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Anopheles arabiensis and Anopheles funestus sensu stricto mosquitoes are major East African malaria vectors. Understanding their dispersal and population structure is critical for developing effective malaria control tools. Three mark-release-recapture (MRR) experiments were conducted for 51 nights to assess daily survival and flight range of An. arabiensis and An. funestus mosquitoes in south-eastern, Tanzania. Mosquitoes were marked with a fluorescent dye as they emerged from breeding sites via a self-marking device. Mosquitoes were collected indoors and outdoors using human landing catches (HLC) and Centers for Disease Control and Prevention light traps (CDC-LT). In total, 4210 An. arabiensis and An. funestus were collected with 316 (7.5%) marked and recaptured (MR). Daily mean MR was 6.8, standard deviation (SD ± 7.6) for An. arabiensis and 8.9 (SD ± 8.3) for An. funestus. Probability of daily survival was 0.76 for An. arabiensis and 0.86 for An. funestus translating into average life expectancy of 3.6 days for An. arabiensis and 6.5 days for An. funestus . Dispersal distance was 654 m for An. arabiensis and 510 m for An. funestus . An. funestus life expectancy was substantially longer than that of An. arabiensis . The MRR method described here could be routinely utilized when evaluating the impact of new vector control tools on mosquito survival.

As insecticide resistance spreads in Africa, next-generation insecticide-treated nets (ITNs) are increasingly being deployed to protect vulnerable populations against malaria. While these nets provide greater entomological efficacy against resistant mosquitoes, their effectiveness against malaria transmission also depends on other factors, such as durability, access, usage, and activity patterns of hosts and vectors. Here, we quantify the impact of two next-generation ITNs, namely Interceptor®G2 (chlorfenapyr-pyrethroid) and Olyset® Plus (piperonyl butoxide-pyrethroid), in a cascade from entomological efficacy to population-level effectiveness. We use a mathematical model that we parameterize with entomological data and validate against results from randomized controlled trials. We found that, beyond entomological factors, operational factors including functional survival, ITN use and in-bed exposure critically impact ITN effectiveness overall and per ITN types. Our results obtained for Tanzania can be extended to other contexts in a dashboard allowing users to explore product selection based on setting-specific factors that influence ITN effectiveness. Insecticide resistance can limit the effectiveness of insecticide-treated nets for malaria prevention, but other factors such as access and durability also contribute. Here, the authors quantify impacts of this ‘cascade’ of factors using a mathematical model.

Background Increasing metabolic resistance in malaria vector mosquitoes resulted in the development of insecticide-treated nets (ITNs) with active ingredients (AI) that target them. Bioassays that accurately measure the mortality induced by these AIs on ITNs are needed. Mosquito metabolic enzyme expression follows a circadian rhythm. Thus, this study assessed (i) influence of the time of day of mosquito exposure and (ii) timing of assessment of mortality post exposure (24 and 72 h) to ITNs against vectors that are susceptible to pyrethroids and those with metabolic and knockdown resistance mechanisms. Methods Two cone bioassay experiments were conducted following World Health Organization (WHO) guidelines. Firstly, on ITNs incorporated with 2 g AI/kg of deltamethrin (DM) alone, or combined with 8 g AI/kg piperonyl butoxide (PBO) synergist, during the day (9:00–14:00 h) and repeated in the evening (18:00–20:00 h). This was followed by a confirmatory experiment during the afternoon (12:00–14:00 h) and repeated in the night (22:00–24:00 h) using mosquitoes unexposed or pre-exposed to PBO for 1 h before exposure to DM ITNs. Each net piece was tested with a minimum of eight cones per time (N = 24). The outcome was mortality after 24 h (M24) or 72 h (M72) of holding. Results The cone bioassays performed using metabolic resistant mosquitoes during the evening showed significantly lower M24 than those performed in the day for DM: odds ratio (OR) 0.14 [95% confidence interval (CI) 0.06–0.30, p  < 0.0001] and DM PBO [OR 0.29 (95% CI 0.18—0.49, p  < 0.0001). M72 was higher than M24 for metabolic resistant mosquitoes exposed to DM [OR 1.44 (95% CI 1.09–1.88), p  = 0.009] and DM PBO [OR 1.82 (95% CI 1.42–2.34), p  < 0.0001]. An influence of hour of experiment and time of assessment was not observed for mosquitoes that had knockdown resistance or that were pyrethroid-susceptible. Conclusions Time of day of experiment and hour of assessment of delayed mortality after exposure of mosquitoes are important considerations in evaluating insecticides that interact with mosquito metabolism to counter metabolic resistant mosquitoes. This is important when evaluating field-aged ITNs that may have lower concentrations of AI. Graphical Abstract

