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1.
Nat Commun ; 12(1): 1750, 2021 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-33741942

RESUMO

Malaria elimination requires tools that interrupt parasite transmission. Here, we characterize B cell receptor responses among Malian adults vaccinated against the first domain of the cysteine-rich 230 kDa gamete surface protein Pfs230, a key protein in sexual stage development of P. falciparum parasites. Among nine Pfs230 human monoclonal antibodies (mAbs) that we generated, one potently blocks transmission to mosquitoes in a complement-dependent manner and reacts to the gamete surface; the other eight show only low or no blocking activity. The structure of the transmission-blocking mAb in complex with vaccine antigen reveals a large discontinuous conformational epitope, specific to domain 1 of Pfs230 and comprising six structural elements in the protein. The epitope is conserved, suggesting the transmission-blocking mAb is broadly functional. This study provides a rational basis to improve malaria vaccines and develop therapeutic antibodies for malaria elimination.


Assuntos
Anticorpos Monoclonais/farmacologia , Anticorpos Antiprotozoários/farmacologia , Epitopos/imunologia , Células Germinativas/imunologia , Malária Falciparum/prevenção & controle , Plasmodium falciparum/efeitos dos fármacos , Adulto , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Antiprotozoários/imunologia , Antígenos de Protozoários/química , Antígenos de Protozoários/imunologia , Sítios de Ligação , Células Cultivadas , Epitopos/química , Interações Hospedeiro-Parasita/efeitos dos fármacos , Interações Hospedeiro-Parasita/imunologia , Humanos , Vacinas Antimaláricas/administração & dosagem , Vacinas Antimaláricas/imunologia , Malária Falciparum/parasitologia , Malária Falciparum/transmissão , Mosquitos Vetores/parasitologia , Plasmodium falciparum/imunologia , Plasmodium falciparum/fisiologia , Conformação Proteica , Proteínas de Protozoários/química , Proteínas de Protozoários/imunologia
2.
Nat Commun ; 12(1): 1494, 2021 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-33686061

RESUMO

Transmission-blocking vaccines that interrupt malaria transmission from humans to mosquitoes are being tested in early clinical trials. The activity of such a vaccine is commonly evaluated using membrane-feeding assays. Understanding the field efficacy of such a vaccine requires knowledge of how heavily infected wild, naturally blood-fed mosquitoes are, as this indicates how difficult it will be to block transmission. Here we use data on naturally infected mosquitoes collected in Burkina Faso to translate the laboratory-estimated activity into an estimated activity in the field. A transmission dynamics model is then utilised to predict a transmission-blocking vaccine's public health impact alongside existing interventions. The model suggests that school-aged children are an attractive population to target for vaccination. Benefits of vaccination are distributed across the population, averting the greatest number of cases in younger children. Utilising a transmission-blocking vaccine alongside existing interventions could have a substantial impact against malaria.


Assuntos
Vacinas Antimaláricas/imunologia , Malária/prevenção & controle , Malária/transmissão , Saúde Pública , Adolescente , Adulto , Burkina Faso/epidemiologia , Criança , Pré-Escolar , Humanos , Lactente , Malária/epidemiologia , Malária Falciparum/prevenção & controle , Pessoa de Meia-Idade , Prevalência , Vacinação , Adulto Jovem
3.
Nat Commun ; 12(1): 1063, 2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33594061

RESUMO

The most advanced P. falciparum circumsporozoite protein-based malaria vaccine, RTS,S/AS01 (RTS,S), confers partial protection but with antibody titers that wane relatively rapidly, highlighting the need to elicit more potent and durable antibody responses. Here, we elucidate crystal structures, binding affinities and kinetics, and in vivo protection of eight anti-NANP antibodies derived from an RTS,S phase 2a trial and encoded by three different heavy-chain germline genes. The structures reinforce the importance of homotypic Fab-Fab interactions in protective antibodies and the overwhelmingly dominant preference for a germline-encoded aromatic residue for recognition of the NANP motif. In this study, antibody apparent affinity correlates best with protection in an in vivo mouse model, with the more potent antibodies also recognizing epitopes with repeating secondary structural motifs of type I ß- and Asn pseudo 310 turns; such insights can be incorporated into design of more effective immunogens and antibodies for passive immunization.


Assuntos
Anticorpos Antiprotozoários/imunologia , Malária Falciparum/imunologia , Malária Falciparum/prevenção & controle , Plasmodium falciparum/imunologia , Sequências Repetitivas de Aminoácidos , Motivos de Aminoácidos , Sequência de Aminoácidos , Animais , Afinidade de Anticorpos/imunologia , Cristalografia por Raios X , Epitopos/química , Epitopos/imunologia , Fragmentos Fab das Imunoglobulinas/química , Fragmentos Fab das Imunoglobulinas/imunologia , Cinética , Camundongos Endogâmicos C57BL , Modelos Moleculares , Parasitos/imunologia , Peptídeos/química , Peptídeos/metabolismo , Ligação Proteica
4.
Cochrane Database Syst Rev ; 1: CD013398, 2021 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-33471371

