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BACKGROUND: A detailed understanding of the contribution of the asymptomatic Plasmodium reservoir to the occurrence of clinical malaria at individual and community levels is needed to guide effective elimination interventions. This study investigated the relationship between asymptomatic Plasmodium falciparum carriage and subsequent clinical malaria episodes in the Dielmo and Ndiop villages in Senegal. METHODS: The study used a total of 2792 venous and capillary blood samples obtained from asymptomatic individuals and clinical malaria datasets collected from 2013 to 2016. Mapping, spatial clustering of infections, and risk analysis were performed using georeferenced households. RESULTS: High incidences of clinical malaria episodes were observed to occur predominantly in households of asymptomatic P falciparum carriers. A statistically significant association was found between asymptomatic carriage in a household and subsequent episode of clinical malaria occurring in that household for each individual year (P values were 0.0017, 6 × 10-5, 0.005, and 0.008 for the years 2013, 2014, 2015, and 2016 respectively) and the combined years (P = 8.5 × 10-8), which was not found at the individual level. In both villages, no significant patterns of spatial clustering of P falciparum clinical cases were found, but there was a higher risk of clinical episodes <25 m from asymptomatic individuals in Ndiop attributable to clustering within households. CONCLUSION: The findings provide strong epidemiological evidence linking the asymptomatic P falciparum reservoir to clinical malaria episodes at household scale in Dielmo and Ndiop villagers. This argues for a likely success of a mass testing and treatment intervention to move towards the elimination of malaria in the villages of Dielmo and Ndiop.
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Malaria Falciparum , Malaria , Plasmodium , Infecciones Asintomáticas/epidemiología , Estudios Transversales , Humanos , Malaria/epidemiología , Malaria Falciparum/epidemiología , Malaria Falciparum/prevención & control , Plasmodium falciparum , PrevalenciaRESUMEN
The era of genome-wide association studies (GWAS) has led to the discovery of numerous genetic variants associated with disease. Better understanding of whether these or other variants interact leading to differential risk compared with individual marker effects will increase our understanding of the genetic architecture of disease, which may be investigated using the family-based study design. We present M-TDT (the multi-locus transmission disequilibrium test), a tool for detecting family-based multi-locus multi-allelic effects for qualitative or quantitative traits, extended from the original transmission disequilibrium test (TDT). Tests to handle the comparison between additive and epistatic models, lack of independence between markers and multiple offspring are described. Performance of M-TDT is compared with a multifactor dimensionality reduction (MDR) approach designed for investigating families in the hypothesis-free genome-wide setting (the multifactor dimensionality reduction pedigree disequilibrium test, MDR-PDT). Other methods derived from the TDT or MDR to investigate genetic interaction in the family-based design are also discussed. The case of three independent biallelic loci is illustrated using simulations for one- to three-locus alternative hypotheses. M-TDT identified joint-locus effects and distinguished effectively between additive and epistatic models. We showed a practical example of M-TDT based on three genes already known to be implicated in malaria susceptibility. Our findings demonstrate the value of M-TDT in a hypothesis-driven context to test for multi-way epistasis underlying common disease etiology, whereas MDR-PDT-based methods are more appropriate in a hypothesis-free genome-wide setting.
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Epistasis Genética , Genoma , Estudio de Asociación del Genoma Completo , Humanos , Desequilibrio de Ligamiento , Modelos Genéticos , LinajeRESUMEN
BACKGROUND: Malaria is a leading cause of mortality and morbidity in tropical countries, especially in sub-Saharan Africa. In Senegal, a control plan implemented in the beginning of the 2000s has enabled a substantial reduction of mortality and morbidity due to malaria. However, eradication of malaria requires a vaccine that protects against Plasmodium falciparum the deadliest species of the parasite that causes this disease. Plasmodium falciparum is characterized by an extensive genetic diversity that makes vaccine development challenging. In this study, the diversity of P. falciparum isolates was analysed from asymptomatic children residing in the district of Toubacouta, Senegal. METHODS: A nested PCR approach was used to perform genotyping of the msp-1 and msp-2 loci in samples from 87 asymptomatic children infected with P. falciparum, collected during a cross sectional survey in November and December 2010. Parasite densities in blood samples were determined by microscopic examination and statistical analyses were used to identify association of parasite genotype and parasitaemia. RESULTS: Genotyping was successful in 84/87 and 82/87 samples for msp-1 and msp-2, respectively. A strong genetic diversity was found with a total of 15 and 21 different alleles identified for msp-1 and msp-2, respectively. RO33 was the most frequent allelic family of msp-1 followed by MAD20, then by K1. Regarding msp-2 allelic families, 3D7 was more common than FC27. Multiple infections were predominant, since 69% and 89% of the samples genotyped for msp-1 and msp-2 showed more than one clone of P. falciparum with complexity of infection (COI) of 2.5 and 4.7, respectively. Expected heterozygosity (HE) was 0.57 and 0.55 for msp-1 and msp-2, respectively. Interestingly, polyclonal infections were significantly associated with higher parasitaemia. CONCLUSIONS: The strong genetic diversity of P. falciparum clones and the association of polyclonal infection with high parasitaemia call for a multi-allelic approach in the design of vaccine candidates for efficient malaria eradication.
