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1.
Am J Trop Med Hyg ; 2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33782209

RESUMO

Distribution of long-lasting insecticide-treated nets (LLINs), passive detection and treatment with artemisinin-based combination therapy (ACT), and intermittent preventive treatment in pregnancy (IPTp) are the mainstay malaria control measures of Guinea-Bissau's national control programme. This study aimed to estimate the prevalence of Plasmodium falciparum on Bubaque, the most populous island of the country's remote Bijagos archipelago. A cross-sectional survey was performed at the start of the rainy season in August 2017. Participants were recruited using systematic random sampling in a two-stage stratified cluster design. Malaria parasitemia was detected using rapid diagnostic tests (RDTs) and quantitative PCR (qPCR). Data on housing, education, larval source management, socioeconomic status, anemia, and malaria preventive measures were collected. Multivariable logistic regression models were constructed to identify associations with P. falciparum infection. Four hundred four persons (aged 6 months-79 years, median 17 years) were enrolled in the study. The prevalence of P. falciparum parasitemia was 5.8% by RDT (95% CI: 3.55-9.33) and 16.9% by qPCR (95% CI: 13.09-21.71). The prevalence of anemia was 74.3% (95% CI: 69.04-78.85) as defined by the WHO criteria. All sampled houses were found to have open eaves; 99.5% of the surveyed population reported sleeping under a bednet (95% CI: 97.8-99.9). Although reported LLIN use is high, there remains an appreciable prevalence of malaria, suggesting that transmission is ongoing and further tools are required to reduce the burden of the disease.

3.
BMC Infect Dis ; 20(1): 741, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33036564

RESUMO

BACKGROUND: Cholera remains a major global health challenge. Uvira, in the Democratic Republic of the Congo (DRC), has had endemic cholera since the 1970's and has been implicated as a possible point of origin for national outbreaks. A previous study among this population, reported a case confirmation rate of 40% by rapid diagnostic test (RDT) among patients at the Uvira Cholera Treatment Centre (CTC). This study considers the prevalence and diversity of 15 enteric pathogens in suspected cholera cases seeking treatment at the Uvira CTC. METHODS: We used the Luminex xTAG® multiplex PCR to test for 15 enteric pathogens, including toxigenic strains of V. cholerae in rectal swabs preserved on Whatman FTA Elute cards. Results were interpreted on MAGPIX® and analyzed on the xTAG® Data Analysis Software. Prevalence of enteric pathogens were calculated and pathogen diversity was modelled with a Poisson regression. RESULTS: Among 269 enrolled CTC patients, PCR detected the presence of toxigenic Vibrio cholerae in 38% (103/269) of the patients, which were considered to be cholera cases. These strains were detected as the sole pathogen in 36% (37/103) of these cases. Almost half (45%) of all study participants carried multiple enteric pathogens (two or more). Enterotoxigenic Escherichia coli (36%) and Cryptosporidium (28%) were the other most common pathogens identified amongst all participants. No pathogen was detected in 16.4% of study participants. Mean number of pathogens was highest amongst boys and girls aged 1-15 years and lowest in women aged 16-81 years. Ninety-three percent of toxigenic V. cholerae strains detected by PCR were found in patients having tested positive for V. cholerae O1 by RDT. CONCLUSIONS: Our study supports previous results from DRC and other cholera endemic areas in sub-Sahara Africa with less than half of CTC admissions positive for cholera by PCR. More research is required to determine the causes of severe acute diarrhea in these low-resource, endemic areas to optimize treatment measures. TRIAL REGISTRATION: This study is part of the impact evaluation study entitled: "Impact Evaluation of Urban Water Supply Improvements on Cholera and Other Diarrheal Diseases in Uvira, Democratic Republic of Congo" registered on 10 October 2016 at clinicaltrials.gov Identification number: NCT02928341 .


Assuntos
Cólera/epidemiologia , Criptosporidiose/epidemiologia , Cryptosporidium/genética , Diarreia/epidemiologia , Surtos de Doenças , Escherichia coli Enterotoxigênica/genética , Infecções por Escherichia coli/epidemiologia , Vibrio cholerae/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Criança , Pré-Escolar , Cólera/microbiologia , Criptosporidiose/parasitologia , República Democrática do Congo/epidemiologia , Testes Diagnósticos de Rotina , Diarreia/microbiologia , Doenças Endêmicas , Infecções por Escherichia coli/microbiologia , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Multiplex , Prevalência , Microbiologia da Água , Adulto Jovem
4.
Am J Trop Med Hyg ; 103(2): 558-560, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32553046

RESUMO

Rapid diagnostic tests (RDTs) play a critical role in malaria diagnosis and control. The emergence of Plasmodium falciparum parasites that can evade detection by RDTs threatens control and elimination efforts. These parasites lack or have altered genes encoding histidine-rich proteins (HRPs) 2 and 3, the antigens recognized by HRP2-based RDTs. Surveillance of such parasites is dependent on identifying false-negative RDT results among suspected malaria cases, a task made more challenging during the current pandemic because of the overlap of symptoms between malaria and COVID-19, particularly in areas of low malaria transmission. Here, we share our perspective on the emergence of P. falciparum parasites lacking HRP2 and HRP3, and the surveillance needed to identify them amid the COVID-19 pandemic.