RESUMO

BACKGROUND: Despite being preventable, malaria remains an important public health problem. The World Health Organization (WHO) reports that overall progress in malaria control has plateaued for the first time since the turn of the century. Researchers and policymakers are therefore exploring alternative and supplementary malaria vector control tools. Research in 1900 indicated that modification of houses may be effective in reducing malaria: this is now being revisited, with new research now examining blocking house mosquito entry points or modifying house construction materials to reduce exposure of inhabitants to infectious bites. OBJECTIVES: To assess the effects of house modifications on malaria disease and transmission. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register; Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; MEDLINE (PubMed); Embase (OVID); Centre for Agriculture and Bioscience International (CAB) Abstracts (Web of Science); and the Latin American and Caribbean Health Science Information database (LILACS), up to 1 November 2019. We also searched the WHO International Clinical Trials Registry Platform (www.who.int/ictrp/search/en/), ClinicalTrials.gov (www.clinicaltrials.gov), and the ISRCTN registry (www.isrctn.com/) to identify ongoing trials up to the same date. SELECTION CRITERIA: Randomized controlled trials, including cluster-randomized controlled trials (cRCTs), cross-over studies, and stepped-wedge designs were eligible, as were quasi-experimental trials, including controlled before-and-after studies, controlled interrupted time series, and non-randomized cross-over studies. We only considered studies reporting epidemiological outcomes (malaria case incidence, malaria infection incidence or parasite prevalence). We also summarised qualitative studies conducted alongside included studies. DATA COLLECTION AND ANALYSIS: Two review authors selected eligible studies, extracted data, and assessed the risk of bias. We used risk ratios (RR) to compare the effect of the intervention with the control for dichotomous data. For continuous data, we presented the mean difference; and for count and rate data, we used rate ratios. We presented all results with 95% confidence intervals (CIs). We assessed the certainty of evidence using the GRADE approach. MAIN RESULTS: Six cRCTs met our inclusion criteria, all conducted in sub-Saharan Africa; three randomized by household, two by village, and one at the community level. All trials assessed screening of windows, doors, eaves, ceilings or any combination of these; this was either alone, or in combination with eave closure, roof modification or eave tube installation (a "lure and kill" device that reduces mosquito entry whilst maintaining some airflow). In two trials, the interventions were insecticide-based. In five trials, the researchers implemented the interventions. The community implemented the interventions in the sixth trial. At the time of writing the review, two of the six trials had published results, both of which compared screened houses (without insecticide) to unscreened houses. One trial in Ethiopia assessed screening of windows and doors. Another trial in the Gambia assessed full screening (screening of eaves, doors and windows), as well as screening of ceilings only. Screening may reduce clinical malaria incidence caused by Plasmodium falciparum (rate ratio 0.38, 95% CI 0.18 to 0.82; 1 trial, 184 participants, 219.3 person-years; low-certainty evidence; Ethiopian study). For malaria parasite prevalence, the point estimate, derived from The Gambia study, was smaller (RR 0.84, 95% CI 0.60 to 1.17; 713 participants, 1 trial; low-certainty evidence), and showed an effect on anaemia (RR 0.61, 95% CI 0.42, 0.89; 705 participants; 1 trial, moderate-certainty evidence). Screening may reduce the entomological inoculation rate (EIR): both trials showed lower estimates in the intervention arm. In the Gambian trial, there was a mean difference in EIR between the control houses and treatment houses ranging from 0.45 to 1.50 (CIs ranged from -0.46 to 2.41; low-certainty evidence), depending on the study year and treatment arm. The Ethiopian trial reported a mean difference in EIR of 4.57, favouring screening (95% CI 3.81 to 5.33; low-certainty evidence). Pooled analysis of the trials showed that individuals living in fully screened houses were slightly less likely to sleep under a bed net (RR 0.84, 95% CI 0.65 to 1.09; 2 trials, 203 participants). In one trial, bed net usage was also lower in individuals living in houses with screened ceilings (RR 0.69, 95% CI 0.50 to 0.95; 1 trial, 135 participants). AUTHORS' CONCLUSIONS: Based on the two trials published to date, there is some evidence that screening may reduce malaria transmission and malaria infection in people living in the house. The four trials awaiting publication are likely to enrich the current evidence base, and we will add these to this review when they become available.


Assuntos
Materiais de Construção , Habitação , Malária Falciparum/prevenção & controle , Adolescente , Adulto , África ao Sul do Saara/epidemiologia , Anemia/diagnóstico , Anemia/epidemiologia , Animais , Arquitetura , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Inseticidas , Malária Falciparum/epidemiologia , Malária Falciparum/parasitologia , Masculino , Mosquiteiros , Mosquitos Vetores , Plasmodium falciparum , Gravidez , Prevalência , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos
5.
Biochem Biophys Res Commun ; 534: 86-93, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33316544

RESUMO

This work describes a methodology for developing a minimal, subunit-based, multi-epitope, multi-stage, chemically-synthesised, anti-Plasmodium falciparum malaria vaccine. Some modified high activity binding peptides (mHABPs) derived from functionally relevant P. falciparum MSP, RH5 and AMA-1 conserved amino acid regions (cHABPs) for parasite binding to and invasion of red blood cells (RBC) were selected. They were highly immunogenic as assessed by indirect immunofluorescence (IFA) and Western blot (WB) assays and protective immune response-inducers against malarial challenge in the Aotus monkey experimental model. NetMHCIIpan 4.0 was used for predicting peptide-Aotus/human major histocompatibility class II (MHCII) binding affinity in silico due to the similarity between Aotus and human immune system molecules; ∼50% of Aotus MHCII allele molecules have a counterpart in the human immune system, being Aotus-specific, whilst others enabled recognition of their human counterparts. Some peptides' 1H-NMR-assessed structural conformation was determined to explain residue modifications in mHABPs inducing secondary structure changes. These directly influenced immunological behaviour, thereby highlighting the relationship with MHCII antigen presentation. The data obtained in such functional, immunological, structural and predictive approach suggested that some of these peptides could be excellent components of a fully-protective antimalarial vaccine.


Assuntos
Eritrócitos/parasitologia , Vacinas Antimaláricas/farmacologia , Plasmodium falciparum/patogenicidade , Animais , Antígenos de Protozoários/química , Aotidae , Proteínas de Transporte/química , Epitopos , Eritrócitos/efeitos dos fármacos , Antígenos de Histocompatibilidade Classe II/metabolismo , Interações Hospedeiro-Parasita/efeitos dos fármacos , Humanos , Espectroscopia de Ressonância Magnética , Vacinas Antimaláricas/imunologia , Vacinas Antimaláricas/metabolismo , Malária Falciparum/imunologia , Malária Falciparum/prevenção & controle , Peptídeos/imunologia , Peptídeos/metabolismo , Proteínas de Protozoários/química , Vacinas de Subunidades/imunologia , Vacinas de Subunidades/farmacologia
6.
Vaccine ; 39(4): 687-698, 2021 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-33358704

