Matthew J. Clarke

Pandemic versus Epidemic Influenza Mortality: A Pattern of Changing Age Distribution

Almost all deaths related to current influenza epidemics occur among the elderly. However, mortality was greatest among the young during the 1918-1919 pandemic. This study compared the age distribution of influenza-related deaths in the United States during this centurys three influenza A pandemics with that of the following epidemics. Half of influenza-related deaths during the 1968-1969 influenza A (H3N2) pandemic and large proportions of influenza-related deaths during the 1957-1958 influenza A (H2N2) and the 1918-1919 influenza A (H1N1) pandemics occurred among persons <65 years old. However, this group accounted for decrementally smaller proportions of deaths during the first decade following each pandemic. A model suggested that this mortality pattern may be explained by selective acquisition of protection against fatal illness among younger persons. The large proportion of influenza-related deaths during each pandemic and the following decade among persons <65 years old should be considered in planning for pandemics.

The impact of influenza epidemics on mortality: introducing a severity index.

OBJECTIVES The purpose of this study was to assess the impact of recent influenza epidemics on mortality in the United States and to develop an index for comparing the severity of individual epidemics. METHODS A cyclical regression model was applied to weekly national vital statistics from 1972 through 1992 to estimate excesses in pneumonia and influenza mortality and all-cause mortality for each influenza season. Each season was categorized on the basis of increments of 2000 pneumonia and influenza excess deaths, and each of these severity categories was correlated with a range of all-cause excess mortality. RESULTS Each of the 20 influenza seasons studied was associated with an average of 5600 pneumonia and influenza excess deaths (range, 0-11,800) and 21,300 all-cause excess deaths (range, 0-47,200). Most influenza A(H3N2) seasons fell into severity categories 4 to 6 (23,000-45,000 all-cause excess deaths), whereas most A(H1N1) and B seasons were ranked in categories 1 to 3 (0-23,000 such deaths). CONCLUSIONS From 1972 through 1992, influenza epidemics accounted for a total of 426,000 deaths in the United States, many times more than those associated with recent pandemics. The influenza epidemic severity index was useful for categorizing severity and provided improved seasonal estimates of the total number of influenza-related deaths.

Bronchiolitis-Associated Mortality and Estimates of Respiratory Syncytial Virus—Associated Deaths among US Children, 1979–1997

A 1985 estimate that 4500 respiratory syncytial virus (RSV)-associated deaths occur annually among US children has not been updated using nationally representative data. Thus, 1979-1997 multiple cause-of-death records for children <5 years old listing bronchiolitis, pneumonia, or any respiratory tract disease were examined. Deaths among children associated with any respiratory disease declined from 4631 in 1979 to 2502 in 1997. During the 19-year study period, 1806 bronchiolitis-associated deaths occurred (annual mean, 95 deaths; range, 66-127 deaths). Of these deaths, 1435 (79%) occurred among infants <1 year old. Congenital heart disease, lung disease, or prematurity was listed in death records of 179 (9.9%), 99 (5.5%), and 76 (4.2%) children dying with bronchiolitis, respectively. By applying published proportions of children hospitalized for bronchiolitis or pneumonia who were RSV-infected to bronchiolitis and pneumonia deaths, it was estimated that < or =510 RSV-associated deaths occurred annually during the study period, fewer than previously estimated.

Antibody Response in Individuals Infected with Avian Influenza A (H5N1) Viruses and Detection of Anti-H5 Antibody among Household and Social Contacts

The first documented outbreak of human respiratory disease caused by avian influenza A (H5N1) viruses occurred in Hong Kong in 1997. The kinetics of the antibody response to the avian virus in H5N1-infected persons was similar to that of a primary response to human influenza A viruses; serum neutralizing antibody was detected, in general, >/=14 days after symptom onset. Cohort studies were conducted to assess the risk of human-to-human transmission of the virus. By use of a combination of serologic assays, 6 of 51 household contacts, 1 of 26 tour group members, and none of 47 coworkers exposed to H5N1-infected persons were positive for H5 antibody. One H5 antibody-positive household contact, with no history of poultry exposure, provided evidence that human-to-human transmission of the avian virus may have occurred through close physical contact with H5N1-infected patients. In contrast, social exposure to case patients was not associated with H5N1 infection.

Hospitalizations Associated with Rotavirus Diarrhea in the United States, 1993 through 1995: Surveillance Based on the New ICD-9-CM Rotavirus-Specific Diagnostic Code

The introduction of a specific International Classification of Diseases code for rotavirus diarrhea in 1992 prompted examination of the National Hospital Discharge Survey (NHDS) for trends in rotavirus-associated hospitalizations among US children aged 1 month through 4 years. During 1993-1995, 13.5% of hospitalizations were associated with diarrhea (n = 162,478/year). Rotavirus was the most common pathogen identified, coded in 16.5% of diarrhea cases (n = 26,798/year), and increased from 13.3% in 1993 to 18.9% in 1995. The age distribution and seasonality of hospitalizations of presumed noninfectious and viral etiology resembled those associated with rotavirus. Rotavirus was reported as a cause of diarrhea more frequently by hospitals that were large (> or =100 beds), proprietary-owned, or in the West/Midwest. Although these findings suggest incomplete detection of rotavirus diarrhea cases, the large number of rotavirus-associated hospitalizations underscores the need for vaccines and indicates that NHDS data could be used to monitor the impact of a US rotavirus immunization program.