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Infecciones Asintomáticas , Variación Genética , Genotipo , Malaria Falciparum/parasitología , Parasitemia/parasitología , Plasmodium falciparum/clasificación , Plasmodium falciparum/genética , Animales , Antígenos de Protozoos/genética , Niño , Preescolar , Coinfección/parasitología , Estudios Transversales , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Microscopía , Carga de Parásitos , Reacción en Cadena de la Polimerasa , SenegalRESUMEN
Dramatic changes in transmission intensity can impact Plasmodium population diversity. Using samples from 2 distant time-points in the Dielmo/Ndiop longitudinal cohorts from Senegal, we applied a molecular barcode tool to detect changes in parasite genotypes and complexity of infection that corresponded to changes in transmission intensity. We observed a striking statistically significant difference in genetic diversity between the 2 parasite populations. Furthermore, we identified a genotype in Dielmo and Ndiop previously observed in Thiès, potentially implicating imported malaria. This genetic surveillance study validates the molecular barcode as a tool to assess parasite population diversity changes and track parasite genotypes.
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Genética de Población , Genotipo , Malaria/parasitología , Plasmodium/clasificación , Plasmodium/genética , Adolescente , Adulto , Niño , Preescolar , Código de Barras del ADN Taxonómico , Femenino , Genoma de Protozoos , Humanos , Lactante , Estudios Longitudinales , Masculino , Plasmodium/aislamiento & purificación , Senegal , Adulto JovenRESUMEN
Assessing the influence of climate on the incidence of Plasmodium falciparum malaria worldwide and how it might impact local malaria dynamics is complex and extrapolation to other settings or future times is controversial. This is especially true in the light of the particularities of the short- and long-term immune responses to infection. In sites of epidemic malaria transmission, it is widely accepted that climate plays an important role in driving malaria outbreaks. However, little is known about the role of climate in endemic settings where clinical immunity develops early in life. To disentangle these differences among high- and low-transmission settings we applied a dynamical model to two unique adjacent cohorts of mesoendemic seasonal and holoendemic perennial malaria transmission in Senegal followed for two decades, recording daily P. falciparum cases. As both cohorts are subject to similar meteorological conditions, we were able to analyze the relevance of different immunological mechanisms compared with climatic forcing in malaria transmission. Transmission was first modeled by using similarly unique datasets of entomological inoculation rate. A stochastic nonlinear human-mosquito model that includes rainfall and temperature covariates, drug treatment periods, and population variability is capable of simulating the complete dynamics of reported malaria cases for both villages. We found that under moderate transmission intensity climate is crucial; however, under high endemicity the development of clinical immunity buffers any effect of climate. Our models open the possibility of forecasting malaria from climate in endemic regions but only after accounting for the interaction between climate and immunity.
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Clima , Malaria Falciparum/epidemiología , Modelos Teóricos , Humanos , Incidencia , Malaria Falciparum/transmisiónRESUMEN
BACKGROUND: Coordinated scaled-up malaria control interventions have substantially contributed to the dramatic decrease of malaria-related morbidity and mortality in several endemic countries, including Senegal. However, the impacts of a given malaria control intervention on vector and parasite populations, acquired immunity, and disease burden remain very poorly documented largely due to the lack of continuous surveys. This study took advantage of the sera bank established as part of the Dielmo longitudinal project to investigate the dynamics of IgG antibody responses that accompanied the epidemiological changes resulting from malaria control interventions. Schizonts crude extract of a local strain of Plasmodium falciparum (Pfsch07/03) was used in ELISA to measure and compare seroprevalence and magnitude of IgG antibody responses from 2000 to 2012. RESULTS: The prevalence of Pfsch07/03 IgG antibody responses progressively decreased from 97.25% in 2000 to 57.3% in 2012. The prevalence of Pfsch07/03 antibodies categorized between three different age groups (<7, 7-15, and >15 years) revealed increased seroprevalence with age ranging from 47.19 to 62.67 and 89.45%, respectively in (<7, 7-15, and >15 years) old age groups. A marked drop in seroprevalence was observed after 2008 and was significant in the younger (<7 years) and intermediate (7-15 years) age groups, unlike older individuals aged >15 years (p = 1.00). CONCLUSIONS: The study revealed a substantial contribution of all malaria control interventions to the decrease of IgG antibodies responses to Pfsch07/03 throughout prevention of human-mosquitos contacts, or reduction of parasite biomass. The present study demonstrates the wider potential of sero-epidemiological analysis in monitoring changes in malaria transmission resulting from a given malaria control intervention.
