Global Role and Burden of Influenza in Pediatric Respiratory Hospitalizations, 1982-2012: A Systematic Analysis.

BACKGROUND: The global burden of pediatric severe respiratory illness is substantial, and influenza viruses contribute to this burden. Systematic surveillance and testing for influenza among hospitalized children has expanded globally over the past decade. However, only a fraction of the data has been used to estimate influenza burden. In this analysis, we use surveillance data to provide an estimate of influenza-associated hospitalizations among children worldwide. METHODS AND FINDINGS: We aggregated data from a systematic review (n = 108) and surveillance platforms (n = 37) to calculate a pooled estimate of the proportion of samples collected from children hospitalized with respiratory illnesses and positive for influenza by age group (<6 mo, <1 y, <2 y, <5 y, 5-17 y, and <18 y). We applied this proportion to global estimates of acute lower respiratory infection hospitalizations among children aged <1 y and <5 y, to obtain the number and per capita rate of influenza-associated hospitalizations by geographic region and socio-economic status. Influenza was associated with 10% (95% CI 8%-11%) of respiratory hospitalizations in children <18 y worldwide, ranging from 5% (95% CI 3%-7%) among children <6 mo to 16% (95% CI 14%-20%) among children 5-17 y. On average, we estimated that influenza results in approximately 374,000 (95% CI 264,000 to 539,000) hospitalizations in children <1 y-of which 228,000 (95% CI 150,000 to 344,000) occur in children <6 mo-and 870,000 (95% CI 610,000 to 1,237,000) hospitalizations in children <5 y annually. Influenza-associated hospitalization rates were more than three times higher in developing countries than in industrialized countries (150/100,000 children/year versus 48/100,000). However, differences in hospitalization practices between settings are an important limitation in interpreting these findings. CONCLUSIONS: Influenza is an important contributor to respiratory hospitalizations among young children worldwide. Increasing influenza vaccination coverage among young children and pregnant women could reduce this burden and protect infants <6 mo.

Differences in the Epidemiology of Human Cases of Avian Influenza A(H7N9) and A(H5N1) Viruses Infection.

BACKGROUND: The pandemic potential of avian influenza viruses A(H5N1) and A(H7N9) remains an unresolved but critically important question. METHODS: We compared the characteristics of sporadic and clustered cases of human H5N1 and H7N9 infection, estimated the relative risk of infection in blood-related contacts, and the reproduction number (R). RESULTS: We assembled and analyzed data on 720 H5N1 cases and 460 H7N9 cases up to 2 November 2014. The severity and average age of sporadic/index cases of H7N9 was greater than secondary cases (71% requiring intensive care unit admission vs 33%, P = .007; median age 59 years vs 31, P < .001). We observed no significant differences in the age and severity between sporadic/index and secondary H5N1 cases. The upper limit of the 95% confidence interval (CI) for R was 0.12 for H5N1 and 0.27 for H7N9. A higher proportion of H5N1 infections occurred in clusters (20%) compared to H7N9 (8%). The relative risk of infection in blood-related contacts of cases compared to unrelated contacts was 8.96 for H5N1 (95% CI, 1.30, 61.86) and 0.80 for H7N9 (95% CI, .32, 1.97). CONCLUSIONS: The results are consistent with an ascertainment bias towards severe and older cases for sporadic H7N9 but not for H5N1. The lack of evidence for ascertainment bias in sporadic H5N1 cases, the more pronounced clustering of cases, and the higher risk of infection in blood-related contacts, support the hypothesis that susceptibility to H5N1 may be limited and familial. This analysis suggests the potential pandemic risk may be greater for H7N9 than H5N1.

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

H5N1-SeroDetect EIA and rapid test: a novel differential diagnostic assay for serodiagnosis of H5N1 infections and surveillance.

