Heritability of Plasmodium parasite density in a rural Ugandan community.
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ABSTRACT:
SUBMITTER: Pullan RL
PROVIDER: S-EPMC2963957 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Artemisinin-based combination therapy (ACT) is widely recommended as first-line therapy for uncomplicated Plasmodium falciparum malaria worldwide. Artemisinin resistance has now been reported in Southeast Asia with a clinical phenotype manifested by slow parasite clearance. Although there are no reliable reports of artemisinin resistance in Africa, there is a need to better understand the dynamics of parasite clearance in African children treated with ACT in order to better detect the emergence of artemisinin resistance.Data from a cohort of Ugandan children four to five years old, enrolled in a longitudinal, randomized, clinical trial comparing two leading ACT, artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP), were analysed. For all episodes of uncomplicated P. falciparum malaria over a 14-month period, daily blood smears were performed for three days following the initiation of therapy. Associations between pre-treatment variables of interest and persistent parasitaemia were estimated using multivariate, generalized, estimating equations with adjustment for repeated measures in the same patient.A total of 202 children were included, resulting in 416 episodes of malaria treated with AL and 354 episodes treated with DP. The prevalence of parasitaemia on days 1, 2, and 3 following initiation of therapy was 67.6, 5.6 and 0% in those treated with AL, and 52.2, 5.7 and 0.3% in those treated with DP. Independent risk factors for persistent parasitaemia on day 1 included treatment with AL vs DP (RR?=?1.34, 95% CI 1.20-1.50, p?<?0.001), having a temperature ?38.0°C vs?<?37.0°C (RR?=?1.19, 95% CI 1.05-1.35, p?=?0.007) and having a parasite density >20,000/?L vs <4,000/?L (RR?=?3.37, 95% CI 2.44-4.49, p?<?0.001). Independent risk factors for having persistent parasitaemia on day 2 included elevated temperature, higher parasite density, and being HIV infected.Among Ugandan children, parasite clearance following treatment with AL or DP was excellent with only one of 752 patients tested having a positive blood slide three days after initiation of therapy. The type of ACT given, pre-treatment temperature, pre-treatment parasite density and HIV status were associated with differences in persistent parasitaemia, one or two days following therapy.Current Controlled Trials Identifier NCT00527800.
| S-EPMC3909240 | biostudies-literature
Project description:The recent focus on the elimination of malaria has led to an increased interest in the role of sexual stages in its transmission. We introduce Plasmodium falciparum gametocyte exported protein-5 (PfGEXP5) transcript analysis as an important tool for evaluating the earliest (ring) stage sexual gametocytes in the blood of infected individuals. We show that gametocyte rings are detected in the peripheral blood immediately following establishment of asexual infections-without the need for triggers such as high-density asexual parasitemia or drug treatment. Committed gametocytes are refractory to the commonly used drug piperaquine, and mature gametocytes reappear in the bloodstream 10 days after the initial appearance of gametocyte rings. A further wave of commitment is observed following recrudescent asexual parasitemia, and these gametocytes are again refractory to piperaquine treatment. This work has implications for monitoring gametocyte and transmission dynamics and responses to drug treatment.
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Project description:Background: Market vendors occupy a strategic position in the fight against the spread of SARS CoV-2 in rural Uganda. To successfully contain the spread of the virus, special attention needs to be given to this set of people by assessing the type of information, source of information, and practices they inculcate as regards adherence to WHO guidelines in the fight against COVID-19 in Uganda. The study aimed to assess the role of information sources, education level, and phone internet connectivity in influencing COVID-19 knowledge among the rural market vendors; and the relationship existing between knowledge, attitude, and practices among them. Methods: The study was a descriptive cross-sectional study among rural market vendors (n = 248) in southwestern Uganda. Information was collected using a questionnaire and descriptively presented as frequency and percentages. Results: The study showed that the majority of the rural market vendors had sufficient information regarding COVID-19 with the majority being female individuals and have attained a secondary level of education, The general percentage score for knowledge, attitude, and practices were (75.57, 82.6, and 76.50% respectively). There was a positive correlation between attitude and practices (r = 0.17, p = 0.007), as well as their knowledge with practices (r = 0.29, p < 0.001). The majority of the people in the population did not have their phones connected to the internet (OR = 1.96, 95%CI: 1.16-3.31, P = 0.01). The majority of people received their information regarding COVID-19 from one source (radio) (OR = 1.55). Conclusion: Where and how the rural market vendors get their information and education level are vital in breaking COVID 19 infection circle in line with WHO guidelines. Therefore, sources of information and education level played a key role in molding their knowledge and practices. However, the level of knowledge on COVID 19 among our respondents was not linked with phone internet connectivity.
