Re-Visiting Insecticide Resistance Status in Anopheles gambiae from C?te d'Ivoire: A Nation-Wide Informative Survey

Insecticide resistance constitutes a major threat that may undermine current gain in malaria control in most endemic countries. National Malaria Control Programmes (NMCPs) need as much information as possible on the resistance status of malaria vectors and underlying mechanisms in order to implement the most relevant and efficient control strategy. Bioassays, biochemical and molecular analysis were performed on An. gambiae collected in six sentinel sites in Côte d''Ivoire. The sites were selected on the basis of their bioclimatic status and agricultural practices. An. gambiae populations across sites showed high levels of resistance to organochloride, pyrethroid and carbamate insecticides. The kdr and ace-1^R mutations were detected in almost all sentinel sites with mosquitoes on the coastal and cotton growing areas mostly affected by these mutations. At almost all sites, the levels of detoxifying enzymes (mixed-function oxidases (MFOs), non-specific esterases (NSE) and glutathione-S-transferases (GSTs)) in An. gambiae populations were significantly higher than the levels found in the susceptible strain Kisumu. Pre-exposure of mosquitoes to PBO, an inhibitor of MFOs and NSEs, significantly increased mortality rates to pyrethroids and carbamates in mosquitoes but resistance in most cases was not fully synergised by PBO, inferring a residual role of additional mechanisms, including kdr and ace-1 site insensitivity. The large distribution of resistance in Côte d''Ivoire raises an important question of whether to continue to deploy pyrethroid-based long-lasting insecticidal nets (LLINs) and insecticide residual spraying (IRS) towards which resistance continues to rise with no guarantee that the level of resistance would not compromise their efficacy. Innovative strategies that combine insecticide and synergists in LLINs or spatially LLIN and an effective non-pyrethroid insecticide for IRS could be in the short term the best practice for the NMCP to manage insecticide resistance in malaria vectors in Côte d''Ivoire and other endemic countries facing resistance.     

Climate influences on the cost-effectiveness of vector-based interventions against malaria in elimination scenarios

Despite the dependence of mosquito population dynamics on environmental conditions, the associated impact of climate and climate change on present and future malaria remains an area of ongoing debate and uncertainty. Here, we develop a novel integration of mosquito, transmission and economic modelling to assess whether the cost-effectiveness of indoor residual spraying (IRS) and long-lasting insecticidal nets (LLINs) against Plasmodium falciparum transmission by Anopheles gambiae s.s. mosquitoes depends on climatic conditions in low endemicity scenarios. We find that although temperature and rainfall affect the cost-effectiveness of IRS and/or LLIN scale-up, whether this is sufficient to influence policy depends on local endemicity, existing interventions, host immune response to infection and the emergence rate of insecticide resistance. For the scenarios considered, IRS is found to be more cost-effective than LLINs for the same level of scale-up, and both are more cost-effective at lower mean precipitation and higher variability in precipitation and temperature. We also find that the dependence of peak transmission on mean temperature translates into optimal temperatures for vector-based intervention cost-effectiveness. Further cost-effectiveness analysis that accounts for country-specific epidemiological and environmental heterogeneities is required to assess optimal intervention scale-up for elimination and better understand future transmission trends under climate change.     

Impact of Insecticide Resistance on the Effectiveness of Pyrethroid-Based Malaria Vectors Control Tools in Benin: Decreased Toxicity and Repellent Effect

Since the first evidence of pyrethroids resistance in 1999 in Benin, mutations have rapidly increased in mosquitoes and it is now difficult to design a study including a control area where malaria vectors are fully susceptible. Few studies have assessed the after effect of resistance on the success of pyrethroid based prevention methods in mosquito populations. We therefore assessed the impact of resistance on the effectiveness of pyrethroids based indoor residual spraying (IRS) in semi-field conditions and long lasting insecticidal nets (LLINs) in laboratory conditions. The results observed showed low repulsion and low toxicity of pyrethroids compounds in the test populations. The toxicity of pyrethroids used in IRS was significantly low with An. gambiae s.l (< 46%) but high for other predominant species such as Mansonia africana (93% to 97%). There were significant differences in terms of the repellent effect expressed as exophily and deterrence compared to the untreated huts (P<0.001). Furthermore, mortality was 23.71% for OlyseNet® and 39.06% for PermaNet®. However, with laboratory susceptible “Kisumu”, mortality was 100% for both nets suggesting a resistance within the wild mosquito populations. Thus treatment with pyrethroids at World Health Organization recommended dose will not be effective at reducing malaria in the coming years. Therefore it is necessary to study how insecticide resistance decreases the efficacy of particular pyrethroids used in pyrethroid-based vector control so that a targeted approach can be adopted.     