Continuing evolution of highly pathogenic (HP) H5N1 influenza viruses in wild birds with transmission to domestic poultry and humans poses a pandemic threat. There is an urgent need for a simple and rapid serological diagnostic assay which can differentiate between antibodies to seasonal and H5N1 strains and that could provide surveillance tools not dependent on virus isolation and nucleic acid technologies. Here we describe the establishment of H5N1 SeroDetect enzyme-linked immunosorbent assay (ELISA) and rapid test assays based on three peptides in HA2 (488-516), PB1-F2 (2-75), and M2e (2-24) that are highly conserved within H5N1 strains. These peptides were identified by antibody repertoire analyses of H5N1 influenza survivors in Vietnam using whole-genome-fragment phage display libraries (GFPDLs). To date, both platforms have demonstrated high levels of sensitivity and specificity in detecting H5N1 infections (clade 1 and clade 2.3.4) in Vietnamese patients as early as 7 days and up to several years postinfection. H5N1 virus-uninfected individuals in Vietnam and the United States, including subjects vaccinated with seasonal influenza vaccines or with confirmed seasonal virus infections, did not react in the H5N1-SeroDetect assays. Moreover, sera from individuals vaccinated with H5N1 subunit vaccine with moderate anti-H5N1 neutralizing antibody titers did not react positively in the H5N1-SeroDetect ELISA or rapid test assays. The simple H5N1-SeroDetect ELISA and rapid tests could provide an important tool for large-scale surveillance for potential exposure to HP H5N1 strains in both humans and birds.

Social contexts of risk behaviors for HIV among male, unskilled, unregistered laborers in urban Vietnam.

In Vietnam there has been relatively little success in controlling the HIV epidemic, in part because the subpopulations most exposed to the virus are often difficult to engage in prevention research and programs. In this qualitative study we explored social contexts shaping HIV risk behaviors among Vietnamese men involved in unskilled, unregistered, and low-income labor in urban settings. Based on self-disclosed behaviors, it is clear that these men were at high risk of sexually transmitted infection (STI). Evidence emerged from the interview data highlighting equivalent influences of individual psychological factors, social integration, social barriers, and accessibility regarding drug use and sexual risk behavior. Psychological influences such as tedium, distress, fatalism and revenge, and the strong effects of collective decision making and fear of social isolation appeared important for these men living on the economic and social margins of this rapidly urbanizing society. The study findings suggest directions for research and culturally appropriate HIV preventive education and services for these men.

Epidemiological and comparative genomic analysis of Bacillus anthracis isolated from northern Vietnam.

To understand the epidemiological and genetic background of anthrax cases occurring in Vietnam from 2011 to 2015, we surveilled and genetically analyzed Bacillus anthracis isolated in the north of the country. Epidemiological surveillance showed that most human cutaneous anthrax cases occurred in association with animal dissection. Whole-genome sequences were obtained from six B. anthracis strains from human patients with cutaneous anthrax in the endemic area. Comparative genomic analysis showed that the genetic homogeneity among Vietnamese B. anthracis strains was very high. All Vietnamese B. anthracis strains belonged to the canSNP lineage of A.Br.011/009, which mostly consists of strains of the trans-Eurasian (TEA) group, including the most closely related strain, Carbosap. To clarify the genetic diversity of Vietnamese strains and strains belonging to A.Br.011/009 and A.Br.008/011 canSNP lineages, we applied a reference genome-based single-nucleotide polymorphism (SNP) and gene-by-gene genomic analysis (whole-genome MLST) strategy. The phylogeny from core genome SNPs revealed that the Vietnamese strains were positioned close to each other; moreover, several SNPs specific to Vietnamese B. anthracis were identified. Whole-genome MLST analysis revealed the differences in the number of SNPs between Vietnamese strains, which could enable discrimination at the strain level.

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

Impact of Adverse Events Following Immunization in Viet Nam in 2013 on chronic hepatitis B infection.

Adverse Events Following Immunization in Viet Nam in 2013 led to substantial reductions in hepatitis B vaccination coverage (both the birth dose and the three-dose series). In order to estimate the impact of the reduction in vaccination coverage on hepatitis B transmission and future mortality, a widely-used mathematical model was applied to the data from Viet Nam. Using the model, we estimated the number of chronic infections and deaths that are expected to occur in the birth cohort in 2013 and the number of excessive infections and deaths attributable to the drop in immunization coverage in 2013. An excess of 90,137 chronic infections and 17,456 future deaths were estimated to occur in the 2013 birth cohort due to the drop in vaccination coverage. This analysis highlights the importance of maintaining high vaccination coverage and swiftly responding to reported Adverse Events Following Immunization in order to regain consumer confidence in the hepatitis B vaccine.

