Nicolas Dégallier

Climate-based models for understanding and forecasting dengue epidemics.

Background Dengue dynamics are driven by complex interactions between human-hosts, mosquito-vectors and viruses that are influenced by environmental and climatic factors. The objectives of this study were to analyze and model the relationships between climate, Aedes aegypti vectors and dengue outbreaks in Noumea (New Caledonia), and to provide an early warning system. Methodology/Principal Findings Epidemiological and meteorological data were analyzed from 1971 to 2010 in Noumea. Entomological surveillance indices were available from March 2000 to December 2009. During epidemic years, the distribution of dengue cases was highly seasonal. The epidemic peak (March–April) lagged the warmest temperature by 1–2 months and was in phase with maximum precipitations, relative humidity and entomological indices. Significant inter-annual correlations were observed between the risk of outbreak and summertime temperature, precipitations or relative humidity but not ENSO. Climate-based multivariate non-linear models were developed to estimate the yearly risk of dengue outbreak in Noumea. The best explicative meteorological variables were the number of days with maximal temperature exceeding 32°C during January–February–March and the number of days with maximal relative humidity exceeding 95% during January. The best predictive variables were the maximal temperature in December and maximal relative humidity during October–November–December of the previous year. For a probability of dengue outbreak above 65% in leave-one-out cross validation, the explicative model predicted 94% of the epidemic years and 79% of the non epidemic years, and the predictive model 79% and 65%, respectively. Conclusions/Significance The epidemic dynamics of dengue in Noumea were essentially driven by climate during the last forty years. Specific conditions based on maximal temperature and relative humidity thresholds were determinant in outbreaks occurrence. Their persistence was also crucial. An operational model that will enable health authorities to anticipate the outbreak risk was successfully developed. Similar models may be developed to improve dengue management in other countries.

Inadequate management of natural ecosystem in the Brazilian Amazon region results in the emergence and reemergence of arboviruses

A total of 187 different species of arboviruses and other viruses in vertebrates were identified at the Evandro Chagas Institute (IEC) from 1954 to 1998, among more than 10,000 arbovirus strains isolated from humans, hematophagous insects, and wild and sentinel vertebrates. Despite intensive studies in the Brazilian Amazon region, especially in Pará State, very little is known about most of these viruses, except for information on date, time, source, and method of isolation, as well as their capacity to infect laboratory animals. This paper reviews ecological and epidemiological data and analyzes the impact of vector and host population changes on various viruses as a result of profound changes in the natural environment. Deforestation, mining, dam and highway construction, human colonization, and urbanization were the main manmade environmental changes associated with the emergence and/or reemergence of relevant arboviruses, including some known pathogens for humans.

Influence of spatial heterogeneity on an emerging infectious disease: the case of dengue epidemics

The importance of spatial heterogeneity and spatial scales (at a village or neighbourhood scale) has been explored with individual-based models. Our reasoning is based on the Chilean Easter Island (EI) case, where a first dengue epidemic occurred in 2002 among the relatively small population localized in one village. Even in this simple situation, the real epidemic is not consistent with homogeneous models. Conversely, including contact heterogeneity on different scales (intra-households, inter-house, inter-areas) allows the recovery of not only the EI epidemiological curve but also the qualitative patterns of Brazilian urban dengue epidemic in more complex situations.

LARVICIDAL ACTIVITY OF SOME CERRADO PLANT EXTRACTS AGAINST AEDES AEGYPTI

ABSTRACT One hundred ninety hexanic and ethanolic extracts from 27 plant species from the Cerrado biome of Brazil were tested for larvicidal activity against 3rd-stage Aedes aegypti larvae at 500 μg/ml. Fourteen extracts from 7 species showed activity (>65% mortality) against the larvae. Of these, Duguetia furfuracea, Piptocarpha rotundifolia, Casearia sylvestris var. lingua, Serjania lethalis, and Xylopia aromatica were active at 56.6, 162.31, 232.4, 285.76, and 384.37 μg/ml, respectively. Annona crassiflora and Cybistax antisyphilitica showed activity at 23.06 and 27.61 μg/ml. The larvicidal properties of these species are described for the first time, and may prove to be promising in active chemical compound isolation.

