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Malaria remains endemic in 17 countries in the Americas, where 723,000 cases were reported in 2019. The majority (> 90%) of the regional malaria burden is found within the Amazon Basin, which includes nine countries and territories in South America. Locally generated evidence is critical to provide information to public health decision makers upon which the design of efficient and regionally directed malaria control and elimination programs can be built. Plasmodium vivax is the predominant malaria parasite in the Amazon Basin. This parasite species appears to be more resilient to malaria control strategies worldwide. Asymptomatic Plasmodium infections constitute a potentially infectious reservoir that is typically missed by routine microscopy-based surveillance and often remains untreated. The primary Amazonian malaria vector, Nyssorhynchus (formerly Anopheles) darlingi, has changed its behavior to feed and rest predominantly outdoors, reducing the efficiency of core vector control measures such as indoor residual spraying and distribution of long-lasting insecticide-treated bed nets. We review public health implications of recent field-based research carried out by the Amazonia International Center of Excellence in Malaria Research in Peru and Brazil. We discuss the relative role of traditional and novel tools and strategies for better malaria control and elimination across the Amazon, including improved diagnostic methods, new anti-relapse medicines, and biological larvicides, and emphasize the need to integrate research and public health policymaking.

The 1990s saw the rapid reemergence of malaria in Amazonia, where it remains an important public health priority in South America. The Amazonian International Center of Excellence in Malaria Research (ICEMR) was designed to take a multidisciplinary approach toward identifying novel malaria control and elimination strategies. Based on geographically and epidemiologically distinct sites in the Northeastern Peruvian and Western Brazilian Amazon regions, synergistic projects integrate malaria epidemiology, vector biology, and immunology. The Amazonian ICEMR's overarching goal is to understand how human behavior and other sociodemographic features of human reservoirs of transmission-predominantly asymptomatically parasitemic people-interact with the major Amazonian malaria vector, Nyssorhynchus (formerly Anopheles) darlingi, and with human immune responses to maintain malaria resilience and continued endemicity in a hypoendemic setting. Here, we will review Amazonian ICEMR's achievements on the synergies among malaria epidemiology, Plasmodium-vector interactions, and immune response, and how those provide a roadmap for further research, and, most importantly, point toward how to achieve malaria control and elimination in the Americas.

Background: Larvicides are typically applied to fixed and findable mosquito breeding sites, such as fish farming ponds used in commercial aquaculture, to kill immature forms and thereby reduce the size of adult malaria vector populations. However, there is little evidence suggesting that larviciding may suppress community-wide malaria transmission outside Africa. Here, we tested whether the biological larvicide VectoMax FG applied at monthly intervals to fish farming ponds can reduce malaria incidence in Amazonian Brazil., Methods: This study was carried out in Vila Assis Brasil (VAB; population 1700), a peri-urban malaria hotspot in northwestern Brazil with a baseline annual parasite incidence of 553 malaria cases per 1000 inhabitants. The intervention consisted of monthly treatments with 20 kg/ha of VectoMax FG of all water-filled fish ponds in VAB (n ranging between 167 and 170) with a surface area between 20 and 8000 m 2 , using knapsack power mistblowers. We used single-group interrupted time-series analysis to compare monthly larval density measurements in fish ponds during a 14-month pre-intervention period (September 2017-October 2018), with measurements made during November 2018-October 2019 and shortly after the 12-month intervention (November 2019). We used interrupted time-series analysis with a comparison group to contrast the malaria incidence trends in VAB and nearby nonintervention localities before and during the intervention., Results: Average larval densities decreased tenfold in treated fish farming ponds, from 0.467 (95% confidence interval [CI], 0.444-0.490) anopheline larvae per dip pre-intervention (September 2017-October 2018) to 0.046 (95% CI, 0.041-0.051) larvae per dip during (November 2018-October 2019) and shortly after the intervention (November 2019). Average malaria incidence rates decreased by 0.08 (95% CI, 0.04-0.11) cases per 100 person-months (P < 0.0001) during the intervention in VAB and remained nearly unchanged in comparison localities. We estimate that the intervention averted 24.5 (95% CI, 6.2-42.8) malaria cases in VAB between January and December 2019., Conclusions: Regular larviciding is associated with a dramatic decrease in larval density and a modest but significant decrease in community-wide malaria incidence. Larviciding may provide a valuable complementary vector control strategy in commercial aquaculture settings across the Amazon., (© 2021. The Author(s).)