Assuntos
Infecções por Coronavirus/epidemiologia , Testes Diagnósticos de Rotina/métodos , Malária Falciparum/diagnóstico , Plasmodium falciparum/isolamento & purificação , Pneumonia Viral/epidemiologia , África , Antígenos de Protozoários/análise , Betacoronavirus , Humanos , Malária Falciparum/epidemiologia , Pandemias , Proteínas de Protozoários/análise
5.
EBioMedicine ; 55: 102757, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32403083

RESUMO

BACKGROUND: Many health facilities in malaria endemic countries are dependent on Rapid diagnostic tests (RDTs) for diagnosis and some National Health Service (NHS) hospitals without expert microscopists rely on them for diagnosis out of hours. The emergence of P. falciparum lacking the gene encoding histidine-rich protein 2 and 3 (HRP2 and HRP3) and escaping RDT detection threatens progress in malaria control and elimination. Currently, confirmation of RDT negative due to the deletion of pfhrp2 and pfhrp3, which encodes a cross-reactive protein isoform, requires a series of PCR assays. These tests have different limits of detection and many laboratories have reported difficulty in confirming the absence of the deletions with certainty. METHODS: We developed and validated a novel and rapid multiplex real time quantitative (qPCR) assay to detect pfhrp2, pfhrp3, confirmatory parasite and human reference genes simultaneously. We also applied the assay to detect pfhrp2 and pfhrp3 deletion in 462 field samples from different endemic countries and UK travellers. RESULTS: The qPCR assay demonstrated diagnostic sensitivity of 100% (n = 19, 95% CI= (82.3%; 100%)) and diagnostic specificity of 100% (n = 31; 95% CI= (88.8%; 100%)) in detecting pfhrp2 and pfhrp3 deletions. In addition, the assay estimates P. falciparum parasite density and accurately detects pfhrp2 and pfhrp3 deletions masked in polyclonal infections. We report pfhrp2 and pfhrp3 deletions in parasite isolates from Kenya, Tanzania and in UK travellers. INTERPRETATION: The new qPCR is easily scalable to routine surveillance studies in countries where P. falciparum parasites lacking pfhrp2 and pfhrp3 are a threat to malaria control.

6.
Lancet Infect Dis ; 20(8): 953-963, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32277908

RESUMO

BACKGROUND: Passively collected malaria case data are the foundation for public health decision making. However, because of population-level immunity, infections might not always be sufficiently symptomatic to prompt individuals to seek care. Understanding the proportion of all Plasmodium spp infections expected to be detected by the health system becomes particularly paramount in elimination settings. The aim of this study was to determine the association between the proportion of infections detected and transmission intensity for Plasmodium falciparum and Plasmodium vivax in several global endemic settings. METHODS: The proportion of infections detected in routine malaria data, P(Detect), was derived from paired household cross-sectional survey and routinely collected malaria data within health facilities. P(Detect) was estimated using a Bayesian model in 431 clusters spanning the Americas, Africa, and Asia. The association between P(Detect) and malaria prevalence was assessed using log-linear regression models. Changes in P(Detect) over time were evaluated using data from 13 timepoints over 2 years from The Gambia. FINDINGS: The median estimated P(Detect) across all clusters was 12·5% (IQR 5·3-25·0) for P falciparum and 10·1% (5·0-18·3) for P vivax and decreased as the estimated log-PCR community prevalence increased (adjusted odds ratio [OR] for P falciparum 0·63, 95% CI 0·57-0·69; adjusted OR for P vivax 0·52, 0·47-0·57). Factors associated with increasing P(Detect) included smaller catchment population size, high transmission season, improved care-seeking behaviour by infected individuals, and recent increases (within the previous year) in transmission intensity. INTERPRETATION: The proportion of all infections detected within health systems increases once transmission intensity is sufficiently low. The likely explanation for P falciparum is that reduced exposure to infection leads to lower levels of protective immunity in the population, increasing the likelihood that infected individuals will become symptomatic and seek care. These factors might also be true for P vivax but a better understanding of the transmission biology is needed to attribute likely reasons for the observed trend. In low transmission and pre-elimination settings, enhancing access to care and improvements in care-seeking behaviour of infected individuals will lead to an increased proportion of infections detected in the community and might contribute to accelerating the interruption of transmission. FUNDING: Wellcome Trust.


