Pandemic influenza--including a risk assessment of H5N1.

Influenza pandemics and epidemics have apparently occurred since at least the Middle Ages. When pandemics appear, 50% or more of an affected population can be infected in a single year, and the number of deaths caused by influenza can dramatically exceed what is normally expected. Since 1500, there appear to have been 13 or more influenza pandemics. In the past 120 years there were undoubted pandemics in 1889, 1918, 1957, 1968, and 1977. Although most experts believe we will face another influenza pandemic, it is impossible to predict when it will appear, where it will originate, or how severe it will be. Nor is there agreement about the subtype of influenza virus most likely to cause the next pandemic. The continuing spread of H5N1 highly pathogenic avian influenza viruses has heightened interest in pandemic prediction. Despite uncertainties in the historical record of the pre-virology era, study of previous pandemics may help guide future pandemic planning and lead to a better understanding of the complex ecobiology underlying the formation of pandemic strains of influenza A viruses.

Cigarette smoking and protection from Parkinson's disease: false association or etiologic clue?

We reviewed 46 published reports associating cigarette smoking and Parkinson's disease. Although the majority indicated an approximate halving of smoking frequency in persons with Parkinson's disease, many observers have suggested that the effect could be a spurious result. That the association may be real is suggested by at least six observations: (1) the consistency of findings between independent studies of different design, conducted by different investigators, in different nations, over 35 years; (2) the association's predominance and strength in prospective studies; (3) the apparent detection of a dose-response relation; (4) the inability to explain the association by confounding variables; (5) the flaws in certain arguments against the association's validity; and (6) the identification of a similar association, of similar magnitude, between smoking and reduced occurrence of Alzheimer's disease. A protective association of cigarette smoking for Parkinson's disease may constitute an important etiologic clue.

Case-control study of idiopathic Parkinson's disease and dietary vitamin E intake.

A nested case-control study of 84 incident cases of patients with idiopathic Parkinson's disease (PD) detected by June 30, 1994 and 336 age-matched control subjects, compared previously-documented intake of total dietary vitamin E and of selected vitamin E-containing foods. All study subjects had been followed for 27 to 30 years after diet recording in the 8,006-man Honolulu Heart Study cohort. We determined PD outcomes by periodic cohort re-examination and neurologic testing, private physician reports, examination of O'ahu neurologists' office records, and continual death certificate and hospital discharge diagnosis surveillance. Data on vitamin E intake, obtained from three dietary data sets at the time of cohort enrollment (1965 to 1968), included a food-frequency questionnaire and a 24-hour photograph-assisted dietary recall administered by trained dietitians. Although absence of PD was significantly associated with prior consumption of legumes (adjusted OR = 0.27, 95% CI 0.09 to 0.78), a dietary variable preselected for high vitamin E content, neither food categories nor quartiles nor continuous variables of vitamin E consumption were significantly associated with PD occurrence. Though consistent with prior reports of PD protection afforded by legumes, and with speculation on the possible benefits of dietary or supplemental vitamin E in preventing PD, these preliminary data do not conclusively document a beneficial effect of dietary vitamin E on PD occurrence.

Epidemiologic observations on Parkinson's disease: incidence and mortality in a prospective study of middle-aged men.

We determined age-specific and age-adjusted incidence rates and mortality rates of idiopathic Parkinson's disease (PD) in a cohort of men followed for 29 years. Since enrollment in 1965, the Honolulu Heart Study has followed 8,006 American men of Japanese or Okinawan ancestry. Rescreening of the entire cohort, completed in 1994, included attempts to detect all prevalent and incident cases of PD, parkinsonism, and related conditions. PD incidence rates and age-incidence patterns were similar to rates previously published for Caucasian men in Europe and the United States, and were higher than incidence rates published for Asian men living in Asian nations. Prevalence patterns appeared to correspond more closely to patterns observed in developed nations than in Asian nations. PD was associated with markedly increased mortality that appeared to result from effects of both absolute age and disease duration. There was no firm evidence for differences in birth cohort risks of PD. These data may have implications for maturational and environmental theories of PD etiology.

National surveillance of Kawasaki disease.

