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1.
Lancet ; 395(10232): 1292-1303, 2020 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-32305094

RESUMO

BACKGROUND: Long-lasting insecticidal nets (LLINs) are the primary malaria prevention tool, but their effectiveness is threatened by pyrethroid resistance. We embedded a pragmatic cluster-randomised trial into Uganda's national LLIN campaign to compare conventional LLINs with those containing piperonyl butoxide (PBO), a synergist that can partially restore pyrethroid susceptibility in mosquito vectors. METHODS: 104 health sub-districts, from 48 districts in Uganda, were randomly assigned to LLINs with PBO (PermaNet 3.0 and Olyset Plus) and conventional LLINs (PermaNet 2.0 and Olyset Net) by proportionate randomisation using an iterative process. At baseline 6, 12, and 18 months after LLIN distribution, cross-sectional surveys were done in 50 randomly selected households per cluster (5200 per survey); a subset of ten households per cluster (1040 per survey) were randomly selected for entomological surveys. The primary outcome was parasite prevalence by microscopy in children aged 2-10 years, assessed in the as-treated population at 6, 12, and 18 months. This trial is registered with ISRCTN, ISRCTN17516395. FINDINGS: LLINs were delivered to households from March 25, 2017, to March 18, 2018, 32 clusters were randomly assigned to PermaNet 3.0, 20 to Olyset Plus, 37 to PermaNet 2.0, and 15 to Olyset Net. In the as-treated analysis, three clusters were excluded because no dominant LLIN was received, and four clusters were reassigned, resulting in 49 PBO LLIN clusters (31 received PermaNet 3.0 and 18 received Olyset Plus) and 52 non-PBO LLIN clusters (39 received PermaNet 2.0 and 13 received Olyset Net). At 6 months, parasite prevalence was 11% (386/3614) in the PBO group compared with 15% (556/3844) in the non-PBO group (prevalence ratio [PR] adjusted for baseline values 0·74, 95% CI 0·62-0·87; p=0·0003). Parasite prevalence was similar at month 12 (11% vs 13%; PR 0·73, 95% CI 0·63-0·85; p=0·0001) and month 18 (12% vs 14%; PR 0·84, 95% CI 0·72-0·98; p=0·029). INTERPRETATION: In Uganda, where pyrethroid resistance is high, PBO LLINs reduced parasite prevalence more effectively than did conventional LLINs for up to 18 months. This study provides evidence needed to support WHO's final recommendation on use of PBO LLINs. FUNDING: The Against Malaria Foundation, UK Department for International Development, Innovative Vector Control Consortium, and Bill and Melinda Gates Foundation.


Assuntos
Mosquiteiros Tratados com Inseticida/estatística & dados numéricos , Malária/prevenção & controle , Sinergistas de Praguicidas/farmacologia , Butóxido de Piperonila/farmacologia , Animais , Anopheles/parasitologia , Anopheles/fisiologia , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Resistência a Inseticidas , Malária/sangue , Masculino , Mosquitos Vetores/parasitologia , Mosquitos Vetores/fisiologia , Uganda
2.
Pan Afr Med J ; 35: 11, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32117526

RESUMO

Globally, Nigeria contributes the greatest proportion of the malaria disease burden. She currently bears the heaviest malaria burden (25% cases) and (19% deaths). Malaria is caused by Plasmodium parasites transmitted by female Anopheles mosquitoes however, a higher parasite biomass (99%) is found in man while only one (1%) is found in mosquitoes. Lending credence to this is the outcome of investigations carried out in Gboko and Otukpo Local Government Areas (LGAs); in which more humans (36.8%) had the malaria parasites than the anthropophagic female Anopheles (0.5%). Control efforts focused on mosquitoes are undermined by the actions or inactions of humans. Nigeria needs to self-audit her role in sustaining the heaviest burden of a preventable, curable disease that can also be eliminated. She can only ignore this imperative at her own peril.


Assuntos
Anopheles/parasitologia , Malária/epidemiologia , Mosquitos Vetores , Animais , Feminino , Humanos , Malária/transmissão , Nigéria/epidemiologia , Plasmodium/parasitologia
3.
PLoS Negl Trop Dis ; 14(2): e0008059, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32032359

RESUMO

During a blood meal, female Anopheles mosquitoes are potentially exposed to diverse microbes in addition to the malaria parasite, Plasmodium. Human and animal African trypanosomiases are frequently co-endemic with malaria in Africa. It is not known whether exposure of Anopheles to trypanosomes influences their fitness or ability to transmit Plasmodium. Using cell and molecular biology approaches, we found that Trypanosoma brucei brucei parasites survive for at least 48h after infectious blood meal in the midgut of the major malaria vector, Anopheles coluzzii before being cleared. This transient survival of trypanosomes in the midgut is correlated with a dysbiosis, an alteration in the abundance of the enteric bacterial flora in Anopheles coluzzii. Using a developmental biology approach, we found that the presence of live trypanosomes in mosquito midguts also reduces their reproductive fitness, as it impairs the viability of laid eggs by affecting their hatching. Furthermore, we found that Anopheles exposure to trypanosomes enhances their vector competence for Plasmodium, as it increases their infection prevalence. A transcriptomic analysis revealed that expression of only two Anopheles immune genes are modulated during trypanosome exposure and that the increased susceptibility to Plasmodium was microbiome-dependent, while the reproductive fitness cost was dependent only on the presence of live trypanosomes but was microbiome independent. Taken together, these results demonstrate multiple effects upon Anopheles vector competence for Plasmodium caused by eukaryotic microbes interacting with the host and its microbiome, which may in turn have implications for malaria control strategies in co-endemic areas.


