Death after cure: mortality among pulmonary tuberculosis survivors in rural Uganda.

OBJECTIVE: To determine the incidence of mortality and its predictors among pulmonary TB (PTB) survivors treated at a rural Ugandan tertiary hospital. METHODS: We conducted a retrospective chart review of data between 2013 and 2023. We included all people that met the WHO's definition of tuberculosis cure and traced them or their next of kin to determine vital status (alive/deceased). We estimated the cumulative incidence of mortality per 1,000 population, crude all-cause mortality rate per 1,000 person-years, and median years of potential life lost (YPLL) for deceased individuals. Using Cox proportional hazard models, we investigated predictors of mortality. RESULTS: Of 334 PTB survivors enrolled, 38 (11.4%) had died. The cumulative incidence of all-cause mortality was 113.7 per 1,000 population, and the crude all-cause mortality rate was 28.5 per 1,000 person-years. The median YPLL for deceased individuals was 23.8 years (IQR: 9.6-32.8). Hospitalization (aHR: 4.3, 95% CI: 1.1-16.6) and unemployment (aHR: 7.04, 95% CI: 1.5-31.6) at TB treatment initiation predicted mortality. CONCLUSION: PTB survivors experience post high mortality rates after TB cure. Survivors who were hospitalized and unemployed at treatment initiation were more likely to die after cure. Social protection measures and long-term follow-up of previously hospitalized patients could improve the long-term survival of TB survivors.

Association between biomarkers of inflammation and dyslipidemia in drug resistant tuberculosis in Uganda.

BACKGROUND: Active tuberculosis (TB) significantly increases the risk of cardiovascular disease, but the underlying mechanisms remain unclear. This study aimed to investigate the association between inflammation biomarkers and dyslipidemia in patients with drug-resistant TB (DR-TB). METHODS: This was a secondary analysis of data from a cross-sectional multi-center study in Uganda conducted 2021. Participants underwent anthropometric measurements and laboratory tests included a lipid profile, full haemogram and serology for HIV infection. Dyslipidemia was defined as total cholesterol > 5.0 mmol/l and/or low-density lipoprotein cholesterol > 4.14 mmol/l, and/or triglycerides (TG) ≥ 1.7 mmol/l, and/or high density lipoprotein cholesterol (HDL-c) < 1.03 mmol/l for men and < 1.29 mmol/l for women. Biomarkers of inflammation were leukocyte, neutrophil, lymphocyte, monocyte, and platelet counts, as well as neutrophil/lymphocyte (NLR), platelet/lymphocyte, and lymphocyte/monocyte (LMR) ratios, mean corpuscular volume (MCV), and the systemic immune inflammation index (SII) (neutrophil × platelet/lymphocyte). Modified Poisson Regression analysis was used for determining the association of the biomarkers and dyslipidemia. RESULTS: Of 171 participants, 118 (69.0%) were co-infected with HIV. The prevalence of dyslipidemia was 70.2% (120/171) with low HDL-c (40.4%, 69/171) and hypertriglyceridemia (22.5%, 38/169) being the most common components. Patients with dyslipidemia had significantly higher lymphocyte (P = 0.008), monocyte (P < 0.001), and platelet counts (P = 0.014) in addition to a lower MCV (P < 0.001) than those without dyslipidemia. Further, patients with dyslipidemia had lower leucocyte (P < 0.001) and neutrophil (P = 0.001) counts, NLR (P = 0.008), LMR (P = 0.006), and SII (P = 0.049). The MCV was inversely associated with low HDL-C (adjusted prevalence ratio (aPR) = 0.97, 95% CI 0.94-0.99, P = 0.023) but was positively associated with hypertriglyceridemia (aPR = 1.04, 95% CI 1.00-1.08, P = 0.052). CONCLUSIONS: Individuals with dyslipidemia exhibited elevated lymphocyte, monocyte, and platelet counts compared to those without. However, only MCV demonstrated an independent association with specific components of dyslipidemia. There is need for further scientific inquiry into the potential impact of dyslipidemia on red cell morphology and a pro-thrombotic state among patients with TB.

Neutrophil-Lymphocyte and Platelet-Lymphocyte Ratios in Distinguishing Lung Cancer in People with HIV.

