Publications by authors named "Marc Choisy"

48 Publications

Age-structured non-pharmaceutical interventions for optimal control of COVID-19 epidemic.

PLoS Comput Biol 2021 03 4;17(3):e1008776. Epub 2021 Mar 4.

MIVEGEC, Univ. Montpellier, IRD, CNRS, Montpellier, France.

In an epidemic, individuals can widely differ in the way they spread the infection depending on their age or on the number of days they have been infected for. In the absence of pharmaceutical interventions such as a vaccine or treatment, non-pharmaceutical interventions (e.g. physical or social distancing) are essential to mitigate the pandemic. We develop an original approach to identify the optimal age-stratified control strategy to implement as a function of the time since the onset of the epidemic. This is based on a model with a double continuous structure in terms of host age and time since infection. By applying optimal control theory to this model, we identify a solution that minimizes deaths and costs associated with the implementation of the control strategy itself. We also implement this strategy for three countries with contrasted age distributions (Burkina-Faso, France, and Vietnam). Overall, the optimal strategy varies throughout the epidemic, with a more intense control early on, and depending on host age, with a stronger control for the older population, except in the scenario where the cost associated with the control is low. In the latter scenario, we find strong differences across countries because the control extends to the younger population for France and Vietnam 2 to 3 months after the onset of the epidemic, but not for Burkina Faso. Finally, we show that the optimal control strategy strongly outperforms a constant uniform control exerted over the whole population or over its younger fraction. This improved understanding of the effect of age-based control interventions opens new perspectives for the field, especially for age-based contact tracing.
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http://dx.doi.org/10.1371/journal.pcbi.1008776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7963091PMC
March 2021

Novel Mutation of SARS-CoV-2, Vietnam, July 2020.

Emerg Infect Dis 2021 Mar 1;27(5). Epub 2021 Mar 1.

A cluster of severe acute respiratory syndrome coronavirus 2 infections in Danang, Vietnam, began July 25, 2020, and resulted in 551 confirmed cases and 35 deaths as of February 2021. We analyzed 26 sequences from this cluster and identified a novel shared mutation in nonstructural protein 9, suggesting a single introduction into Vietnam.
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http://dx.doi.org/10.3201/eid2705.210013DOI Listing
March 2021

Trends of the Dengue Serotype-4 Circulation with Epidemiological, Phylogenetic, and Entomological Insights in Lao PDR between 2015 and 2019.

Pathogens 2020 Sep 3;9(9). Epub 2020 Sep 3.

Arbovirus and Emerging Viral Diseases Laboratory, Institut Pasteur du Lao PDR, Vientiane 01030, Laos.

Dengue outbreaks have regularly been recorded in Lao People's Democratic Republic (PDR) since the first detection of the disease in 1979. In 2012, an integrated arbovirus surveillance network was set up in Lao PDR and an entomological surveillance has been implemented since 2016 in Vientiane Capital. Here, we report a study combining epidemiological, phylogenetic, and entomological analyzes during the largest DENV-4 epidemic ever recorded in Lao PDR (2015-2019). Strikingly, from 2015 to 2019, we reported the DENV-4 emergence and spread at the country level after two large epidemics predominated by DENV-3 and DENV-1, respectively, in 2012-2013 and 2015. Our data revealed a significant difference in the median age of the patient infected by DENV-4 compared to the other serotypes. Phylogenetic analysis demonstrated the circulation of DENV-4 Genotype I at the country level since at least 2013. The entomological surveillance showed a predominance of compared to and high abundance of these vectors in dry and rainy seasons between 2016 and 2019, in Vientiane Capital. Overall, these results emphasized the importance of an integrated approach to evaluate factors, which could impact the circulation and the epidemiological profile of dengue viruses, especially in endemic countries like Lao PDR.
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http://dx.doi.org/10.3390/pathogens9090728DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7557816PMC
September 2020

The first 100 days of SARS-CoV-2 control in Vietnam.

Clin Infect Dis 2020 Aug 1. Epub 2020 Aug 1.

Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, UK.

Background: One hundred days after SARS-CoV-2 was first reported in Vietnam on January 23rd, 270 cases were confirmed, with no deaths. We describe the control measures used by the Government and their relationship with imported and domestically-acquired case numbers, with the aim of identifying the measures associated with successful SARS-CoV-2 control.

Methods: Clinical and demographic data on the first 270 SARS-CoV-2 infected cases and the timing and nature of Government control measures, including numbers of tests and quarantined individuals, were analysed. Apple and Google mobility data provided proxies for population movement. Serial intervals were calculated from 33 infector-infectee pairs and used to estimate the proportion of pre-symptomatic transmission events and time-varying reproduction numbers.

Results: A national lockdown was implemented between April 1st and 22nd. Around 200 000 people were quarantined and 266 122 RT-PCR tests conducted. Population mobility decreased progressively before lockdown. 60% (163/270) of cases were imported; 43% (89/208) of resolved infections remained asymptomatic for the duration of infection. The serial interval was 3·24 days, and 27·5% (95% confidence interval, 15·7%-40·0%) of transmissions occurred pre-symptomatically. Limited transmission amounted to a maximum reproduction number of 1·15 (95% confidence interval, 0·37-2·36). No community transmission has been detected since April 15th.

Conclusions: Vietnam has controlled SARS-CoV-2 spread through the early introduction of mass communication, meticulous contact-tracing with strict quarantine, and international travel restrictions. The value of these interventions is supported by the high proportion of asymptomatic and imported cases, and evidence for substantial pre-symptomatic transmission.
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http://dx.doi.org/10.1093/cid/ciaa1130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454342PMC
August 2020

Seroepidemiologic Study Designs for Determining SARS-COV-2 Transmission and Immunity.

Emerg Infect Dis 2020 Sep 16;26(9):1978-1986. Epub 2020 Jun 16.

Serologic studies are crucial for clarifying dynamics of the coronavirus disease pandemic. Past work on serologic studies (e.g., during influenza pandemics) has made relevant contributions, but specific conditions of the current situation require adaptation. Although detection of antibodies to measure exposure, immunity, or both seems straightforward conceptually, numerous challenges exist in terms of sample collection, what the presence of antibodies actually means, and appropriate analysis and interpretation to account for test accuracy and sampling biases. Successful deployment of serologic studies depends on type and performance of serologic tests, population studied, use of adequate study designs, and appropriate analysis and interpretation of data. We highlight key questions that serologic studies can help answer at different times, review strengths and limitations of different assay types and study designs, and discuss methods for rapid sharing and analysis of serologic data to determine global transmission of severe acute respiratory syndrome coronavirus 2.
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http://dx.doi.org/10.3201/eid2609.201840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454079PMC
September 2020

Does sunlight drive seasonality of TB in Vietnam? A retrospective environmental ecological study of tuberculosis seasonality in Vietnam from 2010 to 2015.

