A comparative cross-sectional study of prevalence and intensity of soil-transmitted helminthic infection between healthy and severe acutely malnourished pre-school aged children in Kano, Northern Nigeria.

BACKGROUND: Soil-transmitted helminthic (STH) infections are common in Sub-Saharan Africa. One method used for control of these helminths is mass anti-helminthic administration in populations at risk of STH infections. In this regard, empiric treatment of children with Severe Acute Malnutrition (SAM) for STH infection is practiced in this region. It is however unclear if children with SAM suffer more from STH infection than healthy children. The objective of this study was to compare prevalence and intensity of STH infection between pre-school aged children with SAM and healthy children. METHODS: We approached 1114 pre-school aged children attending care in two health facilities in Kano, Nigeria to partake in this study. Of this number, we recruited 620 (55.7%) children, comprising 310 well-nourished children from well-baby clinics and 310 children with SAM from Community Management for Acute Malnutrition (CMAM) centres in these facilities. We assessed their nutritional status using World Health Organisation (WHO) growth charts and collected stool samples which we analysed using Formal-Ether Concentration technique to identify STH infection and Stoll's technique to assess intensities of STH infection. We fitted a logistic regression model to determine if there was any association between nutrition status and helminthic infection, adjusting for the confounding effects of socio-economic status and age. We compared intensity of STH infection (measured as eggs per gram of faeces) between both nutrition groups using the independent t-test. RESULTS: Overall STH prevalence in our population was low (2.7%) and we found no significant association between nutritional status and presence of STH infection (OR = 1.10, 95% CI 0.38 to 3.21). Majority of our study participants had either low or moderate (94.2%) and there was no statistically significant difference between intensity of STH infection (t value = - 1.52, P value = 0.13) in children with SAM and those who were well-nourished. CONCLUSIONS: The overall STH prevalence among pre-school children was low in Kano and we did not find prevalence and intensity of STH infection to differ significantly between preschool children with SAM and well-nourished children. Our findings confirm the WHO recommendation that at low levels of prevalence and intensity, interventions to control STH are unnecessary.

Design and application of a novel two-amplicon approach for defining eukaryotic microbiota.

BACKGROUND: Due to a lack of systematic diagnostics, our understanding of the diversity and role of eukaryotic microbiota in human health is limited. While studies have shown fungal communities to be significant modulators of human health, information on the prevalence of taxa such as protozoa and helminths has been limited to a small number of species for which targeted molecular diagnostics are available. To probe the diversity of eukaryotic microbes and their relationships with other members of the microbiota, we applied in silico and experimental approaches to design a novel two-amplicon surveillance tool, based on sequencing regions of ribosomal RNA genes and their internal transcribed spacers. We subsequently demonstrated the utility of our approach by characterizing the eukaryotic microbiota of 46 hospitalized Malawian children suffering from Severe Acute Malnutrition (SAM). RESULTS: Through in silico analysis and validation on a diverse panel of eukaryotes, we identified 18S rRNA variable genetic regions 4 and 5 (18S V4 V5), together with a region encoding 28S rRNA variable genetic region 2 and the internal transcribed spacers (transITS), as optimal for the systematic classification of eukaryotes. Sequencing of these regions revealed protozoa in all stool samples from children with SAM and helminths in most, including several eukaryotes previously implicated in malnutrition and diarrheal disease. Clinical comparisons revealed no association between protozoan parasites and diarrhea or HIV reactivity. However, the presence of Blastocystis correlated with bacterial alpha diversity and increased abundance of specific taxa, including Sporobacter, Cellulosibacter, Oscillibacter, and Roseburia. CONCLUSION: We suggest this novel two-amplicon based strategy will prove an effective tool to deliver new insights into the role of eukaryotic microbiota in health and disease.

Efficacy of artemether-lumefantrine in relation to drug exposure in children with and without severe acute malnutrition: an open comparative intervention study in Mali and Niger.

BACKGROUND: Severe acute malnutrition (SAM) affects almost all organs and has been associated with reduced intestinal absorption of medicines. However, very limited information is available on the pharmacokinetic properties of antimalarial drugs in this vulnerable population. We assessed artemether-lumefantrine (AL) clinical efficacy in children with SAM compared to those without. METHODS: Children under 5 years of age with uncomplicated P. falciparum malaria were enrolled between November 2013 and January 2015 in Mali and Niger, one third with uncomplicated SAM and two thirds without. AL was administered under direct observation with a fat intake consisting of ready-to-use therapeutic food (RUTF - Plumpy'Nut®) in SAM children, twice daily during 3 days. Children were followed for 42 days, with PCR-corrected adequate clinical and parasitological response (ACPR) at day 28 as the primary outcome. Lumefantrine concentrations were assessed in a subset of participants at different time points, including systematic measurements on day 7. RESULTS: A total of 399 children (360 in Mali and 39 in Niger) were enrolled. Children with SAM were younger than their non-SAM counterparts (mean 17 vs. 28 months, P < 0.0001). PCR-corrected ACPR was 100 % (95 % CI, 96.8-100 %) in SAM at both day 28 and 42, versus 98.8 % (96.4-99.7 %) at day 28 and 98.3 % (95.6-99.4 %) at day 42 in non-SAM (P = 0.236 and 0.168, respectively). Compared to younger children, children older than 21 months experienced more reinfections and SAM was associated with a greater risk of reinfection until day 28 (adjusted hazard ratio = 2.10 (1.04-4.22), P = 0.038). Day 7 lumefantrine concentrations were significantly lower in SAM than non-SAM (median 251 vs. 365 ng/mL, P = 0.049). CONCLUSIONS: This study shows comparable therapeutic efficacy of AL in children without SAM and in those with SAM when given in combination with RUTF, but a higher risk of reinfection in older children suffering from SAM. This could be associated with poorer exposure to the antimalarials as documented by a lower lumefantrine concentration on day 7. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01958905 , registration date: October 7, 2013.