Analytical models approximating individual processes: a validation method.

Upscaling population models from fine to coarse resolutions, in space, time and/or level of description, allows the derivation of fast and tractable models based on a thorough knowledge of individual processes. The validity of such approximations is generally tested only on a limited range of parameter sets. A more general validation test, over a range of parameters, is proposed; this would estimate the error induced by the approximation, using the original model's stochastic variability as a reference. This method is illustrated by three examples taken from the field of epidemics transmitted by vectors that bite in a temporally cyclical pattern, that illustrate the use of the method: to estimate if an approximation over- or under-fits the original model; to invalidate an approximation; to rank possible approximations for their qualities. As a result, the application of the validation method to this field emphasizes the need to account for the vectors' biology in epidemic prediction models and to validate these against finer scale models.

Larvicidal activity of some Cerrado plant extracts against Aedes aegypti.

One hundred ninety hexanic and ethanolic extract from 27 plant species from the Cerrado biome of Brazil were tested for larvicidal activity against 3rd-stage Aedes aegypti larvae at 500 microg/ml. Fourteen extracts from 7 species showed activity (>65% mortality) against the larvae. Of these Dugeutia 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 microg/ml, respectively. Annona crassiflora and Cybistax antisyphilitica showed activity at 23.06 and 27.61 microg/ml. The larvicidal properties of these species are described for the first time, and may prove to be promising in active chemical compound isolation.

[First autochthonous cases, caused by the Dengue-3 serotype in Federal District, Brazil]. / Apparition des premiers cas autochtones causes par le sérotype Dengue-3 dans le District fédéral, Brésil.

During the first four months of 2003, the survey laboratory of the Federal District (LACEN Laboratory of Virology), Brasília, Brazil, isolated ten strains of dengue virus serotype 3, five of them autochthonous, and the remaining ones from cases imported from Tocantins, Goias and Bahia States. The virus isolations were performed in C6/36 cell culture inoculated with total blood collected between the 1st and the 5th days after the onset of the symptoms. The age of the patients varied from 26 to 59 years old. The strains were typed as DEN-3 by indirect immunofluorescence assay using serotype-specific monoclonal antibodies. Viral RNAs were extracted from total blood using the trizol method. The nested RT-PCR method detected DNA products of 290 bp, confirming the serotype identifications. The introduction of DEN-3 in Brazil and especially in the Federal District represents a serious threat, since most people are susceptible to this serotype and many have already been infected by serotypes DEN-1 or DEN-2, thus increasing the risk of epidemic of more severe forms of the disease. The use of a fast and reliable method for continuous monitoring of the circulation of this serotype is of primary importance for the prevention and control of future epidemics.

Early determination of the reproductive number for vector-borne diseases: the case of dengue in Brazil.

OBJECTIVE: To evaluate a new method of deriving the reproductive number for vector-borne diseases from the early epidemic curves for vector-borne diseases with incubations in the vectors and in the hosts. METHOD: We applied the model to several dengue epidemics in different climatic regions of Brazil: Brasilia, Belém, Fortaleza, Boa Vista. RESULTS: The new method leads to higher estimates of the reproductive number than previous models. CONCLUSION: At present, Aedes aegypti densities, the meeting of more compatible strains of viruses and mosquitoes, may lead to re-emergence of urban yellow fever epidemics.

Trocara virus: a newly recognized Alphavirus (Togaviridae) isolated from mosquitoes in the Amazon Basin.

This report describes Trocara virus, a newly recognized member of the genus Alphavirus, that has been isolated from Aedes serratus mosquitoes collected at two widely separated sites in the Amazon Basin. Biological, antigenic and genetic characteristics of the new virus are given. Results of these studies indicate that Trocara virus is the first member of a newly discovered antigenic complex within the family Togaviridae genus Alphavirus. The public health and veterinary importance of Trocara virus is still unknown.

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.

First isolation of dengue 1 virus from Aedes aegypti in Federal District, Brazil.

Dengue is present in the Federal District since 1991 and virological studies of the vector began in 1998. Two strains of DEN1 were isolated from 9 pools of female Aedes aegypti (78 mosq.), collected in April in Gama county, where the Breteau index was 5.4, and 32 autochtonous human cases were notified.

People's knowledge and practice about dengue, its vectors, and control means in Brasilia (DF), Brazil: its relevance with entomological factors.