Objective: The neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) demonstrate good diagnostic accuracy in distinguishing lung cancer patients from healthy individuals, primarily in HIV-negative populations. We determined the sensitivity (Se), specificity (Sp), and area under the curve (AUC) of the NLR and PLR in discriminating between people living with HIV (PLWH) with and without lung cancer. Methods: This is a comparative analysis of secondary data. Cases were PLWH with lung cancer from a retrospective cohort treated at the Uganda Cancer Institute. Controls were unmatched PLWH without lung cancer who were randomly selected from three HIV clinics in Uganda. Se, Sp, and AUC analysis and determination of optimal cutoffs were performed using receiver operating characteristic (ROC) curves. Results: Of 115 PLWH (18 cases and 97 controls), 83 (72.2%) were female, 110 (95.7) were on ART, and the median (IQR) age was 46 (38-51) years. The median (IQR) NLR was higher among cases than controls (3.53 (3.14-7.71) vs. 0.92 (0.67-1.09), p < 0.001). Similarly, the PLR was higher among cases than controls (237.5 (177.8-361.6) vs. 123.6 (100.6-155.4), p=0.001). At a cutoff of 2.44, the respective Se, Sp, and AUC of the NLR were 87.5% (95% CI: 61.7%-98.4%), 100% (95% CI: 96.2%-100%), and 0.94 (95% CI: 0.85-1.00, p < 0.001). Similarly, the respective Se, Sp, and AUC for the PLR were 75% (95% CI: 47.6%-92.7%), 87.2% (95% CI: 78.8%-93.2%), and 0.81 (95% CI: 0.70-0.93, p < 0.001) at a cutoff of 196.3. Conclusion: The NLR and PLR discriminated PLWH with and without lung cancer and could be useful in PLWH with respiratory symptoms in whom lung cancer can easily be misdiagnosed as other lung pathology.

Diagnostic Accuracy of Clinical Diagnostic Scoring Systems for Childhood Tuberculosis: A Systematic Review and Meta-analysis.

Background: Diagnosis of childhood tuberculosis (TB) poses several challenges. Therefore, point-based scoring systems and diagnostic algorithms have been developed to improve the diagnostic yields in this population. However, there are no updated systematic reviews of the existing childhood TB scoring systems and algorithms. Hence, we systematically reviewed the diagnostic accuracy of the childhood TB diagnostic scoring systems and algorithms. Methods: We systematically searched PubMed, CINAHL, Embase, Scopus, and Google Scholar databases for relevant articles published until 30 March 2023. QUADAS-2 was used to assess their study quality. Diagnostic accuracy measures (ie, sensitivity, specificity, diagnostic odds ratio, positive and negative likelihood ratios) were pooled using a random-effects model. Results: We included 15 eligible studies, with a total of 7327 study participants aged <15 years, with 10 evaluations of childhood TB diagnostic scoring systems and algorithms. Among these algorithms and scoring systems, only 3 were evaluated more than once. These were the Keith Edwards scoring system with 5 studies (sensitivity, 81.9%; specificity, 81.2%), Kenneth Jones criteria with 3 studies (sensitivity, 80.1%; specificity, 45.7%), and the Ministry of Health-Brazil algorithm with 3 studies (sensitivity, 79.9%; specificity, 73.2%). Conclusions: We recommend using the Keith Edwards scoring system because of its high sensitivity and specificity. Further research is necessary to assess the effectiveness of scoring systems and algorithms in identifying TB in children with HIV and malnutrition.

Respiratory morbidity in Schistosoma mansoni infection: a rapid review of literature.