Congenital rubella syndrome (CRS) in Vietnam 2011-2012--CRS epidemic after rubella epidemic in 2010-2011.

BACKGROUND: Rubella is endemic in Vietnam with epidemics occurring every 4-5 years. In 2011, Vietnam experienced the large nationwide rubella epidemic. During the rubella epidemic, many infants born with congenital rubella syndrome (CRS) were identified and reported from the neonatal units or cardiology departments of the national hospitals. To understand the burden of CRS, National Expanded Program on Immunization (NEPI) established sentinel CRS surveillance system. METHOD: Three national paediatric hospitals in Hanoi and Ho Chi Minh City (HCMC) were selected as CRS sentinel surveillance sites. Blood specimens from the infants were collected for rubella specific IgM and ELISA testing was performed at the national measles and rubella laboratory. RESULTS: From January 2011 to December 2012, 424 infants with suspected CRS were identified and reported. Among them 406 (96%) had specimens obtained, 284 (70%) cases were IgM positive including 279 laboratory confirmed CRS and 5 Congenital Rubella Infection (CRI). 13 cases were clinically confirmed and 127 (30%) were discarded. Total 292 infants were confirmed as CRS. Of the 292 infants with CRS, 69% of mothers had a history of "fever and rash" during pregnancy, of which 85% was in the first trimester. The most common clinical defects were congenital heart disease and cataract(s). However, 81.9% of the infants had a combination of major and minor signs and symptoms. Low birth weight in full term infants with confirmed CRS was observed in 114 infants (39%). CONCLUSIONS: The newly established CRS sentinel surveillance system documented the significant burden of CRS in Vietnam and provided evidence to the policy makers for the introduction of rubella containing vaccine (RCV) into Vietnam. This report highlights the importance of countries with rubella epidemic to establish CRS surveillance rapidly in order to support the introduction of RCV into the routine Expanded Programme on Immunization (EPI) immunization.

Thirty years of vaccination in Vietnam: Impact and cost-effectiveness of the national Expanded Programme on Immunization.

INTRODUCTION: Countries like Vietnam transitioning to middle-income status increasingly bear the cost of both existing and new vaccines. However, the impact and cost-effectiveness of the Expanded Programme on Immunization (EPI) as a whole has never been assessed on a country level. METHODS: Data on vaccine-preventable disease incidence and mortality from Vietnam's national surveillance was analysed to estimate the likely impact that vaccination in 1980-2010 may have had. Adjustment for under-reporting was made by examining trends in reported mumps incidence and in case-fatality risks for each disease. The same data were separately analysed using the Lives Saved Tool (LiST) to give an alternative estimate of impact. The financial cost of EPI in 1996-2010 was also estimated from the perspective of service provider. RESULTS: National surveillance data suggests that up to 5.7 million diseases cases and 26,000 deaths may have been prevented by EPI. Analysis using LiST suggests that even more deaths (370,000) may have been prevented by measles and pertussis vaccination alone. The cost-effectiveness of EPI is estimated to be around $1000-$27,000 per death prevented. CONCLUSION: Two separate approaches to assessing EPI impact in Vietnam give different quantitative results but a common conclusion: that EPI has made a substantial impact on mortality and represents good value for money.

Field evaluation of the establishment potential of wMelPop Wolbachia in Australia and Vietnam for dengue control.