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Anticuerpos Antiprotozoarios/sangre , Inmunoglobulina G/sangre , Malaria Falciparum/epidemiología , Malaria Falciparum/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antígenos de Protozoos/inmunología , Niño , Preescolar , Control de Enfermedades Transmisibles , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Plasmodium falciparum/inmunología , Prevalencia , Senegal/epidemiología , Estudios Seroepidemiológicos , Adulto JovenRESUMEN
BACKGROUND: Evaluation of local Plasmodium falciparum malaria transmission has been investigated previously using the reversible catalytic model based on prevalence of antibody responses to single antigen to estimate seroconversion rates. High correlations were observed between seroconversion rates and entomological inoculation rates (EIR). However, in this model, the effects of malaria control interventions and clinical episodes on serological measurements were not assessed. This study monitors the use of antibody responses to P. falciparum crude extracts for assessing malaria transmission, compares seroconversion rates estimated from longitudinal data to those derived from cross-sectional surveys and investigates the effects of malaria control interventions on these measures in an area of declining malaria transmission. In addition, the validity of this model was evaluated by comparison with the alternative model. METHODS: Five cross-sectional surveys were carried out at the end of the wet season in Dielmo, a malaria-endemic Senegalese rural area in 2000, 2002, 2008, 2010 and 2012. Antibodies against schizonts crude extract of a local P. falciparum strain adapted to culture (Pf 07/03) were measured by ELISA. Age-specific seroprevalence model was used both for cross-sectional surveys and longitudinal data (combined data of all surveys). RESULTS: A total of 1504 plasma samples obtained through several years follow-up of 350 subjects was used in this study. Seroconversion rates based on P. falciparum schizonts crude extract were estimated for each cross-sectional survey and were found strongly correlated with EIR. High variability between SCRs from cross-sectional and longitudinal surveys was observed. In longitudinal studies, the alternative catalytic reversible model adjusted better with serological data than the catalytic model. Clinical malaria attacks and malaria control interventions were found to have significant effect on seroconversion. DISCUSSION: The results of the study suggested that crude extract was a good serological tool that could be used to assess the level of malaria exposure in areas where malaria transmission is declining. However, additional parameters such as clinical malaria and malaria control interventions must be taken into account for determining serological measurements for more accuracy in transmission assessment.
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Enfermedades Endémicas , Malaria Falciparum/epidemiología , Malaria Falciparum/transmisión , Plasmodium falciparum/fisiología , Factores de Edad , Anticuerpos Antiprotozoarios/sangre , Estudios Transversales , Femenino , Humanos , Estudios Longitudinales , Masculino , Modelos Teóricos , Prevalencia , Esquizontes/fisiología , Senegal/epidemiología , Estudios SeroepidemiológicosRESUMEN
Background: Despite significant progress in malaria control over the past twenty years, malaria remains a leading cause of child morbidity and mortality in Tropical Africa. As most patients do not consult any health facility much uncertainty persists about the true burden of the disease and the range of individual differences in susceptibility to malaria. Methods: Over a 25-years period, from 1990 to 2015, the inhabitants of Dielmo village, Senegal, an area of intense malaria transmission, have been monitored daily for their presence in the village and the occurrence of diseases. In case of fever thick blood films were systematically examined through microscopy for malaria parasites and patients received prompt diagnosis and treatment. Findings: We analysed data collected in 111 children and young adults monitored for at least 10 years (mean 17.3 years, maximum 25 years) enrolled either at birth (95 persons) or during the two first years of life. A total of 11,599 episodes of fever were documented, including 5268 malaria attacks. The maximum number of malaria attacks in a single person was 112. Three other persons suffered one hundred or more malaria attacks during follow-up. The minimum number of malaria attacks in a single person was 11. The mean numbers of malaria attacks in children reaching their 4th, 7th, and 10th birthdays were 23.0, 37.7, and 43.6 attacks since birth, respectively. Sixteen children (14.4%) suffered ten or more malaria attacks each year at ages 1-3 years, and six children (5.4%) each year at age 4-6 years. Interpretation: Long-term close monitoring shows that in highly endemic areas the malaria burden is higher than expected. Susceptibility to the disease may vary up to 10-fold, and for most children childhood is an endless history of malaria fever episodes. No other parasitic, bacterial or viral infection in human populations has such an impact on health. Funding: The Pasteur Institutes of Dakar and Paris, the Institut de Recherche pour le Développement, and the French Ministry of Cooperation provided funding.