Background: Deforestation and land use change is widespread in Madagascar, altering local ecosystems and creating opportunities for disease vectors, such as the Anopheles mosquito, to proliferate and more easily reach vulnerable, rural populations. Knowledge of risk factors associated with malaria infections is growing globally, but these associations remain understudied across Madagascar's diverse ecosystems experiencing rapid environmental change. This study aims to uncover socioeconomic, demographic, and ecological risk factors for malaria infection across regions through analysis of a large, cross-sectional dataset., Methods: The objectives were to assess (1) the ecological correlates of malaria vector breeding through larval surveys, and (2) the socioeconomic, demographic, and ecological risk factors for malaria infection in four ecologically distinct regions of rural Madagascar. Risk factors were determined using multilevel models for the four regions included in the study., Results: The presence of aquatic agriculture (both within and surrounding communities) is the strongest predictive factor of habitats containing Anopheles larvae across all regions. Ecological and socioeconomic risk factors for malaria infection vary dramatically across study regions and range in their complexity., Conclusions: Risk factors for malaria transmission differ dramatically across regions of Madagascar. These results may help stratifying current malaria control efforts in Madagascar beyond the scope of existing interventions.

Despite historical and contemporary evidence of its effectiveness, larval source management with insecticides remains little used by most malaria control programs worldwide. Here we show that environmentally safe biological larvicides under field conditions can significantly reduce anopheline larval density in fish farming ponds that have became major larval habitats across the Amazon Basin. Importantly, the primary local malaria vector, Anopheles darlingi Root (Diptera: Culicidae), feeds and rests predominantly outdoors, being little affected by interventions such as long-lasting insecticidal bed net distribution and indoor residual spraying. We found >95% reduction in late-instar density up to 7 d after the first application of VectoMax FG or VectoLex CG (both from Valent BioSciences), and up to 21 d after larvicide reapplication in fish ponds (n = 20) situated in the main residual malaria pocket of Brazil, irrespective of the formulation or dosage (10 or 20 kg/ha) used. These results are consistent with a substantial residual effect upon retreatment and support the use of biological larvicides to reduce the density of anopheline larvae in this and similar settings across the Amazon where larval habitats are readily identified and accessible., (© The Author(s) 2019. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Dar es Salaam has an extensive drain network, mostly with inadequate water flow, blocked by waste, causing flooding after rainfall. The presence of Anopheles and Culex larvae is common, which is likely to impact the transmission of lymphatic filariasis and malaria by the resulting adult mosquito populations. However, the importance of drains as larval habitats remains unknown., Methodology: Data on mosquito larval habitats routinely collected by the Urban Malaria Control Program (UMCP) and a special drain survey conducted in 2006 were used to obtain a typology of habitats. Focusing on drains, logistic regression was used to evaluate potential factors impacting the presence of mosquito larvae. Spatial variation in the proportion of habitats that contained larvae was assessed through the local Moran's I indicator of spatial association., Principal Findings: More than 70% of larval habitats in Dar es Salaam were human-made. Aquatic habitats associated with agriculture had the highest proportion of Anopheles larvae presence and the second highest of Culex larvae presence. However, the majority of aquatic habitats were drains (42%), and therefore, 43% (1,364/3,149) of all culicine and 33% (320/976) of all anopheline positive habitats were drains. Compared with drains where water was flowing at normal velocity, the odds of finding Anopheles and Culex larvae were 8.8 and 6.3 (p<0.001) times larger, respectively, in drains with stagnant water. There was a positive association between vegetation and the presence of mosquito larvae (p<0.001). The proportion of habitats with mosquito larvae was spatially correlated., Conclusion: Restoring and maintaining drains in Dar es Salaam has the potential to eliminate more than 40% of all potential mosquito larval habitats that are currently treated with larvicides by the UMCP. The importance of human-made larval habitats for both lymphatic filariasis and malaria vectors underscores the need for a synergy between on-going control efforts of those diseases.

A cross-sectional survey of agricultural areas, combined with routinely monitored mosquito larval information, was conducted in urban Dar es Salaam, Tanzania, to investigate how agricultural and geographical features may influence the presence of Anopheles larvae. Data were integrated into a geographical information systems framework, and predictors of the presence of Anopheles larvae in farming areas were assessed using multivariate logistic regression with independent random effects. It was found that more than 5% of the study area (total size 16.8 km2) was used for farming in backyard gardens and larger open spaces. The proportion of habitats containing Anopheles larvae was 1.7 times higher in agricultural areas compared to other areas (95% confidence interval = 1.56-1.92). Significant geographic predictors of the presence of Anopheles larvae in gardens included location in lowland areas, proximity to river, and relatively impermeable soils. Agriculture-related predictors comprised specific seedbed types, mid-sized gardens, irrigation by wells, as well as cultivation of sugar cane or leafy vegetables. Negative predictors included small garden size, irrigation by tap water, rainfed production and cultivation of leguminous crops or fruit trees. Although there was an increased chance of finding Anopheles larvae in agricultural sites, it was found that breeding sites originated by urban agriculture account for less than a fifth of all breeding sites of malaria vectors in Dar es Salaam. It is suggested that strategies comprising an integrated malaria control effort in malaria-endemic African cities include participatory involvement of farmers by planting shade trees near larval habitats.

