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Abstract Background Cholera outbreaks have occurred in Tanzania since 1974. To date, the genetic epidemiology of these outbreaks has not been assessed. Methods 96 Vibrio cholerae O1 isolates from five regions were characterized, and their genetic relatedness assessed using multi-locus variable-number tandem-repeat analysis (MLVA) and whole genome sequencing (WGS). Results Of the 48 MLVA genotypes observed, 3 were genetically unrelated to any others, while the remaining 45 genotypes separated into three MLVA clonal complexes (CCs) - each comprised of genotypes differing by a single allelic change. In Kigoma, two separate outbreaks, 4 months apart (January and May, 2015), were each caused by genetically distinct strains by MLVA and WGS. Remarkably, one MLVA CC contained isolates from both the May outbreak and ones from the 2011/2012 outbreak in Dar-es-Salaam. However, WGS revealed the isolates from the two outbreaks to be distinct clades. The outbreak that started in August 2015 in Dar-es-Salaam and spread to Morogoro, Singida and Mara was comprised of a single MLVA CC and WGS clade. Isolates from within an outbreak were closely related differing at fewer than 5 nucleotides. All isolates were part of the 3rd wave of the 7th pandemic and were found in four clades related to isolates from Kenya and Asia. Conclusions We conclude that genetically related V. cholerae cluster in outbreaks, and distinct strains circulate simultaneously.

Abstract Background The Dual-Active Ingredient long-lasting insecticidal nets (Dual-AI LLIN) have been developed to counteract the reduced efficacy of pyrethroid (PY)-only nets due to widespread pyrethroid insecticide resistance in malaria vector mosquitoes. They constitute half of the nets distributed in sub-Saharan Africa between 2022 and 2024. However, their effectiveness once they develop holes is unclear, particularly in pyrethroid-resistant settings. This study evaluates the textile integrity of three dual- AI LLINs compared to standard PY LLN, over 3 years of use in a community in Tanzania and the associated impact on malaria prevalence and incidence. Methods A secondary analysis of data from a randomized controlled trial (RCT) in North-western Tanzania was conducted to evaluate the effectiveness of α-cypermethrin only; pyriproxyfen and α-cypermethrin (PPF-PY); chlorfenapyr and α-cypermethrin (chlorfenapyr-PY); and the synergist piperonyl butoxide and permethrin (PBO-PY) LLINs on malaria infection prevalence and case incidence. The association between the net textile condition and 1/malaria prevalence over 3 years of use between 2019 and 2022, and 2/malaria case incidence in a cohort of children over 2 years of follow-up was assessed between 2019 and 2021. Results There was no significant association between damaged (OR 0.98, 95% CI 0.71–1.37, p-value = 0.655) and too-torn (OR 1.07, 95% CI 0.77–1.47, p-value = 0.694) compared to intact nets on malaria prevalence for all net types. However, there were reduced rates of malaria case incidence in children sleeping under a net in good condition compared to too-torn nets (incidence rate ratio (IRR) 0.76 [95% CI 0.63–0.92], p = 0.005). Malaria incidence was also consistently lower in too-torn PBO-PY LLIN (IRR = 0.37 [95% CI 0.19–0.72], p = 0.003) and chlorfenapyr-PY LLIN (IRR = 0.45 [95% CI 0.33–0.97], p = 0.053) compared to an intact PY-only LLIN during the first year of follow up. In year 2, the incidence was only significantly lower in intact chlorfenapyr-PY LLIN (IRR = 0.49 [95% CI 0.29–0.81], p = 0.006) compared to intact PY LLIN. Conclusion The study confirmed that sleeping under a chlorfenapyr-PY LLIN or PBO-PY LLIN offered superior protection to pyrethroid-only nets even when torn. Preventing the development of holes is essential as they impact the level of protection offered against malaria infection. Trial registration: ClinicalTrials.gov, number (NCT03554616)

Abstract Background After decades of success in reducing malaria through the scale-up of pyrethroid long-lasting insecticidal nets (LLINs), the decline in the malaria burden has stalled, coinciding with the rapid spread of pyrethroid resistance. In a previously reported study, nets treated with a pyrethroid and a synergist, piperonyl butoxide (PBO), demonstrated superior efficacy compared to standard pyrethroid LLINs (std-LLINs) against malaria. Evidence was used to support the public health recommendation of PBO-Pyrethroid-LLIN by the World Health Organization in 2018. This study looks at the third year of rollout of these nets in Muleba district, Tanzania to inform whether policy guidelines need to be updated. Methods A four-group cluster randomized trial (CRT) using a two-by-two factorial design was carried out between January 2014 and December 2017. A total of 48 clusters, were randomized in a 1:1:1:1 ratio to the following treatment groups, each intervention being provided once in 2015: 1/std-LLIN; 2/PBO-pyrethroid LLIN; 3/std-LLIN + Indoor Residual Spraying (IRS) and 4/PBO-Pyrethroid-LLIN + IRS. During the third year follow-up, malaria infection prevalence in 80 children per cluster, aged 6 months to 14 years, was measured at 28- and 33-months post-intervention and analysed as intention-to-treat (ITT) and per protocol (PP). Mosquito collections were performed monthly in all clusters, using CDC light traps in 7 randomly selected houses per cluster. Results At 28 and 33 months, study net usage among household participants was only 47% and 31%, respectively. In ITT analysis, after 28 months malaria infection prevalence among 7471 children was 80.9% in the two std-LLIN groups compared to 69.3% in the two PBO-Pyrethroid-LLIN (Odds Ratio: 0.45, 95% Confidence Interval: 0.21–0.95, p-value: 0.0364). After 33 months the effect was weaker in the ITT analysis (prevalence 59.6% versus 49.9%, OR: 0.60, 95%CI:0.32–1.13, p-value: 0.1131) but still evident in the PP analysis (57.2% versus 44.2%, OR: 0.34, 95%CI: 0.16–0.71, p-value: 0.0051). Mean number of Anopheles per night collected per house was similar between PBO-Pyrethroid-LLIN groups (5.48) and std-LLIN groups (5.24) during the third year. Conclusions Despite low usage of PBO- Pyrethroid LLIN, a small impact of those nets on malaria infection prevalence was still observed in the 3rd year with the most protection offered to children still using them. To maximize impact, it is essential that net re-distribution cycles are aligned with this LLIN lifespan to maintain maximum coverage. Trial registration: The trial was registered with ClinicalTrials.gov (registration number NCT02288637).