Assuntos
Infecções Assintomáticas/epidemiologia , Reservatórios de Doenças/estatística & dados numéricos , Malária Falciparum/epidemiologia , Malária Vivax/epidemiologia , Adolescente , Adulto , África/epidemiologia , Idoso , Idoso de 80 Anos ou mais , América/epidemiologia , Ásia/epidemiologia , Teorema de Bayes , Criança , Pré-Escolar , Análise por Conglomerados , Estudos Transversais , Reservatórios de Doenças/parasitologia , Feminino , Instalações de Saúde/estatística & dados numéricos , Humanos , Lactente , Estudos Longitudinais , Malária Falciparum/transmissão , Malária Vivax/transmissão , Masculino , Pessoa de Meia-Idade , Prevalência , Vigilância em Saúde Pública/métodos , Estações do Ano , Adulto Jovem
7.
Malar J ; 18(1): 430, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31852480

RESUMO

BACKGROUND: Sulfadoxine-pyrimethamine (SP) is a cornerstone of malaria chemoprophylaxis and is considered for programmes in the Democratic Republic of Congo (DRC). However, SP efficacy is threatened by drug resistance, that is conferred by mutations in the dhfr and dhps genes. The World Health Organization has specified that intermittent preventive treatment for infants (IPTi) with SP should be implemented only if the prevalence of the dhps K540E mutation is under 50%. There are limited current data on the prevalence of resistance-conferring mutations available from Eastern DRC. The current study aimed to address this knowledge gap. METHODS: Dried blood-spot samples were collected from clinically suspected malaria patients [outpatient department (OPD)] and pregnant women attending antenatal care (ANC) in four sites in North and South Kivu, DRC. Quantitative PCR (qPCR) was performed on samples from individuals with positive and with negative rapid diagnostic test (RDT) results. Dhps K450E and A581G and dhfr I164L were assessed by nested PCR followed by allele-specific primer extension and detection by multiplex bead-based assays. RESULTS: Across populations, Plasmodium falciparum parasite prevalence was 47.9% (1160/2421) by RDT and 71.7 (1763/2421) by qPCR. Median parasite density measured by qPCR in RDT-negative qPCR-positive samples was very low with a median of 2.3 parasites/µL (IQR 0.5-25.2). Resistance genotyping was successfully performed in RDT-positive samples and RDT-negative/qPCR-positive samples with success rates of 86.2% (937/1086) and 55.5% (361/651), respectively. The presence of dhps K540E was high across sites (50.3-87.9%), with strong evidence for differences between sites (p < 0.001). Dhps A581G mutants were less prevalent (12.7-47.2%). The dhfr I164L mutation was found in one sample. CONCLUSIONS: The prevalence of the SP resistance marker dhps K540E exceeds 50% in all four study sites in North and South Kivu, DRC. K540E mutations regularly co-occurred with mutations in dhps A581G but not with the dhfr I164L mutation. The current results do not support implementation of IPTi with SP in the study area.


Assuntos
Antimaláricos/farmacologia , Resistência a Medicamentos , Malária/prevenção & controle , Plasmodium/efeitos dos fármacos , Pirimetamina/farmacologia , Sulfadoxina/farmacologia , Adolescente , Biomarcadores/sangue , Quimioprevenção/estatística & dados numéricos , Criança , Pré-Escolar , República Democrática do Congo , Combinação de Medicamentos , Feminino , Humanos , Lactente , Recém-Nascido , Masculino
8.
J Infect Dis ; 220(12): 1946-1949, 2019 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-31418017

RESUMO

To determine the presence and species composition of malaria infections, we screened a subset of samples collected during a cross-sectional survey in Northern Sabah, Malaysia using highly sensitive molecular techniques. Results identified 54 asymptomatic submicroscopic malaria infections, including a large cluster of Plasmodium falciparum and 3 P. knowlesi infections. We additionally identified 2 monoinfections with the zoonotic malaria Plasmodium cynomolgi, both in individuals reporting no history of forest activities or contact with macaques. Results highlight the need for improved surveillance strategies to detect these infections and determine public health impacts.