Background: The use of larval source management is not prioritized by contemporary malaria control programs in sub-Saharan Africa despite historical success. Larviciding, in particular, could be effective in urban areas where transmission is focal and accessibility to Anopheles breeding habitats is generally easier than in rural settings. The objective of this study is to assess the effectiveness of a community-based microbial larviciding intervention to reduce the prevalence of malaria infection in Dar es Salaam, United Republic of Tanzania. Methods and Findings: Larviciding was implemented in 3 out of 15 targeted wards of Dar es Salaam in 2006 after two years of baseline data collection. This intervention was subsequently scaled up to 9 wards a year later, and to all 15 targeted wards in 2008. Continuous randomized cluster sampling of malaria prevalence and socio-demographic characteristics was carried out during 6 survey rounds (2004–2008), which included both cross-sectional and longitudinal data (N = 64,537). Bayesian random effects logistic regression models were used to quantify the effect of the intervention on malaria prevalence at the individual level. Effect size estimates suggest a significant protective effect of the larviciding intervention. After adjustment for confounders, the odds of individuals living in areas treated with larviciding being infected with malaria were 21% lower (Odds Ratio = 0.79; 95% Credible Intervals: 0.66–0.93) than those who lived in areas not treated. The larviciding intervention was most effective during dry seasons and had synergistic effects with other protective measures such as use of insecticide-treated bed nets and house proofing (i.e., complete ceiling or window screens). Conclusion: A large-scale community-based larviciding intervention significantly reduced the prevalence of malaria infection in urban Dar es Salaam. [ABSTRACT FROM AUTHOR]

Background: Historically, environmental management has brought important achievements in malaria control and overall improvements of health conditions. Currently, however, implementation is often considered not to be cost-effective. A community-based environmental management for malaria control was conducted in Dar es Salaam between 2005 and 2007. After community sensitization, two drains were cleaned followed by maintenance. This paper assessed the impact of the intervention on community awareness, prevalence of malaria infection, and Anopheles larval presence in drains. Methods: A survey was conducted in neighbourhoods adjacent to cleaned drains; for comparison, neighbourhoods adjacent to two drains treated with larvicides and two drains under no intervention were also surveyed. Data routinely collected by the Urban Malaria Control Programme were also used. Diverse impacts were evaluated through comparison of means, odds ratios (OR), logistic regression, and time trends calculated by moving averages. Results: Individual awareness of health risks and intervention goals were significantly higher among sensitized neighbourhoods. A reduction in the odds of malaria infection during the post-cleaning period in intervention neighbourhoods was observed when compared to the pre-cleaning period (OR = 0.12, 95% CI 0.05-0.3, p < 0.001). During the post-cleaning period, a higher risk of infection (OR = 1.7, 95% CI 1.1-2.4, p = 0.0069) was observed in neighbourhoods under no intervention compared to intervention ones. Eighteen months after the initial cleaning, one of the drains was still clean due to continued maintenance efforts (it contained no waste materials and the water was flowing at normal velocity). A three-month moving average of the percentage of water habitats in that drain containing pupae and/or Anopheles larvae indicated a decline in larval density. In the other drain, lack of proper resources and local commitment limited success. Conclusion: Although environmental management was historically coordinated by authoritarian/ colonial regimes or by industries/corporations, its successful implementation as part of an integrated vector management framework for malaria control under democratic governments can be possible if four conditions are observed: political will and commitment, community sensitization and participation, provision of financial resources for initial cleaning and structural repairs, and inter-sectoral collaboration. Such effort not only is expected to reduce malaria transmission, but has the potential to empower communities, improve health and environmental conditions, and ultimately contribute to poverty alleviation and sustainable development. [ABSTRACT FROM AUTHOR]

Background: As the population of Africa rapidly urbanizes, large populations could be protected from malaria by controlling aquatic stages of mosquitoes if cost-effective and scalable implementation systems can be designed. Methods: A recently initiated Urban Malaria Control Programme in Dar es Salaam delegates responsibility for routine mosquito control and surveillance to modestly-paid community members, known as Community-Owned Resource Persons (CORPs). New vector surveillance, larviciding and management systems were designed and evaluated in 15 city wards to allow timely collection, interpretation and reaction to entomologic monitoring data using practical procedures that rely on minimal technology. After one year of baseline data collection, operational larviciding with Bacillus thuringiensis var. israelensis commenced in March 2006 in three selected wards. Results: The procedures and staff management systems described greatly improved standards of larval surveillance relative to that reported at the outset of this programme. In the first year of the programme, over 65,000 potential Anopheles habitats were surveyed by 90 CORPs on a weekly basis. Reaction times to vector surveillance at observations were one day, week and month at ward, municipal and city levels, respectively. One year of community-based larviciding reduced transmission by the primary malaria vector, Anopheles gambiae s.l., by 31% (95% C.I. = 21.6-37.6%; p = 0.04). Conclusion: This novel management, monitoring and evaluation system for implementing routine larviciding of malaria vectors in African cities has shown considerable potential for sustained, rapidly responsive, data-driven and affordable application. Nevertheless, the true programmatic value of larviciding in urban Africa can only be established through longer-term programmes which are stably financed and allow the operational teams and management infrastructures to mature by learning from experience. [ABSTRACT FROM AUTHOR]