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Showing papers by "Timothy M. Uyeki published in 2007"


Journal ArticleDOI
TL;DR: A strong recommendation to treat H5N1 patients with oseltamivir was made in part because of the severity of the disease, and strong recommendations were made to use neuraminidase inhibitors as chemoprophylaxis in high-risk exposure populations.
Abstract: Recent spread of avian influenza A (H5N1) virus to poultry and wild birds has increased the threat of human infections with H5N1 virus worldwide. Despite international agreement to stockpile antivirals, evidence-based guidelines for their use do not exist. WHO assembled an international multidisciplinary panel to develop rapid advice for the pharmacological management of human H5N1 virus infection in the current pandemic alert period. A transparent methodological guideline process on the basis of the Grading Recommendations, Assessment, Development and Evaluation (GRADE) approach was used to develop evidence-based guidelines. Our development of specific recommendations for treatment and chemoprophylaxis of sporadic H5N1 infection resulted from the benefits, harms, burden, and cost of interventions in several patient and exposure groups. Overall, the quality of the underlying evidence for all recommendations was rated as very low because it was based on small case series of H5N1 patients, on extrapolation from preclinical studies, and high quality studies of seasonal influenza. A strong recommendation to treat H5N1 patients with oseltamivir was made in part because of the severity of the disease. Similarly, strong recommendations were made to use neuraminidase inhibitors as chemoprophylaxis in high-risk exposure populations. Emergence of other novel influenza A viral subtypes with pandemic potential, or changes in the pathogenicity of H5N1 virus strains, will require an update of these guidelines and WHO will be monitoring this closely.

174 citations


Journal ArticleDOI
TL;DR: Sporadic and family clusters of cases of H5N1 virus infection, with a high case-fatality proportion, occurred throughout Indonesia during 2005-2006 and extensive efforts are needed to reduce human contact with sick and dead poultry.
Abstract: Background Highly pathogenic avian influenza A (H5N1) virus was detected in domestic poultry in Indonesia beginning in 2003 and is now widespread among backyard poultry flocks in many provinces. The first human case of H5N1 virus infection in Indonesia was identified in July 2005. Methods Respiratory specimens were collected from persons with suspected H5N1 virus infection and were tested by reverse-transcriptase polymerase chain reaction and viral culture. Serum samples were tested by a modified hemagglutinin inhibition antibody and/or microneutralization assay. Epidemiological, laboratory, and clinical data were collected through interviews and medical records review. Close contacts of persons with confirmed H5N1 virus infection were investigated. Results From July 2005 through June 2006, 54 cases of H5N1 virus infection were identified, with a case-fatality proportion of 76%. The median age was 18.5 years, and 57.4% of patients were male. More than one-third of cases occurred in 7 clusters of blood-related family members. Seventy-six percent of cases were associated with poultry contact, and the source of H5N1 virus infection was not identified in 24% of cases. Conclusions Sporadic and family clusters of cases of H5N1 virus infection, with a high case-fatality proportion, occurred throughout Indonesia during 2005-2006. Extensive efforts are needed to reduce human contact with sick and dead poultry to prevent additional cases of H5N1 virus infection.

146 citations


Journal ArticleDOI
TL;DR: A systematic, transparent approach used by the World Health Organization to develop rapid advice guidelines in response to requests from member states confronted with uncertainty about the pharmacological management of avian influenza A (H5N1) virus infection is described.
Abstract: Emerging health problems require rapid advice. We describe the development and pilot testing of a systematic, transparent approach used by the World Health Organization (WHO) to develop rapid advice guidelines in response to requests from member states confronted with uncertainty about the pharmacological management of avian influenza A (H5N1) virus infection. We first searched for systematic reviews of randomized trials of treatment and prevention of seasonal influenza and for non-trial evidence on H5N1 infection, including case reports and animal and in vitro studies. A panel of clinical experts, clinicians with experience in treating patients with H5N1, influenza researchers, and methodologists was convened for a two-day meeting. Panel members reviewed the evidence prior to the meeting and agreed on the process. It took one month to put together a team to prepare the evidence profiles (i.e., summaries of the evidence on important clinical and policy questions), and it took the team only five weeks to prepare and revise the evidence profiles and to prepare draft guidelines prior to the panel meeting. A draft manuscript for publication was prepared within 10 days following the panel meeting. Strengths of the process include its transparency and the short amount of time used to prepare these WHO guidelines. The process could be improved by shortening the time required to commission evidence profiles. Further development is needed to facilitate stakeholder involvement, and evaluate and ensure the guideline's usefulness.