Pyrethroid-treated long-lasting insecticidal nets (LLINs) have been the main contributor to the reduction in malaria in the past two decades in sub-Saharan Africa. The development of pyrethroid insecticide resistance threatens the future of LLINs, especially when nets become holed and pyrethroid decays. In this study, three new classes of dual-active ingredient (AI) LLINs were evaluated for their physical durability: (1) Royal Guard, combining pyriproxyfen, which disrupts female fertility, and a pyrethroid, alpha-cypermethrin; (2) Interceptor G2, which combines the pyrrole chlorfenapyr and a pyrethroid (alpha-cypermethrin); (3) Olyset Plus, which incorporates the pyrethroid permethrin and the synergist piperonyl butoxide, to enhance the pyrethroid potency; and Interceptor, a reference net that contains alpha-cypermethrin as the sole active ingredient. About 40,000 nets of each type were distributed in February 2019 to different villages in Misungwi. A total of 3072 LLINs were followed up every 6–12 months up to 36 months to assess survivorship and fabric integrity. The median functional survival was less than three years with Interceptor, Interceptor G2, and Royal Guard showing 1.9 years each and Olyset Plus showing 0.9 years. After 36 months, 90% of Olyset Plus and Royal Guard and 87% of Interceptor G2 were no longer in use (discarded) due to wear and tear, compared to 79% for Interceptor. All dual-AI LLINs exhibited poor textile durability, with Olyset Plus being the worst.

BackgroundAfter a decade of successful control, malaria is on the rise again. The prevalence of malaria in Tanzania has increased from 7% in 2017 to 8% in 2022 and reached 18% in Kagera region in the North West of Tanzania. Malaria vectors in Muleba district Kagera have high level of pyrethroid resistance. The aim of this paper is to explore factors associated with malaria infection prevalence in children aged 6 months to 14 years in Muleba, where Long Lasting Insecticidal Net (LLIN) combining a pyrethroid insecticide and synergist piperonyl butoxide (PBO) that counteract resistance in the mosquitoes, was first distributed under trial conditions in 2015.MethodsThe trial was a community randomized control in which there were two malaria prevalence cross-sectional household surveys each year (June and December) from 2015 to 2017 in Muleba. In this study we conducted a secondary data analysis of the December surveys only. Multilevel Poisson regression analysis was used to assess factors associated with malaria infection.ResultsA total of 10,941 children and 4,611 households were included in this study. Overall malaria prevalence was 35.8%, 53.3% and 54.4% in the year 2015, 2016 and 2017 respectively. Living in an area with standard LLIN as opposed to the novel PBO synergist LLIN, being a male child, above 5 years of age, living in a house with open eaves, living in house without IRS, having head of household with no formal education, lower socioeconomic status and survey year were associated with increased risk of malaria infection.ConclusionsUsing PBO LLIN reduced the risk of malaria infection. However, additional measures could further reduce malaria infection in areas of insecticide resistance such as housing improvement.

Assessing the readiness of health facilities to deliver safe male circumcision services is more important in sub-Saharan Africa because of the inadequacy state of health facilities in many ways. The World Health Organization recommends that only facilities equipped with available trained staff, capable to perform at least minor surgery, able to offer minimum MC package and appropriate equipment for resuscitation, and compliant with requirements for sterilization and infection control should be allowed to deliver safe circumcision services. A cross-sectional study using quantitative data collection technique was conducted to assess the readiness of the health facilities to deliver safe circumcision services in selected districts of Tanzania. All hospitals, health centres and 30% of all dispensaries in these districts were selected to participate in the study. Face-toface questionnaires were administered to the heads of the health facilities and to health practitioners. Overall, 49/69 (59%) of the facilities visited provided circumcision services and only 46/203 (24%) of the health practitioners performed circumcision procedures. These were mainly assistant medical officers and clinical officers. The vast majority – 190/203 (95%) – of the health practitioners require additional training prior to providing circumcision services. Most facilities – 63/69 (91%) – had all basic supplies (gloves, basin, chlorine and waste disposal) necessary for infection prevention, 44/69 (65%) provided condoms, HIV counselling and testing, and sexuallytransmitted infections services, while 62/69 (90%) had the capability to perform at least minor surgery. However, only 25/69 (36%) and 15/69 (22%) of the facilities had functioning sterilization equipment and appropriate resuscitation equipment, respectively. There is readiness for roll out of circumcision services; however, more practitioners need to be trained on circumcision procedures, demand forecasting. Sterilization equipment for infection prevention and resuscitation equipment should also be made available.

