Drug resistance mediating Plasmodium falciparum polymorphisms and clinical presentations of parasitaemic children in Uganda.

BackgroundPlasmodium falciparum genetic polymorphisms that mediate altered drug sensitivity may impact upon virulence. In a cross-sectional study, Ugandan children with infections mutant at pfcrt K76T, pfmdr1 N86Y, or pfmdr1 D1246Y had about one-fourth the odds of symptomatic malaria compared to those with infections with wild type (WT) sequences. However, results may have been confounded by greater likelihood in those with symptomatic disease of higher density mixed infections and/or recent prior treatment that selected for WT alleles.MethodsPolymorphisms in samples from paired episodes of asymptomatic and symptomatic parasitaemia in 114 subjects aged 4-11 years were followed longitudinally in Tororo District, Uganda. Paired episodes occurred within 3-12 months of each other and had no treatment for malaria in the prior 60 days. The prevalence of WT, mixed, and mutant alleles was determined using multiplex ligase detection reaction-fluorescent microsphere assays.ResultsConsidering paired episodes in the same subject, the odds of symptomatic malaria were lower for infections with mutant compared to WT or mixed sequence at N86Y (OR 0.26, 95% CI 0.09-0.79, p = 0.018), but not K76T or D1246Y. However, symptomatic episodes (which had higher densities) were more likely than asymptomatic to be mixed (for N86Y OR 2.0, 95% CI 1.04-4.0, p = 0.036). Excluding mixed infections, the odds of symptomatic malaria were lower for infections with mutant compared to WT sequence at N86Y (OR 0.33, 95% CI 0.11-0.98, p = 0.046), but not the other alleles. However, if mixed genotypes were grouped with mutants in this analysis or assuming that mixed infections consisted of 50% WT and 50% mutant genotypes, the odds of symptomatic infection did not differ between infections that were mutant or WT at the studied alleles.ConclusionsAlthough infections with only the mutant pfmdr1 86Y genotype were associated with symptomatic infection, this association could primarily be explained by greater parasite densities and therefore greater prevalence of mixed infections in symptomatic children. These results indicate limited association between the tested polymorphisms and risk of symptomatic disease and highlight the value of longitudinal studies for assessing associations between parasite factors and clinical outcomes

Drivers of Tracking Administration of Malaria Drugs in Health Units in Uganda. A Descriptive and Correlational Study.

Background: This study aimed at examining malaria intrinsic factors and technology controls as drivers of tracking administration malaria drugs focusing on the roles of both health workers and health units.  Methodology: Descriptive and correlational research designs were employed upon 465 health workers from 564 health units in the central districts of Uganda for which purposive and randomization techniques were used.   Results:  8.5% of health workers don’t test blood in hospitals, HC III and clinics majorly private facilities that have existed between 5-9 years, nurses noticeably base on just own experience to examination malaria patients. 11.8% don’t use slides to examine blood, health units that have existed as below as five years fall suit. Difficulty in electronic data exchange (26.7%), lack freedom to use electronic systems to access information on malaria drugs (41.9%), poor networks connectivity (60.0%) and poor response time (50.5%) are prominent. Perceptions, attitudes, knowledge, and skills of use of ICTs affect tracking administration of malaria drugs.  Conclusion: Parasites’ identification, quantification, and speciation concerns decrease from hospitals, clinics, HC III to IV in public health units that existed for 15 and below 5 years. Junior nurses with certificates and diplomas with work experience of 1-5 years mostly in general, pediatrics and “others” departments manage malaria issues with minimum guidance and supervision. Engagement of Rapid Diagnostic Test kits is higher in hospitals, clinics, pharmacies, HC III, and IV.  Recommendations: MoH should improve on planning, surveillance, and supervision of health facilities across to enforce diagnosis for malaria cases management and reduction drug resistance. Regulate a holistic and non-discriminative policy on diagnosis, treatment (drugs), and control of malaria and emphasized balanced, effective, and sustainable results. Gargets, training to handle malaria cases regardless of whether the facility is public or privately be prioritized for good tracking administration of malaria drugs

Detection of persistent Plasmodium spp. infections in Ugandan children after artemether-lumefantrine treatment

