Evaluation of Long-lasting insecticidal nets (LLINs) for malaria control in an endemic area in Brazil.

BACKGROUND: Most cases of malaria in Brazil are concentrated in the Amazon region. One of the vector control alternatives recommended by the WHO is the long-lasting insecticidal net (LLIN). This tool is used in the nine federal states of the Brazilian Legal Amazon, where LLINs are essential for reducing vector density and disease transmission as they prevent contact between the mosquito and the individual. The objective of this study was to evaluate the residuality and use of LLIN insecticides in different health regions in a city located in the Brazilian Amazon. METHODS: A total of 17,027 LLINs were installed in the third, fifth and ninth health regions of the municipality of Porto Velho, Rondonia State, Brazil. The LLINs were of two types: Olyset (permethrin), for around the bed, and Interceptor (alphacypermethrin), for around hammocks. The residuality of 172 LLINs was evaluated using cone bioassays to verify the mortality rate of the mosquito Nyssorhynchus darlingi, over a period of 2 years. Structured questionnaires on the acceptance and use of LLINs were distributed to the participating population (n = 391), covering a total sample of 1147 mosquito nets. The mortality rate was evaluated both in terms of days after LLIN installation and the type of insecticide used. Statistical analyses were based on analysis of variance (ANOVA) and Chi-square and were performed using the SPSS statistical program. RESULTS: For the Ny. darlingi mosquito, Interceptor-type LLINs showed residual efficacy, with mortality rates ≥ 80% during the 2-year study period, as determined by the WHO. In contrast, Olyset-type LLINs were associated with a reduction in mortality rates, with 76% and 45% mortality rates in the last two assessments, which occurred during the last 6 months of the study period. Based on the structured questionnaires, the acceptance rate, i.e. percentage of individuals accepting the permanence of the 1147 LLINs sampled, in the three health regions of Porto Velho was 93.8% (of 1076 LLINs). CONCLUSION: The alphacypermethrin-impregnated LLIN was more effective than the LLIN impregnated with permethrin. The results indicate that the correct use of mosquito nets-and consequently the protection of the population-needs to be supported by health promotion actions. These initiatives are considered to be essential for the success of this vector control strategy. New studies that consider the monitoring of the placement of mosquito nets are necessary to provide effective support in the correct use of this methodology.

Modeling Sustained Transmission of Wolbachia among Anopheles Mosquitoes: Implications for Malaria Control in Haiti.

Wolbachia infection in Anopheles albimanus mosquitoes can render mosquitoes less capable of spreading malaria. We developed and analyzed a mechanistic compartmental ordinary differential equation model to evaluate the effectiveness of Wolbachia-based vector control strategies among wild Anopheles mosquitoes in Haiti. The model tracks the mosquito life stages, including egg, larva, and adult (male and female). It also accounts for critical biological effects, such as the maternal transmission of Wolbachia through infected females and cytoplasmic incompatibility, which effectively sterilizes uninfected females when they mate with infected males. We derive and interpret dimensionless numbers, including the basic reproductive number and next-generation numbers. The proposed system presents a backward bifurcation, which indicates a threshold infection that needs to be exceeded to establish a stable Wolbachia infection. The sensitivity analysis ranks the relative importance of the epidemiological parameters at baseline. We simulate different intervention scenarios, including prerelease mitigation using larviciding and thermal fogging before the release, multiple releases of infected populations, and different release times of the year. Our simulations show that the most efficient approach to establishing Wolbachia is to release all the infected mosquitoes immediately after the prerelease mitigation process. Moreover, the model predicts that it is more efficient to release during the dry season than the wet season.

Time-Varying Effects of Meteorological Variables on Malaria Epidemiology in the Context of Interrupted Control Efforts in the Amazon Rainforest, 2000-2017.

