Feasibility of task-sharing with community health workers for the identification, emergency management and referral of women with pre-eclampsia, in Mozambique

Background: Maternal mortality is an important public health problem in low-income countries. Delays in reaching health facilities and insufficient health care professionals call for innovative community-level solutions. There is limited evidence on the role of community health workers in the management of pregnancy complications. This study aimed to describe the feasibility of task-sharing the initial screening and initiation of obstetric emergency care for pre-eclampsia/eclampsia from the primary healthcare providers to community health workers in Mozambique and document healthcare facility preparedness to respond to referrals. Method: The study took place in Maputo and Gaza Provinces in southern Mozambique and aimed to inform the Community-Level Interventions for Pre-eclampsia (CLIP) cluster randomized controlled trial. This was a mixed-methods study. The quantitative data was collected through self-administered questionnaires completed by community health workers and a health facility survey; this data was analysed using Stata v13. The qualitative data was collected through focus group discussions and in-depth interviews with various community groups, health care providers, and policymakers. All discussions were audio-recorded and transcribed verbatim prior to thematic analysis using QSR NVivo 10. Data collection was complemented by reviewing existing documents regarding maternal health and community health worker policies, guidelines, reports and manuals. Results: Community health workers in Mozambique were trained to identify the basic danger signs of pregnancy; however, they have not been trained to manage obstetric emergencies. Furthermore, barriers at health facilities were identified, including lack of equipment, shortage of supervisors, and irregular drug availability. All primary and the majority of secondary-level facilities (57%) do not provide blood transfusions or have surgical capacity, and thus such cases must be referred to the tertiary-level. Although most healthcare facilities (96%) had access to an ambulance for referrals, no transport was available from the community to the healthcare facility.Medicine, Faculty ofNon UBCObstetrics and Gynaecology, Department ofReviewedFacultyResearche

Efficacy and safety of dihydroartemisinin-piperaquine for treatment of Plasmodium falciparum uncomplicated malaria in adult patients on antiretroviral therapy in Malawi and Mozambique: an open label non-randomized interventional trial

Background: HIV-infected individuals on antiretroviral therapy (ART) require treatment with artemisinin-based combination therapy (ACT) when infected with malaria. Dihydroartemisinin–piperaquine (DPQ) is recommended for treatment of Plasmodium falciparum malaria, but its efcacy and safety has not been evaluated in HIV-infected individuals on ART, among whom drug–drug interactions are expected. Day-42 adequate clinical and parasitological response (ACPR) and incidence of adverse events were assessed in HIV-infected individuals on non-nucleoside reverse transcriptase inhibitor-based ART (efavirenz and nevirapine) with uncomplicated P. falciparum malaria treated with dihydroartemisinin–piperaquine. Methods: An open label single arm clinical trial was conducted in Malawi (Blantyre and Chikhwawa districts) and Mozambique (Manhiça district) involving patients aged 15–65 years with uncomplicated P. falciparum malaria who were on efavirenz-based or nevirapine-based ART. They received a directly-observed 3-day standard treatment of DPQ and were followed up until day 63 for malaria infection and adverse events. Day-42 PCR-corrected-ACPRs (95% confdence interval [CI]) were calculated for the intention-to-treat (ITT) population. Results: The study enrolled 160 and 61 patients on efavirenz and nevirapine-based ART, with a baseline geometric mean (95% CI) parasite density of 2681 (1964–3661) and 9819 (6606–14,593) parasites/µL, respectively. The day-42 PCR-corrected ACPR (95% CI) was 99.4% (95.6–99.9%) in the efavirenz group and 100% in the nevirapine group. Seri‑ ous adverse events occurred in 5.0% (8/160) and 3.3% (2/61) of the participants in the efavirenz and nevirapine group, respectively, but none were defnitively attributable to DPQ. Cases of prolonged QT interval (>60 ms from baseline) occurred in 31.2% (48/154) and 13.3% (8/60) of the patients on the efavirenz and nevirapine ART groups, respectively. These were not clinically signifcant and resolved spontaneously over time. As this study was not designed to com‑ pare the efcacy and safety of DPQ in the two ART groups, no formal statistical comparisons were made between the two ART groups. Conclusions: DPQ was highly efcacious and safe for the treatment of malaria in HIV-infected patients concurrently taking efavirenz- or nevirapine-based ART, despite known pharmacokinetic interactions between dihydroartemisinin– piperaquine and efavirenz- or nevirapine-based ART regimen

Efficacy and safety of pyronaridine-artesunate (PYRAMAX) for the treatment of P. falciparum uncomplicated malaria in African pregnant women (PYRAPREG): study protocol for a phase 3, non-inferiority, randomised open-label clinical trial

Introduction Malaria infection during pregnancy increases the risk of low birth weight and infant mortality and should be prevented and treated. Artemisinin-based combination treatments are generally well tolerated, safe and effective; the most used being artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP). Pyronaridine-artesunate (PA) is a new artemisinin-based combination. The main objective of this study is to determine the efficacy and safety of PA versus AL or DP when administered to pregnant women with confirmed Plasmodium falciparum infection in the second or third trimester. The primary hypothesis is the pairwise non-inferiority of PA as compared with either AL or DP.Methods and analysis A phase 3, non-inferiority, randomised, open-label clinical trial to determine the safety and efficacy of AL, DP and PA in pregnant women with malaria in five sub-Saharan, malaria-endemic countries (Burkina Faso, Democratic Republic of the Congo, Mali, Mozambique and the Gambia). A total of 1875 pregnant women will be randomised to one of the treatment arms. Women will be actively monitored until Day 63 post-treatment, at delivery and 4–6 weeks after delivery, and infants’ health will be checked on their first birthday. The primary endpoint is the PCR-adjusted rate of adequate clinical and parasitological response at Day 42 in the per-protocol population.Ethics and dissemination This protocol has been approved by the Ethics Committee for Health Research in Burkina Faso, the National Health Ethics Committee in the Democratic Republic of Congo, the Ethics Committee of the Faculty of Medicine and Odontostomatology/Faculty of Pharmacy in Mali, the Gambia Government/MRCG Joint Ethics Committee and the National Bioethics Committee for Health in Mozambique. Written informed consent will be obtained from each individual prior to her participation in the study. The results will be published in peer-reviewed open access journals and presented at (inter)national conferences and meetings.Trial registration number PACTR202011812241529