COVID19: uncovering interindividual variability for tailoring appropriate therapeutic interventions / COVID19: a variabilidade individual da resposta imunoinflamatória

The severity of SARS-CoV2 infection, Covid19 disease, should account for the diversity of human individual immu-noinflammatory responses. Serum immunological markers during Covid19 illness may lead to individualized thera-peutics with better outcomes. Efficient treatment for Covid19 may require: 1) early disease detection, 2) combined drug therapy for 3) targeting the virus replication cycle, and 4) individualized drug treatment for specific immu-noinflammatory human profile responses administered in a 5) timely manner. Covid19 is unlikely to be the last emergent human disease with fast pandemic potential. Gathering knowledge on the individual human host profiles of immunoinflammatory responses is an opportunity that could lead us to understand individual differences in re-sponse to infection at the individual and population level, paving the way to faster, more efficient strategies to tack-le upcoming infectious diseases. This is a position paper based on an integrative non-exhaustive literature revision (AU)

A diversidade das respostas imunoinflamatórias individuais humanas muito provavelmente tem papel na gravidade da doença Covid19 causada pela infecção pelo vírus SARS-CoV2. Marcadores imunológicos séricos durante a Covid19 po-dem guiar a escolha de terapias individualizadas com melhores resultados. O tratamento eficiente para Covid19 pode exigir: 1) detecção precoce da doença, 2) terapia medicamentosa combinada com alvo ao 3) ciclo de replicação do ví-rus e 4) terapia anti-inflamatória individualizada para perfis de respostas imunoinflamatórias humanas, administradas em tempo hábil. É improvável que a Covid19 seja a última doença humana emergente com potencial de alastramento veloz pandêmico. Reunir conhecimento sobre perfis de respostas imunoinflamatórias individuais dos hospedeiros humanos é uma oportunidade ímpar que pode nos levar a entender as diferenças dessas respostas entre indivíduos, abrindo caminho para estratégias terapêuticas mais rápidas e eficientes no combate à futuras epidemias (AU)

Malaria in Haiti: A descriptive study on spatial and temporal profile from 2009 to 2018

ABSTRACT Background: Haiti is one of the Caribbean countries where malaria persists. More than 99% of malaria cases are caused by Plasmodium falciparum, the main vector being the mosquito Anopheles albimanus. In this paper, we describe the epidemiological profile of malaria in Haiti between 2009 and 2018. Methods We analyzed information on cases reported by the Ministry of Health of Haiti and the World Health Organization (WHO). Results: Between 2009 and 2018, 232,479 malaria cases were reported by the Ministry of Public Health and Population (MSPP); an increase in the incidence of malaria in the country in 2010, followed by a decrease in 2011, was primarily observed. Due to recent efforts to reduce malaria by 2020, its incidence declined from 60,130 cases in 2010 to 8,978 cases in 2018. Controversially, in terms of the number of reported cases, the MSPP and WHO report conflicting data. However, the results from both datasets present the same trend in Haiti from 2009 to 2018. The results also illustrate the endemicity of the disease throughout Haiti, both in rural and urban areas, especially along the coast. Conclusions: This study emphasizes the need to promote official data collection and analyses, as well as the application of epidemiological surveillance of malaria at the municipal level, for a better understanding of the real impact of malaria on the Haitian population and to create more appropriate interventions.