Background Vector mosquito biting intensity is an important measure to understand malaria transmission. Human landing catch (HLC) is an effective but labour-intensive, expensive, and potentially hazardous entomological surveillance tool. The Centres for Disease Control light trap (CDC-LT) and the human decoy trap (HDT) are exposure-free alternatives. This study compared the CDC-LT and HDT against HLC for measuring Anop heles biting in rural Tanzania and assessed their suitability as HLC proxies. Methods Indoor mosquito surveys using HLC and CDC-LT and outdoor surveys using HLC and HDT were conducted in 2017 and in 2019 in Ulanga, Tanzania in 19 villages, with one trap/house/night. Species composition, sporozoite rates and density/trap/night were compared. Aggregating the data by village and month, the Bland–Altman approach was used to assess agreement between trap types. Results Overall, 66,807 Anopheles funestus and 14,606 Anopheles arabiensis adult females were caught with 6,013 CDC-LT, 339 indoor-HLC, 136 HDT and 195 outdoor-HLC collections. Indoors, CDC-LT caught fewer An. arabiensis (Adjusted rate ratio [Adj.RR] = 0.35, 95% confidence interval [CI]: 0.27–0.46, p < 0.001) and An. funestus (Adj.RR = 0.63, 95%CI: 0.51–0.79, p < 0.001) than HLC per trap/night . Outdoors, HDT caught fewer An. arabiensis (Adj.RR = 0.04, 95%CI: 0.01–0.14, p < 0.001) and An. funestus (Adj.RR = 0.10, 95%CI: 0.07–0.15, p < 0.001) than HLC. The bias and variability in number of mosquitoes caught by the different traps were dependent on mosquito densities. The relative efficacies of both CDC-LT and HDT in comparison to HLC declined with increased mosquito abundance. The variability in the ratios was substantial for low HLC counts and decreased as mosquito abundance increased. The numbers of sporozoite positive mosquitoes were low for all traps. Conclusions CDC-LT can be suitable for comparing mosquito populations between study arms or over time if accuracy in the absolute biting rate, compared to HLC, is not required. CDC-LT is useful for estimating sporozoite rates because large numbers of traps can be deployed to collect adequate mosquito samples. The present design of the HDT is not amenable for use in large-scale entomological surveys. Use of HLC remains important for estimating human exposure to mosquitoes as part of estimating the entomological inoculation rate (EIR).

Background Quality assurance (QA) of insecticide-treated nets (ITNs) delivered to malaria-endemic countries is conducted by measuring physiochemical parameters, but not bioefficacy against malaria mosquitoes. This study explored utility of cone bioassays for pre-delivery QA of pyrethroid ITNs to test the assumption that cone bioassays are consistent across locations, mosquito strains, and laboratories. Methods Double-blinded bioassays were conducted on twenty unused pyrethroid ITNs of 4 brands (100 nets, 5 subsamples per net) that had been delivered for mass distribution in Papua New Guinea (PNG) having passed predelivery inspections. Cone bioassays were performed on the same net pieces following World Health Organization (WHO) guidelines at the PNG Institute of Medical Research (PNGIMR) using pyrethroid susceptible Anopheles farauti sensu stricto ( s.s .) and at Ifakara Health Institute (IHI), Tanzania using pyrethroid susceptible Anopheles gambiae s.s . Additionally, WHO tunnel tests were conducted at IHI on ITNs that did not meet cone bioefficacy thresholds. Results from IHI and PNGIMR were compared using Spearman’s Rank correlation, Bland–Altman (BA) analysis and analysis of agreement. Literature review on the use of cone bioassays for unused pyrethroid ITNs testing was conducted. Results In cone bioassays, 13/20 nets (65%) at IHI and 8/20 (40%) at PNGIMR met WHO bioefficacy criteria. All nets met WHO bioefficacy criteria on combined cone/tunnel tests at IHI. Results from IHI and PNGIMR correlated on 60-min knockdown (KD60) (r s  = 0.6, p  = 0.002,n = 20) and 24-h mortality (M24) (r s  = 0.9, p  < 0.0001,n = 20) but BA showed systematic bias between the results. Of the 5 nets with discrepant result between IHI and PNGIMR, three had confidence intervals overlapping the 80% mortality threshold, with averages within 1–3% of the threshold. Including these as a pass, the agreement between the results to predict ITN failure was good with kappa = 0.79 (0.53–1.00) and 90% accuracy. Conclusions Based on these study findings, the WHO cone bioassay is a reproducible bioassay for ITNs with > 80% M24, and for all ITNs provided inherent stochastic variation and systematic bias are accounted for. The literature review confirms that WHO cone bioassay bioefficacy criteria have been previously achieved by all pyrethroid ITNs (unwashed), without the need for additional tunnel tests. The 80% M24 threshold remains the most reliable indicator of pyrethroid ITN quality using pyrethroid susceptible mosquitoes. In the absence of alternative tests, cone bioassays could be used as part of pre-delivery QA.