| S-EPMC7357280 | biostudies-literature
Project description:Most malaria-endemic countries are heavily reliant upon rapid diagnostic tests (RDT) for malaria case identification and treatment. RDT previously used for malaria diagnosis can subsequently be used for molecular assays, including qualitative assessment of parasite species present or the carriage of resistance markers, because parasite DNA can be extracted from the blood inside the RDT which remains preserved on the internal components. However, the quantification of parasite density has not previously been possible from used RDT. In this study, blood samples were collected from school-age children in Western Kenya, in the form of both dried blood spots on Whatman filter paper, and the blood spot that is dropped into rapid diagnostic tests during use. Having first validated a robotic DNA extraction method, the parasite density was determined from both types of sample by duplex qPCR, and across a range of densities. The methods showed good agreement. The preservation of both parasite and human DNA on the nitrocellulose membrane inside the RDT was stable even after more than one year's storage. This presents a useful opportunity for researchers or clinicians wishing to gain greater information about the parasite populations that are being studied, without significant investment of resources.
| S-EPMC6434039 | biostudies-literature
Project description:Transient regulation of Plasmodium numbers below the density that induces fever has been observed in chronic malaria infections in humans and this species transcending control cannot be explained by immunity alone. Using an in vitro system we have observed density dependent regulation of malaria parasitemia as a mechanism to possibly explain these in vivo observations. P. falciparum blood stages from a high but not low-density environment exhibited what appeared to be programmed changes during the late trophozoite and schizont stages of the intraerythrocytic cycle.
2017-12-31 | GSE91188 | GEO
Project description:Malaria infections occurring below the limit of detection of standard diagnostics are common in all endemic settings. However, key questions remain surrounding their contribution to sustaining transmission and whether they need to be detected and targeted to achieve malaria elimination. In this study we analyse a range of malaria datasets to quantify the density, detectability, course of infection and infectiousness of subpatent infections. Asymptomatically infected individuals have lower parasite densities on average in low transmission settings compared to individuals in higher transmission settings. In cohort studies, subpatent infections are found to be predictive of future periods of patent infection and in membrane feeding studies, individuals infected with subpatent asexual parasite densities are found to be approximately a third as infectious to mosquitoes as individuals with patent (asexual parasite) infection. These results indicate that subpatent infections contribute to the infectious reservoir, may be long lasting, and require more sensitive diagnostics to detect them in lower transmission settings.
| S-EPMC6440965 | biostudies-literature
Project description:Background: Kidney disease is an important cause of morbidity and mortality globally. However, there are limited data on the prevalence of impaired kidney function in sub-Saharan Africa. We aimed to determine the prevalence of reduced kidney function and associated factors in a rural Ugandan population. Methods: We undertook a study of a representative sample of the General Population Cohort in South-western Uganda. We systematically collected data on cardiovascular disease risk factors, anthropometric measurements and blood tests including haemoglobin, HIV, HbA1c and serum creatinine. The estimated glomerular filtration rate (eGFR) was calculated using the CKD-Epi equation, without the race component of the equation. Results: A total of 5,979/6,397 (93.5%) participants had valid creatinine results. The mean age was 39 years (Range:16-103 years) and 3,627 (60.7%) were female. HIV prevalence was 9.7% and about 40% of the population were pre-hypertensive or hypertensive. The mean serum creatinine level was 0.75 mg/dl (95% CI 0.74-0.75), and the average eGFR was 109.3 ml/min/1.73 m 2 (95% CI 108.8-109.9). The overall prevalence of eGFR <60 ml/min/1.73 m 2 was 1.64% (98/5,979) (95% CI 1.34-1.99). Additionally, 4,792(80.2%) were classified as normal eGFR (≥90 ml/min/1.73 m 2), 1,089(18.2%) as low eGFR (60-89 ml/min/1.73 m 2), 91(1.52%) as moderately reduced eGFR (30-59 ml/min/1.73 m 2), 4(0.07%) as severely reduced eGFR (15-29 ml/min/1.73 m 2), and 3(0.05%) classified as having kidney failure (eGFR<15 ml/min/1.73 m 2). When age-standardised to the WHO Standard Population the prevalence of eGFR<60 ml/min/1.73 m 2 was 1.79%. Age above 35 years and the presence of hypertension (OR 2.86, 95% CI 1.15-7.08) and anaemia (OR 2.14, 95% CI 1.12-4.09) were associated with eGFR<60 ml/min/1.73 m 2. Conclusion: In a systematic survey of people in rural Uganda, we found a substantial proportion had eGFR<60 ml/min/1.73 m 2. More population based studies are needed to further characterize kidney disease in sub-Saharan Africa.