RESUMO

BACKGROUND: The evaluation of immune responses to RTS,S/AS01 has traditionally focused on immunoglobulin (Ig) G antibodies that are only moderately associated with protection. The role of other antibody isotypes that could also contribute to vaccine efficacy remains unclear. Here we investigated whether RTS,S/AS01E elicits antigen-specific serum IgA antibodies to the vaccine and other malaria antigens, and we explored their association with protection. METHODS: Ninety-five children (age 5-17 months old at first vaccination) from the RTS,S/AS01E phase 3 clinical trial who received 3 doses of RTS,S/AS01E or a comparator vaccine were selected for IgA quantification 1 month post primary immunization. Two sites with different malaria transmission intensities (MTI) and clinical malaria cases and controls, were included. Measurements of IgA against different constructs of the circumsporozoite protein (CSP) vaccine antigen and 16 vaccine-unrelated Plasmodium falciparum antigens were performed using a quantitative suspension array assay. RESULTS: RTS,S vaccination induced a 1.2 to 2-fold increase in levels of serum/plasma IgA antibodies to all CSP constructs, which was not observed upon immunization with a comparator vaccine. The IgA response against 13 out of 16 vaccine-unrelated P. falciparum antigens also increased after vaccination, and levels were higher in recipients of RTS,S than in comparators. IgA levels to malaria antigens before vaccination were more elevated in the high MTI than the low MTI site. No statistically significant association of IgA with protection was found in exploratory analyses. CONCLUSIONS: RTS,S/AS01E induces IgA responses in peripheral blood against CSP vaccine antigens and other P. falciparum vaccine-unrelated antigens, similar to what we previously showed for IgG responses. Collectively, data warrant further investigation of the potential contribution of vaccine-induced IgA responses to efficacy and any possible interplay, either synergistic or antagonistic, with protective IgG, as identifying mediators of protection by RTS,S/AS01E immunization is necessary for the design of improved second-generation vaccines. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT008666191.


Assuntos
Vacinas Antimaláricas , Malária Falciparum , Malária , Adolescente , Anticorpos Antiprotozoários , Antígenos de Protozoários , Criança , Pré-Escolar , Humanos , Imunoglobulina A , Lactente , Malária/prevenção & controle , Malária Falciparum/prevenção & controle , Plasmodium falciparum , Proteínas de Protozoários
7.
Cochrane Database Syst Rev ; 10: CD013398, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-33058136

RESUMO

BACKGROUND: Despite being preventable, malaria remains an important public health problem. The World Health Organization (WHO) reports that overall progress in malaria control has plateaued for the first time since the turn of the century. Researchers and policymakers are therefore exploring alternative and supplementary malaria vector control tools. Research in 1900 indicated that modification of houses may be effective in reducing malaria: this is now being revisited, with new research now examining blocking house mosquito entry points or modifying house construction materials to reduce exposure of inhabitants to infectious bites. OBJECTIVES: To assess the effects of house modifications on malaria disease and transmission. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register; Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; MEDLINE (PubMed); Embase (OVID); Centre for Agriculture and Bioscience International (CAB) Abstracts (Web of Science); and the Latin American and Caribbean Health Science Information database (LILACS), up to 1 November 2019. We also searched the WHO International Clinical Trials Registry Platform (www.who.int/ictrp/search/en/), ClinicalTrials.gov (www.clinicaltrials.gov), and the ISRCTN registry (www.isrctn.com/) to identify ongoing trials up to the same date. SELECTION CRITERIA: Randomized controlled trials, including cluster-randomized controlled trials (cRCTs), cross-over studies, and stepped-wedge designs were eligible, as were quasi-experimental trials, including controlled before-and-after studies, controlled interrupted time series, and non-randomized cross-over studies. We only considered studies reporting epidemiological outcomes (malaria case incidence, malaria infection incidence or parasite prevalence). We also summarised qualitative studies conducted alongside included studies. DATA COLLECTION AND ANALYSIS: Two review authors selected eligible studies, extracted data, and assessed the risk of bias. We used risk ratios (RR) to compare the effect of the intervention with the control for dichotomous data. For continuous data, we presented the mean difference; and for count and rate data, we used rate ratios. We presented all results with 95% confidence intervals (CIs). We assessed the certainty of evidence using the GRADE approach. MAIN RESULTS: Six cRCTs met our inclusion criteria, all conducted in sub-Saharan Africa; three randomized by household, two by village, and one at the community level. All trials assessed screening of windows, doors, eaves, ceilings or any combination of these; this was either alone, or in combination with eave closure, roof modification or eave tube installation (a "lure and kill" device that reduces mosquito entry whilst maintaining some airflow). In two trials, the interventions were insecticide-based. In five trials, the researchers implemented the interventions. The community implemented the interventions in the sixth trial. At the time of writing the review, two of the six trials had published results, both of which compared screened houses (without insecticide) to unscreened houses. One trial in Ethiopia assessed screening of windows and doors. Another trial in the Gambia assessed full screening (screening of eaves, doors and windows), as well as screening of ceilings only. Screening may reduce clinical malaria incidence caused by Plasmodium falciparum (rate ratio 0.38, 95% CI 0.18 to 0.82; 1 trial, 184 participants, 219.3 person-years; low-certainty evidence; Ethiopian study). For malaria parasite prevalence, the point estimate, derived from The Gambia study, was smaller (RR 0.84, 95% CI 0.60 to 1.17; 713 participants, 1 trial; moderate-certainty evidence), and showed an effect on anaemia (RR 0.61, 95% CI 0.42, 0.89; 705 participants; 1 trial, moderate-certainty evidence). Screening may reduce the entomological inoculation rate (EIR): both trials showed lower estimates in the intervention arm. In the Gambian trial, there was a mean difference in EIR between the control houses and treatment houses ranging from 0.45 to 1.50 (CIs ranged from -0.46 to 2.41; low-certainty evidence), depending on the study year and treatment arm. The Ethiopian trial reported a mean difference in EIR of 4.57, favouring screening (95% CI 3.81 to 5.33; low-certainty evidence). Pooled analysis of the trials showed that individuals living in fully screened houses were slightly less likely to sleep under a bed net (RR 0.84, 95% CI 0.65 to 1.09; 2 trials, 203 participants). In one trial, bed net usage was also lower in individuals living in houses with screened ceilings (RR 0.69, 95% CI 0.50 to 0.95; 1 trial, 135 participants). AUTHORS' CONCLUSIONS: Based on the two trials published to date, there is some evidence that screening may reduce malaria transmission and malaria infection in people living in the house. The four trials awaiting publication are likely to enrich the current evidence base, and we will add these to this review when they become available.


