Treatment Outcome of MDR/RR TB in a Resource-Constrained Setup: A Four-Year Retrospective Analysis.

Introduction: The emergence of drug resistance in TB treatment is a major public health threat. However, there are limited studies which are directed towards identifying factors that explain the gap in achieving treatment targets. Objective: : This study aimed to assess the treatment outcome and its associated factors among patients with MDR/RR-TB in Dilchora Hospital Treatment Initiation Center from January 2014 to December 2018. Method: : A retrospective cross-sectional study was conducted on patients with MDR/RR TB who initiated treatment between January 2014 and December 2018. Data were extracted from patient medical charts using a structured questionnaire. SPSS version 26 was used for analysis. Reports are presented using percentages and frequency. Independently associated factors for unfavorable outcome were identified using binary logistic regression model. Adjusted and crude odds ratio with 95% CI was used. P-value less than 0.05 was used to declare statistical significance. Result: : A total of 146 patients were included in this study. The overall prevalence of unfavorable outcomes in this study for those with known outcomes was 8.6%. People living with HIV had a 6.47 times (95% CI: 1.14-36.68) increased odds of death as compared to those who are HIV negative. For every 1kg/m2 increment in BMI, there was a 35.3% (AOR = 0.647; CI: 0.44-0.95) reduction in the odds of death as compared to those who had a 1kg/m2 lower BMI. Each additional month without culture conversion also increased the odds of death 2.24 times (95%CI: 1.08-4.66). Conclusion & Recommendation: : The findings of our study showed an appreciably low poor treatment outcome for this outpatient program. HIV screening and early initiation of HAART, early identification and treatment of those who are underweight and a critical follow-up to the time of sputum culture conversion could help in further improving the outcomes.

Clinical significance of normal chest radiographs among HIV-seropositive patients with suspected tuberculosis in Uganda.

BACKGROUND AND OBJECTIVE: The frequency, aetiologies and outcomes of normal chest radiographs (CXRs) among HIV-seropositive patients with suspected pulmonary tuberculosis (TB) have been infrequently described. METHODS: Consecutive HIV-seropositive adults hospitalized for cough of ≥2 weeks duration at Mulago Hospital (Kampala, Uganda), between September 2007 and July 2008, were enrolled. Baseline CXRs were obtained on admission. Patients with sputum smears that were negative for acid-fast bacilli (AFB) were referred for bronchoscopy with bronchoalveolar lavage (BAL). BAL fluid was examined for mycobacteria, Pneumocystis jirovecii and other fungi. Patients were followed for 2 months after enrolment. RESULTS: Of the 334 patients, 54 (16%) had normal CXRs. These patients were younger (median age 30 vs 34 years, P = 0.002), had lower counts of CD4+ T lymphocytes (median 13 vs 57 cells/µL, P < 0.001), and were less likely to be smear positive for AFB (17% vs 39%, P = 0.002) than those with abnormal CXRs. Pulmonary TB was the most frequent diagnosis (44%) among those with normal CXRs, followed by unknown diagnoses, pulmonary aspergillosis and pulmonary cryptococcosis. The frequency of normal CXRs was 12% among pulmonary TB patients. There was a trend towards increased 2-month mortality among patients with normal CXRs compared to those with abnormal CXRs (40% vs 29%, P = 0.15). CONCLUSIONS: Normal CXR findings were common among HIV-seropositive patients with suspected TB, especially those who were young, those with low CD4+ T cell counts and those with sputum smears that were negative for AFB. Mortality was high among those with normal CXRs. Normal CXR findings should not preclude further diagnostic evaluation in this population.

Mortality and its predictors among patients treated for acute exacerbations of chronic obstructive respiratory diseases in Jimma Medical Center; Jimma, Ethiopia: Prospective observational study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) and asthma exacerbations are associated with ill health, increased mortality, and health care costs. However, there is limited evidence regarding mortality and its predictors among patients treated for COPD and asthma exacerbations in low-income nations, particularly in Ethiopia. METHODS: A-6 month prospective observational study was conducted from April 20-September 20, 2019. Data were collected on socio-demographic, baseline clinical characteristics and outcomes of asthma and COPD exacerbations. Data were entered into Epi-Data version 4.02.01 for cleaning and exported to STATA 14.0 for analysis. Kaplan-Meier (Log-rank test) was used to compare the baseline survival experience of the study participants and Cox proportional hazard regression analysis was conducted to determine the predictors of mortality. Adjusted hazard ratios (AHRs) with two-sided p-value <0.05 were considered statistically significant. RESULTS: A total of 130 patients (60% males) were included. The median (interquartile range (IQR)) age of the study participants was 59(50-70) years. The median (IQR) survival time to death was 17.5 (10-26) days. The total proportion of in-hospital mortality was 10.78% (14/130), and the incidence rate of mortality was 2.56 per 1000 person-years. The duration of oxygen therapy ≥16hours/day (AHR = 6.330, 95% CI [1.092-36.679], and old age (AHR = 1.066, 95% CI [1.0001-1.136] were the independent predictors of in-hospital mortality. CONCLUSION: In this study, the in-hospital mortality rate was very high. Moreover, prolonged oxygen therapy (≥16hours/day) and old age were independently associated with in-hospital mortality. Therefore, special attention should be given to recipients of prolonged oxygen therapy and the elderly during hospital stay.