Background: Schistosomiasis contributes to 2.5 million disability-adjusted life years globally. Acute and chronic respiratory morbidity of Schistosoma mansoni (S. mansoni) is poorly documented in the literature. We conducted a rapid literature review of the burden of respiratory symptoms and lung function abnormalities among patients with S. mansoni. We also report the immunologic and lung imaging findings from the studies reviewed. Methods: We carried out a comprehensive literature search in Embase and MEDLINE from the inception of the databases to 13th March 2023. Results: A total of 2243 patients with S. mansoni were reported from 24 case reports, 11 cross-sectional studies, 7 case series, 2 cohort studies and 2 randomized controlled trials. The prevalence of any respiratory symptom was 13.3-63.3% (total number of patients studied, n = 149). The prevalence of the individual symptoms among patients with S. mansoni in whom respiratory symptoms were sought for was as follows: cough (8.3-80.6%, n = 338), dyspnea (1.7-100.0%, n = 200), chest pain (9.0-57.1%, n = 86), sputum production (20.0-23.3%, n = 30) and wheezing (0.0 - 20.0%, n = 1396). The frequency of the symptoms tended to be higher in acute schistosomiasis. Restrictive lung disease was prevalent in 29.0% (9/31). The commonest chest imaging findings reported were nodules (20-90%, n = 103) and interstitial infiltrates (12.5-23.0%, n = 89). Peripheral blood eosinophilia was prevalent in 72.0-100.0% of patients (n = 130) with acute schistosomiasis and correlated with symptoms and imaging abnormalities. Three case reports in chronic S. mansoni reported elevated C-reactive protein, leucocyte, neutrophil and absolute eosinophil counts, eosinophil percentage, IgE and IgG4. Conclusion: There is a high prevalence of respiratory morbidity among patients with S. mansoni, particularly in the acute stage of the infection, although the studies are relatively small. Larger studies are needed to characterize respiratory morbidity in chronic schistosomiasis and determine the underlying clinical and immunological mechanisms.

Respiratory problems in people with bilharzia Bilharzia causes significant health problems among those affected. However, little is known about respiratory problems associated with bilharzia. We systematically searched for studies published on bilharzia and respiratory problems in literature. We found that a high proportion of people with bilharzia report cough, difficulty in breathing, chest pain, sputum production and wheezing. Also, a good number have lung function impairment and abnormalities on X-ray imaging. Blood eosinophils tended to be associated with the respiratory symptoms and imaging abnormalities which suggests that eosinophils may be involved in causing respiratory problems. We conclude that lung problems are common among people with bilharzia although the studies reviewed were small and mostly among people with acute infection. Larger studies are needed to further characterise lung problems in Bilharzia.

Feasibility and acceptability of undertaking postmortem studies for tuberculosis medical research in a low income country.

Introduction: If we are to break new ground in difficult-to-treat or difficult-to-vaccinate diseases (such as HIV, malaria, or tuberculosis), we must have a better understanding of the immune system at the site of infection in humans. For tuberculosis (TB), the initial site of infection is the lungs, but obtaining lung tissues from subjects suffering from TB has been limited to bronchoalveolar lavage (BAL) or sputum sampling, or surgical resection of diseased lung tissue. Methods: We examined the feasibility of undertaking a postmortem study for human tuberculosis research at Mulago National Referral Hospital in Kampala, Uganda. Results: Postmortem studies give us an opportunity to compare TB-involved and -uninvolved sites, for both diseased and non-diseased individuals. We report good acceptability of the next-of-kin to consent for their relative's tissue to be used for medical research; that postmortem and tissue processing can be undertaken within 8 hours following death; and that immune cells remain viable and functional up to 14 hours after death. Discussion: Postmortem procedures remain a valuable and essential tool both to establish cause of death, and to advance our medical and scientific understanding of infectious diseases.

Clinical features, resistance patterns and treatment outcomes of drug-resistant extra-pulmonary tuberculosis: A scoping review.

