A quasi-experimental study estimating the impact of long-lasting insecticidal nets with and without piperonyl butoxide on pregnancy outcomes

Background Long-lasting insecticidal nets (LLINs) are the main vector control tool for pregnant women, but their efficacy may be compromised, in part, due to pyrethroid resistance. In 2017, the Ugandan Ministry of Health embedded a cluster randomized controlled trial into the national LLIN campaign, where a random subset of health subdistricts (HSDs) received LLINs treated with piperonyl butoxide (PBO), a chemical synergist known to partially restore pyrethroid sensitivity. Using data from a small, non-randomly selected subset of HSDs, this secondary analysis used quasi-experimental methods to quantify the overall impact of the LLIN campaign on pregnancy outcomes. In an exploratory analysis, differences between PBO and conventional (non-PBO) LLINs on pregnancy outcomes were assessed. Methods Birth registry data (n = 39,085) were retrospectively collected from 21 health facilities across 12 HSDs, 29 months before and 9 months after the LLIN campaign (from 2015 to 2018). Of the 12 HSDs, six received conventional LLINs, five received PBO LLINs, and one received a mix of conventional and PBO LLINs. Interrupted time-series analyses (ITSAs) were used to estimate changes in monthly incidence of stillbirth and low birthweight (LBW; <2500 g) before-and-after the campaign. Poisson regression with robust standard errors modeled campaign effects, adjusting for health facility-level differences, seasonal variation, and time-varying maternal characteristics. Comparisons between PBO and conventional LLINs were estimated using difference-in-differences estimators. Results ITSAs estimated the campaign was associated with a 26% [95% CI: 7–41] reduction in stillbirth incidence (incidence rate ratio (IRR) = 0.74 [0.59–0.93]) and a 15% [-7, 33] reduction in LBW incidence (IRR=0.85 [0.67–1.07]) over a 9-month period. The effect on stillbirth incidence was greatest for women delivering 7–9 months after the campaign (IRR=0.60 [0.41–0.87]) for whom the LLINs would have covered most of their pregnancy. The IRRs estimated from difference-in-differences analyses comparing PBO to conventional LLINs was 0.78 [95% CI: 0.52, 1.16] for stillbirth incidence and 1.15 [95% CI: 0.87, 1.52] for LBW incidence. Conclusions In this region of Uganda, where pyrethroid resistance is high, this study found that a mass LLIN campaign was associated with reduced stillbirth incidence. Effects of the campaign were greatest for women who would have received LLINs early in pregnancy, suggesting malaria protection early in pregnancy can have important benefits that are not necessarily realized through antenatal malaria services. Results from the exploratory analyses comparing PBO and conventional LLINs on pregnancy outcomes were inconclusive, largely due to the wide confidence intervals that crossed the null. Thus, future studies with larger sample sizes are needed.

Effect of Short-Term Heating on Bioefficacy of Deltamethrin-Coated Long-Lasting Insecticidal Nets

The authors recently reported that long-lasting insecticidal nets (LLINs) distributed in Papua New Guinea (PNG) between 2013 and 2019, exhibited severely diminished efficacy to knock down and kill susceptible Anopheles mosquitoes. This coincided with a rise in malaria observed in PNG since 2015. Here, the authors show that LLIN bioefficacy is increased by heating LLINs prior to WHO cone bioassays. Unused LLINs with low bioefficacy, delivered to PNG in 2019, were heated to 120°C for 5 minutes. Cone bioassays were performed before and at 1 hour, 7 days, and 30 days after heating. This led to a significant increase in 24-hour mortality (17–61%) and 60-minute knock down (31–72%). The effect was sustained over 30 days. Bioassays are crucial in quality assurance of LLIN products. Our findings indicate that bioefficacy of LLINs can be increased by heating. This may have implications for quality assurance procedures used to assess LLINs.

