Treatment outcomes for multidrug- and rifampicin-resistant tuberculosis in Central and West Africa: a systematic review and meta-analysis.

OBJECTIVES: We aimed to investigate published data on treatment outcomes of multidrug-resistant (MDR)/rifampicin-resistant tuberculosis (TB) in Central and West Africa because these, to the best of our knowledge, are sparsely available. METHODS: Systematic review and meta-analysis. RESULTS: A total of 14 studies were included, representing 4268 individuals in 14 of the 26 countries. Using a random-effects model meta-analysis, we observed a pooled success rate of 80.8% (95% confidence interval [CI] 56.0-93.3) for the Central African subgroup and 69.2% (95% CI 56.3-79.7) for the West African subgroup (P = 0.0522). The overall treatment success for all studies was 74.6% (95% CI 65.0-82.2). We found high heterogeneity among included studies (I2 = 96.1%). The estimated proportion of successfully treated individuals with MDR/rifampicin-resistant TB was considerably higher than the global estimate provided by the World Health Organization (59%), reaching the 2015 World Health Organization target of at least 75% treatment success for MDR-TB. CONCLUSION: The use of shorter treatment regimens and the standardized treatment conditions, including directly observed therapy in these studies, could have contributed to a high treatment success. Yet, the available literature was not fully representative of the regions, possibly highlighting the sparse resources in many of these countries. The review was registered at PROSPERO (https://www.crd.york.ac.uk/prospero/) (CRD42022353163).

The first-line antituberculosis drugs, and their fixed-dose combination induced abnormal sperm morphology and histological lesions in the testicular cells of male mice.

Rifampicin (RIF), Isoniazid (INH), Ethambutol (EMB), Pyrazinamide (PZA), and/or their fixed-dose combination (FDC) are extensively prescribed in the cure of Tuberculosis (TB) globally. In spite of the beneficial effect, these drugs are capable of inducing cellular toxicity. Existing information on the genotoxic effects of the first-line anti-TB drugs is limited and contentious. Herein, we evaluated the reproductive genotoxicity of RIF, INH, EMB, PZA, and their FDC utilizing the mouse sperm morphology assay. Histological examination of the testes of exposed mice was also performed. Male Swiss albino mice (11-13 weeks old) were intraperitoneally exposed for 5 consecutive days to each of the anti-TB drugs at four different doses of 6.25, 12.5, 25, and 50 mg/kg bw of PZA; 2.5, 5.0, 10, and 20 mg/kg bw of RIF; 1.25, 2.5, 5.0 and 10 mg/kg bw of INH; 3.75, 7.5, 15 and 30 mg/kg bw of EMB; and 7, 14, 28 and 56 mg/kg bw of FDC corresponding respectively to ×0.25, ×0.5, ×1 and ×2.0 of the standard daily dose. In comparison with the negative control (normal saline), there was no significant difference in the testicular weight and organo-somatic index of exposed mice. There was an increase (p > 0.05) in the frequency of abnormal spermatozoa at most of the tested doses of each drug and a dose-dependent decrease with the FDC. Each of the anti-TB drugs except the FDC induced pathological lesions in the testes. These findings suggest that the individual first-line anti-TB drug unlike the FDC has the potential to provoke testicular anomalies in male mice.

Alcohol use disorders in multidrug resistant tuberculosis (MDR-TB) patients and their non-tuberculosis family contacts in Nigeria.

INTRODUCTION: the main aim of this study was to determine the prevalence and associated factors of alcohol use disorder (AUD) in patients with Multi-Drug Treatment-Resistant Tuberculosis (MDR-TB) compared with their non-tuberculosis control, and its association with disease pattern and associated medical comorbidities. METHODS: MDR-TB patients (128) and their respective caregivers were interviewed in a treatment unit in Nigeria. Diagnosis of AUD was made using the Structured Clinical Interview for DSM-IV Axis I Disorder, information was obtained on the severity of the TB and associated health problems. RESULTS: prevalence of AUD was (21.9%) and was significantly higher among cases than in controls (2.3%), p = 0.006. Severe TB, OR = 3.33 (1.56-6.83), hematological diseases, OR = 2.34 (1.06-4.33) and HIV/AIDS, OR = 3.01 (1.67-7.01) were the strongest predictors of AUD at 95% CI. Conclusion: AUD was highly prevalent in MDR-TB and was associated with certain medical comorbidities and increased severity of the illness.

Models for Predicting Time to Sputum Conversion Among Multi-Drug Resistant Tuberculosis Patients in Lagos, South-West Nigeria.

