Cardiac safety of dihydroartemisinin-piperaquine and sulfadoxine pyrimethamine among pregnant women with and without asymptomatic parasitaemia in Tanzania: results from an open-label, parallel-group, randomised phase II trial

Background: Dihydroartemisinin-Piperaquine (DP) can induce transient prolongation of the corrected QT interval (QTc) and is a candidate for use with sulfadoxine-pyrimethamine (SP) in intermittent preventive treatment of malaria in pregnancy (IPTp). Pregnancy can alter pharmacokinetics of antimalarial drugs. Acute malaria infection can increase QTc prolongation. Whether DP alters cardiac function in pregnant women with or without asymptomatic parasitaemia is not well characerised. Methods: This was an open-label, parallel-group, randomised phase 2 study among pregnant women in Handeni, Tanzania (NCT02909712). Women were screened for P. falciparum by microscopy and, if positive, received a rapid diagnostic test (RDT). If RDT-positive, they received DP or SP, and the next microscopy-negative woman was randomly allocated to receive DP or SP. Enrolment and allocation continued in this alternating manner to reach 200 (50/group): Grp 1 (neg; SP), Grp 2 (pos; SP), Grp 3 (neg: DP), Grp 4 (pos: DP). Standard 12-lead ECGs were used to record cardiac function in triplicate. DP groups were measured on day 0 (predose), day 2 (predose and hours 3,4,5,6,7,8), and day 7; SP groups had day 0 (predose), and day 7 ECGs. Results: DP resulted in QTcF prolongation that peaked ~30 msec at 5-h post dose 3 on day 2 (schedule: days 0,1,2). The mean maximum increase was slightly more in group 4 compared to group 3 (33.1 vs 29.1 msec). On day 7, QTcF returned to baseline in group 3; a small and non-clinically significant increase of 3.4 (90%CI: 0.3, 6.5) msec was still present among RDT-positive women. QTcB measurements were similar. There was a marked decrease in heart rate (HR) among all DP recipients on day 2, which appeared greater in group 4 compared to group 3 (13.3 vs 8.9 bpm), baseline HR was higher in group 4 than group 3 (92.7 vs 88.5 bpm). This potentially represents a regression towards the mean. On day 7, HR had returned to baseline in both groups. Conclusion: Parasite presence did not alter the effect of DP on the different ECG parameters with the possible exception of HR. No marked differences were observed between pregnant women with and without asymptomatic parasitaemia

Facilitators and barriers to seasonal malaria chemoprevention (SMC) uptake in Nigeria: a qualitative approach

BACKGROUND: SMC was adopted in Nigeria in 2014 and by 2021 was being implemented in 18 states, over four months between June and October by 143000 community drug distributors (CDDs) to a target population of 23million children. Further expansion of SMC is planned, extending to 21 states with four or five monthly cycles. In view of this massive scale-up, the National Malaria Elimination Programme undertook qualitative research in five states shortly after the 2021 campaign to understand community attitudes to SMC so that these perspectives inform future planning of SMC delivery in Nigeria. METHODS: In 20 wards representing urban and rural areas with low and high SMC coverage in five states, focus group discussions were held with caregivers, and in-depth interviews conducted with community leaders and community drug distributors. Interviews were also held with local government area and State malaria focal persons and at national level with the NMEP coordinator, and representatives of partners working on SMC in Nigeria. Interviews were recorded and transcribed, those in local languages translated into English, and transcripts analysed using NVivo software. RESULTS: In total, 84 focus groups and 106 interviews were completed. Malaria was seen as a major health concern, SMC was widely accepted as a key preventive measure, and community drug distributors (CDDs) were generally trusted. Caregivers preferred SMC delivered door-to-door to the fixed-point approach, because it allowed them to continue daily tasks, and allowed time for the CDD to answer questions. Barriers to SMC uptake included perceived side-effects of SMC drugs, a lack of understanding of the purpose of SMC, mistrust and suspicions that medicines provided free may be unsafe or ineffective, and local shortages of drugs. CONCLUSIONS: Recommendations from this study were shared with all community drug distributors and others involved in SMC campaigns during cascade training in 2022, including the need to strengthen communication about the safety and effectiveness of SMC, recruiting distributors from the local community, greater involvement of state and national level pharmacovigilance coordinators, and stricter adherence to the planned medicine allocations to avoid local shortages. The findings reinforce the importance of retaining door-to-door delivery of SMC