Increased risks of malaria due to limited residual life of insecticide and outdoor biting versus protection by combined use of nets and indoor residual spraying on Bioko Island, Equatorial Guinea

ABSTRACT: BACKGROUND: Malaria is endemic on Bioko Island, Equatorial Guinea, with year-round transmission. In 2004 an intensive malaria control strategy primarily based on indoor residual spraying (IRS) was launched. The limited residual life of IRS poses particular challenges in a setting with year-round transmission, such as Bioko. Recent reports of outdoor biting by Anopheles gambiae are an additional cause for concern. In this study, the effect of the short residual life of bendiocarb insecticide and of children spending time outdoors at night, on malaria infection prevalence was examined. METHODS: Data from the 2011 annual malaria indicator survey and from standard WHO cone bioassays were used to examine the relationship between time since IRS, mosquito mortality and prevalence of infection in children. How often children spend time outside at night and the association of this behaviour with malaria infection were also examined. RESULTS: Prevalence of malaria infection in two to 14 year-olds in 2011 was 18.4 %, 21.0 % and 28.1 % in communities with median time since IRS of three, four and five months respectively. After adjusting for confounders, each extra month since IRS corresponded to an odds ratio (OR) of 1.44 (95 % CI 1.15-1.81) for infection prevalence in two to 14 year-olds. Mosquito mortality was 100 %, 96 %, 81 % and 78 %, at month 2, 3, 4 and 5 respectively after spraying. Only 4.1 % of children spent time outside the night before the survey between the hours of 22.00 and 06.00 and those who did were not at a higher risk of infection (OR 0.87, 95 % CI 0.50-1.54). Sleeping under a mosquito net provided additive protection (OR 0.68, 95 % CI 0.54-0.86). CONCLUSIONS: The results demonstrate the epidemiological impact of reduced mosquito mortality with time since IRS. The study underscores that in settings of year-round transmission there is a compelling need for longer-lasting IRS insecticides, but that in the interim, high coverage of long-lasting insecticidal nets (LLINs) may ameliorate the loss of effect of current shorterlasting IRS insecticides. Moreover, continued use of IRS and LLINs for indoor-oriented vector control is warranted given that there is no evidence that spending time outdoors at night increases infection prevalence in children.     

Large-scale use of mosquito larval source management for malaria control in Africa: a cost analysis

Background

At present, large-scale use of two malaria vector control methods, long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) is being scaled up in Africa with substantial funding from donors. A third vector control method, larval source management (LSM), has been historically very successful and is today widely used for mosquito control globally, except in Africa. With increasing risk of insecticide resistance and a shift to more exophilic vectors, LSM is now under re-evaluation for use against afro-tropical vector species. Here the costs of this intervention were evaluated.

Methods

The 'ingredients approach' was used to estimate the economic and financial costs per person protected per year (pppy) for large-scale LSM using microbial larvicides in three ecologically diverse settings: (1) the coastal metropolitan area of Dar es Salaam in Tanzania, (2) a highly populated Kenyan highland area (Vihiga District), and (3) a lakeside setting in rural western Kenya (Mbita Division). Two scenarios were examined to investigate the cost implications of using alternative product formulations. Sensitivity analyses on product prices were carried out.

Results

The results show that for programmes using the same granular formulation larviciding costs the least pppy in Dar es Salaam (US$0.94), approximately 60% more in Vihiga District (US$1.50) and the most in Mbita Division (US$2.50). However, these costs are reduced substantially if an alternative water-dispensable formulation is used; in Vihiga, this would reduce costs to US$0.79 and, in Mbita Division, to US$1.94. Larvicide and staff salary costs each accounted for approximately a third of the total economic costs per year. The cost pppy depends mainly on: (1) the type of formulation required for treating different aquatic habitats, (2) the human population density relative to the density of aquatic habitats and (3) the potential to target the intervention in space and/or time.