The effect of long-lasting insecticidal nets (LLINs) physical integrity on utilization

Background In Ethiopia, despite improvements in coverage and access, utilization of long-lasting insecticidal nets (LLINs) remains a challenge. Different household-level factors have been identified as associated with LLIN use. However, the contribution of LLIN physical integrity to their utilization is not well investigated and documented. This study aimed to assess the association between the physical integrity of LLINs and their use. Methods This study employed a nested case-control design using secondary data from the Ethiopian LLIN durability monitoring study conducted from May 2015 to June 2018. LLINs not used the night before the survey were identified as cases, while those used the previous night were categorized as controls. The physical integrity of LLINs was classified as no holes, good, acceptable, and torn using the proportionate hole index (pHI). A Generalized Estimating Equation (GEE) model was used to assess and quantify the association between LLIN physical integrity and use. The model specifications included binomial probabilistic distribution, logit link, exchangeable correlation matrix structure, and robust standard errors. The factors included in the model were selected first by fitting binary regression, and then by including all factors that showed statistical significance at P-value less than 0.25 and conceptually relevant variables into the multivariate regression model. Results A total of 5277 observations fulfilled the inclusion criteria. Out of these 1767 observations were cases while the remaining 3510 were controls. LLINs that were in torn physical condition had higher odds (AOR [95% CI] = 1.76 [1.41, 2.19]) of not being used compared to LLINs with no holes. Other factors that showed significant association included the age of the LLIN, sleeping place type, washing status of LLINs, perceptions towards net care and repair, LLIN to people ratio, economic status, and study site. Conclusion and recommendation LLINs that have some level of physical damage have a relatively higher likelihood of not being used. Community members need to be educated about proper care and prevention of LLIN damage to delay the development of holes as long as possible and use available LLINs regularly.

The First GLP Compliant Study in Africa for the Evaluation of LLIN’s; Efficacy of SafeNet® and SafeNet NF®

Background: To attain and sustain the universal Long-Lasting Insecticidal Nets (LLINs) coverage, cheap nets that provides equivalent or better protection than the standard LLINs, are required. While it is essential to follow the World Health Organization (WHO) guidelines for the evaluation of LLINs, adherence to the Good Laboratory Practice (GLP) is necessary to generate reliable and reproducible data that will facilitate efficient LLINs to be speedy registered. Adherence to GLP obviate the need to duplicate the assessment and ensures substandard LLINs are not reaching the market. This study aimed to evaluate efficacy of SafeNet NF® and SafeNet® LLIN in accordance to the WHO Pest Evaluation Scheme (WHOPES) and the GLP guidelines. Both candidate LLINs were manufactured with less fabrics to cut down manufacturing costs, motivated by the need for cheaper LLINs to achieve universal coverage. Materials & Methods: SafeNet NF® and SafeNet® LLIN, were assessed in experimental huts against wild, pyrethroid-resistant Anopheles arabiensis mosquitoes. Efficacy in terms of mosquito blood-feeding inhibition and mortality, was compared with Interceptor® LLIN and an untreated net. All nets were washed and artificially holed to simulate a used torn net. The GLP guidelines were followed throughout this study.Results: The mortality of mosquitoes exposed to SafeNet NF® and SafeNet® LLIN were equivalent to that of the reference net. Blood-feeding inhibition was only evident in Interceptor® LLIN. Adherence to GLP was observed throughout the study.Conclusions: Step-wise procedures to conduct LLIN evaluation in compliance to both WHOPES and GLP guidelines are elaborated in this study. SafeNet NF® and SafeNet® LLIN offers equivalent protection as Interceptor® LLIN and can facilitate universal LLIN coverage due to its low manufacturing cost. However, further research is needed to understand durability, acceptability and residual efficacy of these nets in field environments.

Reduction in Malaria Burden Following the Introduction of Indoor Residual Spraying in Areas Protected by Long Lasting Insecticidal Nets in Western Kenya, 2016 – 2018