Anophelines species and the receptivity and vulnerability to malaria transmission in the Pantanal wetlands, Central Brazil

BACKGROUND Studies on malaria vectors in the Pantanal biome, Central Brazil, were conducted more than half a century ago. OBJECTIVES To update anopheline records and assess receptivity and vulnerability to malaria transmission. METHODS Five-day anopheline collections were conducted bimonthly in Salobra, Mato Grosso do Sul state, for one year. Indoors, mosquitoes were collected from their resting places, while in open fields, they were captured using protected human-baited and horse-baited traps near the house and at the Miranda River margin, respectively. Hourly biting activity outdoors was also assessed. Secondary data were collected on the arrival of tourists, economic projects, and malaria cases. FINDINGS A total of 24,894 anophelines belonging to 13 species were caught. The main Brazilian malaria vector Anopheles darlingi was the predominant species, followed by An. triannulatus s.l. Hourly variation in anopheline biting showed three main peaks occurring at sunset, around midnight, and at sunrise, the first and last being the most prominent. The highest density of all species was recorded near the river margin and during the transition period between the rainy and early dry seasons. This coincides with the time of main influx of outsider workers and tourists, whose activities mostly occur in the open fields and frequently start before sunrise and last until sunset. Some of these individuals originate from neighbouring malaria-endemic countries and states, and are likely responsible for the recorded imported and introduced malaria cases. MAIN CONCLUSION Pantanal is a malaria-prone area in Brazil. Surveillance and anopheline control measures must be applied to avoid malaria re-emergence in the region.

New classification of natural breeding habitats for Neotropical anophelines in the Yanomami Indian Reserve, Amazon Region, Brazil and a new larval sampling methodology

Here we present the first in a series of articles about the ecology of immature stages of anophelines in the Brazilian Yanomami area. We propose a new larval habitat classification and a new larval sampling methodology. We also report some preliminary results illustrating the applicability of the methodology based on data collected in the Brazilian Amazon rainforest in a longitudinal study of two remote Yanomami communities, Parafuri and Toototobi. In these areas, we mapped and classified 112 natural breeding habitats located in low-order river systems based on their association with river flood pulses, seasonality and exposure to sun. Our classification rendered seven types of larval habitats: lakes associated with the river, which are subdivided into oxbow lakes and nonoxbow lakes, flooded areas associated with the river, flooded areas not associated with the river, rainfall pools, small forest streams, medium forest streams and rivers. The methodology for larval sampling was based on the accurate quantification of the effective breeding area, taking into account the area of the perimeter and subtypes of microenvironments present per larval habitat type using a laser range finder and a small portable inflatable boat. The new classification and new sampling methodology proposed herein may be useful in vector control programs.

Is there an efficient trap or collection method for sampling Anopheles darlingi and other malaria vectors that can describe the essential parameters affecting transmission dynamics as effectively as human landing catches? - A Review

Distribution, abundance, feeding behaviour, host preference, parity status and human-biting and infection rates are among the medical entomological parameters evaluated when determining the vector capacity of mosquito species. To evaluate these parameters, mosquitoes must be collected using an appropriate method. Malaria is primarily transmitted by anthropophilic and synanthropic anophelines. Thus, collection methods must result in the identification of the anthropophilic species and efficiently evaluate the parameters involved in malaria transmission dynamics. Consequently, human landing catches would be the most appropriate method if not for their inherent risk. The choice of alternative anopheline collection methods, such as traps, must consider their effectiveness in reproducing the efficiency of human attraction. Collection methods lure mosquitoes by using a mixture of olfactory, visual and thermal cues. Here, we reviewed, classified and compared the efficiency of anopheline collection methods, with an emphasis on Neotropical anthropophilic species, especially Anopheles darlingi, in distinct malaria epidemiological conditions in Brazil.

Seasonal dynamics of Aedes aegypti (Diptera: Culicidae) in the northernmost state of Brazil: a likely port-of-entry for dengue virus 4

Roraima is the northernmost state of Brazil, bordering both Venezuela and Guyana. Appropriate climate and vector conditions for dengue transmission together with its proximity to countries where all four dengue serotypes circulate make this state, particularly the capital Boa Vista, strategically important for dengue surveillance in Brazil. Nonetheless, few studies have addressed the population dynamics of Aedes aegypti in Boa Vista. In this study, we report temporal and spatial variations in Ae. aegypti population density using ovitraps in two highly populated neighbourhoods; Centro and Tancredo Neves. In three out of six surveys, Ae. aegypti was present in more than 80 percent of the sites visited. High presence levels of this mosquito suggest ubiquitous human exposure to the vector, at least during part of the year. The highest infestation rates occurred during the peak of the rainy seasons, but a large presence was also observed during the early dry season (although with more variation among years). Spatial distribution of positive houses changed from a sparse and local pattern to a very dense pattern during the dry-wet season transition. These results suggest that the risk of dengue transmission and the potential for the new serotype invasions are high for most of the year.

