Dr Peter Horby

Research Area: Global Health
Scientific Themes: Tropical Medicine & Global Health
Keywords: Public health, influenza, emerging infections, epidemiology and antibiotic resistance
Predicted geographic spread of swine-origin influenza A (H1N1) in Vietnam.  Medians from 1000 model simulations.

Predicted geographic spread of swine-origin influenza A (H1N1) in Vietnam. Medians from 1000 model ...

Training on taking swabs for a household-based influenza transmission study.

Training on taking swabs for a household-based influenza transmission study.

Peter Horby is Senior Clinical Research Fellow and the former Director of the Oxford University Clinical Research Unit in Hanoi, Vietnam. The unit was established in early 2006 and conducts research on infectious diseases which crosses the disciplines of basic science, medical science and public health. The Unit has offices at both the National Institute for Infectious and Tropical Diseases, and the National Institue for Hygiene and Epidemiology. Major interests of the group are influenza and other respiratory infections and antibiotic resistance.

Current projects include: a household-based community cohort to study the transmission of seasonal and pandemic influenza; the role of host genetics in modulating susceptibility to avian influenza A/H5N1; measuring social contact patterns relevant to infectious disease transmission in urban and rural settings; a study of the factors driving high rates of antibiotic resistance; quantifying the immunological selection pressures on influenza; the clinical and molecular epidemiology of Klebsiella pneumoniae infections.

There are no collaborations listed for this principal investigator.

Hoang TT, Dinh SN, Nguyen NV, Van Nguyen H, Horby P, Cobelens F, Wertheim HF. 2014. A household survey on screening practices of household contacts of smear positive tuberculosis patients in Vietnam. BMC Public Health, 14 (1), pp. 713. Read abstract | Read more

Close contacts of tuberculosis (TB) patients are at increased risk of developing tuberculosis. Although passive contact screening guidelines are incorporated in the national TB control program, currently it is unknown how frequent close contacts are screened for TB in Vietnam. This study assesses current contact screening practices in Vietnam and determines the proportion of household contacts screened of newly registered TB patients. Hide abstract

Huong VT, Ha N, Huy NT, Horby P, Nghia HD, Thiem VD, Zhu X, Hoa NT et al. 2014. Epidemiology, Clinical Manifestations, and Outcomes of Streptococcus suis Infection in Humans. Emerg Infect Dis, 20 (7), pp. 1105-1114. Read abstract | Read more

Streptococcus suis, a bacterium that affects pigs, is a neglected pathogen that causes systemic disease in humans. We conducted a systematic review and meta-analysis to summarize global estimates of the epidemiology, clinical characteristics, and outcomes of this zoonosis. We searched main literature databases for all studies through December 2012 using the search term "streptococcus suis." The prevalence of S. suis infection is highest in Asia; the primary risk factors are occupational exposure and eating of contaminated food. The pooled proportions of case-patients with pig-related occupations and history of eating high-risk food were 38.1% and 37.3%, respectively. The main clinical syndrome was meningitis (pooled rate 68.0%), followed by sepsis, arthritis, endocarditis, and endophthalmitis. The pooled case-fatality rate was 12.8%. Sequelae included hearing loss (39.1%) and vestibular dysfunction (22.7%). Our analysis identified gaps in the literature, particularly in assessing risk factors and sequelae of this infection. Hide abstract

Horby PW. 2014. Community studies of influenza: New knowledge, new questions The Lancet Respiratory Medicine, 2 (6), pp. 430-431. | Read more

Horby P. 2014. Systematic review and meta-analysis: For some groups traditionally considered to be 'high risk', the evidence of an increased risk of severe influenza-associated illness is poor quality Evidence-Based Medicine, 19 (3), pp. 110-110. | Read more

Thai PQ, Mai LQ, Welkers MRA, Hang NLK, Thanh LT, Dung VTV, Yen NTT, Duong TN et al. 2014. Pandemic H1N1 virus transmission and shedding dynamics in index case households of a prospective Vietnamese cohort Journal of Infection, 68 (6), pp. 581-590. Read abstract | Read more

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. © 2014 The Authors. Hide abstract

Peto L, Nadjm B, Horby P, Ngan TT, van Doorn R, Van Kinh N, Wertheim HF. 2014. The bacterial aetiology of adult community-acquired pneumonia in Asia: a systematic review. Trans R Soc Trop Med Hyg, 108 (6), pp. 326-337. Read abstract | Read more

Community-acquired pneumonia (CAP) is a major cause of adult mortality in Asia. Appropriate empirical treatment depends on knowledge of the pathogens commonly responsible. However, assessing the aetiological significance of identified organisms is often difficult, particularly with sputum isolates that might represent contamination with oropharyngeal flora. Hide abstract

Fox A, Whitehead S, Anders KL, Hoa LENM, Mai LEQ, Thai PQ, Yen NT, Duong TN et al. 2014. Investigation of dengue and Japanese encephalitis virus transmission in Hanam, Viet Nam. Am J Trop Med Hyg, 90 (5), pp. 892-896. Read abstract | Read more

This study investigated whether a large dengue epidemic that struck Hanoi in 2009 also affected a nearby semirural area. Seroconversion (dengue virus-reactive immunoglobulin G enzyme-linked immunosorbent assay) was high during 2009 compared with 2008, but neutralization assays showed that it was caused by both dengue virus and Japanese encephalitis virus infections. The findings highlight the importance of continued Japanese encephalitis virus vaccination and dengue surveillance. Hide abstract

Nga DOTT, Chuc NT, Hoa NP, Hoa NQ, Nguyen NT, Loan HT, Toan TK, Phuc HD et al. 2014. Antibiotic sales in rural and urban pharmacies in northern Vietnam: an observational study. BMC Pharmacol Toxicol, 15 (1), pp. 6. Read abstract | Read more

The irrational overuse of antibiotics should be minimized as it drives the development of antibiotic resistance, but changing these practices is challenging. A better understanding is needed of practices and economic incentives for antibiotic dispensing in order to design effective interventions to reduce inappropriate antibiotic use. Here we report on both quantitative and qualitative aspects of antibiotic sales in private pharmacies in northern Vietnam. Hide abstract

Wang C, Yu H, Horby PW, Cao B, Wu P, Yang S, Gao H, Li H et al. 2014. Comparison of patients hospitalized with influenza A subtypes H7N9, H5N1, and 2009 pandemic H1N1. Clin Infect Dis, 58 (8), pp. 1095-1103. Read abstract | Read more

Influenza A(H7N9) viruses isolated from humans show features suggesting partial adaptation to mammals. To provide insights into the pathogenesis of H7N9 virus infection, we compared risk factors, clinical presentation, and progression of patients hospitalized with H7N9, H5N1, and 2009 pandemic H1N1 (pH1N1) virus infections. Hide abstract

Thai PQ, Mai LEQ, Welkers MR, Hang NLEK, Thanh LET, Dung VT, Yen NT, Duong TN et al. 2014. Pandemic H1N1 virus transmission and shedding dynamics in index case households of a prospective Vietnamese cohort. J Infect, 68 (6), pp. 581-590. Read abstract | Read more

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. Hide abstract

Dunning JW, Merson L, Rohde GG, Gao Z, Semple MG, Tran D, Gordon A, Olliaro PL et al. 2014. Open source clinical science for emerging infections. Lancet Infect Dis, 14 (1), pp. 8-9. | Read more

Dao TT, Liebenthal D, Tran TK, Ngoc Thi Vu B, Ngoc Thi Nguyen D, Thi Tran HK, Thi Nguyen CK, Thi Vu HL et al. 2014. Klebsiella pneumoniae oropharyngeal carriage in rural and urban Vietnam and the effect of alcohol consumption. PLoS One, 9 (3), pp. e91999. Read abstract | Read more

