Mathematical Assessment of the Role of Intervention Programs for Malaria Control.

Malaria remains a global health problem despite the many attempts to control and eradicate it. There is an urgent need to understand the current transmission dynamics of malaria and to determine the interventions necessary to control malaria. In this paper, we seek to develop a fit-for-purpose mathematical model to assess the interventions needed to control malaria in an endemic setting. To achieve this, we formulate a malaria transmission model to analyse the spread of malaria in the presence of interventions. A sensitivity analysis of the model is performed to determine the relative impact of the model parameters on disease transmission. We explore how existing variations in the recruitment and management of intervention strategies affect malaria transmission. Results obtained from the study imply that the discontinuation of existing interventions has a significant effect on malaria prevalence. Thus, the maintenance of interventions is imperative for malaria elimination and eradication. In a scenario study aimed at assessing the impact of long-lasting insecticidal nets (LLINs), indoor residual spraying (IRS), and localized individual measures, our findings indicate that increased LLINs utilization and extended IRS coverage (with longer-lasting insecticides) cause a more pronounced reduction in symptomatic malaria prevalence compared to a reduced LLINs utilization and shorter IRS coverage. Additionally, our study demonstrates the impact of localized preventive measures in mitigating the spread of malaria when compared to the absence of interventions.

Rapid entomological assessment in eight high malaria endemic regencies in Papua Province revealed the presence of indoor and outdoor malaria transmissions.

Malaria in eastern Indonesia remains high despite significant reduction and elimination in other parts of the country. A rapid entomological assessment was conducted in eight high malaria endemic regencies of Papua Province, Indonesia, to expedite malaria elimination efforts in this region. This study aims to characterize specific, actionable endpoints toward understanding where and when malaria transmission is happening, where interventions may function best, and identify gaps in protection that result in continued transmission. The entomological assessment included identifying potential vectors through human landing catch (HLC), indoor morning and night resting collections, identification of larval sites through surveillance of water bodies, and vector incrimination toward understanding exposure to malaria transmission. Human landing catches (HLCs) and larval collections identified 10 Anopheles species, namely Anopheles koliensis, Anopheles punctulatus, Anopheles farauti, Anopheles hinesorum, Anopheles longirostris, Anopheles peditaeniatus, Anopheles tesselatus, Anopheles vagus, Anopheles subpictus and Anopheles kochi. The most common and abundant species found overall were An. koliensis and An. punctulatus, while An. farauti was found in large numbers in the coastal areas of Mimika and Sarmi Regencies. Vector incrimination on Anopheles collected from HLCs and night indoor resting demonstrated that An. koliensis and An. punctulatus carried Plasmodium in Keerom, Jayapura, and Sarmi Regencies. Analysis of HLCs for the most common species revealed that the An. koliensis and An. punctulatus, bite indoors and outdoors at equal rates, while An. farauti predominantly bite outdoors. Larval surveillance demonstrated that most water bodies in and surrounding residential areas contained Anopheles larvae. This study demonstrated indoor and outdoor exposure to mosquito bites and gaps in protection, enabling exposure to infectious bites in all regencies. This explains why current malaria control efforts focusing on indoor protection have failed to substantially reduce malaria incidence in the region. Optimization of insecticide-treated bed nets (ITNs), as well as installment of mosquito screens in houses, may further reduce indoor transmission. For outdoor transmission, the use of community-centric approaches to reduce or eliminate larval sources within and surrounding the village through the guidance of locally stationed entomologists, along with Social and Behavior Change mediated health education towards the local adoption of mosquito protection tools during outdoor activities, may reduce malaria transmission.

Assessment of environmental and spatial factors influencing the establishment of Anopheles gambiae larval habitats in the malaria endemic province of Woleu-Ntem, northern Gabon.

