Microbiology & Immunology - Research Publications

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    Strongyloides stercoralis seroprevalence in Vietnam
    Nguyen, TND ; Pham, QT ; Nghiem, NMT ; Jaeger, J ; Fox, A ; Horby, P ; Hoang, VMP ; Dang, DA ; Le, TQM ; Van Doorn, HR ; Nadjm, B (CAMBRIDGE UNIV PRESS, 2017-11)
    Strongyloidiasis is a neglected tropical disease caused by the roundworm Strongyloides stercoralis affecting 30-100 million people worldwide. Many Southeast-Asian countries report a high prevalence of S. stercoralis infection, but there are little data from Vietnam. Here, we evaluated the seroprevalence of S. stercoralis related to geography, sex and age in Vietnam through serological testing of anonymized sera. Sera (n = 1710, 1340 adults and 270 children) from an anonymized age-stratified serum bank from four regions in Vietnam between 2012 and 2013 were tested using a commercial Strongyloides ratti immunoglobulin G ELISA. Seroreactivity was found in 29·1% (390/1340) of adults and 5·5% (15/270) of children. Male adults were more frequently seroreactive than females (33·3% vs. 24·9%, P = 0·001). The rural central highlands had the highest seroprevalence (42·4% of adults). Seroreactivity in the other regions was 29·9% (Hue) and 26·0% and 18·2% in the large urban centres of Hanoi and Ho Chi Minh City, respectively. We conclude that seroprevalence of S. stercoralis was high in the Vietnamese adult population, especially in rural areas.
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    Epidemiology and etiology of influenza-like-illness in households in Vietnam; it's not all about the kids!
    Diep, NTN ; Le, QM ; Bryant, JE ; Nguyen, LKH ; Le, NMH ; Nadjm, B ; Pham, QT ; Tran, ND ; Dang, DA ; Horby, P ; van Doorn, HR ; Wertheim, HFL ; Fox, A (ELSEVIER SCIENCE BV, 2016-09)
    BACKGROUND: Household studies provide opportunities to understand influenza-like-illness (ILI) transmission, but data from (sub)tropical developing countries are scarce. OBJECTIVE: To determine the viral etiology and epidemiology of ILI in households. STUDY DESIGN: ILI was detected by active case finding amongst a cohort of 263 northern Vietnam households between 2008 and 2013. Health workers collected nose and throat swabs for virus detection by multiplex real-time RT-PCR. RESULTS: ILI was detected at least once in 219 (23.7%) of 945 household members. 271 (62.3%) of 435 nose/throat swabs were positive for at least one of the 15 viruses tested. Six viruses predominated amongst positive swabs: Rhinovirus (28%), Influenza virus (17%), Coronavirus (8%), Enterovirus (5%), Respiratory syncytial virus (3%), Metapneumovirus virus (2.5%) and Parainfluenza virus 3 (1.8%). There was no clear seasonality, but 78% of episodes occurred in Winter/Spring for Influenza compared to 32% for Rhinovirus. Participants, on average, suffered 0.49 ILI, and 0.29 virus-positive ILI episodes, with no significant effects of gender, age, or household size. In contrast to US and Australian community studies, the frequency of ILI decreased as the number of household members aged below 5 years increased (p=0.006). CONCLUSION: The findings indicate the need for tailored ILI control strategies, and for better understanding of how local childcare practices and seasonality may influence transmission and the role of children.
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    Subclinical Avian Influenza A(H5N1) Virus Infection in Human, Vietnam
    Mai, QL ; Horby, P ; Fox, A ; Hien, TN ; Hang, KLN ; Phuong, MVH ; Khanh, CN ; de Jong, MD ; Jeeninga, RE ; van Doorn, HR ; Farrar, J ; Wertheim, HFL (CENTERS DISEASE CONTROL, 2013-10)
    Laboratory-confirmed cases of subclinical infection with avian influenza A(H5N1) virus in humans are rare, and the true number of these cases is unknown. We describe the identification of a laboratory-confirmed subclinical case in a woman during an influenza A(H5N1) contact investigation in northern Vietnam.
