parasites is critical to the spread of malaria in the human population. The factors that regulate gene expression underlying formation of fertilization-competent gametes, however, remain unknown. Here, we report that P. falciparum expresses a protein with an AT-rich interaction domain (ARID) which, in other organisms, is part of chromatin remodeling complexes. P. falciparum ARID (PfARID) localized to the parasite nucleus and is critical for the formation of male gametes and fertility of female gametes. PfARID gene deletion (Pfarid-) gametocytes showed downregulation of gene expression important for gametogenesis, antigenic variation, and cell signaling and for parasite development in the mosquito. Our study identifies PfARID as a critical nuclear protein involved in regulating the gene expression landscape of mature gametocytes. This establishes fertility and also prepares the parasite for postfertilization events that are essential for infection of the mosquito vector. IMPORTANCE Successful completion of the Plasmodium life cycle requires formation of mature gametocytes and their uptake by the female Anopheles mosquito vector in an infected blood meal. Inside the mosquito midgut the parasite undergoes gametogenesis and sexual reproduction. In the present study, we demonstrate that PfARID is essential for male gametogenesis and female fertility and, thereby, transmission to the mosquito vector. PfARID possibly regulates the chromatin landscape of stage V gametocytes and targeting PfARID function may provide new avenues into designing interventions to prevent malaria transmission.


Assuntos
Anopheles , Malária Falciparum , Malária , Parasitos , Animais , Anopheles/parasitologia , Feminino , Fertilidade , Gametogênese/genética , Humanos , Malária/parasitologia , Malária Falciparum/parasitologia , Masculino , Mosquitos Vetores/parasitologia , Plasmodium falciparum/fisiologia
15.
Nat Commun ; 13(1): 2949, 2022 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-35618711

RESUMO

In mammals, the serine protease plasmin degrades extracellular proteins during blood clot removal, tissue remodeling, and cell migration. The zymogen plasminogen is activated into plasmin by two serine proteases: tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA), a process regulated by plasminogen activator inhibitor 1 (PAI-1), a serine protease inhibitor that specifically inhibits tPA and uPA. Plasmodium gametes and sporozoites use tPA and uPA to activate plasminogen and parasite-bound plasmin degrades extracellular matrices, facilitating parasite motility in the mosquito and the mammalian host. Furthermore, inhibition of plasminogen activation by PAI-1 strongly blocks infection in both hosts. To block parasite utilization of plasmin, we engineered Anopheles stephensi transgenic mosquitoes constitutively secreting human PAI-1 (huPAI-1) in the midgut lumen, in the saliva, or both. Mosquitoes expressing huPAI-1 strongly reduced rodent and human Plasmodium parasite transmission to mosquitoes, showing that co-opting plasmin for mosquito infection is a conserved mechanism among Plasmodium species. huPAI-1 expression in saliva induced salivary gland deformation which affects sporozoite invasion and P. berghei transmission to mice, resulting in significant levels of protection from malaria. Targeting the interaction of malaria parasites with the fibrinolytic system using genetically engineered mosquitoes could be developed as an intervention to control malaria transmission.


Assuntos
Anopheles , Malária , Plasmodium , Animais , Animais Geneticamente Modificados , Anopheles/parasitologia , Fibrinolisina , Humanos , Malária/parasitologia , Mamíferos , Camundongos , Mosquitos Vetores/genética , Plasminogênio , Inibidor 1 de Ativador de Plasminogênio/genética , Plasmodium/fisiologia , Esporozoítos
16.
mSphere ; 7(3): e0010622, 2022 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-35586987

RESUMO

Some antimalarial drugs that have lost clinical usefulness have been repurposed for experimental applications. One example is sulfadiazine, an analog of p-aminobenzoic acid (pABA), which inhibits the parasite's folate synthesis pathway to block DNA synthesis. Sulfadiazine treatment of mice infected with Plasmodium yoelii and P. berghei is routinely used to enrich for gametocytes by killing asexual blood-stage parasites, but it is not well known if there are downstream effects on transmission. To determine if there was a significant effect of sulfadiazine exposure upon transmission, we transmitted Plasmodium yoelii (17XNL strain) parasites to Anopheles stephensi mosquitoes and evaluated the prevalence and intensity of infection under different sulfadiazine treatment conditions. We observed that there was a reduction in both the number of mosquitoes that became infected and in the intensity of infection if parasites were exposed to sulfadiazine in the mouse host or mosquito vector. Sulfadiazine treatment could be marginally overcome if mosquitoes were provided fresh pABA. In contrast, we determined that gametocytes exposed to sulfadiazine could develop into morphologically mature ookinetes in vitro, thus sulfadiazine exposure in the host may be reversible if the drug is washed out and the parasites are supplemented with pABA in the culture media. Overall, this indicates that sulfadiazine dampens host-to-vector transmission and that this inhibition can only be partially overcome by exposure to fresh pABA in vivo and in vitro. Because gametocytes are of great interest for developing transmission-blocking interventions, we recommend the use of less disruptive approaches for gametocyte enrichment. IMPORTANCE In this work, we have uncovered a substantial problem with how many studies of the sexual stages of rodent malaria parasites are conducted. Briefly, the isolation of sexual blood-stage Plasmodium parasites, or gametocytes, is essential to study pretransmission and transmission-stage biology of malaria. A routine method for the isolation of this specific stage in rodent-infectious malaria models is drug treatment with sulfadiazine, an antifolate that selectively kills actively replicating asexual blood-stage parasites but not gametocytes. Thus, researchers use this as a convenient way to produce highly enriched gametocyte samples. However, in this work, we describe how this standard drug selection with sulfadiazine not only kills asexual blood-stage parasites but also substantially impacts host-to-vector transmission.