In South America, the epidemiology and ecology of dengue fever are strongly associated with human habits because the vector Aedes aegypti is strictly urban. Thus, the evaluation of people's knowledge and practice (PKP) is of great importance to improve integrated control measures. A PKP evaluation has been done in a suburb of Brasilia. Thirty questions were submitted to 130 habitants about income level, education, sources of information, specific knowledge about dengue, vector biology, and control measures applied. Other questions were about the responsibility of dengue control and the opportunity of applying a fine to people who would not cooperate with the control measures. Level of PKP was fairly high, either for housekeepers, workers, or students. The mosquito bite was cited as source of infection by 60.8% of interviewed people but 22.3% had no knowledge about this topic. The most cited symptoms in association with dengue were fever (73.1%), headache (66.2%), and rash (35.4%). Knowledge about mosquito biology and control was also fairly accurate, as demonstrated by 96.9% of answers. Elimination of water containers was the most efficient means according to 73% of people. Such action should be done mainly by the citizen (75.3% of answers). Despite the good PKP, correlations existed only between the PKP about vector biology and presence of potential breeding containers in March, and between the PKP about the disease and potential breeding containers in April. In conclusion, global educational campaigns may have a real impact on the PKP but this did not result in effective control of the mosquito breeding containers by the people.

Release-recapture experiments with canopy mosquitoes in the genera Haemagogus and Sabethes (Diptera: Culicidae) in Brazilian Amazonia.

In 2 forested areas near Belém (Para State, Brazil), 2 Haemagogus and 6 Sabethes species were marked released and recaptured in May 1989 and in April 1993. The recapture rates were high, 4.9 and 13.1% for Haemagogus and Sabethes spp., respectively. For Haemagogus janthinomys Dyar, females were recaptured until 27 d after release. The duration of the gonotrophic cycle was between 5.0 and 9.5 d and the survival rate was 0.90-0.92. Haemagogus leucocelaenus (Dyar & Shannon) was recaptured once, 21 d after release. Twelve Sabethes chloropterus (Von Humboldt) were recaptured, with a peak at 15-18 d; 1 female was recaptured at 44 d, indicating extended survival. Seven Sabethes amazonicus Gordon & Evans and 7 Sabethes cyaneus (F.) were recaptured, mostly at 14-39 d. These results indicate that Haemagogus and Sabethes spp. have a gonotrophic cycle in nature longer than inferred from laboratory studies, and that cycle length varies seasonally. The capacity of these species to sustain epizootics or epidemics of arboviruses may depend on local weather, with risk greatest at the end of the rainy season.

An epidemic of sylvatic yellow fever in the southeast region of Maranhao State, Brazil, 1993-1994: epidemiologic and entomologic findings.

Yellow fever virus transmission was very active in Maranhao State in Brazil in 1993 and 1994. An investigation was carried out to evaluate the magnitude of the epidemic. In 1993, a total of 932 people was examined for yellow fever from Maranhao: 70 were positive serologically, histopathologically, and/or by virus isolation, and another four cases were diagnosed clinically and epidemiologically. In Mirador (17,565 inhabitants), the incidence was 3.5 per 1,000 people (case fatality rate [number of deaths/number of cases diagnosed] = 16.4%), while in a rural yellow fever risk area (14,659 inhabitants), the incidence was 4.2 and the case-fatality rate was 16.1% (10 of 62). A total of 45.2% (28 of 62) asymptomatic infections were registered. In 1994, 49 serum samples were obtained and 16 cases were confirmed (two by virus isolation, two by seroconversion, and 12 by serology). No fatal cases were reported. In 1993, 936 potential yellow fever vectors were captured in Mirador and a single strain was isolated from a pool of Haemagogus janthinomys (infection rate = 0.16%). In 1994, 16 strains were isolated from 1,318 Hg. janthinomys (infection rate = 1.34%) and one Sabethes chloropterus (infection rate = 1.67%). Our results suggest that this was the most extensive outbreak of yellow fever in the last 20 years in Brazil. It is also clear that the lack of vaccination was the principal reason for the epidemic, which occurred between April and June, during the rainy season, a period in which the mosquito population in the forest increases.

[Dengue and its vectors in Brazil]. / La dengue et ses vecteurs au Brésil.