Assuntos
Materiais de Construção , Habitação , Malária Falciparum/prevenção & controle , Adolescente , Adulto , África ao Sul do Saara , Anemia/diagnóstico , Anemia/epidemiologia , Animais , Arquitetura , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Inseticidas , Malária Falciparum/epidemiologia , Masculino , Mosquitos Vetores , Plasmodium falciparum , Gravidez , Prevalência , Ensaios Clínicos Controlados Aleatórios como Assunto
8.
Nature ; 585(7826): 579-583, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32939086

RESUMO

Malaria has had a major effect on the human genome, with many protective polymorphisms-such as the sickle-cell trait-having been selected to high frequencies in malaria-endemic regions1,2. The blood group variant Dantu provides 74% protection against all forms of severe malaria in homozygous individuals3-5, a similar degree of protection to that afforded by the sickle-cell trait and considerably greater than that offered by the best malaria vaccine. Until now, however, the protective mechanism has been unknown. Here we demonstrate the effect of Dantu on the ability of the merozoite form of the malaria parasite Plasmodium falciparum to invade red blood cells (RBCs). We find that Dantu is associated with extensive changes to the repertoire of proteins found on the RBC surface, but, unexpectedly, inhibition of invasion does not correlate with specific RBC-parasite receptor-ligand interactions. By following invasion using video microscopy, we find a strong link between RBC tension and merozoite invasion, and identify a tension threshold above which invasion rarely occurs, even in non-Dantu RBCs. Dantu RBCs have higher average tension than non-Dantu RBCs, meaning that a greater proportion resist invasion. These findings provide both an explanation for the protective effect of Dantu, and fresh insight into why the efficiency of P. falciparum invasion might vary across the heterogenous populations of RBCs found both within and between individuals.


Assuntos
Antígenos de Grupos Sanguíneos/genética , Eritrócitos/citologia , Eritrócitos/parasitologia , Malária Falciparum/patologia , Malária Falciparum/prevenção & controle , Plasmodium falciparum/metabolismo , Polimorfismo Genético , Antígenos de Grupos Sanguíneos/classificação , Antígenos de Grupos Sanguíneos/metabolismo , Criança , Eritrócitos/metabolismo , Eritrócitos/patologia , Feminino , Genótipo , Humanos , Quênia , Ligantes , Masculino , Merozoítos/metabolismo , Merozoítos/patogenicidade , Microscopia de Vídeo , Plasmodium falciparum/crescimento & desenvolvimento , Plasmodium falciparum/patogenicidade
9.
PLoS Med ; 17(8): e1003177, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32817632

RESUMO

BACKGROUND: The World Health Organization has yet to endorse deployment of topical repellents for malaria prevention as part of public health campaigns. We aimed to quantify the effectiveness of repellent distributed by the village health volunteer (VHV) network in the Greater Mekong Subregion (GMS) in reducing malaria in order to advance regional malaria elimination. METHODS AND FINDINGS: Between April 2015 and June 2016, a 15-month stepped-wedge cluster randomised trial was conducted in 116 villages in Myanmar (stepped monthly in blocks) to test the effectiveness of 12% N,N-diethylbenzamide w/w cream distributed by VHVs, on Plasmodium spp. infection. The median age of participants was 18 years, approximately half were female, and the majority were either village residents (46%) or forest dwellers (40%). No adverse events were reported during the study. Generalised linear mixed modelling estimated the effect of repellent on infection detected by rapid diagnostic test (RDT) (primary outcome) and polymerase chain reaction (PCR) (secondary outcome). Overall Plasmodium infection detected by RDT was low (0.16%; 50/32,194), but infection detected by PCR was higher (3%; 419/13,157). There was no significant protection against RDT-detectable infection (adjusted odds ratio [AOR] = 0.25, 95% CI 0.004-15.2, p = 0.512). In Plasmodium-species-specific analyses, repellent protected against PCR-detectable P. falciparum (adjusted relative risk ratio [ARRR] = 0.67, 95% CI 0.47-0.95, p = 0.026), but not P. vivax infection (ARRR = 1.41, 95% CI 0.80-2.47, p = 0.233). Repellent effects were similar when delayed effects were modelled, across risk groups, and regardless of village-level and temporal heterogeneity in malaria prevalence. The incremental cost-effectiveness ratio was US$256 per PCR-detectable infection averted. Study limitations were a lower than expected Plasmodium spp. infection rate and potential geographic dilution of the intervention. CONCLUSIONS: In this study, we observed apparent protection against new infections associated with the large-scale distribution of repellent by VHVs. Incorporation of repellent into national strategies, particularly in areas where bed nets are less effective, may contribute to the interruption of malaria transmission. Further studies are warranted across different transmission settings and populations, from the GMS and beyond, to inform WHO public health policy on the deployment of topical repellents for malaria prevention. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry (ACTRN12616001434482).


Assuntos
Serviços de Saúde Comunitária/métodos , Repelentes de Insetos/administração & dosagem , Malária Falciparum/epidemiologia , Malária Falciparum/prevenção & controle , Malária Vivax/epidemiologia , Malária Vivax/prevenção & controle , Voluntários , Administração Tópica , Adolescente , Adulto , Criança , Análise por Conglomerados , Serviços de Saúde Comunitária/economia , Análise Custo-Benefício/métodos , Feminino , Humanos , Repelentes de Insetos/economia , Malária Falciparum/economia , Malária Vivax/economia , Masculino , Mianmar/epidemiologia , Gravidez , Resultado do Tratamento , Adulto Jovem
10.
PLoS One ; 15(8): e0237671, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32797068