BMC Infect Dis 2020 Feb 28;20(1):184. Epub 2020 Feb 28.

Oxford University Clinical Research Unit - Hanoi, National Hospital of Tropical Diseases, 78 Giai Phong, Hanoi, Vietnam.

Background: Tuberculosis (TB) is a major global health burden, with an estimated quarter of the world's population being infected. The World Health Organization (WHO) launched the "End TB Strategy" in 2014 emphasising knowing the epidemic. WHO ranks Vietnam 12th in the world of high burden countries. TB spatial and temporal patterns have been observed globally with evidence of Vitamin D playing a role in seasonality. We explored the presence of temporal and spatial clustering of TB in Vietnam and their determinants to aid public health measures.

Methods: Data were collected by the National TB program of Vietnam from 2010 to 2015 and linked to the following datasets: socio-demographic characteristics; climatic variables; influenza-like-illness (ILI) incidence; geospatial data. The TB dataset was aggregated by province and quarter. Descriptive time series analyses using LOESS regression were completed per province to determine seasonality and trend. Harmonic regression was used to determine the amplitude of seasonality by province. A mixed-effect linear model was used with province and year as random effects and all other variables as fixed effects.

Results: There were 610,676 cases of TB notified between 2010 and 2015 in Vietnam. Heat maps of TB incidence per quarter per province showed substantial temporal and geospatial variation. Time series analysis demonstrated seasonality throughout the country, with peaks in spring/summer and troughs in autumn/winter. Incidence was consistently higher in the south, the three provinces with the highest incidence per 100,000 population were Tay Ninh, An Giang and Ho Chi Minh City. However, relative seasonal amplitude was more pronounced in the north. Mixed-effect linear model confirmed that TB incidence was associated with time and latitude. Of the demographic, socio-economic and health related variables, population density, percentage of those under 15 years of age, and HIV infection prevalence per province were associated with TB incidence. Of the climate variables, absolute humidity, average temperature and sunlight were associated with TB incidence.

Conclusion: Preventative public health measures should be focused in the south of Viet Nam where incidence is highest. Vitamin D is unlikely to be a strong driver of seasonality but supplementation may play a role in a package of interventions.
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http://dx.doi.org/10.1186/s12879-020-4908-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7048025PMC
February 2020

Characterization of viral, bacterial, and parasitic causes of disease in small-scale chicken flocks in the Mekong Delta of Vietnam.

Poult Sci 2020 Feb 26;99(2):783-790. Epub 2019 Dec 26.

Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam; Nuffield Department of Medicine, Oxford University, Oxford, United Kingdom.

In the Mekong Delta region of Vietnam, small-scale chicken farming is common. However, high levels of disease or mortality in such flocks impair economic development and challenge the livelihoods of many rural households. We investigated 61 diseased small-scale flocks (122 chickens) for evidence of infection with 5 bacteria, 4 viruses, and helminths. Serological profiles (ELISA) were also determined against 6 of these pathogens. The aims of this study were the following: (1) to investigate the prevalence of different pathogens and to compare the probability of detection of bacterial pathogens using PCR and culture; (2) to investigate the relationship between detection of organisms in birds' tissues and the observed morbidity and mortality, as well as their antibody profile; and (3) to characterize risk factors for infection with specific viral or bacterial pathogens. We used PCR to test for viral (viruses causing infectious bronchitis [IB], highly pathogenic avian influenza [HPAI], Newcastle disease, and infectious bursal disease [IBD]) and bacterial pathogens (Mycoplasma gallisepticum, Pasteurella multocida, Avibacterium paragallinarum, and Ornithobacterium rhinotracheale [ORT]). The latter two were also investigated in respiratory tissues by conventional culture. Colisepticemic Escherichia coli was investigated by liver or spleen culture. In 49 of 61 (80.3%) flocks, at least one bacterial or viral pathogen was detected, and in 29 (47.5%) flocks, more than one pathogen was detected. A. paragallinarum was detected in 62.3% flocks, followed by M. gallisepticum (26.2%), viruses causing IBD (24.6%) and IB (21.3%), septicemic E. coli (14.8%), ORT (13.1%), and HPAI viruses (4.9%). Of all flocks, 67.2% flocks were colonized by helminths. Mortality was highest among flocks infected with HPAI (100%, interquartile range [IQR]: 81.6-100%) and lowest with flocks infected with ORT (5.3%, IQR: 1.1-9.0%). The results indicated slight agreement (kappa ≤ 0.167) between detection by PCR and culture for both A. paragallinarum and ORT, as well as between the presence of cestodes and ORT infection (kappa = 0.317). Control of A. paragallinarum, viruses causing HPAI, IBD, and IB, M. gallisepticum, and gastrointestinal helminths should be a priority in small-scale flocks.
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http://dx.doi.org/10.1016/j.psj.2019.10.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7587710PMC
February 2020

An estimation of total antimicrobial usage in humans and animals in Vietnam.

Antimicrob Resist Infect Control 2020 14;9(1):16. Epub 2020 Jan 14.

1Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.

The accurate assessment of antimicrobial use (AMU) requires relating quantities of active ingredients (AAIs) with population denominators. These data can be used to prioritize potential sources of selective pressure for antimicrobial resistance and to establish reduction targets. Here, we estimated AMU in Vietnam (human population 93.4 M in 2015), and compared it with European Union (EU) data (population 511.5 M in 2014). We extrapolated AMU data on each key animal species and humans from different published sources to calculate overall AMU (in tonnes) in Vietnam. We then compared these data with published statistics on AMU in the European Union (EU). A total of 3838 t of antimicrobials were used in Vietnam, of which 2751 (71.7%) corresponded to animal use, and the remainder (1086 t; 28.3%) to human AMU. This equates to 261.7 mg and 247.3 mg per kg of human and animal biomass, compared with 122.0 mg and 151.5 mg in the EU. The greatest quantities of antimicrobials (in decreasing order) were used in pigs (41.7% of total use), humans (28.3%), aquaculture (21.9%) and chickens (4.8%). Combined AMU in other species accounted for < 1.5%. These results are approximate and highlight the need to conduct targeted surveys to improve country-level estimates of AMU.
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http://dx.doi.org/10.1186/s13756-019-0671-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6961235PMC
January 2020

Plans for Nationwide Serosurveillance Network in Vietnam.