BACKGROUND: This study aimed to assess the spatial distribution of Anopheles mosquito larval habitats and the environmental factors associated with them, as a prerequisite for the implementation of larviciding. METHODS: The study was conducted in December 2021, during the transition period between the end of the short rainy season (September-November) and the short dry season (December-February). Physical, biological, and land cover data were integrated with entomological observations to collect Anopheles larvae in three major towns: Mitzic, Oyem, and Bitam, using the "dipping" method during the transition from rainy to dry season. The collected larvae were then reared in a field laboratory established for the study period. After the Anopheles mosquitoes had emerged, their species were identified using appropriate morphological taxonomic keys. To determine the influence of environmental factors on the breeding of Anopheles mosquitoes, multiple-factor analysis (MFA) and a binomial generalized linear model were used. RESULTS: According to the study, only 33.1% out of the 284 larval habitats examined were found to be positive for Anopheles larvae, which were primarily identified as belonging to the Anopheles gambiae complex. The findings of the research suggested that the presence of An. gambiae complex larvae in larval habitats was associated with various significant factors such as higher urbanization, the size and type of the larval habitats (pools and puddles), co-occurrence with Culex and Aedes larvae, hot spots in ambient temperature, moderate rainfall, and land use patterns. CONCLUSIONS: The results of this research mark the initiation of a focused vector control plan that aims to eradicate or lessen the larval habitats of An. gambiae mosquitoes in Gabon's Woleu Ntem province. This approach deals with the root causes of malaria transmission through larvae and is consistent with the World Health Organization's (WHO) worldwide objective to decrease malaria prevalence in regions where it is endemic.

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

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

Small-scale release of non-gene drive mosquitoes in Burkina Faso: from engagement implementation to assessment, a learning journey.

BACKGROUND: Innovative tools are needed to complement the existing approach for malaria elimination. Gene drive mosquitoes are one potential new technology in the control of malaria vectors. Target Malaria is one of the research projects developing this technology, and in July 2019, the project proceeded to an important step for this evaluation pathway: the small-scale release of non-gene drive sterile male mosquitoes in a village in Burkina Faso. In addition to the entomological and laboratory work to prepare for this important milestone, significant community and stakeholder engagement work was done. The existing guidelines on gene drive mosquito provide an overall framework for such engagement work. However, they do not provide a road map on how to proceed or what benchmarks should be used to assess this work. METHODS: This study provides a review of engagement activities relevant to field trials on non-gene drive genetically-modified mosquitoes as well as an assessment framework-using both qualitative and quantitative studies as well as an audit procedure. The latter was implemented to evaluate whether the release activities could proceed with the appropriate level of agreement from the community. RESULTS: This paper shows the importance of this first phase of work to innovate and learn about engagement processes for responsible research in the field of genetic approaches for malaria vector control. The function of these assessments is crucial for the learning agenda. The assessments demonstrated ways to increase understanding and ensure effective progress with field studies and, therefore, the pathway for responsible research. CONCLUSION: Gene drive technology is increasingly considered as a promising approach to control vector borne diseases, in particular malaria. Stakeholders' involvement in this research process is one of the recurring requirements in international guidance documents. With this paper Target Malaria offers an opportunity to explore the practical achievements and challenges of stakeholder engagement during early phases of a technology evaluation, and in particular how it implemented an assessment framework to learn from its experience.

Identification and phylogenetic analysis of voltage-gated sodium channel haplotypes in the malaria vector Anopheles sinensis using a high-throughput amplicon sequencing approach.

BACKGROUND: Anopheles sinensis is a dominant vector for malaria transmission in Asian countries. Voltage-gated sodium channel (VGSC) mutation-mediated knock-down resistance (kdr) has developed in many A. sinensis populations because of intensive and long-term use of pyrethroids. Our previous study showed that multiple mutations at position 1014 of the VGSC were heterogeneously distributed in A. sinensis populations across Sichuan, China. METHODS: To understand resistance genotypes at the haplotype level and reconstruct the phylogenetic relationship of VGSC haplotypes, a cost-effective next-generation sequencing (NGS)-based amplicon sequencing approach was established to clarify haplotypes containing codon 1014 of the VGSC gene from a total of 446 adults collected in 12 locations of Sichuan, China. RESULTS: Nineteen (19) haplotypes were identified, including 11 wild 1014L, 6 resistance 1014F, and 2 resistance 1014C haplotypes. We found that resistance haplotypes of A. sinensis VGSC were widely distributed at frequencies ranging from 3.67 to 92.61%. The frequencies of the 1014C haplotype in the southeast of Sichuan (Luzhou, Guangan, and Suining) were relatively higher than those in other sampling locations. Phylogenetic analyses support that kdr-type mutation at position 1014 is not singly originated and resistance 1014C haplotypes evolve from TTT-encoding 1014F. CONCLUSIONS: A cost-effective next-generation sequencing (NGS)-based amplicon sequencing approach has been established in this study. The data revealed the patchy distribution of VGSC resistance haplotypes with overall high frequencies in Sichuan, China. Phylogenetic analyses support multiple origins and sequential evolution (1014L → 1014F → 1014C) for kdr-type mutations in A. sinensis.

