Mycobacterium tuberculosis Sub-Lineage 4.2.2/SIT149 as Dominant Drug-Resistant Clade in Northwest Ethiopia 2020-2022: In-silico Whole-Genome Sequence Analysis.

Introduction: Drug resistance (DR) in Mycobacterium tuberculosis complex (MTBC) is mainly associated with certain lineages and varies across regions and countries. The Beijing genotype is the leading resistant lineage in Asia and western countries. M. tuberculosis (Mtb) (sub) lineages responsible for most drug resistance in Ethiopia are not well described. Hence, this study aimed to identify the leading drug resistance sub-lineages and characterize first-line anti-tuberculosis drug resistance-associated single nucleotide polymorphisms (SNPs). Methods: A facility-based cross-sectional study was conducted in 2020-2022 among new and presumptive multidrug resistant-TB (MDR-TB) cases in Northwest Ethiopia. Whole-genome sequencing (WGS) was performed on 161 isolates using Illumina NovaSeq 6000 technology. The SNP mutations associated with drug resistance were identified using MtbSeq and TB profiler Bioinformatics softwares. Results: Of the 146 Mtb isolates that were successfully genotyped, 20 (13.7%) harbored one or more resistance-associated SNPs. L4.2.2.ETH was the leading drug-resistant sub-lineage, accounting for 10/20 (50%) of the resistant Mtb. MDR-TB isolates showed extensive mutations against first-line anti-TB drugs. Ser450Leu/(tcg/tTg) for Rifampicin (RIF), Ser315Thr/(agc/aCc) for Isoniazid (INH), Met306Ile/(atg/atA(C)) for Ethambutol (EMB), and Gly69Asp for Streptomycin (STR) were the leading resistance associated mutations which accounted for 56.5%, 89.5%, 47%, and 29.4%, respectively. The presence of both clustered and non-clustered drug resistance (DR) isolates indicated that the epidemics is driven by both new DR development and acquired resistance. Conclusion: The high prevalence of drug-resistant TB due to geographically restricted sub-lineages (L4.2.2.ETH) indicates the ongoing local micro epidemics. The Mtb drug resistance surveillance system must be improved. Further evolutionary analysis of L4.2.2.ETH strain is highly desirable to understand evolutionary forces that leads L4.2.2.ETH in to high level DR and transmissible sub-lineage.

Feature importance: Opening a soil-transmitted helminth machine learning model via SHAP.

In the field of landscape epidemiology, the contribution of machine learning (ML) to modeling of epidemiological risk scenarios presents itself as a good alternative. This study aims to break with the "black box" paradigm that underlies the application of automatic learning techniques by using SHAP to determine the contribution of each variable in ML models applied to geospatial health, using the prevalence of hookworms, intestinal parasites, in Ethiopia, where they are widely distributed; the country bears the third-highest burden of hookworm in Sub-Saharan Africa. XGBoost software was used, a very popular ML model, to fit and analyze the data. The Python SHAP library was used to understand the importance in the trained model, of the variables for predictions. The description of the contribution of these variables on a particular prediction was obtained, using different types of plot methods. The results show that the ML models are superior to the classical statistical models; not only demonstrating similar results but also explaining, by using the SHAP package, the influence and interactions between the variables in the generated models. This analysis provides information to help understand the epidemiological problem presented and provides a tool for similar studies.

Environmental characteristics around the household and their association with hookworm infection in rural communities from Bahir Dar, Amhara Region, Ethiopia.

Soil-Transmitted Helminths (STH) are highly prevalent Neglected Tropical Disease in Ethiopia, an estimated 26 million are infected. Geographic Information Systems and Remote Sensing (RS) technologies assist data mapping and analysis, and the prediction of the spatial distribution of infection in relation to environmental variables. The influence of socioeconomic, environmental and soil characteristics on hookworm infection at the individual and household level is explored in order to identify spatial patterns of infection in rural villages from Zenzelema (Amhara region). Inhabitants greater than 5 years old were recruited in order to assess the presence of STH. Socioeconomic and hookworm infection variables at the household level and environmental variables and soil characteristics using RS were obtained. The dominant STH found was hookworm. Individuals which practiced open defecation and those without electricity had a significant higher number of hookworm eggs in their stool. Additionally, adults showed statistically higher hookworm egg counts than children. Nonetheless, the probability of hookworm infection was not determined by socioeconomic conditions but by environmental characteristics surrounding the households, including a combination of vigorous vegetation and bare soil, high temperatures, and compacted soils (high bulk density) with more acidic pH, given a pH of 6.0 is optimal for hatching of hookworm eggs. The identification of high-risk environmental areas provides a useful tool for planning, targeting and monitoring of control measures, including not only children but also adults when hookworm is concerned.

Epidemiology of intestinal helminthiases in a rural community of Ethiopia: Is it time to expand control programs to include Strongyloides stercoralis and the entire community?

BACKGROUND: Soil transmitted helminths are highly prevalent worldwide. Globally, approximately 1.5 billion people are infected with Ascaris lumbricoides, Trichuris trichiura or hookworm. Endemic countries carry out periodic mass treatment of at-risk populations with albendazole or mebendazole as a control measure. Most prevalence studies have focused on school aged children and therefore control programs are implemented at school level, not at community level. In this study, the prevalence of intestinal helminths, including Strongyloides stercoralis, was examined using a comprehensive laboratory approach in a community in north-western Ethiopia. METHODS: A cross-sectional survey was conducted on 792 individuals ≥5 years old in randomly selected houses in a rural district. Stools were examined using three techniques: a formol-ether concentration, the Baermann technique and a real time polymerase chain reaction test (these last two specific for S. stercoralis). Statistical analyses were performed between two large age groups, children (≤14 years old) and adults (≥15 years old). RESULTS: The prevalence of helminths was 91.3%; (95% CI: 89.3-93.3%). Hookworm was the most prevalent, 78.7% (95% CI 75.6-81.4%), followed by S. stercoralis 55.7% (95% CI 52.2-59.1%). Co-infection with both was detected in 45.4% (95% CI 42.0-49.0%) of the participants. The mean age of hookworm-infected individuals was significantly higher than non-infected ones (p = 0.003). Also, S. stercoralis infection was significantly associated with age, being more prevalent in adults (p = 0.002). CONCLUSIONS: This is the highest prevalence of S. stercoralis detected in Ethiopia so far. Our results highlight the need of searching specifically for infection by this parasite since it usually goes unnoticed if helminth studies rely only on conventional diagnostic techniques, i.e. Kato-Katz. Moreover, the focus of these programs on children undermines the actual prevalence of hookworm. The adult population acts as a reservoir for both hookworm and S. stercoralis and this fact may negatively impact the current control programs in Ethiopia which only target treatment of school aged children. This reservoir, together with a lack of adequate water, sanitation and hygiene, increases the probability of re-infection in children. Finally, the high prevalence of S. stercoralis found calls for a comprehensive diagnostic approach in endemic areas in addition to a revision of control measures that is, adding ivermectin to current albendazole/mebendazole, since it is the drug of choice for S. stercoralis.