Conclusion

Costs for LSM compare favourably with costs for IRS and LLINs, especially in areas with moderate and focal malaria transmission where mosquito larval habitats are accessible and well defined. LSM presents an attractive tool to be integrated in ongoing malaria control effort in such settings. Further data on the epidemiological health impact of larviciding is required to establish cost effectiveness.     

The role of vector control in stopping the transmission of malaria: threats and opportunities

Malaria control, and that of other insect borne diseases such as dengue, is heavily dependent on our ability to control the mosquito populations that transmit these diseases. The major push over the last decade to reduce the global burden of malaria has been driven by the distribution of pyrethroid insecticide-treated bednets and an increase in coverage of indoor residual spraying (IRS). This has reduced malaria deaths by a third. Progress towards the goal of reducing this further is threatened by lack of funding and the selection of drug and insecticide resistance. When malaria control was initially scaled up, there was little pyrethroid resistance in the major vectors, today there is no country in Africa where the vectors remain fully susceptible to pyrethroids. The first pyrethroid resistance mechanisms to be selected produced low-level resistance which had little or no operational significance. More recently, metabolically based resistance has been selected, primarily in West Africa, which in some mosquito populations produces more than 1000-fold resistance. As this spreads the effectiveness of pyrethroid-based bednets and IRS will be compromised. New public health insecticides are not readily available. The pipeline of agrochemical insecticides that can be re-purposed for public health dried up 30 years ago when the target product profile for agricultural insecticides shifted from broad spectrum, stable, contact-acting insecticides to narrow spectrum stomach poisons that could be delivered through the plant. A public–private partnership, the Innovative Vector Control Consortium, was established in 2005 to stimulate the development of new public health pesticides. Nine potential new classes of chemistry are in the pipeline, with the intention of developing three into new insecticides. While this has been successfully achieved, it will still take 6–9 years for new insecticides to reach the market. Careful management of the resistance situation in the interim will be needed if current gains in malaria control are not to be reversed.     

Multiple insecticide resistance: an impediment to insecticide-based malaria vector control program

Background

Indoor Residual Spraying (IRS), insecticide-treated nets (ITNs) and long-lasting insecticidal nets (LLINs) are key components in malaria prevention and control strategy. However, the development of resistance by mosquitoes to insecticides recommended for IRS and/or ITNs/LLINs would affect insecticide-based malaria vector control. We assessed the susceptibility levels of Anopheles arabiensis to insecticides used in malaria control, characterized basic mechanisms underlying resistance, and evaluated the role of public health use of insecticides in resistance selection.

Methodology/Principal findings

Susceptibility status of An. arabiensis was assessed using WHO bioassay tests to DDT, permethrin, deltamethrin, malathion and propoxur in Ethiopia from August to September 2009. Mosquito specimens were screened for knockdown resistance (kdr) and insensitive acetylcholinesterase (ace-1^R) mutations using AS-PCR and PCR-RFLP, respectively. DDT residues level in soil from human dwellings and the surrounding environment were determined by Gas Chromatography with Electron Capture Detector. An. arabiensis was resistant to DDT, permethrin, deltamethrin and malathion, but susceptible to propoxur. The West African kdr allele was found in 280 specimens out of 284 with a frequency ranged from 95% to 100%. Ace-1^R mutation was not detected in all specimens scored for the allele. Moreover, DDT residues were found in soil samples from human dwellings but not in the surrounding environment.

Conclusion

The observed multiple-resistance coupled with the occurrence of high kdr frequency in populations of An. arabiensis could profoundly affect the malaria vector control programme in Ethiopia. This needs an urgent call for implementing rational resistance management strategies and integrated vector control intervention.     