Aerosols emitted from wildfires are becoming one of the main sources of poor air quality on the US mainland. Their extinction in UVB (the wavelength range from 280 to 315 nm) is difficult to retrieve using simple lidar techniques because of the impact of ozone (O3) absorption and the lack of information about the lidar ratios at those wavelengths. Improving the characterization of lidar ratios at the abovementioned wavelengths will enable aerosol monitoring with different instruments and will also permit the correction of the aerosol impact on O3 lidar data. The 2018 Long Island Sound Tropospheric Ozone Study (LISTOS) campaign in the New York City region utilized a comprehensive set of instruments that enabled the characterization of the lidar ratio for UVB aerosol retrieval. The NASA Langley High Altitude Lidar Observatory (HALO) produced the 532 nm aerosol extinction product along with the lidar ratio for this wavelength using a high-spectral-resolution technique. The Langley Mobile Ozone Lidar (LMOL) is able to compute the extinction provided that it has the lidar ratio at 292 nm. The lidar ratio at 292 nm and the Ångström exponent (AE) between 292 and 532 nm for the aerosols were retrieved by comparing the two observations using an optimization technique. We evaluate the aerosol extinction error due to the selection of these parameters, usually done empirically for 292 nm lasers. This is the first known 292 nm aerosol product intercomparison between HALO and Tropospheric Ozone Lidar Network (TOLNet) O3 lidar. It also provides the characterization of the UVB optical properties of aerosols in the lower troposphere affected by transported wildfire emissions.

Next-generation insecticide-treated bed nets (ITNs) combining two insecticides or an insecticide with a synergist are vital in combating malaria, especially in areas with pyrethroid-resistant mosquitoes where standard pyrethroid long-lasting insecticidal net (LLIN) may be less effective. A community durability study was conducted in Misungwi, Tanzania, during a cluster randomised controlled trial. This study assessed the bio-efficacy of three net brands combining a pyrethroid insecticide and either a synergist PBO for Olyset Plus, or a second insecticide pyriproxyfen for Royal Guard, and chlorfenapyr for Interceptor G2 over three years. These nets were compared to Interceptor, a standard pyrethroid-only net. A total of 1950 nets were enrolled across 10 clusters in each treatment arm. Thirty nets per type were collected every 6 months up to 30 months, with 50 nets sampled at 36 months. WHO cone bioassays and tunnel tests were performed at 0, 12, 24, 30 and 36 months. Both susceptible An. gambiae (s.s.) Kisumu strain and resistant An. gambiae (s.s.) Muleba-Kis strain were exposed. Over 80% of nets tested against the susceptible Kisumu strain met the WHO criteria after three years of community use. In tunnel tests, mortality (72 h) of the resistant Anopheles varied between 52% and 20%, in Interceptor G2 and was higher than standard Interceptor net up to 24 months. Olyset Plus mortality (24 h) ranged between 84% and 33% in tunnel tests with superior efficacy compared to Interceptor at 0, 24 and 36 months. Sterility effects in Royal Guard were higher when these nets were new and at six months but decreased to less than 10% after 12 months. Royal Guard consistently induced higher mortality compared to Interceptor up to 30 months while next-generation ITNs demonstrated higher efficacy in terms of mortality compared to standard LLINs against resistant strains; this superior bio-efficacy did not persist for the full three years. The impact of active ingredient (dual-AI) and PBO diminished relatively quickly. Aside from the initial period when the nets were new, the differences in mortality for Interceptor G2 and Olyset Plus and in sterility for Royal Guard, compared to the standard LLINs, were relatively small thereafter.

Abstract Anopheles funestus is playing an increasing role in malaria transmission in parts of sub-Saharan Africa, where An. gambiae s.s. has been effectively controlled by long-lasting insecticidal nets. We investigated vector population bionomics, insecticide resistance and malaria transmission dynamics in 86 study clusters in North-West Tanzania. An. funestus s.l. represented 94.5% (4740/5016) of all vectors and was responsible for the majority of malaria transmission (96.5%), with a sporozoite rate of 3.4% and average monthly entomological inoculation rate (EIR) of 4.57 per house. Micro-geographical heterogeneity in species composition, abundance and transmission was observed across the study district in relation to key ecological differences between northern and southern clusters, with significantly higher densities, proportions and EIR of An. funestus s.l. collected from the South. An. gambiae s.l. (5.5%) density, principally An. arabiensis (81.1%) and An. gambiae s.s. (18.9%), was much lower and closely correlated with seasonal rainfall. Both An. funestus s.l. and An. gambiae s.l. were similarly resistant to alpha-cypermethrin and permethrin. Overexpression of CYP9K1, CYP6P3, CYP6P4 and CYP6M2 and high L1014S-kdr mutation frequency were detected in An. gambiae s.s. populations. Study findings highlight the urgent need for novel vector control tools to tackle persistent malaria transmission in the Lake Region of Tanzania.