Background: Long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) are the main malaria vector control measures. Kenya has employed multiple approaches, including free mass net distribution campaigns, for distributing LLINs to the community that resulted in increased household ownership of one or more nets from 44% in 2010 to 63 % in 2015. Migori and Homa Bay Counties are among the malaria endemic counties in Western Kenya that benefitted from three free mass net distribution campaigns between 2012 and 2018.. Widespread pyrethroid resistance among the primary vectors in Western Kenya has necessitated the re-introduction of IRS using an organophosphate insecticide, pirimiphos-methyl (Actellic® 300CS), as part of a strategy to manage insecticide-resistance. Evaluation of the effectiveness of the combined use of non-pyrethroid IRS and LLINs have yielded varied results. We aimed to evaluate malaria indicators before and after the introduction of IRS in a high malaria transmission area compared with an adjacent area where IRS was not introduced until one year later to estimate the effect of the intervention in an area with pyrethroid resistance.Methods: We reviewed records (MoH 405 A, 405 B, and 706) and tallied monthly aggregate of outpatient department (OPD) attendance, suspected malaria cases, those tested for malaria and those testing positive for malaria at two health facilities, one from Nyatike, an intervention sub-county, and one from Suba, a comparison sub-county, both located in Western Kenya, from February 1, 2016, through March 31, 2018. The first round of IRS was conducted in February – March 2017 in Nyatike sub-county and the second round one year later in both Nyatike and Suba sub-counties while the mass distribution of LLINs has been conducted in both locations. We performed a descriptive analysis and estimated the effect of the interventions and temporal changes of malaria indicators using Poisson regression for a period before and after implementation of the first round of IRS.Results: A higher reduction in the intervention area in total OPD, the proportion of OPD visits due to suspected malaria, testing positivity rate and annual malaria incidences except for the total OPD visits among the under 5 children where 59% decrease was observed in the comparison area while 33% decrease was observed in the intervention area (net change -27%, P <0.001). The percentage decline in annual malaria incidence observed in the intervention area was more than twice the observed percentage decline in the comparison area across all the age groups. A marked decline in the monthly testing positivity rate (TPR) was noticed in the intervention area, while no major changes were observed in the comparison area upon introduction of the non-pyrethroid IRS in the intervention area. The monthly TPR reduced from 46% in February 2016 (start of review period) to 11% in February 2018 (end of review period), representing a 76% absolute decrease in TPR among all ages (RR=0.24, 95% CI 0.12–0.46). In the comparison area, TPR was 16% in both February 2016 and February 2018 (RR=1.0, 95% CI 0.52–2.09). A month-by-month comparison revealed that the TPR in Year 2 remained lower than in Year 1 in the intervention area for most of the one year after the introduction of the IRS.Conclusions: Our findings demonstrated a reduced malaria burden among population protected by both non-pyrethroid IRS and LLINs implying a possible additional benefit afforded by the combined intervention in malaria endemic zone.

Effect of short-term heating on bioefficacy of deltamethrin-coated long-lasting insecticidal nets

We recently reported that long-lasting insecticidal nets (LLINs) distributed in Papua New Guinea (PNG) between 2013 and 2019, exhibited severely diminished efficacy to knock down and kill susceptible Anopheles mosquitoes. This coincided with a rise in malaria observed in PNG since 2015. Here we show that LLIN bioefficacy is increased by heating LLINs prior to WHO cone bioassays. Unused LLINs with low bioefficacy, delivered to PNG in 2019, were heated to 120 degrees Celsius for 5 minutes. Cone bioassays were performed before and at 1 h, 7 days and 30 days after heating. This led to a significant increase in 24 h mortality (17% to 61%) and 60 min knock down (31% to 72%). The effect was sustained over 30 days. Bioassays are crucial in quality assurance of LLIN products. Our findings indicate that bioassay results can easily be manipulated. This may have implications for quality assurance procedures used to assess LLINs.

Predictors of knowledge and use of long-lasting insecticidal nets for the prevention of malaria among the pregnant women in Pakistan

