Abstract
BackgroundLittle is known about the kinetics of anti-H5 neutralizing antibodies in naturally H5N1-infected patients with severe clinical illness or asymptomatic infection.MethodsUsing H5N1 microneutralisation (MN) and H5-pseudotype particle-based microneutralisation assays (H5pp) we analyzed sera sequentially obtained from 11 severely ill patients diagnosed by RT-PCR (follow-up range 1–139 weeks of disease onset) and 31 asymptomatically infected individuals detected in a sero-epidemiological study after exposure to H5N1 virus (follow-up range: 1–2 month –11 months after exposure).ResultsOf 44 sera from 11 patients with H5N1 disease, 70% tested positive by MN (antibody titre ≥80) after 2 weeks and 100% were positive by 3 weeks after disease onset. The geometric mean MN titers in severely ill patients were 540 at 1–2 months and 173 at 10–12 months and thus were higher than the titers from asymptomatic individuals (149 at 1–2 months, 62.2 at 10–12 months). Fractional polynomial regression analysis demonstrated that in all severely ill patients, positive titers persisted beyond 2 years of disease onset, while 10 of 23 sera collected 10–11 months after exposure in asymptomatically infected individuals tested negative.ConclusionsOur results indicate that people with asymptomatic H5N1 infection have lower H5N1 antibody titres compared to those with severe illness and that in many asymptomatically infected patients the antibody titer decreased to levels below the threshold of positivity within one year. These data are essential for the design and interpretation of sero-epidemiological studies.
Highlights
Since 1997, the highly pathogenic avian influenza A (H5N1) virus has spread among poultry and possibly in wild birds in Asia, Middle-East, Europe and Africa and caused over 470 cases of reported human diseases with more than 280 deaths [1]
We analyzed the characteristics of the antibody response in individuals from Vietnam and Cambodia infected by clade 1 H5N1 virus who experienced a spectrum of illness ranging from fatal or severe disease to moderate illness or asymptomatic infection
Serum samples Human sera were collected at the Hospital for Tropical Disease (HTD) Ho Chi Minh City, Vietnam, from patients with severe H5N1 virus infection confirmed by RT-PCR [13,14,15]
Summary
Since 1997, the highly pathogenic avian influenza A (H5N1) virus has spread among poultry and possibly in wild birds in Asia, Middle-East, Europe and Africa and caused over 470 cases of reported human diseases with more than 280 deaths [1]. The presence of the pandemic virus in pigs may provide an increased risk of reassortment between avian H5N1 viruses with the pandemic H1N1 virus This may allow additional opportunities for H5N1 virus adaptation to human-to-human transmission posing potentially new threats to public health. It is important to conduct sero-epidemiological studies to monitor the extent of asymptomatic or clinically mild H5N1 illness among humans. Such studies will help define the risk factors for human infections [4,5,6,7,8,9,10]. Little is known about the kinetics of anti-H5 neutralizing antibodies in naturally H5N1-infected patients with severe clinical illness or asymptomatic infection
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