Abstract Background The spread of pyrethroid resistance in malaria vectors threatens the effectiveness of standard long-lasting insecticidal nets (LLIN). Synergist nets combine pyrethroid (Py) and piperonyl-butoxide (PBO) to enhance potency against resistance mediated by mono-oxygenase mechanisms. Our project assessed personal protection of the World Health Organization first-in-class PBO-Py LLIN (Olyset Plus) versus the standard LLIN (Olyset net) against pyrethroid-resistant Anopheles gambiae sensu lato (s.l.) and An. funestus in North-West Tanzania after 20 months of household use. Methods From a household survey, 39 standard Olyset net and 39 Olyset Plus houses were selected. The physical integrity and hole index (HI) of the nets were assessed, and resting mosquitoes were collected from inside nets and from room walls. The indoor abundance was estimated using CDC light traps and species identified using PCR. The bioefficacy of PBO and standard LLINs against wild Anopheles was assessed using 30-minute cylinder bioassays. Results Of 2397 Anopheles collected, 8.9% (n = 213) were resting inside standard Olyset nets, while none were found inside Olyset Plus nets (PBO-Py LLINs) of any HI category. Resting density of blood-fed mosquitoes was higher on walls of sleeping rooms with Olyset nets compared to Olyset Plus (0.62 vs 0.10, density ratio [DR]: 0.03, 95% CI 0.01–0.13, p

Two billion pyrethroid long-lasting insecticidal nets (LLINs) have been distributed since 2004 for malaria prevention in Sub-Saharan Africa. Current malaria control strategies rely on an assumed effective 3-year lifespan for LLINs. PBO synergist LLINs are a newly recommended class of net but there is limited information on their life span and long-term protective efficacy in communities. To assess their operational survival, a cohort of 390 PBO LLINs (Olyset Plus) and 367 standard pyrethroid LLIN (Olyset net) from 396 households were followed for 36 months in Western Tanzania. To assess the association between the condition of the LLIN and malaria infection, nets from at least 480 randomly selected households were assessed during malaria prevalence cross-sectional surveys at 4, 9, 16, 21, 28, and 33 months post-distribution. Information on the presence and condition of nets, and demographic information from the household, were collected to evaluate factors influencing net durability. After 3 years less than 17% of nets distributed still remained in the households. The fabric condition was not associated with malaria infection in either type of net. The difference between the net types was highest when nets were between 1–2 years old, when PBO nets appeared to be similarly protective as nets less than a year old, whereas standard nets were considerably less protective as they aged, regardless of fabric condition. There was no statistical difference in the estimated median functional survival time between net types with 1.6 years (95% CI 1.38–1.87) for PBO LLIN and 1.9 years (95% CI 1.67–2.06) for standard LLINs. After 3 years, there was a loss of 55% of permethrin (pyrethroid) content for both nets, and 97% of PBO content was lost in PBO LLIN. These results highlight that functional survival is less than the recommended 3 years for both net types. However, even as the nets age, the PBO nets remained more protective than standard nets, regardless of their condition.

Introduction The massive scale-up of long-lasting insecticidal nets (LLINs) has led to major reductions in malaria burden in many sub-Saharan African countries. This progress is threatened by widespread insecticide resistance among malaria vectors. This cluster-randomised controlled trial (c-RCT) compares three of the most promising dual active ingredients LLINs (dual-AI LLINs), which incorporate mixtures of insecticides or insecticide synergists to standard LLINs in an area of pyrethroid insecticide resistance.Methods A four-arm, single-blinded, c-RCT will evaluate the effectiveness of three types of dual-AI LLINs (1) Royal Guard, combining two insecticides, pyriproxyfen and the pyrethroid alpha-cypermethrin; (2) Interceptor G2, combining chlorfenapyr and alpha-cypermethrin; (3) Olyset Plus, an LLIN combining a synergist, piperonyl butoxide and the pyrethroid permethrin, compared with; (4) Interceptor LN, a standard LLIN containing the pyrethroid alpha-cypermethrin as the sole AI. The primary outcomes are malaria infection prevalence in children aged 6 months–14 years and entomological inoculation rate (EIR), as a standard measure of malaria transmission at 24 months postintervention and cost-effectiveness.Ethics and dissemination Ethical approval was received from the institutional review boards of the Tanzanian National Institute for Medical Research, Kilimanjaro Christian Medical University College, London School of Hygiene and Tropical Medicine, and University of Ottawa. Study findings will be actively disseminated via reports and presentations to stakeholders, local community leaders, and relevant national and international policy makers as well as through conferences, and peer-reviewed publications.Trial registration number NCT03554616.

Intermittent preventive treatment in infants (IPTi) is a new malaria control tool. However, it is uncertain whether IPTi works mainly through chemoprophylaxis or treatment of existing infections. Understanding the mechanism is essential for development of replacements for sulfadoxine-pyrimethamine (SP) where it is no longer effective. This study investigated how protection against malaria given by SP, chlorproguanil-dapsone (CD) and mefloquine (MQ), varied with time since administration of IPTi.A secondary analysis of data from a randomised, placebo-controlled trial in an area of high antifolate resistance in Tanzania was conducted. IPTi using SP, CD, MQ or placebo was given to 1280 infants at 2, 3 and 9 months of age. Poisson regression with random effects to adjust for potential clustering of malaria episodes within children was used to calculate incidence rate ratios for clinical malaria in defined time strata following IPTi. The short-acting antimalarial CD gave no protection against clinical malaria, whereas long-acting MQ gave two months of substantial protection (protective efficacy (PE) 73.1% (95% CI: 23.9, 90.5) and 73.3% (95% CI: 0, 92.9) in the first and second month respectively). SP gave some protection in the first month after treatment (PE 64.5% (95% CI: 10.6, 85.9)) although it did not reduce the incidence of malaria up to 12 months of age. There was no evidence of either long-term protection or increased risk of malaria for any of the regimens.Post-treatment chemoprophylaxis appears to be the main mechanism by which IPTi protects children against malaria. Long-acting antimalarials are therefore likely to be the most effective drugs for IPTi, but as monotherapies could be vulnerable to development of drug resistance. Due to concerns about tolerability, the mefloquine formulation used in this study is not suitable for IPTi. Further investigation of combinations of long-acting antimalarials for IPTi is needed.Clinicaltrials.gov NCT00158574.