Background Insecticide-treated nets (ITNs) and house modifications are proven vector control tools, yet in most regions, full coverage has not been achieved. This study investigates household factors associated with access to ITNs and house modification in Tanzania. Methods Baseline cross-sectional survey data from previous studies on spatial repellants and indoor residual spray evaluation was analysed from 6757 households in Bagamoyo (60 km north of Dar es Salaam) and 1241 households in Ulanga (a remote rural area in southeast Tanzania), respectively. Regression models were used to estimate the associations between the outcomes: population access to ITNs, access to ITN per sleeping spaces, window screens and closed eaves, and the covariates household size, age, gender, pregnancy, education, house size, house modification (window screens and closed eaves) and wealth. Results Population access to ITNs (households with one ITN per two people that stayed in the house the previous night of the survey) was 69% (n = 4663) and access to ITNs per sleeping spaces (households with enough ITNs to cover all sleeping spaces used the previous night of the survey) was 45% (n = 3010) in Bagamoyo, 3 years after the last mass campaign. These findings are both lower than the least 80% coverage target of the Tanzania National Malaria Strategic Plan (Tanzania NMSP). In Ulanga, population access to ITNs was 92% (n = 1143) and ITNs per sleeping spaces was 88% (n = 1093), 1 year after the last Universal Coverage Campaign (UCC). Increased household size was significantly associated with lower access to ITNs even shortly after UCC. House modification was common in both areas but influenced by wealth. In Bagamoyo, screened windows were more common than closed eaves (65% vs 13%), whereas in Ulanga more houses had closed eaves than window screens (55% vs 12%). Conclusion Population access to ITNs was substantially lower than the targets of the Tanzania NMSP after 3 years and lower among larger households after 1 year following ITN campaign. House modification was common in both areas, associated with wealth. Improved access to ITNs and window screens through subsidies and Behaviour Change Communication (BCC) strategies, especially among large and poor households and those headed by people with a low level of education, could maximize the uptake of a combination of these two interventions.

Background The fabric integrity of insecticide-treated nets (ITNs) deteriorates over time during household use, often leading households to discard or stop using damaged nets. This study quantified the extent to which net loss from households is attributable to declining fabric integrity, accounting for variation in user behaviour and environmental conditions. Methods This secondary analysis used data from an ITN durability trial in Bagamoyo, Tanzania. A total of 2,514 ITNs (three pyrethroid-PBO and one pyrethroid-only) distributed among 1,509 households were included because they had the outcome of interest (attrition). Fabric integrity was classified as good, damaged, or too-torn according to WHO ITN guidelines and assessed at 12-month intervals. The association between fabric integrity and net attrition over the subsequent 12 months was evaluated using an adjusted logistic regression model, accounting for net type, household risk index, household size, and age of the household head as fixed effects, with household as a random effect. Results Attrition increased over time, from 20% at one year to 53% at two years, and 83% at three years post-distribution, and it was associated with net type, household risk index, household size, and age of the household head. Damaged ITNs at one year were more likely to be lost by year two. Compared to nets in good condition, damaged nets had higher odds of attrition (OR: 1.73, 95% CI 1.06–2.82), and too-torn nets were at greater risk (OR: 9.82, 95% CI 5.87–16.4). Similar patterns were observed between years two and three (damaged: OR = 1.55, 95% CI 0.83–2.90; too-torn: OR = 11.7, 95% CI 6.16–22.3). Conclusion Fabric integrity was the main driver of rapid ITN attrition and the strongest predictor of loss. Damaged nets were approximately twice as likely to be discarded after one year and at least ten times more likely to be lost in years two and three. These findings highlight the importance of promoting proper net care practices and procuring durable nets that withstand harsh household conditions, ensuring sustained population coverage.