Disseminated Coccidioidomycosis in Africa.

BACKGROUND: Coccidioidomycosis is an endemic disease in the Americas. No cases have been reported in Africa. PATIENT: A 23-year-old HIV seronegative Ugandan man was referred to Mulago National Referral Hospital in Kampala, Uganda with a 10-month history of haemoptysis and difficulty breathing, and a 6-month history of localized swellings on the extremities. He had associated weight loss and drenching sweats, but no fevers. He had taken anti-tuberculosis medicine for 2 months with no improvement. He had never travelled out of Uganda. On physical examination, he had cystic swellings and ulcerated lesions on the extremities. He had tachypnoea, crackles in the chest and mild hepatomegaly. Bronchoscopic examination showed two masses occluding the right main bronchus. Bronchoscopic biopsy showed findings consistent with coccidioidomycosis. The patient improved with antifungal treatment and was discharged. CONCLUSION: We report the first case of disseminated coccidioidomycosis with pulmonary and cutaneous manifestations in Africa. LEARNING POINTS: Coccidioidomycosis is an endemic disease in the Americas and may now be present in Africa.The patient had taken anti-tuberculosis medicine for 2 months with no improvement.Coccidioidomycosis should be considered in the differential diagnosis of tuberculosis.

Predictors and short-term outcomes of recurrent pulmonary tuberculosis, Uganda: a cohort study.

INTRODUCTION: Recurrent tuberculosis (TB) occurring >2 years after completing treatment for a prior TB episode is most often due to reinfection with a new strain of M. tuberculosis. OBJECTIVES: We determined the prevalence and outcome of late recurrent TB among hospitalized patients in Kampala, Uganda. METHODS: We conducted a retrospective analysis of patients admitted to Mulago Hospital who had cough of >2 weeks' duration and completed TB treatment >2 years prior to admission. All patients had mycobacterial culture performed on two sputum specimens and vital status ascertained 2-months post-enrollment. We performed modeling to identify predictors of recurrent TB and of survival. RESULTS: Among 234 patients, 84 (36%) had recurrent TB. Independent predictors included younger age (aOR=0.64, 95% CI=0.42-0.97, p=0.04), chest pain >2 weeks (aOR=3.32, 95% CI=1.38-8.02, p=0.007), severe weight loss ≥5 kilograms (aOR=4.88, 95% CI=1.66-14.29, p=0.004) and presence of ≥1 WHO danger sign of severe illness (aOR=3.55, 95% CI=1.36-9.29, p=0.01). Two-month mortality was 17.8% (95% CI=10.5-29.2%), and was higher among patients not initiated on TB treatment (aHR=16.67, 95% CI=1.18-200, p=0.04), not on ART if HIV-positive (aHR=16.99, 95% CI=1.17-246.47, p=0.04) and with a history of smoking (aHR=1.20, 95% CI=1.03-1.40, p=0.02). CONCLUSION: The high prevalence of late recurrent TB likely reflects high levels of TB transmission in Kampala. Increased use of empiric TB treatment and early ART treatment initiation if HIV-positive should be considered in patients with a prior history of TB, particularly if young, with weight loss ≥5kgs, chest pain >2 weeks or ≥1 WHO danger sign of severe illness.

Prevalence and outcomes of cryptococcal antigenemia in HIV-seropositive patients hospitalized for suspected tuberculosis in Uganda.