During a longitudinal study investigating the dynamics of malaria in Ugandan lakeshore communities, a consistently high malaria prevalence was observed in young children despite regular treatment. To explore the short-term performance of artemether-lumefantrine (AL), a pilot investigation into parasite carriage after treatment(s) was conducted in Bukoba village. A total of 163 children (aged 2–7 years) with a positive blood film and rapid antigen test were treated with AL; only 8·7% of these had elevated axillary temperatures. On day 7 and then on day 17, 40 children (26·3%) and 33 (22·3%) were positive by microscopy, respectively. Real-time PCR analysis demonstrated that multi-species Plasmodium infections were common at baseline, with 41·1% of children positive for Plasmodium falciparum/Plasmodium malariae, 9·2% for P. falciparum/ Plasmodium ovale spp. and 8·0% for all three species. Moreover, on day 17, 39·9% of children infected with falciparum malaria at baseline were again positive for the same species, and 9·2% of those infected with P. malariae at baseline were positive for P. malariae. Here, chronic multi-species malaria infections persisted in children after AL treatment(s). Better point-of-care diagnostics for non-falciparum infections are needed, as well as further investigation of AL performance in asymptomatic individuals

Measuring socioeconomic inequalities in relation to malaria risk: a comparison of metrics in rural Uganda

ocioeconomic position (SEP) is an important risk factor for malaria, but there is no consensus on how to measure SEP in malaria studies. We evaluated the relative strength of four indicators of SEP in predicting malaria risk in Nagongera, Uganda. 318 children resident in 100 households were followed for 36 months to measure parasite prevalence routinely every three months and malaria incidence by passive case detection. Household SEP was determined using: (1) two wealth indices, (2) income, (3) occupation and (4) education. Wealth Index I (reference) included only asset ownership variables. Wealth Index II additionally included food security and house construction variables, which may directly affect malaria. In multivariate analysis, only Wealth Index II and income were associated with the human biting rate, only Wealth Indices I and II were associated with parasite prevalence and only caregiver’s education was associated with malaria incidence. This is the first evaluation of metrics beyond wealth and consumption indices for measuring the association between SEP and malaria. The wealth index still predicted malaria risk after excluding variables directly associated with malaria, but the strength of association was lower. In this setting, wealth indices, income and education were stronger predictors of socioeconomic differences in malaria risk than occupation

Epidemiology and control of intestinal schistosomiasis on the Sesse Islands, Uganda: integrating malacology and parasitology to tailor local treatment recommendations

<p>Abstract</p> <p>Background</p> <p>Intestinal schistosomiasis is often widespread among the populations living around Lake Victoria and on its islands. The Sesse Island group (containing some 84 islands), however, is typically assumed to be a low prevalence zone, with limited transmission, but has never been surveyed in detail. Here, we present a rapid mapping assessment, bringing together snail and parasite information, at 23 sites for the presence of intermediate host snails and at 61 sites for the prevalence of intestinal schistosomiasis in school-aged children (N = 905). Two different diagnostic tools were used and compared at 45 of these sites: Kato-Katz thick faecal smears and circulating cathodic antigen (CCA) urine dipsticks.</p> <p>Results</p> <p><it>Biomphalaria </it>snails were found at 11 sites but in low numbers; none was found shedding schistosome cercariae. At 22 out of the 45 sites, local prevalence by urine and/or stool diagnostics was in excess of 50%, although mean prevalence of intestinal schistosomiasis overall was 34.6% (95% confidence intervals (CI) = 31.0-38.3%) by Kato-Katz and 46.5% (95% CI = 42.7-50.4%) by CCA if 'trace' reactions were considered infection-positive (if considered infection-negative, mean prevalence was 28.1% (95% CI = 24.7-31.7%)). Diagnostic congruence between CCA and Kato-Katz was poor and significant discordance in estimated prevalence by location was found, with each often inferring different mass drug administration regimes.</p> <p>Conclusions</p> <p>Accurate estimation of schistosome prevalence is important for determining present and future treatment needs with praziquantel; the wide range of schistosome prevalence across the Sesse Island group requires a treatment regime largely tailored to each island. In high prevalence locations, further malacological sampling is required to confirm the extent of local transmission, especially on the northern islands within the group. The observation that different diagnostic tests can provide varying results in terms of estimating prevalence by location, and hence change treatment recommendations, suggests that care must be taken in interpreting raw prevalence data. In particular, further research into the reasons for the differences in the poorer performance of the CCA test should be pursued.</p