Community acquired K. pneumoniae pneumonia is still common in Asia and is reportedly associated with alcohol use. Oropharyngeal carriage of K. pneumoniae could potentially play a role in the pathogenesis of K. pneumoniae pneumonia. However, little is known regarding K. pneumoniae oropharyngeal carriage rates and risk factors. This population-based cross-sectional study explores the association of a variety of demographic and socioeconomic factors, as well as alcohol consumption with oropharyngeal carriage of K. pneumoniae in Vietnam. Hide abstract

Horby PW. 2014. Community studies of influenza: new knowledge, new questions The Lancet Respiratory Medicine, | Read more

Horby P. 2014. For some groups traditionally considered to be 'high risk', the evidence of an increased risk of severe influenza-associated illness is poor quality. Evid Based Med, 19 (3), pp. 110. | Read more

Nguyen KV, Thi Do NT, Chandna A, Nguyen TV, Pham CV, Doan PM, Nguyen AQ, Thi Nguyen CK et al. 2013. Antibiotic use and resistance in emerging economies: a situation analysis for Viet Nam. BMC Public Health, 13 (1), pp. 1158. Read abstract | Read more

Antimicrobial resistance is a major contemporary public health threat. Strategies to contain antimicrobial resistance have been comprehensively set forth, however in developing countries where the need for effective antimicrobials is greatest implementation has proved problematic. A better understanding of patterns and determinants of antibiotic use and resistance in emerging economies may permit more appropriately targeted interventions.Viet Nam, with a large population, high burden of infectious disease and relatively unrestricted access to medication, is an excellent case study of the difficulties faced by emerging economies in controlling antimicrobial resistance. Hide abstract

Le MQ, Lam HM, Cuong VD, Lam TT, Halpin RA, Wentworth DE, Hien NT, Thanh LET, Phuong HV, Horby P, Boni MF. 2013. Migration and persistence of human influenza A viruses, Vietnam, 2001-2008. Emerg Infect Dis, 19 (11), pp. 1756-1765. Read abstract | Read more

Understanding global influenza migration and persistence is crucial for vaccine strain selection. Using 240 new human influenza A virus whole genomes collected in Vietnam during 2001-2008, we looked for persistence patterns and migratory connections between Vietnam and other countries. We found that viruses in Vietnam migrate to and from China, Hong Kong, Taiwan, Cambodia, Japan, South Korea, and the United States. We attempted to reduce geographic bias by generating phylogenies subsampled at the year and country levels. However, migration events in these phylogenies were still driven by the presence or absence of sequence data, indicating that an epidemiologic study design that controls for prevalence is required for robust migration analysis. With whole-genome data, most migration events are not detectable from the phylogeny of the hemagglutinin segment alone, although general migratory relationships between Vietnam and other countries are visible in the hemagglutinin phylogeny. It is possible that virus lineages in Vietnam persisted for >1 year. Hide abstract

Le MQ, Horby P, Fox A, Nguyen HT, Le Nguyen HK, Hoang PM, Nguyen KC, de Jong MD et al. 2013. Subclinical avian influenza A(H5N1) virus infection in human, Vietnam. Emerg Infect Dis, 19 (10), pp. 1674-1677. Read abstract | Read more

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. Hide abstract

Van Kerkhove MD, Hirve S, Koukounari A, Mounts AW, H1N1pdm serology working group. 2013. Estimating age-specific cumulative incidence for the 2009 influenza pandemic: a meta-analysis of A(H1N1)pdm09 serological studies from 19 countries. Influenza Other Respir Viruses, 7 (5), pp. 872-886. Read abstract | Read more

The global impact of the 2009 influenza A(H1N1) pandemic (H1N1pdm) is not well understood. Hide abstract

South East Asia Infectious Disease Clinical Research Network. 2013. Effect of double dose oseltamivir on clinical and virological outcomes in children and adults admitted to hospital with severe influenza: double blind randomised controlled trial. BMJ, 346 (may30 2), pp. f3039. Read abstract | Read more

To investigate the validity of recommendations in treatment guidelines to use higher than approved doses of oseltamivir in patients with severe influenza. Hide abstract

Alexander N, Fox A, Lien VTK, Dong T, Lee LY-H, Hang NLK, Mai LQ, Horby P. 2013. Defining ELISpot cut-offs from unreplicated test and control wells JOURNAL OF IMMUNOLOGICAL METHODS, 392 (1-2), pp. 57-62. Read abstract | Read more

In the absence of replication of wells, empirical criteria for enzyme-linked immunospot (ELISpot) positivity use fixed differences or ratios between spot forming units (SFU) counts between test and control. We propose an alternative approach which first identifies the optimally variance-stabilizing transformation of the SFU counts, based on the Bland-Altman plot of the test and control wells. The second step is to derive a positivity threshold from the difference in between-plate distribution functions of the transformed test and control SFU counts. This method is illustrated using 1309 assay results from a cohort study of influenza in Vietnam in which some, but not all, of the peptide pools have clear tendencies for SFU counts to be higher in test than control wells. © 2013 Elsevier B.V. Hide abstract

Horby PW, Pfeiffer D, Oshitani H. 2013. Prospects for emerging infections in East and southeast Asia 10 years after severe acute respiratory syndrome. Emerg Infect Dis, 19 (6), pp. 853-860. Read abstract | Read more

It is 10 years since severe acute respiratory syndrome (SARS) emerged, and East and Southeast Asia retain a reputation as a hot spot of emerging infectious diseases. The region is certainly a hot spot of socioeconomic and environmental change, and although some changes (e.g., urbanization and agricultural intensification) may reduce the probability of emerging infectious diseases, the effect of any individual emergence event may be increased by the greater concentration and connectivity of livestock, persons, and products. The region is now better able to detect and respond to emerging infectious diseases than it was a decade ago, but the tools and methods to produce sufficiently refined assessments of the risks of disease emergence are still lacking. Given the continued scale and pace of change in East and Southeast Asia, it is vital that capabilities for predicting, identifying, and controlling biologic threats do not stagnate as the memory of SARS fades. Hide abstract

Liverani M, Waage J, Barnett T, Pfeiffer DU, Rushton J, Rudge JW, Loevinsohn ME, Scoones I et al. 2013. Understanding and managing zoonotic risk in the new livestock industries. Environ Health Perspect, 121 (8), pp. 873-877. Read abstract | Read more

In many parts of the world, livestock production is undergoing a process of rapid intensification. The health implications of this development are uncertain. Intensification creates cheaper products, allowing more people to access animal-based foods. However, some practices associated with intensification may contribute to zoonotic disease emergence and spread: for example, the sustained use of antibiotics, concentration of animals in confined units, and long distances and frequent movement of livestock. Hide abstract

Horby P. 2013. H7N9 is a virus worth worrying about. Nature, 496 (7446), pp. 399. | Read more

Tran ST, Renschler JP, Le HT, Dang HT, Dao TM, Pham AN, Nguyen LT, Van Nguyen H et al. 2013. Correction: Diagnostic Accuracy of Microscopic Observation Drug Susceptibility (MODS) Assay for Pediatric Tuberculosis in Hanoi, Vietnam. PLoS One, 8 (9), Read abstract | Read more

[This corrects the article on p. e72100 in vol. 8.]. Hide abstract

Murhekar M, Arima Y, Horby P, Vandemaele KA, Vong S, Zijian F, Lee CK, Li A, World Health Organization Regional Office for the Western Pacific Event Management Team. 2013. Avian influenza A(H7N9) and the closure of live bird markets. Western Pac Surveill Response J, 4 (2), pp. 4-7. | Read more