Assuntos
Anopheles/parasitologia , Malária/parasitologia , Plasmodium yoelii/fisiologia , Trypanosoma/fisiologia , Animais , Coinfecção , Interações Hospedeiro-Parasita , Camundongos , Reação em Cadeia da Polimerase , Reprodução
4.
PLoS One ; 15(2): e0224718, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32097407

RESUMO

BACKGROUND: Understanding the interactions between increased insecticide resistance and resting behaviour patterns of malaria mosquitoes is important for planning of adequate vector control. This study was designed to investigate the resting behavior, host preference and rates of Plasmodium falciparum infection in relation to insecticide resistance of malaria vectors in different ecologies of western Kenya. METHODS: Anopheles mosquito collections were carried out during the dry and rainy seasons in Kisian (lowland site) and Bungoma (highland site), both in western Kenya using pyrethrum spray catches (PSC), mechanical aspiration (Prokopack) for indoor collections, clay pots, pit shelter and Prokopack for outdoor collections. WHO tube bioassay was used to determine levels of phenotypic resistance of indoor and outdoor collected mosquitoes to deltamethrin. PCR-based molecular diagnostics were used for mosquito speciation, genotype for knockdown resistance mutations (1014S and 1014F) and to determine specific host blood meal origins. Enzyme-linked Immunosorbent Assay (ELISA) was used to determine mosquito sporozoite infections. RESULTS: Anopheles gambiae s.l. was the most predominant species (75%, n = 2706) followed by An. funestus s.l. (25%, n = 860). An. gambiae s.s hereafter (An. gambiae) accounted for 91% (95% CI: 89-93) and An. arabiensis 8% (95% CI: 6-9) in Bungoma, while in Kisian, An. arabiensis composition was 60% (95% CI: 55-66) and An. gambiae 39% (95% CI: 34-44). The resting densities of An. gambiae s.l and An. funestus were higher indoors than outdoor in both sites (An. gambiae s.l; F1, 655 = 41.928, p < 0.0001, An. funestus; F1, 655 = 36.555, p < 0.0001). The mortality rate for indoor and outdoor resting An. gambiae s.l F1 progeny was 37% (95% CI: 34-39) vs 67% (95% CI: 62-69) respectively in Bungoma. In Kisian, the mortality rate was 67% (95% CI: 61-73) vs 76% (95% CI: 71-80) respectively. The mortality rate for F1 progeny of An. funestus resting indoors in Bungoma was 32% (95% CI: 28-35). The 1014S mutation was only detected in indoor resitng An. arabiensis. Similarly, the 1014F mutation was present only in indoor resting An. gambiae. The sporozoite rates were highest in An. funestus followed by An. gambiae, and An. arabiensis resting indoors at 11% (34/311), 8% (47/618) and 4% (1/27) respectively in Bungoma. Overall, in Bungoma, the sporozoite rate for indoor resting mosquitoes was 9% (82/956) and 4% (8/190) for outdoors. In Kisian, the sporozoite rate was 1% (1/112) for indoor resting An. gambiae. None of the outdoor collected mosquitoes in Kisian tested positive for sporozoite infections (n = 73). CONCLUSION: The study reports high indoor resting densities of An. gambiae and An. funestus, insecticide resistance, and persistence of malaria transmission indoors regardless of the use of long-lasting insecticidal nets (LLINs). These findings underline the difficulties of controlling malaria vectors resting and biting indoors using the current interventions. Supplemental vector control tools and implementation of sustainable insecticide resistance management strategies are needed in western Kenya.


Assuntos
Anopheles/genética , Malária Falciparum/epidemiologia , Malária Falciparum/prevenção & controle , Controle de Mosquitos/métodos , Mosquitos Vetores/fisiologia , Plasmodium falciparum/imunologia , Descanso/fisiologia , Animais , Anopheles/classificação , Anopheles/parasitologia , Ensaio de Imunoadsorção Enzimática , Comportamento Alimentar/efeitos dos fármacos , Feminino , Genótipo , Comportamento de Busca por Hospedeiro/efeitos dos fármacos , Resistência a Inseticidas/genética , Mosquiteiros Tratados com Inseticida , Inseticidas/farmacologia , Quênia/epidemiologia , Malária Falciparum/transmissão , Nitrilos/farmacologia , Reação em Cadeia da Polimerase , Piretrinas/farmacologia , Esporozoítos/imunologia
5.
Rev Soc Bras Med Trop ; 52: e20190308, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31800921

RESUMO

Malaria, a mosquito-borne infectious disease, is considered a significant global health burden. Climate changes or different weather conditions may impact infectious diseases, specifically those transmitted by insect vectors and contaminated water. Based on the current predictions for climate change associated with the increase in carbon dioxide concentrations in the atmosphere and the increase in atmospheric temperature, the Intergovernmental Panel on Climate Change predicts that in 2050, malaria may threaten some previously unexposed areas worldwide and cause a 50% higher probability of malaria cases. Climate-based distribution models of malaria depict an increase in the geographic distribution of the disease as global environmental temperatures and conditions worsen. Researchers have studied the influence of changes in climate on the prevalence of malaria using different mathematical models that consider different variables and predict the conditions for malaria distribution. In this context, we conducted a mini-review to elucidate the important aspects described in the literature on the influence of climate change in the distribution and transmission of malaria. It is important to develop possible risk management strategies and enhance the surveillance system enhanced even in currently malaria-free areas predicted to experience malaria in the future.