RESUMO

In high malaria transmission settings, the use of sulfadoxine-pyrimethamine-based intermittent preventive treatment during pregnancy (IPTp-SP) has resulted in decreased antibody (Ab) levels to VAR2CSA. However, information of Ab levels in areas of low or intermediate malaria transmission after long-term implementation of IPTp-SP is still lacking. The present study sought to evaluate antibody prevalence and levels in women at delivery in Etoudi, a peri-urban area in the capital of Yaoundé, Cameroon, that is a relatively low-malaria transmission area. Peripheral plasma samples from 130 pregnant women were collected at delivery and tested for IgG to the full-length recombinant VAR2CSA (FV2) and its most immunogenic subdomain, DBL5. The study was conducted between 2013 and 2015, approximately ten years after implementation of IPTp-SP in Cameroon. About 8.6% of the women attending the clinic had placental malaria (PM). One, two or 3 doses of SP did not impact significantly on either the percentage of women with Ab to FV2 and DBL5 or Ab levels in Ab-positive women compared to women not taking SP. The prevalence of Ab to FV2 and DBL5 was only 36.9% and 36.1%, respectively. Surprisingly, among women who had PM at delivery, only 61.5% and 57.7% had Ab to FV2 and DBL5, respectively, with only 52.9% and 47.1% in PM-positive paucigravidae and 77.7% of multigravidae having Ab to both antigens. These results suggest that long-term implementation of IPTp-SP in a low-malaria transmission area results in few women having Ab to VAR2CSA.


Assuntos
Anticorpos Antiprotozoários/imunologia , Antígenos de Protozoários/imunologia , Antimaláricos/uso terapêutico , Malária Falciparum/prevenção & controle , Complicações Parasitárias na Gravidez/prevenção & controle , Pirimetamina/uso terapêutico , Sulfadoxina/uso terapêutico , Adulto , Anticorpos Antiprotozoários/sangue , Camarões/epidemiologia , Combinação de Medicamentos , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Malária/sangue , Malária/epidemiologia , Malária/imunologia , Malária/prevenção & controle , Malária Falciparum/sangue , Malária Falciparum/epidemiologia , Malária Falciparum/imunologia , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/imunologia , Gravidez , Complicações Parasitárias na Gravidez/sangue , Complicações Parasitárias na Gravidez/epidemiologia , Complicações Parasitárias na Gravidez/imunologia , Adulto Jovem
11.
PLoS Med ; 17(8): e1003227, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32797101

RESUMO

BACKGROUND: Malaria eradication remains the long-term vision of the World Health Organization (WHO). However, whether malaria elimination is feasible in areas of stable transmission in sub-Saharan Africa with currently available tools remains a subject of debate. This study aimed to evaluate a multiphased malaria elimination project to interrupt Plasmodium falciparum malaria transmission in a rural district of southern Mozambique. METHODS AND FINDINGS: A before-after study was conducted between 2015 and 2018 in the district of Magude, with 48,448 residents living in 10,965 households. Building on an enhanced surveillance system, two rounds of mass drug administrations (MDAs) per year over two years (phase I, August 2015-2017), followed by one year of reactive focal mass drug administrations (rfMDAs) (phase II, September 2017-June 2018) were deployed with annual indoor residual spraying (IRS), programmatically distributed long-lasting insecticidal nets (LLINs), and standard case management. The four MDA rounds covered 58%-72% of the population, and annual IRS reported coverage was >70%. Yearly parasite surveys and routine surveillance data were used to monitor the primary outcomes of the study-malaria prevalence and incidence-at baseline and annually since the onset of the project. Parasite prevalence by rapid diagnostic test (RDT) declined from 9.1% (95% confidence interval [CI] 7.0-11.8) in May 2015 to 2.6% (95% CI 2.0-3.4), representing a 71.3% (95% CI 71.1-71.4, p < 0.001) reduction after phase I, and to 1.4% (95% CI 0.9-2.2) after phase II. This represented an 84.7% (95% CI 81.4-87.4, p < 0.001) overall reduction in all-age prevalence. Case incidence fell from 195 to 75 cases per 1,000 during phase I (61.5% reduction) and to 67 per 1,000 during phase II (65.6% overall reduction). Interrupted time series (ITS) analysis was used to estimate the level and trend change in malaria cases associated with the set of project interventions and the number of cases averted. Phase I interventions were associated with a significant immediate reduction in cases of 69.1% (95% CI 57.5-77.6, p < 0.001). Phase II interventions were not associated with a level or trend change. An estimated 76.7% of expected cases were averted throughout the project (38,369 cases averted of 50,005 expected). One malaria-associated inpatient death was observed during the study period. There were 277 mild adverse events (AEs) recorded through the passive pharmacovigilance system during the four MDA rounds. One serious adverse event (SAE) that resulted in death was potentially related to the drug. The study was limited by the incomplete coverage of interventions, the quality of the routine and cross-sectional data collected, and the restricted accuracy of ITS analysis with a short pre-intervention period. CONCLUSION: In this study, we observed that the interventions deployed during the Magude project fell short of interrupting P. falciparum transmission with the coverages achieved. While new tools and strategies may be required to eventually achieve malaria elimination in stable transmission areas of sub-Saharan Africa, this project showed that innovative mixes of interventions can achieve large reductions in disease burden, a necessary step in the pathway towards elimination. TRIAL REGISTRATION: ClinicalTrials.gov NCT02914145.


Assuntos
Antimaláricos/administração & dosagem , Controle de Infecções/métodos , Malária Falciparum/prevenção & controle , Malária Falciparum/transmissão , Controle de Mosquitos/métodos , Adolescente , Adulto , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Controle de Infecções/tendências , Malária Falciparum/epidemiologia , Masculino , Pessoa de Meia-Idade , Controle de Mosquitos/tendências , Moçambique , Adulto Jovem
12.
PLoS One ; 15(8): e0236920, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32745085