BACKGROUND: Cryptococcal infection occurs in HIV-seropositive patients and is associated with high mortality. However, limited information is available on the prevalence and outcomes of cryptococcal antigenemia among hospitalized HIV-seropositive patients in sub-Saharan Africa. OBJECTIVES: To determine the prevalence of and risk factors for cryptococcal antigenemia among HIV-seropositive patients presenting to Mulago Hospital (Kampala, Uganda) with unexplained cough ≥2 weeks and suspected tuberculosis (TB) and also to determine if antigenemia is associated with an increased mortality. METHODS: Between September 2009 and September 2010, we enrolled consecutive HIV-seropositive adults hospitalized at Mulago Hospital with cough ≥2 weeks and suspected TB. Banked serum was tested for cryptococcal antigen. We compared demographic and clinical characteristics, and 2-month mortality in patients with and without cryptococcal antigenemia. RESULTS: Of 563 HIV-seropositive patients, 32 (5.7%) were cryptococcal antigen (CrAg) positive. None had Cryptococcus neoformans detected on fungal culture of bronchoalveolar lavage fluid (n = 116). CrAg-positive patients had a lower median CD4 count compared with CrAg-negative patients (25 vs. 55 cells/µL, P = 0.02), and a substantial proportion of CrAg-positive patients also had concurrent TB (31%). A positive CrAg test was not associated with increased mortality during the 2-month follow-up period (hazard ratio: 0.99, 95% confidence interval: 0.63 to 1.54, P = 0.95) after adjusting for CD4 count and antiretroviral therapy use at enrollment and/or follow-up. CONCLUSIONS: Occult cryptococcal antigenemia occurs commonly among hospitalized HIV-seropositive patients with suspected TB. CrAg testing should be considered in hospitalized HIV-seropositive patients with CD4 count <50 cells/µL, coupled with longer follow-up to evaluate the diagnostic value of CrAg and therapeutic interventions in patients with asymptomatic cryptococcal antigenemia.

Low prevalence of Pneumocystis pneumonia (PCP) but high prevalence of pneumocystis dihydropteroate synthase (dhps) gene mutations in HIV-infected persons in Uganda.

Pneumocystis jirovecii pneumonia (PCP) is an important opportunistic infection in patients infected with HIV, but its burden is incompletely characterized in those areas of sub-Saharan Africa where HIV is prevalent. We explored the prevalence of both PCP in HIV-infected adults admitted with pneumonia to a tertiary-care hospital in Uganda and of putative P. jirovecii drug resistance by mutations in fungal dihydropteroate synthase (dhps) and dihydrofolate reductase (dhfr). In 129 consecutive patients with sputum smears negative for mycobacteria, 5 (3.9%) were diagnosed with PCP by microscopic examination of Giemsa-stained bronchoalveolar lavage fluid. Concordance was 100% between Giemsa stain and PCR (dhps and dhfr). PCP was more prevalent in patients newly-diagnosed with HIV (11.4%) than in patients with known HIV (1.1%; p = 0.007). Mortality at 2 months after discharge was 29% overall: 28% among PCP-negative patients, and 60% (3 of 5) among PCP-positive patients. In these 5 fungal isolates and an additional 8 from consecutive cases of PCP, all strains harbored mutant dhps haplotypes; all 13 isolates harbored the P57S mutation in dhps, and 3 (23%) also harbored the T55A mutation. No non-synonymous dhfr mutations were detected. PCP is an important cause of pneumonia in patients newly-diagnosed with HIV in Uganda, is associated with high mortality, and putative molecular evidence of drug resistance is prevalent. Given the reliability of field diagnosis in our cohort, future studies in sub-Saharan Africa can investigate the clinical impact of these genotypes.

Low prevalence of Pneumocystis jirovecii lung colonization in Ugandan HIV-infected patients hospitalized with non-Pneumocystis pneumonia.

Pneumocystis jirovecii is an important opportunistic infection in human immunodeficiency virus (HIV)-infected patients. In the developed world, P. jirovecii epidemiology is marked by frequent colonization in immunosuppressed patients, but data on the prevalence of colonization are very limited in sub-Saharan Africa, where the majority of persons living with HIV reside. Our objective was to describe the epidemiology of P. jirovecii colonization among HIV-positive patients in a cross-sectional, hospital-based study of patients admitted with suspected pneumonia in Kampala, Uganda. P. jirovecii was detectable in bronchoalveolar lavage fluid from 7 (6%) of 124 consecutive patients with non-Pneumocystis pneumonia. Colonization was not associated with patient demographic or clinical information. This prevalence is substantially lower than in published studies in the developed world and suggests that there is a limited reservoir of organisms for clinical infections in this Ugandan population. These findings may partially explain the low incidence of Pneumocystis pneumonia in Uganda and other sub-Saharan African countries.

Bronchoalveolar lavage enzyme-linked immunospot for diagnosis of smear-negative tuberculosis in HIV-infected patients.