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    Avian influenza - A review for doctors in travel medicine
    Taylor, WRJ ; Burhan, E ; Wertheim, H ; Soepandi, PZ ; Horby, P ; Fox, A ; Benamore, R ; de Simone, L ; Hien, TT ; Chappuis, F (ELSEVIER SCI LTD, 2010-01)
    First identified in humans in Hong Kong, influenza A/H5N1, known commonly as avian influenza, has caused human disease in 15 countries around the world. Although the current number of confirmed patients is tiny compared to seasonal and the recently emerged H1N1 'swine' influenza, H5N1 remains a candidate for the next highly pathogenic influenza pandemic. Currently, H5N1 has very limited ability to spread from person-to-person but this may change because of mutation or reassortment with other influenza viruses leading to an influenza pandemic with high mortality. If this occurs travellers are likely to be affected and travel medicine doctors will need to consider avian influenza in returning febrile travellers. The early clinical features may be dismissed easily as 'the flu' resulting in delayed treatment. Treatment options are limited. Oral oseltamivir alone has been the most commonly used drug but mortality remains substantial, up to 80% in Indonesia. Intravenous peramivir has been filed for registration and IV zanamivir is being developed. This review will focus on the epidemiological and clinical features of influenza A/H5N1 avian influenza and will highlight aspects relevant to travel medicine doctors.
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    Influenza Infection Rates, Measurement Errors and the Interpretation of Paired Serology
    Cauchemez, S ; Horby, P ; Fox, A ; Le, QM ; Le, TT ; Pham, QT ; Le, NMH ; Nguyen, TH ; Ferguson, NM ; Fouchier, RAM (PUBLIC LIBRARY SCIENCE, 2012-12)
    Serological studies are the gold standard method to estimate influenza infection attack rates (ARs) in human populations. In a common protocol, blood samples are collected before and after the epidemic in a cohort of individuals; and a rise in haemagglutination-inhibition (HI) antibody titers during the epidemic is considered as a marker of infection. Because of inherent measurement errors, a 2-fold rise is usually considered as insufficient evidence for infection and seroconversion is therefore typically defined as a 4-fold rise or more. Here, we revisit this widely accepted 70-year old criterion. We develop a Markov chain Monte Carlo data augmentation model to quantify measurement errors and reconstruct the distribution of latent true serological status in a Vietnamese 3-year serological cohort, in which replicate measurements were available. We estimate that the 1-sided probability of a 2-fold error is 9.3% (95% Credible Interval, CI: 3.3%, 17.6%) when antibody titer is below 10 but is 20.2% (95% CI: 15.9%, 24.0%) otherwise. After correction for measurement errors, we find that the proportion of individuals with 2-fold rises in antibody titers was too large to be explained by measurement errors alone. Estimates of ARs vary greatly depending on whether those individuals are included in the definition of the infected population. A simulation study shows that our method is unbiased. The 4-fold rise case definition is relevant when aiming at a specific diagnostic for individual cases, but the justification is less obvious when the objective is to estimate ARs. In particular, it may lead to large underestimates of ARs. Determining which biological phenomenon contributes most to 2-fold rises in antibody titers is essential to assess bias with the traditional case definition and offer improved estimates of influenza ARs.
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    The Epidemiology of Interpandemic and Pandemic Influenza in Vietnam, 2007-2010 The Ha Nam Household Cohort Study I
    Horby, P ; Le, QM ; Fox, A ; Pham, QT ; Nguyen, TTY ; Le, TT ; Nguyen, LKH ; Tran, ND ; Dang, DT ; Farrar, J ; Wolbers, M ; Nguyen, TH (OXFORD UNIV PRESS INC, 2012-05-15)
    Prospective community-based studies have provided fundamental insights into the epidemiology of influenza in temperate regions, but few comparable studies have been undertaken in the tropics. The authors conducted prospective influenza surveillance and intermittent seroprevalence surveys in a household-based cohort in Vietnam between December 2007 and April 2010, resulting in 1,793 person-seasons of influenza surveillance. Age- and sex-standardized estimates of the risk of acquiring any influenza infection per season in persons 5 years of age or older were 21.1% (95% confidence interval: 17.4, 24.7) in season 1, 26.4% (95% confidence interval: 22.6, 30.2) in season 2, and 17.0% (95% confidence interval: 13.6, 20.4) in season 3. Some individuals experienced multiple episodes of infection with different influenza types/subtypes in the same season (n = 27) or reinfection with the same subtype in different seasons (n = 22). The highest risk of influenza infection was in persons 5-9 years old, in whom the risk of influenza infection per season was 41.8%. Although the highest infection risk was in school-aged children, there were important heterogeneities in the age of infection by subtype and season. These heterogeneities could influence the impact of school closure and childhood vaccination on influenza transmission in tropical areas, such as Vietnam.