Tran ST, Renschler JP, Le HT, Dang HT, Dao TM, Pham AN, Nguyen LT, Van Nguyen H et al. 2013. Diagnostic accuracy of microscopic Observation Drug Susceptibility (MODS) assay for pediatric tuberculosis in Hanoi, Vietnam. PLoS One, 8 (9), pp. e72100. Read abstract | Read more

icroscopic Observation Drug Susceptibility (MODS) has been shown to be an effective and rapid technique for early diagnosis of tuberculosis (TB). Thus far only a limited number of studies evaluating MODS have been performed in children and in extra-pulmonary tuberculosis. This study aims to assess relative accuracy and time to positive culture of MODS for TB diagnosis in children admitted to a general pediatric hospital in Vietnam. Hide abstract

Horby P, Nguyen NY, Dunstan SJ, Baillie JK. 2013. An updated systematic review of the role of host genetics in susceptibility to influenza. Influenza Other Respir Viruses, 7 Suppl 2 (SUPPL.2), pp. 37-41. Read abstract | Read more

The World Health Organization has identified studies of the role of host genetics on susceptibility to severe influenza as a priority. A systematic review was conducted in June 2011 to summarise the evidence on the role of host genetics in susceptibility to influenza, and this report updates that previously published review. Animal studies suggest that genetic control of susceptibility to severe influenza in mice is complex and not controlled by a single locus, but there is encouraging evidence that some of the host genetic determinants of susceptibility to severe disease may be common across influenza subtypes. Although a number of studies on genetic susceptibility to influenza in humans have been published recently, all are underpowered and unreplicated, so do not provide robust statistical evidence of an association between the identified genetic loci and susceptibility. One study does however present convincing functional evidence for an important role for IFITM3 in susceptibility to severe influenza in mice, and some evidence that this may also be important in human A/H1N1/pdm2009 infection. Hide abstract

Fox A, Hung TM, Wertheim H, Hoa LENM, Vincent A, Lang B, Waters P, Ha NH et al. 2013. Acute measles encephalitis in partially vaccinated adults. PLoS One, 8 (8), pp. e71671. Read abstract | Read more

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. Hide abstract

Dieu Ngan TT, Dat VQ, Trung NV, Ha NH, Van Kinh N, Thomas S, Larsson M, Diep NN, Rogier van Doorn H, Wertheim HFL, Horby P. 2013. First report of human psittacosis in Vietnam Journal of Infection, 66 (5), pp. 461-464. | Read more

Cauchemez S, Horby P, Fox A, Mai LEQ, Thanh LET, Thai PQ, Hoa LENM, Hien NT, Ferguson NM. 2012. Influenza infection rates, measurement errors and the interpretation of paired serology. PLoS Pathog, 8 (12), pp. e1003061. Read abstract | Read more

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. Hide abstract

Hai LET, Bich VT, Ngai LEK, Diep NT, Phuc PH, Hung VP, Taylor WR, Horby P, Liem NT, Wertheim HF. 2012. Fatal respiratory infections associated with rhinovirus outbreak, Vietnam. Emerg Infect Dis, 18 (11), pp. 1886-1888. Read abstract | Read more

During an outbreak of severe acute respiratory infections in 2 orphanages, Vietnam, 7/12 hospitalized children died. All hospitalized children and 26/43 children from outbreak orphanages tested positive for rhinovirus versus 9/40 control children (p = 0.0005). Outbreak rhinoviruses formed a distinct genetic cluster. Human rhinovirus is an underappreciated cause of severe pneumonia in vulnerable groups. Hide abstract

Tran TK, Eriksson B, Nguyen CT, Horby P, Bondjers G, Petzold M. 2012. DodaLab: an urban health and demographic surveillance site, the first three years in Hanoi, Vietnam. Scand J Public Health, 40 (8), pp. 765-772. Read abstract | Read more

Health and demographic surveillance sites (HDSSs) are important sources for health planning and policy in many low and middle income countries. Almost all HDSSs are in rural settings. The article aims to present the experiences and some concrete results for the first three years of operation of an urban HDSS in Hanoi, Vietnam, and discuss advantages and disadvantages of conducting health studies in HDSSs. Hide abstract

Wertheim HF, Ngoc DM, Wolbers M, Binh TT, Hải NT, Loan NQ, Tú PT, Sjodin A et al. 2012. Studying the effectiveness of activated carbon R95 respirators in reducing the inhalation of combustion by-products in Hanoi, Vietnam: a demonstration study. Environ Health, 11 (1), pp. 72. Read abstract | Read more

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. Hide abstract

Gething PW, Elyazar IR, Moyes CL, Smith DL, Battle KE, Guerra CA, Patil AP, Tatem AJ et al. 2012. A long neglected world malaria map: Plasmodium vivax endemicity in 2010. PLoS Negl Trop Dis, 6 (9), pp. e1814. Read abstract | Read more

Current understanding of the spatial epidemiology and geographical distribution of Plasmodium vivax is far less developed than that for P. falciparum, representing a barrier to rational strategies for control and elimination. Here we present the first systematic effort to map the global endemicity of this hitherto neglected parasite. Hide abstract

Larsson M, Nguyen LH, Wertheim HF, Dao TT, Taylor W, Horby P, Nguyen TV, Nguyen MH, Le T, Nguyen KV. 2012. Clinical characteristics and outcome of Penicillium marneffei infection among HIV-infected patients in northern Vietnam. AIDS Res Ther, 9 (1), pp. 24. Read abstract | Read more

This study reports the clinical characteristics and outcome of HIV-associated Penicilliummarneffei infection in northern Vietnam. Hide abstract

Dawood FS, Iuliano AD, Reed C, Shay DK, Cheng P-Y, Montgomery JM, Bresee J, Widdowson M-A et al. 2012. Estimated global mortality associated with the first 12 months of 2009 pandemic influenza A H1N1 virus circulation: A modelling study The Lancet Infectious Diseases, 12 (9), pp. 687-695. Read abstract | Read more

Background: 18 500 laboratory-confirmed deaths caused by the 2009 pandemic influenza A H1N1 were reported worldwide for the period April, 2009, to August, 2010. This number is likely to be only a fraction of the true number of the deaths associated with 2009 pandemic influenza A H1N1. We aimed to estimate the global number of deaths during the first 12 months of virus circulation in each country. Methods: We calculated crude respiratory mortality rates associated with the 2009 pandemic influenza A H1N1 strain by age (0-17 years, 18-64 years, and >64 years) using the cumulative (12 months) virus-associated symptomatic attack rates from 12 countries and symptomatic case fatality ratios (sCFR) from five high-income countries. To adjust crude mortality rates for differences between countries in risk of death from influenza, we developed a respiratory mortality multiplier equal to the ratio of the median lower respiratory tract infection mortality rate in each WHO region mortality stratum to the median in countries with very low mortality. We calculated cardiovascular disease mortality rates associated with 2009 pandemic influenza A H1N1 infection with the ratio of excess deaths from cardiovascular and respiratory diseases during the pandemic in five countries and multiplied these values by the crude respiratory disease mortality rate associated with the virus. Respiratory and cardiovascular mortality rates associated with 2009 pandemic influenza A H1N1 were multiplied by age to calculate the number of associated deaths. Findings: We estimate that globally there were 201 200 respiratory deaths (range 105 700-395 600) with an additional 83 300 cardiovascular deaths (46 000-179 900) associated with 2009 pandemic influenza A H1N1. 80% of the respiratory and cardiovascular deaths were in people younger than 65 years and 51% occurred in southeast Asia and Africa. Interpretation: Our estimate of respiratory and cardiovascular mortality associated with the 2009 pandemic influenza A H1N1 was 15 times higher than reported laboratory-confirmed deaths. Although no estimates of sCFRs were available from Africa and southeast Asia, a disproportionate number of estimated pandemic deaths might have occurred in these regions. Therefore, efforts to prevent influenza need to effectively target these regions in future pandemics. Funding: None. © 2012 Elsevier Ltd. Hide abstract

