Browsing by Author "Chisompola, Namaunga Kasumu"

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    Genetic characterization of drug resistant clinical isolates of Mycobacterium tuberculosis circulating within the Copperbelt province and Northern regions of Zambia.
    (Stellenbosch : Stellenbosch University, 2018-03) Chisompola, Namaunga Kasumu; Sampson, Samantha Leigh; Warren, Robin Mark; Streicher, Elizabeth Maria; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Biomedical Sciences: Molecular Biology and Human Genetics.
    ENGLISH ABSTRACT: The emergence and spread of drug resistant (DR) tuberculosis (TB) strains in the form of multidrug resistant (MDR)- and extensively drug resistant (XDR)-TB is a major threat to the global fight against TB. Treatment for these forms of TB is prolonged, up to 24 months, and involves the use of a combination of highly toxic, less potent anti TB drugs. In 2015 alone, the World Health Organisation (WHO) estimated 580,000 new MDR-TB cases across the world. Nine African countries are listed as high MDR-TB burden countries by the WHO. A review of published research revealed that diverse genotypes are associated with DR TB in Africa, and demonstrated that DR TB strains are associated with community and nosocomial outbreaks. Furthermore, the role of migration in the transmission of DR TB strains has been demonstrated in certain parts of Africa. Of concern is the under-use of molecular epidemiological tools, resulting in gaps in knowledge of the transmission dynamics of DR TB on the continent. This study aims to address some of these gaps by describing the molecular epidemiology of DR TB in regions of the Copperbelt province and Northern regions of Zambia. We used molecular strain typing tools of whole genome sequencing (WGS), Sanger (targeted gene) sequencing, insertion sequence 6110-restriction fragment length polymorphism (IS6110-RFLP) and spoligotyping to describe the genotypes of DR Mycobacterium tuberculosis (M.tb) strains circulating within parts of Zambia. We demonstrated that a variety of genotypes are associated with DR TB in Zambia. The predominant genotype was lineage 4, with majority of strains belonging to Latin American Mediterranean (LAM). Other lineages belonged to 2 and 3. The genotyping analysis showed clustering of strains among patients being from different regions of the country thereby suggesting that DR TB is possibly widespread across the country. In addition, this analysis also identified household transmission of MDR-TB between two household contacts, placing emphasis on the need for routine tracing of MDR-TB patient contacts in Zambia. Further analysis of WGS and Sanger sequencing data identified 8 pre-XDR-TB cases. These belonged to lineage 4.6.1 (Uganda lineage), lineage 2.2 (Beijing genotype) and lineage 4.3 (LAM), giving a preliminary first insight into the genotypes associated with pre-XDR-TB in Zambia. Alarmingly, transmission of these pre-XDR-TB strains was demonstrated, with clustered strains sharing identical drug resistance-conferring mutations and low nucleotide variance differences. This finding emphasises the need for more comprehensive drug susceptibility testing, as failing to identify second line resistance may place the patient at risk of acquisition of additional resistance when treated with a standardised MDR-TB regimen. Nosocomial transmission of DR TB has not been described in Zambia, despite the high risk of transmission in health care facilities. Assessment of the knowledge, attitudes and practices of health care workers at MDR-TB health care facilities in Ndola district revealed knowledge gaps and administrative deficiencies which could be placing these critical personnel at risk of acquiring DR TB at the work place. Findings highlighted continuous infection prevention and control trainings and provision of adequate personal protective equipment (PPE) as key areas of improvement. The current study provides a first insight into the genetics of DR TB strains circulating in Zambia. These findings address knowledge gaps and contribute to our understanding of DR TB in Africa. To address the DR TB epidemic in Zambia, the TB control program need to expand the Xpert test-and-treat diagnostic strategy to all people entering healthcare facilities with symptoms of TB. More comprehensive drug susceptibility testing needs to be done to ensure patients are adequately treated. Following diagnosis of DR TB patients need to be counselled to initiate treatment and families and close contacts should be screened for TB.
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    Molecular epidemiology of drug resistant Mycobacterium tuberculosis in Africa : a systematic review
    (BMC (part of Springer Nature), 2020) Chisompola, Namaunga Kasumu; Streicher, Elizabeth Maria; Muchemwa, Chishala Miriam Kapambwe; Warren, Robin Mark; Sampson, Samantha Leigh
    Background: The burden of drug resistant tuberculosis in Africa is largely driven by the emergence and spread of multidrug resistant (MDR) and extensively drug resistant (XDR) Mycobacterium tuberculosis strains. MDR-TB is defined as resistance to isoniazid and rifampicin, while XDR-TB is defined as MDR-TB with added resistance to any of the second line injectable drugs and any fluoroquinolone. The highest burden of drug resistant TB is seen in countries further experiencing an HIV epidemic. The molecular mechanisms of drug resistance as well as the evolution of drug resistant TB strains have been widely studied using various genotyping tools. The study aimed to analyse the drug resistant lineages in circulation and transmission dynamics of these lineages in Africa by describing outbreaks, nosocomial transmission and migration. Viewed as a whole, this can give a better insight into the transmission dynamics of drug resistant TB in Africa. Methods: A systematic review was performed on peer reviewed original research extracted from PubMed reporting on the lineages associated with drug resistant TB from African countries, and their association with outbreaks, nosocomial transmission and migration. The search terms “Tuberculosis AND drug resistance AND Africa AND (spoligotyping OR molecular epidemiology OR IS6110 OR MIRU OR DNA fingerprinting OR RFLP OR VNTR OR WGS)” were used to identify relevant articles reporting the molecular epidemiology of drug resistant TB in Africa. Results: Diverse genotypes are associated with drug resistant TB in Africa, with variations in strain predominance within the continent. Lineage 4 predominates across Africa demonstrating the ability of “modern strains” to adapt and spread easily. Most studies under review reported primary drug resistance as the predominant type of transmission. Drug resistant TB strains are associated with community and nosocomial outbreaks involving MDRand XDR-TB strains. The under-use of molecular epidemiological tools is of concern, resulting in gaps in knowledge of the transmission dynamics of drug resistant TB on the continent. Conclusions: Genetic diversity of M. tuberculosis strains has been demonstrated across Africa implying that diverse genotypes are driving the epidemiology of drug resistant TB across the continent.