Why is malaria associated with poverty? Findings from a cohort study in rural Uganda

Background Malaria control and sustainable development are linked, but implementation of ‘multisectoral’ intervention is restricted by a limited understanding of the causal pathways between poverty and malaria. We investigated the relationships between socioeconomic position (SEP), potential determinants of SEP, and malaria in Nagongera, rural Uganda. Methods Socioeconomic information was collected for 318 children aged six months to 10 years living in 100 households, who were followed for up to 36 months. Mosquito density was recorded using monthly light trap collections. Parasite prevalence was measured routinely every three months and malaria incidence determined by passive case detection. First, we evaluated the association between success in smallholder agriculture (the primary livelihood source) and SEP. Second, we explored socioeconomic risk factors for human biting rate (HBR), parasite prevalence and incidence of clinical malaria, and spatial clustering of socioeconomic variables. Third, we investigated the role of selected factors in mediating the association between SEP and malaria. Results Relative agricultural success was associated with higher SEP. In turn, high SEP was associated with lower HBR (highest versus lowest wealth index tertile: Incidence Rate Ratio 0.71, 95 % confidence intervals (CI) 0.54–0.93, P = 0.01) and lower odds of malaria infection in children (highest versus lowest wealth index tertile: adjusted Odds Ratio 0.52, 95 % CI 0.35–0.78, P = 0.001), but SEP was not associated with clinical malaria incidence. Mediation analysis suggested that part of the total effect of SEP on malaria infection risk was explained by house type (24.9 %, 95 % CI 15.8–58.6 %) and food security (18.6 %, 95 % CI 11.6–48.3 %); however, the assumptions of the mediation analysis may not have been fully met. Conclusion Housing improvements and agricultural development interventions to reduce poverty merit further investigation as multisectoral interventions against malaria. Further interdisplinary research is needed to understand fully the complex pathways between poverty and malaria and to develop strategies for sustainable malaria control

Clinical consequences of submicroscopic malaria parasitaemia in Uganda.

BACKGROUND: Submicroscopic malaria parasitaemia is common in both high- and low-endemicity settings, but its clinical consequences are unclear. METHODS: A cohort of 364 children (0.5-10 years of age) and 106 adults was followed from 2011 to 2016 in Tororo District, Uganda using passive surveillance for malaria episodes and active surveillance for parasitaemia. Participants presented every 90 days for routine visits (n = 9075); a subset was followed every 30 days. Participants who presented with fever and a positive blood smear were treated for malaria. At all routine visits microscopy was performed and samples from subjects with a negative blood smear underwent loop-mediated isothermal amplification for detection of plasmodial DNA. RESULTS: Submicroscopic parasitaemia was common; the proportion of visits with submicroscopic parasitemia was 25.8% in children and 39.2% in adults. For children 0.5-10 years of age, but not adults, having microscopic and submicroscopic parasitaemia at routine visits was significantly associated with both fever (adjusted risk ratios [95% CI], 2.64 [2.16-3.22], 1.67 [1.37-2.03]) and non-febrile illness (aRR [CI], 1.52 [1.30-1.78], 1.26 [1.09-1.47]), compared to not having parasitaemia. After stratifying by age, significant associations were seen between submicroscopic parasitaemia and fever in children aged 2-< 5 and 5-10 years (aRR [CI], 1.42 [1.03-1.98], 2.01 [1.49-2.71]), and submicroscopic parasitaemia and non-febrile illness in children aged 5-10 years (aRR [CI], 1.44 [1.17-1.78]). These associations were maintained after excluding individuals with a malaria episode within the preceding 14 or following 7 days, and after adjusting for household wealth. CONCLUSIONS: Submicroscopic malaria infections were associated with fever and non-febrile illness in Ugandan children. These findings support malaria control strategies that target low-density infections