Taylor WR, Nguyen K, Nguyen D, Nguyen H, Horby P, Nguyen HL, Lien T, Tran G et al. 2012. The spectrum of central nervous system infections in an adult referral hospital in Hanoi, Vietnam. PLoS One, 7 (8), pp. e42099. Read abstract | Read more

To determine prospectively the causative pathogens of central nervous system (CNS) infections in patients admitted to a tertiary referral hospital in Hanoi, Vietnam. Hide abstract

Horby P, Mai LQ, Fox A, Thai PQ, Thi Thu Yen N, Thanh LT, Le Khanh Hang N, Duong TN et al. 2012. The epidemiology of interpandemic and pandemic influenza in Vietnam, 2007-2010 American Journal of Epidemiology, 175 (10), pp. 1062-1074. Read abstract | Read more

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. © The Author 2012. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.2012This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. © The Author 2012. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. Hide abstract

Horby P, Nguyen NY, Dunstan SJ, Baillie JK. 2012. The role of host genetics in susceptibility to influenza: a systematic review. PLoS One, 7 (3), pp. e33180. Read abstract | Read more

The World Health Organization has identified studies of the role of host genetics on susceptibility to severe influenza as a priority. A systematic review was conducted to summarize the current state of evidence on the role of host genetics in susceptibility to influenza (PROSPERO registration number: CRD42011001380). Hide abstract

Fox A, Le NM, Horby P, van Doorn HR, Nguyen VT, Nguyen HH, Nguyen TC, Vu DP et al. 2012. Severe pandemic H1N1 2009 infection is associated with transient NK and T deficiency and aberrant CD8 responses. PLoS One, 7 (2), pp. e31535. Read abstract | Read more

It is unclear why the severity of influenza varies in healthy adults or why the burden of severe influenza shifts to young adults when pandemic strains emerge. One possibility is that cross-protective T cell responses wane in this age group in the absence of recent infection. We therefore compared the acute cellular immune response in previously healthy adults with severe versus mild pandemic H1N1 infection. Hide abstract

Powell TJ, Fox A, Peng Y, Quynh Mai LET, Lien VT, Hang NL, Wang L, Lee LY et al. 2012. Identification of H5N1-specific T-cell responses in a high-risk cohort in vietnam indicates the existence of potential asymptomatic infections. J Infect Dis, 205 (1), pp. 20-27. Read abstract | Read more

Most reported human H5N1 viral infections have been severe and were detected after hospital admission. A case ascertainment bias may therefore exist, with mild cases or asymptomatic infections going undetected. We sought evidence of mild or asymptomatic H5N1 infection by examining H5N1-specific T-cell and antibody responses in a high-risk cohort in Vietnam. Hide abstract

Khurana S, Sasono P, Fox A, Nguyen VK, Le QM, Pham QT, Nguyen TH, Nguyen TL, Horby P, Golding H. 2011. H5N1-SeroDetect EIA and rapid test: a novel differential diagnostic assay for serodiagnosis of H5N1 infections and surveillance. J Virol, 85 (23), pp. 12455-12463. Read abstract | Read more

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. Hide abstract

Cuong HQ, Hien NT, Duong TN, Phong TV, Cam NN, Farrar J, Nam VS, Thai KT, Horby P. 2011. Quantifying the emergence of dengue in Hanoi, Vietnam: 1998-2009. PLoS Negl Trop Dis, 5 (9), pp. e1322. Read abstract | Read more

An estimated 2.4 billion people live in areas at risk of dengue transmission, therefore the factors determining the establishment of endemic dengue in areas where transmission suitability is marginal is of considerable importance. Hanoi, Vietnam is such an area, and following a large dengue outbreak in 2009, we set out to determine if dengue is emerging in Hanoi. Hide abstract

Fox A, Le NM, Simmons CP, Wolbers M, Wertheim HF, Pham TK, Tran TH, Trinh TM et al. 2011. Immunological and viral determinants of dengue severity in hospitalized adults in Ha Noi, Viet Nam. PLoS Negl Trop Dis, 5 (3), pp. e967. Read abstract | Read more

The relationships between the infecting dengue serotype, primary and secondary infection, viremia and dengue severity remain unclear. This cross-sectional study examined these interactions in adult patients hospitalized with dengue in Ha Noi. Hide abstract

Horby P, Pham QT, Hens N, Nguyen TT, Le QM, Dang DT, Nguyen ML, Nguyen TH et al. 2011. Social contact patterns in Vietnam and implications for the control of infectious diseases. PLoS One, 6 (2), pp. e16965. Read abstract | Read more

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. Hide abstract

Bui HM, Clements AC, Nguyen QT, Nguyen MH, Le XH, Hay SI, Tran TH, Wertheim HF, Snow RW, Horby P. 2011. Social and environmental determinants of malaria in space and time in Viet Nam. Int J Parasitol, 41 (1), pp. 109-116. Read abstract | Read more

The malaria burden in Viet Nam has been in decline in recent decades, but localised areas of high transmission remain. We used spatiotemporal analytical tools to determine the social and environmental drivers of malaria risk and to identify residual high-risk areas where control and surveillance resources can be targeted. Counts of reported Plasmodium falciparum and Plasmodium vivax malaria cases by month (January 2007-December 2008) and by district were assembled. Zero-inflated Poisson regression models were developed in a bayesian framework. Models had the percentage of the district's population living below the poverty line, percent of the district covered by forest, median elevation, median long-term average precipitation, and minimum temperature included as fixed effects, and terms for temporal trend and residual district-level spatial autocorrelation. Strong temporal and spatial heterogeneity in counts of malaria cases was apparent. Poverty and forest cover were significantly associated with an increased count of malaria cases but the magnitude and direction of associations between climate and malaria varied by socio-ecological zone. There was a declining trend in counts of malaria cases during the study period. After accounting for the social and environmental fixed effects, substantial spatial heterogeneity was still evident. Unmeasured factors which may contribute to this residual variation include malaria control activities, population migration and accessibility to health care. Forest-related activities and factors encompassed by poverty indicators are major drivers of malaria incidence in Viet Nam. Hide abstract

Horby P. 2010. Why are so few people infected with influenza A (H5N1) despite a large exposed population? The role of host genetics INFLUENZA AND OTHER RESPIRATORY VIRUSES, 4 pp. 40-40.

Horby P, Sudoyo H, Viprakasit V, Fox A, Thai PQ, Yu H, Davila S, Hibberd M et al. 2010. What is the evidence of a role for host genetics in susceptibility to influenza A/H5N1? Epidemiol Infect, 138 (11), pp. 1550-1558. Read abstract | Read more

The apparent family clustering of avian influenza A/H5N1 has led several groups to postulate the existence of a host genetic influence on susceptibility to A/H5N1, yet the role of host factors on the risk of A/H5N1 disease has received remarkably little attention compared to the efforts focused on viral factors. We examined the epidemiological patterns of human A/H5N1 cases, their possible explanations, and the plausibility of a host genetic effect on susceptibility to A/H5N1 infection. The preponderance of familial clustering of cases and the relative lack of non-familial clusters, the occurrence of related cases separated by time and place, and the paucity of cases in some highly exposed groups such as poultry cullers, are consistent with a host genetic effect. Animal models support the biological plausibility of genetic susceptibility to A/H5N1. Although the evidence is circumstantial, host genetic factors are a parsimonious explanation for the unusual epidemiology of human A/H5N1 cases and warrant further investigation. Hide abstract

Wertheim HF, Horby P, Viet TL, Tanh TNT, Woodall J. 2010. The making of a world atlas of infectious diseases INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES, 14 pp. E282-E283. | Read more

Le QM, Wertheim HF, Tran ND, van Doorn HR, Nguyen TH, Horby P, Vietnam H1N1 Investigation Team. 2010. A community cluster of oseltamivir-resistant cases of 2009 H1N1 influenza. N Engl J Med, 362 (1), pp. 86-87. | Read more