BACKGROUND: Over diagnosis of malaria contributes to improper treatment, wastage of drugs and resistance to the few available drugs. This paper attempts to estimate the rates of over diagnosis of malaria among children attending dispensaries in rural Tanzania and examines the potential cost implications of improving the quality of diagnosis. METHODOLOGY/PRINCIPAL FINDINGS: The magnitude of over diagnosis of malaria was estimated by comparing the proportion of outpatient attendees of all ages clinically diagnosed as malaria to the proportion of attendees having a positive malaria rapid diagnostic test over a two month period. Pattern of causes of illness observed in a or=5 year age group in the lower transmission site (RR 14.0 95%CI 8.2-24.2). In the low transmission site the proportion of morbidity attributable to malaria was substantially lower in

Sulphadoxine-pyrimethamine (SP) a widely used treatment for uncomplicated malaria and recommended for intermittent preventive treatment of malaria in pregnancy, is being investigated for intermittent preventive treatment of malaria in infants (IPTi). High levels of drug resistance to SP have been reported from north-eastern Tanzania associated with mutations in parasite genes. This study compared the in vivo efficacy of SP in symptomatic 6-59 month children with uncomplicated malaria and in asymptomatic 2-10 month old infants.An open label single arm (SP) standard 28 day in vivo WHO antimalarial efficacy protocol was used in 6 to 59 months old symptomatic children and a modified protocol used in 2 to 10 months old asymptomatic infants. Enrolment was stopped early (87 in the symptomatic and 25 in the asymptomatic studies) due to the high failure rate. Molecular markers were examined for recrudescence, re-infection and markers of drug resistance and a review of literature of studies looking for the 581G dhps mutation was carried out. In symptomatic children PCR-corrected early treatment failure was 38.8% (95% CI 26.8-50.8) and total failures by day 28 were 82.2% (95% CI 72.5-92.0). There was no significant difference in treatment failures between asymptomatic and symptomatic children. 96% of samples carried parasites with mutations at codons 51, 59 and 108 in the dhfr gene and 63% carried a double mutation at codons 437 and 540. 55% carried a third mutation with the addition of a mutation at codon 581 in the dhps gene. This triple: triple haplotype maybe associated with earlier treatment failure.In northern Tanzania SP is a failed drug for treatment and its utility for prophylaxis is doubtful. The study found a new combination of parasite mutations that maybe associated with increased and earlier failure.ClinicalTrials.gov NCT00361114.

