Comparative efficacy of two pyrethroid-piperonyl butoxide nets (Olyset Plus and PermaNet 3.0) against pyrethroid resistant malaria vectors: a non-inferiority assessment

Background Pyrethroid-PBO nets were conditionally recommended for control of malaria transmitted by mosquitoes with oxidase-based pyrethroid-resistance based on epidemiological evidence of additional protective effect with Olyset Plus compared to a pyrethroid-only net (Olyset Net). Entomological studies can be used to assess the comparative performance of other brands of pyrethroid-PBO ITNs to Olyset Plus. Methods An experimental hut trial was performed in Cové, Benin to compare PermaNet 3.0 (deltamethrin plus PBO on roof panel only) to Olyset Plus (permethrin plus PBO on all panels) against wild pyrethroid-resistant Anopheles gambiae sensu lato (s.l.) following World Health Organization (WHO) guidelines. Both nets were tested unwashed and after 20 standardized washes compared to Olyset Net. Laboratory bioassays were also performed to help explain findings in the experimental huts. Results With unwashed nets, mosquito mortality was higher in huts with PermaNet 3.0 compared to Olyset Plus (41% vs. 28%, P < 0.001). After 20 washes, mortality declined significantly with PermaNet 3.0 (41% unwashed vs. 17% after washing P < 0.001), but not with Olyset Plus (28% unwashed vs. 24% after washing P = 0.433); Olyset Plus induced significantly higher mortality than PermaNet 3.0 and Olyset Net after 20 washes. PermaNet 3.0 showed a higher wash retention of PBO compared to Olyset Plus. A non-inferiority analysis performed with data from unwashed and washed nets together using a margin recommended by the WHO, showed that PermaNet 3.0 was non-inferior to Olyset Plus in terms of mosquito mortality (25% with Olyset Plus vs. 27% with PermaNet 3.0, OR = 1.528, 95%CI = 1.02–2.29) but not in reducing mosquito feeding (25% with Olyset Plus vs. 30% with PermaNet 3.0, OR = 1.192, 95%CI = 0.77–1.84). Both pyrethroid-PBO nets were superior to Olyset Net. Conclusion Olyset Plus outperformed PermaNet 3.0 in terms of its ability to cause greater margins of improved mosquito mortality compared to a standard pyrethroid net, after multiple standardized washes. However, using a margin of non-inferiority defined by the WHO, PermaNet 3.0 was non-inferior to Olyset Plus in inducing mosquito mortality. Considering the low levels of mortality observed and increasing pyrethroid-resistance in West Africa, it is unclear whether either of these nets would demonstrate the same epidemiological impact observed in community trials in East Africa.

Health Quantitative Studies

Observational health studies look for associations between exposures and possible subsequent health outcomes. To test hypotheses, case-control studies look backward in time to earlier exposures while cohort studies observe exposed and non-exposed groups forward in time to record outcome incidence data. Both designs test hypotheses for associations while cohorts can also identify causality. Interventions are best tested using randomized controlled trials for efficacy and community trials for effectiveness. These studies utilize complicated methods and require specialist expertise.

Results from two cohort studies in Central Africa show that clearance of Wuchereria bancrofti infection after repeated rounds of mass drug administration with albendazole alone is closely linked to individual adherence

Background Two community trials conducted from 2012 to 2018 in the Republic of Congo and the Democratic Republic of the Congo demonstrated the efficacy of semi-annual mass drug administration (MDA) with albendazole (ALB) alone on lymphatic filariasis (LF). However, a high inter-individual heterogeneity in the clearance of infection was observed. Methods We analyzed trial data to assess the effect of individual adherence to ALB MDA on clearance of circulating filarial antigenemia (CFA) and microfilaremia. Community residents were offered a single dose of ALB every 6 months and tested for LF with a rapid test for CFA at baseline and then annually. CFA test results were scored on a semi-quantitative scale. At each round, microfilaremia was assessed in CFA-positives. All CFA-positive subjects for whom at least one follow-up measure was available were included in the analyses. Parametric survival models were used to assess the influence of treatment adherence on LF infection indicators. Results Out of 2658 subjects enrolled in the trials, 394 and 129 were eligible for analysis of CFA and microfilaremia clearance, respectively. After adjusting for age, sex and initial CFA score, the predicted mean time for clearing CFA was shorter in persons who had taken 2 doses of ALB per year (3.9 years) than in persons who had taken 1 or 0 dose (4.4 and 5.3 years, P & .001 for both). A similar pattern was observed for microfilaremia clearance. Conclusions These results demonstrate a clear dose-response relationship for the effect of ALB on clearance of CFA and microfilaremia.

Rocking the boat of vitamin D research in schizophrenia and depression

SUMMARYA review of studies on vitamin D in schizophrenia and depression found insufficient evidence to inform advice for clinicians. On the basis of the review, I suggest advice for researchers, including better controlling for confounders in observational studies, testing the reverse causality hypothesis, studying vitamin D as a treatment or prevention specifically in patients with more pigmented skin, and prospective community trials of vitamin D supplementation combined with lifestyle advice.DECLARATION OF INTERESTNone.

Coproduction of Research Questions and Research Evidence in Public Health: The Study to Prevent Teen Drinking Parties

Community-based participatory research (CBPR) provides a set of principles and practices intended to foster coproduction of knowledge. However, CBPR often has shortcomings when applied to population-level policy and practice interventions, including a focus on single communities and a lack of focus on policy change. At the same time, community trials focused on policy have shortcomings, including lack of stakeholder involvement in framing research questions and modest engagement in study implementation and interpretation and dissemination of results. We describe an attempt to hybridize CBPR and community trials by creating a partnership that included a national membership organization, a coalition advisory board, intervention and delayed intervention communities, and an academic study team, which collaborated on a study of community strategies to prevent underage drinking parties. We use qualitative and quantitative data to critically assess the partnership. Areas where the partnership was effective included (1) identifying a research question with high public health significance, (2) enhancing the intervention, and (3) improving research methods. Challenges included community coalition representatives’ greater focus on their own communities rather than the production of broader scientific knowledge. This model can be applied in future attempts to narrow the gap between research, policy, and practice.