Background Malaria is endemic to Pakistan with high prevalence among pregnant women and linked with maternal anaemia, intrauterine growth retardation, preterm birth, and low birth weight. The use of long-lasting insecticidal nets (LLINs) is a proven and cost-effective intervention preventing malaria among pregnant women. The present study aimed to explore predictors of knowledge and use of LLINs among pregnant women in Pakistan. Methods This was part of a quasi-experimental study of 200 pregnant women conducted in a rural district of Sindh province in Pakistan. Data were collected using Malaria Indicator Survey questionnaires developed by Roll Back Malaria Partnership to end Malaria Monitoring and Evaluation Reference Group. Pregnant women and mothers with newborns of six months of age were interviewed in their homes. Results The age of the women was from 18 to 45, two thirds of the respondents (72.5%) were uneducated and married (77%). Majority (92%) of the women had received antenatal care during pregnancy, and 29.5% women had received counseling on malaria during their antenatal care visits. Multiple linear regression showed that the type of latrine was the most significant (β = 0.285, p < 0.001) determinant of knowledge about malaria among pregnant women followed by the death of a newborn (β = 0.271, p < 0.001). The use of mobile phone was the most significant (β = 0.247, p < 0.001) predictor of usage of LLINs among pregnant women followed by the death of a newborn (β = 0.232, p < 0.05). Conclusions Maternal education, type of latrine, use of mobile phone, malaria during previous pregnancy and newborn death were strong predictors of knowledge and use of LLINs in pregnant women in Pakistan. There is a need to scale-up programmes that aim to create awareness regarding malaria among pregnant women. Mobile phone technology can be used to implement awareness programmes focusing on malaria prevention among women.

The Unsustainability of Long-Lasting Insecticidal Nets

Long-lasting insecticidal nets (LLINs) are highly effective tools for malaria prevention, and it is clear bed nets are necessary. However, given the environmental concerns of the production, distribution, and disposal of LLINs, the malaria prevention community should look to design sturdier nets that last longer and are made of more sustainable materials to reduce harmful environmental impacts in a time when addressing climate change is urgent. We discuss concerns related to plastic pollution and the environmental health of LLINs in their current form, while recognizing the absolute importance of bed nets for malaria prevention. We call for conversation and innovation among all those involved in malaria prevention to address the unsustainability of LLINs and to maximize the resources available for malaria prevention in a climate of competing global health priorities.

Coverage, determinants of use and repurposing of long-lasting insecticidal nets two years after a mass distribution in Lihir Islands, Papua New Guinea: a cross-sectional study

Background Universal coverage with long-lasting insecticidal nets (LLINs) is an essential component of malaria control programmes. Three-yearly mass distribution of LLINs in Papua New Guinea (PNG) has been successful in reducing infection transmission since 2009, but malaria prevalence ramped up from 2015 onwards. Although LLIN universal coverage is mostly achieved during these campaigns, it may not be related with net use over time. Uses given to LLINs and non-compliance of this strategy were evaluated. Methods A knowledge, attitude and practice (KAP) cross-sectional study was conducted in Lihir Islands, PNG, 2–2.5 years after the last LLIN mass distribution campaign. Data on bed net ownership, use and maintenance behaviour was collected using a household questionnaire administered by trained community volunteers. Logistic regression models were used to identify factors associated with owning at least one LLIN and sleeping under a LLIN the previous night. Results Among 2694 households surveyed, 27.4 % (95 % CI: 25.8–29.2) owned at least one LLIN and 8.7 % (95 % CI: 7.6–9.8) had an adequate LLIN coverage (at least one LLIN for every two people). Out of 13,595 individuals in the surveyed households, 13.6 % (95 % CI: 13.0-–4.2) reported having slept under a LLIN the preceding night. Determinants for sleeping under LLIN included living in a household with adequate LLIN coverage [adjusted OR (aOR) = 5.82 (95 % CI: 3.23–10.49)], household heads knowledge about LLINs [aOR = 16.44 (95 % CI: 8.29–32.58)], and female gender [aOR = 1.92 (95 % CI: 1.53–2.40)] (all p-values < 0.001). LLIN use decreased with older age [aOR = 0.29 (95 % CI: 0.21–0.40) for ≥ 15 year-olds, aOR = 0.38 (95 % CI: 0.27–0.55) for 5–14 year-olds] compared to < 5 year-olds (p-value < 0.001). Knowledge on the use of LLIN was good in 37.0 % of the household heads. Repurposed nets were reported serving as fishing nets (30.4 %), fruits and seedlings protection (26.6 %), covering up food (19.0 %) and bed linen (11.5 %). Conclusions Two years after mass distribution, LLIN coverage and use in Lihir Islands is extremely low. Three yearly distribution campaigns may not suffice to maintain an acceptable LLIN coverage unless knowledge on maintenance and use is promoted trough educational campaigns.