Assuntos
Erradicação de Doenças , Malária/epidemiologia , Malária/prevenção & controle , Plasmodium cynomolgi , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Criança , Pré-Escolar , Estudos Transversais , Feminino , Geografia Médica , Humanos , Lactente , Malária/parasitologia , Malásia/epidemiologia , Masculino , Pessoa de Meia-Idade , Plasmodium cynomolgi/classificação , Vigilância da População , Adulto Jovem , Zoonoses
9.
Lancet Planet Health ; 3(4): e179-e186, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31029229

RESUMO

BACKGROUND: Land use changes disrupt ecosystems, altering the transmission of vector-borne diseases. These changes have been associated with increasing incidence of zoonotic malaria caused by Plasmodium knowlesi; however, the population-level distributions of infection and exposure remain unknown. We aimed to measure prevalence of serological exposure to P knowlesi and assess associated risk factors. METHODS: We did an environmentally stratified, population-based, cross-sectional survey across households in the Kudat, Kota Marudu, Pitas, and Ranau districts in northern Sabah, Malaysia, encompassing a range of ecologies. Using blood samples, the transmission intensity of P knowlesi and other malaria species was measured by specific antibody prevalence and infection detected using molecular methods. Proportions and configurations of land types were extracted from maps derived from satellite images; a data-mining approach was used to select variables. A Bayesian hierarchical model for P knowlesi seropositivity was developed, incorporating questionnaire data about individual and household-level risk factors with selected landscape factors. FINDINGS: Between Sept 17, 2015, and Dec 12, 2015, 10 100 individuals with a median age of 25 years (range 3 months to 105 years) were sampled from 2849 households in 180 villages. 5·1% (95% CI 4·8-5·4) were seropositive for P knowlesi, and marked historical decreases were observed in the transmission of Plasmodium falciparum and Plasmodium vivax. Nine Plasmodium spp infections were detected. Age, male sex, contact with macaques, forest use, and raised house construction were positively associated with P knowlesi exposure, whereas residing at higher geographical elevations and use of insecticide were protective. Agricultural and forest variables, such as proportions and fragmentation of land cover types, predicted exposure at different spatial scales from households. INTERPRETATION: Although few infections were detected, P knowlesi exposure was observed in all demographic groups and was associated with occupational factors. Results suggest that agricultural expansion and forest fragmentation affect P knowlesi exposure, supporting linkages between land use change and P knowlesi transmission. FUNDING: UK Medical Research Council, Natural Environment Research Council, Economic and Social Research Council, and Biotechnology and Biosciences Research Council.


Assuntos
Malária/transmissão , Plasmodium knowlesi/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Infecções Assintomáticas/epidemiologia , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Malária/epidemiologia , Malária/parasitologia , Malásia/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Estudos Soroepidemiológicos , Adulto Jovem , Zoonoses/epidemiologia , Zoonoses/parasitologia , Zoonoses/transmissão
10.
Am J Trop Med Hyg ; 100(3): 572-577, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30608048

RESUMO

Gametocytes are sexual stage malaria parasites responsible for transmission to mosquitoes. Multiple gametocyte-producing clones may be present in natural infections, but the molecular characterization of gametocytes is challenging. Because of their magnetic properties, gametocyte enrichment can be achieved by magnetic fractionation. This increases detection sensitivity and allows specific genotyping of clones that contribute to malaria transmission. Here, we determined the percentage of Plasmodium falciparum gametocytes successfully bound to magnetic activated cell sorting (MACS) LS columns during magnetic fractionation and assessed whether columns can be reused without risking contamination or affecting column binding efficiency. Bound column fractions were quantified using multiplex quantitative reverse transcription polymerase chain reaction (qRT-PCR) for male (pfMGET) and female (CCp4) gametocytes and ring-stage asexual parasites (SBP1). To investigate cross contamination between columns, parasite strain identity was determined by merozoite surface protein 2 genotyping followed by capillary electrophoresis fragment sizing. A reproducible high percentage of gametocytes was bound to MACS LS columns with < 5% gametocytes appearing in the flow-through and < 0.6% asexual ring-stage parasites appearing in the gametocyte fraction. A high yield (> 94%) of gametocyte enrichment was achieved when columns were used up to five times with lower binding success after eight times (79%). We observed no evidence for cross contamination between columns.


Assuntos
Separação Celular/instrumentação , Magnetismo/instrumentação , Plasmodium falciparum/isolamento & purificação , Separação Celular/métodos , Testes Diagnósticos de Rotina , Humanos , Magnetismo/métodos , Malária Falciparum/parasitologia , Parasitemia
11.
Malar J ; 18(1): 14, 2019 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-30665411