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OBJECTIVE: In low malaria transmission areas, the elimination of the disease has been hampered partly by the existence of a reservoir of subpatent Plasmodium falciparum infections within communities. This reservoir, often undetected, serves as a source of parasites and contribute to ongoing transmission and clinical malaria cases. METHODS: This study, spanning a period of nine years from June 2014 to December 2022, examined individual variations and long-term subpatent P. falciparum carriage in two matched cohorts of 44 individuals each living in Dielmo village in the Sudanian area of Senegal. Biannual blood samples, collected in June/July and December of each year, underwent P. falciparum diagnosis by quantitative polymerase chain reaction. QGIS and R analytical tools were used to map infections, assess the occurrence and clustering of subpatent and clinical P. falciparum infections, and determine the risk of infection in the vicinity of asymptomatic P. falciparum carriers. RESULTS: The point frequency and long-term P. falciparum carriage were significantly higher among the qPCR positive cohort compared to the negative cohort across the 16 cross-sectional surveys analysed in this study (19.76% vs 10.99%, p-value < 0.001). Asymptomatic carriage events in qPCR positive group were 18.86 ± 1.72% and significantly greater (p-valueâ¯=â¯0.001) than in the qPCR negative group (11.32 ± 1.32%). The relative risk of P. falciparum infection or clinical malaria calculated with a 95% confidence interval significantly increased in the vicinity of infected individuals, and was 1.44 (p-valueâ¯=â¯0.53) and 2.64 (p-valueâ¯=â¯0.04) when at least one individual in the direct (household) or indirect (block of households) vicinity is infected, respectively. The risk increased to 3.64 (p-value < 0.001) if at least 1/5 of individuals in the indirect vicinity were P. falciparum-infected. CONCLUSION: The study provides a detailed qualitative and quantitative analysis of the asymptomatic P. falciparum reservoir and its temporal and spatial dynamics within two subgroups of P. falciparum-infected and non-infected individuals in Dielmo village. It identified hotpops and hotspots that could be targeted by innovative interventions to accelerate the elimination of malaria in Dielmo village.
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During the COVID-19 pandemic in Senegal, contact tracing was done to identify transmission clusters, their analysis allowed to understand their dynamics and evolution. In this study, we used information from the surveillance data and phone interviews to construct, represent and analyze COVID-19 transmission clusters from March 2, 2020, to May 31, 2021. In total, 114,040 samples were tested and 2153 transmission clusters identified. A maximum of 7 generations of secondary infections were noted. Clusters had an average of 29.58 members and 7.63 infected among them; their average duration was 27.95 days. Most of the clusters (77.3%) are concentrated in Dakar, capital city of Senegal. The 29 cases identified as super-spreaders, i.e., the indexes that had the most positive contacts, showed few symptoms or were asymptomatic. Deepest transmission clusters are those with the highest percentage of asymptomatic members. The correlation between proportion of asymptomatic and degree of transmission clusters showed that asymptomatic strongly contributed to the continuity of transmission within clusters. During this pandemic, all the efforts towards epidemiological investigations, active case-contact detection, allowed to identify in a short delay growing clusters and help response teams to mitigate the spread of the disease.
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COVID-19 , SARS-CoV-2 , Humanos , COVID-19/epidemiología , Trazado de Contacto , Pandemias , Senegal/epidemiologíaRESUMEN
BACKGROUND: When vaccines against the novel COVID-19 were available in Senegal, many questions were raised. How long should non-pharmaceutical interventions (NPIs) be maintained during vaccination roll-out? What are the best vaccination strategies? METHODS: In this study, we used an age-structured dynamic mathematical model. This model uses parameters based on SARS-CoV-2 virus, information on different types of NPIs, epidemiological and demographic data, some parameters relating to hospitalisations and vaccination in Senegal. RESULTS: In all scenarios explored, the model predicts a larger third epidemic wave of COVID-19 in terms of new cases and deaths than the previous waves. In a context of limited vaccine supply, vaccination alone will not be sufficient to control the epidemic, and the continuation of NPIs is necessary to flatten the epidemic curve. Assuming 20% of the population have been vaccinated, the optimal period to relax NPIs would be a few days from the last peak. Regarding the prioritisation of age groups to be vaccinated, the model shows that it is better to vaccinate individuals aged 5-60 years and not just the elderly (over 60 years) and those in high-risk groups. This strategy could be more cost-effective for the government, as it would reduce the high costs associated with hospitalisation. In terms of vaccine distribution, the optimal strategy would be to allocate full dose to the elderly. If vaccine doses are limited, half dose followed by full dose would be sufficient for people under 40 years because whether they receive half or full dose, the reduction in hospitalisations would be similar and their death-to-case ratio is very low. CONCLUSIONS: This study could be presented as a decision support tool to help devise strategies to control the COVID-19 pandemic and help the Ministry of Health to better manage and allocate the available vaccine doses.