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    Studying the effectiveness of activated carbon R95 respirators in reducing the inhalation of combustion by-products in Hanoi, Vietnam: a demonstration study
    Wertheim, HFL ; Dang, MN ; Wolbers, M ; Ta, TB ; Nguyen, TTH ; Nguyen, QL ; Pham, TT ; Sjodin, A ; Romanoff, L ; Li, Z ; Mueller, JF ; Kennedy, K ; Farrar, J ; Stepniewska, K ; Horby, P ; Fox, A ; Nguyen, DB (BMC, 2012-09-26)
    BACKGROUND: Urban air pollution is an increasing health problem, particularly in Asia, where the combustion of fossil fuels has increased rapidly as a result of industrialization and socio-economic development. The adverse health impacts of urban air pollution are well established, but less is known about effective intervention strategies. In this demonstration study we set out to establish methods to assess whether wearing an R95 activated carbon respirator could reduce intake of polycyclic aromatic hydrocarbons (PAH) in street workers in Hanoi, Vietnam. METHODS: In this demonstration study we performed a cross-over study in which non-smoking participants that worked at least 4 hours per day on the street in Hanoi were randomly allocated to specific respirator wearing sequences for a duration of 2 weeks. Urines were collected after each period, i.e., twice per week, at the end of the working day to measure hydroxy PAHs (OH-PAH) using gas chromatography/high resolution mass spectrometry. The primary endpoint was the urinary concentration of 1-hydroxypyrene (1-OHP). RESULTS: Forty-four participants (54.5% male, median age 40 years) were enrolled with the majority being motorbike taxi drivers (38.6%) or street vendors (34.1%). The baseline creatinine corrected urinary level for 1-OHP was much higher than other international comparisons: 1020 ng/g creatinine (IQR: 604-1551). Wearing a R95 mask had no significant effect on 1-OHP levels: estimated multiplicative effect 1.0 (95% CI: 0.92-1.09) or other OH-PAHs, except 1-hydroxynaphthalene (1-OHN): 0.86 (95% CI: 0.11-0.96). CONCLUSIONS: High levels of urine OH-PAHs were found in Hanoi street workers. No effect was seen on urine OH-PAH levels by wearing R95 particulate respirators in an area of high urban air pollution, except for 1-OHN. A lack of effect may be de to gaseous phase PAHs that were not filtered efficiently by the respirator. The high levels of urinary OH-PAHs found, urges for effective interventions. TRIAL REGISTRATION: ISRCTN74390617 (date of assignation: 04/08/2009).
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    Acute Measles Encephalitis in Partially Vaccinated Adults
    Fox, A ; Than, MH ; Wertheim, H ; Le, NMH ; Vincent, A ; Lang, B ; Waters, P ; Nguyen, HH ; Nguyen, VT ; Farrar, J ; Nguyen, VK ; Horby, P ; Diemert, DJ (PUBLIC LIBRARY SCIENCE, 2013-08-13)
    BACKGROUND: The pathogenesis of acute measles encephalitis (AME) is poorly understood. Treatment with immune-modulators is based on theories that post-infectious autoimmune responses cause demyelination. The clinical course and immunological parameters of AME were examined during an outbreak in Vietnam. METHODS AND FINDINGS: Fifteen measles IgM-positive patients with confusion or Glasgow Coma Scale (GCS) score below 13, and thirteen with uncomplicated measles were enrolled from 2008-2010. Standardized clinical exams were performed and blood collected for lymphocyte and measles- and auto-antibody analysis. The median age of AME patients was 21 years, similar to controls. Eleven reported receiving measles vaccination when aged one year. Confusion developed a median of 4 days after rash. Six patients had GCS <8 and four required mechanical ventilation. CSF showed pleocytosis (64%) and proteinorrhachia (71%) but measles virus RNA was not detected. MRI revealed bilateral lesions in the cerebellum and brain stem in some patients. Most received dexamethasone +/- IVIG within 4 days of admission but symptoms persisted for ≥3 weeks in five. The concentration of voltage gated calcium channel-complex-reactive antibodies was 900 pM in one patient, and declined to 609 pM ∼ 3 months later. Measles-reactive IgG antibody avidity was high in AME patients born after vaccine coverage exceeded 50% (∼ 25 years earlier). AME patients had low CD4 (218/µl, p = 0.029) and CD8 (200/µl, p = 0.012) T-cell counts compared to controls. CONCLUSION: Young adults presenting with AME in Vietnam reported a history of one prior measles immunization, and those aged <25 years had high measles-reactive IgG avidity indicative of prior vaccination. This suggests that one-dose measles immunization is not sufficient to prevent AME in young adults and reinforces the importance of maintaining high coverage with a two-dose measles immunization schedule. Treatment with corticosteroids and IVIG is common practice, and should be assessed in randomized clinical trials.