RESUMO

BACKGROUND: Glucose-6-phosphate dehydrogenase deficiency (G6PDd), haemoglobin C (HbC) and S (HbS) are inherited blood disorders (IBD) common in populations in malaria endemic areas. All are associated to some degree with protection against clinical malaria whilst additionally G6PDd is associated with haemolysis following treatment with 8-aminoquinolines. Measuring the prevalence of these inherited blood disorders in affected populations can improve understanding of disease epidemiology. Current methodologies in epidemiological studies commonly rely on individual target amplification and visualization; here a method is presented to simultaneously detect the polymorphisms and that can be expanded to include other single nucleotide polymorphisms (SNPs) of interest. METHODS: Human DNA from whole blood samples was amplified in a novel, multiplex PCR reaction and extended with SNP-specific probes in an allele specific primer extension (ASPE) to simultaneously detect four epidemiologically important human markers including G6PD SNPs (G202A and A376G) and common haemoglobin mutations (HbS and HbC). The products were hybridized to magnetic beads and the median fluorescence intensity (MFI) was read on MAGPIX® (Luminex corp.). Genotyping data was compared to phenotypical data generated by flow cytometry and to established genotyping methods. RESULTS: Seventy-five samples from Burkina Faso (n = 75/78, 96.2%) and 58 samples from The Gambia (n = 58/61, 95.1%) had a G6PD and a HBB genotype successfully assigned by the bead-based assay. Flow cytometry data available for n = 61 samples further supported the concordance between % G6PD normal/deficient cells and genotype. CONCLUSIONS: The bead based assay compares well to alternative measures of genotyping and phenotyping for G6PD. The screening is high throughput, adaptable to inclusion of multiple targets of interest and easily standardized.


Assuntos
Anemia Falciforme/diagnóstico , Técnicas de Genotipagem/métodos , Deficiência de Glucosefosfato Desidrogenase/diagnóstico , Doença da Hemoglobina C/diagnóstico , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Burkina Faso , Criança , Glucosefosfato Desidrogenase/genética , Hemoglobina C/genética , Hemoglobina Falciforme/genética , Humanos , Malária/complicações , Masculino , Pessoa de Meia-Idade , Adulto Jovem
12.
Malar J ; 17(1): 281, 2018 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-30071859

RESUMO

BACKGROUND: 8-Aminoquinolines such as primaquine clear mature Plasmodium falciparum gametocytes that are responsible for transmission from human to mosquitoes and bring radical cure in Plasmodium vivax by clearing dormant liver stages. Deployment of primaquine is thus of relevance for malaria elimination efforts but challenged by the widespread prevalence of glucose-6-phosphate dehydrogenase deficiency (G6PDd) in endemic countries since primaquine in G6PDd individuals may lead to acute haemolysis. In this study, the prevalence of G6PDd was investigated in different settings in Ethiopia using phenotyping and genotyping approaches. METHODS: Community and school based cross-sectional surveys were conducted from October to December 2016 in four administrative regions (Gambela, Benishangul Gumuz, Oromia, and Amhara) in Ethiopia. Finger prick blood samples were collected for G6PD enzyme activity using the CareStart™ G6PD screening test and genotyping of 36 selected single nucleotide polymorphisms (SNPs) located in the G6PD gene and its flanking regions. RESULTS: Overall, the prevalence of phenotypic G6PDd was 1.4% (22/1609). For the first time in the Ethiopian population, the African variant (A-) was detected in 3.5% (7/199) of the limited set of genotyped samples, which were all phenotypically normal. Interestingly, all of these individuals had a variation at the rs2515904 locus. Strong geographical variation was observed for both phenotypic and genotypic G6PDd; three-quarters of the phenotypically G6PDd individuals were detected in Gambela. CONCLUSION: A very low prevalence of G6PDd was detected in the present study populations. The presence of the A- variant alongside other G6PD mutants and the patchy distribution of G6PDd indicate that larger studies specifically designed to unravel the distribution of G6PDd at small geographical scale may be needed to tailor malaria elimination efforts in Ethiopia to the local context.


Assuntos
Deficiência de Glucosefosfato Desidrogenase/epidemiologia , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Criança , Estudos Transversais , Etiópia/epidemiologia , Feminino , Genótipo , Deficiência de Glucosefosfato Desidrogenase/genética , Deficiência de Glucosefosfato Desidrogenase/parasitologia , Humanos , Masculino , Fenótipo , Prevalência , Adulto Jovem
13.
Malar J ; 17(1): 253, 2018 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-29980206

RESUMO

BACKGROUND: The haemolysis associated with clinical episodes of malaria results in the liberation of haem, which activates the enzyme haem oxygenase-1 (HO-1). HO-1 has been shown to reduce neutrophil function and increase susceptibility to invasive bacterial disease. However, the majority of community-associated malaria infections are subclinical, often termed "asymptomatic" and the consequences of low-grade haemolysis during subclinical malaria infection are unknown. STUDY DESIGN AND RESULTS: As part of an ongoing study of subclinical malaria in Burkina Faso, 23 children with subclinical Plasmodium falciparum infections (determined by qPCR) were compared with 21 village-matched uninfected control children. Infected children showed evidence of persistent haemolysis over 35 days, with raised plasma haem and HO-1 concentrations. Concentrations of IL-10, which can also directly activate HO-1, were also higher in infected children compared to uninfected children. Regression analysis revealed that HO-1 was associated with haemolysis, but not with parasite density, anaemia or IL-10 concentration. CONCLUSIONS: This study reveals that subclinical P. falciparum malaria infection is associated with sustained haemolysis and the induction of HO-1. Given the association between HO-1, neutrophil dysfunction and increased risk of Salmonella bacteraemia, prolonged HO-1 induction may explain epidemiological associations and geographic overlap between malaria and invasive bacterial disease. Further studies are needed to understand the consequences of persistent subclinical malaria infection, low-grade haemolysis and raised HO-1 on immune cell function and risk of comorbidities.