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Vacunas contra la COVID-19 , COVID-19 , Adolescente , Adulto , Anciano , Niño , Preescolar , Humanos , Persona de Mediana Edad , Pandemias , SARS-CoV-2 , Senegal/epidemiología , Vacunación , Adulto JovenRESUMEN
BACKGROUND: The novel coronavirus disease 2019 (COVID-19) pandemic has spread from China to the rest of the world. Africa seems less impacted with lower number of cases and deaths than other continents. Senegal recorded its first case on March 2, 2020. We present here data collected from March 2 to October 31, 2020 in Senegal. METHODS: Socio-demographic, epidemiological, clinical and virological information were collected on suspected cases. To determine factors associated with diagnosed infection, symptomatic disease and death, multivariable binary logistic regression and log binomial models were used. Epidemiological parameters such as the reproduction number and growth rate were estimated. RESULTS: 67,608 suspected cases were tested by the IPD laboratories (13,031 positive and 54,577 negative). All age categories were associated with SARS-CoV-2 infection, but also patients having diabetes or hypertension or other cardiovascular diseases. With diagnosed infection, patients over 65 years and those with hypertension and cardiovascular disease and diabetes were highly associated with death. Patients with co-morbidities were associated with symptomatic disease, but only the under 15 years were not associated with. Among infected, 27.67% were asymptomatic (40.9% when contacts were systematically tested; 12.11% when only symptomatic or high-risk contacts were tested). Less than 15 years-old were mostly asymptomatic (63.2%). Dakar accounted for 81.4% of confirmed cases. The estimated mean serial interval was 5.57 (± 5.14) days. The average reproduction number was estimated at 1.161 (95%CI: 1.159-1.162), the growth rate was 0.031 (95%CI: 0.028-0.034) per day. CONCLUSIONS: Our findings indicated that factors associated with symptomatic COVID-19 and death are advanced age (over 65 years-old) and comorbidities such as diabetes and hypertension and cardiovascular disease.
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COVID-19 , Enfermedades Cardiovasculares , Diabetes Mellitus , Hipertensión , Adolescente , Anciano , COVID-19/epidemiología , Diabetes Mellitus/epidemiología , Humanos , Hipertensión/epidemiología , Pandemias , SARS-CoV-2 , Senegal/epidemiologíaRESUMEN
BACKGROUND: In 2006, the Senegalese National Malaria Control Programme (NMCP) has recommended artemisinin-based combination therapy (ACT) as the first-line treatment for uncomplicated malaria and, in 2007, mandated testing for all suspected cases of malaria with a Plasmodium falciparum HRP-2-based rapid diagnostic test for malaria (RDT(Paracheck). Given the higher cost of ACT compared to earlier anti-malarials, the objectives of the present study were i) to study the accuracy of Paracheck compared to the thick blood smear (TBS) in two areas with different levels of malaria endemicity and ii) analyse the cost-effectiveness of the strategy of the parasitological confirmation of clinically suspected malaria cases management recommended by the NMCP. METHODS: A cross-sectional study was undertaken in the villages of Dielmo and Ndiop (Senegal) nested in a cohort study of about 800 inhabitants. For all the individuals consulting between October 2008 and January 2009 with a clinical diagnosis of malaria, a questionnaire was filled and finger-prick blood samples were taken both for microscopic examination and RDT. The estimated costs and cost-effectiveness analysis were made considering five scenarios, the recommendations of the NMCP being the reference scenario. In addition, a sensitivity analysis was performed assuming that all the RDT-positive patients and 50% of RDT-negative patients were treated with ACT. RESULTS: A total of 189 consultations for clinically suspected malaria occurred during the study period. The sensitivity, specificity, positive and negative predictive values were respectively 100%, 98.3%, 80.0% and 100%. The estimated cost of the reference scenario was close to 700 euros per 1000 episodes of illness, approximately twice as expensive as most of the other scenarios. Nevertheless, it appeared to us cost-effective while ensuring the diagnosis and the treatment of 100% of malaria attacks and an adequate management of 98.4% of episodes of illness. The present study also demonstrated that full compliance of health care providers with RDT results was required in order to avoid severe incremental costs. CONCLUSIONS: A rational use of ACT requires laboratory testing of all patients presenting with presumed malaria. Use of RDTs inevitably has incremental costs, but the strategy associating RDT use for all clinically suspected malaria and prescribing ACT only to patients tested positive is cost-effective in areas where microscopy is unavailable.
