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.

Association of coffee and caffeine intake with the risk of Parkinson disease.

CONTEXT: The projected expansion in the next several decades of the elderly population at highest risk for Parkinson disease (PD) makes identification of factors that promote or prevent the disease an important goal. OBJECTIVE: To explore the association of coffee and dietary caffeine intake with risk of PD. DESIGN, SETTING, AND PARTICIPANTS: Data were analyzed from 30 years of follow-up of 8004 Japanese-American men (aged 45-68 years) enrolled in the prospective longitudinal Honolulu Heart Program between 1965 and 1968. MAIN OUTCOME MEASURE: Incident PD, by amount of coffee intake (measured at study enrollment and 6-year follow-up) and by total dietary caffeine intake (measured at enrollment). RESULTS: During follow-up, 102 men were identified as having PD. Age-adjusted incidence of PD declined consistently with increased amounts of coffee intake, from 10.4 per 10,000 person-years in men who drank no coffee to 1.9 per 10,000 person-years in men who drank at least 28 oz/d (P<.001 for trend). Similar relationships were observed with total caffeine intake (P<.001 for trend) and caffeine from non-coffee sources (P=.03 for trend). Consumption of increasing amounts of coffee was also associated with lower risk of PD in men who were never, past, and current smokers at baseline (P=.049, P=.22, and P=.02, respectively, for trend). Other nutrients in coffee, including niacin, were unrelated to PD incidence. The relationship between caffeine and PD was unaltered by intake of milk and sugar. CONCLUSIONS: Our findings indicate that higher coffee and caffeine intake is associated with a significantly lower incidence of PD. This effect appears to be independent of smoking. The data suggest that the mechanism is related to caffeine intake and not to other nutrients contained in coffee. JAMA. 2000;283:2674-2679.

Summary of antibody workshop: The Role of Humoral Immunity in the Treatment and Prevention of Emerging and Extant Infectious Diseases.

In the era before antibiotics, human diseases were commonly treated with immune animal and human sera, often with life-saving results. With the advent of emerging infectious diseases, many of which cannot be adequately treated or prevented, attempts to develop antibody treatments have taken on new importance. The role of humoral immunity in treatment and prevention was the focus of discussion at a 1996 workshop. The cellular and molecular mechanisms of neutralization were examined in detail. It was noted that success in passive immunity has frequently been the key element in devising a successful strategy to develop a vaccine for active immunization. The workshop concluded on a cautious note of optimism that antibody-based treatment and prevention for diseases such as human immunodeficiency virus infection, Ebola fever, and others of clinical and public health importance deserve further development and clinical trial.

Sequence and phylogenetic analyses of HIV-1 infection in Vietnam: subtype E in commercial sex workers (CSW) and injection drug users (IDU).

More than 4,000 persons with human immunodeficiency virus type 1 (HIV-1) infection have been identified in Vietnam through sentinel surveillance since 1990, when the first case of HIV-1 infection was diagnosed in a young woman in Ho Chi Minh City. Currently, the estimated HIV-1 seroprevalences of 10% for injection drug users (IDU) and 3% for female commercial sex workers (CSW) in Vietnam are comparable to those observed in the same risk groups in Thailand five years ago. To clarify if concurrent epidemics with different HIV-1 subtypes (or clades) are occurring among different high-risk behavior groups in Vietnam, we conducted a genotypic analysis of HIV-1 by amplifying and sequencing a 325-nucleotide region spanning the principal neutralizing domain, or V3 loop, of the gp120-encoding env gene from genomic DNA extracted from dried, filter paper-blotted blood samples, collected in April/May and August/September 1995 from 8 HIV-1-seropositive CSW in Ho Chi Minh City, Can Tho and An Giang provinces and from 16 IDU in Ho Chi Minh City, Hanoi, Nha Trang and An Giang province. Sequence alignment and comparison with other HIV-1 subtypes indicated that the HIV-1 strains from CSW and IDU in Vietnam were genetically most similar to subtype E strains from Cambodia. The interstrain genetic variation among the Vietnam HIV-1 env sequences ranged from 0.3% to 9.0% (mean, 4.6%). Phylogenetic analysis verified that some of the Vietnam HIV-1 strains formed discrete clusters and were indistinguishable from other Southeast Asian strains. The demonstration of subtype E in both CSW and IDU in Vietnam contrasts sharply with the previously observed HIV-1 clade restriction in these high-risk behavior groups in nearby Thailand.