Assuntos
Heme Oxigenase-1/genética , Hemólise , Malária Falciparum/metabolismo , Plasmodium falciparum/fisiologia , Infecções Assintomáticas , Burkina Faso , Criança , Pré-Escolar , Feminino , Heme Oxigenase-1/metabolismo , Humanos , Masculino
14.
PLoS Negl Trop Dis ; 12(6): e0006432, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29902171

RESUMO

BACKGROUND: Primarily impacting poor, rural populations, the zoonotic malaria Plasmodium knowlesi is now the main cause of human malaria within Malaysian Borneo. While data is increasingly available on symptomatic cases, little is known about community-level patterns of exposure and infection. Understanding the true burden of disease and associated risk factors within endemic communities is critical for informing evidence-based control measures. METHODOLOGY/PRINCIPAL FINDINGS: We conducted comprehensive surveys in three areas where P. knowlesi transmission is reported: Limbuak, Pulau Banggi and Matunggung, Kudat, Sabah, Malaysia and Bacungan, Palawan, the Philippines. Infection prevalence was low with parasites detected by PCR in only 0.2% (4/2503) of the population. P. knowlesi PkSERA3 ag1 antibody responses were detected in 7.1% (95% CI: 6.2-8.2%) of the population, compared with 16.1% (14.6-17.7%) and 12.6% (11.2-14.1%) for P. falciparum and P. vivax. Sero-prevalence was low in individuals <10 years old for P. falciparum and P. vivax consistent with decreased transmission of non-zoonotic malaria species. Results indicated marked heterogeneity in transmission intensity between sites and P. knowlesi exposure was associated with agricultural work (OR 1.63; 95% CI 1.07-2.48) and higher levels of forest cover (OR 2.40; 95% CI 1.29-4.46) and clearing (OR 2.14; 95% CI 1.35-3.40) around houses. Spatial patterns of P. knowlesi exposure differed from exposure to non-zoonotic malaria and P. knowlesi exposed individuals were younger on average than individuals exposed to non-zoonotic malaria. CONCLUSIONS/SIGNIFICANCE: This is the first study to describe serological exposure to P. knowlesi and associated risk factors within endemic communities. Results indicate community-level patterns of infection and exposure differ markedly from demographics of reported cases, with higher levels of exposure among women and children. Further work is needed to understand these variations in risk across a wider population and spatial scale.


Assuntos
Malária/epidemiologia , Plasmodium knowlesi/isolamento & purificação , Estudos Soroepidemiológicos , Adolescente , Adulto , Animais , Anticorpos Antiprotozoários/sangue , Infecções Assintomáticas/epidemiologia , Criança , Fazendeiros , Feminino , Florestas , Humanos , Malária/imunologia , Malária/parasitologia , Malária/transmissão , Malásia/epidemiologia , Masculino , Pessoa de Meia-Idade , Filipinas/epidemiologia , Plasmodium knowlesi/genética , Plasmodium knowlesi/imunologia , Reação em Cadeia da Polimerase , Saúde Pública , Fatores de Risco , Adulto Jovem , Zoonoses
15.
Int J Parasitol ; 48(8): 671-677, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29738740

RESUMO

Plasmodium falciparum malaria infections often comprise multiple distinct parasite clones. Few datasets have directly assessed infection complexity in humans and mosquitoes they infect. Examining parasites using molecular tools may provide insights into the selective transmissibility of isolates. Using capillary electrophoresis genotyping and next generation amplicon sequencing, we analysed complexity of parasite infections in human blood and in the midguts of mosquitoes that became infected in membrane feeding experiments using the same blood material in two West African settings. Median numbers of clones in humans and mosquitoes were higher in samples from Burkina Faso (4.5, interquartile range 2-8 for humans; and 2, interquartile range 1-3 for mosquitoes) than in The Gambia (2, interquartile range 1-3 and 1, interquartile range 1-3, for humans and mosquitoes, respectively). Whilst the median number of clones was commonly higher in human blood samples, not all transmitted alleles were detectable in the human peripheral blood. In both study sample sets, additional parasite alleles were identified in mosquitoes compared with the matched human samples (10-88.9% of all clones/feeding assay, n = 73 feeding assays). The results are likely due to preferential amplification of the most abundant clones in peripheral blood but confirm the presence of low density clones that produce transmissible sexual stage parasites.


