Gender differences among patients with drug resistant tuberculosis and HIV co-infection in Uganda: a countrywide retrospective cohort study

Background Gender differences among patients with drug resistant tuberculosis (DRTB) and HIV co-infection could affect treatment outcomes. We compared characteristics and treatment outcomes of DRTB/HIV co-infected men and women in Uganda. Methods We conducted a retrospective chart review of patients with DRTB from 16 treatment sites in Uganda. Eligible patients were aged ≥ 18 years, had confirmed DRTB, HIV co-infection and a treatment outcome registered between 2013 and 2019. We compared socio-demographic and clinical characteristics and tuberculosis treatment outcomes between men and women. Potential predictors of mortality were determined by cox proportional hazard regression analysis that controlled for gender. Statistical significance was set at p < 0.05. Results Of 666 DRTB/HIV co-infected patients, 401 (60.2%) were men. The median (IQR) age of men and women was 37.0 (13.0) and 34.0 (13.0) years respectively (p < 0.001). Men were significantly more likely to be on tenofovir-based antiretroviral therapy (ART), high-dose isoniazid-containing DRTB regimen and to have history of cigarette or alcohol use. They were also more likely to have multi-drug resistant TB, isoniazid and streptomycin resistance and had higher creatinine, aspartate and gamma-glutamyl aminotransferase and total bilirubin levels. Conversely, women were more likely to be unemployed, unmarried, receive treatment from the national referral hospital and to have anemia, a capreomycin-containing DRTB regimen and zidovudine-based ART. Treatment success was observed among 437 (65.6%) and did not differ between the genders. However, mortality was higher among men than women (25.7% vs. 18.5%, p = 0.030) and men had a shorter mean (standard error) survival time (16.8 (0.42) vs. 19.0 (0.46) months), Log Rank test (p = 0.046). Predictors of mortality, after adjusting for gender, were cigarette smoking (aHR = 4.87, 95% CI 1.28–18.58, p = 0.020), an increase in alanine aminotransferase levels (aHR = 1.05, 95% CI 1.02–1.07, p < 0.001), and history of ART default (aHR = 3.86, 95% CI 1.31–11.37, p = 0.014) while a higher baseline CD4 count was associated with lower mortality (aHR = 0.94, 95% CI 0.89–0.99, p = 0.013 for every 10 cells/mm$^{3}$ increment). Conclusion Mortality was higher among men than women with DRTB/HIV co-infection which could be explained by several sociodemographic and clinical differences

Treatment of Histoplasmosis

Histoplasmosis, caused by the thermally dimorphic fungus Histoplasma capsulatum, is an uncommon multisystem disease with a global distribution. The spectrum of clinical manifestations ranges from an asymptomatic or minimally symptomatic acute pulmonary disease following inhalation of a large inoculum of Histoplasma microconidia to chronic pulmonary disease in patients with underlying structural lung disease. It also extends to acute progressive disseminated disease in patients with severe immunodeficiency. Generally, antifungal therapy is indicated for patients with progressive acute pulmonary histoplasmosis, chronic pulmonary histoplasmosis and acute progressive disseminated histoplasmosis. In immunocompetent patients, acute pulmonary histoplasmosis may be a self-limiting disease without the need for systemic antifungal therapy. Oral triazole antifungal drugs alone are recommended for less severe disease. However, moderate-to-severe acute pulmonary histoplasmosis requires intravenous amphotericin B therapy for at least 1–2 weeks followed by oral itraconazole for at least 12 weeks. For acute progressive disseminated histoplasmosis, intravenous amphotericin B therapy is given for at least 2 weeks (4–6 weeks if meningeal involvement) or until a patient can tolerate oral therapy, followed by oral itraconazole (or an alternative triazole) for at least 12 months. Chronic cavitary pulmonary histoplasmosis is treated with oral itraconazole for 1–2 years. There is insufficient evidence to support the use of isavuconazole or the echinocandins for the treatment of histoplasmosis

Cardiovascular risk factors among people with drug-resistant tuberculosis in Uganda