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Análisis Costo-Beneficio/economía , Pruebas Diagnósticas de Rutina/economía , Malaria Falciparum/diagnóstico , Parasitemia/diagnóstico , Plasmodium falciparum/aislamiento & purificación , Juego de Reactivos para Diagnóstico/economía , Adolescente , Antígenos de Protozoos/inmunología , Antimaláricos/economía , Antimaláricos/uso terapéutico , Artemisininas/economía , Artemisininas/uso terapéutico , Niño , Preescolar , Estudios Transversales , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Costos de la Atención en Salud , Humanos , Lactante , Malaria Falciparum/tratamiento farmacológico , Malaria Falciparum/economía , Malaria Falciparum/parasitología , Masculino , Microscopía , Plasmodium falciparum/inmunología , Valor Predictivo de las Pruebas , Proteínas Protozoarias/inmunología , Juego de Reactivos para Diagnóstico/parasitología , SenegalRESUMEN
INTRODUCTION: Submicroscopic Plasmodium infections are common in malaria endemic countries, but very little studies have been done in Senegal. This study investigates the genetic diversity and complexity of submicroscopic P. falciparum infections among febrile patients in low transmission areas in Senegal. MATERIALS AND METHODS: Hundred and fifty blood samples were collected from febrile individuals living in Dielmo and Ndiop (Senegal) between August 2014 and January 2015, tested for microscopic and sub-microscopic P. falciparum infections and characterized for their genetic diversity and complexity of infections using msp-1 and msp-2 genotyping. RESULTS: Submicroscopic P. falciparum infections were 19.6% and 25% in Dielmo and Ndiop, respectively. K1 and 3D7 were the predominant msp-1 and msp-2 allelic types with respective frequencies of 67.36% and 67.10% in microscopic isolates and 58.24% and 78% in submicroscopic ones. Frequencies of msp-1 allelic types were statistically comparable between the studied groups (p>0.05), and were respectively 93.54% vs 87.5% for K1, 60% vs 54.83% for MAD20 and 41.93% vs 22.5% for RO33 while frequencies of msp-2 allelic types were significantly highest in the microscopy group for FC27 (41.93% vs 10%, Fisher's Exact Test, p = 0.001) and 3D7 (61.29% vs 32.5%, Fisher's Exact Test, p = 0.02). Multiplicities of infection were lowest in submicroscopic P. falciparum isolates. CONCLUSIONS: The study revealed a high submicroscopic P. falciparum carriage among patients in the study areas, and that submicroscopic P. falciparum isolates had a lower genetic diversity and complexity of malaria infections.
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Portador Sano/parasitología , Fiebre/parasitología , Malaria Falciparum/parasitología , Plasmodium falciparum/genética , Polimorfismo Genético , Adolescente , Antígenos de Protozoos/genética , Portador Sano/sangre , Portador Sano/transmisión , Niño , Femenino , Fiebre/sangre , Humanos , Malaria Falciparum/sangre , Malaria Falciparum/transmisión , Masculino , Proteína 1 de Superficie de Merozoito/genética , Proteínas Protozoarias/genética , Senegal , Adulto JovenRESUMEN
BACKGROUND: In the progress towards malaria elimination, the accurate diagnosis of low-density asymptomatic infections is critical. Low-density asymptomatic submicroscopic malaria infections may act as silent reservoirs that maintain low-level residual malaria transmission in the community. Light microscopy, the gold standard in malaria diagnosis lacks the sensitivity to detect low-level parasitaemia. In this study, the presence and prevalence of submicroscopic Plasmodium carriage were investigated to estimate the parasites reservoir among asymptomatic individuals living in low transmission areas in Dielmo and Ndiop, Senegal during the dry season. METHODS: A total of 2,037 blood samples were collected during cross-sectional surveys prior the malaria transmission season in July 2013 (N = 612), June 2014 (N = 723) and June 2015 (N = 702) from asymptomatic individuals living in Dielmo and Ndiop, Senegal. Samples were used to determine the prevalence of submicroscopic Plasmodium carriage by real time PCR (qPCR) in comparison to microscopy considered as gold standard. RESULTS: The prevalence of submicroscopic Plasmodium carriage was 3.75% (23/612), 12.44% (90/723) and 6.41% (45/702) in 2013, 2014 and 2015, respectively. No Plasmodium carriage was detected by microscopy in 2013 while microscopy-based prevalence of Plasmodium carriage accounted for only 0.27% (2/723) and 0.14% (1/702) in 2014 and 2015, respectively. Plasmodium falciparum accounted for the majority of submicroscopic infections and represented 86.95% (20/23), 81.11% (73/90) and 95.55 (43/45) of infections in 2013, 2014 and 2015 respectively. CONCLUSION: Low-density submicroscopic asymptomatic Plasmodium carriage is common in the study areas during the dry season indicating that traditional measures are insufficient to assess the scale of parasite reservoir when transmission reaches very low level. Control and elimination strategies may wish to consider using molecular methods to identify parasites carriers to guide Mass screening and Treatment strategies.