Assuntos
Anopheles/parasitologia , Genótipo , Malária Falciparum/parasitologia , Plasmodium falciparum/genética , Animais , Burkina Faso/epidemiologia , Gâmbia/epidemiologia , Interações Hospedeiro-Parasita , Humanos , Malária Falciparum/epidemiologia , Mosquitos Vetores/parasitologia
16.
Elife ; 72018 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-29357976

RESUMO

Variation in biting frequency by Anopheles mosquitoes can explain some of the heterogeneity in malaria transmission in endemic areas. In this study in Burkina Faso, we assessed natural exposure to mosquitoes by matching the genotype of blood meals from 1066 mosquitoes with blood from residents of local households. We observed that the distribution of mosquito bites exceeded the Pareto rule (20/80) in two of the three surveys performed (20/85, 76, and 96) and, at its most pronounced, is estimated to have profound epidemiological consequences, inflating the basic reproduction number of malaria by 8-fold. The distribution of bites from sporozoite-positive mosquitoes followed a similar pattern, with a small number of individuals within households receiving multiple potentially infectious bites over the period of a few days. Together, our findings indicate that heterogeneity in mosquito exposure contributes considerably to heterogeneity in infection risk and suggest significant variation in malaria transmission potential.


Assuntos
Anopheles/fisiologia , Transmissão de Doença Infecciosa , Malária/transmissão , Animais , Número Básico de Reprodução , Sangue , Burkina Faso , Comportamento Alimentar , Técnicas de Genotipagem
17.
Wellcome Open Res ; 3: 159, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30828645

RESUMO

Background: Individuals living in malaria-endemic regions develop immunity against severe malaria, but it is unclear whether immunity against pre-erythrocytic stages that blocks initiation of blood-stage infection after parasite inoculation develops following continuous natural exposure. Methods: We cleared schoolchildren living in an area (health district of Saponé, Burkina Faso) with highly endemic seasonal malaria of possible sub-patent infections and examined them weekly for incident infections by nested PCR. Plasma samples collected at enrolment were used to quantify antibodies to the pre-eryhrocytic-stage antigens circumsporozoite protein (CSP) and Liver stage antigen 1 (LSA-1). In vitro sporozoite gliding inhibition and hepatocyte invasion inhibition by naturally acquired antibodies were assessed using Plasmodium falciparum NF54 sporozoites. Associations between antibody responses, functional pre-erythrocytic immunity phenotypes and time to infection detected by 18S quantitative PCR were studied. Results: A total of 51 children were monitored. Anti-CSP antibody titres showed a positive association with sporozoite gliding motility inhibition (P<0.0001, Spearman's ρ=0.76). In vitro hepatocyte invasion was inhibited by naturally acquired antibodies (median inhibition, 19.4% [IQR 15.2-40.9%]), and there were positive correlations between invasion inhibition and gliding inhibition (P=0.005, Spearman's ρ=0.67) and between invasion inhibition and CSP-specific antibodies (P=0.002, Spearman's ρ=0.76). Survival analysis indicated longer time to infection in individuals displaying higher-than-median sporozoite gliding inhibition activity (P=0.01), although this association became non-significant after adjustment for blood-stage immunity (P = 0.06). Conclusions: In summary, functional antibodies against the pre-erythrocytic stages of malaria infection are acquired in children who are repeatedly exposed to Plasmodium parasites. This immune response does not prevent them from becoming infected during a malaria transmission season, but might delay the appearance of blood stage parasitaemia. Our approach could not fully separate the effects of pre-erythrocytic-specific and blood-stage-specific antibody-mediated immune responses in vivo; epidemiological studies powered and designed to address this important question should become a research priority.

18.
Nat Commun ; 8(1): 1133, 2017 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-29074880

RESUMO

A detailed understanding of the human infectious reservoir is essential for improving malaria transmission-reducing interventions. Here we report a multi-regional assessment of population-wide malaria transmission potential based on 1209 mosquito feeding assays in endemic areas of Burkina Faso and Kenya. Across both sites, we identified 39 infectious individuals. In high endemicity settings, infectious individuals were identifiable by research-grade microscopy (92.6%; 25/27), whilst one of three infectious individuals in the lowest endemicity setting was detected by molecular techniques alone. The percentages of infected mosquitoes in the different surveys ranged from 0.05 (4/7716) to 1.6% (121/7749), and correlate positively with transmission intensity. We also estimated exposure to malaria vectors through genetic matching of blood from 1094 wild-caught bloodfed mosquitoes with that of humans resident in the same houses. Although adults transmitted fewer parasites to mosquitoes than children, they received more mosquito bites, thus balancing their contribution to the infectious reservoir.