Partial indoor residual spraying with pirimiphos-methyl as an effective and cost-saving measure for the control of Anopheles gambiae s.l. in northern Ghana.

The scale up of indoor residual spraying (IRS) and insecticide treated nets have contributed significantly to global reductions in malaria prevalence over the last two decades. However, widespread pyrethroid resistance has necessitated the use of new and more expensive insecticides for IRS. Partial IRS with pirimiphos-methyl in experimental huts and houses in a village-wide trial was evaluated against Anopheles gambiae s.l. in northern Ghana. Four different scenarios in which either only the top or bottom half of the walls of experimental huts were sprayed, with or without also spraying the ceiling were compared. Mortality of An. gambiae s.l. on partially sprayed walls was compared with the standard procedures in which all walls and ceiling surfaces are sprayed. A small-scale trial was then conducted to assess the effectiveness, feasibility, and cost of spraying only the upper walls and ceiling as compared to full IRS and no spraying in northern Ghana. Human landing catches were conducted to estimate entomological indices and determine the effectiveness of partial IRS. An established transmission dynamics model was parameterized by an analysis of the experimental hut data and used to predict the epidemiological impact and cost effectiveness of partial IRS for malaria control in northern Ghana. In the experimental huts, partial IRS of the top (IRR 0.89, p = 0.13) or bottom (IRR 0.90, p = 0.15) half of walls and the ceiling was not significantly less effective than full IRS in terms of mosquito mortality. In the village trial, the annual entomological inoculation rate was higher for the unsprayed control (217 infective bites/person/year (ib/p/yr)) compared with the fully and partially sprayed sites, with 28 and 38 ib/p/yr, respectively. The transmission model predicts that the efficacy of partial IRS against all-age prevalence of malaria after six months would be broadly equivalent to a full IRS campaign in which 40% reduction is expected relative to no spray campaign. At scale, partial IRS in northern Ghana would have resulted in a 33% cost savings ($496,426) that would enable spraying of 36,000 additional rooms. These findings suggest that partial IRS is an effective, feasible, and cost saving approach to IRS that could be adopted to sustain and expand implementation of this key malaria control intervention.

A global assessment of surveillance methods for dominant malaria vectors.

The epidemiology of human malaria differs considerably between and within geographic regions due, in part, to variability in mosquito species behaviours. Recently, the WHO emphasised stratifying interventions using local surveillance data to reduce malaria. The usefulness of vector surveillance is entirely dependent on the biases inherent in the sampling methods deployed to monitor mosquito populations. To understand and interpret mosquito surveillance data, the frequency of use of malaria vector collection methods was analysed from a georeferenced vector dataset (> 10,000 data records), extracted from 875 manuscripts across Africa, the Americas and the Asia-Pacific region. Commonly deployed mosquito collection methods tend to target anticipated vector behaviours in a region to maximise sample size (and by default, ignoring other behaviours). Mosquito collection methods targeting both host-seeking and resting behaviours were seldomly deployed concurrently at the same site. A balanced sampling design using multiple methods would improve the understanding of the range of vector behaviours, leading to improved surveillance and more effective vector control.

Agent-based modelling of complex factors impacting malaria prevalence.