Epidemia de febre classica de dengue causada pelo sorotipo 2 Em Araguaina, Tocantins, Brasil

Registramos a ocorrencia de epidemia de dengue causada pelo sorotipo 2 (DEN 2) na cidade de Araguaina, estado do Tocantins (TO) situado no Brasil central. Quatrocentos individuos de 74 familias, residentes nos bairros S. Joao, Araguaina Sul e Neblina foram entrevistados e sangrados, independentemente de terem adoecido ou nao. Os soros tanto de adultos quanto de criancas de ambos os sexos foram usados para pesquisa de anticorpos inibidores da hemaglutinacao (IH) e IgM atraves de ensaio imunoenzimatico (MAC ELISA). Nas casas onde haviam doentes no momento do inquerito, sangue total tambem foi colhido para tentativa de isolamento de virus. O quadro clinico apresentado pelos pacientes foi caracterizado por febre, cefaleia, mialgias, artralgias e exantema do tipo maculo-papular nao pruriginoso. A infeccao foi mais frequente em mulheres (33.9%) do que nos homens (23.8%), ocorrendo em todas as faixas etarias, inclusive em criancas com menos de um ano de idade, bem como em maiores de 70 anos. Um total de 1105 mosquitos (56 femeas e 45 machos de Culex quinquefasciatus e 567 femeas e 437 machos de Aedes aegypti) foram obtidos a partir de larvas coletadas em Araguaina. As femeas de Ae. aegypti obtidas das larvas fizeram repasto sanguineo em 8 pacientes febris. O diagnostico laboratorial foi feito por isolamento de virus (cultura de celulas de Aedes albopictus, clone C6/36) e por sorologia (IH e MAC ELISA). Foram isoladas 5 amostras de DEN 2 de pacientes febris e tipadas por imunofluorescencia indireta usando anticorpos monoclonais de dengue. Nenhuma amostra viral foi isolada de mosquitos. Outrossim, comprovou-se infeccao em 111 pessoas sangradas, o que revelou um indice de positividade de 27.75% (111 em 400), sendo que 66.2% das familias estudadas apresentaram pelo menos um individuo positivo. Ocorreram ainda, 26.1% de infeccoes assintomati-cas. Por outro lado, a correlacao de positividade entre os dois testes usados (IH e MAC ELISA) foi de 94.6%. Estimamos que ocorreram aproximadamente 83.250 casos da doenca, entre 15 de marco a 31 de maio de 1991. Esta e a primeira epidemia de DEN 2 em um estado da Amazonia Brasileira, portanto em area endemica de febre amarela, e a primeira evidencia da interiorizacao do DEN 2, ate entao restrito ao Rio de Janeiro.We report the first outbreak of dengue fever caused by dengue 2 (DEN 2) in Araguaina, Tocantins State. Four hundred people of 74 families, living at S. João, Araguaina Sul and Neblina districts were questioned and then bled, in order to obtain sera to test for anti-dengue antibodies. If a person was sick, a small quantity of blood was collected for virus isolation. The main clinical picture of disease was characterized by fever, headache, myalgias, arthralgias and skin rash. Were obtained 1,105 (56 females and 45 males of Culex quinquefasciatus and 567 females and 437 males of Aedes aegypti) mosquitoes from larvae collected in Araguaina. The females of Aedes aegypti obtained