Community engagement among forest goers in a malaria prophylaxis trial: implementation challenges and implications.

BACKGROUND: Malaria transmission in Southeast Asia is increasingly confined to forests, where marginalized groups are exposed primarily through their work. Anti-malarial chemoprophylaxis may help to protect these people. This article examines the effectiveness and practical challenges of engaging forest-goers to participate in a randomized controlled clinical trial of anti-malarial chemoprophylaxis with artemether-lumefantrine (AL) versus a control (multivitamin, MV) for malaria in northeast Cambodia. METHODS: The impact of engagement in terms of uptake was assessed as the proportion of people who participated during each stage of the trial: enrolment, compliance with trial procedures, and drug intake. During the trial, staff recorded the details of engagement meetings, including the views and opinions of participants and community representatives, the decision-making processes, and the challenges addressed during implementation. RESULTS: In total, 1613 participants were assessed for eligibility and 1480 (92%) joined the trial, 1242 (84%) completed the trial and received prophylaxis (AL: 82% vs MV: 86%, p = 0.08); 157 (11%) were lost to follow-up (AL: 11% vs MV: 11%, p = 0.79); and 73 (5%) discontinued the drug (AL-7% vs MV-3%, p = 0.005). The AL arm was associated with discontinuation of the study drug (AL: 48/738, 7% vs 25/742, 3%; p = 0.01). Females (31/345, 9%) were more likely (42/1135, 4%) to discontinue taking drugs at some point in the trial (p = 0.005). Those (45/644, 7%) who had no previous history of malaria infection were more likely to discontinue the study drug than those (28/836, 3%) who had a history of malaria (p = 0.02). Engagement with the trial population was demanding because many types of forest work are illegal; and the involvement of an engagement team consisting of representatives from the local administration, health authorities, community leaders and community health workers played a significant role in building trust. Responsiveness to the needs and concerns of the community promoted acceptability and increased confidence in taking prophylaxis among participants. Recruitment of forest-goer volunteers to peer-supervise drug administration resulted in high compliance with drug intake. The development of locally-appropriate tools and messaging for the different linguistic and low-literacy groups was useful to ensure participants understood and adhered to the trial procedures. It was important to consider forest-goers` habits and social characteristics when planning the various trial activities. CONCLUSIONS: The comprehensive, participatory engagement strategy mobilized a wide range of stakeholders including study participants, helped build trust, and overcame potential ethical and practical challenges. This locally-adapted approach was highly effective as evidenced by high levels of trial enrolment, compliance with trial procedures and drug intake.

Cost, health impacts and cost effectiveness of iceless refrigeration in India's last-mile vaccine cold chain delivery.

BACKGROUND: Compared with ice-based vaccine carriers (IBVCs), iceless vaccine carrier (ILVC) last-mile delivery could optimize vaccine effectiveness by reducing spoilage. We estimated ILVC-associated spoilage costs averted and cost effectiveness. METHODS: IBVC vaccine spoilage costs were estimated for six vaccines. ILVC incremental costs were based on yearly ILVC cost over total doses. Cost effectiveness was estimated via Markov modeling of rotavirus vaccine. RESULTS: The spoilage cost using IBVCs was US$9 603 294. Using ILVCs, the incremental cost per vaccine dose was US$0.026, the cost-benefit ratio was 0.28, the number of averted disability-adjusted life years was 0.03 per child and there was a saving of US$0.80 per child vaccinated. CONCLUSIONS: ILVCs may bring cost savings and health gains compared with IBVCs.

Antimalarial chemoprophylaxis for forest goers in southeast Asia: an open-label, individually randomised controlled trial.