Assuntos
Anopheles , Malária , Plasmodium yoelii , Ácido 4-Aminobenzoico , Animais , Anopheles/parasitologia , Malária/parasitologia , Camundongos , Sulfadiazina/farmacologia , Sulfadiazina/uso terapêutico
17.
Nat Microbiol ; 7(5): 707-715, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35437328

RESUMO

The mosquito microbiota can influence host physiology and vector competence, but a detailed understanding of these processes is lacking. Here we found that the gut microbiota of Anopheles stephensi, a competent malaria vector, is involved in tryptophan metabolism and is responsible for the catabolism of the peritrophic matrix impairing tryptophan metabolites. Antibiotic elimination of the microbiota led to the accumulation of tryptophan and its metabolites-kynurenine, 3-hydroxykynurenine (3-HK) and xanthurenic acid. Of these metabolites, 3-HK impaired the structure of the peritrophic matrix and promoted Plasmodium berghei infection. Among the major gut microbiota members in A. stephensi, Pseudomonas alcaligenes catabolized 3-HK as revealed by whole-genome sequencing and LC-MS metabolic analysis. The genome of P. alcaligenes encodes kynureninase (KynU) that is responsible for the conversion of 3-HK to 3-hydroxyanthranilic acid. Mutation of KynU resulted in a P. alcaligenes strain that was unable to metabolize 3-HK and unable to protect the peritrophic matrix. Colonization of A. stephensi with KynU-mutated P. alcaligenes failed to protect mosquitoes against parasite infection as compared with mosquitoes colonized with wild-type P. alcaligenes. In summary, this study identifies an unexpected function of mosquito gut microbiota in controlling mosquito tryptophan metabolism, with important implications for vector competence.


Assuntos
Anopheles , Microbioma Gastrointestinal , Malária , Animais , Anopheles/parasitologia , Malária/parasitologia , Mosquitos Vetores/genética , Triptofano
18.
Malar J ; 21(1): 124, 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35428264

RESUMO

BACKGROUND: Malaria is a life-threatening public health problem globally with particularly heavy burden in the sub-Saharan Africa including Sudan. The understanding of feeding preference of malaria vectors on different hosts is a major challenge for hindering the transmission cycle of malaria. In this study, blood meals taken by blood-fed Anopheles mosquitoes collected from the field in malaria endemic areas of Sudan were analysed for source of blood meal and malaria parasite presence. METHODS: Anopheles mosquitoes were collected from different regions in Sudan: Khartoum state, Sennar state, Northern state, and El Gedarif state between September 2020 and February 2021. Anopheles mosquitoes were collected using the standard pyrethrum spray catch and back-pack aspirator. Mosquito samples were sorted and morphologically identified to species level using international identification keys. Morphologically identified mosquito species were also confirmed using PCR. Genomic DNA was extracted from mosquitoes for molecular identification of blood meal source and parasite detection. The presence of Plasmodium species DNA in each mosquito sample was investigated using semi-nested PCR. Frequency of each blood meal source, Anopheles mosquito vector, and malaria parasite detected was calculated. Positivity rate of each fed female Anopheles mosquito was calculated for each species. RESULTS: A total of 2132 Anopheles mosquitoes were collected. 571 (26.8%) were males and 1561 (73.2%) were females classified based on their abdominal status into 1048 (67.1%) gravid, 274 (17.6%) fed, and 239 (15.3%) unfed females. Among the blood fed Anopheles mosquitoes, 263 (96.0%) were morphologically identified and confirmed using PCR to Anopheles arabiensis, 9 (3.3%) to Anopheles stephensi, and 2 (0.7%) to Anopheles rufipes. Of 274 blood-fed An. arabiensis, 68 (25.9%) fed on mixed blood meals from human and cattle, 8 (3.0%) fed on cattle and goat, and 13 (4.8%) fed on human, cattle and goat. For single blood meal sources, 70 (26.6%) fed on human, 95 (36.1%) fed on cattle, 8 (3.0%) fed on goat, and 1 (0.4%) fed on dog. While An. rufipes and An. stephensi fed on dog (2; 0.75%) and cattle (9; 3.3%), respectively. Plasmodium parasite detection in the blood meals showed that 25/274 (9.1%) An. arabiensis meals were positive for Plasmodium vivax and 19/274 (6.9%) An. arabiensis meals were positive for Plasmodium falciparum. The rate of positivity of An. arabiensis with any Plasmodium species was 16.7%. However, the positivity rate with P. falciparum only was 7.2%, while P. vivax was 9.5%. Both An. rufipes and An. stephensi were having positivity rates of 0.0% each. CONCLUSIONS: This study which was mainly on blood-fed Anopheles mosquitoes showed a diversity in the type of diet from human, cattle, and goat. Anopheles mosquitoes especially An. arabiensis in Sudan, are opportunistic blood feeders and can feed broadly on both human and cattle. The application of blood meal identification is not only important in malaria vector epidemiological surveillance but also is very useful in areas where arthropods exhibit zoophilic feeding behaviour for mammals.