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Malaria/diagnóstico , Malaria/prevención & control , Malaria/parasitología , Plasmodium/aislamiento & purificación , Estaciones del Año , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Portador Sano/diagnóstico , Portador Sano/epidemiología , Portador Sano/parasitología , Niño , Preescolar , Estudios Transversales , ADN Protozoario/aislamiento & purificación , ADN Protozoario/metabolismo , Eritrocitos/parasitología , Femenino , Humanos , Lactante , Malaria/epidemiología , Masculino , Persona de Mediana Edad , Plasmodium/genética , Senegal/epidemiología , Adulto JovenRESUMEN
INTRODUCTION: Malaria is a leading cause of morbidity and mortality in sub-Saharan Africa. Detailed characterization of the risks for malaria, among populations living in areas where the disease is endemic, is an important priority, especially for planning and evaluating future malaria-control tools. A prospective cohort study was implemented in children under ten years living in rural areas with high Plasmodium falciparum transmission in Senegal. METHODS: Malaria incidence was prospectively evaluated over three year follow-up among a cohort of children aged less than 10 years old living in eight villages of the Sokone health district. The parents of 1316 children comprising a passive case detection cohort were encouraged to seek care from the study health centers at any time their child felt sick. In the event of reported history of fever within 24 hours or measured axillary temperature ≥ 37.5°C, a Rapid Diagnostic Test (RDT) was performed. RESULTS: From November 2010 to October 2013, among the 1468 reported febrile episodes, 264 were confirmed malaria episodes. Over the 3 years, 218 (16.9%) children experienced at least one clinical malaria episode. Cumulative malaria incidence was 7.3 episodes per 100 children-year at risk, with remarkably heterogeneous rates from 2.5 to 10.5 episodes per 100 children-year at risk. Clinical malaria prevalence ranged from 11.5 to 28.4% in the high transmission season versus from 9.6 to 21.2% in the low transmission season. CONCLUSION: This longitudinal community-based study shows that occurrence of clinical malaria was not evenly distributed among all the cohort children in the eight villages. It demonstrates the complexity of spatial distribution of malaria incidence at a local level, even in a region of vegetation and altitudinal homogeneity.
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Malaria/epidemiología , Niño , Preescolar , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Estudios Longitudinales , Masculino , Prevalencia , Senegal/epidemiologíaRESUMEN
Malaria transmission intensity is highly heterogeneous even at a very small scale. Implementing targeted intervention in malaria transmission hotspots offers the potential to reduce the burden of disease both locally and in adjacent areas. Transmission of malaria parasites from man to mosquito requires the production of gametocyte stage parasites. Cluster analysis of a 19-year long cohort study for gametocyte carriage revealed spatially defined gametocyte hotspots that occurred during the time when chloroquine was the drug used for clinical case treatment. In addition to known risk factors for gametocyte carriage, notably young age (<15 years old) and associated with a clinical episode, blood groups B and O increased risk compared to groups A and AB. A hotspot of clinical P. falciparum clinical episodes that overlapped the gametocyte hotspots was also identified. Gametocyte positivity was found to be increased in individuals who had been treated with chloroquine, as opposed to other drug treatment regimens, for a clinical P. falciparum episode up to 30 days previously. It seems likely the hotspots were generated by a vicious circle of ineffective treatment of clinical cases and concomitant gametocyte production in a sub-population characterized by an increased prevalence of all the identified risk factors. While rapid access to treatment with an effective anti-malarial can reduce the duration of gametocyte carriage and onward parasite transmission, localised hotspots represent a challenge to malaria control and eventual eradication.