BACKGROUND: Introduced Wolbachia bacteria can influence the susceptibility of Aedes aegypti mosquitoes to arboviral infections as well as having detrimental effects on host fitness. Previous field trials demonstrated that the wMel strain of Wolbachia effectively and durably invades Ae. aegypti populations. Here we report on trials of a second strain, wMelPop-PGYP Wolbachia, in field sites in northern Australia (Machans Beach and Babinda) and central Vietnam (Tri Nguyen, Hon Mieu Island), each with contrasting natural Ae. aegypti densities. METHODS: Mosquitoes were released at the adult or pupal stages for different lengths of time at the sites depending on changes in Wolbachia frequency as assessed through PCR assays of material collected through Biogents-Sentinel (BG-S) traps and ovitraps. Adult numbers were also monitored through BG-S traps. Changes in Wolbachia frequency were compared across hamlets or house blocks. RESULTS: Releases of adult wMelPop-Ae. aegypti resulted in the transient invasion of wMelPop in all three field sites. Invasion at the Australian sites was heterogeneous, reflecting a slower rate of invasion in locations where background mosquito numbers were high. In contrast, invasion across Tri Nguyen was relatively uniform. After cessation of releases, the frequency of wMelPop declined in all sites, most rapidly in Babinda and Tri Nguyen. Within Machans Beach the rate of decrease varied among areas, and wMelPop was detected for several months in an area with a relatively low mosquito density. CONCLUSIONS: These findings highlight challenges associated with releasing Wolbachia-Ae. aegypti combinations with low fitness, albeit strong virus interference properties, as a means of sustainable control of dengue virus transmission.

HIV/AIDS epidemics in Vietnam: evolution and responses.

The goal of this study was to describe the evolution of the HIV epidemic in Vietnam and its responses. Surveillance was conducted in 8 provinces in 1994, expanded to 12 in 1995, 20 in 1996, and 30 in 2001. Sentinel populations were sexually transmitted disease (STD) patients, female sex workers (FSWs), injection drug users (IDUs), tuberculosis (TB) patients, antenatal women, and military conscripts. Vietnam is in the concentrated epidemic stage. HIV prevalence had increased significantly in all surveillance population groups in the 1990s. HIV prevalence in the south is higher than in other regions of the country. The national HIV prevalence increased from 10.1% in 1996 to 32% in 2002 among IDUs, from 0.6% in 1994 to 6.6% in 2002 among FSWs, from 0.4% in 1994 to 2.4% in 2002 among STD patients, from 0.03% in 1994 to 0.34% in 2002 among pregnant women, from 0% in 1994 to 0.7% in 2002 among army military recruits, and from 0.5% in 1994 to 3.6% in 2002 among TB patients. The government has a strong commitment to control the epidemic and has implemented many activities for HIV prevention and control. Vietnam's HIV epidemic is predominantly among IDUs. Current intervention activities have not been sufficient to reduce HIV transmission. Vietnam needs to strengthen responses by scaling up the best practices in the most affected population groups by implementing internationally recognised effective interventions appropriately.

A reduction in chronic hepatitis B virus infection prevalence among children in Vietnam demonstrates the importance of vaccination.

BACKGROUND: Vietnam has high endemic hepatitis B virus infection with >8% of adults estimated to have chronic infection. Hepatitis B vaccine was first introduced in the national childhood immunization program in 1997 in high-risk areas, expanded nationwide in 2002, and included birth dose vaccination in 2003. This survey aimed to assess the impact of Vietnam's vaccination programme by estimating the prevalence of hepatitis B surface antigen (HBsAg) among children born during 2000-2008. METHODS: This nationally representative cross-sectional survey sampled children based on a stratified three-stage cluster design. Demographic and vaccination data were collected along with a whole blood specimen that was collected and interpreted in the field with a point-of-care HBsAg test. RESULTS: A total of 6,949 children were included in the survey analyses. The overall HBsAg prevalence among surveyed children was 2.70% (95% confidence interval (CI): 2.20-3.30). However, HBsAg prevalence was significantly higher among children born in 2000-2003 (3.64%) compared to children born 2007-2008 (1.64%) (prevalence ratio (PR: 2.22, CI 1.55-3.18)). Among all children included in the survey, unadjusted HBsAg prevalence among children with ≥3 doses of hepatitis B vaccine including a birth dose (1.75%) was significantly lower than among children with ≥3 doses of hepatitis B vaccine but lacked a birth dose (2.98%) (PR: 1.71, CI: 1.00-2.91) and significantly lower than among unvaccinated children (3.47%) (PR: 1.99, CI: 1.15-3.45). Infants receiving hepatitis B vaccine >7 days after birth had significantly higher HBsAg prevalence (3.20%) than those vaccinated 0-1 day after birth (1.52%) (PR: 2.09, CI: 1.27-3.46). CONCLUSION: Childhood chronic HBV infection prevalence has been markedly reduced in Vietnam due to vaccination. Further strengthening of timely birth dose vaccination will be important for reducing chronic HBV infection prevalence of under 5 children to <1%, a national and Western Pacific regional hepatitis B control goal.