BACKGROUND: Malaria in the eastern Greater Mekong subregion has declined to historic lows. Countries in the Greater Mekong subregion are accelerating malaria elimination in the context of increasing antimalarial drug resistance. Infections are now increasingly concentrated in remote, forested foci. No intervention has yet shown satisfactory efficacy against forest-acquired malaria. The aim of this study was to assess the efficacy of malaria chemoprophylaxis among forest goers in Cambodia. METHODS: We conducted an open-label, individually randomised controlled trial in Cambodia, which recruited participants aged 16-65 years staying overnight in forests. Participants were randomly allocated 1:1 to antimalarial chemoprophylaxis, a 3-day course of twice-daily artemether-lumefantrine followed by the same daily dosing once a week while travelling in the forest and for a further 4 weeks after leaving the forest (four tablets per dose; 20 mg of artemether and 120 mg of lumefantrine per tablet), or a multivitamin with no antimalarial activity. Allocations were done according to a computer-generated randomisation schedule, and randomisation was in permuted blocks of size ten and stratified by village. Investigators and participants were not masked to drug allocation, but laboratory investigations were done without knowledge of allocation. The primary outcome was a composite endpoint of either clinical malaria with any Plasmodium species within 1-28, 29-56, or 57-84 days, or subclinical infection detected by PCR on days 28, 56, or 84 using complete-case analysis of the intention-to-treat population. Adherence to study drug was assessed primarily by self-reporting during follow-up visits. Adverse events were assessed in the intention-to-treat population as a secondary endpoint from self-reporting at any time, plus a physical examination and symptom questionnaire at follow-up. This trial is registered at ClinicalTrials.gov (NCT04041973) and is complete. FINDINGS: Between March 11 and Nov 20, 2020, 1480 individuals were enrolled, of whom 738 were randomly assigned to artemether-lumefantrine and 742 to the multivitamin. 713 participants in the artemether-lumefantrine group and 714 in the multivitamin group had a PCR result or confirmed clinical malaria by rapid diagnostic test during follow-up. During follow-up, 19 (3%, 95% CI 2-4) of 713 participants had parasitaemia or clinical malaria in the artemether-lumefantrine group and 123 (17%, 15-20) of 714 in the multivitamin group (absolute risk difference 15%, 95% CI 12-18; p<0·0001). During follow-up, there were 166 malaria episodes caused by Plasmodium vivax, 14 by Plasmodium falciparum, and five with other or mixed species infections. The numbers of participants with P vivax were 18 (3%, 95% CI 2-4) in the artemether-lumefantrine group versus 112 (16%, 13-19) in the multivitamin group (absolute risk difference 13%, 95% CI 10-16; p<0·0001). The numbers of participants with P falciparum were two (0·3%, 95% CI 0·03-1·01) in the artemether-lumefantrine group versus 12 (1·7%, 0·9-2·9) in the multivitamin group (absolute risk difference 1·4%, 95% CI 0·4-2·4; p=0·013). Overall reported adherence to the full course of medication was 97% (95% CI 96-98; 1797 completed courses out of 1854 courses started) in the artemether-lumefantrine group and 98% (97-98; 1842 completed courses in 1885 courses started) in the multivitamin group. Overall prevalence of adverse events was 1·9% (355 events in 18 806 doses) in the artemether-lumefantrine group and 1·1% (207 events in 19 132 doses) in the multivitamin group (p<0·0001). INTERPRETATION: Antimalarial chemoprophylaxis with artemether-lumefantrine was acceptable and well tolerated and substantially reduced the risk of malaria. Malaria chemoprophylaxis among high-risk groups such as forest workers could be a valuable tool for accelerating elimination in the Greater Mekong subregion. FUNDING: The Global Fund to Fight AIDS, Tuberculosis and Malaria; Wellcome Trust.

Forest malaria and prospects for anti-malarial chemoprophylaxis among forest goers: findings from a qualitative study in Thailand.

BACKGROUND: Across the Greater Mekong Subregion, malaria remains a dangerous infectious disease, particularly for people who visit forested areas where residual transmission continues. Because vector control measures offer incomplete protection to forest goers, chemoprophylaxis has been suggested as a potential supplementary measure for malaria prevention and control. To implement prophylaxis effectively, additional information is needed to understand forest goers' activities and their willingness to use malaria prevention measures, including prophylaxis, and how it could be delivered in communities. Drawing on in-depth interviews with forest goers and stakeholders, this article examines the potential acceptability and implementation challenges of malaria prophylaxis for forest goers in northeast Thailand. METHODS: In-depth interviews were conducted with forest goers (n = 11) and stakeholders (n = 16) including healthcare workers, community leaders, and policymakers. Interviews were audio-recorded, transcribed and coded using NVivo, employing an inductive and deductive approach, for thematic analysis. RESULTS: Forest goers were well aware of their (elevated) malaria risk and reported seeking care for malaria from local health care providers. Forest goers and community members have a close relationship with the forest but are not a homogenous group: their place and time-at-risk varied according to their activities and length of stay in the forest. Among stakeholders, the choice and cost of anti-malarial prophylactic regimen-its efficacy, length and complexity, number of tablets, potential side effects, and long-term impact on users-were key considerations for its feasibility. They also expressed concern about adherence to the preventive therapy and potential difficulty treating malaria patients with the same regimen. Prophylaxis was considered a low priority in areas with perceived accessible health system and approaching malaria elimination. CONCLUSIONS: In the context of multi-drug resistance, there are several considerations for implementing malaria prophylaxis: the need to target forest goers who are at-risk with a clear period of exposure, to ensure continued use of vector control measures and adherence to prophylactic anti-malarials, and to adopt an evidence-based approach to determine an appropriate regimen. Beyond addressing current intervention challenges and managing malaria incidence in low-transmission setting, it is crucial to keep malaria services available and accessible at the village level especially in areas home to highly mobile populations.

Forest malaria and prospects for anti-malarial chemoprophylaxis among forest goers: findings from a qualitative study in Lao PDR.

