Migration and spread of drug resistant tuberculosis (DRTB) in Zimbabwe
| dc.contributor.advisor | Streicher, Elizabeth Maria | en_ZA |
| dc.contributor.advisor | Warren, Robin Mark | en_ZA |
| dc.contributor.advisor | Sampson, Samantha Leigh | en_ZA |
| dc.contributor.author | Chirenda, Joconiah | en_ZA |
| dc.contributor.other | Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Biomedical Sciences: Molecular Biology and Human Genetics. | en_ZA |
| dc.date.accessioned | 2020-02-26T07:27:34Z | |
| dc.date.accessioned | 2020-04-28T15:15:28Z | |
| dc.date.available | 2020-02-26T07:27:34Z | |
| dc.date.available | 2020-04-28T15:15:28Z | |
| dc.date.issued | 2020-03 | |
| dc.description | Thesis (PhD)--Stellenbosch University, 2020. | en_ZA |
| dc.description.abstract | 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. | en_ZA |
| dc.description.abstract | AFRIKAANSE OPSOMMING: Die Suider-Afrikaanse Ontwikkelingsgemeenskap (SAOG) word gekenmerk deur armoede, wanvoeding, hoë voorkoms van menslike immuniteitsgebreke (MIV) in die volwasse bevolking en swak gesondheidstelsels. Hierdie faktore bevorder die oordrag van tuberkulose (TB), rifampisien-weerstandige en multi middelweerstandige (RR / MDR) -TB. Lande met 'n hoë voorkoms van TB in die SAOG-streek is Suid-Afrika (768 / 100.000), Namibië (729 / 100.000), Botswana (360 / 100.000), Lesotho (411 / 100.000) en Swaziland 854 / 100.000. Zimbabwe, met 'n geraamde TB-voorkoms van 221 / 100,000, het swak beheerde grense met twee hoë TB voorkoms buurlande, Suid-Afrika en Mosambiek het. Alhoewel die Wêreldgesondheidsorganisasie (WGO) beraam dat RR / MDR-TB-voorkoms vir Zimbabwe 1 500 per jaar is, het die land in 2018 406 gevalle gerapporteer. Die medisyne-weerstandige opname (DRS) het geskat dat die RR-TB voorkoms 4% onder nuwe pasiënte was. en 14,2% onder gevalle van herbehandeling in 2016. Sedert die land begin met die diagnose, behandeling en versorging van RR / MDR-TB, was die maksimum aangemelde gevalle in 2014 net meer as 500 gevalle, 'n aanduiding van die lae RR / MDR-TB- bevindings. Na raming is daar 3 miljoen Zimbabwiërs immigrante in SAOG-lande. Die min bewyse oor grens migrasie en oordrag van RR / MDR-TB in hoë las TB lande, het hierdie studie gemotiveer om die bydrae van menslike migrasie tot die verspreiding van DR- TB in Zimbabwe te beskryf. Ons het gepubliseerde literatuur van migrasie en verspreiding van DR-TB op wêreld- and streeksvlak nagegaan. 'n Geografiese-ontledingstudie van TB in Harare is gedoen om te bepaal of omgewingstoestande soortgelyk aan immigrante TB-oordrag kan bevorder. RR-TB-isolate wat gereeld versamel en gestoor is, is gespoligotipeer en die hele genoom volgorde bepaling (WGS) is gedoen, om die teenwoordigheid te bepaal van TB-stamme wat nog nooit in Zimbabwe aangemeld is nie, gedefinieer as vreemde stamme. 