from larvae were allowed to feed on 8 febrile patients. The diagnosis of infection was made by both virus isolation into Aedes albopictus (C6/36) cells, and serology, by Hemagglutination-inhibition (HI) and IgM capture ELISA (MAC ELISA). No virus was isolated from mosquitoes. Although five strains of DEN 2 were obtained from humans, and another 111 infections were diagnosed serologically (IgM positive). The positivity rate of the samples was 27.75% (111 of 400), while that of the families was 66.2% (45 of 72), where at least one member of the each family was infected. It was also detected 26.1% of asymptomatic infections. All age groups were affected. Therefore, the infection was more frequent in females (33.5%) than males (23.8%).(ABSTRACT TRUNCATED AT 250 WORDS)Registramos a ocorrencia de epidemia de dengue causada pelo sorotipo 2 (DEN 2) na cidade de Araguaina, estado do Tocantins (TO) situado no Brasil central. Quatrocentos individuos de 74 familias, residentes nos bairros S. Joao, Araguaina Sul e Neblina foram entrevistados e sangrados, independentemente de terem adoecido ou nao. Os soros tanto de adultos quanto de criancas de ambos os sexos foram usados para pesquisa de anticorpos inibidores da hemaglutinacao (IH) e IgM atraves de ensaio imunoenzimatico (MAC ELISA). Nas casas onde haviam doentes no momento do inquerito, sangue total tambem foi colhido para tentativa de isolamento de virus. O quadro clinico apresentado pelos pacientes foi caracterizado por febre, cefaleia, mialgias, artralgias e exantema do tipo maculo-papular nao pruriginoso. A infeccao foi mais frequente em mulheres (33.9%) do que nos homens (23.8%), ocorrendo em todas as faixas etarias, inclusive em criancas com menos de um ano de idade, bem como em maiores de 70 anos. Um total de 1105 mosquitos (56 femeas e 45 machos de Culex quinquefasciatus e 567 femeas e 437 machos de Aedes aegypti) foram obtidos a partir de larvas coletadas em Araguaina. As femeas de Ae. aegypti obtidas das larvas fizeram repasto sanguineo em 8 pacientes febris. O diagnostico laboratorial foi feito por isolamento de virus (cultura de celulas de Aedes albopictus, clone C6/36) e por sorologia (IH e MAC ELISA). Foram isoladas 5 amostras de DEN 2 de pacientes febris e tipadas por imunofluorescencia indireta usando anticorpos monoclonais de dengue. Nenhuma amostra viral foi isolada de mosquitos. Outrossim, comprovou-se infeccao em 111 pessoas sangradas, o que revelou um indice de positividade de 27.75% (111 em 400), sendo que 66.2% das familias estudadas apresentaram pelo menos um individuo positivo. Ocorreram ainda, 26.1% de infeccoes assintomati-cas. Por outro lado, a correlacao de positividade entre os dois testes usados (IH e MAC ELISA) foi de 94.6%. Estimamos que ocorreram aproximadamente 83.250 casos da doenca, entre 15 de marco a 31 de maio de 1991. Esta e a primeira epidemia de DEN 2 em um estado da Amazonia Brasileira, portanto em area endemica de febre amarela, e a primeira evidencia da interiorizacao do DEN 2, ate entao restrito ao Rio de Janeiro.