Assuntos
Anopheles , Malária Falciparum , Malária Vivax , Malária , Parasitos , Animais , Anopheles/parasitologia , DNA , Comportamento Alimentar , Feminino , Malária Falciparum/epidemiologia , Masculino , Mamíferos/genética , Refeições , Mosquitos Vetores/parasitologia , Sudão
19.
Sci Rep ; 12(1): 6315, 2022 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-35428783

RESUMO

Entomopathogenic fungi have been explored as a potential biopesticide to counteract the insecticide resistance issue in mosquitoes. However, little is known about the possibility that genetic resistance to fungal biopesticides could evolve in mosquito populations. Here, we detected an important genetic component underlying Anopheles coluzzii survival after exposure to the entomopathogenic fungus Metarhizium anisopliae. A familiality study detected variation for survival among wild mosquito isofemale pedigrees, and genetic mapping identified two loci that significantly influence mosquito survival after fungus exposure. One locus overlaps with a previously reported locus for Anopheles susceptibility to the human malaria parasite Plasmodium falciparum. Candidate gene studies revealed that two LRR proteins encoded by APL1C and LRIM1 genes in this newly mapped locus are required for protection of female A. coluzzii from M. anisopliae, as is the complement-like factor Tep1. These results indicate that natural Anopheles populations already segregate frequent genetic variation for differential mosquito survival after fungal challenge and suggest a similarity in Anopheles protective responses against fungus and Plasmodium. However, this immune similarity raises the possibility that fungus-resistant mosquitoes could also display enhanced resistance to Plasmodium, suggesting an advantage of selecting for fungus resistance in vector populations to promote naturally diminished malaria vector competence.


Assuntos
Anopheles , Malária , Metarhizium , Plasmodium , Animais , Anopheles/parasitologia , Feminino , Humanos , Metarhizium/genética , Mosquitos Vetores/genética
20.
EMBO Rep ; 23(7): e54719, 2022 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-35403820

RESUMO

During transmission of malaria-causing parasites from mosquitoes to mammals, Plasmodium sporozoites migrate rapidly in the skin to search for a blood vessel. The high migratory speed and narrow passages taken by the parasites suggest considerable strain on the sporozoites to maintain their shape. Here, we show that the membrane-associated protein, concavin, is important for the maintenance of the Plasmodium sporozoite shape inside salivary glands of mosquitoes and during migration in the skin. Concavin-GFP localizes at the cytoplasmic periphery and concavin(-) sporozoites progressively round up upon entry of salivary glands. Rounded concavin(-) sporozoites fail to pass through the narrow salivary ducts and are rarely ejected by mosquitoes, while normally shaped concavin(-) sporozoites are transmitted. Strikingly, motile concavin(-) sporozoites disintegrate while migrating through the skin leading to parasite arrest or death and decreased transmission efficiency. Collectively, we suggest that concavin contributes to cell shape maintenance by riveting the plasma membrane to the subtending inner membrane complex. Interfering with cell shape maintenance pathways might hence provide a new strategy to prevent a malaria infection.


Assuntos
Anopheles , Malária , Parasitos , Plasmodium , Animais , Anopheles/parasitologia , Mamíferos , Esporozoítos/metabolismo
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