History of dengue in Brazil is covered from the first citations in the XIXth century to the great outbreaks of the last ten years. DEN-1 and DEN-4 viruses have been isolated for the first time in 1982 during an epidemic in Boa Vista, Roraima State. In 1986-1987, epidemics of dengue type 1 covered an extended area from Rio de Janeiro/Sào Paulo States to the North East States of Brazil. During 1990-1991, dengue type 2 epidemics have been notified in the South East (Rio de Janeiro/São Paulo) and in some States of the interior of the country (Mato Grosso do Sul, Tocantins). DEN-1 virus was also circulating the same year in São Paulo and Minas Gerais States. Recently (1994), an important outbreak has been studied in Ceará State, where DEN-2 and DEN-1 viruses have been isolated. In Rio de Janeiro and Ceara (1990 and 1994, respectively), it is probably the succession of infections by DEN-1 and DEN-2 viruses which has caused many DHF/DSS cases. The urban vector has always been the mosquito Aedes aegypti, from which 4, 7 and 16 strains of DEN-4, DEN-1 and DEN-2 have been isolated, respectively. In Brazil, transovarial transmission of dengue viruses by this species has not yet been shown to occur in nature.

[Outbreak of classical fever of dengue caused by serotype 2 in Araguaiana, Tocantins, Brazil]. / Epidemia de febre clássica de dengue causada pelo sorotipo 2 em Araguaina, Tocantins, Brasil.

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)

[Characterization and antigenic relationship of 3 new Bunyaviruses in the group Anopheles A (Bunyaviridae) of arboviruses]. / Caracterização e relacionamento antigênico de três novos Bunyavirus no grupo Anopheles A (Bunyaviridae) dos arbovirus.

The isolation and characterization of three new viruses obtained from the Tucuruí hydroelectric dam region is reported. These three agents belong to the Anopheles A serogroup, genus Bunyavirus, Bunyaviridae. The Tucuruí (TUC), caraipé (CPE) and Arumateua (ART) viruses have close relationships with each other and with Trombetas (TBT) virus, an Anopheles A virus previously isolated in the Amazon Region of Brazil. These viruses form the "Trombetas complex". TUC, CPE and ART viruses were obtained from pools of Anopheles (Nyssorhynchus) sp captured in Tucuruí, Pará State, in February, August and October of 1984, respectively. Until 1990 TUC, CPE and ART were isolated 12, 32 and 28 times respectively, in the Tucuruí hydroelectric dam region. At the moment, these viruses have only been obtained from mosquitoes of the Anopheles (Nyssorhynchus) complex, especially from An. (Nys.) nuneztovari and An. (Nys.) triannulatus, that are considered to be secondary vectors of Plasmodium in Amazonia. Serological tests performed with human and wild animal sera were negative, except for one specimen Nasua nasua that had neutralization antibodies to TUC.

[Epidemiology of encephalitis caused by arbovirus in the Brazilian Amazonia]. / Epidemiologia das encefalities por arbovírus na Amazônia brasileira.

An overview of ecological, epidemiological and clinical findings of potential arthropod-borne encephalitis viruses circulating in the Amazon Region of Brazil are discussed. These viruses are the Eastern Equine Encephalitis (EEE), Western Equine Encephalitis (WEE), St. Louis Encephalitis (SLE), Mucambo (MUC) and Pixuna (PIX). These last two are subtypes (III and IV) of Venezuelan Equine Encephalitis virus. The areas of study were the highways and projects of development, as well as places where outbreaks of human diseases caused by arboviruses had been detected. These viruses are widespread in all Amazonia, and at least four of them, EEE, WEE, SLE and MUC are pathogenic to man. EEE and WEE infections were detected by serology, while SLE and MUC by either serology and virus isolation. The PIX virus has the lowest prevalence and, it was isolated in only a few cases, one being from a laboratory infection. Wild birds are the main hosts for all these viruses, except MUC, whose major hosts are rodents. The symptoms presented by infected people were generally a mild febrile illness. Although, jaundice was observed in two individuals from whom SLE was isolated. A comparison of the clinical symptoms presented by the patients in the Amazon Region and other areas of America, especially in the USA is made. In Brazilian Amazon region epidemics have not been detected although, at least, one EEE epizootic was recorded in Bragança, Para State, in 1960. At that time, of 500 horses that were examined 61% were positive to EEE by HI and of them 8.2% died. On the other hand, SLE has caused four epizootics in a forest near Belem. Wild birds and sentinel monkeys were infected, but no human cases were reported.

