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Abstract 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

Abstract Background Long-lasting insecticidal nets (LLINs) have contributed to the reduction of malaria in sub-Saharan Africa, including Tanzania. However, they rely on daily user behaviour and high coverage which is difficult to maintain. Also, insecticide resistance among malaria vector mosquitoes is contributing to reduced efficacy of control tools. To overcome these problems, we propose to evaluate a new tool for house modification, the insecticide-treated eave nets (ITENs) in combination with insecticide-treated window screens (ITWS) incorporated with dual active ingredient (dual AI) for the control of malaria. Methods Four hundred and fifty (450) households with intact walls, open eaves without screens or nets on the windows in Chalinze district will be eligible and recruited upon written informed consent. The households will be randomly allocated into two arms: one with ITENs and ITWS installed and the other without. Malaria parasite detection using a quantitative polymerase chain reaction (qPCR) will be conducted shortly after the long rain (June/July, 2022) as the primary outcome and shortly after the short rain (January/February, 2022) as the secondary outcome. Other secondary outcomes include clinical malaria cases, and density of malaria vectors and nuisance after the short rain and long rain. In addition, surveys will be conducted in households with ITENs and ITWS to estimate the intervention’s cost during installation, adverse effects one month after installation, and presence, fabric integrity and user acceptance six and twelve months after installation. Bioefficacy and chemical content will be evaluated twelve months after installation. Discussion ITENs and ITWS have been shown in Kenya to reduce indoor mosquito density. However, it is not known if indoor mosquito density reduction translates into reduction of malaria cases. Data from the study will measure the potential public health value of an additional intervention for malaria control at the household level in areas of mosquito insecticide resistance that does not require daily adherence. Trial registration The study is registered on ClinicalTrials.gov .

BackgroundTwo billion long-lasting insecticidal nets (LLINs) have been procured for malaria control. A functional LLIN is one that is present, is in good physical condition, and remains insecticidal, thereby providing protection against vector-borne diseases through preventing bites and killing disease vectors. The World Health Organization (WHO) prequalifies LLINs that remain adequately insecticidal 3 years after deployment. Therefore, institutional buyers often assume that prequalified LLINs are functionally identical with a 3-year lifespan. We measured the lifespans of 3 LLIN products, and calculated their cost per year of functional life, to demonstrate the economic and public health importance of procuring the most cost-effective LLIN product based on its lifespan.Methods and findingsA randomised double-blinded trial of 3 pyrethroid LLIN products (10,571 nets in total) was conducted at 3 follow-up points: 10 months (August-October 2014), 22 months (August-October 2015), and 36 months (October-December 2016) among 3,393 households in Tanzania using WHO-recommended methods. Primary outcome was LLIN functional survival (LLIN present and in serviceable condition). Secondary outcomes were (1) bioefficacy and chemical content (residual insecticidal activity) and (2) protective efficacy for volunteers sleeping under the LLINs (bite reduction and mosquitoes killed). Median LLIN functional survival was significantly different between the 3 net products (p = 0.001): 2.0 years (95% CI 1.7-2.3) for Olyset, 2.5 years (95% CI 2.2-2.8) for PermaNet 2.0 (hazard ratio [HR] 0.73 [95% CI 0.64-0.85], p = 0.001), and 2.6 years (95% CI 2.3-2.8) for NetProtect (HR = 0.70 [95% CI 0.62-0.77], p < 0.001). Functional survival was affected by accumulation of holes, leading to users discarding nets. Protective efficacy also significantly differed between products as they aged. Equivalent annual cost varied between US$1.2 (95% CI $1.1-$1.4) and US$1.5 (95% CI $1.3-$1.7), assuming that each net was priced identically at US$3. The 2 longer-lived nets (PermaNet and NetProtect) were 20% cheaper than the shorter-lived product (Olyset). The trial was limited to only the most widely sold LLINs in Tanzania. Functional survival varies by country, so the single country setting is a limitation.ConclusionsThese results suggest that LLIN functional survival is less than 3 years and differs substantially between products, and these differences strongly influence LLIN value for money. LLIN tendering processes should consider local expectations of cost per year of functional life and not unit price. As new LLIN products come on the market, especially those with new insecticides, it will be imperative to monitor their comparative durability to ensure that the most cost-effective products are procured for malaria control.

Abstract Background In Tanzania, the roles of men and women are classified based on the local cultural context. While men are usually the breadwinners, women are traditionally responsible for most domestic chores. Particularly for malaria prevention, studies in Africa have revealed women as being responsible for daily up-keep of the net. Using social role theory, this study explored the role of men and women in net care and repair and gender-related motivation and barriers to net care and repair in Tanzania. Methods The study was conducted in the two villages of Ruangwa district in Lindi Region. The study applied qualitative approaches and carried out in-depth interviews and focus group discussions with men, women, women with children under the age of five, and village key informants. Results Mosquito nets were valued by all participants as a protection measure against mosquitoes. Study findings indicate that net care and repair falls under a woman’s daily household responsibilities. While men were said to assist in stitching damaged nets, washing dirty bed nets was regarded inappropriate for men and not traditionally accepted. Motivation for net care and repair was reported to come from both men and women; for a woman keeping the net clean defined a caring and responsible woman, while men indirectly promoted net washing when complaining about nets being dirty. Women reported that men could do everything that women do regarding net care and repair, but that it does not fit into societal norms. Conclusion With increased globalization in Tanzania, more women are becoming part of the workforce, which may limit their full commitment to net care and repair activities, leading to increased net damage, malaria incidences and higher costs for malaria treatment. The National Malaria Control Programme should consider incorporating research-informed gender-transformative messages into their behaviour change communication on mosquito nets and work closely with trusted Community Health Workers to inform communities about the importance of sharing responsibilities in net care and repair. It is acknowledged that changing people’s behaviour and practices is a long process, which will require a deep cultural and political shift.