Background: Drug-resistant tuberculosis (DR-TB) is a threat to tuberculosis (TB) control. Extra-pulmonary forms of DR-TB (DR-epTB) are not well characterized. This review summarizes the clinical features, resistance patterns and treatment outcomes of DR-epTB. Methods: We searched EMBASE to identify studies that reported drug-resistance among extra-pulmonary TB sites. All age groups were included in this review. Studies which did not describe drug-resistance patterns at extra-pulmonary TB sites were excluded. We summarized the proportion of resistance to individual anti-TB drugs as well as multi-drug resistant (MDR), pre-extensively drug resistant (pre-XDR) and extensively drug-resistant (XDR) TB. Results: Eighteen studies with a total of 10,222 patients with extra-pulmonary TB of whom 1,236 (12.0%) had DR-epTB, were included in this review. DR-epTB was mostly reported in young people aged 28 to 46 years. While TB meningitis is the most commonly studied form, adenitis is the commonest form of DR-epTB reported in 21% to 47%. Central nervous system TB (3.8% to 51.6%), pleural TB (11.3% to 25.9%), skeletal TB (9.4% to 18.1%), abdominal TB (4.3% to 6.5%), and disseminated TB (3.8%) are also encountered. The HIV co-infection rate is reported to be 5.0% to 81.3% while 2.6% to 25.4 % have diabetes mellitus. Clinical symptoms of DR-epTB are consistent with morbidity in the affected body system. Among patients with DR-epTB, the proportion of MDR TB was 5% to 53% while that for pre-XDR TB and XDR TB was 3% to 40% and 4% to 33%, respectively. Treatment success is achieved in 26% to 83% of patients with DR-epTB while death, treatment loss-to-follow up, and treatment failure occur in 2% to 76%, 7% to 15%, and 0% to 4% respectively. Patients with DR-epTB were reported to have poorer outcomes than those with pulmonary DR-TB and extra-pulmonary drug-susceptible TB. Conclusion: Clinical features of DR-epTB are similar to those observed among people with drug-susceptible EPTB but patients with DR-epTB post worse treatment outcomes.

High blood pressure prevalence, awareness, treatment, and blood pressure control among Ugandans with rheumatic and musculoskeletal disorders.

BACKGROUND: Rheumatic and musculoskeletal disorders (RMDs) are associated with cardiovascular diseases (CVDs), with hypertension being the most common. We aimed to determine the prevalence of high blood pressure (HBP), awareness, treatment, and blood pressure control among patients with RMDs seen in a Rheumatology clinic in Uganda. METHODS: We conducted a cross-sectional study at the Rheumatology Clinic of Mulago National Referral Hospital (MNRH), Kampala, Uganda. Socio-demographic, clinical characteristics and anthropometric data were collected. Multivariable logistic regression was performed using STATA 16 to determine factors associated with HBP in patients with RMDs. RESULTS: A total of 100 participants were enrolled. Of these, majority were female (84%, n = 84) with mean age of 52.1 (standard deviation: 13.8) years and median body mass index of 28 kg/m2 (interquartile range (IQR): 24.8 kg/m2-32.9 kg/m2). The prevalence of HBP was 61% (n = 61, 95% CI: 51.5-70.5), with the majority (77%, n = 47, 95% CI: 66.5-87.6) being aware they had HTN. The prevalence of HTN was 47% (n = 47, 37.2-56.8), and none had it under control. Factors independently associated with HBP were age 46-55years (adjusted prevalence ratio (aPR): 2.5, 95% confidence interval (CI): 1.06-5.95), 56-65 years (aPR: 2.6, 95% CI: 1.09-6.15), >65 years (aPR: 2.5, 95% CI: 1.02-6.00), obesity (aPR: 3.7, 95% CI: 1.79-7.52), overweight (aPR: 2.7, 95% CI: 1.29-5.77). CONCLUSION: There was a high burden of HBP among people with RMDs in Uganda with poor blood pressure control, associated with high BMI and increasing age. There is a need for further assessment of the RMD specific drivers of HBP and meticulous follow up of patients with RMDs.

Mortality rate and associated factors among patients co-infected with drug resistant tuberculosis/HIV at Mulago National Referral Hospital, Uganda, a retrospective cohort study.