RESUMO

BACKGROUND: Twenty-seven villages were selected in southwest Burkina Faso to implement new vector control strategies in addition to long lasting insecticidal nets (LLINs) through a Randomized Controlled Trial (RCT). We conducted entomological surveys in the villages during the dry cold season (January 2017), dry hot season (March 2017) and rainy season (June 2017) to describe malaria vectors bionomics, insecticide resistance and transmission prior to this trial. METHODS: We carried out hourly catches (from 17:00 to 09:00) inside and outside 4 houses in each village using the Human Landing Catch technique. Mosquitoes were identified using morphological taxonomic keys. Specimens belonging to the Anopheles gambiae complex and Anopheles funestus group were identified using molecular techniques as well as detection of Plasmodium falciparum infection and insecticide resistance target-site mutations. RESULTS: Eight Anopheles species were detected in the area. Anopheles funestus s.s was the main vector during the dry cold season. It was replaced by Anopheles coluzzii during the dry hot season whereas An. coluzzii and An. gambiae s.s. were the dominant species during the rainy season. Species composition of the Anopheles population varied significantly among seasons. All insecticide resistance mechanisms (kdr-w, kdr-e and ace-1 target site mutations) investigated were found in each members of the An. gambiae complex but at different frequencies. We observed early and late biting phenotypes in the main malaria vector species. Entomological inoculation rates were 2.61, 2.67 and 11.25 infected bites per human per month during dry cold season, dry hot season and rainy season, respectively. CONCLUSION: The entomological indicators of malaria transmission were high despite the universal coverage with LLINs. We detected early and late biting phenotypes in the main malaria vector species as well as physiological insecticide resistance mechanisms. These data will be used to evaluate the impact of complementary tools to LLINs in an upcoming RCT.


Assuntos
Anopheles , Resistência a Inseticidas/genética , Malária Falciparum/transmissão , Mosquitos Vetores/genética , Animais , Anopheles/classificação , Anopheles/genética , Anopheles/parasitologia , Burkina Faso/epidemiologia , Culex/classificação , Culex/genética , Culex/parasitologia , Culicidae/classificação , Culicidae/genética , Culicidae/parasitologia , Ecologia , Genótipo , Humanos , Malária Falciparum/prevenção & controle , Controle de Mosquitos/métodos , Controle de Mosquitos/organização & administração , Mosquitos Vetores/classificação , Mosquitos Vetores/parasitologia , Plasmodium falciparum/isolamento & purificação , Estações do Ano
13.
BMC Infect Dis ; 20(1): 573, 2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32758164

RESUMO

BACKGROUND: Malaria during pregnancy leads to serious adverse effects on mothers and the fetus. Approximately 25 million pregnant women in sub-Saharan Africa live at risk of malaria. This study would help to achieve Sustainable Development Goals (SDGs) by improving programs that deal with the prevention of malaria. Therefore, this study aimed to assess the prevalence and associated factors of malaria among pregnant women. METHODS: A community-based cross-sectional study was conducted from July to August 2018 in Sherkole district, West Ethiopia. A multi-stage sampling technique was used to select 504 pregnant women. The interviewer-administered semi-structured questionnaire was used for data collection. Malaria was also diagnosed using a rapid diagnostic test. The data was entered using EPI info version 7.2.2.2 and transferred to SPSS version 20 for analysis. Descriptive statistics were done using frequency and percentages. Both bivariable and multivariable logistic regression models were employed. Variables having p-value < 0.2 were included in the final multivariable model. Variables having p-values < 0.05 from the multivariable model were considered to be significantly associated with the dependent variable. The adjusted odds ratio with its 95% confidence interval (CI) was used as a measure of association. RESULTS: Of the total 498 pregnant women who participated in this study, 51(10.2, 95% CI: 7.72-13.24) were found to have malaria. Of these, 46 (90.2%) and 5 (9.8%) were caused by Plasmodium falciparum and Plasmodium vivax, respectively. Decreasing Age (Adjusted Odds Ratio (AOR) 0.78; 95% CI 0.67-0.911), not using insecticide-treated bed net (ITN) (AOR 12.5; 95% CI 4.86-32.21), lack of consultation and health education about malaria prevention (AOR 7.18; 95% CI 2.74-18.81), being on second-trimester pregnancy (AOR 7.58; 95% CI 2.84-20.2), gravidae II (AOR 5.99; 95% CI 1.68-21.44) were found to be significantly associated with malaria during pregnancy. CONCLUSION: Malaria is still a public health problem among pregnant women in the Sherkole district. Age, ITN use, gravidity, gestational age, and health education had a significant association with malaria. Screening pregnant women for asymptomatic malaria infection and educating and consulting on the appropriate malaria preventive methods shall be provided.


Assuntos
Malária Falciparum/epidemiologia , Malária Vivax/epidemiologia , Plasmodium falciparum/imunologia , Plasmodium vivax/imunologia , Complicações Parasitárias na Gravidez/epidemiologia , Adolescente , Adulto , Antígenos de Protozoários/sangue , Infecções Assintomáticas , Estudos Transversais , Testes Diagnósticos de Rotina/métodos , Etiópia/epidemiologia , Feminino , Seguimentos , Humanos , Mosquiteiros Tratados com Inseticida , Modelos Logísticos , Malária Falciparum/prevenção & controle , Malária Vivax/prevenção & controle , Razão de Chances , Gravidez , Complicações Parasitárias na Gravidez/prevenção & controle , Prevalência , Fatores de Risco , Inquéritos e Questionários , Adulto Jovem
14.
Nat Commun ; 11(1): 3799, 2020 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-32732892

RESUMO

Plasmodium falciparum in pregnancy is a major cause of adverse pregnancy outcomes. We combine performance estimates of standard rapid diagnostic tests (RDT) from trials of intermittent screening and treatment in pregnancy (ISTp) with modelling to assess whether screening at antenatal visits improves upon current intermittent preventative therapy with sulphadoxine-pyrimethamine (IPTp-SP). We estimate that RDTs in primigravidae at first antenatal visit are substantially more sensitive than in non-pregnant adults (OR = 17.2, 95% Cr.I. 13.8-21.6), and that sensitivity declines in subsequent visits and with gravidity, likely driven by declining susceptibility to placental infection. Monthly ISTp with standard RDTs, even with highly effective drugs, is not superior to monthly IPTp-SP. However, a hybrid strategy, recently adopted in Tanzania, combining testing and treatment at first visit with IPTp-SP may offer benefit, especially in areas with high-grade SP resistance. Screening and treatment in the first trimester, when IPTp-SP is contraindicated, could substantially improve pregnancy outcomes.


