Failure of secondary infection with American genotype dengue 2 to cause dengue haemorrhagic fever

DM Watts, KR Porter, P Putvatana, B Vasquez… - The Lancet, 1999 - thelancet.com
DM Watts, KR Porter, P Putvatana, B Vasquez, C Calampa, CG Hayes, SB Halstead
The Lancet, 1999thelancet.com
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 …
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]gM capture ELISA and an indirect]gG ELISA In addition, serum samples collected annually between 1993 and 1996 from a large cohort of students were tested for dengue]gG 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
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