Impact of Point-of-Care Rapid Diagnostic Tests on Antibiotic Prescription Among Patients Aged <18 Years in Primary Healthcare Settings in 2 Peri-Urban Districts in Ghana: Randomized Controlled Trial Results.

Background: Inappropriate antibiotic prescriptions are a known driver of antimicrobial resistance in settings with limited diagnostic capacity. This study aimed to assess the impact of diagnostic algorithms incorporating rapid diagnostic tests on clinical outcomes and antibiotic prescriptions compared with standard-of-care practices, of acute febrile illness cases at outpatient clinics in Shai-Osudoku and Prampram districts in Ghana.

Methods: This was an open-label, centrally randomized controlled trial in 4 health facilities.

Advancing Access to Diagnostic Tools Essential for Universal Health Coverage and Antimicrobial Resistance Prevention: An Overview of Trials in Sub-Saharan Africa.

We introduce the Antimicrobial Resistance Diagnostic Use Accelerator program, and the articles in this Supplement, which cover the program in 3 sub-Saharan Africa countries.

Synthesis and Meta-analysis of 3 Randomized Trials Conducted in Burkina Faso, Ghana, and Uganda Comparing the Effects of Point-of-Care Tests and Diagnostic Algorithms Versus Routine Care on Antibiotic Prescriptions and Clinical Outcomes in Ambulatory Patients <18 Years of Age With Acute Febrile Illness.

This meta-analysis included 3 randomized trials conducted in sub-Saharan Africa comparing the effects of point-of-care tests and diagnostic algorithms versus routine care on antibiotic prescriptions and clinical outcomes in ambulatory patients presenting at outpatient facilities with acute uncomplicated febrile illness.

Understanding Health Worker and Community Antibiotic Prescription-Adherence Practices for Acute Febrile Illness: A Nested Qualitative Study in the Shai-Osudoku District of Ghana and the Development of a Training-and-Communication Intervention.

Background: The aim was to explore behavioral factors relating to the prescription and communication of prescription-adherence messages for patients with acute febrile illness, from which to develop a training-and-communication (T&C) intervention to be delivered as part of a clinical trial.

Methods: The study undertook a content analysis of primary, qualitative data collection using in-depth interviews and focus group discussions, informed by the Capability, Opportunity, Motivation (COM-B) theory of behavior, the Theoretical Domains Framework (TDF), and Behavior Change Wheel (BCW) approach, in health facilities (39 health workers) and communities (66 community members) in the Shai-Osudoku District of Ghana.

Results: Health workers perceive that prescribers' and dispensers' communication with patients is influenced by the following factors: patient's educational level, existing disease conditions, health worker's workload, patient's religion, language barrier between health worker and patient, outcome of laboratory results, and medicine availability.

Viewpoint: Antimicrobial Resistance Diagnostics Use Accelerator: Qualitative Research on Adherence to Prescriptions.

In this Viewpoint, the authors explore the determinants of patients' prescription adherence behaviors as part of FIND's Advancing Access to Diagnostic Innovation essential for Universal Health Coverage and AMR Prevention (ADIP) trials (ClinicalTrials.gov identifier: NCT04081051). Research findings from Burkina Faso, Ghana, and Uganda show that basic knowledge and understanding of prescription instructions are essential for adherence and can be improved through better communication.

Prospective observational study to evaluate the clinical and biological safety profile of pyronaridine-artesunate in a rural health district in Burkina Faso.

The assessment in real-life conditions of the safety and efficacy of new antimalarial drugs is of greatest interest. This study aimed to monitor and evaluate both clinical and biological safety of pyronaridine-artesunate (PA) in real-life conditions in Burkina Faso's health system. This was a single-arm, open-label study, where patients attending Nanoro health facilities with uncomplicated malaria were consented to be part of a cohort event monitoring (CEM).

Impact of a package of diagnostic tools, clinical algorithm, and training and communication on outpatient acute fever case management in low- and middle-income countries: protocol for a randomized controlled trial.

