Safety and tolerability of repeated doses of dihydroartemisinin-piperaquine for intermittent preventive treatment of malaria in pregnancy: a systematic review and an aggregated data meta-analysis of randomized controlled trials.

BACKGROUND: Malaria infection during pregnancy is an important cause of maternal and infant mortality and morbidity with the greatest effect being concentrated in sub-Saharan Africa. In areas of moderate to high malaria transmission, the World Health Organization (WHO) recommends the administration of intermittent preventive treatment of malaria in pregnancy (IPTp) using sulfadoxine-pyrimethamine (SP) to be given to all pregnant women at each scheduled antenatal care visit at monthly intervals. However, there is concern that increased resistance has compromised its effectiveness. This has led to a need for evaluation of alternatives to SP for IPTp with dihydroartemisinin-piperaquine (DP) emerging as a very promising candidate. Thus, this systematic review and aggregated data meta-analysis was conducted to establish the safety and tolerability of repeated doses with DP in IPTp. METHODS: A systematic review and aggregated data meta-analysis of randomized controlled trials (RCTs) was performed by searching electronic databases of PubMed, Science Direct, ClinicalTrials.gov and Google Scholar. RCTs comparing IPTp DP versus recommended standard treatment for IPTp with these outcome measures were analyzed; change in QTc interval, serious adverse events (SAE), grade 3 or 4 adverse events possibly related to study drug and vomiting within 30 min after study drug administration. The search was performed up to 24th June 2023. Data was extracted from eligible studies and an aggregated data meta-analysis was carried out with data pooled as risk ratio (RR) with a 95% confidence interval (CI), using RevMan software (5.4). This study is registered with PROSPERO, CRD42022310041. RESULTS: Six RCTs involving 7969 participants were included in this systematic review and aggregated data meta-analysis. The pooled analysis showed that DP was associated with a change from baseline of the QTc interval although this change was not associated with cardiotoxicity. There was no statistically significant difference in the risk of occurrence of SAEs among participants in both treatment groups (RR = 0.80, 95% CI [0.52-1.24], P = 0.32). However, significant difference was observed in grade 3 or 4 AEs possibly related to study drug where analysis showed that subjects on IPT DP were statistically significantly more likely to experience an AE possibly related to study drug than subjects on IPT SP (RR = 6.65, 95% CI [1.18-37.54], P = 0.03) and in vomiting within 30 min after study drug administration where analysis showed that the risk of vomiting is statistically significantly higher in subjects receiving IPT DP than in subjects receiving IPT SP (RR = 1.77, 95% CI [1.02-3.07], P = 0.04). CONCLUSION: DP was associated with a higher risk of grade 3 or 4 AEs possibly related to study drug and a higher risk of vomiting within 30 min after study drug administration. However, these were experienced in a very small percentage of women and did not affect adherence to study drugs. DP was also better tolerated in these studies as compared to most alternatives that have been proposed to replace SP which have proved to be too poorly tolerated in IPTp use.

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.

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.

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.

Programmatic challenges in managing multidrug-resistant tuberculosis in Malawi.

Background: Multidrug-resistant tuberculosis (MDR-TB) is one of the most urgent challenges that Malawi tends to take a firm public health action. A recent increase in multidrug MDR-TB cases, a decrease in treatment success rate, and a double increase of lost-to-follow-up call into question the country's programmatic management of MDR-TB (PMDT). As such, the study aimed at exploring programmatic challenges in managing MDR-TB in Malawi. Methods: A comprehensive and nonsystematic search was made in PubMed and Google Scholar using mainly the keywords "MDR-TB" "extensively drug-resistant TB," Malawi. The study reviewed existing guidelines and gray literature and reviewed data obtained from the national TB program (NTP) as well. Results: The study found the following challenges affecting PMDT: decrease in funding, partial access to GeneXpert, delay in diagnosis, long treatment duration, lack of adequate personal protective equipment, the long turnaround time of culture results, failure to initiate all diagnosed patients on treatment, absence of alternative second-line medicines, and lack of transport from health facilities to patient homes. Conclusion: If the Malawi NTP is to achieve a vision of a "TB-free Malawi," rigorous efforts at all levels must be made, including mobilizing domestic resources for improved MDR-TB program performance. Developing partners should continue providing the much-needed funding to the Malawi government to stand in the wake of the MDR-TB crisis.

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.