Assuntos
Malária Falciparum/diagnóstico , Malária Falciparum/prevenção & controle , Programas de Rastreamento/métodos , Complicações Parasitárias na Gravidez/prevenção & controle , Cuidado Pré-Natal/métodos , Antimaláricos/uso terapêutico , Combinação de Medicamentos , Feminino , Política de Saúde , Humanos , Malária Falciparum/tratamento farmacológico , Testes de Sensibilidade Parasitária , Plasmodium falciparum/efeitos dos fármacos , Gravidez , Complicações Parasitárias na Gravidez/tratamento farmacológico , Primeiro Trimestre da Gravidez , Pirimetamina/uso terapêutico , Sulfadoxina/uso terapêutico , Tanzânia , Organização Mundial da Saúde
15.
Rev. cuba. med. trop ; 72(2): e459, mayo.-ago. 2020. tab
Artigo em Espanhol | LILACS, CUMED | ID: biblio-1149909

RESUMO

Introducción: El paludismo es una enfermedad febril aguda potencialmente mortal causada por parásitos que se transmiten al ser humano por la picadura de mosquitos del género Anopheles. Cuba logró eliminar la transmisión de esta enfermedad gracias a grandes esfuerzos encaminados a conseguirlo, por lo que es necesario adoptar una serie de medidas para evitar su reaparición, mediante la vigilancia y el Programa de Control Sanitario Internacional. Objetivo: Caracterizar clínicamente un grupo de pacientes con paludismo importado. Métodos: Se realizó un estudio descriptivo de corte transversal de 46 pacientes adultos con paludismo importado, ingresados en el Instituto de Medicina Tropical Pedro Kourí desde enero 2015 a diciembre 2016. Los datos fueron tomados de las historias clínicas. El análisis de las variables cualitativas fue expresado en tablas de frecuencias absolutas y relativas. Resultados: Predominaron los pacientes del sexo masculino, con una edad media de 37,4 años. Entre los pacientes, 38 (82,6 por ciento) arribaron del continente africano, la mayoría de ellos de Angola (26,1 por ciento del total de casos). Fue significativa la relación existente entre el supuesto estado no inmune de los pacientes con la severidad del cuadro clínico y presencia de comorbilidades; así como la severidad del cuadro clínico con mayor parasitemia y la especie Plasmodium falciparum. La respuesta al tratamiento resultó excelente con los esquemas combinados utilizados a base de quinina y cloroquina según la especie. Conclusiones: La demora desde el arribo al ingreso hospitalario de los pacientes constituye un riesgo extraordinario para la reintroducción del paludismo en Cuba y para la vida de estos(AU)


Introduction: Malaria is an acute potentially fatal febrile disease caused by parasites transmitted to humans through the bite of mosquitoes from the genus Anopheles. Cuba succeeded in eliminating transmission of this disease thanks to great efforts geared to such an end. It is therefore necessary to take a number of measures aimed at preventing its re-emergence via surveillance and the International Health Control Program. Objective: Clinically characterize a group of patients with imported malaria. Methods: A descriptive cross-sectional study was conducted of 46 adult patients with imported malaria admitted to Pedro Kourí Tropical Medicine Institute from January 2015 to December 2016. The data were collected from the patients' medical records. Results of the analysis of qualitative variables were transferred onto absolute and relative frequency tables. Results: Male patients prevailed, with a mean age of 37.4 years. Of the patients studied, 38 (82.6 percent) were from the African continent, most of them from Angola (26.1 percent of the total cases). A significant relationship was found between the supposed non-immune status of patients and the severity of the clinical status and the presence of comorbidities, as well as between the severity of the clinical status and greater parasitemia and the presence of the species Plasmodium falciparum. An excellent response was obtained to treatment with combined schemes based on quinine and chloroquine, depending on the species. Conclusions: Delay between arrival and hospital admittance of patients is an extraordinary risk for the reintroduction of malaria in Cuba and to the patients' lives(AU)


Assuntos
Humanos , Medicina Tropical , Política Nacional de Vigilância Sanitária , Cloroquina/uso terapêutico , Epidemiologia Descritiva , Estudos Transversais , Malária Falciparum/prevenção & controle , Cuba
16.
Am J Trop Med Hyg ; 103(2_Suppl): 28-36, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32618242

RESUMO

From 2014 to 2016, a community-randomized controlled trial in Southern Province, Zambia, compared mass drug administration (MDA) and focal MDA (fMDA) with the standard of care. Acceptability of the intervention was assessed quantitatively using closed-ended and Likert scale-based questions posed during three household surveys conducted from April to May in 2014, 2015, and 2016 in 40 health catchments that implemented MDA and fMDA and 20 catchments that served as trial controls. In 2014 and 2015, 47 households per catchment were selected, targeting 1,880 households in MDA and fMDA trial arms; in 2016, 55 households per catchment were selected for a target of 2,200 households in MDA and fMDA trial arms. Concurrently, 27 focus group discussions and 23 in-depth interviews with 248 participants were conducted on reasons for testing and treatment refusal, reasons for nonadherence, and community perception of the MDA campaign. Results demonstrated that the MDA campaign was highly accepted with more than 99% of respondents stating that they would take treatment if positive for malaria. High acceptability at baseline could be associated with test-and-treat campaigns recently conducted in the study area. There was a large increase in the acceptability of prophylactic treatment if negative for malaria from the baseline to follow-up survey for adults and children, from 62% to 96% for each. This likely resulted from an intensive community-wide sensitization program that occurred before the first treatment round at each household during community health worker visits.