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    Social Contact Patterns in Vietnam and Implications for the Control of Infectious Diseases
    Horby, P ; Pham, QT ; Hens, N ; Nguyen, TTY ; Le, QM ; Dang, DT ; Nguyen, ML ; Nguyen, TH ; Alexander, N ; Edmunds, WJ ; Tran, ND ; Fox, A ; Nguyen, TH ; Munayco, C (PUBLIC LIBRARY SCIENCE, 2011-02-14)
    BACKGROUND: The spread of infectious diseases from person to person is determined by the frequency and nature of contacts between infected and susceptible members of the population. Although there is a long history of using mathematical models to understand these transmission dynamics, there are still remarkably little empirical data on contact behaviors with which to parameterize these models. Even starker is the almost complete absence of data from developing countries. We sought to address this knowledge gap by conducting a household based social contact diary in rural Vietnam. METHODS AND FINDINGS: A diary based survey of social contact patterns was conducted in a household-structured community cohort in North Vietnam in 2007. We used generalized estimating equations to model the number of contacts while taking into account the household sampling design, and used weighting to balance the household size and age distribution towards the Vietnamese population. We recorded 6675 contacts from 865 participants in 264 different households and found that mixing patterns were assortative by age but were more homogenous than observed in a recent European study. We also observed that physical contacts were more concentrated in the home setting in Vietnam than in Europe but the overall level of physical contact was lower. A model of individual versus household vaccination strategies revealed no difference between strategies in the impact on R(0). CONCLUSIONS AND SIGNIFICANCE: This work is the first to estimate contact patterns relevant to the spread of infections transmitted from person to person by non-sexual routes in a developing country setting. The results show interesting similarities and differences from European data and demonstrate the importance of context specific data.
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    Pandemic H1N1 virus transmission and shedding dynamics in index case households of a prospective Vietnamese cohort
    Pham, QT ; Le, QM ; Welkers, MRA ; Nguyen, LKH ; Le, TT ; Vu, TVD ; Nguyen, TTY ; Tran, ND ; Le, NMH ; Dang, DT ; Hoang, THT ; de Jong, MD ; Wertheim, H ; Nguyen, TH ; Horby, P ; Fox, A (W B SAUNDERS CO LTD, 2014-06)
    OBJECTIVES: Influenza household transmission studies are required to guide prevention strategies but most passively recruit index cases that seek healthcare. We investigated A(H1N1)pdm09 transmission in a household-based cohort during 2009. METHODS: Health-workers visited 270 households weekly, and collected swabs from influenza-like-illness cases. If A(H1N1)pdm09 was RT-PCR-confirmed, all household members had symptoms assessed and swabs collected daily for 10-15 days. Viral RNA was quantified and sequenced and serology performed on pre-pandemic sera. RESULTS: Index cases were detected in 20 households containing 81 people. 98.5% lacked A(H1N1)pdm09 neutralizing antibodies in pre-pandemic sera. Eleven (18.6%, 95% CI 10.7-30.4%) of 59 contacts were infected. Virus genetic diversity within households was negligible and less than between households. Index and secondary cases were distributed between mothers, daughters and sons, and had similar virus-RNA shedding and symptom dynamics. Fathers were rarely infected. Five secondary cases (45%) had no apparent symptoms and three shed virus before symptoms. Secondary infection was associated with index case wet cough (OR 1.56, 95% CI 1.22-1.99). CONCLUSIONS: In this cohort of A(H1N1)pdm09 susceptible persons, virus sequencing was capable of discriminating household from community transmission. Household transmission involved mothers and children but rarely fathers. Asymptomatic or pre-symptomatic shedding was common.