This work was funded by the National Institute for Health Research through the Royal Society of Tropical Medicine and Hygiene.Background Tuberculosis (TB) and its risk factors are independently associated with cardiovascular disease (CVD). We determined the prevalence and associations of CVD risk factors among people with drug-resistant tuberculosis (DRTB) in Uganda. Methods In this cross-sectional study, we enrolled people with microbiologically confirmed DRTB at four treatment sites in Uganda between July to December 2021. The studied CVD risk factors were any history of cigarette smoking, diabetes mellitus (DM) hypertension, high body mass index (BMI), central obesity and dyslipidaemia. We used modified Poisson regression models with robust standard errors to determine factors independently associated with each of dyslipidaemia, hypertension, and central obesity. Results Among 212 participants, 118 (55.7%) had HIV. Overall, 196 (92.5%, 95% confidence interval (CI) 88.0-95.3) had ≥ 1 CVD risk factor. The prevalence; 95% CI of individual CVD risk factors was: dyslipidaemia (62.5%; 55.4–69.1), hypertension (40.6%; 33.8–47.9), central obesity (39.3%; 32.9–46.1), smoking (36.3%; 30.1–43.1), high BMI (8.0%; 5.0–12.8) and DM (6.5%; 3.7–11.1). Dyslipidaemia was associated with an increase in glycated haemoglobin (adjusted prevalence ratio (aPR) 1.14, 95%CI 1.06–1.22). Hypertension was associated with rural residence (aPR 1.89, 95% CI 1.14–3.14) and previous history of smoking (aPR 0.46, 95% CI 0.21–0.98). Central obesity was associated with increasing age (aPR 1.02, 95%CI 1.00–1.03), and elevated diastolic blood pressure (aPR 1.03 95%CI 1.00–1.06). Conclusion There is a high prevalence of CVD risk factors among people with DRTB in Uganda, of which dyslipidaemia is the commonest. We recommend integrated services for identification and management of CVD risk factors in DRTB.Publisher PDFPeer reviewe

Cryptococcosis complicating diabetes mellitus: a scoping review.

BACKGROUND: A better understanding of the epidemiology of cryptococcal infection in HIV-negative individuals is an international research interest. Immune dysfunction in diabetes mellitus (DM) significantly increases the risk of acquiring and reactivation of infection due to Cryptococcus neoformans. Risk factors and outcomes of cryptococcosis in DM are not well documented. OBJECTIVE: The objective of this study was to determine the clinical characteristics and outcomes of cryptococcal infections in persons living with DM. METHODS: MEDLINE (via PubMed), EMBASE, and the Cochrane Library databases were searched in November 2020. The searches covered the period between 1980 and 2020.We included studies that reported confirmed cryptococcosis in patients with DM. Reference lists of included articles were also searched, and additional studies were included if appropriate. No language restriction was applied. Single case reports, case series and original articles were included whereas review articles were excluded. RESULTS: A total of 28 studies (24 single case reports, 4 retrospectives) were included involving 47 unique patients from Asia (17 cases), North America (six cases), South America (three cases) and Africa (two cases). Men constituted 75% (n = 18) of the cases. Median age was 60.5 (range: 27-79) years. The majority of the patients had cryptococcal meningitis (68.1%, n = 32) followed by disseminated cryptococcosis (6.4%, n = 7), and others (isolated cutaneous disease one, peritonitis one, pleural one, thyroid one, adrenal one). Diagnosis was achieved through either culture and microscopy (38/47), cryptococcal antigen tests (9/47) or histopathology (9/47) singly or in a combination. All-cause mortality was 38.3% (n = 18). Among those with meningitis mortality was 36.2%. CONCLUSION: A wide spectrum of cryptococcal infections with varying severity occurs in DM. Mortality remains unacceptably high. There is a need for more studies to characterize better cryptococcal disease in DM

Optimizing diabetes mellitus care to improve COVID-19 outcomes in resource-limited settings in Africa

Diabetes mellitus (DM) is an important risk factor for both severe disease and death due to coronavirus-2019 (COVID-19). About 19 million of the 463 million persons living with DM (PLWD) globally are found in sub-Saharan Africa (SSA). The dual burden of DM and poverty in SSA, coupled with the rising number of cases of COVID-19 in this region, predisposes PLWD to inadequate care and poor glycemic controls due to the disruption to the economy and the healthcare system. The risk of acquisition of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) among PLWD is the same as those in the general population. Therefore, the standard preventive measures outlined by the World Health Organization must be strictly adhered to. In addition, maintaining adequate glycemic control is associated with better outcomes in DM patients with COVID-19. In SSA, adequate supply of DM medication while patients stay at home is crucial to minimize routine hospital visits since DM clinics are usually overcrowded and have longer waiting times, which may maximize risk of SARS-CoV-2 transmission to PLWD across the region. Psychosocial support to improve adherence to anti-hyperglycemic medications may improve COVID-19 outcomes. Trained healthcare professionals should diagnose and evaluate severity comprehensively as well as evaluate the need for in-patient care for PLWD with COVID-19 irrespective of disease severity. Due to the increased risk of severe disease, a multi-disciplinary approach to the management of COVID-19 in PLWD should preferably be in a setting where close monitoring is available, typically a health facility, even for mild disease that may require home management according to local guidelines. In conclusion, DM complicates COVID-19 outcomes and the on-going COVID-19 pandemic adversely affects DM care at individual and global public health levels. PLWD should be prioritized as COVID-19 vaccines are being rolled out