Horby P, Wertheim H, Ha NH, Trung NV, Trinh DT, Taylor W, Ha NM, Lien TT, Farrar J, Van Kinh N. 2010. Stimulating the development of national Streptococcus suis guidelines in Viet Nam through a strategic research partnership. Bull World Health Organ, 88 (6), pp. 458-461. Read abstract | Read more

Streptococcus suis is a common cause of adult bacterial meningitis in Viet Nam, and possibly other parts of Asia, yet this disabling infection has been largely neglected. Prevention, diagnosis and treatment are relatively straightforward and affordable but, in early 2007, no national diagnostic, case management or prevention guidelines existed in Viet Nam. Hide abstract

Fox A, Horby P, Ha NH, Hoa LENM, Lam NT, Simmons C, Farrar J, Van Kinh N, Wertheim H. 2010. Influenza A H5N1 and HIV co-infection: case report. BMC Infect Dis, 10 (1), pp. 167. Read abstract | Read more

The role of adaptive immunity in severe influenza is poorly understood. The occurrence of influenza A/H5N1 in a patient with HIV provided a rare opportunity to investigate this. Hide abstract

Taylor WR, Burhan E, Wertheim H, Soepandi PZ, Horby P, Fox A, Benamore R, de Simone L, Hien TT, Chappuis F. 2010. Avian influenza--a review for doctors in travel medicine. Travel Med Infect Dis, 8 (1), pp. 1-12. Read abstract | Read more

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. Hide abstract

Taylor WR, Tran GV, Nguyen TQ, Dang DV, Nguyen VK, Nguyen CT, Nguyen LT, Luong CQ et al. 2009. Acute febrile myalgia in Vietnam due to trichinellosis following the consumption of raw pork. Clin Infect Dis, 49 (7), pp. e79-e83. Read abstract | Read more

Trichinellosis outbreaks occur occasionally in Vietnam following the consumption of undercooked pork. Diagnosing trichinella can be problematic because fever and myalgia are nonspecific, and diagnosis may be delayed. We describe 5 Vietnamese patients in whom trichinellosis was diagnosed after several weeks of illness. Hide abstract

Liem NT, Tung CV, Hien ND, Hien TT, Chau NQ, Long HT, Hien NT, Mai LEQ et al. 2009. Clinical features of human influenza A (H5N1) infection in Vietnam: 2004-2006. Clin Infect Dis, 48 (12), pp. 1639-1646. Read abstract | Read more

The first cases of avian influenza A (H5N1) in humans in Vietnam were detected in early 2004, and Vietnam has reported the second highest number of cases globally. Hide abstract

Wertheim HF, Nguyen TQ, Nguyen KA, de Jong MD, Taylor WR, Le TV, Nguyen HH, Nguyen HT, Farrar J, Horby P, Nguyen HD. 2009. Furious rabies after an atypical exposure. PLoS Med, 6 (3), pp. e44. | Read more

Wertheim HF, Nguyen HN, Taylor W, Lien TT, Ngo HT, Nguyen TQ, Nguyen BN, Nguyen HH et al. 2009. Streptococcus suis, an important cause of adult bacterial meningitis in northern Vietnam. PLoS One, 4 (6), pp. e5973. Read abstract | Read more

Streptococcus suis can cause severe systemic infection in adults exposed to infected pigs or after consumption of undercooked pig products. S. suis is often misdiagnosed, due to lack of awareness and improper testing. Here we report the first fifty cases diagnosed with S. suis infection in northern Viet Nam. Hide abstract

Boni MF, Manh BH, Thai PQ, Farrar J, Hien TT, Hien NT, Van Kinh N, Horby P. 2009. Modelling the progression of pandemic influenza A (H1N1) in Vietnam and the opportunities for reassortment with other influenza viruses. BMC Med, 7 (1), pp. 43. Read abstract | Read more

A novel variant of influenza A (H1N1) is causing a pandemic and, although the illness is usually mild, there are concerns that its virulence could change through reassortment with other influenza viruses. This is of greater concern in parts of Southeast Asia, where the population density is high, influenza is less seasonal, human-animal contact is common and avian influenza is still endemic. Hide abstract

Wertheim HF, Farrar J, Horby P. 2009. Online video sharing and patients' privacy. BMJ, 339 pp. b3991. | Read more

Phan PH, Wertheim H, Luong ST, Ngo BT, Pham HV, Nguyen TT, Le HT, Taylor W, Horby P, Liem NT. 2008. Fatal Lower Respiratory Tract Infections with Rhinovirus A in Infants in Vietnam INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES, 12 pp. E81-E81. | Read more

Nguyen TH, Farrar J, Horby P. 2008. Person-to-person transmission of influenza A (H5N1). Lancet, 371 (9622), pp. 1392-1394. | Read more

Taylor WR, Thinh BN, Anh GT, Horby P, Wertheim H, Lindegardh N, de Jong MD, Stepniewska K et al. 2008. Oseltamivir is adequately absorbed following nasogastric administration to adult patients with severe H5N1 influenza. PLoS One, 3 (10), pp. e3410. Read abstract | Read more

In the absence of a parenteral drug, oral oseltamivir is currently recommended by the WHO for treating H5N1 influenza. Whether oseltamivir absorption is adequate in severe influenza is unknown. We measured the steady state, plasma concentrations of nasogastrically administered oseltamivir 150 mg bid and its active metabolite, oseltamivir carboxylate (OC), in three, mechanically ventilated patients with severe H5N1 (male, 30 yrs; pregnant female, 22 yrs) and severe H3N2 (female, 76 yrs). Treatments were started 6, 7 and 8 days after illness onset, respectively. Both females were sampled while on continuous venovenous haemofiltration. Admission and follow up specimens (trachea, nose, throat, rectum, blood) were tested for RNA viral load by reverse transcriptase PCR. In vitro virus susceptibility to OC was measured by a neuraminidase inhibition assay. Admission creatinine clearances were 66 (male, H5N1), 82 (female, H5N1) and 6 (H3N2) ml/min. Corresponding AUC(0-12) values (5932, 10,951 and 34,670 ng.h/ml) and trough OC concentrations (376, 575 and 2730 ng/ml) were higher than previously reported in healthy volunteers; the latter exceeded 545 to 3956 fold the H5N1 IC(50) (0.69 ng/ml) isolated from the H5N1 infected female. Two patients with follow-up respiratory specimens cleared their viruses after 5 (H5N1 male) and 5 (H3N2 female) days of oseltamivir. Both female patients died of respiratory failure; the male survived. 150 mg bid of oseltamivir was well absorbed and converted extensively to OC. Virus was cleared in two patients but two patients died, suggesting viral efficacy but poor clinical efficacy. Hide abstract

Le MT, Wertheim HF, Nguyen HD, Taylor W, Hoang PV, Vuong CD, Nguyen HL, Nguyen HH et al. 2008. Influenza A H5N1 clade 2.3.4 virus with a different antiviral susceptibility profile replaced clade 1 virus in humans in northern Vietnam. PLoS One, 3 (10), pp. e3339. Read abstract | Read more

Prior to 2007, highly pathogenic avian influenza (HPAI) H5N1 viruses isolated from poultry and humans in Vietnam were consistently reported to be clade 1 viruses, susceptible to oseltamivir but resistant to amantadine. Here we describe the re-emergence of human HPAI H5N1 virus infections in Vietnam in 2007 and the characteristics of the isolated viruses. Hide abstract

Horby P. 2007. Determining risk factors for infection with influenza A (H5N1) - Response EMERGING INFECTIOUS DISEASES, 13 (6), pp. 956-956.