Assuntos
Anopheles/parasitologia , Mudança Climática , Malária/transmissão , Mosquitos Vetores/parasitologia , Animais , Modelos Biológicos , Dinâmica Populacional
6.
Malar J ; 18(1): 426, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31849326

RESUMO

BACKGROUND: The circumsporozoite protein (CSP) of Plasmodium is a key surface antigen that induces antibodies and T-cells, conferring immune protection in animal models and humans. However, much of the work on CSP and immunity has been developed based on studies using rodent or non-human primate CSP antigens, which may not be entirely translatable to CSP expressed by human malaria parasites, especially considering the host specificity of the different species. METHODS: Using a genetically engineered strain of Plasmodium berghei that expresses luciferase, GFP and the Plasmodium falciparum orthologue of CSP, the effect of laboratory preparation, mosquito treatment and mouse factors on sporozoite infectivity was assessed using an in vivo bioluminescence assay on mice. This assay was compared with a PCR-based protection assay using an already described monoclonal antibody that can provide sterile protection against sporozoite challenge. RESULTS: Bioluminescence assay demonstrated similar detection levels of the quantity and kinetics of liver-stage infection, compared to PCR-based detection. This assay was used to evaluate treatment of sporozoite and delivery method on mouse infectivity, as well as the effects of age, sex and strain of mice. Finally, this assay was used to test the protective capacity of monoclonal antibody AB317; results strongly recapitulate the findings of previous work on this antibody. CONCLUSIONS: The PbGFP-Luc line and in vivo bioluminescence imaging provide highly sensitive read-outs of liver-stage infection in mice, and this method can be useful to reliably evaluate potency of pre-erythrocytic interventions.


Assuntos
Malária/imunologia , Plasmodium berghei/fisiologia , Animais , Anopheles/parasitologia , Feminino , Ensaios de Triagem em Larga Escala , Fígado/parasitologia , Luciferases/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Microrganismos Geneticamente Modificados/genética , Microrganismos Geneticamente Modificados/fisiologia , Plasmodium berghei/genética , Plasmodium falciparum/genética , Proteínas de Protozoários/metabolismo , Esporozoítos/crescimento & desenvolvimento
7.
PLoS Pathog ; 15(12): e1008216, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31887217

RESUMO

Eukaryotes of the genus Plasmodium cause malaria, a parasitic disease responsible for substantial morbidity and mortality in humans. Yet, the nature and abundance of any viruses carried by these divergent eukaryotic parasites is unknown. We investigated the Plasmodium virome by performing a meta-transcriptomic analysis of blood samples taken from patients suffering from malaria and infected with P. vivax, P. falciparum or P. knowlesi. This resulted in the identification of a narnavirus-like sequence, encoding an RNA polymerase and restricted to P. vivax samples, as well as an associated viral segment of unknown function. These data, confirmed by PCR, are indicative of a novel RNA virus that we term Matryoshka RNA virus 1 (MaRNAV-1) to reflect its analogy to a "Russian doll": a virus, infecting a parasite, infecting an animal. Additional screening revealed that MaRNAV-1 was abundant in geographically diverse P. vivax derived from humans and mosquitoes, strongly supporting its association with this parasite, and not in any of the other Plasmodium samples analyzed here nor Anopheles mosquitoes in the absence of Plasmodium. Notably, related bi-segmented narnavirus-like sequences (MaRNAV-2) were retrieved from Australian birds infected with a Leucocytozoon-a genus of eukaryotic parasites that group with Plasmodium in the Apicomplexa subclass hematozoa. Together, these data support the establishment of two new phylogenetically divergent and genomically distinct viral species associated with protists, including the first virus likely infecting Plasmodium parasites. As well as broadening our understanding of the diversity and evolutionary history of the eukaryotic virosphere, the restriction to P. vivax may be of importance in understanding P. vivax-specific biology in humans and mosquitoes, and how viral co-infection might alter host responses at each stage of the P. vivax life-cycle.