BACKGROUND: Increasingly complex models have been developed to characterize the transmission dynamics of malaria. The multiplicity of malaria transmission factors calls for a realistic modelling approach that incorporates various complex factors such as the effect of control measures, behavioural impacts of the parasites to the vector, or socio-economic variables. Indeed, the crucial impact of household size in eliminating malaria has been emphasized in previous studies. However, increasing complexity also increases the difficulty of calibrating model parameters. Moreover, despite the availability of much field data, a common pitfall in malaria transmission modelling is to obtain data that could be directly used for model calibration. METHODS: In this work, an approach that provides a way to combine in situ field data with the parameters of malaria transmission models is presented. This is achieved by agent-based stochastic simulations, initially calibrated with hut-level experimental data. The simulation results provide synthetic data for regression analysis that enable the calibration of key parameters of classical models, such as biting rates and vector mortality. In lieu of developing complex dynamical models, the approach is demonstrated using most classical malaria models, but with the model parameters calibrated to account for such complex factors. The performance of the approach is tested against a wide range of field data for Entomological Inoculation Rate (EIR) values. RESULTS: The overall transmission characteristics can be estimated by including various features that impact EIR and malaria incidence, for instance by reducing the mosquito-human contact rates and increasing the mortality through control measures or socio-economic factors. CONCLUSION: Complex phenomena such as the impact of the coverage of the population with long-lasting insecticidal nets (LLINs), changes in behaviour of the infected vector and the impact of socio-economic factors can be included in continuous level modelling. Though the present work should be interpreted as a proof of concept, based on one set of field data only, certain interesting conclusions can already be drawn. While the present work focuses on malaria, the computational approach is generic, and can be applied to other cases where suitable in situ data is available.

Special Programme for Research and Training in Tropical Diseases-coordinated Multicountry Study to Determine the Burden and Causes of Residual Malaria Across Different Regions.

The burden and causes of residual malaria were investigated between 2015 and 2019 through 5 research projects coordinated by the Special Program for Research and Training in Tropical Diseases (TDR), cosponsored by the United Nations Development Programme, UNICEF, the World Bank, the World Health Organization (WHO) and the WHO Global Malaria Programme. The 5 projects included 10 countries in 4 WHO regions: Africa, the Americas, South-East Asia, and the Western Pacific. The countries represented a range of malaria endemicities, from low to high levels of transmission. The main findings of the projects indicate that overall the core malaria vector control tools (long-lasting insecticidal nets [LLIN] and indoor residual spraying) were not deployed in the optimal way and/or not efficient in many settings of the supported projects. Furthermore, vector biting behavior and human activity-associated factors strongly contributed to malaria persistence. Changes in vector species composition and abundance, with an increase in outdoor biting, were also reported. Some of these factors may be an adaptation of the vectors to the deployment of the tools and/or can be linked to other sectors, such as agricultural practices, environmental changes, social factors, and water management. Human behaviors and sleeping habits that included activities and sleeping outside villages in unprotected dwellings were another part of the problem. The evidence collated demonstrates the need for new approaches, such as the multisectoral one and new vector control tools, all adapted to the local contexts and integrated into current malaria programs.

Cost and cost-effectiveness of indoor residual spraying with pirimiphos-methyl in a high malaria transmission district of Mozambique with high access to standard insecticide-treated nets.

BACKGROUND: As malaria cases increase in some of the highest burden countries, more strategic deployment of new and proven interventions must be evaluated to meet global malaria reduction goals. METHODS: The cost and cost-effectiveness of indoor residual spraying (IRS) with pirimiphos-methyl (Actellic®300 CS) were assessed in a high transmission district (Mopeia) with high access to pyrethroid insecticide-treated nets (ITNs), compared to ITNs alone. The major mosquito vectors in the area were susceptible to primiphos-methyl, but resistant to pyrethoids. A decision analysis approach was followed to conduct deterministic and probabilistic sensitivity analyses in a theoretical cohort of 10,000 children under five years of age (U5) and 10,000 individuals of all ages, separately. Model parameters and distributions were based on prospectively collected cost and epidemiological data from a cluster-randomized control trial and a literature review. The primary analysis used health facility-malaria incidence, while community cohort incidence and cross-sectional prevalence rates were used in sensitivity analyses. Lifetime costs, malaria cases, deaths and disability-adjusted life-years (DALYs) were calculated to determine the incremental costs per DALY averted through IRS. RESULTS: The average IRS cost per person protected was US$8.26 and 51% of the cost was insecticide. IRS averted 46,609 (95% CI 46,570-46,646) uncomplicated and 242 (95% CI 241-243) severe lifetime cases in a theoretical children U5 cohort, yielding an incremental cost-effectiveness ratio (ICER) of US$400 (95% CI 399-402) per DALY averted. In the all-age cohort, the ICER was higher: US$1,860 (95% CI 1,852-1,868) per DALY averted. Deterministic and probabilistic results were consistent. When adding the community protective effect of IRS, the cost per person protected decreased (US$7.06) and IRS was highly cost-effective in children U5 (ICER = US$312) and cost-effective in individuals of all ages (ICER = US$1,431), compared to ITNs alone. CONCLUSION: This study provides robust evidence that IRS with pirimiphos-methyl can be cost-effective in high transmission regions with high pyrethroid ITN coverage where the major vector is susceptible to pirimiphos-methyl but resistant to pyrethroids. The finding that insecticide cost is the main driver of IRS costs highlights the need to reduce the insecticide price without jeopardizing effectiveness. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02910934 (Registered 22 September 2016). https://clinicaltrials.gov/ct2/show/NCT02910934?term=NCT02910934&draw=2&rank=1.

