Genomic epidemiological analysis identifies high relapse among individuals with recurring tuberculosis and provides evidence of recent household-related transmission of tuberculosis in Ghana

Abstract

To retrospectively investigate the cause of recurring tuberculosis (rcTB) among participants with pulmonary TB recruited from a prospective population-based study conducted between July 2012 and December 2015. Methods: Mycobacterium tuberculosis complex isolates obtained from rcTB cases were characterized by standard mycobacterial genotyping tools, whole-genome sequencing, and phylogenetic analysis carried out to assess strain relatedness. Results: The majority (58.3%, 21/36) of study participants with rcTB episodes had TB recurrence within 12 months post treatment. TB strains with isoniazid (INH) resistance were found in 19.4% (7/36) of participants at the primary episode, of which 29% (2/7) were also rifampicin-resistant. On TB recurrence, an INH-resistant strain was found in a larger proportion of participants, 27.8% (10/36), of which 40% (4/10) were MDR-TB strains. rcTB was attributed to relapse (same strain) in 75.0% (27/36) of participants and 25.0% (9/36) to re-infection. Conclusion:Our findings indicate that previous unresolved infectiondue to inadequate treatment, may be the major cause of rcTB.

The Relevance of Genomic Epidemiology for Control of Tuberculosis in West Africa

“…This means that established relapse cases may not actually be relapse events hence we advocate for the use of WGS which is more robust and relatively free from convergence evolution. Using WGS, it was possible to accurately detect relapse from a Ghanaian cohort; this study identified a couple of individuals who were previously infected with drug sensitive strains but later had TB recurrence harboring drug resistant strains (121). This shows the possibility to track such recurring cases and highlights the need to foster genomic epidemiology to aid early detection of drug resistance emergence to provide an effective TB control.…”

“…Surveillance activities geared toward understanding MTBC transmission are necessary to complement conventional control efforts to allow the establishment of good preventive strategies, appropriate therapy, and a better understanding of the pathogen biology thereby contributing to the development of future control tools and ultimately helping eliminate TB. These surveillance activities are specifically needed (1) To correctly identify, characterize and track MTBC lineages/strains; (2) To detect risk factors associated with the disease; (3) To understand MTBC person-to-person transmission dynamics, which has been studied extensively in developed countries of North America and Europe as well as other parts of the world and has been useful for identification of outbreaks as well as most at risk groups (33,48,(118)(119)(120) for targeted control activities and; (4) To track TB strains among recurring TB patients and provide indications of the cause of secondary case source (121)(122)(123), for appropriate treatment, evaluation of performance and epidemiology (32,124). To effectively control TB in West Africa, it is therefore paramount to undertake such investigations in a populationbased scale which will contribute to knowledge on factors that enhance spread of the disease in the sub-region.…”

“…Predominance of relapse over re-infection indicates high-quality public health practices and a low risk of local transmission. Many studies have employed genotyping tools like MIRU-VNTR, IS6110 RFLP, and WGS technique to explore relapse and re-infection among TB patients (121)(122)(123)(169)(170)(171)(172)(173)(174). However, very few of these studies originated from West Africa.…”

From research to health policy: The Noguchi story in the past, present and next 25 years

“…The NMIMR has collaborated with the National TB control programme (NTP) since 2002 in the development of laboratory manuals, training of laboratory personnel across Ghana on TB microscopy and quality assurance (41,42) and in 2013 assisted the NTP to conduct the first nationwide TB survey (43). Having understood the genotypic distribution of members of the causative organism, Mycobacterium tuberculosis complex (MTBC) (44, 45), novel in Ghana, the Institute has performed populationbased molecular epidemiological studies to identify hotspots of TB transmission (46) detect factors that drive recurrence of the disease (47) as well as identifying other predisposing factors such as ethnicity (48, 49) and diabetes (50). The results have been used by the NTP to direct control measures to help curb the disease burden.…”