Background: Multi-drug resistant tuberculosis (MDR-TB) develops due to problems such as irregular drug supply, poor drug quality, inappropriate prescription, and poor adherence to treatment. These factors allow the development and subsequent transmission of resistant strains of the pathogen. However, due to the chronic nature of MDR-TB, cure models allow us to investigate the covariates that are associated with the long-term effects of time-to-sputum conversion among multi-drug resistant (MDR-TB) tuberculosis individuals. Therefore, this study was designed to develop suitable cure models that can predict time to sputum conversion among MDR-TB patients. Methods: A retrospective clinic-based cohort study was conducted on 413 records of patients who were diagnosed of MDR-TB and met inclusion criteria from April 2012 to October 2016 at the Infectious Disease Hospital, Lagos. The main outcome measure (time-to-sputum conversion) was the time from the date of MDR-TB treatment to the date of specimen collection for the first of two consecutive negative smear and culture taken 30 days apart. The predictor variables of interest include: demographic (age, gender and marital status) and clinical (registration group, number of drugs resistant to at treatment initiation, HIV status, diabetes status, and adherence with medication) characteristics. Kaplan-Meier estimates of a detailed survivorship pattern among the patients were examined using Cox regression models. Mixture Cox cure models were fitted to the main outcome variable using Log-normal, Log-logistic and Weibull models as alternatives to the violation of Proportional Hazard (PH) assumption. Akaike Information Criterion (AIC) was used for models comparison based on different distributions, while the effect of predictors of time to sputum conversion was reported as Hazard Ratio (HR) at α0.05. Results: Age was 36.8 ± 12.7 years, 60.8% were male and 67.6% were married. Majority of the patients (58.4%) converted to sputum negatives. Patients who were resistant to two drugs at treatment initiation had 39% rate of conversion than those resistant to at least three drugs [HR: 1.39; CI: 0.98, 1.98]. The likelihood of sputum conversion time was shorter among non-diabetic patients compared to diabetics [HR: 0.55; CI: 0.24, 0.85]. The overall median time for sputum conversion was 5.5 (IQR: 1.5-11.5). In the cure model, resistance to more drugs at the time of initiation was significantly associated with a longer time to sputum culture conversion for Log normal Cox mixture [2.06 (1.36-3.47)]; Log-logistic Cox mixture cure [2.56(1.85-4.09)]; and Weibull Cox mixture [2.81(1.94-4.19)]. Diabetic patients had a significantly higher sputum conversion rate compared to non-diabetics; Log-normal Cox mixture [2.03(1.17-3.58)]; Log-logistic Cox mixture cure [2.11(1.25-3.82)]; and Weibull Cox mixture [2.02(1.17-3.34)]. However, Log-normal PH model gave the best fit and provided the fitness statistics [(-2LogL: 519.84); (AIC: 1053.68); (BIC: 1078.04)]. The best fitting Log-normal PH model was Y = 1.00X1+2.06X2+0.98X3+2.03X4+ε where Y is time to sputum conversion and Xs are age, number of drugs, adherence, and diabetes status. Conclusion: The models confirmed the presence of some factors related with sputum conversion time in Nigeria. The quantum of drugs resistant at treatment initiation and diabetes status would aid the clinicians in predicting the rate of sputum conversion of patients.

Thyroid function in multidrug-resistant tuberculosis patients with or without human immunodeficiency virus (HIV) infection before commencement of MDR-TB drug regimen.

BACKGROUND: Mycobacterium tuberculosis and human immunodeficiency virus (HIV) are known to cause abnormal thyroid function. There is little information on whether HIV infection aggravates alteration of thyroid function in patients with MDR-TB. OBJECTIVES: This study was carried out to determine if HIV co-infection alters serum levels of thyroid hormones (T3, T4) and thyroid stimulating hormone (TSH) in patients with MDR-TB patients and to find out the frequency of subclinical thyroid dysfunction before the commencement of MDR-TB therapy. METHODS: This observational and cross-sectional study involved all the newly admitted patients in MDR-TB Referral Centre, University College Hospital, Ibadan, Nigeria between July 2010 and December 2014. Serum levels of thyroid stimulating hormone (TSH), free thyroxine (fT4) and free triiodothyronine (fT3) were determined using ELISA. RESULTS: Enrolled were 115 patients with MDR-TB, out of which 22 (19.13%) had MDR-TB/HIV co-infection. Sick euthyroid syndrome (SES), subclinical hypothyroidism and subclinical hyperthyroidism were observed in 5 (4.35%), 9 (7.83%) and 2 (1.74%) patients respectively. The median level of TSH was insignificantly higher while the median levels of T3 and T4 were insignificantly lower in patients with MDR-TB/HIV co-infection compared with patients with MDRT-TB only. CONCLUSION: It could be concluded from this study that patients with MDR-TB/HIV co-infection have a similar thyroid function as patients having MDR-TB without HIV infection before commencement of MDR-TB drug regimen. Also, there is a possibility of subclinical thyroid dysfunction in patients with MDR-TB/HIV co-infection even, before the commencement of MDR-TB therapy.

Psychosocial wellbeing of patients with multidrug resistant tuberculosis voluntarily confined to long-term hospitalisation in Nigeria.

BACKGROUND AND OBJECTIVE: Patient isolation, which is a widely successful treatment strategy for tuberculosis (TB), has been suspected to have effects on patient psychosocial wellbeing. We assessed the psychosocial wellbeing of multidrug resistant TB (MDR-TB) patients in voluntary and isolated long-term hospitalisation in Nigeria. METHODS: 98 accessible and consenting patients in four drug-resistant treatment centres (University College Hospital and Government Chest Hospital, Ibadan; Mainland Hospital, Lagos, and Lawrence Henshaw Memorial Hospital, Calabar) were enrolled in this study. Data were collected using an 18-item psychosocial wellbeing questionnaire including sociodemographic characteristics. We used descriptive statistics to present demographic characteristics; the χ2 test was used to assess associations between psychosocial wellbeing and independent variables and the relationship was modelled using logistic regression. RESULTS: The mean age of respondents was 36.1±11.9 years and 63% were males. Respondents had been in hospital an average of 4.5±1.9 months. Females had more psychosocial concerns compared with males. The most common concerns recorded among respondents were concern that people will get to know that the respondent had a bad type of TB (70%), discontent with being separated from and longing for the company of their marital partner (72%), concerns that they may have taken too many drugs (73%), and displeasure with being unable to continue to engage in their usual social and economic activities (75%). Respondents who were employed had eight times the odds of having more psychosocial concerns than the median number among respondents. Respondents who were supported by their own families during hospitalisation experienced a lower burden of psychosocial concerns compared with those who were supported by third parties. CONCLUSIONS: Prolonged hospitalisation resulted in significant psychosocial burden for the MDR-TB patients in our study centres. There is a need to consider alternative approaches that place less psychosocial burden on patients without compromising quality of care.