Multi-Indicator and Multistep Assessment of Malaria Transmission Risks in Western Kenya.

Malaria risk factor assessment is a critical step in determining cost-effective intervention strategies and operational plans in a regional setting. We develop a multi-indicator multistep approach to model the malaria risks at the population level in western Kenya. We used a combination of cross-sectional seasonal malaria infection prevalence, vector density, and cohort surveillance of malaria incidence at the village level to classify villages into malaria risk groups through unsupervised classification. Generalized boosted multinomial logistics regression analysis was performed to determine village-level risk factors using environmental, biological, socioeconomic, and climatic features. Thirty-six villages in western Kenya were first classified into two to five operational groups based on different combinations of malaria risk indicators. Risk assessment indicated that altitude accounted for 45-65% of all importance value relative to all other factors; all other variable importance values were < 6% in all models. After adjusting by altitude, villages were classified into three groups within distinct geographic areas regardless of the combination of risk indicators. Risk analysis based on altitude-adjusted classification indicated that factors related to larval habitat abundance accounted for 63% of all importance value, followed by geographic features related to the ponding effect (17%), vegetation cover or greenness (15%), and the number of bed nets combined with February temperature (5%). These results suggest that altitude is the intrinsic factor in determining malaria transmission risk in western Kenya. Malaria vector larval habitat management, such as habitat reduction and larviciding, may be an important supplement to the current first-line vector control tools in the study area.

Effectiveness and cost-effectiveness of reactive, targeted indoor residual spraying for malaria control in low-transmission settings: a cluster-randomised, non-inferiority trial in South Africa.

BACKGROUND: Increasing insecticide costs and constrained malaria budgets could make universal vector control strategies, such as indoor residual spraying (IRS), unsustainable in low-transmission settings. We investigated the effectiveness and cost-effectiveness of a reactive, targeted IRS strategy. METHODS: This cluster-randomised, open-label, non-inferiority trial compared reactive, targeted IRS with standard IRS practice in northeastern South Africa over two malaria seasons (2015-17). In standard IRS clusters, programme managers conducted annual mass spray campaigns prioritising areas using historical data, expert opinion, and other factors. In targeted IRS clusters, only houses of index cases (identified through passive surveillance) and their immediate neighbours were sprayed. The non-inferiority margin was 1 case per 1000 person-years. Health service costs of real-world implementation were modelled from primary and secondary data. Incremental costs per disability-adjusted life-year (DALY) were estimated and deterministic and probabilistic sensitivity analyses conducted. This study is registered with ClinicalTrials.gov, NCT02556242. FINDINGS: Malaria incidence was 0·95 per 1000 person-years (95% CI 0·58 to 1·32) in the standard IRS group and 1·05 per 1000 person-years (0·72 to 1·38) in the targeted IRS group, corresponding to a rate difference of 0·10 per 1000 person-years (-0·38 to 0·59), demonstrating non-inferiority for targeted IRS (p<0·0001). Per additional DALY incurred, targeted IRS saved US$7845 (2902 to 64 907), giving a 94-98% probability that switching to targeted IRS would be cost-effective relative to plausible cost-effectiveness thresholds for South Africa ($2637 to $3557 per DALY averted). Depending on the threshold used, targeted IRS would remain cost-effective at incidences of less than 2·0-2·7 per 1000 person-years. Findings were robust to plausible variation in other parameters. INTERPRETATION: Targeted IRS was non-inferior, safe, less costly, and cost-effective compared with standard IRS in this very-low-transmission setting. Saved resources could be reallocated to other malaria control and elimination activities. FUNDING: Joint Global Health Trials.

Accessing the syndemic of COVID-19 and malaria intervention in Africa.