Dengue 1 virus binding to human hepatoma HepG2 and simian Vero cell surfaces differs.

We analysed the binding and infectivity of dengue virus serotype 1 (DEN-1) for the human hepatoma cell line HepG2 in comparison with the simian kidney cell line Vero. The higher susceptibility of Vero cells to DEN-1 correlated with greater binding affinity of DEN-1 to these cells. In contrast, the capacity of virus attachment was higher for HepG2 than for Vero cells. Profiles of DEN-1 binding at different pH were markedly different between the two cell types. A type-specific neutralizing monoclonal antibody reduced initial virus binding to both cell types similarly but complex- and group-specific neutralizing antibodies affected virus adhesion differently. Altogether, these results suggest the involvement of different receptors or receptors presented in a different environment on the cell surface in the two cell lines. The sensitivity to proteolytic enzymes and to ionic detergent of the binding sites on the two cell types was tested and results indicated that they may be multimeric proteins or protein complexes.

Observations on serum uric acid levels and the risk of idiopathic Parkinson's disease.

Uric acid, an antioxidant found in high concentrations in serum and in the brain, has been hypothesized to protect against oxidative damage and cell death in Parkinson's disease. The authors tested this hypothesis among men participating in a 30-year prospective study known as the Honolulu Heart Program. Serum uric acid was measured in 7,968 men at the baseline examination held from 1965 to 1968. Of these men, 92 subsequently developed idiopathic Parkinson's disease (IPD). In analyses adjusted for age and smoking, men with uric acid concentrations above the median at enrollment had a 40% reduction in IPD incidence (rate ratio (RR) = 0.6; 95% confidence interval (CI) 0.4-1.0). Reduced IPD incidence rates persisted in analyses restricted to nonsmokers (RR = 0.5; 95% CI 0.3-1.0) and cases younger than age 75 years (RR = 0.5; 95% CI 0.3-0.9). Incidence rates were not notably affected when analyses were restricted to cases that occurred more than 5 years after uric acid measurement (RR = 0.6; 95% CI 0.4-1.0). Inclusion of known or computed correlates of uric acid in regression models did not substantially change risk of IPD. This study provides prospective evidence of an association between uric acid and reduced occurrence of IPD and indicates that further investigations of this association are warranted.

Evidence against the operation of selective mortality in explaining the association between cigarette smoking and reduced occurrence of idiopathic Parkinson disease.

To investigate the association between idiopathic Parkinson disease (IPD) and reduced frequency of prior cigarette smoking, the authors compared the 29-year follow-up mortality rates and IPD incidence rates of men who were either cigarette smokers or nonsmokers at the time of enrollment in the Honolulu Heart Study (1965-1968). Based on IPD cases detected up to June 30, 1994, the age-adjusted incidence rate in smokers was less than half that in nonsmokers: 34.4 versus 94.2 cases per 100,000 person-years of pre-illness follow-up, respectively. When data were stratified by 5-year age group, lower IPD incidence in smokers was observed at all ages between 50 and 90 years. Age-specific mortality trends for smokers and nonsmokers with and without IPD suggested that increased mortality in IPD patients was mostly associated with IPD itself and not with smoking. The slight excess mortality in smokers without IPD, versus nonsmokers without IPD, appeared insufficient to account for the "missing" incident IPD cases in smokers. These IPD incidence and mortality data are not highly consistent with the "selective mortality" hypothesis, which attributes reduced prior smoking frequency, typically reported by persons with IPD, to accelerated mortality in undiagnosed IPD-affected persons who smoke. The "protective" association of cigarette smoking with IPD occurrence may thus be real, suggesting the need for further study of biologic mechanisms of protection.

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

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.

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.