Aedes albopictus may not be vector of dengue virus in human epidemics in Brazil

Over 60,500 dengue cases were reported in the state of Espírito Santo (ES), Brazil, between 1995 and 1998. The studys purpose was to identify whether Aedes albopictus was transmitting the dengue virus during an epidemic in the locality of Vila Beth nia (Viana County),Vitória, ES. From April 3 to 9, 1998, blood and serum samples were collected daily for virus isolation and serological testing. Four autochthonous cases were confirmed through DEN 1 virus isolation and two autochthonous cases through MAC ELISA testing. Of 37 Ae. aegypti and 200 Ae. albopictus adult mosquitoes collected and inoculated, DEN1 virus was isolated only from a pool of two Ae. aegypti female mosquitoes. The study results suggest that Ae. albopictus still cannot be considered an inter-human vector in dengue epidemics in Brazil.

Primeiro registro de epidemias causadas pelo vírus Oropouche nos Estados do Maranhão e Goiás, Brasil

The authors describe the occurrence of outbreaks caused by Oropouche virus (ORO) in the states of Maranhão and Goiás, Brazil in 1988. 36 strains of the virus were obtained from the intracerebral inoculation of the blood of 120 patients into 2-3 day-old infant mice. The illness was characterized by headache, fever, pain in the muscles, joints and back, photophobia, retrobulbar pain, nausea and dizziness. 128 of 197 people examined in Porto Franco, MA, had hemagglutination-inhibiting antibodies to the agent, while 106 of them had IgM antibodies by MAC ELISA test. All age groups were infected, although the incidence was higher among who had 10 to 19 years old. There was no difference, in relation to sex infections. Recurrence of symptoms was reported in 56% of sick people. Mice inoculated with 3624 Culicoides paraensis (Ceratopogonidae) and 1970 Culex (Cux.) quinquefasciatus (Culicidae) collected in Porto Franco resulted in one single isolation of ORO virus, from the Culicoides. These are the first confirmed cases of ORO infection in Maranhão and Goiás states.The authors describe the occurrence of outbreaks caused by Oropouche virus (ORO) in the states of Maranhao and Goias, Brazil in 1988. 36 strains of the virus were obtained from the intracerebral inoculation of the blood of 120 patients into 2-3 day-old infant mice. The illness was characterized by headache, fever, pain in the muscles, joints and back, photophobia, retrobulbar pain, nausea and dizziness. 128 of 197 people examined in Porto Franco, MA, had hemagglutination-inhibiting antibodies to the agent, while 106 of them had IgM antibodies by MAC ELISA test. All age groups were infected, although the incidence was higher among who had 10 to 19 years old. There was no difference, in relation to sex infections. Recurrence of symptoms was reported in 56% of sick people. Mice inoculated with 3624 Culicoides paraensis (Ceratopogonidae) and 1970 Culex (Cux.) quinquefasciatus (Culicidae) collected in Porto Franco resulted in one single isolation of ORO virus, from the Culicoides. These are the first confirmed cases of ORO infection in Maranhao and Goias states.Os autores descrevem a ocorrencia de epidemias causadas pelo virus Oropouche (ORO) nos Estados do Maranhao (MA) e Goias (GO) em 1988. 36 amostras de virus foram obtidas a partir da inoculacao do sangue de 120 pacientes em camundongos recem nascidos. A doenca foi caracterizada por febre, cefaleia, dores musculares, articulares, fotofobia, dor retro ocular, nauseas e tontura. 128 das 197 pessoas examinadas em Porto Franco, MA, tinham anticorpos inibidores da hemaglutinacao (IH) para o agente e, em 106 foram detectados anticorpos IgM por MAC ELISA. Todos os grupos etarios foram infectados, embora a incidencia tenha sido mais elevada entre aqueles com 10 a 19 anos de idade. Quanto ao sexo, a infeccao ocorreu igualmente em ambos os sexos. Recorrencia dos sintomas foi observada em 56% dos casos positivos estudados. A inoculacao em camundongos Swiss recem nascidos de 3.624 Culicoides paraensis (Ceratopogonidae) e 1.970 Culex (Culex) quinquefasciatus (Culicidae), coletados em Porto Franco-MA, resultou em um unico isolamento do virus ORO a partir dos Culicoides. Essa e a primeira descricao de casos confirmados de infeccao pelo virus Oropouche nos Estados do Maranhao e Goias, Brasil.

Socio-economic and Climate Factors Associated with Dengue Fever Spatial Heterogeneity: A Worked Example in New Caledonia.