Transmission-blocking vaccines are among the novel tools under development for malaria control and elimination. Understanding the human immune response to the sexual stages of Plasmodium falciparum is essential for progressing transmission-blocking vaccine development. A serosurvey was conducted in Tanzania, from May to August 2022 among 290 participants, consisting of 114 children (5–12 years), 44 adolescents (13–17 years), and 132 adults (18–45 years). The participants were tested for malaria parasites using quantitative polymerase chain reaction, and standardized enzyme-linked immunosorbent assays were performed to detect the presence of IgG antibodies against transmission-blocking target antigens—Pfs230D1M, Pfs48/45, and Pfs25. A set of 10 plasma samples that were reactive to Pfs230DIM and/or Pfs48/45 were tested individually for transmission-reducing activity via standard membrane feeding assays. Of the participants tested, 56% (157/281) had detectable Pfs230D1M antibodies, and 49% (141/290) were positive for Pfs48/45 IgG. Approximately 30% were seropositive for both. However, Pfs25 IgG was not detected in any of the 117 participants tested. The seroprevalence for Pfs230D1M and Pfs48/45 IgG increased significantly with participants’ age, with adults more likely to have antibodies than children: Pfs230D1M (adjusted odds ratio: 3.16, 95% confidence interval: 1.81–5.53, p -value ≤ 0.0001) and Pfs45/48 (OR: 3.06, 95% CI: 1.79–5.25, p ≤ 0.0001). There was no significant difference in antibody titers for Pfs230D1M and Pfs48/45 antibodies across age groups. A significant transmission-reducing activity was observed in 2/10 participants, who were highly reactive to Pfs230D1M and Pfs48/45. Naturally acquired antibody responses to both full-length Pfs48/45 and Pfs230D1M proteins are prevalent and appeared to be stable, suggesting that semi-immune populations may be ideal to evaluate boosting transmission-blocking vaccine candidates.

Background The WHO cone bioassay is routinely used to evaluate the bioefficacy of insecticide-treated nets (ITNs) for product pre-qualification and confirmation of continued ITN performance during operational monitoring. Despite its standardized nature, variability is often observed between tests. We investigated the influence of temperature in the testing environment, mosquito feeding status and mosquito density on cone bioassay results. Methods Cone bioassays were conducted on MAGNet (alphacypermethrin) and Veeralin (alphacypermethrin and piperonyl butoxide (PBO)) ITNs, using laboratory-reared pyrethroid-resistant Anopheles funestus sensu stricto (FUMOZ strain) mosquitoes. Three experiments were conducted using standard cone bioassays following WHO-recommended test parameters, with one variable changed in each bioassay: (i) environmental temperature during exposure: 22–23 °C, 26–27 °C, 29–30 °C and 32–33 °C; (ii) feeding regimen before exposure: sugar starved for 6 h, blood-fed or sugar-fed; and (iii) mosquito density per cone: 5, 10, 15 and 20 mosquitoes. For each test, 15 net samples per treatment arm were tested with four cones per sample ( N  = 60). Mortality after 24, 48 and 72 h post-exposure to ITNs was recorded. Results There was a notable influence of temperature, feeding status and mosquito density on An. funestus mortality for both types of ITNs. Mortality at 24 h post-exposure was significantly higher at 32–33 °C than at 26–27 °C for both the MAGNet [19.33% vs 7%; odds ratio (OR): 3.96, 95% confidence interval (CI): 1.99–7.87, P  < 0.001] and Veeralin (91% vs 47.33%; OR: 22.20, 95% CI: 11.45–43.05, P  < 0.001) ITNs. Mosquito feeding status influenced the observed mortality. Relative to sugar-fed mosquitoes, The MAGNet ITNs induced higher mortality among blood-fed mosquitoes (7% vs 3%; OR: 2.23, 95% CI: 0.94–5.27, P  = 0.068) and significantly higher mortality among starved mosquitoes (8% vs 3%, OR: 2.88, 95% CI: 1.25–6.63, P  = 0.013); in comparison, the Veeralin ITNs showed significantly lower mortality among blood-fed mosquitoes (43% vs 57%; OR: 0.56, 95% CI: 0.38–0.81, P  = 0.002) and no difference for starved mosquitoes (58% vs 57%; OR: 1.05, 95% CI: 0.72–1.51, P  = 0.816). Mortality significantly increased with increasing mosquito density for both the MAGNet (e.g. 5 vs 10 mosquitoes: 7% vs 12%; OR: 1.81, 95% CI: 1.03–3.20, P  = 0.040) and Veeralin (e.g. 5 vs 10 mosquitoes: 58% vs 71%; OR 2.06, 95% CI: 1.24–3.42, P  = 0.005) ITNs. Conclusions The results of this study highlight that the testing parameters temperature, feeding status and mosquito density significantly influence the mortality measured in cone bioassays. Careful adherence to testing parameters outlined in WHO ITN testing guidelines will likely improve the repeatability of studies within and between product testing facilities. Graphical Abstract