Emerg Infect Dis 2020 01;26(1)

In recent years, serosurveillance has gained momentum as a way of determining disease transmission and immunity in populations, particularly with respect to vaccine-preventable diseases. At the end of 2017, the Oxford University Clinical Research Unit and the National Institute of Hygiene and Epidemiology held a meeting in Vietnam with national policy makers, researchers, and international experts to discuss current seroepidemiologic projects in Vietnam and future needs and plans for nationwide serosurveillance. This report summarizes the meeting and the plans that were discussed to set up nationwide serosurveillance in Vietnam.
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http://dx.doi.org/10.3201/eid2601.190641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6924907PMC
January 2020

High-Resolution Monitoring of Antimicrobial Consumption in Vietnamese Small-Scale Chicken Farms Highlights Discrepancies Between Study Metrics.

Front Vet Sci 2019 21;6:174. Epub 2019 Jun 21.

Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.

Chicken is, among farmed species, the target of the highest levels of antimicrobial use (AMU). There are considerable knowledge gaps on how and when antimicrobials are used in commercial small-scale chicken farms. These shortcomings arise from cross-sectional study designs and poor record keeping practiced by many such farmers. Furthermore, there is a large diversity of AMU metrics, and it is not clear how these metrics relate to each other. We performed a longitudinal study on a cohort of small-scale chicken farms ( = 102) in the Mekong Delta (Vietnam), an area regarded as a hotspot of AMU, from October 2016 to May 2018. We collected data on all medicine products administered to 203 flocks with the following aims: (1) to describe types and quantities of antimicrobial active ingredients (AAIs) used; (2) to describe critical time points of AMU; and (3) to compare AMU using three quantitative metrics: (a) weight of AAIs related to bird weight at the time of treatment (mg/kg at treatment); (b) weight of AAIs related to weight of birds sold (mg/kg sold); and (c) "treatment incidence" (TI), or the number of daily doses per kilogram of live chicken [Vietnamese animal daily dose (ADDvetVN)] per 1,000 days. Antimicrobials contained in commercial feed, administered by injection ( = = 6), or antimicrobials for human medicine ( = = 16) were excluded. A total of 236 products were identified, containing 42 different AAIs. A total of 76.2% products contained AAIs of "critical importance" according to the World Health Organization (WHO). On average, chickens consumed 791.8 (SEM ±16.7) mg/kg at treatment, 323.4 (SEM ±11.3) mg/kg sold, and the TI was 382.6 (SEM ±5.5) per 1,000 days. AMU was more common early in the production cycle and was highly skewed, with the upper 25% quantile of flocks accounting for 60.7% of total AMU. The observed discrepancies between weight- and dose-based metrics were explained by differences in the strength of AAIs, mortality levels, and the timing of administration. Results suggest that in small-scale chicken production, AMU reduction efforts should preferentially target the early (brooding) period, which is when birds are most likely to be exposed to antimicrobials, whilst restricting access to antimicrobials of critical importance for human medicine.
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http://dx.doi.org/10.3389/fvets.2019.00174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6598194PMC
June 2019

Assessing antimicrobial misuse in small-scale chicken farms in Vietnam from an observational study.

BMC Vet Res 2019 Jun 20;15(1):206. Epub 2019 Jun 20.

Oxford University Clinical Research Unit, Hanoi, Vietnam.

Background: Antimicrobials are used by poultry farmers in Vietnam as a tool to treat and prevent infectious diseases. We aimed to determine the fraction of disease episodes likely to remain untreated due to the administration of antimicrobials on non-susceptible pathogens in chicken flocks in the Mekong Delta of Vietnam. Weekly data on antimicrobial use and clinical signs were collected from 88 randomly chosen chicken flocks over 124 full production cycles (i.e. time between restocking flocks with day-old chicks and sale for slaughter). A naïve Bayes model was trained to infer the probabilities of disease episodes having been caused by each of 24 pathogens, given the observed clinical sign profile, and expert knowledge on their relative incidence.

Results: A total of 224 disease episodes were observed, of which 44.8% were attributed to viruses (95% CI 31.1-58.4%), 54.6% (CI 40.4-68.7%) to bacteria, and 0.6% (CI 0-1.7%) to a protozoan (Eimeria spp.). Antimicrobials were more frequently administered on weeks with disease than on weeks without disease (43.3% vs. 17.8%; p < 0.001). A median of 2 [IQR 0-4] antimicrobials were used by episode. The choice of specific antimicrobials was independent on whether the flocks had disease clinical signs or not. Antimicrobials were not used in 30.3% of the episodes. The overall probability that episodes were not effectively treated was 74.2, and 53.7% when discounting cases where the inferred aetiology is viral. Considering only episodes where antimicrobials were given, these probabilities were 57.4 and 23.8% respectively.

Conclusions: This study highlights untargeted use of antimicrobials on small-scale Vietnamese chicken farms, as well as the limitations of antimicrobials as effective tools to control infectious diseases.
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http://dx.doi.org/10.1186/s12917-019-1947-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6585117PMC
June 2019

Antimicrobial susceptibility testing and antibiotic consumption results from 16 hospitals in Viet Nam: The VINARES project 2012-2013.

J Glob Antimicrob Resist 2019 09 12;18:269-278. Epub 2019 Jun 12.

Oxford University Clinical Research Unit, Viet Nam; Department of Medical Microbiology and Radboudumc Center for Infectious Diseases, Radboudumc, Nijmegen, Netherlands.

Objective: To establish a hospital-based surveillance network with national coverage for antimicrobial resistance (AMR) and antibiotic consumption in Viet Nam.

Methods: A 16-hospital network (Viet Nam Resistance: VINARES) was established and consisted of national and provincial-level hospitals across the country. Antimicrobial susceptibility testing results from routine clinical diagnostic specimens and antibiotic consumption data in Defined Daily Dose per 1000 bed days (DDD/1000 patient-days) were prospectively collected and analysed between October 2012 and September 2013.

Results: Data from a total of 24 732 de-duplicated clinical isolates were reported. The most common bacteria were: Escherichia coli (4437 isolates, 18%), Klebsiella spp. (3290 isolates, 13%) and Acinetobacter spp. (2895 isolates, 12%). The hospital average antibiotic consumption was 918 DDD/1000 patient-days. Third-generation cephalosporins were the most frequently used antibiotic class (223 DDD/1000 patient-days, 24%), followed by fluoroquinolones (151 DDD/1000 patient-days, 16%) and second-generation cephalosporins (112 DDD/1000 patient-days, 12%). Proportions of antibiotic resistance were high: 1098/1580 (69%) Staphylococcus aureus isolates were methicillin-resistant (MRSA); 115/344 isolates (33%) and 90/358 (25%) Streptococcus pneumoniae had reduced susceptibility to penicillin and ceftriaxone, respectively. A total of 180/2977 (6%) E. coli and 242/1526 (16%) Klebsiella pneumoniae were resistant to imipenem, respectively; 602/1826 (33%) Pseudomonas aeruginosa were resistant to ceftazidime and 578/1765 (33%) to imipenem. Of Acinetobacter spp. 1495/2138 (70%) were resistant to carbapenems and 2/333 (1%) to colistin.