An assessment of the readiness for introduction of the HPV vaccine in Uganda

Formative research assessing human papillomavirus (HPV) vaccine readiness in Uganda was conducted in 2007. The objective was to generate evidence for government decision-making and operationalplanning for HPV vaccine introduction. Qualitative research methods with children, parents, teachers, community leaders, health workers, technical experts and political leaders were used to captureunderstanding of socio-cultural, health system and policy environments. We found low levels of knowledge about cervical cancer and HPV. Vaccination and its benefits were well-understood;respondents were positive about HPV vaccination. Health systems were deemed adequate for HPV vaccine delivery. Schools were identifie as a vaccination venue, given high attendance by girls aged10-12 years. Communication and advocacy strategies to foster acceptance should provide information on cervical cancer, HPV vaccine safety, and side effects. Policymakers requested further detail on costs.Introduction of HPV vaccine could be integrated into existing reproductive health and immunization policies (Afr J Reprod Health 2008; 12[3]:159-172)

The impact of storage conditions on human stool 16S rRNA microbiome composition and diversity

Background: Multiple factors can influence stool sample integrity upon sample collection. Preservation of faecal samples for microbiome studies is therefore an important step, particularly in tropical regions where resources are limited and high temperatures may significantly influence microbiota profiles. Freezing is the accepted standard to preserve faecal samples however, cold chain methods are often unfeasible in fieldwork scenarios particularly in low and middle-income countries and alternatives are required. This study therefore aimed to address the impact of different preservative methods, time-to-freezing at ambient tropical temperatures, and stool heterogeneity on stool microbiome diversity and composition under real-life physical environments found in resource-limited fieldwork conditions. Methods: Inner and outer stool samples collected from one specimen obtained from three children were stored using different storage preservation methods (raw, ethanol and RNAlater) in a Ugandan field setting. Mixed stool was also stored using these techniques and frozen at different time-to-freezing intervals post-collection from 0–32 h. Metataxonomic profiling was used to profile samples, targeting the V1–V2 regions of 16S rRNA with samples run on a MiSeq platform. Reads were trimmed, combined and aligned to the Greengenes database. Microbial diversity and composition data were generated and analysed using Quantitative Insights Into Microbial Ecology and R software. Results: Child donor was the greatest predictor of microbiome variation between the stool samples, with all samples remaining identifiable to their child of origin despite the stool being stored under a variety of conditions. However, significant differences were observed in composition and diversity between preservation techniques, but intra-preservation technique variation was minimal for all preservation methods, and across the time-to-freezing range (0–32 h) used. Stool heterogeneity yielded no apparent microbiome differences. Conclusions: Stool collected in a fieldwork setting for comparative microbiome analyses should ideally be stored as consistently as possible using the same preservation method throughout

Selection of cooking banana genotypes for yield and black Sigatoka resistance in different locations in Uganda

It is imperative to systematically evaluate new banana genotypes in different locations before national release. This enables selection and recommendation of superior genotypes as new varieties for a wider range of environments. The objective of the present study was to select banana genotypes with stable and high performance for bunch yield and leaf black Sigatoka resistance. Eleven cooking banana genotypes developed by the Uganda National Agricultural Research Organization in collaboration with Bioversity International, and two check varieties were evaluated in multi-location preliminary yield trials in Uganda. Data collected were analyzed using Additive Main Effects and Multiplicative Interaction (AMMI) model, AMMI Stability Value, and Genotype Selection Index (GSI). Genotype × location interaction was significant for all the traits assessed. Most of the new genotypes had low interaction effects with locations for bunch yield (69.2%) and black Sigatoka (92.3%). The most stable genotypes for bunch yield were NABIO815, NABIO1117, NABIO216 and NABIO306 whereas for black Sigatoka resistance, were NABIO1011, NABIO815, NABIO1009 and NABIO216. Using the GSI that defines the most desirable genotypes as those that combine high agronomic performance and stability across environments, four genotypes (NABIO306, NABIO1011, NABIO808 and NABIO1009) were selected. These genotypes, in addition to their high performance for agronomic traits and stability, had soft and yellow fruit pulp on cooking, and will be advanced on farm for further evaluatio