Assuntos
Malária Vivax/parasitologia , Parasitos/genética , Plasmodium vivax/genética , Plasmodium/genética , Vírus de RNA/genética , Animais , Anopheles/parasitologia , Doenças das Aves , Humanos , Malária Falciparum/parasitologia , Plasmodium falciparum/genética
8.
PLoS Genet ; 15(10): e1008453, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31609965

RESUMO

Determining the genetic basis of fitness is central to understanding evolution and transmission of microbial pathogens. In human malaria parasites (Plasmodium falciparum), most experimental work on fitness has focused on asexual blood stage parasites, because this stage can be easily cultured, although the transmission of malaria requires both female Anopheles mosquitoes and vertebrate hosts. We explore a powerful approach to identify the genetic determinants of parasite fitness across both invertebrate and vertebrate life-cycle stages of P. falciparum. This combines experimental genetic crosses using humanized mice, with selective whole genome amplification and pooled sequencing to determine genome-wide allele frequencies and identify genomic regions under selection across multiple lifecycle stages. We applied this approach to genetic crosses between artemisinin resistant (ART-R, kelch13-C580Y) and ART-sensitive (ART-S, kelch13-WT) parasites, recently isolated from Southeast Asian patients. Two striking results emerge: we observed (i) a strong genome-wide skew (>80%) towards alleles from the ART-R parent in the mosquito stage, that dropped to ~50% in the blood stage as selfed ART-R parasites were selected against; and (ii) repeatable allele specific skews in blood stage parasites with particularly strong selection (selection coefficient (s) ≤ 0.18/asexual cycle) against alleles from the ART-R parent at loci on chromosome 12 containing MRP2 and chromosome 14 containing ARPS10. This approach robustly identifies selected loci and has strong potential for identifying parasite genes that interact with the mosquito vector or compensatory loci involved in drug resistance.


Assuntos
Interações Hospedeiro-Parasita/genética , Estágios do Ciclo de Vida/genética , Malária Falciparum/parasitologia , Plasmodium falciparum/genética , Proteínas de Protozoários/genética , Animais , Anopheles/parasitologia , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Artemisininas/farmacologia , Artemisininas/uso terapêutico , Mapeamento Cromossômico , Modelos Animais de Doenças , Resistência a Medicamentos/genética , Feminino , Frequência do Gene , Loci Gênicos , Humanos , Malária Falciparum/tratamento farmacológico , Masculino , Camundongos , Mosquitos Vetores/parasitologia , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/crescimento & desenvolvimento , Polimorfismo de Nucleotídeo Único , Proteínas Ribossômicas/genética , Seleção Genética , Quimeras de Transplante
9.
Malar J ; 18(1): 351, 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31623623

RESUMO

BACKGROUND: Plasmodium falciparum drug resistance surveillance is key to successful disease control and eradication. Contemporary methods that only allow determination of prevalence of resistance are expensive, time consuming and require ethical considerations. A newer method involving Next Generation Sequencing (NGS) permits obtaining frequency of resistance while allowing to detect minority variants in mixed infections. Here, NGS was tested for P. falciparum resistance marker detection in mosquito samples as a feasible and suitable alternative for molecular resistance surveillance. Anopheles funestus were collected in southern Mozambique using CDC light traps and manual collections. DNA was extracted from either whole mosquito, head-thorax and abdomen separately or pools of five mosquitoes. These samples were screened for P. falciparum and if positive for k13, pfcrt, pfmdr1, pfdhps and pfdhfr mutations related to anti-malarial drug resistance with Sanger sequencing and NGS. RESULTS: Among the 846 samples screened for P. falciparum, 122 were positive by 18S ssrDNA qPCR with an infection rate of 23.6%. No mutations were observed for k13 and pfcrt72-76 and almost zero for pfmdr86, but quintuple pfdhfr/pfdhps mutations were near fixation and about half of the isolates contained the pfmdr184F polymorphism. Similar allele frequencies of resistance markers were estimated with NGS in comparison with the prevalence of markers obtained with the gold standard Sanger sequencing. CONCLUSIONS: Pooled deep sequencing of P. falciparum isolates extracted from mosquitoes is a promising, efficient and cost-effective method to quantify allele frequencies at population level which allows to detect known and unknown markers of resistance in single and mixed infections in a timelier manner. Using mosquitoes as sentinel group and focusing on allele frequency opposed to prevalence, permits active surveillance across a more homogeneous geographical range.


Assuntos
Anopheles/parasitologia , Antimaláricos/farmacologia , Resistência a Medicamentos/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Plasmodium falciparum/efeitos dos fármacos , Proteínas de Protozoários/genética , Animais , Feminino , Sequenciamento de Nucleotídeos em Larga Escala/economia , Moçambique , Proteínas de Protozoários/metabolismo
10.
Int J Mol Sci ; 20(20)2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31615031

RESUMO

Transmission of the malaria parasite Plasmodium falciparum from the human to the mosquito is initiated by specialized sexual cells, the gametocytes. In the human, gametocytes are formed in response to stress signals and following uptake by a blood-feeding Anopheles mosquito initiate sexual reproduction. Gametocytes need to fine-tune their gene expression in order to develop inside the mosquito to continue life-cycle progression. Previously, we showed that post-translational histone acetylation controls gene expression during gametocyte development and transmission. However, the role of histone methylation remains poorly understood. We here use the histone G9a methyltransferase inhibitor BIX-01294 to investigate the role of histone methylation in regulating gene expression in gametocytes. In vitro assays demonstrated that BIX-01294 inhibits intraerythrocytic replication with a half maximal inhibitory concentration (IC50) of 13.0 nM. Furthermore, BIX-01294 significantly impairs gametocyte maturation and reduces the formation of gametes and zygotes. Comparative transcriptomics between BIX-01294-treated and untreated immature, mature and activated gametocytes demonstrated greater than 1.5-fold deregulation of approximately 359 genes. The majority of these genes are transcriptionally downregulated in the activated gametocytes and could be assigned to transcription, translation, and signaling, indicating a contribution of histone methylations in mediating gametogenesis. Our combined data show that inhibitors of histone methylation may serve as a multi-stage antimalarial.