Tuan PA, Horby P, Dinh PN, Mai LT, Zambon M, Shah J, Huy VQ, Bloom S et al. 2007. SARS transmission in Vietnam outside of the health-care setting. Epidemiol Infect, 135 (3), pp. 392-401. Read abstract | Read more

To evaluate the risk of transmission of SARS coronavirus outside of the health-care setting, close household and community contacts of laboratory-confirmed SARS cases were identified and followed up for clinical and laboratory evidence of SARS infection. Individual- and household-level risk factors for transmission were investigated. Nine persons with serological evidence of SARS infection were identified amongst 212 close contacts of 45 laboratory-confirmed SARS cases (secondary attack rate 4.2%, 95% CI 1.5-7). In this cohort, the average number of secondary infections caused by a single infectious case was 0.2. Two community contacts with laboratory evidence of SARS coronavirus infection had mild or sub-clinical infection, representing 3% (2/65) of Vietnamese SARS cases. There was no evidence of transmission of infection before symptom onset. Physically caring for a symptomatic laboratory-confirmed SARS case was the only independent risk factor for SARS transmission (OR 5.78, 95% CI 1.23-24.24). Hide abstract

Horby P. 2007. The global war on terrorism. Clin Infect Dis, 44 (1), pp. 151. | Read more

Roberton SI, Bell DJ, Smith GJ, Nicholls JM, Chan KH, Nguyen DT, Tran PQ, Streicher U et al. 2006. Avian influenza H5N1 in viverrids: implications for wildlife health and conservation. Proc Biol Sci, 273 (1595), pp. 1729-1732. Read abstract | Read more

The Asian countries chronically infected with avian influenza A H5N1 are 'global hotspots' for biodiversity conservation in terms of species diversity, endemism and levels of threat. Since 2003, avian influenza A H5N1 viruses have naturally infected and killed a range of wild bird species, four felid species and a mustelid. Here, we report fatal disseminated H5N1 infection in a globally threatened viverrid, the Owston's civet, in Vietnam, highlighting the risk that avian influenza H5N1 poses to mammalian and avian biodiversity across its expanding geographic range. Hide abstract

Reynolds MG, Anh BH, Thu VH, Montgomery JM, Bausch DG, Shah JJ, Maloney S, Leitmeyer KC et al. 2006. Factors associated with nosocomial SARS-CoV transmission among healthcare workers in Hanoi, Vietnam, 2003. BMC Public Health, 6 pp. 207. Read abstract | Read more

In March of 2003, an outbreak of Severe Acute Respiratory Syndrome (SARS) occurred in Northern Vietnam. This outbreak began when a traveler arriving from Hong Kong sought medical care at a small hospital (Hospital A) in Hanoi, initiating a serious and substantial transmission event within the hospital, and subsequent limited spread within the community. Hide abstract

World Health Organization Writing Group, Bell D, Nicoll A, Fukuda K, Horby P, Monto A, Hayden F, Wylks C, Sanders L, Van Tam J. 2006. Non-pharmaceutical interventions for pandemic influenza, international measures. Emerg Infect Dis, 12 (1), pp. 81-87. Read abstract | Read more

Since global availability of vaccine and antiviral agents against influenza caused by novel human subtypes is insufficient, the World Health Organization (WHO) recommends non-pharmaceutical public health interventions to contain infection, delay spread, and reduce the impact of pandemic disease. Virus transmission characteristics will not be completely known in advance, but difficulties in influenza control typically include peak infectivity early in illness, a short interval between cases, and to a lesser extent, transmission from persons with incubating or asymptomatic infection. Screening and quarantining entering travelers at international borders did not substantially delay virus introduction in past pandemics, except in some island countries, and will likely be even less effective in the modern era. Instead, WHO recommends providing information to international travelers and possibly screening travelers departing countries with transmissible human infection. The principal focus of interventions against pandemic influenza spread should be at national and community levels rather than international borders. Hide abstract

World Health Organization Writing Group, Bell D, Nicoll A, Fukuda K, Horby P, Monto A, Hayden F, Wylks C, Sanders L, van Tam J. 2006. Non-pharmaceutical interventions for pandemic influenza, national and community measures. Emerg Infect Dis, 12 (1), pp. 88-94. Read abstract | Read more

The World Health Organization's recommended pandemic influenza interventions, based on limited data, vary by transmission pattern, pandemic phase, and illness severity and extent. In the pandemic alert period, recommendations include isolation of patients and quarantine of contacts, accompanied by antiviral therapy. During the pandemic period, the focus shifts to delaying spread and reducing effects through population-based measures. Ill persons should remain home when they first become symptomatic, but forced isolation and quarantine are ineffective and impractical. If the pandemic is severe, social distancing measures such as school closures should be considered. Nonessential domestic travel to affected areas should be deferred. Hand and respiratory hygiene should be routine; mask use should be based on setting and risk, and contaminated household surfaces should be disinfected. Additional research and field assessments during pandemics are essential to update recommendations. Legal authority and procedures for implementing interventions should be understood in advance and should respect cultural differences and human rights. Hide abstract

Dinh PN, Long HT, Tien NT, Hien NT, Mai LETQ, Phong LEH, Tuan LEV, Van Tan H et al. 2006. Risk factors for human infection with avian influenza A H5N1, Vietnam, 2004. Emerg Infect Dis, 12 (12), pp. 1841-1847. Read abstract | Read more

To evaluate risk factors for human infection with influenza A subtype H5N1, we performed a matched case-control study in Vietnam. We enrolled 28 case-patients who had laboratory-confirmed H5N1 infection during 2004 and 106 age-, sex-, and location-matched control-respondents. Data were analyzed by matched-pair analysis and multivariate conditional logistic regression. Factors that were independently associated with H5N1 infection were preparing sick or dead poultry for consumption < or =7 days before illness onset (matched odds ratio [OR] 8.99, 95% confidence interval [CI] 0.98-81.99, p = 0.05), having sick or dead poultry in the household < or =7 days before illness onset (matched OR 4.94, 95% CI 1.21-20.20, p = 0.03), and lack of an indoor water source (matched OR 6.46, 95% CI 1.20-34.81, p = 0.03). Factors not significantly associated with infection were raising healthy poultry, preparing healthy poultry for consumption, and exposure to persons with an acute respiratory illness. Hide abstract

Horby P, Macintyre CR, McIntyre PB, Gilbert GL, Staff M, Hanlon M, Heron LG, Cagney M, Bennett C. 2005. A boarding school outbreak of pertussis in adolescents: value of laboratory diagnostic methods. Epidemiol Infect, 133 (2), pp. 229-236. Read abstract | Read more

Culture for Bordetella pertussis (B. pertussis) is the traditional gold standard for laboratory diagnosis of pertussis but is insensitive, especially later in the course of illness and in vaccinated persons. Interpretation of serology is limited by the lack of an appropriate reference standard. An outbreak of pertussis in a crowded boarding-school dormitory allowed evaluation of laboratory correlates of infection. Questionnaires, serum samples and throat swabs were collected from members of the exposed group. Serum samples from unexposed controls of a similar age group were used for comparison. B. pertussis PCR was performed on throat swabs, and sera were tested for IgA antibodies against whole-cell (WC) B. pertussis antigen and IgG antibodies to pertussis toxin (PT). The Centers for Disease Control and Prevention definition for pertussis was used to define clinical cases. We evaluated the use of a previously published cut-off for PT IgG of 125 EIA units (EU)/ml. Completed questionnaires were obtained from 115 students, of whom 85 (74%) reported coughing symptoms, including 32 (28%) who met the clinical case definition for pertussis. B. pertussis was detected by PCR in 17 (15%) and WC IgA in 22 (19%) students; neither correlated with symptoms, but dormitory of residence strongly predicted PCR status. The mean PT IgG geometric mean concentration, in this situation of high pertussis exposure, correlated with severity of symptoms and was significantly higher in both symptomatic and asymptomatic children exposed during the outbreak (P < 0.001) than in control children. A cut-off for PT IgG of 125 EU/ml was too high in an outbreak situation to be sensitive enough to identify pertussis cases. A case of pertussis in a crowded boarding-school dormitory resulted rapidly in an outbreak. Serology and PCR were useful in identifying the outbreak and commencing disease control measures. The use of serology has mostly been evaluated in community serosurveys, where it is not possible to determine if immunity reflects vaccination, asymptomatic disease or symptomatic disease. This outbreak gave us the opportunity to evaluate the value of serology and PCR in the presence of confirmed exposure to pertussis. Hide abstract

