Tuberculosis and diabetes mellitus comorbidity in an adult Ugandan population.

BACKGROUND: Diabetes mellitus (DM) has a direct impact on the clinical manifestation and prognosis of active tuberculosis disease (TB) and is known to increase the chance of developing the condition. We sought to determine the prevalence of DM in adult Ugandan patients with recently diagnosed TB and the associated sociodemographic, anthropometric, and metabolic characteristics of TB-DM comorbidity. METHODS: In this cross-sectional study conducted at the adult TB treatment centres of three tertiary healthcare facilities in Uganda, we screened adult participants with recently diagnosed TB (diagnosed in < 2 months) for DM. All participants were screened with five tests; initially with a random blood glucose (RBG) test, and then later with fasting blood glucose (FBG), laboratory-based glycated hemoglobin (HbA1c), point-of-care (POC) HbA1c, and oral glucose tolerance test (OGTT) if the RBG was ≥ 6.1 mmol/l. The WHO guidelines for diagnosing and managing DM were used to support the DM diagnosis. To identify the factors associated with DM-TB comorbidity, logistic regression was used. RESULTS: A total of 232 participants with recently diagnosed TB were screened for DM. Of these, 160 (69%) were female. The median (IQR) age, body mass index, and RBG of all study participants was 35 (27-42) years, 19.2 (17.6-21.3) kg/m2, and 6.1 (5.5-7.2) mmol/l, respectively. About half of the participants (n = 117, 50.4%) had RBG level ≥ 6.1 mmol/l. Of these, 75 (64.1%) participants returned for re-testing. Diabetes mellitus was diagnosed in 32 participants, corresponding to a prevalence of 13.8% (95% CI 9.9-18.9). A new diagnosis of DM was noted in 29 (90.6%) participants. On logistic regression, age ≥ 40 years was associated with increased odds of TB and DM comorbidity (AOR 3.12, 95% CI 1.35-7.23, p = 0.008) while HIV coinfection was protective (AOR 0.27, 95% CI 0.10-0.74, p = 0.01). CONCLUSION: TB and DM comorbidity was relatively common in this study population. Routine screening for DM in adult Ugandan patients with recently diagnosed TB especially among those aged ≥ 40 years and HIV-negative patients should be encouraged in clinical practice.

Diagnostic accuracy of two confirmatory tests for diabetes mellitus in adult Ugandans with recently diagnosed tuberculosis.

Objective: The optimal confirmatory tests for diabetes mellitus (DM) in patients with tuberculosis (TB) vary across populations. This study aimed to evaluate the performance of two confirmatory tests for DM against the oral glucose tolerance test (OGTT) as the reference test in adult Ugandans with recently diagnosed TB. Methods: A total of 232 adult participants receiving TB treatment underwent initial screening for DM with random blood glucose (RBG) measurement. Participants with a RBG level ⩾6.1 mmol/l received additional screening with fasting blood glucose (FBG), laboratory-measured glycated haemoglobin (HbA1c) and an OGTT. Using the latter as the gold standard and reference test, we evaluated the diagnostic accuracy of laboratory-measured HbA1c and FBG. Results: Of the 232 participants initially screened for DM using RBG measurement, 117 participants (50.4%) had RBG level ⩾6.1 mmol/l and were scheduled to return for additional blood glucose testing. Of these, 75 (64.1%) participants returned for FBG and HbA1c measurements. A diagnosis of DM was made in 32 participants, corresponding to a prevalence of 13.8% [95% CI 9.9-18.9].The areas under the curve (AUC) for FBG and laboratory-measured HbA1c were 0.69 [95% CI 0.47-0.90] and 0.65 [95% CI 0.43-0.87], respectively. The sensitivity and specificity of a FBG level of ⩾7 mmol/l were 57.1% [95% CI 18.4-90.1] and 74.6% [95% CI 62.5-84.5], respectively, whereas the sensitivity and specificity for laboratory-measured HbA1c of ⩾6.5 mmol/l (48 mmol/mol) were 14.3% [95% CI 0.40-57.9] and 95.3% (86.9-99.0%), respectively. Conclusion: FBG may be better than laboratory-measured HbA1c in confirming DM in adult Ugandans with recently diagnosed TB. However, because of the small study sample size, larger studies evaluating the diagnostic utility of these diabetes screening tests in adult Ugandans with TB are needed to confirm these findings.

Appropriate diabetes test in patients with tuberculosis Diabetes mellitus (DM) is a common condition in patients with tuberculosis and proactively screening for the condition is encouraged in all adult patients with tuberculosis. In this study, a total of 232 adult Ugandans with recently diagnosed tuberculosis were screened for DM using random glucose test, fasting blood glucose test, glycated haemoglobin test and an oral glucose tolerance test (OGTT), as the gold-standard and reference test. Compared with the OGTT, a fasting blood glucose test was noted to be a better screening test for diabetes mellitus than glycated haemoglobin in these patients and may be used as a follow-up test to random blood glucose in the screening and diagnosis of DM in adult Ugandans with tuberculosis.