Assessing the impact of low-technology emanators alongside long-lasting insecticidal nets to control malaria

Malaria control in sub-Saharan Africa relies on the widespread use of long-lasting insecticidal nets (LLINs) or the indoor residual spraying of insecticide. Disease transmission may be maintained even when these indoor interventions are universally used as some mosquitoes will bite in the early morning and evening when people are outside. As countries seek to eliminate malaria, they can target outdoor biting using new vector control tools such as spatial repellent emanators, which emit airborne insecticide to form a protective area around the user. Field data are used to incorporate a low-technology emanator into a mathematical model of malaria transmission to predict its public health impact across a range of scenarios. Targeting outdoor biting by repeatedly distributing emanators alongside LLINs increases the chance of elimination, but the additional benefit depends on the level of anthropophagy in the local mosquito population, emanator effectiveness and the pre-intervention proportion of mosquitoes biting outdoors. High proportions of pyrethroid-resistant mosquitoes diminish LLIN impact because of reduced mosquito mortality. When mosquitoes are highly anthropophagic, this reduced mortality leads to more outdoor biting and a reduced additional benefit of emanators, even if emanators are assumed to retain their effectiveness in the presence of pyrethroid resistance. Different target product profiles are examined, which show the extra epidemiological benefits of spatial repellents that induce mosquito mortality.This article is part of the theme issue ‘Novel control strategies for mosquito-borne diseases’.     

Indoor residual spraying of insecticide and malaria morbidity in a high transmission intensity area of Uganda

Background

Recently the use of indoor residual spraying of insecticide (IRS) has greatly increased in Africa; however, limited data exist on the quantitative impacts of IRS on health outcomes in highly malaria endemic areas.

Methodology/Principal Findings

Routine data were collected on more than 90,000 patient visits at a single health facility over a 56 month period covering five rounds of IRS using three different insecticides. Temporal associations between the timing of IRS and the probability of a patient referred for microscopy having laboratory confirmed malaria were estimated controlling for seasonality and age. Considering patients less than five years of age there was a modest decrease in the odds of malaria following the 1^st round of IRS using DDT (OR = 0.76, p<0.001) and the 2^nd round using alpha-cypermethrin (OR = 0.83, p = 0.002). Following rounds 3–5 using bendiocarb there was a much greater decrease in the odds of malaria (ORs 0.34, 0.16, 0.17 respectively, p<0.001 for all comparisons). Overall, the impact of IRS was less pronounced among patients 5 years or older.

Conclusions/Significance

IRS was associated with a reduction in malaria morbidity in an area of high transmission intensity in Uganda and the benefits appeared to be greatest after switching to a carbamate class of insecticide.     

Reducing Plasmodium falciparum Malaria Transmission in Africa: A Model-Based Evaluation of Intervention Strategies

Background

Over the past decade malaria intervention coverage has been scaled up across Africa. However, it remains unclear what overall reduction in transmission is achievable using currently available tools.

Methods and Findings

We developed an individual-based simulation model for Plasmodium falciparum transmission in an African context incorporating the three major vector species (Anopheles gambiae s.s., An. arabiensis, and An. funestus) with parameters obtained by fitting to parasite prevalence data from 34 transmission settings across Africa. We incorporated the effect of the switch to artemisinin-combination therapy (ACT) and increasing coverage of long-lasting insecticide treated nets (LLINs) from the year 2000 onwards. We then explored the impact on transmission of continued roll-out of LLINs, additional rounds of indoor residual spraying (IRS), mass screening and treatment (MSAT), and a future RTS,S/AS01 vaccine in six representative settings with varying transmission intensity (as summarized by the annual entomological inoculation rate, EIR: 1 setting with low, 3 with moderate, and 2 with high EIRs), vector–species combinations, and patterns of seasonality. In all settings we considered a realistic target of 80% coverage of interventions. In the low-transmission setting (EIR∼3 ibppy [infectious bites per person per year]), LLINs have the potential to reduce malaria transmission to low levels (<1% parasite prevalence in all age-groups) provided usage levels are high and sustained. In two of the moderate-transmission settings (EIR∼43 and 81 ibppy), additional rounds of IRS with DDT coupled with MSAT could drive parasite prevalence below a 1% threshold. However, in the third (EIR = 46) with An. arabiensis prevailing, these interventions are insufficient to reach this threshold. In both high-transmission settings (EIR∼586 and 675 ibppy), either unrealistically high coverage levels (>90%) or novel tools and/or substantial social improvements will be required, although considerable reductions in prevalence can be achieved with existing tools and realistic coverage levels.