Background: The management of acute febrile illnesses places a heavy burden on clinical services in many low- and middle-income countries (LMICs). Bacterial and viral aetiologies of acute fevers are often clinically indistinguishable and, in the absence of diagnostic tests, the 'just-in-case' use of antibiotics by many health workers has become common practice, which has an impact on drug-resistant infections. Our study aims to answer the following question: in patients with undifferentiated febrile illness presenting to outpatient clinics/peripheral health centres in LMICs, can we demonstrate an improvement in clinical outcomes and reduce unnecessary antibiotic prescription over current practice by using a combination of simple, accurate diagnostic tests, clinical algorithms, and training and communication (intervention package)?

Methods: We designed a randomized, controlled clinical trial to evaluate the impact of our intervention package on clinical outcomes and antibiotic prescription rates in acute febrile illnesses.

Pooled Multicenter Analysis of Cardiovascular Safety and Population Pharmacokinetic Properties of Piperaquine in African Patients with Uncomplicated Falciparum Malaria.

Dihydroartemisinin-piperaquine has shown excellent efficacy and tolerability in malaria treatment. However, concerns have been raised of potentially harmful cardiotoxic effects associated with piperaquine. The population pharmacokinetics and cardiac effects of piperaquine were evaluated in 1,000 patients, mostly children enrolled in a multicenter trial from 10 sites in Africa.

Factors affecting the electrocardiographic QT interval in malaria: A systematic review and meta-analysis of individual patient data.

Background: Electrocardiographic QT interval prolongation is the most widely used risk marker for ventricular arrhythmia potential and thus an important component of drug cardiotoxicity assessments. Several antimalarial medicines are associated with QT interval prolongation. However, interpretation of electrocardiographic changes is confounded by the coincidence of peak antimalarial drug concentrations with recovery from malaria.

Adherence to Dihydroartemisinin-Piperaquine Treatment among Patients with Uncomplicated Malaria in Northern Ghana.

Treatment adherence has been described as the process whereby patients take medications, follow diet, and effect other lifestyle changes that relate to agreed recommendations from healthcare providers. The determinants of such treatment adherence include patient, the health condition, therapy type, socioeconomic conditions, and the healthcare system. The study examined adherence in malaria patients treated with dihydroartemisinin-piperaquine in routine clinical care in northern Ghana.

High adherence level to artemisinin-based combination therapies in rural settlement 11 years after their introduction in the health system, Nanoro, Burkina Faso.

Purpose: In 2005, Burkina Faso changed its first-line treatment for uncomplicated malaria from chloroquine to artemisinin-based combination therapies (ACTs). Patient adherence to ACTs regimen is a keystone to achieve the expected therapeutic outcome and prevent the emergence and spread of parasite resistance. Eleven years after the introduction of ACTs in the health system, this study aimed to measure adherence level of patients in rural settlement and investigate the determinants of nonadherence.

Post-licensure safety evaluation of dihydroartemisinin piperaquine in the three major ecological zones across Ghana.

Background: Uncommon and rare adverse events (AEs), with delayed onset may not be detected before new drugs are licensed and deployed. The present study examined the post licensure safety of dihydroartemisinin-piperaquine (DHP) as an additional treatment for malaria in Ghana. The relationship between the incidence of AEs, treatment completion rate, participant characteristics and concomitant medications are reported.

Multi-Country Evaluation of Safety of Dihydroartemisinin/Piperaquine Post-Licensure in African Public Hospitals with Electrocardiograms.

The antimalarial drug piperaquine is associated with delayed ventricular depolarization, causing prolonged QT interval (time taken for ventricular de-polarisation and re-polarisation). There is a lack of safety data regarding dihydroartemisinin/piperaquine (DHA/PPQ) for the treatment of uncomplicated malaria, which has limited its use. We created a platform where electrocardiograms (ECG) were performed in public hospitals for the safety assessment of DHA/PPQ, at baseline before the use of dihydroartemisinin/piperaquine (Eurartesim®), and on day 3 (before and after administration of the final dose) and day 7 post-administration.

Treatment outcomes in a safety observational study of dihydroartemisinin/piperaquine (Eurartesim(®)) in the treatment of uncomplicated malaria at public health facilities in four African countries.

