Tuberculosis risk among people with diabetes mellitus in Sub-Saharan Africa: A systematic review.

OBJECTIVES: People with diabetes mellitus (DM) have a higher tuberculosis (TB) risk, but the evidence from sub-Saharan Africa (SSA) was scarce until recently and not included in earlier global summaries. Therefore, this systematic review aims to determine the risk of active TB disease among people with DM in SSA and whether HIV alters this association. METHODS: Medline, Embase, CINAHL, Web of Science, Global Health and African Index Medicus were searched between January 1980 and February 2021. Cohort, case-control and cross-sectional studies from SSA, which assessed the association between DM and active TB, were included if adjusted for age. Two researchers independently assessed titles, abstracts, full texts, extracted data and assessed the risk of bias. Estimates for the association between DM and TB were summarised using a random effects meta-analysis. PROSPERO: CRD42021241743. RESULTS: Nine eligible studies were identified, which reported on 110,905 people from 5 countries. Individual study odds ratios (OR) of the TB-DM association ranged from 0.88 (95% CI 0.17-4.58) to 10.7 (95% CI 4.5-26). The pooled OR was 2.77 (95% CI 1.90-4.05). High heterogeneity was reduced in sensitivity analysis (from I2  = 57% to I2  = 6.9%), by excluding one study which ascertained DM by HbA1c. Risk of bias varied widely between studies, especially concerning the way in which DM status was determined. CONCLUSIONS: There is a strong positive association between DM and active TB in SSA. More research is needed to determine whether HIV, a key risk factor for TB in SSA, modifies this relationship.

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.

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.

Indicators of optimal diabetes care and burden of diabetes complications in Africa: a systematic review and meta-analysis.

OBJECTIVE: Contemporary data on the attainment of optimal diabetes treatment goals and the burden of diabetes complications in adult populations with type 2 diabetes in Africa are lacking. We aimed to document the current status of attainment of three key indicators of optimal diabetes care and the prevalence of five diabetes complications in adult African populations with type 2 diabetes. METHODS: We systematically searched Embase, PubMed and the Cochrane library for published studies from January 2000 to December 2020. Included studies reported any information on the proportion of attainment of optimal glycated haemoglobin (HbA1c), blood pressure (BP) and low-density lipoprotein cholesterol (LDLC) goals and/or prevalence of five diabetes complications (diabetic peripheral neuropathy, retinopathy, nephropathy, foot ulcers and peripheral arterial disease). Random effect model meta-analysis was performed to determine the pooled proportion of attainment of the three treatment goals and the prevalence of five diabetes complications. RESULTS: In total, 109 studies with a total of 63 890 participants (53.3% being females) were included in the meta-analysis. Most of the studies were conducted in Eastern African countries (n=44, 40.4%). The pooled proportion of attainment of an optimal HbA1c, BP and LDLC goal was 27% (95% CI 24 to 30, I2=94.7%), 38% (95% CI 30 to 46, I2=98.7%) and 42% (95% CI 32 to 52, I2=97.4%), respectively. The pooled prevalence of diabetic peripheral neuropathy, retinopathy, diabetic nephropathy, peripheral arterial disease and foot ulcers was 38% (95% CI 31 to 45, I2=98.2%), 32% (95% CI 28 to 36, I2=98%), 31% (95% CI 22 to 41, I2=99.3%), 19% (95% CI 12 to 25, I2=98.1%) and 11% (95% CI 9 to 14, I2=97.4%), respectively. CONCLUSION: Attainment of optimal diabetes treatment goals, especially HbA1c, in adult patients with type 2 diabetes in Africa remains a challenge. Diabetes complications, especially diabetic peripheral neuropathy and retinopathy, are highly prevalent in adult populations with type 2 diabetes in Africa.

Rifapentine and isoniazid for prevention of tuberculosis in people with diabetes (PROTID): protocol for a randomised controlled trial.

BACKGROUND: Diabetes mellitus (DM) increases the risk of tuberculosis (TB) and will hamper global TB control due to the dramatic rise in type 2 DM in TB-endemic settings. In this trial, we will examine the efficacy and safety of TB preventive therapy against the development of TB disease in people with DM who have latent TB infection (LTBI), with a 12-week course of rifapentine and isoniazid (3HP). METHODS: The 'Prevention of tuberculosis in diabetes mellitus' (PROTID) consortium will randomise 3000 HIV-negative eligible adults with DM and LTBI, as evidenced by a positive tuberculin skin test or interferon gamma release assay, to 12 weeks of 3HP or placebo. Participants will be recruited through screening adult patients attending DM clinics at referral hospitals in Tanzania and Uganda. Patients with previous TB disease or treatment with a rifamycin medication or isoniazid (INH) in the previous 2 years will be excluded. The primary outcome is the occurrence of definite or probable TB disease; secondary outcome measures include adverse events, all-cause mortality and treatment completion. The primary efficacy analysis will be intention-to-treat; per-protocol analyses will also be carried out. We will estimate the ratio of TB incidence rates in intervention and control groups, adjusting for the study site using Poisson regression. Results will be reported as efficacy estimates (1-rate ratio). Cumulative incidence rates allowing for death as a competing risk will also be reported. Approximately 1000 LTBI-negative, HIV-negative participants will be enrolled consecutively into a parallel cohort study to compare the incidence of TB in people with DM who are LTBI negative vs positive. A number of sub-studies will be conducted among others to examine the prevalence of LTBI and active TB, estimate the population impact and cost-effectiveness of LTBI treatment in people living with DM in these African countries and address gaps in the prevention and therapeutic management of combined TB-DM. DISCUSSION: PROTID is anticipated to generate key evidence to guide decisions over the use of TB preventive treatment among people with DM as an important target group for better global TB control. TRIAL REGISTRATION: ClinicalTrials.gov NCT04600167 . Registered on 23 October 2020.

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.

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.

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.

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.