Conclusions: These data are valuable in providing a baseline for AMR among common bacterial pathogens in Vietnamese hospitals and to assess the impact of interventions.
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http://dx.doi.org/10.1016/j.jgar.2019.06.002DOI Listing
September 2019

Clinical Manifestations and Molecular Diagnosis of Scrub Typhus and Murine Typhus, Vietnam, 2015-2017.

Emerg Infect Dis 2019 04;25(4)

Rickettsioses are endemic to Vietnam; however, only a limited number of clinical studies have been performed on these vectorborne bacteria. We conducted a prospective hospital-based study at 2 national referral hospitals in Hanoi to describe the clinical characteristics of scrub typhus and murine typhus in northern Vietnam and to assess the diagnostic applicability of quantitative real-time PCR assays to diagnose rickettsial diseases. We enrolled 302 patients with acute undifferentiated fever and clinically suspected rickettsiosis during March 2015-March 2017. We used a standardized case report form to collect clinical information and laboratory results at the time of admission and during treatment. We confirmed scrub typhus in 103 (34.1%) patients and murine typhus in 12 (3.3%) patients. These results highlight the need for increased emphasis on training for healthcare providers for earlier recognition, prevention, and treatment of rickettsial diseases in Vietnam.
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http://dx.doi.org/10.3201/eid2504.180691DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6433017PMC
April 2019

Sero-Prevalence Surveillance to Predict Vaccine-Preventable Disease Outbreaks; A Lesson from the 2014 Measles Epidemic in Northern Vietnam.

Open Forum Infect Dis 2019 Mar 24;6(3):ofz030. Epub 2019 Jan 24.

Oxford University Clinical Research Unit, Wellcome Trust Asia Programme, Hanoi, Vietnam.

Background: During the first half of 2014, a severe outbreak of measles occurred in northern Vietnam, causing 15 033 confirmed cases and 146 deaths.

Methods: To evaluate the population-level seroprevalence of protection against measles in the period before the outbreak, we made use of an existing age-stratified serum bank, collected over the year before the outbreak, between November 2012 and December 2013, from 4 sites across the country (Hanoi, Hue, Dak Lak, and Ho Chi Minh City). Data from the UNICEF's Multiple Indicator Clustered Surveys (MICS), carried out in Vietnam during the first quarter of 2014, were used to assess the vaccine coverage in 6 ecological regions of Vietnam.

Results: Results revealed a large discrepancy between levels of protection, as estimated from the serology and vaccine coverage estimated by UNICEF's MICS. Variation in seroprevalence across locations and age groups corresponded with reported numbers of measles cases, most of which were among the 0-2-year-old age group and in the northern part of the country.

Conclusions: Our study presents a strong case in favor of a serosurveillance sentinel network that could be used to proactively tune vaccination policies and other public health interventions.
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http://dx.doi.org/10.1093/ofid/ofz030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6405937PMC
March 2019

Mortality, disease and associated antimicrobial use in commercial small-scale chicken flocks in the Mekong Delta of Vietnam.

Prev Vet Med 2019 Apr 11;165:15-22. Epub 2019 Feb 11.

Oxford University Clinical Research Unit, Vietnam; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, Oxford University, Oxford, United Kingdom.

Raising chickens in small-scale flocks following all-in-all-out management is common in the Mekong Delta of Vietnam. These flocks represent an intermediate category between backyard and intensive (industrial) farming systems. However, little is known about the occurrence and burden of disease and/or mortality in such flocks, and their potential association with antimicrobial usage (AMU). We investigated mortality, disease and weekly antimicrobial use (AMU) in 124 cycles of meat chicken flocks raised in 88 farms in the Mekong Delta of Vietnam (with a median cycle duration of 18 weeks [inter-quartile range IQR 17-20]). We visited each farm 4 times per cycle to review data collected weekly by the farmers on clinical signs, mortality, and AMU. The overall probability of disease and AMU were 0.31 (95% CI 0.29-0.32) and 0.26 (95% CI 0.24-0.28), respectively. The average weekly incidence of mortality was 2.6 (95% CI 2.2-3.0) per 100 birds. Both the probabilities of a flock experiencing disease and mortality, as well as of using antimicrobials decreased with the flock's age. However, mortality peaked at the 5-10 week period. The only significant explanatory factors associated with presence of disease was the stage of production ≥5 weeks (protective) (OR ≤ 0.51). Factors independently associated with AMU (p < 0.05) were: (1) Number of chickens (log) (OR=1.46), (2) Stage of production ≥5 weeks (OR≤0.67) (protective), (3) Cao Lanh district (OR=2.23), (4) Density of veterinary drug shops at commune level (log) (OR=1.58), and (5) Disease in flocks (OR=1.80). Factors independently associated with overall increased weekly incidence of mortality (p < 0.05) were: (1) High level of education attainment (secondary education or higher) (Hazard rate Ratio [HR]=1.70), (2) number of chickens (log) (HR=1.39), and (3) Stage of production >5 weeks (HR≤2.14). In flocks reporting disease, AMU significantly reduced the incidence of mortality (HR=0.90). These results confirm an exceptionally high mortality in chicken flocks in the area, jeopardizing the profitability and sustainability of these small-scale farming systems. The data also suggest an association between nearby access to antimicrobials and AMU, and a high correlation of AMU over consecutive cycles. The atomized farming landscape of the Mekong Delta, the high incidence of disease and mortality, and the unrestricted and easy access to antimicrobials present major challenges to the implementation of policies aimed at AMU reductions.
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http://dx.doi.org/10.1016/j.prevetmed.2019.02.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6418316PMC
April 2019

Seasonal and interannual risks of dengue introduction from South-East Asia into China, 2005-2015.

PLoS Negl Trop Dis 2018 11 9;12(11):e0006743. Epub 2018 Nov 9.

School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education, Shanghai, China.

Due to worldwide increased human mobility, air-transportation data and mathematical models have been widely used to measure risks of global dispersal of pathogens. However, the seasonal and interannual risks of pathogens importation and onward transmission from endemic countries have rarely been quantified and validated. We constructed a modelling framework, integrating air travel, epidemiological, demographical, entomological and meteorological data, to measure the seasonal probability of dengue introduction from endemic countries. This framework has been applied retrospectively to elucidate spatiotemporal patterns and increasing seasonal risk of dengue importation from South-East Asia into China via air travel in multiple populations, Chinese travelers and local residents, over a decade of 2005-15. We found that the volume of airline travelers from South-East Asia into China has quadrupled from 2005 to 2015 with Chinese travelers increased rapidly. Following the growth of air traffic, the probability of dengue importation from South-East Asia into China has increased dramatically from 2005 to 2015. This study also revealed seasonal asymmetries of transmission routes: Sri Lanka and Maldives have emerged as origins; neglected cities at central and coastal China have been increasingly vulnerable to dengue importation and onward transmission. Compared to the monthly occurrence of dengue reported in China, our model performed robustly for importation and onward transmission risk estimates. The approach and evidence could facilitate to understand and mitigate the changing seasonal threat of arbovirus from endemic regions.
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http://dx.doi.org/10.1371/journal.pntd.0006743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6248995PMC
November 2018

Disentangling complex parasite interactions: Protection against cerebral malaria by one helminth species is jeopardized by co-infection with another.

