Mei-Shang Ho

Estimates of morbidity and mortality rates for diarrheal diseases in American children

Although the importance of diarrhea as a prime cause of morbidity and death in developing countries is well recognized, the disease burden in the United States has never been thoroughly examined. We have prepared national estimates of the annual number of cases of diarrhea in children less than 5 years of age and of the outcome, measured in terms of visits to a physician, hospitalizations, and deaths. The annual number of diarrheal episodes was estimated by reviewing longitudinal studies of childhood diarrhea conducted in the United States and extrapolating these data to the nation. Estimates of physician visits, hospitalizations, and deaths were prepared from a variety of national data sources. We estimate that 16.5 million children less than 5 years of age have between 21 and 37 million episodes of diarrhea annually. Of these, 2.1 to 3.7 million episodes lead to a physician visit, a total of 220,000 patients are hospitalized, and 325 to 425 children die. The major cost of diarrhea lies in the high numbers and cost of hospitalizations, because approximately 10.6% of hospitalizations in this age group are for diarrhea. Diarrheal deaths occur in relatively small numbers, are more common in the South and among black persons, are potentially avoidable, and could represent as much as 10% of the preventable postneonatal infant death in the United States. These estimates underscore the extensive burden of diarrheal illness in children in the United States and suggest that interventions to prevent disease or decrease its severity could be cost-effective.

Protection against lethal enterovirus 71 infection in newborn mice by passive immunization with subunit VP1 vaccines and inactivated virus.

Enterovirus 71 (EV71), the newest member of Enteroviridae, is notable for its etiological role in epidemics of severe neurological diseases in children. Developing effective vaccines is considered a top choice among all control measures. We compared the inactivated virus vaccine (10 microg protein/mouse) with subunit vaccines--VP1 DNA vaccine (100 microg/mouse) or recombinant VP1 protein (10 microg/mouse)--in its ability to elicit maternal antibody and to provide protection against lethal infection of EV71 in suckling mice. Prior to gestation, all three groups of vaccinated dams possessed similar levels of neutralizing antibody. With a challenge dose of 2300 LD(50) virus/mouse, suckling mice born to dams immunized with inactivated virus showed 80% survival. The subunit vaccines provided protection only at a lower challenge dosage of 230 LD(50) per mouse, with 40% survival for DNA vaccine and 80% survival for VP1 protein. The cytokine profile produced by splenocytes showed a high level of IL-4 in the inactivated virus group, high levels of IFN-gamma and IL-12 in the DNA vaccine group, and high levels of IL-10 and IFN-gamma in the VP1 protein group. Overall, the inactivated virus elicited a much greater magnitude of immune response than the subunit vaccines, including total IgG, all four IgG subtypes, and T-helper-cell responses; these antibodies were shown to be protective against lethal infection when passively transferred to susceptible newborn mice. Our data indicated that inactivated virus is the choice of vaccine preparation capable of fulfilling the demand for effective control, and that VP1 subunit vaccines remain promising vaccine strategies that require further refinement.

Enterovirus 71 Outbreaks, Taiwan: Occurrence and Recognition

Enterovirus 71 (EV71) caused a large outbreak in Taiwan in 1998 with 78 deaths, and smaller outbreaks recurred in 2000 and 2001. The outbreak was recognized because of a large number of hand, foot, and mouth disease cases and the rapid deaths of children with the disease. Virologic and pathologic studies indicated that EV71 was the most important agent related to severe and fatal cases and that a neurogenic inflammatory response was involved in the pathogenesis of cardiopulmonary collapse resulting from fulminant EV71 infection. Seroepidemiologic study suggested that EV71 had circulated for at least 16 years and that the accumulation of susceptible hosts might have triggered the 1998 outbreak. However, a change in EV71 neurovirulence and host genetic susceptibility may also have affected the clinical outcome. The Taiwan outbreak shows that worldwide attention should be paid to such outbreaks, new antiviral drugs should be developed, and that vaccination of children under 5 years of age may be warranted.