Successful malaria control interventions, mostly based on the training of health workers, distribution of insecticide-treated nets, and spraying, decrease malaria incidence; however, when these interventions are interrupted, a resurgence may occur. In the Peruvian Amazon, after discontinuing the control activities implemented by the PAMAFRO project (2006-2010)-a Global Fund-sponsored project for the strengthening of malaria control and surveillance in multiple countries in Latin America- malaria cases re-emerged dramatically. In parallel, meteorological factors determine the conditions suitable for the development, reproduction, and survival of mosquito vectors and parasites. This study hypothesized that interruption of malaria interventions may have modified the meteorological-malaria relationships over time (i.e., temporal changes in the dose-response between meteorological variables and malaria incidence). In this panel data analysis, we assessed the extent that relationships between meteorological variables and malaria changed temporally using data of monthly malaria incidence due to Plasmodium vivax or P. falciparum in Loreto, Peru (2000-2017). Generalized additive models were used to explore how the effects of meteorological variables changed in magnitude before, during, and after the PAMAFRO intervention. We found that once the PAMAFRO intervention had been interrupted, the estimated effects (dose-response) of meteorological variables on incidence rates decreased for both malaria parasite species. However, these fitted effect estimates did not reach their baseline levels (before the PAMAFRO period); variations of time-varying slopes between 0.45 and 2.07 times were observed after the PAMAFRO intervention. We also reported significant heterogeneity in the geographical distributions of malaria, parasite species, and meteorological variables. High malaria transmission occurred consistently in the northwestern provinces of Loreto Department. Since the end of the PAMAFRO period, a higher effect of precipitation and actual evapotranspiration was described on P. falciparum compared to P. vivax. The effect of temperature on malaria was greater over a shorter time (1-month lag or less), compared with precipitation and actual evapotranspiration (12-month lag). These findings demonstrate the importance of sustained malaria control efforts since interruption may enhance the links between meteorological factors and malaria. Our results also emphasize the importance of considering the time-varying effect of meteorological factors on malaria incidence to tailor control interventions, especially to better manage the current and future climate change crisis.

Diagnostic Methods for Non-Falciparum Malaria.

Malaria is a serious public health problem that affects mostly the poorest countries in the world, killing more than 400,000 people per year, mainly children under 5 years old. Among the control and prevention strategies, the differential diagnosis of the Plasmodium-infecting species is an important factor for selecting a treatment and, consequently, for preventing the spread of the disease. One of the main difficulties for the detection of a specific Plasmodium sp is that most of the existing methods for malaria diagnosis focus on detecting P. falciparum. Thus, in many cases, the diagnostic methods neglect the other non-falciparum species and underestimate their prevalence and severity. Traditional methods for diagnosing malaria may present low specificity or sensitivity to non-falciparum spp. Therefore, there is high demand for new alternative methods able to differentiate Plasmodium species in a faster, cheaper and easier manner to execute. This review details the classical procedures and new perspectives of diagnostic methods for malaria non-falciparum differential detection and the possibilities of their application in different circumstances.

Setting-up a cross-border action-research project to control malaria in remote areas of the Amazon: describing the birth and milestones of a complex international project (Malakit).

BACKGROUND: In French Guiana, gold miners working illegally represents a major reservoir of malaria. This mobile population, mainly of Brazilian descent, enters the French Guianese forest from neighbouring countries, Suriname and Brazil. A complex and innovative intervention was piloted as a cooperation with the three involved countries involved to control malaria in this specific population. The principle was that health workers called "facilitators" provide the participants with a self-diagnosis and self-treatment kit along with adequate training and material to rapidly manage an episode of malaria symptoms on their own, when they find themselves isolated from health care services. METHODS: This paper describes the design, development, content of the intervention and players' organization of this multi-country project, the opportunities and constraints encountered, and the lessons learnt at this stage. RESULTS: The choice not to implement the usual "Test and Treat" approach within the community is mainly driven by regulatory reasons. The content of medical messages tends to balance the tension between thoroughness, accuracy and efficacy. The wide range of tools developed through a participatory approach was intended to cope with the challenges of the literacy level of the target population. Despite the difficulties encountered due to language, regulation differences and distance between partners, cooperation was fruitful, due to the complementary of stakeholders, their involvement at all important stages and regular face-to-face meetings. DISCUSSION AND CONCLUSION: This experience shows the feasibility of an ambitious project of action-research in a border malaria context, involving several countries and with a mobile and undocumented population. It reveals some factors of success which may be transferable in analogous settings.