123 citations


Journal ArticleDOI
TL;DR: Continued surveillance for H5N1 cases in humans and further seroprevalence investigations are needed to assess the risk of avian-to-human transmission, given that H 5N1 viruses continue to circulate and evolve among poultry.
Abstract: Background In February 2006, poultry outbreaks of highly pathogenic avian influenza A (H5N1) virus were confirmed in Nigeria. A serosurvey was conducted to assess H5N1 transmission among poultry workers and laboratory workers in Nigeria. Methods From 21 March through 3 April 2006, 295 poultry workers and 25 laboratory workers with suspected exposure to H5N1 virus were administered a questionnaire to assess H5N1 exposures, medical history, and health care utilization. A serum specimen was collected from participants to test for H5N1 neutralizing antibodies by microneutralization assay. Results The 295 poultry workers reported a median of 14 days of exposure to suspected or confirmed H5N1-infected poultry without antiviral chemoprophylaxis and with minimal personal protective equipment. Among 25 laboratory workers, all handled poultry specimens with suspected H5N1 virus infection. All participants tested negative for H5N1 neutralizing antibodies. Conclusions Despite widespread exposure to poultry likely infected with H5N1 virus, no serological evidence of H5N1 virus infection was identified among participants. Continued surveillance for H5N1 cases in humans and further seroprevalence investigations are needed to assess the risk of avian-to-human transmission, given that H5N1 viruses continue to circulate and evolve among poultry.

77 citations


Journal ArticleDOI
TL;DR: Investigating potential sources of infection for 6 confirmed influenza A (H5N1) patients who resided in urban areas of People’s Republic of China found none had known exposure to sick poultry or poultry that died from illness, but all had visited wet poultry markets before illness.
Abstract: We investigated potential sources of infection for 6 confirmed influenza A (H5N1) patients who resided in urban areas of People's Republic of China. None had known exposure to sick poultry or poultry that died from illness, but all had visited wet poultry markets before illness.

64 citations


Journal ArticleDOI
TL;DR: Statistical modeling can provide useful and supportive insights but should not be viewed as an alternative to a detailed field epidemiologic investigation combined with laboratory data.
Abstract: To the Editor: This letter is in response to a recently published article about statistical modeling to assess human-to-human transmission of avian influenza A (H5N1) viruses in 2 case clusters (1). Sporadic cases and clusters of human infection with highly pathogenic avian influenza A (H5N1) viruses have occurred after direct contact with diseased or dead poultry (2,3). Limited, nonsustained human-to-human transmission of avian influenza (H5N1) viruses is believed to have occurred in some clusters (4). Every human infection with a novel influenza A virus should be investigated, and suspected clusters should be investigated immediately to assess exposures and transmission patterns. Yang et al. applied a statistical model to evaluate publicly available data from 2 case clusters of human infection with avian influenza A (H5N1) viruses (1). These clusters were investigated in detail during 2006 by field epidemiologic investigation teams. Yang et al. suggest that statistical methods can prove or confirm human-to-human transmission, but this suggestion is misleading. Modeling approaches can suggest transmission modalities to account for case patterns, but determination of human-to-human transmission requires detailed field epidemiologic investigations in which human, animal, and environmental exposures as well as clinical and laboratory data are assessed and interpreted. Indication that a novel influenza A virus has acquired the ability to spread among humans could be reflected by a change in the epidemiology of clusters, such as increases in 1) size and frequency of clusters, 2) cases among nonrelated persons, and 3) clinically mild cases. This ability could also be reflected in accompanying changes in viruses isolated from case-patients. When facing emerging infectious disease threats such as those posed by highly pathogenic avian influenza A (H5N1) viruses, surveillance should rapidly detect human cases and case clusters and facilitate accurate identification of the agent. Field epidemiologic investigations, initiation of evidence-based clinical management of case-patients, and epidemiologic disease-control methods (including appropriate infection control measures) should be implemented immediately. Statistical modeling can provide useful and supportive insights but should not be viewed as an alternative to a detailed field epidemiologic investigation combined with laboratory data. Timely and comprehensive field investigations remain most critical to guiding decisions about containment efforts for pandemic influenza and other emerging infectious diseases (5).