Conclusions

Interventions using current tools can result in major reductions in P. falciparum malaria transmission and the associated disease burden in Africa. Reduction to the 1% parasite prevalence threshold is possible in low- to moderate-transmission settings when vectors are primarily endophilic (indoor-resting), provided a comprehensive and sustained intervention program is achieved through roll-out of interventions. In high-transmission settings and those in which vectors are mainly exophilic (outdoor-resting), additional new tools that target exophagic (outdoor-biting), exophilic, and partly zoophagic mosquitoes will be required. Please see later in the article for the Editors'' Summary     

Importance of factors determining the effective lifetime of a mass, long-lasting, insecticidal net distribution: a sensitivity analysis

Background

Long-lasting insecticidal nets (LLINs) reduce malaria transmission by protecting individuals from infectious bites, and by reducing mosquito survival. In recent years, millions of LLINs have been distributed across sub-Saharan Africa (SSA). Over time, LLINs decay physically and chemically and are destroyed, making repeated interventions necessary to prevent a resurgence of malaria. Because its effects on transmission are important (more so than the effects of individual protection), estimates of the lifetime of mass distribution rounds should be based on the effective length of epidemiological protection.

Methods

Simulation models, parameterised using available field data, were used to analyse how the distribution's effective lifetime depends on the transmission setting and on LLIN characteristics. Factors considered were the pre-intervention transmission level, initial coverage, net attrition, and both physical and chemical decay. An ensemble of 14 stochastic individual-based model variants for malaria in humans was used, combined with a deterministic model for malaria in mosquitoes.

Results

The effective lifetime was most sensitive to the pre-intervention transmission level, with a lifetime of almost 10 years at an entomological inoculation rate of two infectious bites per adult per annum (ibpapa), but of little more than 2 years at 256 ibpapa. The LLIN attrition rate and the insecticide decay rate were the next most important parameters. The lifetime was surprisingly insensitive to physical decay parameters, but this could change as physical integrity gains importance with the emergence and spread of pyrethroid resistance.

Conclusions

The strong dependency of the effective lifetime on the pre-intervention transmission level indicated that the required distribution frequency may vary more with the local entomological situation than with LLIN quality or the characteristics of the distribution system. This highlights the need for malaria monitoring both before and during intervention programmes, particularly since there are likely to be strong variations between years and over short distances. The majority of SSA's population falls into exposure categories where the lifetime is relatively long, but because exposure estimates are highly uncertain, it is necessary to consider subsequent interventions before the end of the expected effective lifetime based on an imprecise transmission measure.     

Shift in species composition in the Anopheles gambiae complex after implementation of long‐lasting insecticidal nets in Dielmo,Senegal

Long‐lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) are the cornerstones of malaria vector control. However, the effectiveness of these control tools depends on vector ecology and behaviour, which also largely determine the efficacy of certain Anopheles mosquitoes (Diptera: Culicidae) as vectors. Malaria vectors in sub‐Saharan Africa are primarily species of the Anopheles gambiae complex, which present intraspecific differences in behaviour that affect how they respond to vector control tools. The focus of this study is the change in species composition in the An. gambiae complex after the implementation of LLINs in Dielmo, Senegal. The main findings referred to dramatic decreases in the proportions of Anopheles coluzzii and An. gambiae after the introduction of LLINs, and an increase in the proportion of Anopheles arabiensis. Two years after LLINs were first introduced, An. arabiensis remained the most prevalent species and An. gambiae had begun to rebound. This indicated a need to develop additional vector control tools that can target the full range of malaria vectors.     