Affinity and diversity indices for anopheline immature forms

As for the entire Amazon Region, malaria continues to be a major health public problem in Roraima that presented an Annual Parasitic Index of 85.4 in 2005, the highest in Brazil. Information on anopheline breeding sites is an essential component in malaria control strategies. Aiming to contribute to the limited knowledge on anopheline immature forms in Roraima, collections and breeding site observations were performed in 10 breeding sites around the capital city Boa Vista. Collections were carried out in the rainy and dry season periods between April 2004 and January 2005. Breeding sites comprised natural and artificial water reservoirs. A total of 623 immature forms were collected belonging to Anopheles albitarsis s.l., An.triannulatus s.l., An. nuneztovari/dunhami, An. braziliensis, An. evansae, An. oswaldoi s.l., An. strodei and An. darlingi. An. albitarsis and An. braziliensis were the most frequently found species. Eight larvae of An. darlingi were found in only one breeding site located in the forest. An. triannulatus/An. nuneztovari and An. albitarsis/An. braziliensis were the pairs of species that mostly occurred together. Both pair of species displayed the highest affinity index what might indicate a high compatibility for the same breeding conditions and/or a synergistic co-occurrence. Species diversity index was higher for the dry season.

Como para toda a Amazônia, a malária representa um importante problema de saúde pública em Roraima. Roraima apresentou um índice parasitário anual de 85,4 em 2005, o maior do Brasil. O conhecimento dos criadouros de anofelinos constitui-se num componente primordial nas estratégias de controle da malária. No intuito de contribuir para o limitado conhecimento dos criadouros de anofelinos em Roraima, coleções de imaturos e observações dos criadouros foram realizadas no entorno da capital Boa Vista. As coletas foram feitas nas estações seca e chuvosa entre abril de 2004 e janeiro de 2005. Os criadouros observados foram reservatórios de água naturais e artificiais. Um total de 623 formas imaturas foram coletadas pertencentes às espécies An. albitarsis s.l., An.triannulatus s.l., An. nuneztovari/dunhami, An. braziliensis, An. evansae, An. oswaldoi s.l., An. strodei e An. darlingi. An. braziliensis e An. albitarsis foram as espécies mais freqüentemente encontradas. Oito larvas de An. darlingi foram encontradas em apenas um criadouro na floresta. An. triannulatus/An. nuneztovari e An. albitarsis/An. braziliensis foram os pares de espécies de maior co-ocorrência. Ambos pares de espécies apresentaram o maior índice de afinidade o que pode indicar compatibilidade para as mesmas condições prevalentes nos criadouros e/ou sinergismo. O índice de diversidade de espécies foi maior para a estação seca.

An ecoregional classification for the state of Roraima, Brazil: the importance of landscape in malaria biology

