Postmortem for Intensified Missed Tuberculosis Case Finding in High Human Immunodeficiency Virus and Tuberculosis-burdened Settings in Sub-Saharan Africa among Adults' Population: Systematic Review and Meta-analysis.

Tuberculosis (TB) is the leading infectious cause of mortality in sub-Saharan Africa (SSA); the high prevalence of TB in this region is due to human immunodeficiency virus (HIV)-coinfection. Despite the advent of modalities to diagnose TB, undiagnosed TB-related deaths among HIV-infected patients remain significantly high. This systematic review aims at characterizing missed TB cases from postmortem studies. This review informs on the burden of TB missed diagnosis and highlights the need of improving TB case-finding strategies, especially among the high-risk groups and early TB therapy initiation to keeping in with the World Health Organization's end TB strategy. We searched PubMed, Cochrane, Web of Science, and African journals online for studies that looked into missed TB cases following postmortem using the following key terms: postmortem, TB diagnosis, and HIV; we included cross-sectional and cohorts from 1980 in the English language that were carried out in SSA among adults' population. Authors used the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines for reporting, the quality of the included studies was assessed using the Newcastle-Ottawa Scale for observational studies, and STATA 17.0 software was used for analysis. This study was registered in the International Prospective Register of Systematic Reviews with registration number CRD42024507515. The combined prevalence of postmortem missed TB diagnosis among the 6025 participants was 27.13% (95% confidence interval [CI] =14.52-41.89), with a high level of heterogeneity at 98.65% (P < 0.001). The prevalence varied significantly across the included studies, ranging from 1.21% (95% CI = 0.93-1.59) in the general population to 66.67% (95% CI = 50.98-79.37) in people living with HIV (PLWHIV). This current literature suggests that SSA is a region with a high prevalence of missed TB cases but with significant variations between countries. In addition, this study confirms a high number of missed TB infections within the PLWHIV. These results highlight the immediate need for targeted screening and diagnosis strategies and relevant policies.

Advances in HIV self-testing: Systematic review of current developments and the road ahead in high-burden countries of Africa.

Objectives: Although HIV self-testing technologies have created new opportunities for achieving national and global HIV testing goals, current developments have not been compiled to inform policy and practice, especially in high HIV burden countries of Africa. We aimed to compile and synthesize the evidence about HIV self-testing technologies, strategies, and uptake in the top-10 high HIV burden countries of Africa. Methods: We searched CINAHL, PubMed, Web of Science, PsycINFO, Social Science Citation Index, and EMBASE to include eligible articles published in English between January 2012 and November 2022. Results: In total, 865 articles were retrieved and only 16 studies conducted in five African countries were eligible and included in this review. The two types of HIV self-testing modalities presently being used in Africa are: The first is Home Self-Test which is done entirely at home or in another private location by using oral fluid or blood specimen. The second modality is Mail-In Self-Test (self-sampling), where the user collects their own sample and sends this to a laboratory for testing. Perceived opportunities for the uptake of HIV self-testing were autonomy and self-empowerment, privacy, suitability, creating a chance to test, and simplicity of use. The potential barriers to HIV self-testing included fear and worry of a positive test result, concern of the test results is not reliable, low literacy, and potential psychological and social harms. The oral-fluid self-testing is preferred by most users because it is easy to use, less invasive, and painless. The difficulty of instructions on how to use self-test kits, and the presence of different products of HIV self-testing kits, increase rates of user errors. Conclusion: Adopting HIV self-testing by overcoming the challenging potential barriers could enable early detection, care, treatment, and prevention of the disease to achieve the 95-95-95 goal by 2030. Further study is necessary to explore the actual practices related to HIV self-testing among different populations in Africa.

Efficacy and safety of different regimens in the treatment of patients with latent tuberculosis infection: a systematic review and network meta-analysis of randomized controlled trials.