Background: Insecticide treated nets (ITNs) are the most important malaria prevention tool in Africa but the rise of pyrethroid resistance in mosquitoes is likely impeding control. WHO has recommended a novel pyrethroid-pyrrole ITN following evidence of epidemiological benefit in two cluster-randomised, controlled trials (CRTs). It remains unclear how effective more costly pyrethroid-pyrrole ITNs are compared with other tools, or whether they should be deployed when budgets are limited. We aimed to compare the epidemiological impact and cost-effectiveness of the mass distribution of pyrethroid-pyrrole ITNs relative to other ITNs over 3 years in different African settings., Methods: In this individual-based malaria transmission dynamics modelling study we characterise the entomological impact of ITNs using data from a systematic review of experimental hut trials from across Africa. This African entomological data was used to inform an individual-based malaria transmission dynamics model, which was validated against CRT results from Benin and Tanzania. The full impact of new ITNs was quantified for trial sites and simulation was used to project impact in different settings which were included within an accessible interface (the Malaria Intervention Tool) to support National Malaria Programmes to explore how vector control tools and budgets could be allocated across regions to avert the most cases., Findings: The model projects that distributing pyrethroid-pyrrole ITNs averted 65% (95% credible interval 48-74) of cases over 3 years in Tanzania, and 75% (28-93) in Benin. The model indicates that trials might have underestimated the benefits of switching ITNs by 12-16% over 3 years because participants stopped using trial-allocated nets. In moderate endemicity non-trial settings, pyrethroid-pyrrole ITNs are projected to reduce malaria prevalence by 25-60% and switching from pyrethroid-only ITNs is probably highly cost-effective in most locations given current prices, averting an additional 10-30% of cases., Interpretation: The benefit of pyrethroid-pyrrole ITNs varies by setting but is generally the most cost-effective indoor vector control intervention in Africa. National Malaria Programmes can strategise deployment to maximise impact. Entomological data could broadly predict epidemiological impact, although there are some inconsistencies, illustrating the challenge in capturing the dynamics across diverse settings., Funding: Unitaid, Bill & Melinda Gates Foundation, the UK Medical Research Council, Wellcome Trust, and the UK Foreign, Commonwealth & Development Office., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: High-grade Plasmodium falciparum resistance to sulfadoxine-pyrimethamine in East and Southern Africa has prompted numerous trials evaluating intermittent preventive treatment in pregnancy (IPTp) with dihydroartemisinin-piperaquine as an alternative to sulfadoxine-pyrimethamine., Methods: We conducted individual participant data meta-analyses of randomised trials comparing IPTp with dihydroartemisinin-piperaquine to sulfadoxine-pyrimethamine on maternal, birth, and infant outcomes. We searched the WHO International Clinical Trials Registry Platform, ClinicalTrials.Gov, PubMed, and the Malaria in Pregnancy Consortium Library. Eligible trials enrolled HIV-uninfected pregnant women, followed participants to delivery, included participants with no prior IPTp use during the current pregnancy, and were conducted in areas with high-level parasite resistance to sulfadoxine-pyrimethamine (i.e., PfDHPS 540E≥90% and/or 581G>0%). Only singleton pregnancies were analysed. Meta-analyses used a two-stage approach: first, study-specific estimates were generated and then pooled using a random-effects model. Gravidity subgroup analyses were performed. Causal mediation analyses were used to investigate the maternal mechanisms underlying the effect of IPTp regimens on birth outcomes. The meta-analysis is registered in PROSPERO (CRD42020196127)., Findings: Of 85 screened records, six trials (one multi-country trial) contributed data on 6646 pregnancies. Compared to sulfadoxine-pyrimethamine, dihydroarteminsinin-piperaquine was associated with a 69% [95% CI: 45%-82%] lower incidence of clinical malaria during pregnancy, a 62% [37%-77%] lower risk of placental parasitaemia, and a 17% [0%-31%] lower incidence of moderate maternal anaemia (Hb<9 g/dL). In contrast, sulfadoxine-pyrimethamine was associated with higher mean weekly maternal weight gain (34 grams/week [17-51]). There were no statistically significant differences in the composite adverse pregnancy outcome between the two IPTp regimens (RR=1·05 [95% CI: 0·92-1·19]; I 2 =48%), although the risk of small-for-gestational-age was 15% [3%-24%] lower in the sulfadoxine-pyrimethamine arm. Among multigravidae, participants of the sulfadoxine-pyrimethamine arm were 20% [8%-30%] and 35% [17%-49%] less likely to have stunted and underweight infants by two months compared to the dihydroartemisinin-piperaquine arm. Infant wasting by two months was 13% [3%-22%] lower in the sulfadoxine-pyrimethamine arm, regardless of gravidity. Mediation analyses indicated that 15% [0%-19%] of sulfadoxine-pyrimethamine's superior effect on reducing small-for-gestational-age risk was mediated by its greater impact on gestational weight gain., Interpretation: In areas of high P. falciparum sulfadoxine-pyrimethamine resistance, dihydroartemisin-inpiperaquine is a more efficacious antimalarial than sulfadoxine-pyrimethamine. However, replacing sulfadoxine-pyrimethamine with dihydroartemisinin-piperaquine alone will not result in better maternal, birth, or infant outcomes. It could increase the risk of SGA, since much of the effect of sulfadoxine-pyrimethamine may be exerted through non-malarial mechanisms. Future research evaluating the alternative strategies for IPTp are needed, including with the combination of sulfadoxine-pyrimethamine and dihydroartemisinin-piperaquine., Funding: This work was supported by the Bill and Melinda Gates Foundation and Eunice Kennedy Shriver National Institute of Child Health and Human Development., Competing Interests: Declaration of interests All authors declare no competing interests.

Indiscriminate use of pesticides in the public health and agriculture sectors has contributed to the development of resistance in malaria vectors following exposure to sub-lethal concentrations. To preserve the efficacy of vector control tools and prevent resistance from spreading, early resistance detection is urgently needed to inform management strategies. The introduction of new insecticides for controlling malaria vectors such as clothianidin and chlorfenapyr requires research to identify early markers of resistance which could be used in routine surveillance. This study investigated phenotypic resistance of Anopheles gambiae ( sensu stricto ) Muleba-Kis strain using both WHO bottle and tube assays following chlorfenapyr, clothianidin, and alpha-cypermethrin selection against larvae and adults under laboratory conditions. High mortality rates were recorded for both chlorfenapyr-selected mosquitoes that were consistently maintained for 10 generations (24-h mortality of 92-100% and 72-h mortality of 98-100% for selected larvae; and 24-h mortality of 95-100% and 72-h mortality of 98-100% for selected adults). Selection with clothianidin at larval and adult stages showed a wide range of mortality (18-91%) compared to unselected progeny where mortality was approximately 99%. On the contrary, mosquitoes selected with alpha-cypermethrin from the adult selection maintained low mortality (28% at Generation 2 and 23% at Generation 4) against discrimination concentration compared to unselected progeny where average mortality was 51%. The observed resistance in the clothianidin-selected mosquitoes needs further investigation to determine the underlying resistance mechanism against this insecticide class. Additionally, further investigation is recommended to develop molecular markers for observed clothianidin phenotypic resistance., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Objectives: In 2019, the WHO released guidelines on HIV testing service (HTS). We aim to assess the adoption of six of these recommendations on HIV testing strategies among African countries., Design: Policy review., Setting: 47 countries within the WHO African region., Participants: National HTS policies from the WHO African region as of December 2021., Primary and Secondary Outcome Measures: Uptake of WHO recommendations across national HTS policies including the standard three-test strategy; discontinuation of a tiebreaker test to rule in HIV infection; discontinuation of western blotting (WB) for HIV diagnosis; retesting prior to antiretroviral treatment (ART) initiation and the use of dual HIV/syphilis rapid diagnostic tests (RDTs) in antenatal care. Country policy adoption was assessed on a continuum, based on varying levels of complete adoption., Results: National policies were reviewed for 96% (n=45/47) of countries in the WHO African region, 38% (n=18) were published before 2019 and 60% (n=28) adopted WHO guidance. Among countries that had not fully adopted WHO guidance, not yet adopting a three-test strategy was the most common reason for misalignment (45%, 21/47); of which 31% and 22% were in low-prevalence (<5%) and high-prevalence (≥5%) countries, respectively. Ten policies (21%) recommended the use of WB and 49% (n=23) recommended retesting before ART initiation. Dual HIV/syphilis RDTs were recommended in 45% (n=21/47) of policies., Conclusions: Many countries in the African region have adopted WHO-recommended HIV testing strategies; however, efforts are still needed to fully adopt WHO guidance. Countries should accelerate their efforts to adopt and implement a three-test strategy, retesting prior to ART initiation and the use of dual HIV/syphilis RDTs., Competing Interests: Competing interests: None declared., (© World Health Organization 2023. Licensee BMJ.)