Social contact patterns in Vietnam and implications for the control of infectious diseases.

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.

Sexual risk and bridging behaviors among young people in Hai Phong, Vietnam.

The risk of the HIV epidemic spreading from high-risk groups to the general population in Vietnam depends on sexual risk and bridging behaviors between high- and low-risk individuals. A cross-sectional study was used to describe sexual activities of youth aged 18-29 years. Nearly half (41.4%) were sexually active. Premarital sex was reported by 43.3% of them; 78.3% of sexually active males and 13.5% of sexually active females. Multiple sex partners were reported by 31.0%; 56.7% of males and 9.2% of females. Almost 27% of males and 5% of females engaged in sexual bridging behaviors. Being unmarried was significantly associated with having sex with non-regular partners. Being unmarried and early age at first intercourse were associated with having sex with a sex worker. Consistent condom use was high with commercial sex workers but low with regular partners. Education to delay early sexual debut, increased employment, and strategies to inform young sexually active people to adopt safer behaviors are urgently needed.

Lack of transmission of H5N1 avian-human reassortant influenza viruses in a ferret model.

Avian influenza A H5N1 viruses continue to spread globally among birds, resulting in occasional transmission of virus from infected poultry to humans. Probable human-to-human transmission has been documented rarely, but H5N1 viruses have not yet acquired the ability to transmit efficiently among humans, an essential property of a pandemic virus. The pandemics of 1957 and 1968 were caused by avian-human reassortant influenza viruses that had acquired human virus-like receptor binding properties. However, the relative contribution of human internal protein genes or other molecular changes to the efficient transmission of influenza viruses among humans remains poorly understood. Here, we report on a comparative ferret model that parallels the efficient transmission of H3N2 human viruses and the poor transmission of H5N1 avian viruses in humans. In this model, an H3N2 reassortant virus with avian virus internal protein genes exhibited efficient replication but inefficient transmission, whereas H5N1 reassortant viruses with four or six human virus internal protein genes exhibited reduced replication and no transmission. These findings indicate that the human virus H3N2 surface protein genes alone did not confer efficient transmissibility and that acquisition of human virus internal protein genes alone was insufficient for this 1997 H5N1 virus to develop pandemic capabilities, even after serial passages in a mammalian host. These results highlight the complexity of the genetic basis of influenza virus transmissibility and suggest that H5N1 viruses may require further adaptation to acquire this essential pandemic trait.

Intravenous drug use among street-based sex workers: a high-risk behavior for HIV transmission.

BACKGROUND: HIV prevalence among sex workers in Ho Chi Minh City has increased rapidly, from 6.5% in 1999 to 18.1% in 2000. This study examined whether injecting drug use among street-based sex workers (SSWs) in Ho Chi Minh City is a high-risk factor for HIV infection. GOAL: The goal of this study was to determine the correlates and prevalence of intravenous drug users among SSWs in Ho Chi Minh City. STUDY DESIGN: A cross-sectional study was conducted among SSWs in Ho Chi Minh City during December 2000. The SSWs were interviewed and tested for HIV-1. RESULTS: HIV-1 seroprevalence was 16.3%. Regression analysis indicated that injecting drugs and being younger than 25 years of age were independently associated with HIV seropositivity. CONCLUSION: Young SSWs who inject drugs are at the greatest risk of contracting HIV and acting as a bridge for HIV to the sexually active population.