| S-EPMC6560494 | biostudies-literature
Project description:BackgroundAreas endemic for malaria and Hepatitis B virus (HBV) infection largely overlap geographically. A recent study has suggested the existence of an interaction between the two pathogens in symptomatic co-infected individuals on the South-American continent. We examined this issue in a hyperendemic area for both pathogens in sub-Saharan Africa.Methodology and findingsPre-transfusion samples from a retrospective cohort of 154 blood transfusion recipients were screened for both serological and molecular markers of HBV and Plasmodium genomes using species-specific nested PCR and quantitative real-time PCR. Thirty-seven individuals met exclusion criteria and were subsequently eliminated from further analysis. Of 117 participants, 90% of recipients exhibited evidence of exposure to HBV, 42% with HBsAg and/or HBV DNA and 48% anti-HBc reactive without detectable HBV DNA. Plasmodium genome prevalence by NAT was 50%. Parasitemic individuals were significantly younger than non-parasitemic individuals (P = 0.04). Parasitemia level was not significantly lower in individuals with HBV DNA positive infections compared to those with HBV DNA negative exposures. HBV DNA load was not significantly different in parasitemic and non-parasitemic individuals.ConclusionThe data presented suggests that, in sub-Saharan Africa, asymptomatic co-infections with these two ubiquitous pathogens do not appear to significantly affect each other and evolve independently.
| S-EPMC3503819 | biostudies-literature
Project description:Heterogeneity in malaria exposure is most readily recognized in areas with low-transmission patterns. By comparison, little research has been done on spatial patterns in malaria exposure in high-endemic settings. We determined the spatial clustering of clinical malaria incidence, asymptomatic parasite carriage, and Anopheles density in two villages in Mali exposed to low- and mesoendemic-malaria transmission. In the two study areas that were < 1 km(2) in size, we observed evidence for spatial clustering of Anopheles densities or malaria parasite carriage during the dry season. Anopheles density and malaria prevalence appeared associated in some of our detected hotspots. However, many households with high parasite prevalence or high Anopheles densities were located outside the identified hotspots. Our findings indicate that within small villages exposed to low- or mesoendemic-malaria transmission, spatial patterns in mosquito densities and parasite carriage are best detected in the dry season. Considering the high prevalence of parasite carriage outside detected hotspots, the suitability of the area for targeting control efforts to households or areas of more intense malaria transmission may be limited.
| S-EPMC4596601 | biostudies-literature
Project description:Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is a variant surface antigen family expressed on infected red blood cells that plays a role in immune evasion and mediates adhesion to vascular endothelium. PfEMP1s are potential targets of protective antibodies as suggested by previous seroepidemiology studies. Here, we used previously reported proteomic analyses of PfEMP1s of clinical parasite isolates collected from Malian children to identify targets of immunity. We designed a peptide library representing 11 PfEMP1 domains commonly identified on clinical isolates by membrane proteomics and then examined peptide-specific antibody responses in Malian children. The number of previous malaria infections was associated with development of PfEMP1 antibodies to peptides from domains CIDRα1.4, DBLγ11, DBLβ3, and DBLδ1. A zero-inflated negative binomial model with random effects (ZINBRE) was used to identify peptide reactivities that were associated with malaria risk. This peptide selection and serosurvey strategy revealed that high antibody levels to peptides from DBLγ11 and DBLδ1 domains correlated with decreased parasite burden in future infections, supporting the notion that specific PfEMP1 domains play a role in protective immunity. IMPORTANCE Plasmodium infection causes devastating disease and high mortality in young children. Immunity develops progressively as children acquire protection against severe disease, although reinfections and recrudescences still occur throughout life in areas of endemicity, partly due to parasite immunoevasion via switching of variant proteins such as Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) expressed on the infected erythrocyte surface. Understanding the mechanisms behind antibody protection can advance development of new therapeutic interventions that address this challenge. PfEMP1 domain-specific antibodies have been linked to reduction in severe malaria; however, the large diversity of PfEMP1 domains in circulating parasites has not been fully investigated. We designed representative peptides based on B cell epitopes of PfEMP1 domains identified in membranes of clinical parasite isolates and surveyed peptide-specific antibody responses among young Malian children in a longitudinal birth cohort. We examined previous infections and age as factors contributing to antibody acquisition and identified antibody specificities that predict malaria risk.
| S-EPMC8269226 | biostudies-literature