Liem NT, Lim W, World Health Organization International Avian Influenza Investigation Team, Vietnam. 2005. Lack of H5N1 avian influenza transmission to hospital employees, Hanoi, 2004. Emerg Infect Dis, 11 (2), pp. 210-215. Read abstract | Read more

To establish whether human-to-human transmission of influenza A H5N1 occurred in the healthcare setting in Vietnam, we conducted a cross-sectional seroprevalence survey among hospital employees exposed to 4 confirmed and 1 probable H5N1 case-patients or their clinical specimens. Eighty-three (95.4%) of 87 eligible employees completed a questionnaire and provided a serum sample, which was tested for antibodies to influenza A H5N1. Ninety-five percent reported exposure to > or = 1 H5N1 case-patients; 59 (72.0%) reported symptoms, and 2 (2.4%) fulfilled the definition for a possible H5N1 secondary case-patient. No study participants had detectable antibodies to influenza A H5N1. The data suggest that the H5N1 viruses responsible for human cases in Vietnam in January 2004 are not readily transmitted from person to person. However, influenza viruses are genetically variable, and transmissibility is difficult to predict. Therefore, persons providing care for H5N1 patients should continue to take measures to protect themselves. Hide abstract

Horby PW, Williams A, Burgess MA, Wang H. 2005. Prevalence and determinants of influenza vaccination in Australians aged 40 years and over--a national survey. Aust N Z J Public Health, 29 (1), pp. 35-37. Read abstract | Read more

To determine influenza vaccination coverage in 2001 in Australian adults aged > or = 40 years, assess awareness of and attitudes to influenza vaccine, factors associated with vaccination, and estimate uptake of free vaccine provided to those aged > or = 65 years. Hide abstract

Hethcote HW, Horby P, McIntyre P. 2004. Using computer simulations to compare pertussis vaccination strategies in Australia. Vaccine, 22 (17-18), pp. 2181-2191. Read abstract | Read more

High levels of notified pertussis in adolescents and adults, persisting severe disease (hospitalization and deaths) in infants despite high childhood immunization coverage, together with the availability of adult-formulated pertussis vaccines, have made alternate strategies for vaccine control of pertussis an important issue in Australia. An age-structured computer simulation model was used to compare the likely effects of adopting different vaccination strategies in Australia on pertussis transmission by age group over a 50 year time period. Epidemiological parameters and vaccination coverage in Australia were estimated from previous pertussis modeling studies and existing data. In the simulations, replacing the pertussis booster at 18 months with a booster dose for adolescents at an age between 12 and 17 years, assuming 80% coverage, led to decreases in pertussis cases of 30% in children of ages 0-23 months (who have the highest complication rates) and of 25% in adolescents, but an increase of 15% in cases in 2-4-year-old children. The simulations did not suggest any shift of pertussis cases into the adult child-bearing years. Varying parameter values in the simulations in a series of sensitivity analyses showed the model predictions to be robust over a plausible range. The results of these simulations suggest that the recent change in the Australian pertussis vaccination schedule, replacing the 18 month dose with a pertussis booster in 15-17-year-old adolescents, is very likely to reduce overall pertussis incidence in Australia without increasing the cost of the current vaccine program. Hide abstract

Tran TH, Nguyen TL, Nguyen TD, Luong TS, Pham PM, Nguyen VV, Pham TS, Vo CD et al. 2004. Avian influenza A (H5N1) in 10 patients in Vietnam. N Engl J Med, 350 (12), pp. 1179-1188. Read abstract | Read more

Recent outbreaks of avian influenza A (H5N1) in poultry throughout Asia have had major economic and health repercussions. Human infections with this virus were identified in Vietnam in January 2004. Hide abstract

Le DH, Bloom SA, Nguyen QH, Maloney SA, Le QM, Leitmeyer KC, Bach HA, Reynolds MG et al. 2004. Lack of SARS transmission among public hospital workers, Vietnam. Emerg Infect Dis, 10 (2), pp. 265-268. Read abstract | Read more

The severe acute respiratory syndrome (SARS) outbreak in Vietnam was amplified by nosocomial spread within hospital A, but no transmission was reported in hospital B, the second of two designated SARS hospitals. Our study documents lack of SARS-associated coronavirus transmission to hospital B workers, despite variable infection control measures and the use of personal protective equipment. Hide abstract

Chow JY, Anderson SR, Delpech V, Leese J, Horby P, Sedgwick JE, Rooney CI, Nicoll A, Watson JM. 2003. SARS: UK public health response--past, present and future. Commun Dis Public Health, 6 (3), pp. 209-215. Read abstract

The emergence of severe acute respiratory syndrome (SARS) in China, the occurrence of epidemics of SARS in China and a number of Southeast Asian countries, and its spread to countries elsewhere, have presented major challenges to public health systems throughout the world. Although very few true cases of SARS were detected in the United Kingdom, the public health response to the threat of SARS was considerable. The main components of this response were the early detection, isolation and reporting of cases, and the provision of comprehensive information to health professionals, cases, their contacts and the public. The development of the response to SARS raised a number of more general issues relevant to future infectious epidemic threats. Although the World Health Organisation has now declared SARS 'contained', the possibility of re-emergence is ever present. All countries will need to be vigilant and plan their response to the possibility of a renewed SARS epidemic. Hide abstract

Horby P, Gilmour R, Wang H, McIntyre P. 2003. Progress towards eliminating Hib in Australia: an evaluation of Haemophilus influenzae type b prevention in Australia, 1 July 1993 to 30 June 2000. Commun Dis Intell Q Rep, 27 (3), pp. 324-341. Read abstract

The status of Haemophilus influenzae (Hib) disease and its prevention by vaccination was reviewed for the period 1997 to 2000. This forms the background to a change in national vaccine policy, from the use of two Hib vaccines to the use of PRP-OMP only throughout Australia from May 2000. Notifications of Hib in the 7-year period between 1993 and 2000 declined by 87 per cent among children 0-4 years of age; adjustment for likely under-reporting increase this to a 95 per cent reduction. Among age groups not included in the immunisation program, there was also a substantial decline in notified cases. Overall, a minimum 430 cases and 13 deaths were prevented by Hib immunisation annually in Australia. Enhanced Hib surveillance recorded 532 cases over seven years, with 353 in unvaccinated persons, 74 fulfilling criteria for true vaccine failure and 75 partially immunised. Of unvaccinated cases, 60 and 182 were eligible for routine and catch-up immunisation respectively. Although the overall incidence for 0-4 years of age declined from 15 to 1.2 cases per 100,000 population, the proportion of cases under six months of age increased from 11 per cent to 23 per cent. Overall vaccine effectiveness, estimated using data from the last five years of the program, was 83 per cent (95% CI 71-91%), increasing to 90 per cent (95% CI 83-94%) when adjusted for under-reporting to the Australian Childhood Immunisation Register. Among Aboriginal and Torres Strait Islander people, the incidence of invasive Hib disease fell from 4.6 cases per 100,000 population to 0.7 cases per 100,000 population but the proportion of cases now occurring among Aboriginal or Torres Strait Islander people increased significantly, from 7 to 15 per cent. The Hib immunisation program in Australia has been highly successful. Nevertheless, experience in Australia and elsewhere indicates that continued careful monitoring of Hib disease, with high quality laboratory surveillance, remains important. Hide abstract