Understanding the different background landscapes in which malaria transmission occurs is fundamental to understanding malaria epidemiology and to designing effective local malaria control programs. Geology, geomorphology, vegetation, climate, land use, and anopheline distribution were used as a basis for an ecological classification of the state of Roraima, Brazil, in the northern Amazon Basin, focused on the natural history of malaria and transmission. We used unsupervised maximum likelihood classification, principal components analysis, and weighted overlay with equal contribution analyses to fine-scale thematic maps that resulted in clustered regions. We used ecological niche modeling techniques to develop a fine-scale picture of malaria vector distributions in the state. Eight ecoregions were identified and malaria-related aspects are discussed based on this classification, including 5 types of dense tropical rain forest and 3 types of savannah. Ecoregions formed by dense tropical rain forest were named as montane (ecoregion I), submontane (II), plateau (III), lowland (IV), and alluvial (V). Ecoregions formed by savannah were divided into steppe (VI, campos de Roraima), savannah (VII, cerrado), and wetland (VIII, campinarana). Such ecoregional mappings are important tools in integrated malaria control programs that aim to identify specific characteristics of malaria transmission, classify transmission risk, and define priority areas and appropriate interventions. For some areas, extension of these approaches to still-finer resolutions will provide an improved picture of malaria transmission patterns.

Associations between dengue and combinations of weather factors in a city in the Brazilian Amazon

OBJECTIVES: Dengue has become the most important endemic disease in Brazil. The Amazonian state of Roraima has one of the highest incidence rates of dengue in the country. The objective of this study was to determine whether significant temporal relationships exist between the number of reported dengue cases and short-term climate measures for the city of Boa Vista, the capital of Roraima. If such relationships exist, that suggests that it may be possible to predict dengue case numbers based on antecedent climate, thus helping develop a climate-based dengue early-warning system for Boa Vista. METHODS: Seasonal Pearson product-moment correlations were developed between 3-week running averages of daily numbers of reported dengue cases for September 1998-December 2001 and certain meteorological variables (thermal, hydroclimatic, wind, atmospheric pressure, and humidity) up to 25 weeks before. Two-sample t tests were also applied to test for statistically significant differences between samples of daily dengue cases with above-average values and samples with below-average values for three-variable meteorological combinations. These multivariate combinations consisted of the three climate measures that together explained the greatest portion of the variance in the number of dengue cases for the particular season. RESULTS: The strength of the individual averaged correlations varied from weak to moderate. The correlations differed according to the period of the year, the particular climatic variable, and the lag period between the climate indicator and the number of dengue cases. The seasonal correlations in our study showed far stronger relationships than had daily, full-year measures reported in previous studies. Two-sample t tests of multivariate meteorological combinations of atmospheric pressure, wind, and humidity values showed statistically significant differences in the number of reported dengue cases. CONCLUSIONS: Relationships between...

A Triatoma maculata ( Hemiptera, Reduviidae, Triatominae ) population from Roraima, Amazon region, Brazil, has some bionomic characteristics of a potential Chagas disease vector

A doença de Chagas é de rara ocorrência na Região Amazônica Brasileira, onde contudo as condições para o estabelecimento de ciclos domésticos existem. Um estudo previamente realizado em áreas de colonização agrícola no Estado de Roraima, mostrou a possibilidade de ciclos autóctones de transmissão virem a ocorrer uma vez que todos os elementos estavam lá presentes, indivíduos infectados por Trypanosoma cruzi, espécies de triatomíneos anteriormente descritas como infectadas por T. cruzi na Região Amazônica de países fronteiriços e, ambientes domiciliares e peri-domiciliares favoráveis à colonização de triatomíneos. Triatoma maculata foi a espécie mais frequentemente encontrada, tendo sido coletada em galinheiros no peridomicílio e esporadicamente nos domicílios. Visando investigar a potencialidade de T. maculata como espécie vetora na área, algumas características bionômicas foram estudadas em condições de laboratório incluindo freqüência de alimentação, tempo de defecação pós-prandial, tempo de jejum voluntário na pré- e na pós-ecdise, período inter-mudas, períodos de pré-oviposição e de oviposição, índice de oviposição, período de incubação, viabilidade dos ovos, índices de longevidade e de mortalidade. Os resultados mostraram que a população de T. maculata da Colônia Agrícola do Passarão deve ser considerada vetora em potencial do T. cruzi uma vez que mostrou capacidade de infestar ecótopos artificiais no peridomicílio, de se alimentar com freqüência durante o período ninfal, de possuir um ciclo de desenvolvimento relativamente curto com 2,9 gerações/ano, de possuir hábitos ecléticos de alimentação, de defecar imediatamente após a hematofagia quando ainda no hospedeiro e devido ao fato de ter sido previamente encontrada infectada por T. cruzi.