Background Non-inferiority trials are recommended by the World Health Organization (WHO) to demonstrate that health products show comparable efficacy to that of existing standard of care. As part of the WHO Global Malaria Programme (GMP) process of assessment of malaria vector control products, a second-in-class insecticide-treated net (ITN) must be shown to be non-inferior to a first-in-class product based on mosquito mortality. The public health impact of the first-in-class pyrethroid-piperonyl butoxide (PBO) ITN, Olyset ® Plus, has been demonstrated in epidemiological trials in areas with insecticide-resistant mosquitoes, but there is a need to determine the efficacy of other pyrethroid-PBO nets to ensure timely market availability of nets in order to increase access to ITNs. The non-inferiority of a deltamethrin-PBO ITN Yorkool ® G3 was evaluated entomologically against Olyset ® Plus in experimental huts in Tanzania, following WHO guidelines for non-inferiority trials. Methods The trial of the two pyrethroid-PBO ITNs was conducted in experimental huts in Lupiro, Tanzania, using a randomized 7 × 7 Latin square block design. The study ran for 49 nights in 14 huts assessing the mosquito mortality and blood-feeding of wild, free-flying, pyrethroid-resistant Anopheles arabiensis . Using the non-inferiority approach, the comparative efficacy (primary endpoint was mosquito mortality at 24 h and secondary endpoint was blood-feeding) of unwashed and 20 times field-washed pyrethroid-PBO Yorkool ® G3 ITNs, were compared with the first-in-class product Olyset ® Plus and against a pyrethroid-only ITN, PermaNet ® 2.0 ITNs, as a standard comparator. Results The experimental hut trial demonstrated non-inferiority and superiority of Yorkool ® G3 to Olyset ® Plus based on mosquito mortality [51% vs. 39%, OR 1.68 (95% CI 1.50–1.88)], given that lower 95% CI exceeded 0.74 (delta of 39%) and the margin of no difference (1). Blood-feeding inhibition was high for all treated ITNs (> 90%) and Yorkool® G3 was non-inferior to Olyset® Plus [4% vs. 2%, OR 1.81 (95% CI 1.46–2.39)], given that upper 95% CI was less than 4.85 (delta of 4%). The pyrethroid-PBO ITNs were superior to the pyrethroid-only net, PermaNet ® 2.0, as determined by both the proportion of mortality and blood-feeding of mosquitoes ( p -value < 0.05). Conclusion Yorkool ® G3 ITNs demonstrated non-inferiority to the first-in-class Olyset® Plus and superiority over the standard pyrethroid-only ITN, PermaNet ® 2.0 as measured by mortality and blood-feeding inhibition of wild pyrethroid-resistant An. arabiensis mosquitoes. Yorkool ® G3 ITNs are potential tools for the control of metabolic insecticide-resistant malaria vectors, and their market availability will contribute to the cost-effective selection of ITNs by malaria control programmes to improve population access to ITNs.