BACKGROUND: Treatment of latent tuberculosis infection (LTBI) is effective in preventing progression to TB disease. This study aimed to synthesize available evidence on the efficacy, adherence, and safety of LTBI treatment in order to assist policymakers to design appropriate national treatment policies and treatment protocols. METHOD: The PRISMA-NMA was used to review and report this research. Randomized controlled trials which compared the efficacy and safety of LTBI treatments were included. A systematic literature search was done to identify relevant articles from online databases PubMed/ MEDLINE, Embase, and Cochrane Center for Clinical Trial database (CENTRAL). The network meta-analysis was done using R- studio Version 1.4.1103. RESULT: In this review, 42 studies were included, which enrolled 46,022 people who had recent contact with patients with active tuberculosis, evidence radiological of previous tuberculosis, tuberculin test equal or greater than 5 mm, radiographs that indicated inactive fibrotic or calcified parenchymal and/or lymph node lesions, had conversion to positive results on a tuberculin skin test, participants living with HIV, chronic Silicosis, immigrants, prisoners, old people, and pregnant women who were at risk for latent TB were included. The incidence of TB among people living with HIV who have taken 3RH as TPT was lower, followed by 48%,followed by 6H (41%). However, 3HP has also the potential to reduce the incidence of TB by 36% among HIV negative patients who had TB contact history. Patients' adherence to TPT was higher among patients who have taken 4R (RR 1.38 95% CI 1.0,1.89) followed by 3RH (34%). The proportion of subjects who permanently discontinued a study drug because of an adverse event were three times higher in the 3RH treatment group. Furthermore, the risk of grade 3 and 4 liver toxicity was significantly higher in 9H followed by 1HP, and 6H. CONCLUSION: From this review, it can be concluded 3RH and 6H has a significant impact on the reduction of TB incidence among PLWH and 3HP among HIV negative people who had TB contact history. However, combinations of rifampicin either with isoniazid were significantly associated with adverse events which resulted in permanent discontinuation among adult patients. Furthermore, grade 3 and 4 liver toxicity was more common in patents who have taken 9H, 1HP, and 6H. This may support the current recommended TPT regimen of 3HP, 3RH, and 6H.

New onset type 2 diabetes mellitus risks with integrase strand transfer inhibitors-based regimens: A systematic review and meta-analysis.

Objectives: The development of diabetes mellitus (DM) in patients taking integrase strand transfer inhibitors (INSTIs) has raised concerns. It's critical because, in most guidelines, INSTIs are the preferred third agent at first-line regimens. This study investigates the excess risk of developing DM among people living with HIV (PWH) on INSTIs-based regimens compared to those with other combination antiretroviral therapies (cART). Methods: A search from PubMed, clinicaltrials.gov, Latin America and Caribbean health sciences literature, Cochrane, and google scholar to retrieve case-control and cohort studies were done. The literature search was performed for studies from January 2007 to January 2021. Data were extracted from studies and pooled as risk ratios (RR) with a 95% confidence interval (CI) using Stata 14 software. The protocol was registered in PROSPERO, ID: CRD42021230282. Results: This review included ten studies, resulting in 62 400 participants. There was no significant difference in the incidence of DM between participants receiving INSTIs-based regimens versus other cARTs (RR 0.97, 95% CI: 0.92-1.03; participants = 50 958; studies = 4; I2 = 86.8%, chi-square = 22.67). There is no statistically significant difference in DM among people treated with INSTIs-based regimens compared to those treated with boosted protease inhibitors (PIs)-based regimens (RR 0.97, 95% CI 0.92-1.03; participants = 49 840; studies = 3; I2 = 89.3%, chi-square = 18.65). DM incidence was lower in INSTIs-based regimens than in those using non-nucleoside reverse transcriptase inhibitors (NNRTIs)-based regimens (RR 0.80, 95% CI 0.69-0.91; participants = 42 346; studies = 2; I2 = 0%, chi-square = 0.18). Conclusion: The present review shows a nonsignificant difference in the incidence of DM in patients receiving INSTIs-based regimens compared to other regimens. However, there was a lower incidence of DM in the INSTIs group compared to the NNRTIs-based and PIs compared to the NNRTIs-based. When the INSTIs drugs dolutegravir, raltegravir, and elvitegravir were compared, there was a lower incidence of DM in raltegravir compared with elvitegravir.

Digital health in the era of COVID-19: Reshaping the next generation of healthcare.