BACKGROUND: Peripheral blood interferon-gamma release assays (IGRAs) have sub-optimal sensitivity and specificity for diagnosis of active pulmonary tuberculosis (TB). However, assessment of local immune responses has been reported to improve the accuracy of TB diagnosis. METHODS: We enrolled HIV-infected adults with cough ≥2 weeks' duration admitted to Mulago Hospital in Kampala, Uganda and referred for bronchoscopy following two negative sputum acid-fast bacillus smears. We performed an ELISPOT-based IGRA (T-SPOT.TB®, Oxford Immunotec, Oxford, UK) using peripheral blood and bronchoalveolar lavage (BAL) fluid mononuclear cells, and determined the accuracy of IGRAs using mycobacterial culture results as a reference standard. RESULTS: 94 HIV-infected patients with paired peripheral blood and BAL IGRA results were included. The study population was young (median age 34 years [IQR 28-40 years]) and had advanced HIV/AIDS (median CD4+ T-lymphocyte count 60 cells/µl [IQR 22-200 cells/µl]). The proportion of indeterminate IGRA results was higher in BAL fluid than in peripheral blood specimens (34% vs. 14%, difference 20%, 95% CI 7-33%, p = 0.002). BAL IGRA had moderate sensitivity (73%, 95% CI 50-89%) but poor specificity (48%, 95% CI 32-64%) for TB diagnosis. Sensitivity was similar (75%, 95% CI 57-89%) and specificity was higher (78%, 95% CI 63-88%) when IGRA was performed on peripheral blood. CONCLUSIONS: BAL IGRA performed poorly for the diagnosis of smear-negative TB in a high HIV/TB burden setting. Further studies are needed to examine reasons for the large proportion of indeterminate results and low specificity of BAL IGRA for active TB in high HIV/TB burden settings.

The role of speciation in positive Lowenstein-Jensen culture isolates from a high tuberculosis burden country.

OBJECTIVE: To determine the need for routine speciation of positive Lowenstein-Jensen mycobacterial cultures in HIV-infected patients suspected of having pulmonary tuberculosis at Mulago Hospital in Kampala, Uganda. METHODS: Sputum and bronchoalveolar lavage Lowenstein-Jensen mycobacterial culture isolates from consecutive, HIV-infected patients admitted to Mulago Hospital with 2 weeks or more of cough were subjected to IS6110 PCR and rpoB genetic analysis to determine the presence of Mycobacterium tuberculosis complex (MTBC) and non-tuberculous mycobacteria (NTM). RESULTS: Eighty (100%) mycobacterial cultures from 65 patients were confirmed to be members of MTBC. Subsequent analysis of the cultures from 54 patients by PCR and sequence analyses to identify co-infection with NTM confirmed the presence of MTBC as well as the presence of Micrococcus luteus (n = 4), Janibacter spp. (n = 1) and six cultures had organisms that could not be identified. CONCLUSIONS: Presumptive diagnosis of tuberculosis on the basis of a positive Lowenstein-Jensen culture is sufficient in HIV-infected Ugandans suspected of having tuberculosis. Routine molecular confirmation of positive Lowenstein-Jensen cultures is unnecessary in this low resource setting.

Causes of early mortality in HIV-infected TB suspects in an East African referral hospital.

BACKGROUND: Respiratory infections are a leading cause of death in Africa, especially among HIV-infected patients. Data on the etiology of fatal respiratory diseases are largely based on autopsy studies. We evaluated causes of pneumonia associated with early mortality among hospitalized HIV-infected patients in Kampala, Uganda. METHODS: Prospective cohort study of HIV-infected patients admitted to Mulago Hospital, Kampala, with at least 2 weeks of cough. Consecutively enrolled patients with negative Ziehl Neelsen sputum smears for acid-fast bacilli underwent bronchoscopy with bronchoalveolar lavage and examination for mycobacteria (smear, solid culture), Pneumocystis jirovecii (Giemsa stain), and fungi (KOH mount, India ink stain, Sabouraud culture). Early mortality was defined as death before the 2-month follow-up visit. RESULTS: Follow-up data were available for 353 (87%) of 407 patients enrolled. Of participants with follow-up data, 112 (32%) died within 2 months. Among patients with early mortality, a diagnosis was confirmed in 74 (66%), including tuberculosis (TB) (56%), cryptococcal pneumonia (1%), Pneumocystis pneumonia (3%), pulmonary Kaposi sarcoma (4%), and pneumonia caused by 2 or more disease processes (3%). CONCLUSIONS: Mortality in HIV-infected TB suspects is high, with TB associated with the largest proportion of deaths. A significant proportion of patients die without a confirmed diagnosis.