Doctoral Degrees (Molecular Biology and Human Genetics)
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Browsing Doctoral Degrees (Molecular Biology and Human Genetics) by Author "Chirenda, Joconiah"
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- ItemMigration and spread of drug resistant tuberculosis (DRTB) in Zimbabwe(Stellenbosch : Stellenbosch University, 2020-03) Chirenda, Joconiah; Streicher, Elizabeth Maria; Warren, Robin Mark; Sampson, Samantha Leigh; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Biomedical Sciences: Molecular Biology and Human Genetics.ENGLISH ABSTRACT: The Southern African Development Community (SADC) is characterised by extreme poverty, malnutrition, high human immunodeficiency virus (HIV) prevalence in the adult population and weak health systems. These factors promote transmission of tuberculosis (TB), rifampicin resistant and multidrug resistant (RR/MDR)-TB. Countries with high TB incidence in the SADC region were, South Africa (768/100,000), Namibia (729/100,000), Botswana (360/100,000), Lesotho (411/100,000) and Swaziland 854/100,000 population. Zimbabwe, with an estimated TB incidence of 221/100,000 shares poorly controlled borders with two of her highly burdened neighbours, South Africa and Mozambique. Although the World Health Organization (WHO) estimated RR/MDR-TB prevalence for Zimbabwe was 1,500 per year, the country reported 406 cases in 2018. The drug resistance survey (DRS) estimated that the RR-TB prevalence was 4% among new patients and 14.2% among retreatment cases in 2016. Since the country started providing RR/MDR-TB diagnosis, treatment and care, the maximum reported cases were just above 500 cases in 2014, an indication of low RR/MDR-TB case finding. An estimated three million Zimbabweans are believed to be immigrants in SADC countries. The paucity of evidence on cross border migration and RR/MDR-TB transmission in high burden countries motivated the study to describe the contribution of human migration to the spread of DR-TB in Zimbabwe. We reviewed published literature on migration and spread of DR-TB at both global and regional level. A geospatial analysis study of TB in Harare city aimed to assess whether environmental conditions similar to those faced by immigrants could promote TB transmission. Routinely collected and stored RR-TB isolates were spoligotyped and whole genome sequenced (WGS) to estimate presence of strains that had never been reported in Zimbabwe, defined as foreign strains. A phylogeographic study of the DR-TB Lineage 2 (L2) between South Africa and Zimbabwe aimed to explain the presence of DR-TB L2 strains in Zimbabwe. Evidence of RR/MDR-TB active transmission under migration settings was minimal. DR-TB disease was confined to immigrants with the risk falling after 5 years of stay. Few studies from high RR/MDR-TB burden settings did not show evidence of active transmission. Transmission potential from high burden countries was possible given the associated poverty, high HIV prevalence and high mixing patterns between immigrants and natives. Epidemiological analysis using geospatial techniques showed that high transmission patterns were confined in one health district with a high population of internally displaced people and limited access to health services. Understanding transmission patterns may assist in planning interventions in high burden settings where resources are scarce. The recovery of more than 60% of Mycobacterium tuberculosis (Mtb) isolates was the first description of long term storage at room temperature in low income countries. This could change the scope of TB research as the currently recommendations of minus 700C are not readily available. Drug resistant-TB isolates from Zimbabwe showed the predominance of the L2 strains, 45/184 (24.5%). Compared to previously reports of zero percent and 12% in 2007 and 2011 respectively, this was a significant increase. The DR-TB L2 strains were mainly confined to the southern part of Zimbabwe and northern provinces of South Africa. The Zimbabwean southern province has the highest HIV prevalence rate and strong historical cultural linkages with South African northern provinces. Phylogeographic analysis did not show conclusive results on directional spread of DR- TB L2 strains between Zimbabwe and South Africa despite presence of time and space clustering. Pre-existing Bedaquiline and Delamanid resistance markers of Zimbabwean isolates was disturbing given the importance of these drugs in the proposed new shorter regimens. Although our findings could not categorically demonstrate spread of DR-TB L2 between South Africa and Zimbabwe, the findings provided the first evidence on possible migration related transmission in high burden settings. Our findings may have been affected by presence of re-infection in this high burden settings. We strongly recommend a regional cross border surveillance and treatment project using WGS for diagnosis and contact investigation. The pharmaceutical industry in South Africa and Zimbabwe must work together to develop new anti-tuberculosis drug molecules and respond to the unique drug resistance patterns circulating in the region.