On the possibility of autochthonous Chagas disease in Roraima, Amazon region, Brazil, 2000-2001

A doença de Chagas foi quase inteiramente erradicada das zonas áridas do Brasil Central e Nordeste, onde ciclos autóctones de transmissão praticamente inexistem. Contudo, na última década a doença vem sendo registrada na Região Amazônica. Objetivando investigar a possibilidade da ocorrência de ciclos autóctones de transmissão em áreas de colonização agrícola no Estado de Roraima, foram realizadas coletas de triatomíneos e estudos de sua biologia (a ser mostrado em outro artigo), sorologia (imunofluorescência, hemaglutinação, ELISA) e pesquisa parasitológica (xenodiagnóstico, PCR) entre moradores de Rorainópolis, do Projeto Passarão e da Comunidade da Ilha. Candidatos a doação sanguínea do Hemocentro de Boa Vista também foram avaliados. Foram coletados Triatoma maculata, Rhodnius pictipes, Rhodnius robustus e Panstrongylus geniculatus em palmeiras-buriti Mauritia flexuosa, em anexos peridomiciliares e em domicílios. Nenhum triatomíneo foi encontrado naturalmente infectado. A presença de anticorpos anti-Trypanosoma cruzi foi verificada em 25 indivíduos (1,4% de um total de 1821), 20 dos quais migrantes, todos adultos >15 anos. Apenas dois indivíduos migrantes tiveram mais de dois exames sorológicos positivos (um ainda com xenodiagnóstico positivo e o outro com PCR positivo), estando seguramente infectados. Os resultados mostram que apesar de não ser endêmica, há a presença de todos os elos da cadeia de transmissão da doença de Chagas em Roraima que permitem a sua instalação na ausência de vigilância.

Preliminary assays indicate that Antonia ovata (Loganiaceae) and Derris amazonica (Papilionaceae), ichthyotoxic plants used for fishing in Roraima, Brazil, have an insecticide effect on Lutzomyia longipalpis (Diptera: Psychodidae: Phlebotominae)

Laboratory-reared Lutzomyia longipalpis (Lutz and Neiva 1912) was tested with extracts of two ichthyotoxic plants, known as timbós, used as fishing poison in the Amazon. Phlebotomines, L. longipalpis, and plants, Antonia ovata and Derris amazonica, were collected in the Raposa-Serra do Sol Indian Reserve, a focus of visceral leishmaniasis in the State of Roraima, Brazil. Extracts were prepared from dried leaves of A. ovata and roots of D. amazonica that were percolated in water, filtered and dried out at 50°C. The solid extract obtained was diluted in water at 150, 200 and 250 mg/ml. The solution was blotted in filter paper placed at the bottom of cylindric glass tubes containing sand flies. For each plant extract and dilution, two series of triplicates with 5 male and 5 female specimens of L. longipalpis were used. Mortality was recorded every 2 h during 72 h of exposure. At 72 h the mortality was as high as 80 percent for extracts of A. ovata (LD50 = 233 mg/ ml), and 100 percent for D. amazonica (LD50 = 212 mg/ ml) whereas in the control groups maximum mortality never surpassed 13 percent. Preliminary assays indicated that A. ovata and D. amazonica displayed significant insecticide effect against L. longipalpis

Biting indices, host-seeking activity and natural infection rates of anopheline species in Boa Vista, Roraima, Brazil from 1996 to 1998