Determinants of Bed Net Use in Southeast Nigeria following Mass Distribution of LLINs: Implications for Social Behavior Change Interventions

Millions of long-lasting insecticide treated nets (LLINs) have been distributed as part of the global malaria control strategy. LLIN ownership, however, does not necessarily guarantee use. Thus, even in the ideal setting in which universal coverage with LLINs has been achieved, maximal malaria protection will only be achieved if LLINs are used both correctly and consistently. This study investigated the factors associated with net use, independent of net ownership. Data were collected during a household survey conducted in Ebonyi State in southeastern Nigeria in November 2011 following a statewide mass LLIN distribution campaign and, in select locations, a community-based social behavior change (SBC) intervention. Logistic regression analyses, controlling for household bed net ownership, were conducted to examine the association between individual net use and various demographic, environmental, behavioral and social factors. The odds of net use increased among individuals who were exposed to tailored SBC in the context of a home visit (OR = 17.11; 95% CI 4.45–65.79) or who received greater degrees of social support from friends and family (ptrend < 0.001). Factors associated with decreased odds of net use included: increasing education level (ptrend = 0.020), increasing malaria knowledge level (ptrend = 0.022), and reporting any disadvantage of bed nets (OR = 0.39; 95% CI 0.23–0.78). The findings suggest that LLIN use is significantly influenced by social support and exposure to a malaria-related SBC home visit. The malaria community should thus further consider the importance of community outreach, interpersonal communication and social support on adoption of net use behaviors when designing future research and interventions.     

Comparison of the efficacy of long-lasting insecticidal nets PermaNet® 2.0 and Olyset® against Anopheles albimanus under laboratory conditions

Insecticide-treated nets provide a reduction in human-vector contact through physical barrier, mortality and/or repellent effects that protect both users and non-users, thereby protecting the wider community from vector-borne diseases like malaria. Long-lasting insecticide-treated nets (LLINs) are the best alternative. This study evaluated the bioefficacy of LLINs PermaNet? 2.0 and Olyset? under laboratory conditions with Anopheles albimanus. The laboratory strain was evaluated for insecticide susceptibility with selected insecticides used for malarial control. Regeneration time and wash resistance were evaluated with the standard bioassay cone technique following WHO guidelines. Heat assistance was used for Olyset? nets; the nets were exposed to four different temperatures to speed the regeneration process. The regeneration study of PermaNet? 2.0 showed that efficacy was fully recovered by 24 h after one and three washes and wash resistance persisted for 15 washes. Regeneration of Olyset? nets was not observed for nets washed three times, even with the different temperature exposures for up to seven days. Thus, for Olyset? the wash resistance evaluation could not proceed. Differences in response between the two LLINs may be associated with differences in manufacturing procedures and species response to the evaluated LLINs. PermaNet? 2.0 showed higher and continuous efficacy against An. albimanus.     

Contributions of Anopheles larval control to malaria suppression in tropical Africa: review of achievements and potential

Malaria vector control targeting the larval stages of mosquitoes was applied successfully against many species of Anopheles (Diptera: Culicidae) in malarious countries until the mid-20th Century. Since the introduction of DDT in the 1940s and the associated development of indoor residual spraying (IRS), which usually has a more powerful impact than larval control on vectorial capacity, the focus of malaria prevention programmes has shifted to the control of adult vectors. In the Afrotropical Region, where malaria is transmitted mainly by Anopheles funestus Giles and members of the Anopheles gambiae Giles complex, gaps in information on larval ecology and the ability of An. gambiae sensu lato to exploit a wide variety of larval habitats have discouraged efforts to develop and implement larval control strategies. Opportunities to complement adulticiding with other components of integrated vector management, along with concerns about insecticide resistance, environmental impacts, rising costs of IRS and logistical constraints, have stimulated renewed interest in larval control of malaria vectors. Techniques include environmental management, involving the temporary or permanent removal of anopheline larval habitats, as well as larviciding with chemical or biological agents. This present review covers large-scale trials of anopheline larval control methods, focusing on field studies in Africa conducted within the past 15 years. Although such studies are limited in number and scope, their results suggest that targeting larvae, particularly in human-made habitats, can significantly reduce malaria transmission in appropriate settings. These approaches are especially suitable for urban areas, where larval habitats are limited, particularly when applied in conjunction with IRS and other adulticidal measures, such as the use of insecticide treated bednets.     