Assuntos
Células Germinativas/crescimento & desenvolvimento , Histona-Lisina N-Metiltransferase/genética , Malária Falciparum/genética , Plasmodium falciparum/genética , Animais , Anopheles/efeitos dos fármacos , Anopheles/parasitologia , Antimaláricos/metabolismo , Antimaláricos/uso terapêutico , Azepinas/farmacologia , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Células Germinativas/metabolismo , Histona-Lisina N-Metiltransferase/antagonistas & inibidores , Humanos , Malária Falciparum/tratamento farmacológico , Malária Falciparum/parasitologia , Plasmodium falciparum/crescimento & desenvolvimento , Quinazolinas/farmacologia
11.
BMC Res Notes ; 12(1): 645, 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31585549

RESUMO

OBJECTIVE: We investigated this outbreak to describe the magnitude and associated risk factors due to the malaria outbreak in Tanquae Abergelle district, Tigray, Ethiopia, in 2017. RESULT: Case fatality rate of this study was zero. Among the 62 cases and 124 controls, the presence of mosquito breeding sites [OR = 6.56 CI (2.09-20.58) P value = 0.001], sleeping outside a home [OR = 5.06 CI (1.75-14.61) P-value = 0.003] and having unscreened window [OR = 14.89 CI (1.87-118.25) P-value = 0.011] were associated with illness in multivariate analysis.


Assuntos
Surtos de Doenças , Malária Falciparum/epidemiologia , Malária Vivax/epidemiologia , Mosquiteiros/estatística & dados numéricos , Adolescente , Adulto , Animais , Anopheles/parasitologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Etiópia/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Malária Falciparum/parasitologia , Malária Falciparum/transmissão , Malária Vivax/parasitologia , Malária Vivax/transmissão , Masculino , Pessoa de Meia-Idade , Mosquitos Vetores/parasitologia , Plasmodium falciparum/patogenicidade , Plasmodium vivax/patogenicidade , Fatores de Risco , Sono
12.
Parasit Vectors ; 12(1): 501, 2019 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-31655608

RESUMO

Malaria still has a devastating impact on public health and welfare in Cameroon. Despite the increasing number of studies conducted on disease prevalence, transmission patterns or treatment, there are to date, not enough studies summarising findings from previous works in order to identify gaps in knowledge and areas of interest where further evidence is needed to drive malaria elimination efforts. The present study seeks to address these gaps by providing a review of studies conducted so far on malaria in Cameroon since the 1940s to date. Over 250 scientific publications were consulted for this purpose. Although there has been increased scale-up of vector control interventions which significantly reduced the morbidity and mortality to malaria across the country from a prevalence of 41% of the population reporting at least one malaria case episode in 2000 to a prevalence of 24% in 2017, the situation is not yet under control. There is a high variability in disease endemicity between epidemiological settings with prevalence of Plasmodium parasitaemia varying from 7 to 85% in children aged 6 months to 15 years after long-lasting insecticidal nets (LLINs) scale-up. Four species of Plasmodium have been recorded across the country: Plasmodium falciparum, P. malariae, P. ovale and P. vivax. Several primate-infecting Plasmodium spp. are also circulating in Cameroon. A decline of artemisinin-based combinations therapeutic efficacy from 97% in 2006 to 90% in 2016 have been reported. Several mutations in the P. falciparum chloroquine resistance (Pfcrt) and P. falciparum multidrug resistance 1 (Pfmdr1) genes conferring resistance to either 4-amino-quinoleine, mefloquine, halofanthrine and quinine have been documented. Mutations in the Pfdhfr and Pfdhps genes involved in sulfadoxine-pyrimethamine are also on the rise. No mutation associated with artemisinin resistance has been recorded. Sixteen anopheline species contribute to malaria parasite transmission with six recognized as major vectors: An. gambiae, An. coluzzii, An. arabiensis, An. funestus, An. nili and An. moucheti. Studies conducted so far, indicated rapid expansion of DDT, pyrethroid and carbamate resistance in An. gambiae, An. coluzzii, An. arabiensis and An. funestus threatening the performance of LLINs. This review highlights the complex situation of malaria in Cameroon and the need to urgently implement and reinforce integrated control strategies in different epidemiological settings, as part of the substantial efforts to consolidate gains and advance towards malaria elimination in the country.