BACKGROUND: The pandemic of the coronavirus disease 2019 (COVID-19) has caused substantial disruptions to health services in the low and middle-income countries with a high burden of other diseases, such as malaria in sub-Saharan Africa. The aim of this study is to assess the impact of COVID-19 pandemic on malaria transmission potential in malaria-endemic countries in Africa. METHODS: We present a data-driven method to quantify the extent to which the COVID-19 pandemic, as well as various non-pharmaceutical interventions (NPIs), could lead to the change of malaria transmission potential in 2020. First, we adopt a particle Markov Chain Monte Carlo method to estimate epidemiological parameters in each country by fitting the time series of the cumulative number of reported COVID-19 cases. Then, we simulate the epidemic dynamics of COVID-19 under two groups of NPIs: (1) contact restriction and social distancing, and (2) early identification and isolation of cases. Based on the simulated epidemic curves, we quantify the impact of COVID-19 epidemic and NPIs on the distribution of insecticide-treated nets (ITNs). Finally, by treating the total number of ITNs available in each country in 2020, we evaluate the negative effects of COVID-19 pandemic on malaria transmission potential based on the notion of vectorial capacity. RESULTS: We conduct case studies in four malaria-endemic countries, Ethiopia, Nigeria, Tanzania, and Zambia, in Africa. The epidemiological parameters (i.e., the basic reproduction number [Formula: see text] and the duration of infection [Formula: see text]) of COVID-19 in each country are estimated as follows: Ethiopia ([Formula: see text], [Formula: see text]), Nigeria ([Formula: see text], [Formula: see text]), Tanzania ([Formula: see text], [Formula: see text]), and Zambia ([Formula: see text], [Formula: see text]). Based on the estimated epidemiological parameters, the epidemic curves simulated under various NPIs indicated that the earlier the interventions are implemented, the better the epidemic is controlled. Moreover, the effect of combined NPIs is better than contact restriction and social distancing only. By treating the total number of ITNs available in each country in 2020 as a baseline, our results show that even with stringent NPIs, malaria transmission potential will remain higher than expected in the second half of 2020. CONCLUSIONS: By quantifying the impact of various NPI response to the COVID-19 pandemic on malaria transmission potential, this study provides a way to jointly address the syndemic between COVID-19 and malaria in malaria-endemic countries in Africa. The results suggest that the early intervention of COVID-19 can effectively reduce the scale of the epidemic and mitigate its impact on malaria transmission potential.

New assessment of Anopheles vector species identification using MALDI-TOF MS.

BACKGROUND: Anopheles species identification is essential for an effective malaria vector control programme. Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS) has been developed to identify adult Anopheles species, using the legs or the cephalothorax. The protein repertoire from arthropods can vary according to compartment, but there is no general consensus regarding the anatomic part to be used. METHODS: To determine the body part of the Anopheles mosquitoes best suited for the identification of field specimens, a mass spectral library was generated with head, thorax with wings and legs of Anopheles gambiae, Anopheles arabiensis and Anopheles funestus obtained from reference centres. The MSL was evaluated using two independent panels of 52 and 40 An. gambiae field-collected in Mali and Guinea, respectively. Geographic variability was also tested using the panel from Mali and several databases containing added specimens from Mali and Senegal. RESULTS: Using the head and a database without specimens from the same field collection, the proportion of interpretable and correct identifications was significantly higher than using the other body parts at a threshold value of 1.7 (p < 0.0001). The thorax of engorged specimens was negatively impacted by the blood meal after frozen storage. The addition of specimens from Mali into the database significantly improved the results of Mali panel (p < 0.0001), which became comparable between head and legs. With higher identification scores, the using of the head will allow to decrease the number of technical replicates of protein extract per specimen, which represents a significant improvement for routine use of MALDI-TOF MS. CONCLUSIONS: The using of the head of Anopheles may improve the performance of MALDI-TOF MS. Region-specific mass spectrum databases will have to be produced. Further research is needed to improve the standardization in order to share online spectral databases.

Battleground midgut: The cost to the mosquito for hosting the malaria parasite.