PLoS Negl Trop Dis 2018 05 10;12(5):e0006483. Epub 2018 May 10.

UMMISCO, IRD / Sorbonne Université, Bondy, France.

Multi-species interactions can often have non-intuitive consequences. However, the study of parasite interactions has rarely gone beyond the effects of pairwise combinations of species, and the outcomes of multi-parasite interactions are poorly understood. We investigated the effects of co-infection by four gastrointestinal helminth species on the development of cerebral malaria among Plasmodium falciparum-infected patients. We characterized associations among the helminth parasite infra-community, and then tested for independent (direct) and co-infection dependent (indirect) effects of helminths on cerebral malaria risk. We found that infection by Ascaris lumbricoides and Trichuris trichiura were both associated with direct reductions in cerebral malaria risk. However, the benefit of T. trichiura infection was halved in the presence of hookworm, revealing a strong indirect effect. Our study suggests that the outcome of interactions between two parasite species can be significantly modified by a third, emphasizing the critical role that parasite community interactions play in shaping infection outcomes.
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http://dx.doi.org/10.1371/journal.pntd.0006483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5963812PMC
May 2018

Transmission traits of malaria parasites within the mosquito: Genetic variation, phenotypic plasticity, and consequences for control.

Evol Appl 2018 04 16;11(4):456-469. Epub 2017 Dec 16.

Grand Challenges in Ecosystems and Environment Imperial College London Ascot UK.

Evaluating the risk of emergence and transmission of vector-borne diseases requires knowledge of the genetic and environmental contributions to pathogen transmission traits. Compared to the significant effort devoted to understanding the biology of malaria transmission from vertebrate hosts to mosquito vectors, the strategies that malaria parasites have evolved to maximize transmission from vectors to vertebrate hosts have been largely overlooked. While determinants of infection success within the mosquito host have recently received attention, the causes of variability for other key transmission traits of malaria, namely the duration of parasite development and its virulence within the vector, as well as its ability to alter mosquito behavior, remain largely unknown. This important gap in our knowledge needs to be bridged in order to obtain an integrative view of the ecology and evolution of malaria transmission strategies. Associations between transmission traits also need to be characterized, as they trade-offs and constraints could have important implications for understanding the evolution of parasite transmission. Finally, theoretical studies are required to evaluate how genetic and environmental influences on parasite transmission traits can shape malaria dynamics and evolution in response to disease control.
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http://dx.doi.org/10.1111/eva.12571DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5891056PMC
April 2018

Retrospective analysis assessing the spatial and temporal distribution of paediatric acute respiratory tract infections in Ho Chi Minh City, Vietnam.

BMJ Open 2018 01 21;8(1):e016349. Epub 2018 Jan 21.

Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Program, Ho Chi Minh City, Vietnam.

Background: Acute respiratory tract infections (ARIs) are the leading cause of morbidity and mortality in young children in low/middle-income countries. Using routine hospital data, we aimed to examine the spatial distribution, temporal trends and climatic risk factors of paediatric ARIs in Vietnam.

Methods: Data from hospitalised paediatric (<16 years) patients with ARIs residing in Ho Chi Minh City (HCMC) between 2005 and 2010 were retrieved from the two main Children's Hospitals and the Hospital for Tropical Diseases in HCMC. Spatial mapping and time series analysis were performed after disaggregating data into upper respiratory tract infections (URIs) and lower respiratory tract infections (LRIs).

Results: Over the study period, there were 155 999 paediatric patients admitted with ARIs (33% of all hospital admissions). There were 68 120 URIs (14%) and 87 879 LRIs (19%). The most common diagnoses were acute pharyngitis (28% of all ARI), pneumonia (21%), bronchitis (18%) and bronchiolitis (16%). A significant increasing trend over time was found for both URIs (mean weekly incidence per 1000 population, I=3.12), incidence rate ratio for 1-week increase in time (RR 1.0, 95% CI 1.02 to 1.17) for URI and (I=4.02, RR 1.08 (95% CI 1.006 to 1.16)) for LRI. The weekly URI incidence peaked in May-June and was significantly associated with lags in weekly URI incidence and the average humidity, rainfall and water level. The weekly LRI incidence exhibited significant seasonality (P<0.0001), with an annual peak in September-October and was significantly associated with lags in weekly LRI incidence and lags in weekly average temperature, rainfall and water level.

Conclusions: ARIs are a leading cause of childhood hospitalisation in HCMC, Vietnam. The incidence of ARIs was higher in the wet season and in specific HCMC districts. These results may guide health authorities in where and when to effectively allocate resources for the prevention and control of ARIs.
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http://dx.doi.org/10.1136/bmjopen-2017-016349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5780701PMC
January 2018

Economic factors influencing zoonotic disease dynamics: demand for poultry meat and seasonal transmission of avian influenza in Vietnam.

Sci Rep 2017 07 19;7(1):5905. Epub 2017 Jul 19.

Veterinary Epidemiology, Economics and Public Health Group, Department of Pathobiology and Population Sciences, Royal Veterinary College, University of London, Hawkshead Lane, Hatfield, Hertfordshire, AL97TA, United Kingdom.

While climate is often presented as a key factor influencing the seasonality of diseases, the importance of anthropogenic factors is less commonly evaluated. Using a combination of methods - wavelet analysis, economic analysis, statistical and disease transmission modelling - we aimed to explore the influence of climatic and economic factors on the seasonality of H5N1 Highly Pathogenic Avian Influenza in the domestic poultry population of Vietnam. We found that while climatic variables are associated with seasonal variation in the incidence of avian influenza outbreaks in the North of the country, this is not the case in the Centre and the South. In contrast, temporal patterns of H5N1 incidence are similar across these 3 regions: periods of high H5N1 incidence coincide with Lunar New Year festival, occurring in January-February, in the 3 climatic regions for 5 out of the 8 study years. Yet, daily poultry meat consumption drastically increases during Lunar New Year festival throughout the country. To meet this rise in demand, poultry production and trade are expected to peak around the festival period, promoting viral spread, which we demonstrated using a stochastic disease transmission model. This study illustrates the way in which economic factors may influence the dynamics of livestock pathogens.
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http://dx.doi.org/10.1038/s41598-017-06244-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5517570PMC
July 2017

Prevalence of Hepatitis B Virus Infection among Pregnant Women Attending Antenatal Clinics in Vientiane, Laos, 2008-2014.