Anopheles aquasalis transcriptome reveals autophagic responses to Plasmodium vivax midgut invasion.

BACKGROUND: Elimination of malaria depends on mastering transmission and understanding the biological basis of Plasmodium infection in the vector. The first mosquito organ to interact with the parasite is the midgut and its transcriptomic characterization during infection can reveal effective antiplasmodial responses able to limit the survival of the parasite. The vector response to Plasmodium vivax is not fully characterized, and its specificities when compared with other malaria parasites can be of fundamental interest for specific control measures. METHODS: Experimental infections were performed using a membrane-feeding device. Three groups were used: P. vivax-blood-fed, blood-fed on inactivated gametocytes, and unfed mosquitoes. Twenty-four hours after feeding, the mosquitoes were dissected and the midgut collected for transcriptomic analysis using RNAseq. Nine cDNA libraries were generated and sequenced on an Illumina HiSeq2500. Readings were checked for quality control and analysed using the Trinity platform for de novo transcriptome assembly. Transcript quantification was performed and the transcriptome was functionally annotated. Differential expression gene analysis was carried out. The role of the identified mechanisms was further explored using functional approaches. RESULTS: Forty-nine genes were identified as being differentially expressed with P. vivax infection: 34 were upregulated and 15 were downregulated. Half of the P. vivax-related differentially expressed genes could be related to autophagy; therefore, the effect of the known inhibitor (wortmannin) and activator (spermidine) was tested on the infection outcome. Autophagic activation significantly reduced the intensity and prevalence of infection. This was associated with transcription alterations of the autophagy regulating genes Beclin, DRAM and Apg8. CONCLUSIONS: Our data indicate that P. vivax invasion of An. aquasalis midgut epithelium triggers an autophagic response and its activation reduces infection. This suggests a novel mechanism that mosquitoes can use to fight Plasmodium infection.

Challenges for malaria elimination in Brazil.

Brazil currently contributes 42 % of all malaria cases reported in the Latin America and the Caribbean, a region where major progress towards malaria elimination has been achieved in recent years. In 2014, malaria burden in Brazil (143,910 microscopically confirmed cases and 41 malaria-related deaths) has reached its lowest levels in 35 years, Plasmodium falciparum is highly focal, and the geographic boundary of transmission has considerably shrunk. Transmission in Brazil remains entrenched in the Amazon Basin, which accounts for 99.5 % of the country's malaria burden. This paper reviews major lessons learned from past and current malaria control policies in Brazil. A comprehensive discussion of the scientific and logistic challenges that may impact malaria elimination efforts in the country is presented in light of the launching of the Plan for Elimination of Malaria in Brazil in November 2015. Challenges for malaria elimination addressed include the high prevalence of symptomless and submicroscopic infections, emerging anti-malarial drug resistance in P. falciparum and Plasmodium vivax and the lack of safe anti-relapse drugs, the largely neglected burden of malaria in pregnancy, the need for better vector control strategies where Anopheles mosquitoes present a highly variable biting behaviour, human movement, the need for effective surveillance and tools to identify foci of infection in areas with low transmission, and the effects of environmental changes and climatic variability in transmission. Control actions launched in Brazil and results to come are likely to influence control programs in other countries in the Americas.

G6PD deficiency in Latin America: systematic review on prevalence and variants

Plasmodium vivax radical cure requires the use of primaquine (PQ), a drug that induces haemolysis in glucose-6-phosphate dehydrogenase deficient (G6PDd) individuals, which further hampers malaria control efforts. The aim of this work was to study the G6PDd prevalence and variants in Latin America (LA) and the Caribbean region. A systematic search of the published literature was undertaken in August 2013. Bibliographies of manuscripts were also searched and additional references were identified. Low prevalence rates of G6PDd were documented in Argentina, Bolivia, Mexico, Peru and Uruguay, but studies from Curaçao, Ecuador, Jamaica, Saint Lucia, Suriname and Trinidad, as well as some surveys carried out in areas of Brazil, Colombia and Cuba, have shown a high prevalence (> 10%) of G6PDd. The G6PD A-202A mutation was the variant most broadly distributed across LA and was identified in 81.1% of the deficient individuals surveyed. G6PDd is a frequent phenomenon in LA, although certain Amerindian populations may not be affected, suggesting that PQ could be safely used in these specific populations. Population-wide use of PQ as part of malaria elimination strategies in LA cannot be supported unless a rapid, accurate and field-deployable G6PDd diagnostic test is made available.