[Estimation of the survival rate, the relative density and the infection rate of a population of Haemagogus janthinomys Dyar (Diptera, Culicidae) from which strains of yellow fever were isolated in Brazilian Amazon]. / Estimation du taux de survie, de la densité relative et du taux d'infection d'une population d'Haemagogus janthinomys Dyar (Diptera, Culicidae) ayant fourni des souches de fièvre jaune en Amazonie Brésilienne.

The conditions of maintenance of YF virus in brazilian Amazonia are not yet elucidated. Generally, the presence of the virus is attested by human cases of sylvatic origin. During a survey done at the exact place where a man have probably been contaminated, it was possible for the first time in South America, to estimate the mean parity rate of a population of the potential vector Haemagogus janthinomys, from which the YF virus was actually isolated. The survival rate (Ts = 0.96), the biting rate (0.60 mosquitoes/man x hour), and the infection rate (1.71%) were also determinated for the same mosquitoes and have values compatible with the probable conditions of the human contamination. However, more data are needed, in particular in relation with other possible human contaminations and/or circulation of the YF virus in the monkey population (extension and duration of the epizootic episode), in order to know what maintenance cycle is prevalent in this region: a low level transmission, with the mosquito being a "vector-reservoir", or a "constantly moving epizootic wave".

[1st register of an epidemic caused by Oropouche virus in the states of Maranhão and Goiás, 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.

[Aedes aegypti (L.): importance of its bioecology in the transmission of dengue and other arboviruses. I]. / Aedes aegypti (L.): importance de sa bioécologie dans la transmission de la dengue et des autres arbovirus. Première partie.

The bioecological parameters which are of special importance in the epidemiology of Dengue, Yellow Fever, and other arboviruses are discussed. Three levels are retained: the nature of Aedes aegypti-man contacts, the susceptibility of the mosquito to the pathogen and multiplication of the latter, and the transmission. The trophic preferences, the density variations, the daily survival rate, the egg diapause, and man influences are the main vector-dependent ecological factors. Temperature and genetical nature of viral and mosquito strains are particularly important in susceptibility and multiplication studies. Efficacy of the oral transmission is also temperature-dependent and mainly genetically determined. The true natural role of transovarial transmission is not yet well understood. Thus, the breaking up and/or prevention of epidemics would be possible only with a thorough knowledge of the relation between the above biological factors and the epidemiological situation. A list is provided of the naturally or experimentally Aedes aegypti transmitted arboviruses (103), protozoans (5) and filaria (20).

[Ecology of tick-borne arboviruses in the Central African Republic]. / Ecologie des arbovirus à tiques en République Centrafricaine.

Ticks have been collected on cattle skins for seven consecutive years in Bangui, Berberati, Bangassou and Bouar. 150 strains of arboviruses have been isolated from the four following species: Amblyomma variegatum: Dugbe, Jos, Thogoto, Crimean-Congo Hemorragic Fever (CCHF), Yellow Fever, Bhanja and Pétévo; Boophilus annulatus: Dugbe, Jos and Thogoto; B. decoloratus: Dugbe, Jos, Thogoto and CCHF; Hyalomma nitidum: CCHF. Dugbe (112 isolated strains), Jos (19 isolates) and Thogoto (11 isolates) viruses represent more than 95% of all the strains. Dugbe virus was isolated mostly during the first half of the rainy season. Jos virus shows a maximum rate of infection during the dry season (february) and a second peak in october (2nd half of the rainy season). Most of the strains of Thogoto virus have been isolated during the dry season. These seasonal variations of infection rates follow the seasonal variation of vector population densities. Thus preimagines and imagines of A. variegatum, the main vector of the Dugbe virus in C. A. R. show peaks of abundance respectively during the dry season and during the first half of the rainy season. Adults of Boophilus show maximum densities from december to february (dry season) when the greater number of Jos and Thogoto viruses are isolated. CCHF virus ecology needs more studies in Central African Republic. The importance of ticks in the wild cycle of Yellow Fever virus is not yet understood. Bhanja virus has been isolated only one time in C. A. R. Pétévo is a lately described virus which belongs to a group thus far unknown in Africa (Palyam gr.).