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Litchi–associated Acute Encephalitis in Children, Northern Vietnam, 2004–2009 - - Emerging Infectious Disease journal - CDC

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Litchi–associated Acute Encephalitis in Children, Northern Vietnam, 2004–2009 - - Emerging Infectious Disease journal - CDC

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Volume 18, Number 11–November 2012


Litchi–associated Acute Encephalitis in Children, Northern Vietnam, 2004–2009

Juliette Paireau, Nguyen Hai Tuan, Rémi Lefrançois, Matthew R. Buckwalter, Ngu Duy Nghia, Nguyen Tran Hien, Olivier Lortholary, Sylvain Poirée, Jean-Claude Manuguerra, Antoine Gessain, Matthew L. Albert, Paul T. Brey, Phan Thi Nga, and Arnaud FontanetComments to Author 
Author affiliations: Institut Pasteur, Paris, France (J. Paireau, R. Lefrançois, M.R. Buckwalter, J.-C. Manuguerra, A. Gessain, M.L. Albert, A. Fontanet); National Institute of Hygiene and Epidemiology, Hanoi, Vietnam (N.H. Tuan, N.D. Nghia, P.T. Nga, N.T. Hien); Université Paris X-Nanterre, Paris (R. Lefrançois); INSERM U818, Paris (M.R. Buckwalter, M.L. Albert); Hôpital Necker-Enfants Malades, Paris (O. Lortholary, S. Poirée); Université Paris Descartes, Paris (O. Lortholary, M.L. Albert); CNRS URA 1930, Paris (A. Gessain); Institut Pasteur, Vientiane, Lao People’s Democratic Republic (P.T. Brey); and Conservatoire National des Arts et Métiers, Paris (A. Fontanet)
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Since the end of the 1990s, unexplained outbreaks of acute encephalitis in children coinciding with litchi harvesting (May–July) have been documented in the Bac Giang Province in northern Vietnam. A retrospective ecologic analysis of data for 2004–2009 involving environmental, agronomic, and climatic factors was conducted to investigate the suspected association between the outbreaks and litchi harvesting. The clinical, biological, and immunologic characteristics of the patients suggested a viral etiology. The ecologic study revealed an independent association between litchi plantation surface proportion and acute encephalitis incidence: Incidence rate ratios were 1.52 (95% CI 0.90–2.57), 2.94 (95% CI 1.88–4.60), and 2.76 (95% CI 1.76–4.32) for second, third, and fourth quartiles, respectively, compared with the lowest quartile. This ecologic study confirmed the suspected association between incidence of acute encephalitis and litchi plantations and should be followed by other studies to identify the causative agent for this syndrome.
Acute encephalitis syndrome (AES) is a major public health problem in Asia. The main etiologic agent is the Japanese encephalitis virus (JEV), a positive-sense single-stranded flavivirus transmitted by Culex spp. mosquitoes. It is responsible for ≈50,000 encephalitis cases every year in the region (1). Recently, the Nipah and Chandipura viruses were identified as responsible for acute encephalitis outbreaks in Malaysia and India (2,3). In addition, many other viral encephalitis cases of unknown etiology exist throughout Asia (4).
In Vietnam, according to the National Institute of Hygiene and Epidemiology (NIHE), the annual incidence rate for AES in the general population was 2.24–2.90 cases per 100 000 inhabitants during 1998–2005. This rate corresponds with 1,800–2,300 cases per year, two thirds of which occurred in northern Vietnam. Since the inclusion in 1997 of the JEV vaccine into the Extended Program on Immunization by the World Health Organization (WHO), the relative proportion of non-JE cases has increased substantially among patients hospitalized with AES in Vietnam, from ≈40% in 1996 to ≈90% in 2009 (P.T. Nga, unpub. data).
In northern Vietnam, unexplained outbreaks of non-JE acute encephalitis have been documented since 1999. These outbreaks are unusual because of their specific location (Bac Giang Province), their strict seasonality (92% of unexplained AES occur during May–July), the restricted age group of persons at risk (88% are <15 years old), and the clinical features (abrupt febrile onset, rapid progression to coma, and higher case-fatality rate than for JE). Approximately 50–100 children are referred to the provincial hospital each epidemic season, but the actual number of cases could be underreported because some patients might have died at home.
The local population and public health practitioners have anecdotally attributed the emergence of AES to the recent intensification of litchi production in the province: production rose from 870 tons during 1985–1989 to 400,000 tons during 2000–2005. Bac Giang Province has the highest litchi production in Vietnam, three fourths of which is consumed domestically and the rest is exported mainly to People’s Republic of China (5,6). Vietnamese litchis are mostly of the Thieu variety, which has a short harvest period of ≈1 month during May–July (7), which coincides with the epidemic season of the outbreaks in Bac Giang.
Because of the distinct early clinical manifestations (8), the syndrome has been locally termed Ac Mong encephalitis (AME), after the Vietnamese word for nightmare. The typical clinical illness starts with headache and fever, followed by seizures (often during the night); approximately one third of cases progress to coma and death.
The causative agent of AME has remained unidentified and may be responsible for unexplained acute encephalitis elsewhere in the world, particularly in regions sharing similar ecology and environment. Litchi is widely distributed throughout subtropical and tropical regions. The 5 leading litchi-producing countries are China, India, Taiwan, Thailand, and Vietnam (9).
Our first objective was to describe the epidemiologic and clinical features of this severe encephalitis among children in northern Vietnam. Our second objective was to strengthen or weaken the hypothesis that litchi cultivation is associated with acute outbreaks of AES in Bac Giang Province. We investigated this suspected association using a retrospective ecologic analysis for 2004–2009 in Bac Giang Province that involved various environmental, agronomic, and climatic factors. Confirmation of this association would pave the way for further hypothesis-testing studies investigating the causal mechanisms behind this ecologic correlation.

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