Reduction in Malaria Incidence following Indoor Residual Spraying with Actellic 300 CS in a Setting with Pyrethroid Resistance: Mutasa District,Zimbabwe

Background

More than half of malaria cases in Zimbabwe are concentrated in Manicaland Province, where seasonal malaria epidemics occur despite intensified control strategies. Recently, high levels of pyrethroid and carbamate resistance were detected in Anopheles funestus, the major malaria vector in eastern Zimbabwe. In response, a single round of indoor residual spraying (IRS) using pirimiphos-methyl (an organophosphate) was implemented in four high burden districts of Manicaland Province from November 1, 2014 to December 19, 2014. The objective of this study was to evaluate the effect of this programmatic switch in insecticides on malaria morbidity reported from health care facilities in Mutasa District, one of the worst affected districts in Manicaland Province.

Methods

The number of weekly malaria cases for each health facility 24 months prior to the 2014 IRS campaign and in the subsequent high transmission season were obtained from passive case surveillance. Environmental variables were extracted from remote-sensing data sources and linked to each health care facility. Negative binomial regression was used to model the weekly number of malaria cases, adjusted for seasonality and environmental variables.

Results

From December 2012 to May 2015, 124,206 malaria cases were reported from 42 health care facilities in Mutasa District. Based on a higher burden of malaria, 20 out of 31 municipal wards were sprayed in the district. Overall, 87.3% of target structures were sprayed and 92.1% of the target population protected. During the 6 months after the 2014 IRS campaign, a period when transmission would have otherwise peaked, the incidence of malaria was 38% lower than the preceding 24 months at health facilities in the sprayed wards.

Conclusions

Pirimiphos-methyl had a measurable impact on malaria incidence and is an effective insecticide for the control of An. funestus in eastern Zimbabwe.     

Malaria Risk Factors in North West Tanzania: The Effect of Spraying,Nets and Wealth

Malaria prevalence remains high in many African countries despite massive scaling-up of insecticide treated nets (ITN) and indoor residual spraying (IRS). This paper evaluates the protective effect of pyrethroid IRS and ITNs in relation to risk factors for malaria based on a study conducted in North-West Tanzania, where IRS has been conducted since 2007 and universal coverage of ITNs has been carried out recently. In 2011 community-based cross-sectional surveys were conducted in the two main malaria transmission periods that occur after the short and long rainy seasons. These included 5,152 and 4,325 children aged 0.5–14 years, respectively. Data on IRS and ITN coverage, household demographics and socio-economic status were collected using an adapted version of the Malaria Indicator Survey. Children were screened for malaria by rapid diagnostic test. In the second survey, haemoglobin density was measured and filter paper blood spots were collected to determine age-specific sero-prevalence in each community surveyed. Plasmodium falciparum infection prevalence in children 0.5–14 years old was 9.3% (95%CI:5.9–14.5) and 22.8% (95%CI:17.3–29.4) in the two surveys. Risk factors for infection after the short rains included households not being sprayed (OR = 0.39; 95%CI:0.20–0.75); low community net ownership (OR = 0.45; 95%CI:0.21–0.95); and low community SES (least poor vs. poorest tertile: OR = 0.13, 95%CI:0.05–0.34). Risk factors after the long rains included household poverty (per quintile increase: OR = 0.89; 95%CI:0.82–0.97) and community poverty (least poor vs. poorest tertile: OR = 0.26, 95%CI:0.15–0.44); household IRS or high community ITN ownership were not protective. Despite high IRS coverage and equitable LLIN distribution, poverty was an important risk factor for malaria suggesting it could be beneficial to target additional malaria control activities to poor households and communities. High malaria prevalence in some clusters and the limited protection given by pyrethroid IRS and LLINs suggest that it may be necessary to enhance established vector control activities and consider additional interventions.     