Abstract Background Malaria vector control in Tanzania is based on use of long-lasting insecticide treated nets (LLINs) and indoor residual spraying (IRS), which both rely on the use of chemical insecticides. The effectiveness of these control tools is endangered by the development of insecticide resistance in the major malaria vectors. This study was carried out to monitor the susceptibility status of major malaria vectors to insecticides used for IRS and LLINs in mainland Tanzania. Methods Mosquito larvae were collected in 20 sites of Tanzania mainland in 2015. Phenotypic resistance was determined using standard WHO susceptibility tests. Molecular assay were used to determine distribution of Anopheles gambiae sub-species. A microplate assay approach was used for identifying enzyme levels on single mosquitoes from each sites compared with a susceptible reference strain, An. gambiae sensu stricto (s.s.) Kisumu strain. Results Anopheles arabiensis was the dominant malaria specie in the country, accounting for 52% of the sibling species identified, while An. gambiae s.s. represented 48%. In Arumeru site, the dominant species was An. arabiensis, which was resistant to both pyrethroids (permethrin and deltamethrin), and pirimiphos-methyl, and had significant elevated levels of GSTs, non-specific esterases, and oxidase enzymes. An. arabiensis was also a dominant species in Kilombero and Kondoa sites, both were resistant to permethrin and deltamethrin with significant activity levels of oxidase enzymes. Resistance to bendiocarb was recorded in Ngara site where specie composition is evenly distributed between An. gambiae s.s. and An.arabiensis. Also bendiocarb resistance was recorded in Mbozi site, where An. gambiae s.s. is the dominant species. Conclusions Overall, this study confirmed resistance to all four insecticide classes in An. gambiae sensu lato in selected locations in Tanzania. Results are discussed in relation to resistance mechanisms and the optimization of resistance management strategies.

Abstract Background Larval source management strategies can play an important role in malaria elimination programmes, especially for tackling outdoor biting species and for eliminating parasite and vector populations when they are most vulnerable during the dry season. Effective larval source management requires tools for identifying geographic foci of vector proliferation and malaria transmission where these efforts may be concentrated. Previous studies have relied on surface topographic wetness to indicate hydrological potential for vector breeding sites, but this is unsuitable for karst (limestone) landscapes such as Zanzibar where water flow, especially in the dry season, is subterranean and not controlled by surface topography. Methods We examine the relationship between dry and wet season spatial patterns of diagnostic positivity rates of malaria infection amongst patients reporting to health facilities on Unguja, Zanzibar, with the physical geography of the island, including land cover, elevation, slope angle, hydrology, geology and geomorphology in order to identify transmission hot spots using Boosted Regression Trees (BRT) analysis. Results The distribution of both wet and dry season malaria infection rates can be predicted using freely available static data, such as elevation and geology. Specifically, high infection rates in the central and southeast regions of the island coincide with outcrops of hard dense limestone which cause locally elevated water tables and the location of dolines (shallow depressions plugged with fine-grained material promoting the persistence of shallow water bodies). Conclusions This analysis provides a tractable tool for the identification of malaria hotspots which incorporates subterranean hydrology, which can be used to target larval source management strategies.

Background: The prognostic value of KRAS mutations in colon adenocarcinoma is controversial. We examined this question as an ancillary study of the PETACC8 phase III trial., Patients and Methods: We analyzed the prognostic impact of KRAS exon 2 mutations in stage III colon cancer patients (n = 1657) receiving adjuvant FOLFOX ± cetuximab therapy included in the PETACC8 trial. Patients with BRAF-mutated cancers were excluded and, as no difference was found for time to recurrence (TTR) and disease-free survival (DFS) between treatment arms, both were pooled for analysis. Associations with TTR and DFS were analyzed using a Cox proportional hazards model., Results: KRAS mutations were found in 638 of 1657 tumors and linked to shorter TTR (P < 0.001). However, when specific mutations were compared with wild-type, codon 12 mutations [hazard ratio (HR) 1.67, 95% confidence interval (CI) 1.35-2.04; P < 0.001] but not codon 13 (HR 1.23, 95% CI 0.85-1.79; P = 0.26) were significantly associated with shorter TTR, independently of other covariates. The interaction test showed that, regarding tumor location (distal versus proximal), KRAS genotype affects differently on recurrence (P = 0.02) and DFS (P = 0.042). Subgroup analysis showed that KRAS only affected TTR and DFS in distal tumors (n = 1043; 692 wild type; 351 mutated), with an increased risk of relapse (HR 1.96, 95% CI 1.51-2.56; P < 0.0001) for KRAS codon 12 mutations and a borderline significance for codon 13 mutations (HR 1.59, 95% CI 1.00-2.56; P = 0.051)., Conclusion: KRAS exon 2 mutations are independent predictors of shorter TTR in patients with resected stage III distal colon cancers receiving adjuvant therapy. Future clinical trials in the adjuvant setting should consider both the tumor location and KRAS mutations as important stratification factors., Clinical Trial Number: This is an ancillary study of the PETACC8 trial: EUDRACT 2005-003463-23., (© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)