In eco-evolutionary studies of parasite-host interactions, virulence is defined as a reduction in host fitness as a result of infection relative to an uninfected host. Pathogen virulence may either promote parasite transmission, when correlated with higher parasite replication rate, or decrease the transmission rate if the pathogen quickly kills the host. This evolutionary mechanism, referred to as 'trade-off' theory, proposes that pathogen virulence evolves towards a level that most benefits the transmission. It has been generally predicted that pathogens evolve towards low virulence in their insect vectors, mainly due to the high dependence of parasite transmission on their vector survival. Therefore, the degree of virulence which malaria parasites impose on mosquito vectors may depend on several external and internal factors. Here, we review briefly (i) the role of mosquito in parasite development, with a particular focus on mosquito midgut as the battleground between Plasmodium and the mosquito host. We aim to point out (ii) the histology of the mosquito midgut epithelium and its role in host defence against parasite's countermeasures in the three main battle sites, namely (a) the lumen (microbiota and biochemical environment), (b) the peritrophic membrane (physical barrier) and (c) the tubular epithelium including the basal membrane (physical and biochemical barrier). Lastly, (iii) we describe the impact which malaria parasite and its virulence factors have on mosquito fitness.

Cross-border COVID-19 spread amidst malaria re-emergence in Venezuela: a human rights analysis.

BACKGROUND: Since 2016 Venezuela has seen a collapse in its economy and public health infrastructure resulting in a humanitarian crisis and massive outward migration. With the emergence of the novel coronavirus SARS-CoV-2 at the end of 2019, the public health emergency within its borders and in neighboring countries has become more severe and as increasing numbers of Venezuelans migrants return home or get stuck along migratory routes, new risks are emerging in the region. RESULTS: Despite clear state obligations to respect, protect and fulfil the rights to health and related economic, social, civil and political rights of its population, in Venezuela, co-occurring malaria and COVID-19 epidemics are propelled by a lack of public investment in health, weak governance, and violations of human rights, especially for certain underserved populations like indigenous groups. COVID-19 has put increased pressure on Venezuelan and regional actors and healthcare systems, as well as international public health agencies, to deal with a domestic and regional public health emergency. CONCLUSIONS: International aid and cooperation for Venezuela to deal with the re-emergence of malaria and the COVID-19 spread, including lifting US-enforced economic sanctions that limit Venezuela's capacity to deal with this crisis, is critical to protecting rights and health in the country and region.

Effectiveness of seasonal malaria chemoprevention at scale in west and central Africa: an observational study.

