Seroprotection against tetanus in southern Vietnam.

BACKGROUND: Ongoing tetanus cases and sporadic outbreaks of vaccine-preventable diseases associated with routine vaccination programmes remain problems in many low and middle-income countries, including Vietnam. With no human-to-human transmission or natural immunity, tetanus antibody levels indicate both individual risk of tetanus and gaps in vaccination programmes. METHODS: To investigate gaps in immunity to tetanus in Vietnam, a country with a historically high level of tetanus vaccination coverage, tetanus antibodies were measure by ELISA from samples selected from a long-term serum bank, established for the purposes of general-population seroepidemiological investigations in southern Vietnam. Samples were selected from 10 provinces, focussing on age-groups targeted by national vaccination programmes for infants and pregnant women (Expanded Programme on Immunization, EPI, and Maternal and Neonatal Tetanus, MNT). RESULTS: Antibodies were measured from a total of 3864 samples. Highest tetanus antibody concentrations occurred in children under 4 years old, over 90 % of whom had protective levels. Approximately 70 % of children aged 7-12 years had protective antibody concentrations although there was variation among provinces. For infants and children, there were no significant differences in tetanus protection between males and females, but for adults aged 20-35 years, in five of the ten provinces surveyed, protection against tetanus was higher in females (p < 0.05) who are eligible for booster doses under the MNT programme. In seven of ten provinces, antibody concentrations were inversely related to age (p < 0.01) and protection of older individuals was generally low. CONCLUSION: Widespread immunity to tetanus toxoid is seen in infants and young children consistent with the high coverage rates reported for diptheria tetanus toxoid and pertussis (DTP) in Vietnam. However, the lower antibody concentrations seen in older children and men suggest reduced immunity to tetanus in populations not targeted by EPI and MNT programmes.

Age-seroprevalence curves for the multi-strain structure of influenza A virus.

The relationship between age and seroprevalence can be used to estimate the annual attack rate of an infectious disease. For pathogens with multiple serologically distinct strains, there is a need to describe composite exposure to an antigenically variable group of pathogens. In this study, we assay 24,402 general-population serum samples, collected in Vietnam between 2009 to 2015, for antibodies to eleven human influenza A strains. We report that a principal components decomposition of antibody titer data gives the first principal component as an appropriate surrogate for seroprevalence; this results in annual attack rate estimates of 25.6% (95% CI: 24.1% - 27.1%) for subtype H3 and 16.0% (95% CI: 14.7% - 17.3%) for subtype H1. The remaining principal components separate the strains by serological similarity and associate birth cohorts with their particular influenza histories. Our work shows that dimensionality reduction can be used on human antibody profiles to construct an age-seroprevalence relationship for antigenically variable pathogens.

Nonannual seasonality of influenza-like illness in a tropical urban setting.

BACKGROUND: In temperate and subtropical climates, respiratory diseases exhibit seasonal peaks in winter. In the tropics, with no winter, peak timings are irregular. METHODS: To obtain a detailed picture of influenza-like illness (ILI) patterns in the tropics, we established an mHealth study in community clinics in Ho Chi Minh City (HCMC). During 2009-2015, clinics reported daily case numbers via SMS, with a subset performing molecular diagnostics for influenza virus. This real-time epidemiology network absorbs 6000 ILI reports annually, one or two orders of magnitude more than typical surveillance systems. A real-time online ILI indicator was developed to inform clinicians of the daily ILI activity in HCMC. RESULTS: From August 2009 to December 2015, 63 clinics were enrolled and 36 920 SMS reports were received, covering approximately 1.7M outpatient visits. Approximately 10.6% of outpatients met the ILI case definition. ILI activity in HCMC exhibited strong nonannual dynamics with a dominant periodicity of 206 days. This was confirmed by time series decomposition, stepwise regression, and a forecasting exercise showing that median forecasting errors are 30%-40% lower when using a 206-day cycle. In ILI patients from whom nasopharyngeal swabs were taken, 31.2% were positive for influenza. There was no correlation between the ILI time series and the time series of influenza, influenza A, or influenza B (all P > 0.15). CONCLUSION: This suggests, for the first time, that a nonannual cycle may be an essential driver of respiratory disease dynamics in the tropics. An immunological interference hypothesis is discussed as a potential underlying mechanism.

Structure of general-population antibody titer distributions to influenza A virus.

Seroepidemiological studies aim to understand population-level exposure and immunity to infectious diseases. Their results are normally presented as binary outcomes describing the presence or absence of pathogen-specific antibody, despite the fact that many assays measure continuous quantities. A population's natural distribution of antibody titers to an endemic infectious disease may include information on multiple serological states - naiveté, recent infection, non-recent infection, childhood infection - depending on the disease in question and the acquisition and waning patterns of immunity. In this study, we investigate 20,152 general-population serum samples from southern Vietnam collected between 2009 and 2013 from which we report antibody titers to the influenza virus HA1 protein using a continuous titer measurement from a protein microarray assay. We describe the distributions of antibody titers to subtypes 2009 H1N1 and H3N2. Using a model selection approach to fit mixture distributions, we show that 2009 H1N1 antibody titers fall into four titer subgroups and that H3N2 titers fall into three subgroups. For H1N1, our interpretation is that the two highest-titer subgroups correspond to recent and historical infection, which is consistent with 2009 pandemic attack rates. Similar interpretations are available for H3N2, but right-censoring of titers makes these interpretations difficult to validate.

Production of asiaticoside from centella (Centella asiatica L. Urban) cells in bioreactor.

OBJECTIVE: To investigate the effects of some culture conditions on production of asiaticoside from centella (Centella asiatica L. Urban) cells cultured in 5-L bioreactor. METHODS: The centell cell suspension culture was conducted in 5-L bioreactor to investigate the growth and asiaticoside accumulation under various conditions. Asiaticoside content was determined by HPLC analysis. RESULTS: The results showed that the cell growth and asiaticoside accumulation peaked after 24 d of culture at an agitation speed of 150 r/min and aeration rate of 2.5 L/min. The cell biomass reached a maximum value of 302.45 g fresh weight (31.45 g dry weight) and growth index of 3.03 with inoculum size of 100 g. However, asiaticoside content was the highest (60.08 mg/g dry weight) when culture was initiated with an inoculum size of 50 g. CONCLUSIONS: The present study found the suitable conditions for growth of centella cells and their asiaticoside production in bioreactor.

Population-level antibody estimates to novel influenza A/H7N9.

There are no contemporary data available describing human immunity to novel influenza A/H7N9. Using 1723 prospectively collected serum samples in southern Vietnam, we tested for antibodies to 5 avian influenza virus antigens, using a protein microarray. General-population antibody titers against subtype H7 virus are higher than antibody titers against subtype H5 and lower than titers against H9. The highest titers were observed for human influenza virus subtypes. Titers to avian influenza virus antigens increased with age and with geometric mean antibody titer to human influenza virus antigens. There were no titer differences between the urban and the rural location in our study.