Horby PW, O'Brien SJ, Adak GK, Graham C, Hawker JI, Hunter P, Lane C, Lawson AJ et al. 2003. A national outbreak of multi-resistant Salmonella enterica serovar Typhimurium definitive phage type (DT) 104 associated with consumption of lettuce. Epidemiol Infect, 130 (2), pp. 169-178. Read abstract | Read more

Between 1 August and 15 September 2000, 361 cases of Salmonella enterica serotype Typhimurium definitive phage type (DT) 104, resistant to ampicillin, chloramphenicol, streptomycin, sulphonamides, spectinomycin and tetracycline (R-type ACSSuSpT), were identified in England and Wales residents. Molecular typing of 258 isolates of S. Typhimurium DT104 R-type ACSSuSpT showed that, although isolates were indistinguishable by pulsed-field gel electrophoresis, 67% (174/258) were characterized by a particular plasmid profile. A statistically significant association between illness and consumption of lettuce away from home was demonstrated (OR = 7.28; 95% CI=2.25-23.57; P=0.0006) in an unmatched case-control study. Environmental investigations revealed that a number of food outlets implicated in the outbreak had common suppliers of salad vegetables. No implicated foods were available for microbiological testing. An environmental audit of three farms that might have supplied salad vegetables to the implicated outlets did not reveal any unsafe agricultural practices. The complexity of the food supply chain and the lack of identifying markers on salad stuffs made tracking salad vegetables back to their origin extremely difficult in most instances. This has implications for public health since food hazard warnings and product withdrawal are contingent on accurate identification of the suspect product. Hide abstract

Horby P. 2002. Variant Creutzfeldt-Jakob disease: an unfolding epidemic of misfolded proteins. J Paediatr Child Health, 38 (6), pp. 539-542. Read abstract | Read more

Variant Creutzfeldt-Jakob disease (vCJD) is an emerging infectious disease believed to be the human manifestation of bovine spongiform encephalopathy (BSE). Variant CJD belongs to a family of human and animal diseases called transmissible spongiform encephalopathies (TSE). The pathogenesis of TSE is not fully understood, but a modified form of a normal cellular protein plays a central role. Current measures to control vCJD aim to prevent transmission of the infectious agent from animals to humans through food or pharmaceutical products and to prevent transmission from person to person via medical interventions. The anticipated development of preclinical diagnostic tests and treatments for vCJD will create new control options and difficult choices. Hide abstract

Gillespie IA, O'Brien SJ, Frost JA, Adak GK, Horby P, Swan AV, Painter MJ, Neal KR, Campylobacter Sentinel Surveillance Scheme Collaborators. 2002. A case-case comparison of Campylobacter coli and Campylobacter jejuni infection: a tool for generating hypotheses. Emerg Infect Dis, 8 (9), pp. 937-942. Read abstract | Read more

Preventing campylobacteriosis depends on a thorough understanding of its epidemiology. We used case-case analysis to compare cases of Campylobacter coli infection with cases of C. jejuni infection, to generate hypotheses for infection from standardized, population-based sentinel surveillance information in England and Wales. Persons with C. coli infection were more likely to have drunk bottled water than were those with C. jejuni infection and, in general, were more likely to have eaten pâté. Important differences in exposures were identified for these two Campylobacter species. Exposures that are a risk for infection for both comparison groups might not be identified or might be underestimated by case-case analysis. Similarly, the magnitude or direction of population risk cannot be assessed accurately. Nevertheless, our findings suggest that case-control studies should be conducted at the species level. Hide abstract

McIntyre P, Gidding H, Gilmour R, Lawrence G, Hull B, Horby P, Wang H, Andrews R, Burgess M, National Centre for Immunisation Research and Surveillance of Vaccine Preventable Diseases. 2002. Vaccine preventable diseases and vaccination coverage in Australia, 1999 to 2000. Commun Dis Intell Q Rep, Suppl pp. i-111.

Horby P. 2002. Rendering beef safe. Clin Infect Dis, 34 (1), pp. 129. | Read more

Horby P, Rushdy A, Graham C, O'Mahony M, PHLS Overview of Communicable Diseases Committee. 2001. PHLS overview of communicable diseases 1999. Commun Dis Public Health, 4 (1), pp. 8-17. Read abstract

Every other year since 1995 the Public Health Laboratory Service has undertaken a consultation exercise to identify communicable diseases of high public health priority. The purpose of identifying disease priorities is to guide rational and transparent service planning and resource allocation. Also, the process aims to ensure a customer sensitive service. This paper presents the results of the priority setting exercise undertaken in 1999. A postal questionnaire was sent to 1130 key professionals involved in communicable disease control in the United Kingdom. Respondents were asked to assess the relative priority of 61 communicable diseases and to identify priority areas of work associated with these diseases. Five criteria were used to assess relative priority. The five criteria were; present burden of ill-health, social and economic impact, potential threat to health, health gain opportunity and public concern and confidence. For each disease, respondents were asked to score the importance of each criterion. Forty six percent of participants (518/1130) returned completed questionnaires. There was no significant difference in response rate by professional group. Based on the scores assigned to each of the five criteria, the relative priority of 61 communicable diseases has been established. The top ten diseases in descending order of priority are, HIV/AIDS, meningococcal diseases, Chlamydia trachomatis, influenza, tuberculosis, E. coli O157, Methicillin resistant Staphylococcus aureus, salmonellosis, transmissible spongiform encephalopathies and Helicobacter pylori. The opinion of a large number of health care professionals has been used to establish a priority rank for a wide range of communicable diseases. This work provides planners and policy makers with a synthesis of current professional opinion that can be used as a foundation for making decisions on service developments. Hide abstract

Horby P, Murray V, Cummins A, Mackway-Jones K, Euripidou R. 2000. The capability of accident and emergency departments to safely decontaminate victims of chemical incidents. J Accid Emerg Med, 17 (5), pp. 344-347. Read abstract | Read more

To evaluate the capability of accident and emergency (A&E) departments in six health regions of England to safely decontaminate casualties exposed to hazardous chemicals. Hide abstract

Dyke T, Flew S, Bramwell S, Murray F, Horby P. 1993. Haemophilia A in the highlands: the investigation and management of two families in Tari. P N G Med J, 36 (1), pp. 22-28. Read abstract

A 12-year-old boy from Tari in the Southern Highlands of Papua New Guinea presented with prolonged bleeding from a minor injury to the lip. He had a history of profuse bleeding and joint swelling following minor trauma. He has two younger brothers with a similar history. It was demonstrated that they had a coagulation profile compatible with factor VIII deficiency and a family tree suggestive of haemophilia A. A further case was investigated some months later. Despite the neighbouring places of residence of the two families no familial connection could be established by involved discussions between family members. This was confirmed by reviewing the data held on the demographic surveillance system of the Tari Unit of the Papua New Guinea Institute of Medical Research. These families are considered against a background of the diagnosis and management of this condition in a rural part of Papua New Guinea. The long-term support of these patients and other similarly affected individuals presents difficult clinical and ethical problems for rural health services. Hide abstract

Hien NT, Dharan NJ, Le MT, Vietnam National Influenza Surveillance and Evaluation Team. National influenza surveillance in Vietnam, 2006-2007. Vaccine, 2 (28), pp. 398-402.

Clincial Research in Epidemics

A key lesson from a series of recent outbreaks of emerging pathogens of global public health importance including SARS-CoV, highly pathogenic avian influenza A (H5N1) virus, EV71, Nipah virus and the 2009 pandemic was that mounting clinical research in response to a rapidly emerging infectious disease is extremely challenging and often delayed. The clinical research response was cumbersome and slow despite years of global preparations for a potentially devastating influenza pandemic of avian ...

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