Assuntos
Anopheles/parasitologia , Malária Falciparum/parasitologia , Malária Falciparum/transmissão , Mosquitos Vetores/parasitologia , Plasmodium falciparum/fisiologia , Adolescente , Adulto , Animais , Burkina Faso/epidemiologia , Criança , Pré-Escolar , Doenças Endêmicas , Feminino , Interações Hospedeiro-Parasita , Humanos , Quênia/epidemiologia , Malária Falciparum/epidemiologia , Masculino
19.
Malar J ; 16(1): 253, 2017 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-28619120

RESUMO

BACKGROUND: Plasmodium vivax parasites are the predominant cause of malaria infections in the Brazilian Amazon. Infected individuals are treated with primaquine, which can induce haemolytic anaemia in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals and may lead to severe and fatal complications. This X-linked disorder is distributed globally and is caused by allelic variants with a geographical distribution that closely reflects populations exposed historically to endemic malaria. In Brazil, few studies have reported the frequency of G6PD deficiency (G6PDd) present in malaria-endemic areas. This is particularly important, as G6PDd screening is not currently performed before primaquine treatment. The aim of this study was to determine the prevalence of G6PDd in the region of Alto do Juruá, in the Western Brazilian Amazon, an area characterized by a high prevalence of P. vivax infection. METHODS: Five-hundred and sixteen male volunteers were screened for G6PDd using the fluorescence spot test (Beutler test) and CareStart™ G6PD Biosensor system. Demographic and clinical-epidemiological data were acquired through an individual interview. To assess the genetic basis of G6PDd, 24 SNPs were genotyped using the Kompetitive Allele Specific PCR assay. RESULTS: Twenty-three (4.5%) individuals were G6PDd. No association was found between G6PDd and the number of malaria cases. An increased risk of reported haemolysis symptoms and blood transfusions was evident among the G6PDd individuals. Twenty-two individuals had the G6PDd A(-) variant and one the G6PD A(+) variant. The Mediterranean variant was not present. Apart from one polymorphism, almost all SNPs were monomorphic or with low frequencies (0-0.04%). No differences were detected among ethnic groups. CONCLUSIONS: The data indicates that ~1/23 males from the Alto do Juruá could be G6PD deficient and at risk of haemolytic anaemia if treated with primaquine. G6PD A(-) is the most frequent deficiency allele in this population. These results concur with reported G6PDd in other regions in Brazil. Routine G6PDd screening to personalize primaquine administration should be considered, particularly as complete treatment of patients with vivax malaria using chloroquine and primaquine, is crucial for malaria elimination.


Assuntos
Deficiência de Glucosefosfato Desidrogenase/genética , Malária Vivax/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Anemia Hemolítica/induzido quimicamente , Antimaláricos/efeitos adversos , Antimaláricos/uso terapêutico , Brasil/epidemiologia , Estudos Transversais , Doenças Endêmicas , Genótipo , Deficiência de Glucosefosfato Desidrogenase/epidemiologia , Humanos , Malária Vivax/tratamento farmacológico , Malária Vivax/epidemiologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Prevalência , Primaquina/efeitos adversos , Primaquina/uso terapêutico , Adulto Jovem
20.
Sci Rep ; 6: 26330, 2016 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-27197604

RESUMO

Artemisinin resistance is rapidly spreading in Southeast Asia. The efficacy of artemisinin-combination therapy (ACT) continues to be excellent across Africa. We performed parasite transcriptional profiling and genotyping on samples from an antimalarial treatment trial in Uganda. We used qRT-PCR and genotyping to characterize residual circulating parasite populations after treatment with either ACT or ACT-primaquine. Transcripts suggestive of circulating ring stage parasites were present after treatment at a prevalence of >25% until at least 14 days post initiation of treatment. Greater than 98% of all ring stage parasites were cleared within the first 3 days, but subsequently persisted at low concentrations until day 14 after treatment. Genotyping demonstrated a significant decrease in multiplicity of infection within the first 2 days in both ACT and ACT-primaquine arms. However, multiple clone infections persisted until day 14 post treatment. Our data suggest the presence of genetically diverse persisting parasite populations after ACT treatment. Although we did not demonstrate clinical treatment failures after ACT and the viability and transmissibility of persisting ring stage parasites remain to be shown, these findings are of relevance for the interpretation of parasite clearance transmission dynamics and for monitoring drug effects in Plasmodium falciparum parasites.


Assuntos
Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Malária Falciparum/tratamento farmacológico , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/genética , Primaquina/uso terapêutico , Antimaláricos/administração & dosagem , Artemisininas/administração & dosagem , Criança , Pré-Escolar , DNA de Protozoário/análise , Resistência a Medicamentos , Quimioterapia Combinada , Genótipo , Humanos , Lactente , Malária Falciparum/parasitologia , Plasmodium falciparum/parasitologia , Primaquina/administração & dosagem , Reação em Cadeia da Polimerase em Tempo Real , Uganda
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