Hepat Res Treat 2017 29;2017:1284273. Epub 2017 Mar 29.

Institut de la Francophonie pour la Médecine Tropicale (IFMT), Vientiane, Laos.

The Lao People's Democratic Republic (PDR) is still considered a highly endemic country for hepatitis B, mainly due to perinatal transmission of hepatitis B virus (HBV), despite efforts made since 2004 for universal immunization of newborns. The prevalence of HBV surface antigen (HBsAg) carriage in pregnant women is a relevant marker for the risk of mother-to-child HBV transmission. This study aimed to assess the changes in prevalence of HBV infection among pregnant women attending the Mahosot Prenatal Clinic (Vientiane Capital). . A retrospective study was performed in the Mahosot Hospital Laboratory to collect and analyze all the results of HBsAg testing in pregnant women from 2008 to 2014. . Of a total of 13,238 tested women of mean age of 26 years, 720 women (5,44% [95 CI: 5.1-5.8%]) were found HBsAg positive, the annual prevalence ranging from 4.6% to 6.2%. A slight but steady and significant decrease in prevalence over the 7 years of the study could be documented. . Although below the 8% hyperendemic threshold, the HBsAg prevalence observed in pregnant women in Vientiane reflects a high risk of HBV perinatal transmission and call for a widespread infant immunization with an HBV vaccine birth dose.
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http://dx.doi.org/10.1155/2017/1284273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5390595PMC
March 2017

Hydrological Regime and Water Shortage as Drivers of the Seasonal Incidence of Diarrheal Diseases in a Tropical Montane Environment.

PLoS Negl Trop Dis 2016 12 9;10(12):e0005195. Epub 2016 Dec 9.

Géosciences Environnement Toulouse, Université de Toulouse, CNES, CNRS, IRD, UPS, Toulouse, France.

Background: The global burden of diarrhea is a leading cause of morbidity and mortality worldwide. In montane areas of South-East Asia such as northern Laos, recent changes in land use have induced increased runoff, soil erosion and in-stream suspended sediment loads, and potential pathogen dissemination. To our knowledge, few studies have related diarrhea incidences to catchment scale hydrological factors such as river discharge, and loads of suspended sediment and of Fecal Indicator Bacteria (FIB) such as Escherichia coli, together with sociological factors such as hygiene practices. We hypothesized that climate factors combined with human behavior control diarrhea incidence, either because higher rainfall, leading to higher stream discharges, suspended sediment loads and FIB counts, are associated with higher numbers of reported diarrhea cases during the rainy season, or because water shortage leads to the use of less safe water sources during the dry season. Using E. coli as a FIB, the objectives of this study were thus (1) to characterize the epidemiological dynamics of diarrhea in Northern Laos, and (2) to identify which hydro-meteorological and sociological risk factors were associated with diarrhea epidemics.

Methods: Considering two unconnected river catchments of 22 and 7,448 km2, respectively, we conducted a retrospective time series analysis of meteorological variables (rainfall, air temperature), hydrological variables (discharge, suspended sediments, FIB counts, water temperature), and the number of diarrheal disease cases reported at 6 health centers located in the 5 southern districts of the Luang Prabang Province, Lao PDR. We also examined the socio-demographic factors potentially affecting vulnerability to the effect of the climate factors, such as drinking water sources, hygiene habits, and recreational water exposure.

Results: Using thus a mixed methods approach, we found E. coli to be present all year long (100-1,000 Most Probable Number or MPN 100 mL-1) indicating that fecal contamination is ubiquitous and constant. We found that populations switch their water supply from wells to surface water during drought periods, the latter of which appear to be at higher risk of bacterial contamination than municipal water fountains. We thus found that water shortage in the Luang Prabang area triggers diarrhea peaks during the dry and hot season and that rainfall and aquifer refill ends the epidemic during the wet season. The temporal trends of reported daily diarrhea cases were generally bimodal with hospital admissions peaking in February-March and later in May-July. Annual incidence rates were higher in more densely populated areas and mostly concerned the 0-4 age group and male patients.

Conclusions: We found that anthropogenic drivers, such as hygiene practices, were at least as important as environmental drivers in determining the seasonal pattern of a diarrhea epidemic. For diarrheal disease risk monitoring, discharge or groundwater level can be considered as relevant proxies. These variables should be monitored in the framework of an early warning system provided that a tradeoff is found between the size of the monitored catchment and the frequency of the measurement.
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http://dx.doi.org/10.1371/journal.pntd.0005195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5147807PMC
December 2016

Mycobacterium tuberculosis lineages and anti-tuberculosis drug resistance in reference hospitals across Viet Nam.

BMC Microbiol 2016 07 28;16(1):167. Epub 2016 Jul 28.

MIVEGEC (IRD 224-CNRS 5290-Université de Montpellier), Centre IRD, Montpellier, France.

Background: Mycobacterium tuberculosis, the tuberculosis (TB) pathogen, despite a low level of genetic diversity, has revealed a high variety of biological and epidemiological characteristics linked to their lineages, such as transmissibility, fitness and propensity to acquire drug resistance. This has important implications for the epidemiology of TB. We conducted this first countrywide cross-sectional study to identify the prevalent M. tuberculosis lineages and to assess their epidemiological associations and their relation to drug resistance. The study was conducted among isolates acquired in reference hospitals across Vietnam. Isolates with drug susceptibility testing profiles were identified for their lineages by spoligotyping. Logistic regression was used to investigate the association of M. tuberculosis lineages with location, age and sex of the patients and drug resistance levels.

Results: Results showed that the most prevalent lineage was Beijing (55.4 %), followed by EAI (27.5 %), T (6.4 %), LAM (1.3 %), Haarlem (1 %) and Zero type (0.3 %). The proportion of Beijing isolates in the North (70.4 %) and the South (68 %) was higher than in the Centre (28 %) (OR = 1.7 [95 % CI: 1.4-2.0], p < 0.0001), whereas the proportion of EAI isolates in the North (7.1 %) and the South (17 %) was much lower compared with the Centre (59 %) (OR = 0.5 [95 % CI: 0.4-0.6], p < 0.0001). Overall, Beijing isolates were the most likely to be drug-resistant and EAI isolates were the least likely to be drug-resistant, except in the South of Vietnam where EAI is also highly drug-resistant. The proportion of Beijing isolates was significantly higher (p < 0.01), and the proportion of EAI isolates was significantly lower (p < 0.05) in younger patients. The proportion of drug-resistance was higher in isolates collected from male patients and from patients in the middle age groups.