Assuntos
Artemisininas/administração & dosagem , Atitude Frente a Saúde , Malária Falciparum/prevenção & controle , Administração Massiva de Medicamentos , Aceitação pelo Paciente de Cuidados de Saúde , Quinolinas/administração & dosagem , Adulto , Artemisininas/uso terapêutico , Erradicação de Doenças/métodos , Quimioterapia Combinada , Feminino , Grupos Focais , Humanos , Malária Falciparum/diagnóstico , Malária Falciparum/tratamento farmacológico , Malária Falciparum/epidemiologia , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Quinolinas/uso terapêutico , Zâmbia/epidemiologia
17.
Am J Trop Med Hyg ; 103(2_Suppl): 90-97, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32618244

RESUMO

Whereas data on insecticide resistance and its underlying mechanisms exist for parts of Zambia, data remain limited in the southern part of the country. This study investigated the status of insecticide resistance, metabolic mechanisms, and parasite infection in Anopheles funestus along Lake Kariba in southern Zambia. Indoor-resting mosquitoes were collected from 20 randomly selected houses within clusters where a mass drug administration trial was conducted and raised to F1 progeny. Non-blood-fed 2- to 5-day-old female An. funestus were exposed to WHO insecticide-impregnated papers with 0.05% deltamethrin, 0.1% bendiocarb, 0.25% pirimiphos-methyl, or 4% dichloro-diphenyl-trichloroethane (DDT). In separate assays, An. funestus were pre-exposed to piperonyl butoxide (PBO) to determine the presence of monooxygenases. Wild-caught An. funestus that had laid eggs for susceptibility assays were screened for circumsporozoite protein of Plasmodium falciparum by ELISA, and sibling species were identified by polymerase chain reaction. Anopheles funestus showed resistance to deltamethrin and bendiocarb but remained susceptible to pirimiphos-methyl and DDT. The pre-exposure of An. funestus to PBO restored full susceptibility to deltamethrin but not to bendiocarb. The overall sporozoite infection rate in An. funestus populations was 5.8%. Detection of pyrethroid and carbamate resistance in An. funestus calls for increased insecticide resistance monitoring to guide planning and selection of effective insecticide resistance management strategies. To prevent the development of resistance and reduce the underlying vectorial capacity of mosquitoes in areas targeted for malaria elimination, an effective integrated vector management strategy is needed.


Assuntos
Anopheles/efeitos dos fármacos , Carbamatos , Resistência a Inseticidas , Inseticidas , Piretrinas , Animais , Anopheles/parasitologia , Humanos , Malária Falciparum/epidemiologia , Malária Falciparum/prevenção & controle , Malária Falciparum/transmissão , Controle de Mosquitos , Zâmbia/epidemiologia
18.
Am J Trop Med Hyg ; 103(2_Suppl): 54-65, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32618245

RESUMO

Rigorous evidence of effectiveness is needed to determine where and when to apply mass drug administration (MDA) or focal MDA (fMDA) as part of a malaria elimination strategy. The Zambia National Malaria Elimination Centre recently completed a community-randomized controlled trial in Southern Province to evaluate MDA and fMDA for transmission reduction. To assess the role of MDA and fMDA on infection incidence, we enrolled a longitudinal cohort for an 18-month period of data collection including monthly malaria parasite infection detection based on polymerase chain reaction and compared time to first infection and cumulative infection incidence outcomes across study arms using Cox proportional hazards and negative binomial models. A total of 2,026 individuals from 733 households were enrolled and completed sufficient follow-up for inclusion in analysis. Infection incidence declined dramatically across all study arms during the period of study, and MDA was associated with reduced risk of first infection (hazards ratio: 0.36; 95% CI: 0.16-0.80) and cumulative infection incidence during the first rainy season (first 5 months of follow-up) (incidence rate ratio: 0.34; 95% CI: 0.12-0.95). No significant effect was found for fMDA or for either arm over the full study period. Polymerase chain reaction infection status at baseline was strongly associated with follow-up infection. The short-term effects of MDA suggest it may be an impactful accelerator of transmission reduction in areas with high coverage of case management and vector control and should be considered as part of a malaria elimination strategy.


Assuntos
Malária Falciparum/epidemiologia , Administração Massiva de Medicamentos , Adolescente , Antimaláricos/administração & dosagem , Antimaláricos/uso terapêutico , Artemisininas/administração & dosagem , Artemisininas/uso terapêutico , Criança , Pré-Escolar , Erradicação de Doenças/métodos , Erradicação de Doenças/estatística & dados numéricos , Quimioterapia Combinada , Características da Família , Feminino , Humanos , Incidência , Estudos Longitudinais , Malária Falciparum/tratamento farmacológico , Malária Falciparum/prevenção & controle , Masculino , Administração Massiva de Medicamentos/métodos , Administração Massiva de Medicamentos/estatística & dados numéricos , Quinolinas/administração & dosagem , Quinolinas/uso terapêutico , Adulto Jovem , Zâmbia/epidemiologia
19.
Am J Trop Med Hyg ; 103(2_Suppl): 7-18, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32618247

RESUMO

Over the past decade, Zambia has made substantial progress against malaria and has recently set the ambitious goal of eliminating by 2021. In the context of very high vector control and improved access to malaria diagnosis and treatment in Southern Province, we implemented a community-randomized controlled trial to assess the impact of four rounds of community-wide mass drug administration (MDA) and household-level MDA (focal MDA) with dihydroartemisinin-piperaquine (DHAP) implemented between December 2014 and February 2016. The mass treatment campaigns achieved relatively good household coverage (63-79%), were widely accepted by the community (ranging from 87% to 94%), and achieved very high adherence to the DHAP regimen (81-96%). Significant declines in all malaria study end points were observed, irrespective of the exposure group, with the overall parasite prevalence during the peak transmission season declining by 87.2% from 31.3% at baseline to 4.0% in 2016 at the end of the trial. Children in areas of lower transmission (< 10% prevalence at baseline) that received four MDA rounds had a 72% (95% CI = 12-91%) reduction in malaria parasite prevalence as compared with those with the standard of care without any mass treatment. Mass drug administration consistently had the largest short-term effect size across study end points in areas of lower transmission following the first two MDA rounds. In the context of achieving very high vector control coverage and improved access to diagnosis and treatment for malaria, our results suggest that MDA should be considered for implementation in African settings for rapidly reducing malaria outcomes in lower transmission settings.


Assuntos
Antimaláricos/administração & dosagem , Artemisininas/administração & dosagem , Malária Falciparum/prevenção & controle , Administração Massiva de Medicamentos/métodos , Quinolinas/administração & dosagem , Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Erradicação de Doenças/métodos , Quimioterapia Combinada , Humanos , Incidência , Malária Falciparum/tratamento farmacológico , Malária Falciparum/epidemiologia , Avaliação de Programas e Projetos de Saúde , Quinolinas/uso terapêutico , Zâmbia/epidemiologia
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