COVID-19 is one of the most deadly diseases to have stricken us in recent decades. In the fight against this disease, governments and stakeholders require all the assistance they can get from various systems, including digital health interventions. Digital health technologies are supporting the tracking of the COVID-19 outbreak, diagnosing patients, expediting the process of finding potential medicines and vaccines, and disinfecting the environment, The establishment of electronic medical and health records, computerized clinical decision support systems, telemedicine, and mobile health have shown the potential to strengthen the healthcare system. Recently, these technologies have aided the health sector in a variety of ways, including prevention, early diagnosis, treatment adherence, medication safety, care coordination, documentation, data management, outbreak tracking, and pandemic surveillance. On the other hand, implementation of such technologies has questions of cost, compatibility with existing systems, disruption in patient-provider interactions, and sustainability, calling for more evidence on clinical utility and economic evaluations to help shape the next generation of healthcare. This paper argues how digital health interventions assist in the fight against COVID-19 and their opportunities, implications, and limitations.

Post tuberculosis chronic lung disease in tuberculosis HIV coinfected and non-HIV individuals in Sub-Saharan Africa: A systematic review and meta-analysis.

Background: Post tuberculosis (TB) sequelae are faced by many individuals who survive TB. The most common of all is post-TB chronic lung disease (CLD) and pulmonary impairment. We reviewed studies that estimated the prevalence of post-TB CLD in patients with TB only and those with TB-HIV coinfection. Methods: Searched Google scholar, PubMed, African journals online, Embase, and Cochrane Central Register of Clinical Trials from the year 2000 to 01 March 2022 for all designs of studies that examined the impact of post on lung impairment or damage. The protocol was registered in PROSPERO, ID: chronic respiratory disease 42022304628. Results: Three hundred and thirty-six studies were identified and five studies were identified through other sources, four were finally in the meta-analysis with a total of 4382 enrolled participants. All the studies had a low risk of bias; The prevalence of CLD between the TB HIV coinfection and those with TB only was of no statistical significance between the three of the four studies - new statement: the prevalence of CLD in the TB-HIV coinfected group when compared to the group of participants with TB only was not statistically significant in the study. This was seen in three of the four studies. One study was in favor of the high prevalence of CLD in HIV coinfection participants (relative risk [RR] = 0.75 [0.61-0.89] with 95% confidence interval [0.61-0.89]). Conclusions: Post-TB lung disease is still a burden that needs advocation and an increase of awareness is necessary from the health-care level to the communities and societies, especially in regions of high prevalence. Development of guidelines for health-care workers to aid the management of individuals, multi-disciplinary advocacy is necessary for those whom prevention is not too late.

Treatment outcomes of multi-drug resistant tuberculosis patients with or without human immunodeficiency virus co-infection in Africa and Asia: Systematic review and meta-analysis.

Background: Treatment outcomes of multidrug resistant tuberculosis (MDRTB) is a challenge, especially in resource limited settings. The aim of this study was to compare whether Human Immune Virus (HIV) has influence on the treatment outcomes of MDRTB among patients in Africa and Asia. Methods: Studies were searched from PubMed, Google scholar, African Journals online, EBSCOhost and CENTRAL from year 2000 until January 2021. The participants in the studies were reported of using MDRTB treatment regimen and also included those with HIV. Studies published before 2000 were excluded. Quality of the review was assessed by AMSTEL 2 criteria. The Mantel- Haenszel random effects method was used for the analysis, with risk ratio (RR) as an effect estimate, with 95% confidence interval and using Stata 14 software. Results: Nine studies were included in the meta-analysis. Treatment success was low in HIV negative participants (RR 0.62, 95% CI 0.58-0.67). However, death was higher in the HIV co-infected participants. (RR 1.35, 95% CI 1.25-1.45). There was no significant difference in treatment failure among patients with or without HIV. (RR 1.08, 95% CI 0.97-1.20). Consistently, no significant difference was found in lost to follow up (LTF) between the two groups (RR 1.07, 95% CI 0.93-1.20). Conclusion: Treatment success was lower for the MDRTB and HIV co-infections. No significant difference has been found on other outcomes like failure and lost to follow up between patients with HIV co-infected and HIV negative group. The study limitations are that we had only 2 studies representing Asia, and this could have affected the outcome of results. There is need for interventions to improve treatment success in the HIV co-infected group. Other: The protocol was registered in International prospective register of systematic reviews (PROSPERO), ID: CRD42021247883. There was no funding for the review.

