RESUMO
In 1994-1996, 185 strains of dengue (DEN) virus types 1, 2, and 4 were recovered from febrile United States and other United Nations military personnel in Haiti. We wondered whether risk factors for dengue hemorrhagic fever (DHF) existed and, if so, were DHF cases occurring among Haitian children. Dengue transmission rates were studied in 210 school children (6-13 years old) resident in Carrefour Borough, Port-au-Prince, Haiti. When sera were tested for plaque-reduction neutralizing antibodies to DEN 1-4 viruses, nearly 85% had antibodies to two or more DEN serotypes. The annual transmission rate was estimated at 30%, a rate observed in countries endemic for DHE Haitian DEN 2 isolates were genotype I, which are repeatedly associated with DHF cases in Southeast Asia and American regions. Despite positive virologic pre-conditions, DHF cases were not recorded by experienced Port-au-Prince pediatricians. These observations, which are reminiscent of those in Africa, provide further evidence of a dengue resistance gene in black populations.
Assuntos
Vírus da Dengue/classificação , Dengue Grave/transmissão , Adolescente , Anticorpos Antivirais/sangue , Criança , DNA Viral/química , DNA Viral/genética , DNA Viral/isolamento & purificação , Vírus da Dengue/genética , Vírus da Dengue/isolamento & purificação , Doenças Endêmicas , Imunofluorescência , Haiti/epidemiologia , Humanos , Militares , Testes de Neutralização , Filogenia , Análise de Sequência de DNA , Estudos Soroepidemiológicos , Dengue Grave/epidemiologia , Dengue Grave/imunologia , Nações Unidas , Estados UnidosRESUMO
A small, isolated outbreak of dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) due to dengue virus type 2 (DEN-2) was documented in Santiago de Cuba on the island of Cuba beginning in January 1997. There were 205 DHF/DSS cases, all in persons older than age 15 years. All but three had evidence of a prior dengue infection, with the only known opportunity being the islandwide dengue virus type 1 (DEN-1) epidemic of 1977-1979. Virtually complete clinical and laboratory surveillance of overt disease was achieved. From December 1997 to January 1998, a random, age-stratified serum sample was obtained from 1,151 persons in 40 residential clusters in Santiago. Sera were tested for DEN-1 and DEN-2 neutralizing antibodies. The prevalence of DEN-2 antibodies in children age 15 years and under, born after the 1981 DEN-2 epidemic, was taken as the 1997 DEN-2 infection rate. This was adjusted slightly to accommodate observed cases, resulting in an estimated infection rate of 4.3%. Dengue fever and DHF/DSS attack rates were calculated from estimated total primary and secondary DEN-2 infections. Only 3% of 13,116 primary infections were overt. The DHF/DSS attack rate for adults of all ages was 420 per 10,000 secondary DEN-2 infections.
Assuntos
Anticorpos Antivirais/isolamento & purificação , Vírus da Dengue/isolamento & purificação , Surtos de Doenças , Vigilância da População , Dengue Grave/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Cuba/epidemiologia , Vírus da Dengue/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estações do Ano , Estudos Soroepidemiológicos , Dengue Grave/imunologia , Dengue Grave/mortalidadeRESUMO
During the Cuban dengue epidemics of 1981 and 1997, significant monthly increases were observed in the proportion of total cases that presented as dengue haemorrhagic fever or dengue shock syndrome (DHF/DSS), and in case-fatality rates for both dengue fever and DHF/DSS. We believe that theses increases can be explained by the hypothesis that some of the population of antibodies against dengue 1 virus raised after natural primary infections react with "neutralisation" determinants found on dengue 2 viruses. These heterotypic antibodies do not prevent secondary dengue 2 infections, but serve to down-regulate the disease to mild illness or symptomless infections. A population of dengue 2 viruses that replicates in dengue-1-immune hosts escape heterotypic neutralisation. When inoculated into a new dengue-1-immune host, these viruses are free to interact with the more abundant infection-enhancing antibodies to produce severe disease.
Assuntos
Vírus da Dengue/genética , Surtos de Doenças , Dengue Grave/epidemiologia , Anticorpos Antivirais/imunologia , Cuba/epidemiologia , Vírus da Dengue/imunologia , Regulação para Baixo , Humanos , Mutação , Dengue Grave/classificação , Dengue Grave/mortalidade , Dengue Grave/virologia , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Population-based epidemiological studies have shown that infection with dengue type 2 (DEN-2) virus in individuals previously infected with a different serotype of the virus is a major risk factor for dengue haemorrhagic fever and dengue shock syndrome. However, the western hemisphere was spared epidemics of these two syndromes, until the introduction of a southeast Asian DEN-2 genotype. Possibly American DEN-2 genotype strains lacked properties necessary to cause severe disease. We report on a major epidemic of DEN-2 in Peru in 1995, about 5 years after an epidemic of DEN-1 in the same population. METHODS: In Iquitos, a city of 344,686 inhabitants in Peru, cases of dengue fever were studied prospectively from 1990. Acute phase of illness serum samples from patients were tested for virus in C6/36 cells, and virus isolates were identified by immunofluorescence. Isolates of dengue 2 virus obtained from patients during an outbreak of mild febrile illness in 1995 were sequenced to determine the genotype. Serological analysis of paired samples from the patients was done with an IgM capture ELISA and an indirect IgG ELISA. In addition, serum samples collected annually between 1993 and 1996 from a large cohort of students were tested for dengue IgG antibody by an ELISA. Serum samples from a random sample of 129 students from this cohort were tested for dengue neutralising antibodies to quantify the serotype specific infection rates. FINDINGS: Among the 129 students (aged 7-20 years in 1993) who had serum samples available before and after the epidemic, 78 (60.5%) had a secondary DEN-2 virus infection. By extrapolation, 49,266 of the 81,479 children (aged 5-14 years) in Iquitos would have experienced such infections. From previous studies, between 887 and 10,247 cases of dengue haemorrhagic fever and dengue shock syndrome would have been expected. No cases were found. DEN-2 isolates were of the American genotype. INTERPRETATION: This prospective study shows that secondary infection by the American DEN-2 genotype did not cause dengue haemorrhagic fever and dengue shock syndrome.