The epidemiology of the transmission of malaria parasites varies ecologically. To observe some entomological aspects of the malaria transmission in an urban environment, a longitudinal survey of anopheline fauna was performed in Boa Vista, Roraima, Brazil. A total of 7,263 anophelines was collected in human bait at 13 de Setembro and Caranä districts: Anopheles albitarsis sensu lato (82.8 percent), An. darlingi (10.3 percent), An. braziliensis (5.5 percent), An. peryassui (0.9 percent) and An. nuneztovari (0.5 percent). Nightly 12 h collections showed that An. albitarsis was actively biting throughout the night with peak activities at sunset and at midnight. An. darlingi bit during all night and did not demonstrate a defined biting peak. Highest biting indices, entomological inoculation rates and malaria cases were observed seasonally during the rainy season (April-November). Hourly collections showed host seek activity for all mosquitoes peaked during the first hour after sunset. An. darlingi showed the highest plasmodial malaria infection rate followed by An. albitarsis, An. braziliensis and An. nuneztovari (8.5 percent, 4.6 percent, 3 percent and 2.6 percent, respectively). An. albitarsis was the most frequently collected anopheline, presented the highest biting index and it was the second most frequently collected infected species infected with malaria parasites. An. albitarsis and An. darlingi respectively, are the primary vectors of malaria throughout Boa Vista

Studies on populations of Lutzomyia longipalpis (Lutz & Neiva, 1912) (Diptera: Psychodidae: Phlebotominae) in Brazil

Studies were performed on five Brazilian populations of Lutzomyia longipalpis: Salvaterra (PA), São José do Ribamar (MA), Canindé (CE), Natal (RN) and Gruta da Lapinha, Lagoa Santa (MG). No morphological differences were observed that could distinguish between these populations. Homogeneity tests showed that the allopatric populations display a certain heterogeneity and that the sympatric populations, with different patterns of spots, are homogeneous. The Student-Newman-Keuls test, represented by Euler-Venn diagrams, showed a disjunction between the populations from the north/northeast and the one from Gruta da Lapinha. Genetic distances between the four populations (excluding the Canindé population) were within the range of intrapopulational differences. The Gruta da Lapinha population displayed a heterozygotic deficiency that could be a consequence of high levels of inbreeding due to cryptic habits of living in a small cave. These results do not favor the hypothesis of a L. longipalpis species complex in Brazil, and the species should be considered high polymorphic.

A morphological, isoenzymatic and behavioural study of ten populations of Anopheles(Nyssorhynchus) albitarsis Lynch-Arribalzaga, 1878 (Diptera: culicidae) including from the type-locality - Baradero, Argentina

Anopheles (Nyssorhynchus) albitarsis Lynch-Arribalzaga, 1878 shows morphological and behavioural variations which results in it being sometimes considered as a major malaria vector and at other times as playing no important role in epidemiology. With the aim of clarifying the taxonomy of the species, comparative morphological and isoenzymatic studies were made in populations from the type-locality, Baradero, Argentina and from 9 different localities inBrazil. Morphological studies consisted of the observation of eggs in scanning electron microscopy, of complete chaetotaxy of larvae and pupae and of the detailed drawing of male and female adults. Only Guajara-Mirim and Rio Branco populations, described previously as Anopheles deaneorum sp.n., showed morphological differences. Isoenzymes were studied using 4th instar larvae homogenate and agarosegel electrophoresis. Eleven enzymatic loci were analyzed. By calculation of Nei's Genetic Distance (D), the populations could be separated into 5 groups: i)Baradero, ii)Marajo, iii)Boa Vista, iv)Angra, Itaguai and Paraipaba and v)Guajara-Mirim and Rio Branco. These groups belong to 2 major clusters called I and II, separated by D = 0.345. In the I cluster are groups i, ii and iii and in II clusteriv and v. In I, D=0.246 separates i and ii from iii, while i is separated by D =0.181 from ii. In II, D = 0.223 between iv and v. Only the population of group vcould be distinguished morphologically from the others, leading to the description of an independent species An. deaneorum