A qualitative study exploring perspectives towards rational use of medicines in Pakistan's Malaria Control Program (MCP)

Malaria is one of the most important global public health problems threatening the health of the population owing to prevailing socio-economic conditions and epidemiological reasons in Pakistan. This qualitative study has focused on the perspectives held towards the rational use of medicine intervention among malaria control program officials. Eight semi-structured interviews with all officials working for the malaria control program in Islamabad were conducted. The interviews, which were audio-taped and transcribed verbatim, were evaluated by thematic content analysis and by all authors. All respondents agreed on successful implementation of the malaria control program in Pakistan for controlling malaria by improving diagnostic and treatment facilities and promoting rational case management through training of prescribers. However, funding is still the major challenge faced by the program for its future implementation.

A malária é um dos mais importantes problemas sanitários globais, que ameaça a saúde população devido às condições socioeconômicas e por razões epidemiológicas no Paquistão. Este estudo qualitativo focou-se nas perspectivas no sentido do uso racional da intervenção médica entre os funcionários do programa de controle da malária. Oito entrevistas semiestruturas com todos os funcionários que trabalham no programa de controle da malária foram conduzidas em Islamabad. As entrevistas, que eram gravadas e transcritas, foram avaliadas por análise temática do conteúdo e por todos os autores. Todos os respondentes concordaram com o êxito da implementação do programa de controle da malária no Paquistão por meio do aprimoramento do diagnóstico e de facilidades do tratamento, promovendo a gestão racional por meio do treinamento dos prescritores. Entretanto, o financiamento é, ainda, o principal desafio enfrentado para a implementação futura do programa.

The residual effect of deltametrine in the control of Malaria as observed on fifferent types Of walls In the Brazilian Amazon 1

The residual power of deltametrine FW (25 mg 1 .a/m2) was evaluated and compared to that of DDT (2 g i.a./m2) by means of biological tests. The different kinds of material used in constructing houses in Amazonia, such as: masonry, wood, and wattle and daub, were used. Data from logistic regression showed that the drop in mortality, the inclination of the curve in relation to time, was similar for the two insecticides in the first samples. The negative coeficient for the variable, months after application, confirmed a reduction in the activity of both insecticides. Wooden and wattle walls showed positive and negative coeficiencies respectively from the beginning. The wooden walls retained a residual effect but the wattle walls were shown to be the least indicated for the application of insecticides The experiments demonstrated a more prolonged residual effect for deltametrine as compared to DDT, and that insecticides work better on brick and cement and wooden walls than they do on wattle and daub constructions. For these reasons, it would be necessary to spray brick and cement walls every 8 months, wooden ones every 9 months and wattle constructions every 7 months to control the vectors of malaria.

Controle da Malária pós-transfusional na amazônia brasileira: proposta de modificaçäo das normas técnicas - relatório / Post-transfusion malaria control in brazilian amazon proposal of modifications for tecnicals norms - report

O Encontro sobre controle da malária pós-transfusional em áreas endêmicas permitiu a avaliaçäo dos procedimentos de triagem rotineiramente empregados na hemorrede pública, além de ampliar o debate, no que se refere a malária, para a atualizaçäo das normas técnicas que constam na regulamentaçäo da Medicina Transfusional do Cone Sul. Entre as questöes debatidas pelos participantes, constaram os critérios epidemiológicos de seleçäo de doadores e o emprego de testes sorológicos e ou parasitológicos na identificaçäo de doadores de risco. Como propostas aprovadas ficou estabelecido que se devem rejeitar candidatos a doaçäo que apresentaram malária nos últimos 12 meses, ou febre nos últimos 30 dias, candidato com suspeita de malária nos últimos 30 dias, candidato procedente ou residente em àrea de alto risco de malária. Será aceito, porém, submetido a testes parasitológicos, o candidato que apresentou malária entre 12 a 36 mëses antes da doaçäo e for procedente de àrea de médio e baixo risco de malária. A classificaçäo das áreas em alto, médio e baixo risco deverá ser regularmente fornecida pela Fundaçäo Nacional de Saúde. Näo seräo empregados testes sorológicos na triagem de doadores