Drug resistant tuberculosis (DR-TB)/HIV co-infection remains a growing threat to public health and threatens global TB and HIV prevention and care programs. HIV is likely to worsen the outcomes of DR-TB and DR-TB is likely to worsen the outcomes of HIV despite the scale up of TB and HIV services and advances in treatment and diagnosis. This study determined the mortality rate and factors associated with mortality among persons on treatment co-infected with drug resistant TB and HIV at Mulago National Referral Hospital. We retrospectively reviewed data of 390 persons on treatment that had a DR-TB/HIV co-infection in Mulago National Referral Hospital from January 2014 to December 2019.Modified poisson regression with robust standard errors was used to determine relationships between the independent variables and the dependent variable (mortality) at bivariate and multivariate analysis. Of the 390 participants enrolled, 201(53.9%) were males with a mean age of 34.6 (±10.6) and 129 (33.2%,95% CI = 28.7-38.1%) died. Antiretroviral therapy(ART) initiation (aIRR 0.74, 95% CI = 0.69-0.79), having a body mass index (BMI)≥18.5Kg/m2 (aIRR 1.01, 95% CI = 1.03-1.17), having a documented client phone contact (aIRR 0.85, 95% CI = 0.76-0.97), having a mid-upper arm circumference,(MUAC) ≥18.5cm (aIRR 0.90, 95% CI = 0.82-0.99), being on first and second line ART regimen (aIRR 0.83, 95% CI = 0.77-0.89),having a known viral load (aIRR 1.09, 95% CI = 1.00-1.21) and having an adverse event during the course of treatment (aIRR 0.88, 95% CI = 0.83-0.93) were protective against mortality. There was a significantly high mortality rate due to DR-TB/HIV co-infection. These results suggest that initiation of all persons living with HIV/AIDS (PLWHA) with DR-TB on ART and frequent monitoring of adverse drug events highly reduces mortality.

Effect of COVID-19 pandemic on inpatient service utilization and patient outcomes in Uganda.

COVID-19 has had devastating effects on health systems but reports from sub-Saharan Africa are few. We compared inpatient admissions, diagnostic tests performed, clinical characteristics and inpatient mortality before and during the COVID-19 pandemic at an urban tertiary facility in Uganda. We conducted a retrospective chart review of patients admitted at Kiruddu National Referral Hospital in Uganda between January-July 2019 (before the pandemic) and January-July 2020 (during the pandemic). Of 3749 inpatients, 2014 (53.7%) were female, and 1582 (42.2%) had HIV. There was a 6.1% decline in admissions from 1932 in 2019 to 1817 in 2020. There were significantly fewer diagnostic tests performed in 2020 for malaria, tuberculosis, and diabetes. Overall, 649 (17.3%) patients died. Patients admitted during the COVID-19 pandemic (adjusted odds ratio [aOR] 1.2, 95% confidence interval [CI] 1.04-1.5, p = 0.018), patients aged ≥ 60 years (aOR 1.6, 95% CI 1.2-2.1, p = 0.001), HIV co-infected (aOR 1.5, 95% CI 1.2-1.9, p < 0.001), and those admitted as referrals (aOR 1.5, 95% CI 1.2-1.9, p < 0.001) had higher odds of dying. The COVID-19 pandemic disrupted inpatient service utilization and was associated with inpatient mortality. Policy makers need to build resilience in health systems in Africa to cope with future pandemics.

Mycobacterium tuberculosis infection and cytogenetic abnormalities among people with HIV.

OBJECTIVE: To compare cytogenetic abnormalities among people living with HIV (PLWH) with and without previous exposure to Mycobacterium tuberculosis (Mtb) (both latent tuberculosis infection [LTBI] and active tuberculosis [TB]). METHODS: Adult PLWH (≥18 years) were randomly selected at three HIV clinics in Uganda. Previous active TB was confirmed in the clinics' TB records. LTBI was defined as a positive QuantiFERON-TB Gold Plus assay. Participants' buccal mucosal exfoliated cells were examined (per 2000 cells) using the buccal micronucleus assay for chromosomal aberrations (micronuclei and/or nuclear buds), cytokinetic defects (binucleated cells), proliferative potential (normal differentiated cells and basal cell frequency) and/or cell death (condensed chromatin, karyorrhexis, pyknotic and karyolytic cells). RESULTS: Among 97 PLWH, 42 (43.3%) had exposure to Mtb;16 had previous successfully treated active TB and 26 had LTBI. PLWH with exposure to Mtb had a higher median number of normal differentiated cells (1806.5 [1757.0 - 1842.0] vs. 1784.0 [1732.0 - 1843.0], p = 0.031) and fewer karyorrhectic cells (12.0 [9.0 - 29.0] vs. 18.0 [11.0 - 30.0], p = 0.048) than those without. PLWH with LTBI had fewer karyorrhectic cells than those without (11.5 [8.0 - 29.0] vs. 18.0 [11 - 30], p = 0.006). CONCLUSION: We hypothesized that previous exposure to Mtb is associated with cytogenetic damage among PLWH. We found that exposure to Mtb is associated with more normal differentiated cells and less frequent karyorrhexis (a feature of apoptosis). It is unclear whether this increases the propensity for tumorigenesis.