Background/Objectives Understanding the factors underlying the spatio-temporal distribution of infectious diseases provides useful information regarding their prevention and control. Dengue fever spatio-temporal patterns result from complex interactions between the virus, the host, and the vector. These interactions can be influenced by environmental conditions. Our objectives were to analyse dengue fever spatial distribution over New Caledonia during epidemic years, to identify some of the main underlying factors, and to predict the spatial evolution of dengue fever under changing climatic conditions, at the 2100 horizon. Methods We used principal component analysis and support vector machines to analyse and model the influence of climate and socio-economic variables on the mean spatial distribution of 24,272 dengue cases reported from 1995 to 2012 in thirty-three communes of New Caledonia. We then modelled and estimated the future evolution of dengue incidence rates using a regional downscaling of future climate projections. Results The spatial distribution of dengue fever cases is highly heterogeneous. The variables most associated with this observed heterogeneity are the mean temperature, the mean number of people per premise, and the mean percentage of unemployed people, a variable highly correlated with peoples way of life. Rainfall does not seem to play an important role in the spatial distribution of dengue cases during epidemics. By the end of the 21st century, if temperature increases by approximately 3°C, mean incidence rates during epidemics could double. Conclusion In New Caledonia, a subtropical insular environment, both temperature and socio-economic conditions are influencing the spatial spread of dengue fever. Extension of this study to other countries worldwide should improve the knowledge about climate influence on dengue burden and about the complex interplay between different factors. This study presents a methodology that can be used as a step by step guide to model dengue spatial heterogeneity in other countries.

Scanning electron microscopy study of the egg of Haemagogus (Haemagogus) capricornii Lutz, 1904 (Diptera: Culicidae).

Abstract Morphological details are provided for the dorsal and ventral surfaces of both extremities and the micropylar area of eggs of Haemagogus (Haemagogus) capricornii Lutz, captured in the Biological Reserve of Tinguá, State of Rio de Janeiro, Brazil. The eggs were observed by scanning electron microscopy with a morphometrical analysis of the main structures. The outer chorionic cells on the ventral surface were extremely regular, such as those observed in Hg. equinus and Hg. janthinomys. The tubercles present differences in form, size, and distribution. Filaments to attach to the substrate were observed in this species.

[Scanning electron microscopy of eggs of Haemagogus leucocelaenus (Diptera: Culicidae)].

OBJECTIVE To observe morphological details of the eggs of Haemagogus (Conopostegus) leucocelaenus, seen for the first time via scanning electron microscopy (SEM), with morphometric analysis of the main structures. METHODS Eggs of Hg. leucocelaenus were obtained from females captured in the Biological Reserve of Tinguá, State of Rio de Janeiro. Some of the eggs were kept for hatching and others underwent processing for scanning electron microscopy studies. Three eggs were submitted to morphometric analysis. The material was fixed in 2.5% glutaraldehyde and postfixed in 1% osmium tetroxide, both in 0.1M, pH 7.2 sodium cacodylate buffer, then dehydrated in ethanol and dried using the critical point method. This was then set up on metallic supports, covered with gold and observed using the Jeol 5310 scanning electron microscope. Measurements were made with the aid of the Semafore analysis software coupled to the electron microscope. RESULTS The eggs presented elliptical outlines of approximately 574 mm in length and 169 mm in width, with an egg index (l/w ratio) of 3.39 mm. The exochorion was extremely regular and had ornamentation that was usually hexagonal but sometimes pentagonal. Tubercles were observed on the chorionic cells, symmetrically arranged in relation to the longitudinal axis. Inside the cells, there were smaller, individualized tubercles, some arranged peripherally and others grouped to a greater or lesser extent in the center. The surface of the chorionic reticulum did not present rugosity. The micropylar apparatus was formed by a prominent continuous collar of 8.32 mm in thickness, with a slightly irregular surface. The micropylar disk was very evident, and was continuous with the collar. The micropyle was seen at the center of this disk, measuring 1.6 mm and with a micropylar apparatus of 27.3 mm in diameter. CONCLUSIONS The ornamentation of the exochorion presents differences in relation to the tubercles of chorionic cells and the external chorionic reticulum between the eggs of Hg. Leucocelaenus, in comparison with the eggs of Hg. janthinomys and Hg. equinus, and also in relation to those of Aedes aegypti, Ae. albopictus and Ae. bahamensis. In various aspects, the eggs of Hg. leucocelaenus have more resemblance to those of Hg. Equinus than those of Hg. janthinomys, with greater differences presented in relation to the eggs of Hg. spegazzinii and Hg. lucifer.