Molecular determinants of multidrug-resistant tuberculosis in Sierra Leone.

Multidrug-resistant tuberculosis (MDR-TB) management has become a serious global health challenge. Understanding its epidemic determinants on the regional level is crucial for developing effective control measures. We used whole genome sequencing data of 238 of Mycobacterium tuberculosis complex (MTBC) strains to determine drug resistance profiles, phylogeny, and transmission dynamics of MDR/rifampicin-resistant (RR) MTBC strains from Sierra Leone. Forty-two strains were classified as RR, 196 as MDR, 5 were resistant to bedaquiline (BDQ) and clofazimine (CFZ), but none was found to be resistant to fluoroquinolones. Sixty-one (26%) strains were resistant to all first-line drugs, three of which had additional resistance to BDQ/CFZ. The strains were classified into six major MTBC lineages (L), with strains of L4 being the most prevalent, 62% (n = 147), followed by L6 (Mycobacterium africanum) strains, (21%, n = 50). The overall clustering rate (using ≤d12 single-nucleotide polymorphism threshold) was 44%, stratified into 31 clusters ranging from 2 to 16 strains. The largest cluster (n = 16) was formed by sublineage 2.2.1 Beijing Ancestral 3 strains, which developed MDR several times. Meanwhile, 10 of the L6 strains had a primary MDR transmission. We observed a high diversity of drug resistance mutations, including borderline resistance mutations to isoniazid and rifampicin, and mutations were not detected by commercial assays. In conclusion, one in five strains investigated was resistant to all first-line drugs, three of which had evidence of BDQ/CFZ resistance. Implementation of interventions such as rapid diagnostics that prevent further resistance development and stop MDR-TB transmission chains in the country is urgently needed. IMPORTANCE: A substantial proportion of MDR-TB strains in Sierra Leone were resistant against all first line drugs; however this makes the all-oral-six-month BPaLM regimen or other 6-9 months all oral regimens still viable, mainly because there was no FQ resistance.Resistance to BDQ was detected, as well as RR, due to mutations outside of the hotspot region. While the prevalence of those resistances was low, it is still cause for concern and needs to be closely monitored.

Analysing the implementation of infection prevention and control measures in health care facilities during the COVID-19 pandemic in the African Region.

BACKGROUND: The declaration of SARS-CoV-2 as a public health emergency of international concern in January 2020 prompted the need to strengthen infection prevention and control (IPC) capacities within health care facilities (HCF). IPC guidelines, with standard and transmission-based precautions to be put in place to prevent the spread of SARS-CoV-2 at these HCFs were developed. Based on these IPC guidelines, a rapid assessment scorecard tool, with 14 components, to enhance assessment and improvement of IPC measures at HCFs was developed. This study assessed the level of implementation of the IPC measures in HCFs across the African Region during the COVID-19 pandemic. METHOD: An observational study was conducted from April 2020 to November 2022 in 17 countries in the African Region to monitor the progress made in implementing IPC standard and transmission-based precautions in primary-, secondary- and tertiary-level HCFs. A total of 5168 primary, secondary and tertiary HCFs were assessed. The HCFs were assessed and scored each component of the tool. Statistical analyses were done using R (version 4.2.0). RESULTS: A total of 11 564 assessments were conducted in 5153 HCFs, giving an average of 2.2 assessments per HCF. The baseline median score for the facility assessments was 60.2%. Tertiary HCFs and those dedicated to COVID-19 patients had the highest IPC scores. Tertiary-level HCFs had a median score of 70%, secondary-level HCFs 62.3% and primary-level HCFs 56.8%. HCFs dedicated to COVID-19 patients had the highest scores, with a median of 68.2%, followed by the mixed facilities that attended to both COVID-19 and non-COVID-19 patients, with 64.84%. On the components, there was a strong correlation between high IPC assessment scores and the presence of IPC focal points in HCFs, the availability of IPC guidelines in HCFs and HCFs that had all their health workers trained in basic IPC. CONCLUSION: In conclusion, a functional IPC programme with a dedicated focal person is a prerequisite for implementing improved IPC measures at the HCF level. In the absence of an epidemic, the general IPC standards in HCFs are low, as evidenced by the low scores in the non-COVID-19 treatment centres.

Social and health factors associated with adverse treatment outcomes among people with multidrug-resistant tuberculosis in Sierra Leone: a national, retrospective cohort study.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is a global health emergency. We aimed to evaluate treatment outcomes among people with MDR-TB in Sierra Leone and investigate social and health factors associated with adverse treatment outcomes. METHODS: This national, retrospective cohort study recruited all people notified with MDR-TB to the Sierra Leone National TB Programme, admitted to Lakka hospital (Lakka, Western Area Rural District, Freetown, Sierra Leone) between April, 2017, and September, 2019. Participants were followed up to May, 2021. People who were eligible but had no social or health data available, or were subsequently found to have been misdiagnosed, were excluded from participation. MDR-TB treatment was with the 2017 WHO-recommended short (9-11 month) or long (18-24 month) aminoglycoside-containing regimens. Multivariable logistic regression models examined associations of programmatic social and health data with WHO-defined adverse treatment outcomes (death, treatment failure, loss to follow-up). FINDINGS: Of 370 notified MDR-TB cases, 365 (99%) were eligible for study participation (five participants were excluded due to lack of social or health data or misdiagnosis). Treatment was started by 341 (93%) of 365 participants (317 received the short regimen, 24 received the long regimen, and 24 received no treatment). Median age was 35 years (IQR 26-45), 263 (72%) of 365 were male and 102 (28%) were female, 71 (19%) were HIV-positive, and 127 (35%) were severely underweight (body-mass index <16·5 kg/m2). Overall, 267 (73%) of 365 participants had treatment success, 95 (26%) had an adverse outcome, and three (1%) were still on treatment in May, 2021. Age 45-64 years (adjusted odds ratio [aOR] 2·4, 95% CI 1·2-5·0), severe underweight (aOR 4·2, 1·9-9·3), untreated HIV (aOR 10, 2·6-40·0), chronic lung disease (aOR 2·0, 1·0-4·2), previously unsuccessful drug-sensitive tuberculosis retreatment (aOR 4·3, 1·0-19), and a long regimen (aOR 6·5, 2·3-18·0) were associated with adverse outcomes. A sensitivity analysis showed that prothionamide resistance (aOR 3·1, 95% CI 1·5-10·0) and aminoglycoside-related complete deafness (aOR 6·6, 1·3-35) were independently associated with adverse outcomes. INTERPRETATION: MDR-TB treatment success in Sierra Leone approached WHO targets and the short regimen was associated with higher success. The social and health factors associated with adverse outcomes in this study suggest a role for integrated tuberculosis, HIV, and non-communicable disease services alongside nutritional and socioeconomic support for people with MDR-TB and emphasise the urgent need to scale up coverage of all-oral aminoglycoside-sparing regimens. FUNDING: Wellcome Trust, Joint Global Health Trials.