Assuntos
Malária/epidemiologia , Malária/prevenção & controle , Animais , Anopheles/classificação , Anopheles/genética , Anopheles/parasitologia , Camarões/epidemiologia , Humanos , Resistência a Inseticidas , Malária/terapia , Malária/transmissão , Controle de Mosquitos/tendências , Mosquitos Vetores/classificação , Mosquitos Vetores/genética , Mosquitos Vetores/parasitologia , Plasmodium/classificação , Plasmodium/patogenicidade , Prevalência , Saúde Pública
13.
Nat Commun ; 10(1): 3939, 2019 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477710

RESUMO

Heterogeneity in transmission is a challenge for infectious disease dynamics and control. An 80-20 "Pareto" rule has been proposed to describe this heterogeneity whereby 80% of transmission is accounted for by 20% of individuals, herein called super-spreaders. It is unclear, however, whether super-spreading can be attributed to certain individuals or whether it is an unpredictable and unavoidable feature of epidemics. Here, we investigate heterogeneous malaria transmission at three sites in Uganda and find that super-spreading is negatively correlated with overall malaria transmission intensity. Mosquito biting among humans is 90-10 at the lowest transmission intensities declining to less than 70-30 at the highest intensities. For super-spreaders, biting ranges from 70-30 down to 60-40. The difference, approximately half the total variance, is due to environmental stochasticity. Super-spreading is thus partly due to super-spreaders, but modest gains are expected from targeting super-spreaders.


Assuntos
Algoritmos , Doenças Transmissíveis/transmissão , Malária/transmissão , Modelos Teóricos , Animais , Anopheles/parasitologia , Anopheles/fisiologia , Doenças Transmissíveis/epidemiologia , Doenças Transmissíveis/parasitologia , Humanos , Malária/epidemiologia , Malária/parasitologia , Mosquitos Vetores/parasitologia , Mosquitos Vetores/fisiologia , Plasmodium/fisiologia , Processos Estocásticos , Uganda/epidemiologia
14.
Parasit Vectors ; 12(1): 454, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31533794

RESUMO

BACKGROUND: Despite great success in significantly reducing the malaria burden in Viet Nam over recent years, the ongoing presence of malaria vectors and Plasmodium infection in remote forest areas and among marginalised groups presents a challenge to reaching elimination and a threat to re-emergence of transmission. Often transmission persists in a population despite high reported coverage of long-lasting insecticidal nets (LLINs), the mainstay control method for malaria. To investigate what factors may contribute to this, a mixed-methods study was conducted in Son Thai commune, a community in south-central Viet Nam that has ongoing malaria cases despite universal LLIN coverage. A cross-sectional behavioural and net-coverage survey was conducted along with observations of net use and entomological collections in the village, farm huts and forest sites used by members of the community. RESULTS: Most community members owned a farm hut plot and 71.9% of adults aged 18+ years sometimes slept overnight in the farm hut, while one-third slept overnight in the forest. Ownership and use of nets in the village households was high but in the farm huts and forest was much lower; only 44.4% reported regularly using a bednet in the farm and 12.1% in the forest. No primary anopheline species were captured in the village, but Anopheles dirus (s.l.) (n = 271) and An. maculatus (s.l.) (n = 14) were captured as far as 4.5 km away in farm huts and forest. A high proportion of biting was conducted in the early evening before people were under nets. Entomological inoculation rates (EIR) of An. dirus (s.l.) were 17.8 and 25.3 infectious bites per person per year in the outdoor farm hut sites and forest, respectively, for Plasmodium falciparum and 25.3 in the forest sites for P. vivax. CONCLUSIONS: Despite high net coverage in the village, gaps in coverage and access appear in the farm huts and forest where risk of anopheline biting and parasite transmission is much greater. Since subsistence farming and forest activities are integral to these communities, new personal protection methods need to be explored for use in these areas that can ideally engage with the community, be durable, portable and require minimal behavioural change.


Assuntos
Anopheles/crescimento & desenvolvimento , Anopheles/parasitologia , Transmissão de Doença Infecciosa , Malária/transmissão , Plasmodium falciparum/isolamento & purificação , Plasmodium vivax/isolamento & purificação , Animais , Estudos Transversais , Utilização de Equipamentos e Suprimentos/estatística & dados numéricos , Florestas , Humanos , Mosquiteiros , Vietnã/epidemiologia
15.
Nat Commun ; 10(1): 4300, 2019 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-31541097

RESUMO

Mainstay treatment for Plasmodium vivax malaria has long relied on chloroquine (CQ) against blood-stage parasites plus primaquine against dormant liver-stage forms (hypnozoites), however drug resistance confronts this regimen and threatens malaria control programs. Understanding the basis of P. vivax chloroquine resistance (CQR) will inform drug discovery and malaria control. Here we investigate the genetics of P. vivax CQR by a cross of parasites differing in drug response. Gametocytogenesis, mosquito infection, and progeny production are performed with mixed parasite populations in nonhuman primates, as methods for P. vivax cloning and in vitro cultivation remain unavailable. Linkage mapping of progeny surviving >15 mg/kg CQ identifies a 76 kb region in chromosome 1 including pvcrt, an ortholog of the Plasmodium falciparum CQR transporter gene. Transcriptional analysis supports upregulated pvcrt expression as a mechanism of CQR.