Hyperglycemia in pregnancy diagnosed using glycated hemoglobin (HbA1c) in Uganda: a preliminary cross-sectional report

Background: Hyperglycemia in pregnancy (HIP) is a common medical complication during pregnancy and is associated with several short and long-term maternal-fetal consequences. We aimed to determine the prevalence and factors associated with HIP among Ugandan women. Methods: We consecutively enrolled eligible pregnant women attending antenatal care at Kawempe National Referral Hospital, Kampala, Uganda in September 2020. Mothers known to be living with diabetes mellitus or haemoglobinopathies and those with anemia (hemoglobin &lt;11g/dl) were excluded. Random blood sugar (RBS) and glycated hemoglobin A1c (HbA1c) were measured on peripheral venous blood samples. HIP was defined as an HbA1c ?5.7% with its subsets of diabetes in pregnancy (DIP) and prediabetes defined as HbA1c of ?6.5% and 5.7-6.4% respectively. ROC curve analysis was performed to determine the optimum cutoff of RBS to screen for HIP. Results: A total of 224 mothers with a mean (± SD) age 26±5 years were enrolled, most of whom were in the 2nd or 3rd trimester (94.6%, n=212) with a mean gestation age of 26.6±7.3 weeks. Prevalence of HIP was 11.2% (n=25) (95% CI: 7.7-16.0). Among the mothers with HIP, 2.2% (n=5) had DIP and 8.9% (n=20) prediabetes. Patients with HIP were older (28 years vs. 26 years, p=0.027), had previous tuberculosis (TB) contact (24% vs. 6.5%, p=0.003) and had a bigger hip circumference (107.8 (±10.4) vs. 103.3 (±9.7) cm, p = 0.032). However only previous TB contact was predictive of HIP (odds ratio: 4.4, 95% CI: 1.2-14.0; p=0.022). Using HbA1c as a reference variable, we derived an optimum RBS cutoff of 4.75 mmol/L as predictive of HIP with a sensitivity and specificity of 90.7% and 56.4% (area under the curve = 0.75 (95% CI: 0.70-0.80, p&lt;0.001)), respectively. Conclusions: HIP is common among young Ugandan women, the majority of whom are without identifiable risk factors.</ns4:p

Anemia in Ugandan pregnant women: a cross-sectional, systematic review and meta-analysis study.

Background Anemia in pregnancy represents a global public health concern due to wide ranging maternal and neonatal adverse outcomes in all peripartum periods. We estimated the prevalence and factors associated with anemia in pregnancy at a national obstetrics and gynecology referral hospital in Uganda and in addition performed a systematic review and meta-analysis of the overall burden of anemia in pregnancy in Uganda. Methods We conducted a cross-sectional study among 263 pregnant women attending the antenatal care clinic of Kawempe National Referral Hospital, Kampala, Uganda, in September 2020. Anemia in pregnancy was defined as a hemoglobin level of < 11.0 g/dl and microcytosis as a mean corpuscular volume (MCV) of < 76 fL. We also performed a systematic review (PROSPERO Registration ID: CRD42020213001) and meta-analysis of studies indexed on MEDLINE, Embase, African Journal Online, ClinicalTrials.gov , ICTRP, and the Cochrane Library of systematic review between 1 January 2000 and 31 September 2020 reporting on the prevalence of anemia in pregnancy in Uganda. Results The prevalence of anemia was 14.1% (n= 37) (95%CI 10.4-18.8), of whom 21 (56.8%) had microcytic anemia. All cases of anemia occurred in the second or third trimester of pregnancy and none were severe. However, women with anemia had significantly lower MCV (75.1 vs. 80.2 fL, p<0.0001) and anthropometric measurements, such as weight (63.3 vs. 68.9kg; p=0.008), body mass index (25.2 vs. 27.3, p=0.013), hip (98.5 vs. 103.8 cm, p=0.002), and waist (91.1 vs. 95.1 cm, p=0.027) circumferences and mean systolic blood pressure (BP) (118 vs 125 mmHg, p=0.014). Additionally, most had BP within the normal range (59.5% vs. 34.1%, p=0.023). The comparison meta-analysis of pooled data from 17 published studies of anemia in pregnancy in Uganda, which had a total of 14,410 pregnant mothers, revealed a prevalence of 30% (95% CI 23-37). Conclusions Despite our study having a lower prevalence compared to other studies in Uganda, these findings further confirm that anemia in pregnancy is still of public health significance and is likely to have nutritional causes, requiring targeted interventions. A larger study would be necessary to demonstrate potential use of basic clinical parameters such as weight or blood pressure as screening predictors for anemia in pregnancy

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

Latent Tuberculosis Infection Status of Pregnant Women in Uganda Determined Using QuantiFERON TB Gold-Plus.