Conclusions: The findings suggest ongoing replacement of EAI lineage, which is mainly more drug-susceptible with highly drug-resistant Beijing lineage in all studied regions of Vietnam. Male patients of working ages should be the focus for better control to prevent the emergence of drug-resistant TB.
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http://dx.doi.org/10.1186/s12866-016-0784-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4964266PMC
July 2016

Prevalence and diversity of H9N2 avian influenza in chickens of Northern Vietnam, 2014.

Infect Genet Evol 2016 10 20;44:530-540. Epub 2016 Jun 20.

Oxford University Clinical Research Unit and Wellcome Trust Major Overseas Programme, Hanoi, Vietnam; Center for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK. Electronic address:

Despite their classification as low pathogenicity avian influenza viruses (LPAIV), A/H9N2 viruses cause significant losses in poultry in many countries throughout Asia, the Middle East and North Africa. To date, poultry surveillance in Vietnam has focused on detection of influenza H5 viruses, and there is limited understanding of influenza H9 epidemiology and transmission dynamics. We determined prevalence and diversity of influenza A viruses in chickens from live bird markets (LBM) of 7 northern Vietnamese provinces, using pooled oropharyngeal swabs collected from October to December 2014. Screening by real time RT-PCR revealed 1207/4900 (24.6%) of pooled swabs to be influenza A virus positive; overall prevalence estimates after accounting for pooling (5 swabs/pools) were 5.8% (CI 5.4-6.0). Subtyping was performed on 468 pooled swabs with M gene Ct<26. No influenza H7 was detected; 422 (90.1%) were H9 positive; and 22 (4.7%) were H5 positive. There was no evidence was of interaction between H9 and H5 virus detection rates. We sequenced 17 whole genomes of A/H9N2, 2 of A/H5N6, and 11 partial genomes. All H9N2 viruses had internal genes that clustered with genotype 57 and were closely related to Chinese human isolates of A/H7N9 and A/H10N8. Using a nucleotide divergence cutoff of 98%, we identified 9 distinct H9 genotypes. Phylogenetic analysis suggested multiple introductions of H9 viruses to northern Vietnam rather than in-situ transmission. Further investigations of H9 prevalence and diversity in other regions of Vietnam are warranted to assess H9 endemicity elsewhere in the country.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5036934PMC
http://dx.doi.org/10.1016/j.meegid.2016.06.038DOI Listing
October 2016

Added Value of Avian Influenza (H5) Day-Old Chick Vaccination for Disease Control in Egypt.

Avian Dis 2016 05;60(1 Suppl):245-52

C Food and Agriculture Organization of the United Nations, P.O. Box 2223, Cairo, Egypt.

The immunity profile against H5N1 highly pathogenic avian influenza (HPAI) in the commercial poultry value chain network in Egypt was modeled with the use of different vaccination scenarios. The model estimated the vaccination coverage, the protective seroconversion level, and the duration of immunity for each node of the network and vaccination scenario. Partial budget analysis was used to compare the benefit-cost of the different vaccination scenarios. The model predicted that targeting day-old chick avian influenza (AI) vaccination in industrial and large hatcheries would increase immunity levels in the overall poultry population in Egypt and especially in small commercial poultry farms (from <30% to >60%). This strategy was shown to be more efficient than the current strategy of using inactivated vaccines. Improving HPAI control in the commercial poultry sector in Egypt would have a positive impact to improve disease control.
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http://dx.doi.org/10.1637/11131-050715-ResNoteDOI Listing
May 2016

Evaluation of the SLOMYCO Sensititre(®) panel for testing the antimicrobial susceptibility of Mycobacterium marinum isolates.

Ann Clin Microbiol Antimicrob 2016 May 6;15:30. Epub 2016 May 6.

Département de Bactériologie-Virologie, CHRU Montpellier, Montpellier, France.

Background: The agar dilution method is currently considered as the reference method for Mycobacterium marinum drug susceptibility testing (DST). As it is time-consuming, alternative methods, such as the E-test, were evaluated for M. marinum DST, but without success. The SLOMYCO Sensititre(®) panel, recently commercialized by TREK Diagnostic Systems (Cleveland, OH), can be used for DST in slow-growing mycobacteria and for antimicrobial agents recommended by the Clinical and Laboratory Standards Institute (CLSI) for M. marinum DST. The main goal of this work was to evaluate the SLOMYCO Sensititre(®) panel method for DST in M. marinum isolates from human patients and fish relative to the reference agar dilution method.

Methods/results: The reproducibility of the minimum inhibitory concentration (MIC) determination (±1 log2 dilution) was very good for both the agar dilution method and SLOMYCO Sensititre(®) panel (>90 % agreement). The percentage essential agreement between methods varied, depending on the drug: between 97 and 75 % for ciprofloxacin, moxifloxacin, linezolid, isoniazid, clarithromycin, amikacin, rifabutin and rifampin, 74 % for trimethoprim, 72 % for doxycycline, 70 % for sulfamethoxazole, 59 % for streptomycin, 33 % for ethambutol and only 2.2 % for ethionamide. When the agar dilution and SLOMYCO Sensititre(®) panel results were converted into interpretive criteria, the category agreement was 100 % for amikacin, ciprofloxacin, clarithromycin, moxifloxacin, rifabutin, sulfamethoxazole and trimethoprim, 98 % for ethambutol and 96 % for rifampin and no agreement for doxycycline.

Conclusions: The SLOMYCO Sensititre(®) panel method could provide a potential alternative to the reference agar dilution method, when DST in M. marinum is required, except for doxycycline.
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http://dx.doi.org/10.1186/s12941-016-0145-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4858841PMC
May 2016

Seasonality of absolute humidity explains seasonality of influenza-like illness in Vietnam.

Epidemics 2015 Dec 28;13:65-73. Epub 2015 Aug 28.

Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Hanoi, Viet Nam; Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.

Background: Experimental and ecological studies have shown the role of climatic factors in driving the epidemiology of influenza. In particular, low absolute humidity (AH) has been shown to increase influenza virus transmissibility and has been identified to explain the onset of epidemics in temperate regions. Here, we aim to study the potential climatic drivers of influenza-like illness (ILI) epidemiology in Vietnam, a tropical country characterized by a high diversity of climates. We specifically focus on quantifying and explaining the seasonality of ILI.

Methods: We used 18 years (1993-2010) of monthly ILI notifications aggregated by province (52) and monthly climatic variables (minimum, mean, maximum temperatures, absolute and relative humidities, rainfall and hours of sunshine) from 67 weather stations across Vietnam. Seasonalities were quantified from global wavelet spectra, using the value of the power at the period of 1 year as a measure of the intensity of seasonality. The 7 climatic time series were characterized by 534 summary statistics which were entered into a regression tree to identify factors associated with the seasonality of AH. Results were extrapolated to the global scale using simulated climatic times series from the NCEP/NCAR project.