BACKGROUND: Despite significant decline in malarial incidence and mortality in countries across the Greater Mekong Subregion, the disease remains a public health challenge in the region; transmission continues mainly among people who visit forests in remote areas, often along international borders, where access to primary healthcare is limited. In the absence of effective vector-control measures and limited exposure periods, malaria chemoprophylaxis has been proposed as a strategy to protect forest goers. As a rarely used approach for indigenous populations, questions remain about its feasibility and acceptability. Drawing on in-depth interviews with forest goers and stakeholders, this article examines opportunities and challenges for implementation of anti-malarial chemoprophylaxis for forest goers in Lao PDR. METHODS: In-depth interviews were conducted with 16 forest goers and 15 stakeholders in Savannakhet province, Lao PDR. Interview topics included experience of malaria prevention and health services, and perceptions of prophylaxis as a potential component of malaria elimination strategy. The interviews were transcribed and coded using inductive and deductive approaches for qualitative thematic analysis. RESULTS: In ethnically and geographically diverse villages, awareness of malaria risk prompts forest goers to protect themselves, albeit sub-optimally using available preventive measures. Stakeholders highlighted challenges for targeting at-risk populations and approaches to address forest malaria in southern Lao PDR. Among policymakers, choice and cost of anti-malarials, particularly their efficacy and source of funding, were key considerations for the feasibility of malaria prophylaxis. Acceptability of prophylaxis among forest goers was also influenced by the complexity of the regimen, including the number of tablets and timing of doses. Implementation of prophylaxis may be affected by a lack of transportation and communication barriers in remote communities. CONCLUSION: Adding prophylaxis to existing malaria control activities requires strengthening the capacity of local health workers in Lao PDR. Ideally, this would be part of an integrated approach that includes strategies to address the other febrile illnesses that forest goers describe as priority health concerns. The prophylactic regimen also requires careful consideration in terms of effectiveness and simplicity of dosing.

Acceptability and feasibility of malaria prophylaxis for forest goers: findings from a qualitative study in Cambodia.

BACKGROUND: In the Greater Mekong Subregion, adults are at highest risk for malaria, particularly those who visit forests. The absence of effective vector control strategies and limited periods of exposure during forest visits suggest that chemoprophylaxis could be an appropriate strategy to protect forest goers against malaria. METHODS: Alongside a clinical trial of anti-malarial chemoprophylaxis in northern Cambodia, qualitative research was conducted, including in-depth interviews and observation, to explore the acceptability of malaria prophylaxis for forest goers, the implementation opportunities, and challenges of this strategy. RESULTS: Prophylaxis with artemether-lumefantrine for forest goers was found to be acceptable under trial conditions. Three factors played a major role: the community's awareness and perception of the effectiveness of prophylaxis, their trust in the provider, and malaria as a local health concern. The findings highlight how uptake and adherence to prophylaxis are influenced by the perceived balance between benefits and burden of anti-malarials which are modulated by the seasonality of forest visits and its influence on malaria risk. CONCLUSIONS: The implementation of anti-malarial prophylaxis needs to consider how the preventive medication can be incorporated into existing vector-control measures, malaria testing and treatment services. The next step in the roll out of anti-malarial prophylaxis for forest visitors will require support from local health workers.

Implementation of field detection devices for antimalarial quality screening in Lao PDR-A cost-effectiveness analysis.

Substandard and falsified (SF) antimalarials have devastating consequences including increased morbidity, mortality and economic losses. Portable medicine quality screening devices are increasingly available, but whether their use for the detection of SF antimalarials is cost-effective is not known. We evaluated the cost-effectiveness of introducing such devices in post-market surveillance in pharmacies in Laos, conservatively focusing on their outcome in detecting SF artemisinin-based combination therapies (ACTs). We simulated the deployment of six portable screening devices: two handheld near-infrared [MicroPHAZIR RX, NIR-S-G1], two handheld Raman [Progeny, TruScan RM]; one portable mid-infrared [4500a FTIR] spectrometers, and single-use disposable paper analytical devices [PADs]. We considered two scenarios with high and low levels of SF ACTs. Different sampling strategies in which medicine inspectors would test 1, 2, or 3 sample(s) of each brand of ACT were evaluated. Costs of inspection including device procurement, inspector time, reagents, reference testing, and replacement with genuine ACTs were estimated. Outcomes were measured as disability adjusted life years (DALYs) and incremental cost-effectiveness ratios were estimated for each device compared with a baseline of visual inspections alone. In the scenario with high levels of SF ACTs, all devices were cost-effective with a 1-sample strategy. In the scenario of low levels of SF ACTs, only four devices (MicroPHAZIR RX, 4500a FTIR, NIR-S-G1, and PADs) were cost-effective with a 1-sample strategy. In the multi-way comparative analysis, in both scenarios the NIR-S-G1 testing 2 samples was the most cost-effective option. Routine inspection of ACT quality using portable screening devices is likely to be cost-effective in the Laos context. This work should encourage policy-makers or regulators to further investigate investment in portable screening devices to detect SF medicines and reduce their associated undesired health and economic burdens.