Malaria and schistosomiasis are two major parasitic vector-borne diseases that are a particular threat to young children in Sub-Saharan Africa. In the present study, we investigated factors that are associated with malaria, schistosomiasis, and co-infection among school-aged children, using an explanatory sequential mixed-methods approach. A cross-sectional study was conducted in January 2022 in Misungwi, Tanzania, that sampled 1,122 children aged 5 to 14 years old for malaria and schistosomiasis infection. Mixed-effect logistic regression models were used to assess the association between infection prevalence or seroprevalence, and environmental determinants that create favorable conditions for vectors and parasites and social determinants that relate to disease exposure. Community mapping combined with direct field observations were conducted in August 2022 in three selected villages from the cross-sectional study to understand specific water use behaviors and to identify potential malaria mosquito larval breeding sites and freshwater snail habitat. The prevalence of malaria, seroprevalence of schistosomiasis, and co-infection in this study were 40.4%, 94.3%, and 38.1%, respectively. Individual-level factors emerged as the primary determinants driving the association with infection, with age (every one-year increase in age) and sex (boys vs girls) being statistically and positively associated with malaria, schistosomiasis, and co-infection (P<0.05 for all). Community maps identified many unimproved water sources in all three villages that were used by humans, cattle, or both. We found that children primarily fetched water, and that unprotected wells were dedicated for drinking water whereas ponds were dedicated for other domestic uses and cattle. Although not identified in the community maps, we found hand pumps in all three villages were not in use because of unpleasant taste and high cost. This study improves our understanding of individual, social and environmental factors that are associated with malaria, schistosomiasis, and co-infection, which can inform potential entry points for integrated disease prevention and control., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Duguay et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In the past 2 decades, testing services for diseases such as human immunodeficiency virus (HIV), tuberculosis, and malaria have expanded dramatically. Investments in testing capacity and supportive health systems have often been disease specific, resulting in siloed testing programs with suboptimal capacity, reduced efficiency, and limited ability to introduce additional tests or respond to new outbreaks. Emergency demand for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing overcame these silos and demonstrated the feasibility of integrated testing. Moving forward, an integrated public laboratory infrastructure that services multiple diseases, including SARS-CoV-2, influenza, HIV, tuberculosis, hepatitis, malaria, sexually transmitted diseases, and other infections, will help improve universal healthcare delivery and pandemic preparedness. However, integrated testing faces many barriers including poorly aligned health systems, funding, and policies. Strategies to overcome these include greater implementation of policies that support multidisease testing and treatment systems, diagnostic network optimization, bundled test procurement, and more rapid spread of innovation and best practices across disease programs., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023.)

Objectives: Malaria and sexually transmitted and reproductive tract infections (STIs/RTIs) are highly prevalent in sub-Saharan Africa and associated with poor pregnancy outcomes. We investigated the individual and combined effects of malaria and curable STIs/RTIs on fetal growth in Kenya, Tanzania, and Malawi., Methods: This study was nested within a randomized trial comparing monthly intermittent preventive treatment for malaria in pregnancy with sulfadoxine-pyrimethamine vs dihydroartemisinin-piperaquine, alone or combined with azithromycin. Fetal weight gain was assessed by serial prenatal ultrasound. Malaria was assessed monthly, and Treponema pallidum, Neisseria gonorrhoeae, Trichomonas vaginalis, Chlamydia trachomatis, and bacterial vaginosis at enrollment and in the third trimester. The effect of malaria and STIs/RTIs on fetal weight/birthweight Z-scores was evaluated using mixed-effects linear regression., Results: In total, 1435 pregnant women had fetal/birth weight assessed 3950 times. Compared to women without malaria or STIs/RTIs (n = 399), malaria-only (n = 267), STIs/RTIs only (n = 410) or both (n = 353) were associated with reduced fetal growth (adjusted mean difference in fetal/birth weight Z-score [95% confidence interval]: malaria = -0.18 [-0.31,-0.04], P = 0.01; STIs/RTIs = -0.14 [-0.26,-0.03], P = 0.01; both = -0.20 [-0.33,-0.07], P = 0.003). Paucigravidae experienced the greatest impact., Conclusion: Malaria and STIs/RTIs are associated with poor fetal growth especially among paucigravidae women with dual infections. Integrated antenatal interventions are needed to reduce the burden of both malaria and STIs/RTIs., Competing Interests: Declarations of Competing Interest The authors have no competing interests to declare., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Long-lasting insecticidal nets (LLINs) are prone to reduction in insecticide content and physical strength due to repeated washes and usage. The significant loss to these features jeopardizes their protection against bites from malaria vectors. Insecticide washout is attributed to routine use, friction, and washing, while fabric damage is associated with routine use in households. To maintain coverage and cost-effectiveness, nets should maintain optimal bio-efficacy and physical strength for at least 3 years after distribution. In this study, the bio-efficacy and fabric strength of Olyset plus (OP) LLINs and Interceptor G2 (IG2), that were used for 3 years, were assessed in comparison to untreated and new unwashed counterparts. Both IG2 and OP LLINs (unused, laboratory-washed, and 36 months used) were able to induce significant mortality and blood feeding inhibition (BFI) to mosquitoes compared to the untreated nets. Significantly higher mortality was induced by unused IG2 LLIN and OP LLIN compared to their 36-month-old counterparts against both pyrethroid resistant and susceptible Anopheles gambiae sensu strito. The physical strength of the IG2 LLIN was higher than that of the Olyset Plus LLIN with a decreasing trend from unwashed, laboratory-washed to community usage (36 months old). Malaria control programs should consider bio-efficacy and physical integrity prior to an LLINs' procurement and replacement plan.