Risk of Influenza A (H5N1) Infection among Health Care Workers Exposed to Patients with Influenza A (H5N1), Hong Kong

The first outbreak of avian influenza A (H5N1) occurred among humans in Hong Kong in 1997. To estimate the risk of person-to-person transmission, a retrospective cohort study was conducted to compare the prevalence of H5N1 antibody among health care workers (HCWs) exposed to H5N1 case-patients with the prevalence among nonexposed HCWs. Information on H5N1 case-patient and poultry exposures and blood samples for H5N1-specific antibody testing were collected. Eight (3.7%) of 217 exposed and 2 (0.7%) of 309 nonexposed HCWs were H5N1 seropositive (P=.01). The difference remained significant after controlling for poultry exposure (P=.01). This study presents the first epidemiologic evidence that H5N1 viruses were transmitted from patients to HCWs. Human-to-human transmission of avian influenza may increase the chances for the emergence of a novel influenza virus with pandemic potential.

The epidemiology of necrotizing enterocolitis infant mortality in the United States.

OBJECTIVES This study examined trends and risk factors for infant mortality associated with necrotizing enterocolitis in the United States. METHODS Necrotizing enterocolitis-associated deaths and infant mortality rates from 1979 through 1992 were determined by means of US multiple cause-of-death and linked birth/infant death data. RESULTS Annual necrotizing enterocolitis infant mortality rates decreased from 1979 through 1986 but increased thereafter and were lower during the 3-year period before (1983 through 1985;11.5 per 100,000 live births) the introduction of surfactants than after (1990 through 1992; 12.3 per 100,000). Low-birthweight singleton infants who were Black male, or born to mothers younger than 17 had increased risk for necrotizing enterocolitis-associated death. CONCLUSIONS As mortality among low-birth weight infants continues to decline and smaller newborns survive early causes of death, necrotizing enterocolitis-associated infant mortality may increase.

Pediatric Hospitalizations for Croup (Laryngotracheobronchitis): Biennial Increases Associated with Human Parainfluenza Virus 1 Epidemics

Croup is a common manifestation of respiratory tract infection in children, and human parainfluenza virus 1 (HPIV-1) is the agent most commonly associated with croup. In the United States, HPIV-1 produces a distinctive pattern of biennial epidemics of respiratory illness during the autumn months of odd-numbered years. National Hospital Discharge Survey data for croup hospitalizations among patients <15 years old between 1979 and 1993 were examined along with laboratory-based surveillance data on HPIV-1 activity in the United States. The mean annual number of croup hospitalizations was 41,000 (range, 27,000-62,000/year). Ninety-one percent of hospitalizations occurred among children <5 years of age. Minor peaks in croup hospitalizations occurred each year in February, and major peaks occurred in October of odd-numbered years, coincident with peak HPIV-1 activity. Each biennial epidemic of HPIV-1 was associated with 18,000 excess croup hospitalizations nationwide.

Hidden Mortality Attributable to Rocky Mountain Spotted Fever: Immunohistochemical Detection of Fatal, Serologically Unconfirmed Disease

Rocky Mountain spotted fever (RMSF) is the most severe tickborne infection in the United States and is a nationally notifiable disease. Since 1981, the annual case-fatality ratio for RMSF has been determined from laboratory-confirmed cases reported to the Centers for Disease Control and Prevention (CDC). Herein, a description is given of patients with fatal, serologically unconfirmed RMSF for whom a diagnosis of RMSF was established by immunohistochemical (IHC) staining of tissues obtained at autopsy. During 1996-1997, acute-phase serum and tissue samples from patients with fatal disease compatible with RMSF were tested at the CDC. As determined by indirect immunofluorescence assay, no patient serum demonstrated IgG or IgM antibodies reactive with Rickettsia rickettsii at a diagnostic titer (i.e., >/=64); however, IHC staining confirmed diagnosis of RMSF in all patients. Polymerase chain reaction validated the IHC findings for 2 patients for whom appropriate samples were available for testing. These findings suggest that dependence on serologic assays and limited use of IHC staining for confirmation of fatal RMSF results in underestimates of mortality and of case-fatality ratios for this disease.

Bronchiolitis-associated hospitalizations among American Indian and Alaska Native children.

BACKGROUND Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract illness among infants and young children. Respiratory system diseases account for a large proportion of hospitalizations in American Indian and Alaska Native (AI/AN) children; however, aggregate estimates of RSV-associated hospitalizations among AI/AN children have not been made. METHODS We used Indian Health Service hospitalization data from 1990 through 1995 to describe hospitalizations associated with bronchiolitis, the most characteristic clinical manifestation of RSV infection, among AI/AN children <5 years old. RESULTS The overall bronchiolitis-associated hospitalization rate among AI/AN infants < 1 year old was considerably higher (61.8 per 1,000) than the 1995 estimated bronchiolitis hospitalization rate among all US infants (34.2 per 1,000). Hospitalization rates were higher among male infants (72.2 per 1,000) than among females infants (51.1 per 1,000). The highest infant hospitalization rate was noted in the Navajo Area (96.3 per 1,000). Hospitalizations peaked annually in January or February, consistent with national peaks for RSV detection. Bronchiolitis hospitalizations accounted for an increasing proportion of hospitalizations for lower respiratory tract illnesses. CONCLUSIONS Bronchiolitis-associated hospitalization rates are substantially greater for AI/AN infants than those for all US infants. This difference may reflect an increased likelihood of severe RSV-associated disease or a decreased threshold for hospitalization among AI/AN infants with bronchiolitis compared with all US infants. AI/AN children would receive considerable benefit from lower respiratory tract illness prevention programs, including an RSV vaccine, if and when one becomes available.