Results: The intensity of ILI seasonality in Vietnam is best explained by the intensity of AH seasonality. We find that ILI seasonality is weak in provinces experiencing weak seasonal fluctuations in AH (annual power <17.6), whereas ILI seasonality is strongest in provinces with pronounced AH seasonality (power >17.6). In Vietnam, AH and ILI are positively correlated.

Conclusions: Our results identify a role for AH in driving the epidemiology of ILI in a tropical setting. However, in contrast to temperate regions, high rather than low AH is associated with increased ILI activity. Fluctuation in AH may be the climate factor that underlies and unifies the seasonality of ILI in both temperate and tropical regions. Alternatively, the mechanism of action of AH on disease transmission may be different in cold-dry versus hot-humid settings.
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http://dx.doi.org/10.1016/j.epidem.2015.06.002DOI Listing
December 2015

Region-wide synchrony and traveling waves of dengue across eight countries in Southeast Asia.

Proc Natl Acad Sci U S A 2015 Oct 5;112(42):13069-74. Epub 2015 Oct 5.

Department of Biology, University of Florida, Gainesville, FL 32610; Emerging Pathogens Institute, University of Florida, Gainesville, FL 32610.

Dengue is a mosquito-transmitted virus infection that causes epidemics of febrile illness and hemorrhagic fever across the tropics and subtropics worldwide. Annual epidemics are commonly observed, but there is substantial spatiotemporal heterogeneity in intensity. A better understanding of this heterogeneity in dengue transmission could lead to improved epidemic prediction and disease control. Time series decomposition methods enable the isolation and study of temporal epidemic dynamics with a specific periodicity (e.g., annual cycles related to climatic drivers and multiannual cycles caused by dynamics in population immunity). We collected and analyzed up to 18 y of monthly dengue surveillance reports on a total of 3.5 million reported dengue cases from 273 provinces in eight countries in Southeast Asia, covering ∼ 10(7) km(2). We detected strong patterns of synchronous dengue transmission across the entire region, most markedly during a period of high incidence in 1997-1998, which was followed by a period of extremely low incidence in 2001-2002. This synchrony in dengue incidence coincided with elevated temperatures throughout the region in 1997-1998 and the strongest El Niño episode of the century. Multiannual dengue cycles (2-5 y) were highly coherent with the Oceanic Niño Index, and synchrony of these cycles increased with temperature. We also detected localized traveling waves of multiannual dengue epidemic cycles in Thailand, Laos, and the Philippines that were dependent on temperature. This study reveals forcing mechanisms that drive synchronization of dengue epidemics on a continental scale across Southeast Asia.
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http://dx.doi.org/10.1073/pnas.1501375112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4620875PMC
October 2015

A dengue outbreak on a floating village at Cat Ba Island in Vietnam.

BMC Public Health 2015 Sep 22;15:940. Epub 2015 Sep 22.

Oxford University Clinical Research Unit Hanoi, Hanoi, Vietnam.

Background: A dengue outbreak in an ecotourism destination spot in Vietnam, from September to November 2013, impacted a floating village of fishermen on the coastal island of Cat Ba. The outbreak raises questions about how tourism may impact disease spread in rural areas.

Methods: Epidemiological data were obtained from the Hai Phong Preventive Medical Center (PMC), including case histories and residential location from all notified dengue cases from this outbreak. All household addresses were geo-located. Knox test, a spatio-temporal analysis that enables inference dengue clustering constrained by space and time, was performed on the geocoded locations. From the plasma available from two patients, positive for Dengue serotype 3 virus (DENV3), the Envelope (E) gene was sequenced, and their genetic relationships compared to other E sequences in the region.

Results: Of 192 dengue cases, the odds ratio of contracting dengue infections for people living in the floating villages compared to those living on the island was 4.9 (95 % CI: 3.6-6.7). The space-time analyses on 111 geocoded dengue residences found the risk of dengue infection to be the highest within 4 days and a radius of 20 m of a given case. Of the total of ten detected clusters with an excess risk greater than 2, the cluster with the highest number of cases was in the floating village area (24 patients for a total duration of 31 days). Phylogenetic analysis revealed a high homology of the two DENV3 strains (genotype III) from Cat Ba with DENV3 viruses circulating in Hanoi in the same year (99.1 %).

Conclusions: Our study showed that dengue transmission is unlikely to be sustained on Cat Ba Island and that the 2013 epidemic likely originated through introduction of viruses from the mainland, potentially Hanoi. These findings suggest that prevention efforts should be focused on mainland rather than on the island.
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http://dx.doi.org/10.1186/s12889-015-2235-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4579793PMC
September 2015

Climatic-driven seasonality of emerging dengue fever in Hanoi, Vietnam.

BMC Public Health 2014 Oct 16;14:1078. Epub 2014 Oct 16.

Biostatistics and Medical Informatics Department, Institute of Training for Preventive Medicine and Public Health, Hanoi Medical University, Hanoi, Vietnam.

Background: Dengue fever (DF) has been emerging in Hanoi over the last decade. Both DF epidemiology and climate in Hanoi are strongly seasonal. This study aims at characterizing the seasonality of DF in Hanoi and its links to climatic variables as DF incidence increases from year to year.

Methods: Clinical suspected cases of DF from the 14 central districts of Hanoi were obtained from the Ministry of Health over a 8-year period (2002-2009). Wavelet decompositions were used to characterize the main periodic cycles of DF and climatic variables as well as the mean phase angles of these cycles. Cross-wavelet spectra between DF and each climatic variables were also computed. DF reproductive ratio was calculated from Soper's formula and smoothed to highlight both its long-term trend and seasonality.

Results: Temperature, rainfall, and vapor pressure show strong seasonality. DF and relative humidity show both strong seasonality and a sub-annual periodicity. DF reproductive ratio is increasing through time and displays two clear peaks per year, reflecting the sub-annual periodicity of DF incidence. Temperature, rainfall and vapor pressure lead DF incidence by a lag of 8-10 weeks, constant through time. Relative humidity leads DF by a constant lag of 18 weeks for the annual cycle and a lag decreasing from 14 to 5 weeks for the sub-annual cycle.

Conclusion: Results are interpreted in terms of mosquito population dynamics and immunological interactions between the different dengue serotypes in the human compartment. Given its important population size, its strong seasonality and its dengue emergence, Hanoi offers an ideal natural experiment to test hypotheses on dengue serotypes interactions, knowledge of prime importance for vaccine development.
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http://dx.doi.org/10.1186/1471-2458-14-1078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4287517PMC
October 2014