Assuntos
Antimaláricos/farmacologia , Cloroquina/farmacologia , Cruzamentos Genéticos , Resistência a Medicamentos/genética , Proteínas de Membrana Transportadoras/genética , Plasmodium vivax/efeitos dos fármacos , Plasmodium vivax/genética , Proteínas de Protozoários/genética , Animais , Anopheles/parasitologia , Culicidae/parasitologia , Descoberta de Drogas , Feminino , Expressão Gênica , Genes de Protozoários , Malária/tratamento farmacológico , Malária Vivax/tratamento farmacológico , Malária Vivax/parasitologia , Masculino , Plasmodium falciparum/genética
16.
Nat Commun ; 10(1): 3635, 2019 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-31406175

RESUMO

The ability to culture pathogenic organisms substantially enhances the quest for fundamental knowledge and the development of vaccines and drugs. Thus, the elaboration of a protocol for the in vitro cultivation of the erythrocytic stages of Plasmodium falciparum revolutionized research on this important parasite. However, for P. vivax, the most widely distributed and difficult to treat malaria parasite, a strict preference for reticulocytes thwarts efforts to maintain it in vitro. Cultivation of P. cynomolgi, a macaque-infecting species phylogenetically close to P. vivax, was briefly reported in the early 1980s, but not pursued further. Here, we define the conditions under which P. cynomolgi can be adapted to long term in vitro culture to yield parasites that share many of the morphological and phenotypic features of P. vivax. We further validate the potential of this culture system for high-throughput screening to prime and accelerate anti-P. vivax drug discovery efforts.


Assuntos
Eritrócitos/parasitologia , Macaca/parasitologia , Malária/veterinária , Doenças dos Macacos/parasitologia , Plasmodium cynomolgi/crescimento & desenvolvimento , Animais , Anopheles/parasitologia , Malária/parasitologia , Malária/transmissão
17.
Science ; 365(6455)2019 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-31439762

RESUMO

Malaria parasites adopt a remarkable variety of morphological life stages as they transition through multiple mammalian host and mosquito vector environments. We profiled the single-cell transcriptomes of thousands of individual parasites, deriving the first high-resolution transcriptional atlas of the entire Plasmodium berghei life cycle. We then used our atlas to precisely define developmental stages of single cells from three different human malaria parasite species, including parasites isolated directly from infected individuals. The Malaria Cell Atlas provides both a comprehensive view of gene usage in a eukaryotic parasite and an open-access reference dataset for the study of malaria parasites.


Assuntos
Atlas como Assunto , Genes de Protozoários/fisiologia , Estágios do Ciclo de Vida/genética , Malária/parasitologia , Plasmodium berghei/genética , Plasmodium berghei/fisiologia , Transcriptoma , Animais , Anopheles/parasitologia , Células HeLa , Humanos , Plasmodium berghei/isolamento & purificação , Análise de Célula Única
18.
Malar J ; 18(1): 276, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31426810

RESUMO

BACKGROUND: Parasites from the genus Plasmodium, the aetiological agent of malaria in humans, can also infect non-human primates (NHP), increasing the potential risk of zoonotic transmission with its associated global public health concerns. In Colombia, there are no recent studies on Plasmodium spp. infecting free-ranging NHP. Thus, this study aimed to determine the diversity of Plasmodium species circulating in fragmented forests in central Colombia, both in Anopheles mosquitoes and in the four sympatric NHP in the region (Ateles hybridus, Cebus versicolor, Alouatta seniculus and Aotus griseimembra), in order to evaluate the risk of infection to humans associated with the presence of sylvatic hosts and vectors infected with Plasmodium spp. METHODS: Overall, there were collected 166 fecal samples and 25 blood samples from NHP, and 442 individuals of Anopheles spp. DNA extraction, nested PCR using mitochondrial (cox3 gene) and ribosomal (18S rDNA) primers, electrophoresis and sequencing were conducted in order to identify Plasmodium spp. from the samples. RESULTS: Plasmodium falciparum was detected in two fecal samples of Alouatta seniculus, while Plasmodium vivax/simium infected Ateles hybridus, Cebus versicolor and Alouatta seniculus. Co-infections with P. vivax/simium and Plasmodium malariae/brasilianum were found in three individuals. The highest prevalence from blood samples was found for Plasmodium malariae/brasilianum in two Alouatta seniculus while Plasmodium vivax/simium was most prevalent in fecal samples, infecting four individuals of Alouatta seniculus. Seven Anopheles species were identified in the study site: Anopheles (Anopheles) punctimacula, Anopheles (An.) malefactor, Anopheles (Nyssorhynchus) oswaldoi, Anopheles (Nys.) triannulatus, Anopheles (An.) neomaculipalpus, Anopheles (Nys.) braziliensis and Anopheles (Nys.) nuneztovari. Infection with P. vivax/simium was found in An. nuneztovari, An. neomaculipalpus, and An. triannulatus. Furthermore, An. oswaldoi and An. triannulatus were found infected with P. malariae/brasilianum. The effect of fragmentation and distance to the nearest town measured in five forests with different degrees of fragmentation was not statistically significant on the prevalence of Plasmodium in NHP, but forest fragmentation did have an effect on the Minimum Infection Rate (MIR) in Anopheles mosquitoes. CONCLUSIONS: The presence of Plasmodium spp. in NHP and Anopheles spp. in fragmented forests in Colombia has important epidemiological implications in the human-NHP interface and the associated risk of malaria transmission.