Additional file 1 of Facilitators and barriers to seasonal malaria chemoprevention (SMC) uptake in Nigeria: a qualitative approach

Additional file 1. In Depth Interview Guide. This file contains the questions and prompts used by interviewers during data collection. The guide was developed based on a literature review and pilot testing

The use of video job-aids to improve the quality of seasonal malaria chemoprevention delivery

Mobile phones are increasingly used in community health programmes, but the use of video job-aids that can be displayed on smart phones has not been widely exploited. We investigated the use of video job-aids to support the delivery of seasonal malaria chemoprevention (SMC) in countries in West and Central Africa. The study was prompted by the need for training tools that could be used in a socially distanced manner during the COVID-19 pandemic. Animated videos were developed in English, French, Portuguese, Fula and Hausa, illustrating key steps for administering SMC safely, including wearing masks, washing hands, and social distancing. Through a consultative process with the national malaria programmes of countries using SMC, successive versions of the script and videos were reviewed to ensure accurate and relevant content. Online workshops were held with programme managers to plan how to use the videos in SMC staff training and supervision, and the use of the videos was evaluated in Guinea through focus groups and in-depth interviews with drug distributors and other staff involved in SMC delivery and through direct observations of SMC administration. Programme managers found the videos useful as they reinforce messages, can be viewed at any time and repeatedly, and when used during training sessions, provide a focus of discussion and support for trainers and help retain messages. Managers requested that local specificities of SMC delivery in their setting be included in tailored versions of the video for their country, and videos were required to be narrated in a variety of local languages. In Guinea, SMC drug distributors found the video covered the all the essential steps and found the video easy to understand. However, not all key messages were followed as some of the safety measures, social distancing and wearing masks, were perceived by some as creating mistrust amongst communities. Video job-aids can potentially provide an efficient means of reaching large numbers of drug distributors with guidance for safe and effective distribution of SMC. Not all distributors use android phones, but SMC programmes are increasingly providing drug distributors with android devices to track delivery, and personal ownership of smartphones in sub-Saharan Africa is growing. The use of video job-aids for community health workers to improve the quality delivery of SMC, or of other primary health care interventions, should be more widely evaluated

The use of video job-aids to improve the quality of seasonal malaria chemoprevention delivery

Mobile phones are increasingly used in community health programmes, but the use of video job-aids that can be displayed on smart phones has not been widely exploited. We investigated the use of video job-aids to support the delivery of seasonal malaria chemoprevention (SMC) in countries in West and Central Africa. The study was prompted by the need for training tools that could be used in a socially distanced manner during the COVID-19 pandemic. Animated videos were developed in English, French, Portuguese, Fula and Hausa, illustrating key steps for administering SMC safely, including wearing masks, washing hands, and social distancing. Through a consultative process with the national malaria programmes of countries using SMC, successive versions of the script and videos were reviewed to ensure accurate and relevant content. Online workshops were held with programme managers to plan how to use the videos in SMC staff training and supervision, and the use of the videos was evaluated in Guinea through focus groups and in-depth interviews with drug distributors and other staff involved in SMC delivery and through direct observations of SMC administration. Programme managers found the videos useful as they reinforce messages, can be viewed at any time and repeatedly, and when used during training sessions, provide a focus of discussion and support for trainers and help retain messages. Managers requested that local specificities of SMC delivery in their setting be included in tailored versions of the video for their country, and videos were required to be narrated in a variety of local languages. In Guinea, SMC drug distributors found the video covered the all the essential steps and found the video easy to understand. However, not all key messages were followed as some of the safety measures, social distancing and wearing masks, were perceived by some as creating mistrust amongst communities. Video job-aids can potentially provide an efficient means of reaching large numbers of drug distributors with guidance for safe and effective distribution of SMC. Not all distributors use android phones, but SMC programmes are increasingly providing drug distributors with android devices to track delivery, and personal ownership of smartphones in sub-Saharan Africa is growing. The use of video job-aids for community health workers to improve the quality delivery of SMC, or of other primary health care interventions, should be more widely evaluated