BACKGROUND: Seasonal malaria chemoprevention (SMC) aims to prevent malaria in children during the high malaria transmission season. The Achieving Catalytic Expansion of SMC in the Sahel (ACCESS-SMC) project sought to remove barriers to the scale-up of SMC in seven countries in 2015 and 2016. We evaluated the project, including coverage, effectiveness of the intervention, safety, feasibility, drug resistance, and cost-effectiveness. METHODS: For this observational study, we collected data on the delivery, effectiveness, safety, influence on drug resistance, costs of delivery, impact on malaria incidence and mortality, and cost-effectiveness of SMC, during its administration for 4 months each year (2015 and 2016) to children younger than 5 years, in Burkina Faso, Chad, The Gambia, Guinea, Mali, Niger, and Nigeria. SMC was administered monthly by community health workers who visited door-to-door. Drug administration was monitored via tally sheets and via household cluster-sample coverage surveys. Pharmacovigilance was based on targeted spontaneous reporting and monitoring systems were strengthened. Molecular markers of resistance to sulfadoxine-pyrimethamine and amodiaquine in the general population before and 2 years after SMC introduction was assessed from community surveys. Effectiveness of monthly SMC treatments was measured in case-control studies that compared receipt of SMC between patients with confirmed malaria and neighbourhood-matched community controls eligible to receive SMC. Impact on incidence and mortality was assessed from confirmed outpatient cases, hospital admissions, and deaths associated with malaria, as reported in national health management information systems in Burkina Faso and The Gambia, and from data from selected outpatient facilities (all countries). Provider costs of SMC were estimated from financial costs, costs of health-care staff time, and volunteer opportunity costs, and cost-effectiveness ratios were calculated as the total cost of SMC in each country divided by the predicted number of cases averted. FINDINGS: 12 467 933 monthly SMC treatments were administered in 2015 to a target population of 3 650 455 children, and 25 117 480 were administered in 2016 to a target population of 7 551 491. In 2015, among eligible children, mean coverage per month was 76·4% (95% CI 74·0-78·8), and 54·5% children (95% CI 50·4-58·7) received all four treatments. Similar coverage was achieved in 2016 (74·8% [72·2-77·3] treated per month and 53·0% [48·5-57·4] treated four times). In 779 individual case safety reports over 2015-16, 36 serious adverse drug reactions were reported (one child with rash, two with fever, 31 with gastrointestinal disorders, one with extrapyramidal syndrome, and one with Quincke's oedema). No cases of severe skin reactions (Stevens-Johnson or Lyell syndrome) were reported. SMC treatment was associated with a protective effectiveness of 88·2% (95% CI 78·7-93·4) over 28 days in case-control studies (2185 cases of confirmed malaria and 4370 controls). In Burkina Faso and The Gambia, implementation of SMC was associated with reductions in the number of malaria deaths in hospital during the high transmission period, of 42·4% (95% CI 5·9 to 64·7) in Burkina Faso and 56·6% (28·9 to 73·5) in The Gambia. Over 2015-16, the estimated reduction in confirmed malaria cases at outpatient clinics during the high transmission period in the seven countries ranged from 25·5% (95% CI 6·1 to 40·9) in Nigeria to 55·2% (42·0 to 65·3) in The Gambia. Molecular markers of resistance occurred at low frequencies. In individuals aged 10-30 years without SMC, the combined mutations associated with resistance to amodiaquine (pfcrt CVIET haplotype and pfmdr1 mutations [86Tyr and 184Tyr]) had a prevalence of 0·7% (95% CI 0·4-1·2) in 2016 and 0·4% (0·1-0·8) in 2018 (prevalence ratio 0·5 [95% CI 0·2-1·2]), and the quintuple mutation associated with resistance to sulfadoxine-pyrimethamine (triple mutation in pfdhfr and pfdhps mutations [437Gly and 540Glu]) had a prevalence of 0·2% (0·1-0·5) in 2016 and 1·0% (0·6-1·6) in 2018 (prevalence ratio 4·8 [1·7-13·7]). The weighted average economic cost of administering four monthly SMC treatments was US$3·63 per child. INTERPRETATION: SMC at scale was effective in preventing morbidity and mortality from malaria. Serious adverse reactions were rarely reported. Coverage varied, with some areas consistently achieving high levels via door-to-door campaigns. Markers of resistance to sulfadoxine-pyrimethamine and amodiaquine remained uncommon, but with some selection for resistance to sulfadoxine-pyrimethamine, and the situation needs to be carefully monitored. These findings should support efforts to ensure high levels of SMC coverage in west and central Africa. FUNDING: Unitaid.

Nextgen Vector Surveillance Tools: sensitive, specific, cost-effective and epidemiologically relevant.

BACKGROUND: Vector surveillance provides critical data for decision-making to ensure that malaria control programmes remain effective and responsive to any threats to a successful control and elimination programme. The quality and quantity of data collected is dependent on the sampling tools and laboratory techniques used which may lack the sensitivity required to collect relevant data for decision-making. Here, 40 vector control experts were interviewed to assess the benefits and limitations of the current vector surveillance tools and techniques. In addition, experts shared ideas on "blue sky" indicators which encompassed ideas for novel methods to monitor presently used indicators, or to measure novel vector behaviours not presently measured. Algorithms for deploying surveillance tools and priorities for understanding vector behaviours are also needed for collecting and interpreting vector data. RESULTS: The available tools for sampling and analysing vectors are often hampered by high labour and resource requirements (human and supplies) coupled with high outlay and operating costs and variable tool performance across species and geographic regions. The next generation of surveillance tools needs to address the limitations of present tools by being more sensitive, specific and less costly to deploy to enable the collection and use of epidemiologically relevant vector data to facilitate more proactive vector control guidance. Ideas and attributes for Target Product Profiles (TPPs) generated from this analysis provide targets for research and funding to develop next generation tools. CONCLUSIONS: More efficient surveillance tools and a more complete understanding of vector behaviours and populations will provide a basis for more cost effective and successful malaria control. Understanding the vectors' behaviours will allow interventions to be deployed that target vulnerabilities in vector behaviours and thus enable more effective control. Through defining the strengths and weaknesses of the current vector surveillance methods, a foundation and initial framework was provided to define the TPPs for the next generation of vector surveillance methods. The draft TTPs presented here aim to ensure that the next generation tools and technologies are not encumbered by the limitations of present surveillance methods and can be readily deployed in low resource settings.