Recurrent pneumothorax in a human immunodeficiency virus-positive patient with multidrug-resistant tuberculosis: a rare case of bronchopleural fistula: a case report.

BACKGROUND: Human immunodeficiency virus/tuberculosis coinfections have amplified the multidrug-resistant tuberculosis pandemic in many countries in Sub-Saharan Africa, and multidrug-resistant tuberculosis has become a major public health threat. There is a paucity of data on severe complications of multidrug-resistant tuberculosis in the context of human immunodeficiency virus coinfection despite the increasing prevalence of multidrug-resistant tuberculosis/human immunodeficiency virus coinfection and the complexity of multidrug-resistant tuberculosis treatment. This report describes a rare case of complicated multidrug-resistant tuberculosis in a human immunodeficiency virus-positive individual. CASE PRESENTATION: A 39-year-old human immunodeficiency virus-positive Ugandan male on anti-retroviral therapy for 6 years, who had recently completed treatment for drug-susceptible tuberculosis from a public hospital, presented to the tuberculosis ward of Mulago National Referral Hospital with worsening respiratory symptoms including persistent cough with purulent sputum, fever, right chest pain, and shortness of breath. On admission, a diagnosis of drug-resistant tuberculosis was made following a positive sputum Xpert MTB/Rif test with rifampicin resistance. Culture-based tuberculosis tests and line probe assay confirmed multidrug-resistant tuberculosis. The patient was given multidrug-resistant tuberculosis treatment that included bedaquiline, isoniazid, prothionamide, clofazimine, ethambutol, levofloxacin, and pyrazinamide and switched to second-line anti-retroviral therapy that included tenofovir/lamivudine/lopinavir/ritonavir. Chest X-ray revealed a hydro-pneumothorax, following which a chest tube was inserted. With persistent bubbling from the chest tube weeks later and a check chest X-ray that showed increasing pleural airspace (pneumothorax) and appearance of a new air-fluid level, chest computed tomography scan was performed, revealing a bronchopleural fistula in the right hemithorax. The computed tomography scan also revealed a pyo-pneumothorax and lung collapse involving the right middle and lower lobes as well as a thick-walled cavity in the right upper lobe. With the pulmonary complications, particularly the recurrent pneumothorax, bronchopleural fistula, and empyema thoracis, cardiothoracic surgeons were involved, who managed the patient conservatively and maintained the chest tube. The patient continued to be ill with recurrent pneumothorax despite the chest tube, until relatives opted for discharge against medical advice. CONCLUSIONS: Complicated human immunodeficiency virus-related multidrug-resistant tuberculosis is not uncommon in settings of high human immunodeficiency virus/tuberculosis prevalence and is often associated with significant morbidity and mortality. Early diagnosis and treatment of multidrug-resistant tuberculosis, with rigorous monitoring for human immunodeficiency virus-positive individuals, is necessary to prevent debilitating complications.

Prevalence and factors associated with non-adherence to multi-drug resistant tuberculosis (MDR-TB) treatment at Mulago National Referral Hospital, Kampala, Uganda.

BACKGROUND: In Uganda, 12% of previously treated TB cases and 1.6% of new cases have MDR-TB and require specialized treatment and care. Adherence is crucial for improving MDR-TB treatment outcomes. There is paucity of information on the extent to which these patients adhere to treatment and what the drivers of non-adherence are. METHODS: We conducted a cohort study using retrospectively collected routine program data for patients treated for MDR-TB between January 2012 - May 2016 at Mulago Hospital. We extracted anonymized data on non-adherence (missing 10% or more of DOT), socio-economic, demographic, and treatment characteristics of the patients. All participants were sensitive to MDR-TB drugs after second line Drug Susceptible Testing (DST) at entry into the study. Factors associated with non-adherence to MDR-TB treatment were determined using generalized linear models for the binomial family with log link and robust standard errors. We considered a p- value less than 0.05 as statistically significant. RESULTS: The records of 227 MDR- TB patients met the inclusion criteria, 39.4% of whom were female, 32.6% aged between 25 - 34 years, and 54.6% living with HIV/AIDS. About 11.9% of the patients were non-adherent. The main driver for non-adherence was history of previous DR-TB treatment; previously treated DR-TB patients were 3.46 (Adjusted prevalence ratio: 3.46, 95 % CI: 1.68 - 7.14) times more likely to be non-adherent. CONCLUSION: One in 10 MDR-TB patients treated at Mulago hospital is non-adherent to treatment. History of previous DRTB treatment was significantly associated with non-adherence in this study. MDR-TB program should strengthen adherence counselling, strengthen DST surveillance, and close monitoring for previously treated DR-TB patients.

Discordance of the Repeat GeneXpert MTB/RIF Test for Rifampicin Resistance Detection Among Patients Initiating MDR-TB Treatment in Uganda.