'n Filogeografiese studie van die DR-TB Lineage 2 (L2) tussen Suid-Afrika en Zimbabwe is gedoen om die teenwoordigheid van DR-TB L2-stamfamilie in Zimbabwe te verklaar. Bewyse van aktiewe transmissie van RR/MDR-TB onder migrasie-omgewings was minimaal. Infeksie met DR-TB was beperk tot immigrante met die risiko dat dit na vyf jaar van verblyf daal. Min studies met hoë RR / MDR-TB voorkoms areas is gedoen en het geen bewys van aktiewe transmissie getoon nie. Die oordragpotensiaal van lande met 'n hoë las was moontlik vanweë die gepaardgaande armoede, hoë MIV- voorkoms en 'n hoë mengpatroon tussen immigrante en inboorlinge. Epidemiologiese ontledings met behulp van geografiese tegnieke (GIS) het getoon dat hoë transmissiepatrone in een gesondheidsdistrik beperk was met 'n hoë bevolking van mense wat binnelands verplaas is en beperkte toegang tot gesondheidsdienste het. As transmissiepatrone verstaan word, kan dit help met die beplanning van intervensies in areas met 'n hoë TB voorkoms waar hulpbronne skaars is. Die terugwin van meer as 60% van Mycobacterium tuberculosis (Mtb) isolate was die eerste beskrywing van langtermyn berging by kamertemperatuur in lande met lae inkomste. Dit kan die omvang van TB-navorsing verander, aangesien die huidige aanbevelings van -70°C nie geredelik beskikbaar is nie. Middelweerstandige TB- isolate uit Zimbabwe het die oorheersing van die L2 -TB stamfamilie, 45/184 (24,5%), getoon. In vergelyking met voorheen verslae van onderskeidelik 2007 en 2011 met nul persent en 12%, was dit 'n beduidende toename. Die DR-TB L2 TB stamfamilie was hoofsaaklik beperk tot die suidelike deel van Zimbabwe en die noordelike provinsies van Suid-Afrika. Die Zimbabwiese suidelike provinsie het die hoogste voorkomssyfer van MIV en sterk historiese kulturele bande met Suid-Afrikaanse noordelike provinsies. Filogeografiese ontledings het nie onweerlegbare resultate oplewer oor die rigtingverspreiding van DR-TB L2-stamfamilie tussen Zimbabwe en Suid-Afrika nie, ondanks die feit dat tyd en ruimte saamgroepeer. Die bestaande Bedaquiline- en Delamanid-weerstandmerkers van Zimbabwiese isolate was ontstellend, gegewe die belangrikheid van hierdie middels in die voorgestelde nuwe korter behandelings regimente. Alhoewel ons bevindinge nie die verspreiding van DR-TB L2 tussen Suid-Afrika en Zimbabwe kon demonstreer nie, het die bevindings die eerste bewys gelewer oor moontlike migrasieverwante transmissie in hoë lasomgewing. Ons bevindings is moontlik beïnvloed deur die teenwoordigheid van herbesmetting in hierdie hoë TB las areas. Ons beveel sterk aan dat 'n plaaslike oorgrens toesig- en behandelingsprojek wat gebruik maak van WGS gebruik word vir diagnose en kontakondersoek. Die farmaseutiese industrie in Suid-Afrika en Zimbabwe moet saamwerk om nuwe geneesmiddels teen tuberkulose te ontwikkel en te reageer op die unieke middelweerstandigheidspatrone wat in die streek sirkuleer. | af_ZA |
| dc.description.version | Doctoral | en_ZA |
| dc.embargo.terms | 2021-02-26 | |
| dc.format.extent | 264 pages | en_ZA |
| dc.identifier.uri | http://hdl.handle.net/10019.1/108476 | |
| dc.language.iso | en_ZA | en_ZA |
| dc.publisher | Stellenbosch : Stellenbosch University | en_ZA |
| dc.rights.holder | Stellenbosch University | en_ZA |
| dc.subject | South African Development Community | en_ZA |
| dc.subject | Poverty | en_ZA |
| dc.subject | Malnutrition | en_ZA |
| dc.subject | Human immunodeficiency viruses | en_ZA |
| dc.subject | Multidrug-resistant tuberculosis -- Zimbabwe | en_ZA |
| dc.title | Migration and spread of drug resistant tuberculosis (DRTB) in Zimbabwe | en_ZA |
| dc.type | Thesis | en_ZA |