The meeting on the control of transfusional transmitted malaria in endemic areas evaluated the screenning procedures used in public blood centers and enlarged the discussion about the updating of the technical norms for malaria existent in the regulation of the Transfusion Medicine of the South Cone. The epidemiological criteria for donors selection and the use of sorological and/or parasitological tests in the identification of risk donors were some of the subjects debated by the participants. It was approved and established that candidates for donation that presented malaria in the last 12 months; with fever in the last 30 days; with malaria suspicion in the last 30 days; procedent or resident of an area of high malaria risk, should be rejected. Candidates that presented malaria 12 to 36 months before the donation or coming from area of medium and low malaria risk, will be accepted after submittion to parasitological tests. The classification of the areas in high, medium and low risk should be based on the Annual Parasitic Index, information that should be supplied by the National Health Foundation. Sorological tests will not be used for donor screening.

The residual effect of deltametrine in the control of Malaria as observed on fifferent types Of walls In the Brazilian Amazon 1

The residual power of deltametrine FW (25 mg 1 .a/m2) was evaluated and compared to that of DDT (2 g i.a./m2) by means of biological tests. The different kinds of material used in constructing houses in Amazonia, such as: masonry, wood, and wattle and daub, were used. Data from logistic regression showed that the drop in mortality, the inclination of the curve in relation to time, was similar for the two insecticides in the first samples. The negative coeficient for the variable, months after application, confirmed a reduction in the activity of both insecticides. Wooden and wattle walls showed positive and negative coeficiencies respectively from the beginning. The wooden walls retained a residual effect but the wattle walls were shown to be the least indicated for the application of insecticides The experiments demonstrated a more prolonged residual effect for deltametrine as compared to DDT, and that insecticides work better on brick and cement and wooden walls than they do on wattle and daub constructions. For these reasons, it would be necessary to spray brick and cement walls every 8 months, wooden ones every 9 months and wattle constructions every 7 months to control the vectors of malaria.

Ação de mosquiteiros impregnados com deltametrina sobre a morbidade da malária em uma área da Amazônia Brasileira / Effect of bed nets impregnated with deltamethrin on malaria morbidity in an area of the Brazilian Amazones

Em 1992 foi feita uma investigação sobre o efeito protetor do uso de mosquiteiros impregnados com deltametrina, em uma população do município de Costa Marques, Rondônia, sujeita à transmissão malárica. Os mosquiteiros impregnados se comportaram de modo semelhante aos não impregnados, sem modificar os índices de infecção na época de baixa transmissão. A análise multivariada, por idade e títulos de anticorpos, mostrou uma proteção significante para o grupo com mosquiteiros impregnados contra o risco de infecção, apenas na estação de alta transmissão, quando os mosquiteiros foram usados mais regularmente. Não houve diferença no efeito de ambos os tipos de mosquiteiros na prevenção de elevadas parasitemias. Ao fim do estudo, ocorreu diminuição da prevalência de esplenomegalia em ambos os grupos, porém houve uma aparente recuperação da taxa normal de hematócrito em menores de 15 anos de idade em uso de mosquiteiros impregnados.

In 1992 an investigation regarding the value of insecticide impregnated mosquito nets was conducted in the municipality of Costa Marques, Rondonia. Impregnated mosquito nets gave similar protection to those not impregnated, without modifying the incidence of infection during the season of low transmission. The multivariate analysis for age and antibody titre showed a significant protection of impregnated nets against the risk of infection only in the season of high transmission, when bed nets were used more correctly. There was no difference in the effect of both kinds of bed nets in the prevention of high parasitaemia. At the end of the study, there was a reduction of the prevalence of splenomegaly in both groups but hematocrit values rose to normal in the below 15 year olds using impregnated nets.