Molecular surveillance and temporal monitoring of malaria parasites in focal Vietnamese provinces

In the past decade substantial reduction in malaria morbidity and mortality has been observed through well-implemented case management and vector control strategies. India has also achieved a significant reduction in malaria burden in 2018 and has committed to eliminate malaria by 2030. The Mandla Malaria Elimination Demonstration Project (MEDP) was started in 2017 in 1233 villages of District Mandla to demonstrate malaria elimination in a tribal district with hard-to-reach areas was possible using active and passive surveillance, case management, vector control, and targeted information, education and communication campaigns. An operational plan was developed to strengthen the existing surveillance and malaria elimination systems, through fortnightly active case detection to ensure that all cases including those that are introduced into the communities are rapidly identified and treated promptly. The plan also focused on the reduction of human-mosquito contact through the use of Long-Lasting Insecticial Nets (LLINs) and Indoor Residual Spray (IRS). The operational plan was modified in view of the present COVID-19 pandemic by creating systems of assistance for the local administration for COVID-related work while ensuring the operational integrity of malaria elimination efforts. The use of MEDP study design and operational plan, with its built-in management control systems, has yielded significant (91%) reduction of indigenous cases of malaria during the period from June 2017 to May 2020. The malaria positivity rate was 0.33% in 2017–18, 0.13% in 2018–19, and 0.06% in 2019–20. Mass screening revealed 0.18% malaria positivity in September–October 2018, followed by 0.06% in June 2019, and 0.03% in December 2019, and these were mostly asymptomatic cases in the community. The project has been able to sustain the gains of the past three years during the ongoing COVID-19 pandemic. This paper provides the study design and the operational plan for malaria elimination in a high-burden district of Central India, which presented difficulties of hard to reach areas, forest malaria, and complex epidemiology of urban and rural malaria. The lessons learned could be used for malaria elimination efforts in rest of the country and other parts of South Asia with comparable demography and epidemiology.     

Biological tools for control of larval stages of malaria vectors – a review

The two main interventions presently being deployed for control of malaria vectors, that is, long-lasting insecticide-treated bed nets (LLINs) and indoor residual spraying (IRS) involve the use of chemical insecticides and target adult mosquitoes. Meanwhile, the potential of larval control is increasingly being acknowledged for the reduction of insecticide-resistant and/or exophagic Anopheles populations. Larval control has proven to be cost-effective and ideal for localities where mosquito-breeding sites are well defined and approachable. Utilising biological control tools to control anopheline larvae can lower the problem of resistance development, a common feature of chemical control. Fortunately, there are many options of biological larval control tools. Besides their direct impact on mortality, the effects of these tools can reach beyond the larval stage. Anopheline adults that develop from larvae exposed to biological control tools, such as entomopathogenic fungi, show reduced longevity, fecundity and susceptibility to Plasmodium infections. Combining two or more larval control tools can increase their efficacy against anopheline larvae. However, despite the identification of larval control potential in the laboratory, and in few cases in the field, many potential biological control tools have not been utilised to their fullest extent. This review provides an overview of the existing and potential biological larval control options for malaria vectors and discusses the advantages and requirements to develop them for malaria vector control.     

Application of the malaria management model to the analysis of costs and benefits of DDT versus non-DDT malaria control

Introduction

DDT is considered to be the most cost-effective insecticide for combating malaria. However, it is also the most environmentally persistent and can pose risks to human health when sprayed indoors. Therefore, the use of DDT for vector control remains controversial.

Methods

In this paper we develop a computer-based simulation model to assess some of the costs and benefits of the continued use of DDT for Indoor Residual Spraying (IRS) versus its rapid phase out. We apply the prototype model to the aggregated sub Saharan African region. For putting the question about the continued use of DDT for IRS versus its rapid phase out into perspective we calculate the same costs and benefits for alternative combinations of integrated vector management interventions.

Results

Our simulation results confirm that the current mix of integrated vector management interventions with DDT as the main insecticide is cheaper than the same mix with alternative insecticides when only direct costs are considered. However, combinations with a stronger focus on insecticide-treated bed nets and environmental management show higher levels of cost-effectiveness than interventions with a focus on IRS. Thus, this focus would also allow phasing out DDT in a cost-effective manner. Although a rapid phase out of DDT for IRS is the most expensive of the tested intervention combinations it can have important economic benefits in addition to health and environmental impacts that are difficult to assess in monetary terms. Those economic benefits captured by the model include the avoided risk of losses in agricultural exports.

Conclusions

The prototype simulation model illustrates how a computer-based scenario analysis tool can inform debates on malaria control policies in general and on the continued use of DDT for IRS versus its rapid phase out in specific. Simulation models create systematic mechanisms for analyzing alternative interventions and making informed trade offs.