Effect of hepatitis C and B virus infection on risk of hepatocellular carcinoma : a prospective study

To assess whether there is an additive effect between chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection on the development of hepatocellular carcinoma (HCC), 400 consecutive cirrhotic patients were followed prospectively with periodic abdominal ultrasound examination and measurement of serum alpha-fetoprotein (AFP) level every 4 months. During a follow-up of 1185 person-years, 80 (20%) patients developed HCC, with an annual incidence of 6.8%. The annual incidence was 2.0% in patients negative for hepatitis B surface antigen (HBsAg) and antibodies to HCV (anti-HCV), 6.6% in patients with HBsAg alone, 7.0% in patients with anti-HCV alone and 13.3% in patients co-infected with HBV and HCV. There was a positive linear trend in the annual incidence of HCC among patients without either marker, patients with single viral infection and patients with dual viral infection (P[for trend] < 0.0001). Coxs proportional hazard model indicated that HCV/HBV co-infection [hazard ratio (HR), 6.41; 95% confidence interval (CI), 1.80-22.80], anti-HCV alone (HR, 3.74; 95% CI, 1.07-13.07) and HBsAg alone (HR, 4.06; 95% CI, 1.23-13.34) were independently risk factors of HCC. In conclusion, there is an additive and independent effect modification of HCV and HBV infection on HCC development.

Transmission of hepatitis C virus in Taiwan: Prevalence and risk factors based on a nationwide survey

A nationwide community‐based survey on hepatitis C virus (HCV) was carried out in seven townships in Taiwan. A total of 11,904 men aged 30–64 years were recruited for testing for antibodies against HCV (anti‐HCV) by second‐generation enzyme immunoassay. A total of 272 seropositive cases and 282 seronegative controls were interviewed to explore risk factors for HCV infection in the study areas. Spouses of 214 seropositive cases were identified to assess the concordance of seropositivity of anti‐HCV between spouses; genotypes of HCV were also tested in 26 couples who were both seropositive. A significant geographic variation in seroprevalence of anti‐HCV was observed in the study townships (1.6–19.6%). Blood transfusions, medical injections, acupuncture and tattooing were related to an increased anti‐HCV seroprevalence showing multivariate‐adjusted odds ratios of 8.6, 2.5, 3.1, and 2.2, respectively, with corresponding population attributable risk percentages of 25%, 57%, 16%, and 3%, respectively. The anti‐HCV prevalence in spouses of index cases (24%) was significantly higher than that observed in the general population of the study areas (4%). However, a striking interspousal discrepancy in HCV genotypes (20/26 = 77%) was observed among both seropositive couples. Common exposures to medical injections and acupuncture were reported by 15 (58%) of these couples. This study identified some endemic areas of HCV infection in Taiwan. Iatrogenic factors were common vehicles for HCV infection, and a concordance of anti‐HCV seropositivity between spouses may primarily be due to extrafamilial iatrogenic infectious sources in study areas. J. Med. Virol. 59:290–296, 1999.

VIRAL GASTROENTERITIS ABOARD A CRUISE SHIP

A 32-nm small round structured virus (SRSV), possibly related to the Snow Mountain agent (SMA), was implicated as the cause of recurrent outbreaks of gastroenteritis on a cruise ship. There was no identifiable relation to food or water consumption, but the risk of gastroenteritis among passengers who had shared toilet facilities was twice that of those who had a private bathroom and the rate of illness was related to the number of passengers sharing a communal restroom (ie, with one or more toilets): contaminated bathrooms may be an important vehicle for person-to-person spread of this enteric agent. In each cabin, index patients who had vomited in their cabins were more likely to have had cabinmates who subsequently became ill than were index patients who had not vomited. These epidemiological findings implicate vomitus in the transmission of viral gastroenteritis and they are consistent with the transmission of viral agents by airborne droplets or person-to-person contact. New strategies for prevention of viral gastroenteritis should include protection against environmental contamination by viruses in airborne droplets or vomitus.

Seasonality of infectious diseases and severe acute respiratory syndrome–what we don't know can hurt us

Summary The novel severe acute respiratory syndrome (SARS) coronavirus caused severe disease and heavy economic losses before apparently coming under complete control. Our understanding of the forces driving seasonal disappearance and recurrence of infectious diseases remains fragmentary, thus limiting any predictions about whether, or when, SARS will recur. It is true that most established respiratory pathogens of human beings recur in wintertime, but a new appreciation for the high burden of disease in tropical areas reinforces questions about explanations resting solely on cold air or low humidity. Seasonal variation in host physiology may also contribute. Newly emergent zoonotic diseases such as ebola or pandemic strains of influenza have recurred in unpredictable patterns. Most established coronaviruses exhibit winter seasonality, with a unique ability to establish persistent infections in a minority of infected animals. Because SARS coronavirus RNA can be detected in the stool of some individuals for at least 9 weeks, recurrence of SARS from persistently shedding human or animal reservoirs is biologically plausible.