63 citations


Journal ArticleDOI
TL;DR: Despite their high cost, rapid influenza diagnostic tests are useful tools for influenza research, surveillance, and outbreak investigations in Southeast Asia.

35 citations


Journal ArticleDOI
10 May 2007-Vaccine
TL;DR: In Thailand, the young, elderly, and those with chronic disease were at high risk for hospitalized pneumonia from influenza, and cases were 6.2 and 11.1 times more likely to be among persons<1 year old and >75 years old, respectively, compared with the overall population.

29 citations


Journal ArticleDOI
TL;DR: Recombinant severe acute respiratory syndrome nucleocapsid and spike protein-based immunoglobulin G immunoassays demonstrated high sensitivity and specificity to the SARS coronavirus in sera collected from patients as late as 2 years postonset of symptoms.
Abstract: Recombinant severe acute respiratory syndrome (SARS) nucleocapsid and spike protein-based immunoglobulin G immunoassays were developed and evaluated. Our assays demonstrated high sensitivity and specificity to the SARS coronavirus in sera collected from patients as late as 2 years postonset of symptoms. These assays will be useful not only for routine SARS coronavirus diagnostics but also for epidemiological and antibody kinetic studies.

20 citations


Journal ArticleDOI
TL;DR: Among the 59 reported patients, no evidence of H5N1 virus infection was found; none had had direct contact with poultry, but 42% had evidence of human influenza A.
Abstract: We reviewed reports to the Centers for Disease Control and Prevention of US travelers suspected of having avian influenza A H5N1 virus infection from February 2003 through May 2006. Among the 59 reported patients, no evidence of H5N1 virus infection was found; none had had direct contact with poultry, but 42% had evidence of human influenza A.

14 citations


Book ChapterDOI
01 Jan 2007
TL;DR: The key to preventing human infections with H5N1 virus is to avoid unprotected direct contact with diseased and dead poultry, materials contaminated by poultry feces, and uncooked or inadequately cooked poultry or poultry products.
Abstract: Since 1997, highly pathogenic avian influenza A (H5N1) viruses have caused unprecedented widespread poultry outbreaks with high mortality in a number of Asian, European, Middle Eastern, and African countries; have infected other animal species; and have caused sporadic, severe, and fatal human infections. Influenza viruses are single-stranded, negative-sense RNA viruses with eight gene segments that encode 10 proteins and belong to the family Orthomyxoviridae. It is now known that H5N1 virus emerged in southern China in 1996 and that outbreaks of highly pathogenic avian influenza (HPAI) H5N1 among poultry have occurred in southern China for several years. Epidemiological studies conducted in Hong Kong during the 1997 H5N1 outbreak implicated avian-to-human transmission of H5N1 virus. Clinical case reports of H5N1 infection reflect surveillance for severe respiratory illness in hospitals. There are few descriptions of the clinical features of mild or atypical disease. Detection of H5N1 RNA by conventional or real-time PCR testing of respiratory specimens using H5-specific primers under biosafety level 2 (BSL2) laboratory conditions is the most common method of H5N1 diagnosis. The key to preventing human infections with H5N1 virus is to avoid unprotected direct contact with diseased and dead poultry, materials contaminated by poultry feces, and uncooked or inadequately cooked poultry or poultry products. There are several challenges to producing a pandemic influenza vaccine. Aside from the problems with production capacity and distribution, three additional challenges to creating an H5N1 vaccine are antigenic drift, immunogenicity, and vaccine pathogenicity to embryonated chicken eggs.