Information about 261 cases of Kawasaki disease (KD) was reported to the Center for Disease Control (CDC) between July 1976 and July 1978. KD occurred at all times of the year in young, previously healthy children throughout the United States. KD was more common in infants and toddlers, males, and Asian and part-Asian children. The illness was characterized by acute onset of prolonged high fever; maculopapular or scarlatiniform rash; adenopathy; injection of the conjunctival and mucous membranes of the upper respiratory tract; redness of the palms and soles; indurative edema of the extremities; desquamation, arthralgias; and elevated white blood cell count, erythrocyte sedimentation rate, and platelet count. Complications included gallbladder disease and carditis; 2.8% died. Surviving patients were hospitalized for a mean of 8.9 days.

HIV type 1 subtype E in commercial sex workers and injection drug users in southern Vietnam.

PIP: Nationwide HIV-1 seroprevalence rates in Vietnam are estimated to be almost 10% for IV drug users (IVDUs), 3% for female prostitutes, and 2% for males attending clinics for sexually transmitted diseases. These estimated prevalences are comparable to those observed in the same risk groups in Thailand 5 years ago. Blood samples were analyzed from two female HIV-1-seropositive prostitutes and three male IVDUs in southern Vietnam during April and May 1995. HIV-1 infection was confirmed by nested PCR in all five samples. Sequence alignment and comparison of the 325-nucleotide region with the major HIV-1 subtypes from widely separated geographic regions indicate that the Vietnam HIV-1 strains are genetically most similar to virus strains from Thailand, diverging from well-characterized subtype E strains by 3.1-5.9% and 5.6-12.0% at the nucleotide and deduced amino acid levels, respectively. The interstrain genetic variation among the Vietnam env sequences was 2.5-4.9%. None of the prostitutes and IVDUs studied had traveled to or worked in Thailand or Cambodia, and neither of the prostitutes used IV drugs, suggesting that they were infected sexually with indigenous strains circulating within Vietnam. The phylogenetic clustering of the Vietnam HIV-1 strains and their relative low degree of sequence variability are consistent with a founder effect and the recent introduction of HIV-1 subtype E.^ieng

Non-polio enterovirus disease in the United States, 1971--1975.

Reports to the Center for Disease Control on isolation of non-polio enteroviruses for the years 1971--1975 were analysed. During the 5 year period, enterovirus isolations were reported from 7 075 individuals. 90% of these occurred in the 7 month interval of May--November. Enteroviruses were isolated more frequently from males than females for all age groups in all 5 years. The incidence of reported isolations decreased with increasing age, and an inverse relationship between severity of disease and age was suggested. Clinical diagnoses associated with enteroviral isolations included aseptic meningitis, encephalitis, upper respiratory tract disease, non-specific febrile illness, gastroenteritis, pneumonia and lower respiratory tract disease, exanthem, and enanthem.

Lessons from a nursing home outbreak of influenza A.

OBJECTIVE: To characterize risk factors for outbreak-associated influenza illness and death in a nursing home. DESIGN: Outbreak investigation with predetermined and concurrently determined risk information. SETTING: A nursing home service in a multiward chronic care hospital, Honolulu, Oahu, 1989 to 1990. PATIENTS: Elderly nursing home patients receiving long-term care. INTERVENTIONS: Influenza vaccination, amantadine administration, and infection control measures. RESULTS: Neither routine infection control measures nor vaccination prevented illness, complications, or death in a nursing home outbreak of influenza A. The 55% case-fatality rate resulted from severe pneumonia. Influenza transmission may have been mediated by staff via either contaminated hands or fomites. CONCLUSIONS: Data from this and other outbreaks suggest that recommendations for preventing nosocomial influenza in the nation's 1.5 million nursing home residents should be reconsidered.

Growth of dengue type 2 virus isolates in human peripheral blood leukocytes correlates with severe and mild dengue disease.

We tested three dengue type 2 (DEN-2) isolates from children with clinically apparent but mild secondary dengue infections, and 10 isolates from children with moderately severe dengue hemorrhagic fever, and noted significant growth differences in peripheral blood leukocytes, but not in C6/36 cells. We also observed cytopathic effects in C6/36 cells that correlated with disease severity. These preliminary observations suggest the possibility that viral factors, whether surface antigens, attachment sites for entry into leukocytes, or intrinsic replication properties in human mononuclear phagocytes, might contribute to enhanced DEN infection and to the severity of the disease.

Dengue shock syndrome in an American traveler with primary dengue 3 infection.