Prevalence of occult hepatitis B among HIV-positive individuals in Africa: A systematic review and meta-analysis.

The prevalence of hepatitis B virus among HIV-seropositive individuals is believed to be high, and yet the disease remains neglected in many areas of the continent. Little is known about occult hepatitis in HIV individuals. This review assessed occult hepatitis B infection and its prevalence in the different regions of the African continent. It also determines its prevalence in the HIV population which is endemic in the region. Studies were searched from the Cochrane, google scholar, PubMed/Medline, and African Journals online. Authors included cross-sectional studies, case controls, and cohorts, from 2010 to January 2021, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Participants, Interventions, Comparisons, Outcomes, and Study design frameworks to develop the search strategy. All studies had participants who were HIV-positive, covering different regions of the continent. Risk ratio was used to measure effect size, and Stata 14 software was used for analysis. Eleven studies met the eligibility criteria, with 2567 participants. Overall prevalence of occult hepatitis B was 11.2%. Regional prevalence was 26.5% for the south, 11% for the north, 9.1% for the east, and 8.5% for the western region. Approximately 10% of HIV-seropositive individuals were co-infected with occult hepatitis B virus. Regionally, the prevalence was highest in the southern region and lowest in the west. The prevalence of occult HBV infection was compared between the southern region and the other regions. It was higher in the south compared to the east (risk ratio = 0.87, 95% confidence interval (0.83-0.91)). It was also higher in the south compared to the north (risk ratio = 0.82, 95% confidence interval (0.79-0.85)), and it was also higher in the south compared to the west (risk ratio = 0.85, 95% confidence interval (0.82-0.87)). Public health measures and interventions are required to raise awareness, increase prevention, and reduce spread of the disease. More evidence-based studies need to be carried out.

HIV Protease Inhibitors and Insulin Sensitivity: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Protease inhibitors (PIs) are believed to affect insulin sensitivity. We aimed to analyze the effect of PIs on insulin sensitivity and the onset of diabetes mellitus (DM) in patients with HIV. Methodology: We searched PubMed, Google Scholar, ClinicalTrals.gov, and the WHO International Clinical Trials Registry Platform till November 2020 for randomized controlled trials (RCTs) that studied the effects of PIs on insulin sensitivity and DM in patients with HIV. We followed the PRISMA and PICOS frameworks to develop the search strategy. We used the random-effects meta-analysis model to estimate the mean difference (MD), standardized mean difference (SMD), and risk ratios for our outcomes, using Stata 14 software. Results: We included nine RCTs that enrolled 1,000 participants, with their ages ranging from 18 to 69 years. The parameters and investigations used in the studies to determine insulin sensitivity were glucose disposal rates, hyperglycemia, and mean glucose uptake. The majority of results showed an association between PIs and insulin sensitivity. The pooled analysis showed no statistically significant difference in insulin sensitivity with atazanavir, whether the study was performed on healthy individuals for a short term or long term in combination with other drugs like tenofovir or emtricitabine [SMD = 0.375, 95% CI (0.035, 0.714)]. The analysis showed reduced glucose disposal rates and hence reduced insulin sensitivity with lopinavir (heterogeneity chi-squared = 0.68, I-squared [variation in SMD attributable to heterogeneity] = 0.0%, p = 0.031). The heterogeneity with chi-squared was substantial (61-80%), while with I-squared was not significant (0-40%), p = 0.031). Less adverse events were observed with atazanavir than with lopinavir [RR = 0.987, 95% CI (0.849, 1.124)]. Darunavir and indinavir did not demonstrate any significant changes in insulin sensitivity. Most of the studies were found to have a low risk of bias. Conclusions: There are significant variations in the effects of PIs on insulin sensitivity and onsets of DM. Atazanavir, fosamprenavir, and darunavir did not demonstrate any significant changes in insulin sensitivity, compared to the rest of the group. There is a need to assess the benefits of PIs against the long-term risk of impaired insulin sensitivity. All patients newly diagnosed with HIV should have DM investigations before the start of ARVs and routinely. RCTs should focus on sub-Saharan Africa as the region is worst affected by HIV, but limited studies have been documented.