Coinfection of COVID-19 and Tuberculosis in Uganda.

The clinical features and outcomes of tuberculosis (TB) and COVID-19 coinfection are not well established. This short report describes 11 people with TB/COVID-19 coinfection in Uganda. The mean age was 46.9 ± 14.5 years; eight (72.7%) were male and two (18.2%) were coinfected with HIV. All patients presented with cough whose median duration was 71.1 (interquartile range, 33.1, 109) days. Eight (72.7%) had mild COVID-19 whereas two (18.2%) died, including one with advanced HIV disease. All patients were treated with first-line anti-TB drugs and adjunct therapy for COVID-19 using national treatment guidelines. This report presents the possibility of the coexistence of the two diseases and calls for more vigilance, screening, and collective prevention measures for both COVID-19 and TB.

Diagnostic accuracy of clinical diagnostic scoring systems for childhood tuberculosis: a systematic review and meta-analysis protocol.

INTRODUCTION: Diagnosis of childhood tuberculosis (TB) poses several challenges. Therefore, clinical signs and symptoms, radiological studies, laboratory examinations, point-based scoring systems or diagnostic algorithms have been developed to improve diagnostic yields in this population. However, there are limited data on the diagnostic test accuracy of paediatric TB scoring systems. Therefore, this systematic review and meta-analysis aims to synthesise the available evidence on the diagnostic accuracy of childhood TB diagnostic scoring systems. METHODS AND ANALYSIS: This protocol describes a systematic review, developed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses of Diagnostic Test Accuracy. We will conduct a comprehensive literature search for relevant articles in the following databases: PubMed, CINAHL, Embase, Scopus and Cochrane Databases. The eligibility criteria for studies will be formulated based on the Participants (Population), Index Test, Comparator Test and Target Condition criteria for the review question. The index test will be defined as any attempt to diagnose childhood TB using either a scoring system or a diagnostic algorithm, whereas a composite reference standard will be used as a reference standard. This will include any attempt to confirm diagnosis of TB. Where bacteriological confirmation is not obtained and there are at least two of the following features: chest radiograph consistent with TB, immunological evidence of Mycobacterium tuberculosis infection and/or positive response to TB treatment will also be considered. The QUADAS-2 Tool will be used to assess the quality of the studies. The diagnostic accuracy measures (ie, sensitivity, specificity, negative predictive and positive predictive values) will be pooled with the random-effects or fixed-effects models, as appropriate. All statistical analyses will be performed using the Review Manager V.5.4. ETHICS AND DISSEMINATION: This research is exempt from ethics approval given that this is a protocol for a systematic review, which uses published data. The findings from this review will be disseminated through peer-reviewed publications and scientific conferences. PROSPERO REGISTRATION NUMBER: CRD42022367049.

Early culture conversion is a poor marker of treatment outcome among people with HIV and drug-resistant TB.

OBJECTIVE: Our objective was to determine associations between early (≤2 months) culture conversion (ECC) among people with HIV and drug-resistant tuberculosis (DRTB) in Uganda. METHODS: This was a countrywide retrospective cohort of people with bacteriologically confirmed DRTB and a positive baseline culture at 16 centres in Uganda between 2013 and 2019. Data were abstracted from treatment files and unit DRTB registers. Monthly sputum cultures were performed using the Lowenstein-Jensen solid medium. RESULTS: We included 664 people with DRTB and a positive baseline culture, of whom 353 (53.4%) also had HIV. Among those living with HIV, 225 (63.7%) were male and 331 (94.3%) were on antiretroviral therapy. The median month of culture conversion was 2 (interquartile range [IQR] 1-3). ECC was observed among 226 people living with HIV (64.0%; 95% confidence interval [CI] 58.9-68.9). A DRTB treatment regimen of six or more drugs was associated with ECC among people living with HIV (adjusted odds ratio [aOR]  3.82; 95% CI 1.06-13.82; p = 0.041). Cure and overall treatment success was observed among 232 (65.7%) and 269 (76.2%) people living with HIV, respectively. However, ECC was not associated with cure (crude odds ratio [OR]  0.97; 95% CI 0.61-1.54; p = 0.901), death (OR 1.12; 95% CI 0.61-2.29; p = 0.610), or overall treatment success (OR 1.29; 95% CI 0.78-2.13; p = 0.326). CONCLUSION: The majority of people living with HIV and DRTB achieve ECC. However, ECC does not predict cure, death, or treatment success. Moreover, it may require six or more drugs to achieve ECC. ECC is not an excellent indicator of the effectiveness of DRTB regimens among people living with HIV.