To control pyrethroid-resistant malaria vectors, Indoor Residual Spraying (IRS) and Long-Lasting Insecticidal Nets (LLINs) that include additional ingredients to pyrethroid are being developed. Same progress needs to be made to the pyrethroid-treated blankets, which are more compatible with shelter structures found in emergency settings such as displaced populations. In the current study, efficacy of blankets treated with permethrin and piperonyl butoxide (PBO) was evaluated against pyrethroid-resistant Anopheles gambiae sensu stricto. Efficacy was compared with that of Olyset LLIN, Olyset Plus LLIN and untreated blanket in terms of mortality and blood-feeding inhibition against pyrethroid-resistant Anopheles gambiae mosquitoes. The current study indicates that, in emergency shelters such as migrant and refugee camps where LLINs cannot be used, PBO-permethrin blankets may provide protection against resistant mosquitoes if widely used. No side effects related to the use of the treated blankets were reported from the participants. These results need validation in a large-scale field trial to assess the epidemiological impact of the intervention, durability and acceptability of this new vector control strategy for malaria vector control., (© 2022. The Author(s).)

Global malaria epidemiology has changed in the last decade with a substantial increase in cases and deaths being recorded. Tanzania accounts for about 4% of all cases and deaths reported in recent years. Several factors contribute to the resurgence of malaria, parasite resistance to antimalarials and mosquito resistance to insecticides being at the top of the list. The presence of sub-microscopic infections poses a significant challenge to malaria rapid diagnostic tests (mRDT). Our cross-sectional surveys in Handeni and Moshi, Tanzania assessed the effect of low parasite density on mRDT. Handeni had higher malaria prevalence by mRDT (39.6%), light microscopy (LM) (16.9%) and polymerase chain reaction (PCR) (18.5%), compared to Moshi with prevalence of 0.2%, 1.3% and 2.3%, respectively. A significant difference ( p ˂ 0.001) in malaria prevalence by mRDT, LM and nested PCR was found among age groups. In comparison to all other groups, school-age children (5-15 years) had the highest prevalence of malaria. Our results show that mRDT may miss up to 6% of cases of malaria mainly due to low-density parasitemia when compared to LM and PCR. Routinely used mRDT will likely miss the sub-microscopic parasitemia which will ultimately contribute to the spread of malaria and hinder efforts of elimination.

Background: To sustain high universal Long-Lasting Insecticidal Nets (LLINs) coverage, affordable nets that provide equivalent or better protection than standard LLINs, are required. Test facilities evaluating new LLINs require compliance to Good Laboratory Practice (GLP) standards to ensure the quality and integrity of test data. Following GLP principles allows for the reconstruction of activities during the conduct of a study and minimizes duplication of efficacy testing. This case study evaluated the efficacy of two LLINs: SafeNet NF ® and SafeNet ® LLIN., Methods: The study was conducted according to GLP principles and followed World Health Organization guidelines for evaluating LLINs. The LLINs were assessed in experimental huts against wild, pyrethroid-resistant Anopheles arabiensis mosquitoes. Nets were either unwashed or washed 20 times and artificially holed to simulate a used torn net. Blood-feeding inhibition and mortality were compared with a positive control (Interceptor ® LLIN) and an untreated net., Results: Mosquito entry in the huts was reduced compared to negative control for the unwashed SafeNet NF, washed Safenet LLIN and the positive control arms. Similar exiting rates were found for all the treatment arms. Significant blood-feeding inhibition was only found for the positive control, both when washed and unwashed. All insecticide treatments induced significantly higher mortality compared to an untreated net. Compared to the positive control, the washed and unwashed SafeNet NF ® resulted in similar mortality. For the SafeNet ® LLINs the unwashed net had an equivalent performance, but the mortality for the washed net was significantly lower than the positive control. Internal audits of the study confirmed that all critical phases complied with Standard Operating Procedures (SOPs) and the study plan. The external audit confirmed that the study complied with GLP standards., Conclusions: SafeNet NF ® and SafeNet ® LLIN offered equivalent protection to the positive control (Interceptor ® LLIN). However, further research is needed to investigate the durability, acceptability, and residual efficacy of these nets in the community. This study demonstrated that GLP-compliant evaluation of LLINs can be successfully conducted by African research institutions., (© 2022. The Author(s).)