BACKGROUND: The Global Laboratory Initiative (GLI) guidelines recommend repeat for GeneXpertMTB/RIF (XpertMTB/RIF) in patients with a low pretest probability of rifampicin resistance (RR). METHODS: This was a cross-sectional study using results of sputum specimens collected from participants screened for the STREAM 2 trial. We recruited all patients with XpertMTB/RIF RR-TB detected who were referred for RR/multidrug-resistant (MDR) TB treatment initiation at Mulago National Referral Hospital, Kampala, between September 2017 and October 2019. At baseline, smear microscopy, repeat XpertMTB/RIF, Xpert Ultra, and MTBDRplus assays were done on sputum specimens. Culture-based drug susceptibility testing (DST) was performed on discordant specimens. We analyzed the prevalence and factors associated with discordance between initial and repeat XpertMTB/RIF RR and false XpertMTB/RIF RR. False XpertMTB/RIF RR was defined as no RR detected by any of Xpert Ultra, LPA, or culture DST (reference comparator). RESULTS: A total of 126/130 patients had repeat XpertMTB/RIF results, of whom 97 (77.0%) had M. tuberculosis detected, 81 (83.5%) had RR detected, and 1 (1.0%) had RR indeterminate. The prevalence of discordant XpertMTB/RIF RR was 15/96 (15.6%), whereas false XpertMTB/RIF RR prevalence was 10/96 (10.4%).Low-bacillary load sputum specimens were more likely to have discordant XpertMTB/RIF RR and false XpertMTB/RIF RR results (adjusted odds ratio [aOR], 0.04; 95% CI, 0.00-0.37; P = .01; aOR, 0.02; 95% CI, 0.01-0.35; P = .01, respectively). CONCLUSIONS: Our findings show a high false-positive rifampicin resistance rate in low-TB burden patients, which calls for repeat testing in order to prevent unnecessary prescription of anti-MDR-TB therapy.

Rifampicin susceptibility discordance between Xpert MTB/RIF G4 and Xpert Ultra before MDRT-TB treatment initiation: A case report from Uganda.

Tuberculosis (TB) resistance to rifampicin, the most powerful drug leads to increase in mortality. Globally, half a million new patients develop such resistant TB each year, coupled with both inappropriate diagnosis and treatment initiation. We report a case of rifampicin resistant Mycobacterium tuberculosis whose rifampicin resistance was missed by Xpert MTB/RIF Assay G4 but detected by the Xpert MTB/RIF Ultra assay at different time points leading to increased delays for MDR-TB treatment initiation at Mulago Hospital, Kampala, Uganda. Our case report compels greater urgency in accelerating the transition to the newer assay, Ultra, to benefit from higher sensitivity of rifampicin resistance detection.

Derivation and validation of a universal vital assessment (UVA) score: a tool for predicting mortality in adult hospitalised patients in sub-Saharan Africa.

BACKGROUND: Critical illness is a leading cause of morbidity and mortality in sub-Saharan Africa (SSA). Identifying patients with the highest risk of death could help with resource allocation and clinical decision making. Accordingly, we derived and validated a universal vital assessment (UVA) score for use in SSA. METHODS: We pooled data from hospital-based cohort studies conducted in six countries in SSA spanning the years 2009-2015. We derived and internally validated a UVA score using decision trees and linear regression and compared its performance with the modified early warning score (MEWS) and the quick sepsis-related organ failure assessment (qSOFA) score. RESULTS: Of 5573 patients included in the analysis, 2829 (50.8%) were female, the median (IQR) age was 36 (27-49) years, 2122 (38.1%) were HIV-infected and 996 (17.3%) died in-hospital. The UVA score included points for temperature, heart and respiratory rates, systolic blood pressure, oxygen saturation, Glasgow Coma Scale score and HIV serostatus, and had an area under the receiver operating characteristic curve (AUC) of 0.77 (95% CI 0.75 to 0.79), which outperformed MEWS (AUC 0.70 (95% CI 0.67 to 0.71)) and qSOFA (AUC 0.69 (95% CI 0.67 to 0.72)). CONCLUSION: We identified predictors of in-hospital mortality irrespective of the underlying condition(s) in a large population of hospitalised patients in SSA and derived and internally validated a UVA score to assist clinicians in risk-stratifying patients for in-hospital mortality. The UVA score could help improve patient triage in resource-limited environments and serve as a standard for mortality risk in future studies.

Higher baseline CD4 cell count predicts treatment interruptions and persistent viremia in patients initiating ARVs in rural Uganda.

We examined the association between CD4 cell count and adherence in a cohort of Ugandans initiating antiretrovirals (ARVs). Outcomes were (a) adherence <90%; (b) any treatment interruptions > 72 hours; (c) number of treatment interruptions; and (d) HIV-RNA >400 copies/mL. We fit regression models to estimate associations with our exposure of interest, baseline CD4 cell count ≥ 250 cells/µL (n = 60) vs <250 cells/µL (n = 413). CD4 cell count ≥250 cells/µL was independently associated with increased odds and number of treatment interruptions and increased odds of persistent viremia. Interventions to support adherence in patients with higher CD4 cell counts should be considered as drug availability to this population increases.