Assuntos
Anopheles/parasitologia , Malária/veterinária , Doenças dos Macacos/epidemiologia , Mosquitos Vetores/parasitologia , Plasmodium/isolamento & purificação , Platirrinos , Animais , Colômbia/epidemiologia , Meio Ambiente , Florestas , Malária/epidemiologia , Malária/parasitologia , Doenças dos Macacos/parasitologia , Prevalência
19.
Malar J ; 18(1): 287, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31455343

RESUMO

BACKGROUND: The human infectious reservoir for malaria consists of individuals capable of infecting mosquitoes. Oocyst prevalence and density are typical indicators of human infectivity to mosquitoes. However, identification of oocysts is challenging, particularly in areas of low malaria transmission intensity where few individuals may infect mosquitoes, and infected mosquitoes tend to have few oocysts. Here, features that differentiate oocysts from other oocyst-like in mosquito midguts are explained and illustrated. In addition, the establishment and maintenance of infrastructure to perform malaria transmission experiments is described. This work may support other initiatives to set up membrane feeding infrastructure and guide oocyst detection in low transmission settings. METHODS: In 2014, an insectary was developed and equipped in Tororo district, Uganda. A colony of Anopheles gambiae s.s. mosquitoes (Kisumu strain) was initiated to support infectivity experiments from participants enrolled in a large cohort study. Venous blood drawn from participants who were naturally infected with malaria parasites was used for membrane feeding assays, using 60-80 mosquitoes per experiment. Approximately 9-10 days after feeding, mosquitoes were dissected, and midguts were stained in mercurochrome and examined by light microscopy for Plasmodium falciparum oocysts and similar structures. In supportive experiments, different staining procedures were compared using in vitro cultured parasites. RESULTS: A stable colony of the Kisumu strain of An. gambiae s.s. was achieved, producing 5000-10,000 adult mosquitoes on a weekly basis. Challenges due to temperature fluctuations, mosquito pathogens and pests were successfully overcome. Oocysts were characterized by: presence of malaria pigment, clearly defined edge, round shape within the mosquito midgut or on the peripheral tissue and always attached to the epithelium. The main distinguishing feature between artifacts and mature oocysts was the presence of defined pigment within the oocysts. CONCLUSIONS: Oocysts may be mistaken for other structures in mosquito midguts. Distinguishing real oocysts from oocyst-like structures may be challenging for inexperienced microscopists due to overlapping features. The characteristics and guidelines outlined here support identification of oocysts and reliable detection at low oocyst densities. Practical advice on sustaining a healthy mosquito colony for feeding experiments is provided. Following the reported optimization, the established infrastructure in Tororo allows assessments of infectivity of naturally infected parasite carriers.


Assuntos
Anopheles/parasitologia , Mosquitos Vetores/parasitologia , Oocistos/isolamento & purificação , Plasmodium falciparum/isolamento & purificação , Animais , Feminino , Humanos , Oocistos/citologia , Oocistos/crescimento & desenvolvimento , Plasmodium falciparum/citologia , Plasmodium falciparum/crescimento & desenvolvimento , Uganda
20.
Parasit Vectors ; 12(1): 386, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31370863

RESUMO

BACKGROUND: Anopheles albimanus is a malaria vector in Central America, northern South America and the Caribbean. Although a public health threat, An. albimanus precopulatory mating behaviors are unknown. Acoustics play important roles in mosquito communication, where flight tones allow males to detect and attract potential mates. The importance of sound in precopulatory interactions has been demonstrated in Toxorhynchites brevipalpis, Aedes aegypti, Culex quinquefasciatus and Anopheles gambiae; convergence in a shared harmonic of the wing beat frequency (WBF) during courtship is thought to increase the chance of copulation. To our knowledge, An. albimanus precopulatory acoustic behaviors have not been described to date. Here, we characterized An. albimanus (i) male and female flight tones; (ii) male-female precopulatory acoustic interactions under tethered and free flight conditions; and (iii) male-male acoustic interactions during free flight. RESULTS: We found significant increases in the WBFs of both sexes in free flight compared to when tethered. We observed harmonic convergence between 79% of tethered couples. In free flight, we identified a female-specific behavior that predicts mate rejection during male mating attempts: females increase their WBFs significantly faster during mate rejection compared to a successful copulation. This behavior consistently occurred during mate rejection regardless of prior mating attempts (from the same or differing male). During group flight, males of An. albimanus displayed two distinct flying behaviors: random flight and a swarm-like, patterned flight, each associated with distinct acoustic characteristics. In the transition from random to patterned flight, males converged their WBFs and significantly decreased flight area, male-male proximity and the periodicity of their trajectories. CONCLUSIONS: We show that tethering of An. albimanus results in major acoustic differences compared to free flight. We identify a female-specific behavior that predicts mate rejection during male mating attempts in this species and show that male groups in free flight display distinct flying patterns with unique audio and visual characteristics. This study shows that An. albimanus display acoustic features identified in other mosquito species, further suggesting that acoustic interactions provide worthwhile targets for mosquito intervention strategies. Our results provide compelling evidence for swarming in this species and suggests that acoustic signaling is important for this behavior.


Assuntos
Comunicação Animal , Anopheles/fisiologia , Mosquitos Vetores/fisiologia , Comportamento Sexual Animal , Som , Animais , Anopheles/parasitologia , Feminino , Malária/transmissão , Masculino , Mosquitos Vetores/parasitologia
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