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Estadios del Ciclo de Vida , Malaria Falciparum/parasitología , Plasmodium falciparum/crecimiento & desarrollo , Adolescente , Niño , Preescolar , Análisis por Conglomerados , Humanos , Estudios Longitudinales , Malaria Falciparum/epidemiología , Malaria Falciparum/transmisión , Análisis Multivariante , Prevalencia , Factores de Riesgo , Senegal/epidemiologíaRESUMEN
BACKGROUND: A better understanding of the effect of malaria control interventions on vector and parasite populations, acquired immunity, and burden of the disease is needed to guide strategies to eliminate malaria from highly endemic areas. We monitored and analysed the changes in malaria epidemiology in a village community in Senegal, west Africa, over 22 years. METHODS: Between 1990 and 2012, we did a prospective longitudinal study of the inhabitants of Dielmo, Senegal, to identify all episodes of fever and investigate the relation between malaria host, vector, and parasite. Our study included daily medical surveillance with systematic parasite detection in individuals with fever. We measured parasite prevalence four times a year with cross-sectional surveys. We monitored malaria transmission monthly with night collection of mosquitoes. Malaria treatment changed over the years, from quinine (1990-94), to chloroquine (1995-2003), amodiaquine plus sulfadoxine-pyrimethamine (2003-06), and finally artesunate plus amodiaquine (2006-12). Insecticide-treated nets (ITNs) were introduced in 2008. FINDINGS: We monitored 776 villagers aged 0-101 years for 2â378â150 person-days of follow-up. Entomological inoculation rate ranged from 142·5 infected bites per person per year in 1990 to 482·6 in 2000, and 7·6 in 2012. Parasite prevalence in children declined from 87% in 1990 to 0·3 % in 2012. In adults, it declined from 58% to 0·3%. We recorded 23â546 fever episodes during the study, including 8243 clinical attacks caused by Plasmodium falciparum, 290 by Plasmodium malariae, and 219 by Plasmodium ovale. Three deaths were directly attributable to malaria, and two to severe adverse events of antimalarial drugs. The incidence of malaria attacks ranged from 1·50 attacks per person-year in 1990 to 2·63 in 2000, and to only 0·046 in 2012. The greatest changes were associated with the replacement of chloroquine and the introduction of ITNs. INTERPRETATION: Malaria control policies combining prompt treatment of clinical attacks and deployment of ITNs can nearly eliminate parasite carriage and greatly reduce the burden of malaria in populations exposed to intense perennial malaria transmission. The choice of drugs seems crucial. Rapid decline of clinical immunity allows rapid detection and treatment of novel infections and thus has a key role in sustaining effectiveness of combining artemisinin-based combination therapy and ITNs despite increasing pyrethroid resistance. FUNDING: Pasteur Institutes of Dakar and Paris, Institut de Recherche pour le Développement, and French Ministry of Cooperation.
Asunto(s)
Anopheles/parasitología , Insectos Vectores/parasitología , Malaria/epidemiología , Plasmodium falciparum/efectos de los fármacos , Plasmodium malariae/efectos de los fármacos , Plasmodium ovale/efectos de los fármacos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Antimaláricos/administración & dosificación , Artemisininas/administración & dosificación , Niño , Preescolar , Estudios Transversales , Quimioterapia Combinada , Humanos , Lactante , Recién Nacido , Estudios Longitudinales , Malaria/tratamiento farmacológico , Malaria/prevención & control , Persona de Mediana Edad , Prevalencia , Estudios Prospectivos , Población Rural , Senegal/epidemiología , Adulto JovenRESUMEN
There exists great disparity in the number of clinical P. falciparum episodes among children of the same age and living in similar conditions. The epidemiological determinants of such disparity are unclear. We used a data-mining approach to explore a nineteen-year longitudinal malaria cohort study dataset from Senegal and identify variables associated with increased risk of malaria episodes. These were then verified using classical statistics and replicated in a second cohort. In addition to age, we identified a novel high-risk group of children in whom the history of P. falciparum clinical episodes greatly increased risk of further episodes. Age and a high number of previous falciparum clinical episodes not only play major roles in explaining the risk of P. falciparum episodes but also are risk factors for different groups of people. Combined, they explain the majority of falciparum clinical attacks. Contrary to what is widely believed, clinical immunity to P. falciparum does not de facto occur following many P. falciparum clinical episodes. There exist a sub-group of children who suffer repeated clinical episodes. In addition to posing an important challenge for population stratification during clinical trials, this sub-group disproportionally contributes to the disease burden and may necessitate specific prevention and control measures.