Han Chinese Cell and Genome Bank in Taiwan: Purpose, Design and Ethical Considerations

a Institute of Biomedical Sciences, Academia Sinica, b Department of Political Sciences, National Taiwan University, c Research Center for Humanities and Social Sciencies, Academia Sinica, d Center for Survey Research, Research Center for Humanities and Social Sciencies, Academia Sinica, and e Department of Philosophy, National Chengchi University, Taipei , Taiwan, ROC goal is to develop Taiwan’s competitive edge in medical research particularly for prognosis, diagnosis, and treatment of Taiwanese important genetic diseases. The Han Chinese cell and Genome Bank project was jointly supported by NRPGM and Academia Sinica. Comprehensive cores have been established in NRPGM to complement relevant studies. The National Clinical Core and National High-throughput Genotyping Core, funded by NSC and directed by the Institute of Biomedical Sciences, Academia Sinica, Taiwan, played major roles in carrying out fi eld work and in the genotyping of the genetic material. A policy and mechanisms for the release of DNA information have been established for genetic research communities in Taiwan and abroad. In order to obtain a representative sample of genetic material for the bank; a stratifi ed, 3-staged, probability clustering sampling scheme (see appendix, table 1 , and fi g. 1 ) was adopted. Sampling was designed to have around 278 male and 278 female subjects respectively in each of the 6 age groups (20–, 30–, 40–, 50–, 60–, 70–) so that there would be suffi cient numbers of sex/age matched controls for a range of diseases. Of the people living in the registered households that were contacted, a total of 73.4% took part in the study. Plasma, DNA, and lymphocytes were collected and banked, and measurements including basic blood chemistry, blood pressure, peak fl ow, and anthropometric parameters were taken (see table 2 ). A questionnaire ( table 2 ) on ethnicity, disease history and medication, life styles, and cognitive function of the elderly was administered by trained nurses in a door-to-door survey, following a standardized protocol. Complete questionnaire and bio-specimen data were available for 3,380 people. This information can be used to defi ne phenotypes for association study and to select controls. The EBV-transformed lymphoblastoid cell lines had been established by the Bioresource Collection and Research Center, Hsinchu, Taiwan. From October 1, 2002 to January 14, 2004, the Institute of Biomedical Sciences, Academia Sinica, Taiwan, conducted fi eld work involving interviewing and recruiting 3,380 Han Chinese in order to establish a Han Chinese Cell and Genome Bank in Taiwan. The aims of this undertaking were several fold: (1) to collect representative genetic material for population genetic research, particularly for use as controls in disease association studies in Chinese people, (2) to document the genetic diversity of Han Chinese in Taiwan at the beginning of the 21st century, and (3) to create a bank of material that will prevent the repetitive collection of genetic material from the general public by the academic and medical community. The National Science Council (NSC) in Taiwan has launched the ‘National Research Program for Genomic Medicine (NRPGM)’ in 2002 as the fi rst phase of Taiwan’s Biotechnology Initiative in response to the deciphering of the human genome in 2000. The

Fever Screening at Airports and Imported Dengue

Airport fever screening in Taiwan, July 2003–June 2004, identified 40 confirmed dengue cases. Results obtained by capture immunoglobulin (Ig) M and IgG enzyme-linked immunoassay, real time 1-step polymerase chain reaction, and virus isolation showed that 33 (82.5%) of 40 patients were viremic. Airport fever screening can thus quickly identify imported dengue cases.

Severe Acute Respiratory Syndrome Coronavirus on Hospital Surfaces

Abstract Background. Health care workers continued to contract severe acute respiratory syndrome (SARS), even after barrier precautions were widely implemented. Methods. We explored the possible contribution of contaminated hospital surfaces to SARS transmission by swabbing surfaces in 2 hospitals and testing the swab samples by reverse-transcriptase polymerase chain reaction (RT-PCR) and viral culture. Results. Twenty-six of 94 swab samples tested positive for viral RNA. Swab samples of respiratory secretions from each of the 4 patients examined tested positive by RT-PCR, as were 12 of 43 swabs from patient rooms and 10 of 47 swabs from other parts of the hospital, including the computer mouses at 2 nursing stations and the handrail of the public elevator. Specimens from areas with patients with SARS in the most infectious phase of illness (days 5–15 after onset) were more likely to be RNA positive than were swab specimens from elsewhere (24 of 63 samples vs. 2 of 31 samples; P = .001). All cultures showed no growth. Conclusions. Although the viruses identified may have been noninfectious, health care workers should be aware that SARS coronavirus can contaminate environmental surfaces in the hospital, and fomites should be considered to be a possible mode of transmission of SARS.