Incidence and Predictors of Adverse Drug Events Among People Receiving Drug Resistant Tuberculosis Treatment in Uganda: 8-Year Retrospective Cohort Study.

Background: Adverse drug events (ADEs) are regarded as the most essential therapeutic issue during management of drug-resistant tuberculosis (DR-TB) due to the long duration of therapy and concurrent use of many second-line medications. This study aimed to determine the incidence and factors associated with ADEs among patients receiving DR-TB treatment at Mulago hospital in Uganda. Methods: A retrospective cohort study was conducted among 417 DR-TB patient records at Mulago National Referral Hospital from January 2013 to December 2020. Using the data abstraction form, data were collected on socio-demographic and clinical factors, adverse drug events and treatment follow-up time. Data were double entered in Epi data version 3.2 and later exported to Stata version 14.0 for analysis. The incidence rate of adverse drug events was computed using number of cases of ADE divided by overall patient follow-up time. Poisson regression model was used to determine the factors associated with ADEs. The predictors were considered significant at if p< 0.05. Results: The overall incidence was 5.56 ADEs per 100 person months (95% confidence interval (CI) 5.01, 6.15). Treatment regimens containing an aminoglycoside (incident rate ratio (IRR) 1.106, 95% CI 1.005-1.216 p=0.0391), linezolid (IRR 1.145, 95% CI 1.008-1.229 p = 0.037) or pyrazinamide (IRR 1.226, 95% CI 1.072-1.401 p = 0.003) and the treatment duration (in months) (IRR 1.005, 95% CI 1.001-1.010 p = 0.042) were associated with ADEs. Conclusion: Regimens containing aminoglycosides, linezolid, or pyrazinamide and increase in treatment duration (months) were associated with an increased risk of ADEs. Clinicians should quickly adopt all oral shorter treatment regimens to obviate the need for aminoglycosides and reduce exposure duration.

Invasive Fungal Diseases in Africa: A Critical Literature Review.

Invasive fungal diseases (IFDs) are of huge concern in resource-limited settings, particularly in Africa, due to the unavailability of diagnostic armamentarium for IFDs, thus making definitive diagnosis challenging. IFDs have non-specific systemic manifestations overlapping with more frequent illnesses, such as tuberculosis, HIV, and HIV-related opportunistic infections and malignancies. Consequently, IFDs are often undiagnosed or misdiagnosed. We critically reviewed the available literature on IFDs in Africa to provide a better understanding of their epidemiology, disease burden to guide future research and interventions. Cryptococcosis is the most encountered IFD in Africa, accounting for most of the HIV-related deaths in sub-Saharan Africa. Invasive aspergillosis, though somewhat underdiagnosed and/or misdiagnosed as tuberculosis, is increasingly being reported with a similar predilection towards people living with HIV. More cases of histoplasmosis are also being reported with recent epidemiological studies, particularly from Western Africa, showing high prevalence rates amongst presumptive tuberculosis patients and patients living with HIV. The burden of pneumocystis pneumonia has reduced significantly probably due to increased uptake of anti-retroviral therapy among people living with HIV both in Africa, and globally. Mucormycosis, talaromycosis, emergomycosis, blastomycosis, and coccidiomycosis have also been reported but with very few studies from the literature. The emergence of resistance to most of the available antifungal drugs in Africa is yet of huge concern as reported in other regions. IFDs in Africa is much more common than it appears and contributes significantly to morbidity and mortality. Huge investment is needed to drive awareness and fungi related research especially in diagnostics and antifungal therapy.