A previously reported case of childhood dengue shock syndrome in an American traveler to India was investigated serologically. The original studies neither indicated the infecting serotype nor proved primary or secondary infection. However, BHK suspension PRNT of 6-year convalescent serum now indicates that the child had primary dengue type 3 infection. Dengue, dengue hemorrhagic fever, and dengue shock syndrome are potential hazards for American travelers and American residents of dengue-receptive areas.

Epidemic dengue fever in Puerto Rico, 1977: a cost analysis.

During the period July-December 1977, a widespread epidemic of dengue fever occurred in Puerto Rico. The cost of the epidemic was calculated, using upper and lower limit incidence figures, in terms of direct costs (medical care and epidemic control measures) and indirect costs (lost production of ill workers and parents of ill children). Direct costs were estimated to range between $2.4 and $4.7 million. Indirect costs were calculated by using current (1977) employment and wage data and population extrapolations from the 1970 census, and entailed a loss to the Puerto Rico economy of from $3.7 to $10.9 million. The total cost of this epidemic, therefore, was estimated to be in a range of $6.0 to $15.6 million, of which epidemic control measures comprised 7.8--20.2%.

Acute hemorrhagic conjunctivitis caused by enterovirus type 70: an epidemic in American Samoa.

From December 1981 to February 1982, an estimated 22,000 cases of acute hemorrhagic conjunctivitis (AHC) caused by enterovirus type 70 (EV 70) occurred among Samoan and non-Samoan residents of American Samoa. The overall attack rate was estimated to be 68%. Samoans of all ages resident in traditional housing and of large family size were at greatest risk of acquiring AHC, while non-Samoan adults resident in western style housing were at lowest risk. Epidemiologic aspects of AHC acquisition were also different for the Samoan and non-Samoan communities; index cases in Samoan households were frequently young adults, whereas index cases in non-Samoan households were commonly school age children, suggesting a role for school transmission in non-Samoans only. In this outbreak, subclinical AHC was rare; of 50 asymptomatic members of affected households, only 3 had neutralizing antibody to EV 70 (all with titers of 1:10). Investigation documented the highly contagious nature of AHC caused by EV 70, and the ease with which epidemic transmission may develop under conditions of crowding and frequent interpersonal contact.

Dengue in Puerto Rico, 1977: public health response to characterize and control an epidemic of multiple serotypes.

The largest and most extensive documented dengue epidemic in Puerto Rico struck an estimated 355,000 Puerto Rican residents from July-December 1977. The mixed epidemic of dengue types 2 and 3 coincided with a Caribbean pandemic of dengue type 1, first introduced into the western hemisphere in early 1977 and into Puerto Rico in the fall of that year. Health officials assembled a team to assess the epidemic and mounted a campaign to end it. Attempts to monitor the incidence and spread of dengue were confounded by simultaneous co-circulation of influenza virus, underscoring problems in formulating public health strategies dependent on nonspecific clinical and epidemiologic case criteria, and the need for rapid and reliable diagnostic capabilities. Despite co-circulation of multiple dengue serotypes, a risk factor associated with severe and fatal dengue hemorrhagic fever (DHF) in Southeast Asia, hospital and death certificate surveillance disclosed no cases of DHF in Puerto Rico. The epidemic serves as a reminder that when preventive measures are impossible or infeasible, developed countries with high living standards may be susceptible to large scale epidemics of infectious diseases.

Reye syndrome associated with vaccination with live virus vaccines. An exploration of possible etiologic relationships.

To determine whether vaccination with live virus vaccines may be etiologically related to Reye syndrome, we examined 404 cases reported to the Center for Disease Control. Fifteen of 269 children with Reye syndrome has been inoculated with live virus vaccines within 30 days before onset of illness. Although this temporal relationship may have occurred by chance, seasonal distribution and clustering of incubation periods suggests that live virus vaccines may occasionally serve as cofactors in the etiology of Reye syndrome through undefined mechanisms.

Thoughts on the relevance of medical history.

Clinicians are, by their very nature, historians--a question remains as to whether and how the history of medicine should be studied as a subject. In recent years medical educators have increasingly answered this question by deleting medical history from the curriculum. But this may be a mistake: among other things of value, medical history provides a much-needed perspective of medical knowledge, and a pigeon holer into which essential new facts--basic, clinical, whatever--can be filed without getting lost. But linear learning, the piling-on of facts, is more likely to bring exhaustion than comprehension.