BACKGROUND: The risk of progression of latent tuberculosis infection (LTBI) to active disease increases with pregnancy. This study determined the prevalence and risk factors associated with LTBI among pregnant women in Uganda. METHODS: We enrolled 261 pregnant women, irrespective of gestational age. Participants who had known or suspected active tuberculosis (TB) on the basis of clinical evaluation or who had recently received treatment for TB were excluded. LTBI was defined as an interferon-γ concentration ≥0.35 IU/mL (calculated as either TB1 [eliciting CD4+ T-cell responses] or TB2 [eliciting CD8+ T-cell responses] antigen minus nil) using QuantiFERON TB Gold-Plus (QFT-plus) assay. RESULTS: LTBI prevalence was 37.9% (n = 99) (95% confidence interval [CI], 32.3-44.0). However, 24 (9.2%) subjects had indeterminate QFT-plus results. Among participants with LTBI, TB1 and TB2 alone were positive in 11 (11.1%) and 18 (18.2%) participants, respectively. In multivariable analysis, human immunodeficiency virus (HIV) infection (adjusted odds ratio [aOR], 4.4 [95% confidence interval {CI}, 1.1-18.0]; P = .04) and age 30-39 years (aOR, 4.0 [95% CI, 1.2-12.7]; P = .02) were independently associated with LTBI. Meanwhile, smoking status, alcohol use, nature of residence, crowding index, and TB contact were not associated with LTBI. CONCLUSIONS: Our findings are in keeping with the evidence that HIV infection and advancing age are important risk factors for LTBI in pregnancy. In our setting, we recommend routine screening for LTBI and TB preventive therapy among eligible pregnant women

HIV, tuberculosis, diabetes mellitus and hypertension admissions and premature mortality among adults in Uganda from 2011 to 2019: is the tide turning?

BACKGROUND: The growing burden of diabetes mellitus (DM) and hypertension (HTN) on the background of endemic Human Immuno-deficiency Virus (HIV) and tuberculosis (TB) is a concern in low- and middle-income countries. We aimed to describe annual trends in admissions, mortality rates and premature mortality (years of potential life lost-YPLLs) due to HIV, tuberculosis (TB), diabetes mellitus (DM) and hypertension (HTN) in Uganda. METHODS: We conducted a retrospective cohort study, retrieving electronic records of adults admitted to Mulago and Kiruddu national referral hospitals medical wards between 1st January 2011 and 31st December 2019. We used STATA BE 17.0 and GraphPad Prism 8.0.2 to compute total admissions, inpatient crude mortality rates, and YPLLs; and demonstrate trends using Mann-Kendall test. RESULTS: Of 108,357 admissions, 55,620 (51.3%) were female, 15,300 (14.1%) were recorded in 2012, and 22,997 (21.2%) were aged 21-30 years. HIV, TB, DM and HTN accounted for 26,021 (24.0%); 9537 (8.8%); 13,708 (12.7) and 13,252 (12.2%) of all admissions, respectively. Overall inpatient mortality was 16.7% (18,099/108,357), 53.5% (9674/18,099) were male, 21.5% (3898) were aged 31-40 years and 2597 (14.4%) were registered in 2013. HIV, TB, DM and HTN accounted for 35.6% (6444), 14.6% (2646), 9.1% (1648) and 11.8% (2142) of all deaths, respectively. Total admissions (Kendall's tau-B = - 0.833, p < 0.001) and deaths declined (Kendall's tau-B = - 0.611, p = 0.029). A total of 355,514 (mean = 20.8 years, SD 30.0) YPLLs were recorded, of which 54.6% (191,869) were in males; 36.2% (128,755) were among those aged 21-30 years and were recorded in 2012 (54,717; 15.4%). HIV, TB, DM and HTN accounted for 46.5% (165,352); 19.5% (69,347); 4.8% (16,991) and 4.5% (16,167) of YPLLs, respectively. Proportionate contribution of HIV to deaths and YPLLs declined, remained stagnant for TB; and increased for both DM and HTN. CONCLUSION: TB and HIV account for higher though declining, while DM and HTN account for lower albeit rising morbidity and premature mortality among adult medical patients in Uganda. TB prevention and treatment; and DM/HTN service integration in HIV care should be optimized and scaled up