Assuntos
Vírus da Dengue/patogenicidade , Dengue/virologia , Surtos de Doenças , Dengue Grave/virologia , Superinfecção , Adolescente , Adulto , Criança , Dengue/epidemiologia , Vírus da Dengue/classificação , Feminino , Genótipo , Humanos , Masculino , Peru/epidemiologia , Dengue Grave/epidemiologiaRESUMO
Overcoming stagnation in rabies prevention programs in the developing world requires national strategies that include plans to adopt existing facilities for production of low-cost efficacious tissue culture-based vaccine. Transfer of tissue culture technology for the production of rabies vaccine has been supported by the World Health Organization and The Rockefeller Foundation, and in the fall of 1986 the location of the optimal site for the initial technology transfer program was agreed upon. Funds were provided to assemble training staff and to purchase the supplies and equipment to furnish a production facility at the Veterinary Products Company of Colombia (VECOL) located in Bogota, Colombia.
Assuntos
Países em Desenvolvimento , Vacina Antirrábica , Raiva/prevenção & controle , Avaliação da Tecnologia Biomédica/economia , Animais , Colômbia , Humanos , Vacinas de Produtos Inativados , Células Vero , Organização Mundial da SaúdeRESUMO
Dengue viruses occur as four antigenically related but distinct serotypes transmitted to humans by Aedes aegypti mosquitoes. These viruses generally cause a benign syndrome, dengue fever, in the American and African tropics, and a severe syndrome, dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), in Southeast Asian children. This severe syndrome, which recently has also been identified in children infected with the virus in Puerto Rico, is characterized by increased vascular permeability and abnormal hemostasis. It occurs in infants less than 1 year of age born to dengue-immune mothers and in children 1 year and older who are immune to one serotype of dengue virus and are experiencing infection with a second serotype. Dengue viruses replicate in cells of mononuclear phagocyte lineage, and subneutralizing concentrations of dengue antibody enhance dengue virus infection in these cells. This antibody-dependent enhancement of infection regulates dengue disease in human beings, although disease severity may also be controlled genetically, possibly by permitting and restricting the growth of virus in monocytes. Monoclonal antibodies show heterogeneous distribution of antigenic epitopes on dengue viruses. These epitopes serve to regulate disease: when antibodies to shared antigens partially neutralize heterotypic virus, infection and disease are dampened; enhancing antibodies alone result in heightened disease response. Further knowledge of the structure of dengue genomes should permit rapid advances in understanding the pathogenetic mechanisms of dengue.
Assuntos
Vírus da Dengue , Dengue/etiologia , Adolescente , Anticorpos Antivirais/fisiologia , Antígenos Virais/imunologia , Sudeste Asiático , Criança , Pré-Escolar , Cuba , Dengue/epidemiologia , Dengue/etnologia , Dengue/imunologia , Dengue/microbiologia , Dengue/prevenção & controle , Vírus da Dengue/classificação , Vírus da Dengue/genética , Vírus da Dengue/imunologia , Vírus da Dengue/fisiologia , Feminino , Humanos , Lactente , Masculino , Porto Rico , SorotipagemRESUMO
Since World War II, dengue viruses have progressively extended their geographic domain and have increased as causes of human morbidity and mortality. This complex of four flaviviruses is principally transmitted to humans by the bite of Aedes aegypti, the yellow fever vector. Factors that promote the indoor storage of water are congenial to the breeding of A. aegypti. These include the dislocations of wars, overpopulation , and urbanization. By the mid-20th century, A. aegypti eradication campaigns had nearly succeeded in much of the Western Hemisphere. Since then, there has been a steady degradation in ability to cope with this species despite the fact that a newly emerged, severe immunopathologic disorder, dengue hemorrhagic fever/dengue shock syndrome, endows dengue epidemics with grave consequences. Development of a vaccine against dengue is complicated by the need to develop four different live attenuated vaccines and by a justifiable caution imposed by dengue immunopathology. A wide range of proven methods have been and are available to reduce populations of A. aegypti. This paper argues that the eradication strategy adopted earlier in this century is still viable and cost effective. Critical to a successful control program is a prioritied approach, a thorough, disciplined planning effort, a commitment to assessment, adequate compensation of staff, and, above all, the will to succeed.