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

Burden and associated phenotypic characteristics of tuberculosis infection in adult Africans with diabetes: a systematic review.

Diabetes mellitus (DM) increases the risk of developing tuberculosis infection (TBI). However, the evidence on the burden and phenotypic characteristics of TBI in African patients with DM is limited. This study aimed to determine the prevalence and characterisation of TBI in native African patients living with DM. We searched PubMed, EMBASE, and African Journals Online for original studies reporting information on the prevalence and characteristics of TBI in adult Africans with DM. A forest plot was used to describe the pooled prevalence estimate of TBI and the corresponding 95% confidence intervals (CI). Six studies conducted in four African countries involving 721 participants with DM were included in this systematic review. The pooled prevalence estimate of TBI was 40% (95% CI 20-60%, I2 = 98.52%, p < 0.001). Age ≥ 40 years and glycated haemoglobin levels independently predicted TBI positivity in patients with DM in three studies. Africans with DM have a high prevalence of TBI, especially those who are older or with poorly controlled diabetes. This justifies the need for studies to explore how to screen and manage TBI to avert the progression to active TB disease

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

Causes of Perinatal Death at a Tertiary Care Hospital in Northern Tanzania 2000-2010: A Registry Based Study.

Perinatal mortality reflects maternal health as well as antenatal, intrapartum and newborn care, and is an important health indicator. This study aimed at classifying causes of perinatal death in order to identify categories of potentially preventable deaths. We studied a total of 1958 stillbirths and early neonatal deaths above 500 g between July 2000 and October 2010 registered in the Medical Birth Registry and neonatal registry at Kilimanjaro Christian Medical Centre (KCMC) in Northern Tanzania. The deaths were classified according to the Neonatal and Intrauterine deaths Classification according to Etiology (NICE). Overall perinatal mortality was 57.7/1000 (1958 out of 33 929), of which 1219 (35.9/1000) were stillbirths and 739 (21.8/1000) were early neonatal deaths. Major causes of perinatal mortality were unexplained asphyxia (n=425, 12.5/1000), obstetric complications (n=303, 8.9/1000), maternal disease (n=287, 8.5/1000), unexplained antepartum stillbirths after 37 weeks of gestation (n= 219, 6.5/1000), and unexplained antepartum stillbirths before 37 weeks of gestation (n=184, 5.4/1000). Obstructed/prolonged labour was the leading condition (251/303, 82.8%) among the obstetric complications. Preeclampsia/eclampsia was the leading cause (253/287, 88.2%) among the maternal conditions. When we excluded women who were referred for delivery at KCMC due to medical reasons (19.1% of all births and 36.0% of all deaths), perinatal mortality was reduced to 45.6/1000. This reduction was mainly due to fewer deaths from obstetric complications (from 8.9 to 2.1/1000) and maternal conditions (from 8.5 to 5.5/1000). The distribution of causes of death in this population suggests a great potential for prevention. Early identification of mothers at risk of pregnancy complications through antenatal care screening, teaching pregnant women to recognize signs of pregnancy complications, timely access to obstetric care, monitoring of labour for fetal distress, and proper newborn resuscitation may reduce some of the categories of deaths

Processes and dynamics of linkage to care from mobile/outreach and facility‑based HIV testing models in hard‑to‑reach settings in rural Tanzania. Qualitative findings of a mixed methods study

BACKGROUND: Like other countries, Tanzania instituted mobile and outreach testing approaches to address low HIV testing rates at health facilities and enhance linkage to care. Available evidence from hard-to-reach rural settings of Mbeya region, Tanzania suggests that clients testing HIV+ at facility-based sites are more likely to link to care, and to link sooner, than those testing at mobile sites. This paper (1) describes the populations accessing HIV testing at mobile/outreach and facility-based testing sites, and (2) compares processes and dynamics from testing to linkage to care between these two testing models from the same study context. METHODS: An explanatory sequential mixed-method study (a) reviewed records of all clients (n = 11,773) testing at 8 mobile and 8 facility-based testing sites over 6 months; (b), reviewed guidelines; (c) observed HIV testing sites (n = 10) and Care and Treatment Centers (CTCs) (n = 8); (d) applied questionnaires at 0, 3 and 6 months to a cohort of 1012 HIV newly-diagnosed clients from the 16 sites; and (e) conducted focus group discussions (n = 8) and in-depth qualitative interviews with cohort members (n = 10) and health care providers (n = 20). RESULTS: More clients tested at mobile/outreach than facility-based sites (56% vs 44% of 11,733, p < 0.001). Mobile site clients were more likely to be younger and male (p < 0.001). More clients testing at facility sites were HIV positive (21.5% vs. 7.9% of 11,733, p < 0.001). All sites in both testing models adhered to national HIV testing and care guidelines. Staff at mobile sites showed more proactive efforts to support linkage to care, and clients report favouring the confidentiality of mobile sites to avoid stigma. Clients who tested at mobile/outreach sites faced longer delays and waiting times at treatment sites (CTCs). CONCLUSIONS: Rural mobile/outreach HIV testing sites reach more people than facility based sites but they reach a different clientèle which is less likely to be HIV +ve and appears to be less “linkage-ready”. Despite more proactive care and confidentiality at mobile sites, linkage to care is worse than for clients who tested at facility-based sites. Our findings highlight a combination of (a) patient-level factors, including stigma; and (b) well-established procedures and routines for each step between testing and initiation of treatment in facility-based sites. Long waiting times at treatment sites are a further barrier that must be addressed

Juvenile dermatomyositis in a 4-year-old Kenyan girl

To our knowledge, this is the first case report of juvenile dermatomyositis (JDM) in Tanzania. It demonstrates that the characteristic cutaneous findings of JDM may easily be overlooked, especially on dark skin, and the difficulty of clinical management in resource-constrained settings