Background: Dihydroartemisinin-piperaquine (DHA-PQ) is one of five WHO recommended artemisinin combination therapy (ACT) for the treatment of uncomplicated malaria. However, little was known on its post-registration safety and effectiveness in sub-Saharan Africa. DHA-PQ provides a long post-treatment prophylactic effect against re-infection; however, new infections have been reported within a few weeks of treatment, especially in children.

Feasibility and cost of using mobile phones for capturing drug safety information in peri-urban settlement in Ghana: a prospective cohort study of patients with uncomplicated malaria.

Background: The growing need to capture data on health and health events using faster and efficient means to enable prompt evidence-based decision-making is making the use of mobile phones for health an alternative means to capture anti-malarial drug safety data. This paper examined the feasibility and cost of using mobile phones vis-à-vis home visit to monitor adverse events (AEs) related to artemisinin-based combination therapy (ACT) for treatment of uncomplicated malaria in peri-urban Ghana.

Methods: A prospective, observational, cohort study conducted on 4270 patients prescribed ACT in 21 health facilities.

Prospective observational study to evaluate the clinical safety of the fixed-dose artemisinin-based combination Eurartesim® (dihydroartemisinin/piperaquine), in public health facilities in Burkina Faso, Mozambique, Ghana, and Tanzania.

Background: The World Health Organization recommends artemisinin-based combination (ACT) for the treatment of uncomplicated malaria. Post-licensure safety data on newly registered ACT is critical for evaluating their risk/benefit profile in malaria endemic countries. The clinical safety of the newly registered combination, Eurartesim®, following its introduction into the public health system in four African countries was assessed.

Sustainable development of a GCP-compliant clinical trials platform in Africa: the malaria clinical trials alliance perspective.

Background: The Malaria Clinical Trials Alliance (MCTA), a programme of INDEPTH network of demographic surveillance centres, was launched in 2006 with two broad objectives: to facilitate the timely development of a network of centres in Africa with the capacity to conduct clinical trials of malaria vaccines and drugs under conditions of good clinical practice (GCP); and to support, strengthen and mentor the centres in the network to facilitate their progression towards self-sustaining clinical research centres.

Case Description: Sixteen research centres in 10 African malaria-endemic countries were selected that were already working with the Malaria Vaccine Initiative (MVI) or the Medicines for Malaria Venture (MMV). All centres were visited to assess their requirements for research capacity development through infrastructure strengthening and training.

An evaluation of the immunogenicity and safety of a new trivalent meningococcal polysaccharide vaccine.

The immunogenicity and safety of a meningococcal trivalent A/C/W135 polysaccharide vaccine was compared with that of a tetravalent A/C/Y/W135 polysaccharide vaccine in a randomised, double blind trial. The study included 360 adults, who received either a trivalent or tetravalent polysaccharide meningococcal vaccine. Antibody responses were determined by serum bactericidal antibody (rSBA) assays prior to vaccination and on day 28 and month 11 after vaccination.

Review of Antenatal-Linked Voluntary Counseling and HIV Testing in Sub-Saharan Africa: Lessons and Options for Ghana.

SummaryVoluntary counselling and HIV testing has become an integral part of HIV prevention and care programs in many countries in sub-Saharan Africa. A number of interventions offer potential to reduce mother-to-child HIV transmission. These interventions, including antenatal and or intrapartum administration of antiretroviral drugs require the integration of voluntary counselling and HIV testing for pregnant women into antenatal care.

Cluster randomised trial of intermittent preventive treatment for malaria in infants in area of high, seasonal transmission in Ghana.

Objective: To evaluate the effects of intermittent preventive treatment for malaria in infants (IPTi) with sulfadoxine-pyrimethamine in an area of intense, seasonal transmission.

Design: Cluster randomised placebo controlled trial, with 96 clusters allocated randomly to sulfadoxine-pyrimethamine or placebo in blocks of eight.

Interventions: Children received sulfadoxine-pyrimethamine or placebo and one month of iron supplementation when they received DPT-2, DPT-3, or measles vaccinations and at 12 months of age.