COVID-19 and Health Sector Development Plans in Africa: The Impact on Maternal and Child Health Outcomes in Uganda.

INTRODUCTION: Health Sector Development Plans (HSDPs) aim to accelerate movement towards achieving sustainable development goals for health, reducing inequalities, and ending poverty. Reproductive, maternal, newborn and child health (RMNCH) services are vulnerable to economic imbalances, including health insecurity, unmet need for healthcare, and low health expenditure. The same vulnerability influences the potential of a country to combat global outbreaks such as the COVID-19. We aimed to provide some important insights into the impacts of COVID-19 on RMNCH indicators and outcomes of the HSDP in Uganda. METHODS: We conducted a descriptive study of secondary data obtained from the Ugandan government-led portals, supplemented by analyses of relevant articles published up to 06 May 2021 and deposited in PubMed. RESULTS: Through synthesizing actionable and relevant evidence, we realized that RMNCH in Uganda is highly affected by the COVID-19 pandemic and the lockdown measures. The impact was across immunization, antenatal, sexual and reproductive health, emergency and obstetric, and postnatal care services. There was a decline sharply by 9.6% for under-five vitamin A coverage, 9% for DPT3HibHeb3 coverage, 6.8% for measles vaccination coverage, 6% for isoniazid preventive therapy coverage, and 3% for facility-based deliveries. Maternal and under-five deaths increased by 7.6% and 4%, respectively. Outreaches were rarely conducted in the lockdown period. CONCLUSION: The COVID-19 pandemic has created a multitude of questions regarding the optimal policies to mitigate the disease while minimizing the unintended detrimental consequences of RMNCH. The lockdown restrictions threatened to reverse the progress made on the national HSDP for RMNCH. In Uganda, where young women are vulnerable to early marriage, unintended pregnancies, and unsafe abortion, access to RMNCH services should continue regardless of the COVID-19 status in the country. We urge that Uganda and other African countries should build resilient and sustainable health systems that can withstand emerging diseases like the COVID-19.

Human papillomavirus self-sampling versus standard clinician-sampling for cervical cancer screening in sub-Saharan Africa: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Human papillomavirus (HPV) infection remains a major health threat in sub-Saharan Africa (SSA). HPV self-sampling could help find and treat cervical cancer at an early stage. We aimed to evaluate the effectiveness of HPV self-sampling over the standard health facility-based clinician-sampling for cervical cancer screening through a systematic review and meta-analysis of available randomized controlled trials. METHOD: We searched PubMed, Cochrane Central Register of Controlled Trials, ClinicalTrial.gov, and the WHO Global Health Library for articles in SSA published as of 31 May 2020. We followed the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) 2015 guidelines for the design and reporting of the results. We included randomized control trials that compared HPV self-sampling with the standard of care. The primary endpoint was uptake of cervical cancer screening service. The secondary endpoints were linkage to care, acceptability, screening frequency, and adverse events. We used RevMan V.5.3 software for statistical analysis. We computed random-effect model to provide pooled estimates of available data and I-squared (I2) test to assess heterogeneity. RESULT: Of 77 citations, we included four trials from Nigeria, Ethiopia, Kenya, and Uganda, encompassing 8200 participants with age ranging from 25 to 65 years. The pooled analysis showed significantly higher uptake of cervical cancer screening in women who used HPV self-sampling (risk ratio [RR] 1.72, 95% CI 1.58-1.87; p = 0.01), while this had a considerable heterogeneity as explained by subgroup analysis. Uptake was higher in women who were offered sampling kit at home or work (RR 2.05, 95% CI 1.80-2.33) and those who's kit was mailed to or invited to a nearby health center (RR 1.65, 95% CI 1.58-1.72, I2 = 0%) than those screened with the standard of care. There was no difference between the two groups in the rate of linkage to care of positive cases (RR 1.30, 95% CI 0.90-2.74, I2 = 91%). HPV self-sampling was acceptable and easy to use. None of the trials compared the frequency of screening or adverse events. CONCLUSION: HPV self-sampling is an effective and feasible alternative to the standard health facility-based clinician-sampling for cervical cancer screening in SSA. It could improve the uptake of cervical cancer screening and harness the global strategy towards elimination of cervical cancer by 2030.