Robert C. Holman

Human Prion Diseases in the United States

Background Prion diseases are a family of rare, progressive, neurodegenerative disorders that affect humans and animals. The most common form of human prion disease, Creutzfeldt-Jakob disease (CJD), occurs worldwide. Variant CJD (vCJD), a recently emerged human prion disease, is a zoonotic foodborne disorder that occurs almost exclusively in countries with outbreaks of bovine spongiform encephalopathy. This study describes the occurrence and epidemiology of CJD and vCJD in the United States. Methodology/Principal Findings Analysis of CJD and vCJD deaths using death certificates of US residents for 1979–2006, and those identified through other surveillance mechanisms during 1996–2008. Since CJD is invariably fatal and illness duration is usually less than one year, the CJD incidence is estimated as the death rate. During 1979 through 2006, an estimated 6,917 deaths with CJD as a cause of death were reported in the United States, an annual average of approximately 247 deaths (range 172–304 deaths). The average annual age-adjusted incidence for CJD was 0.97 per 1,000,000 persons. Most (61.8%) of the CJD deaths occurred among persons ≥65 years of age for an average annual incidence of 4.8 per 1,000,000 persons in this population. Most deaths were among whites (94.6%); the age-adjusted incidence for whites was 2.7 times higher than that for blacks (1.04 and 0.40, respectively). Three patients who died since 2004 were reported with vCJD; epidemiologic evidence indicated that their infection was acquired outside of the United States. Conclusion/Significance Surveillance continues to show an annual CJD incidence rate of about 1 case per 1,000,000 persons and marked differences in CJD rates by age and race in the United States. Ongoing surveillance remains important for monitoring the stability of the CJD incidence rates, and detecting occurrences of vCJD and possibly other novel prion diseases in the United States.

Comparison of monocyte separation methods using flow cytometric analysis

We isolated normal, nonactivated human monocytes from peripheral blood by four different methods: (1) rosetting with sheep erythrocytes pretreated with 2-aminoethylisothiouronium bromide hydrobromide (AET) followed by monoclonal antibody (OKT3 (CD3), B1 (CD19), Leu7, Leu11 (CD16] and complement treatment; (2) adherence to gelatin/plasma-coated flasks; (3) adherence to plastic dishes; and (4) separation by the Sepracell technique. We monitored these monocyte separations by determining cell recoveries, OKT4A+ lymphocyte contamination, monocyte binding to human immunodeficiency virus (HIV), number of non-specific esterase-positive cells, and proportion of mononuclear cells reactive with a battery of monoclonal antibodies specific for monocytes. Our results indicate that of the four methods compared, adherence to gelatin/plasma-coated flasks produced the highest purity, recovery, and satisfactory binding to HIV with the fewest contaminating CD4+ T cells.

Trends in Lower Respiratory Tract Infection Hospitalizations among American Indian/Alaska Native Children and the General US Child Population

OBJECTIVEnTo describe trends in the rate of hospitalization for lower respiratory tract infection (LRTI) among American Indian/Alaska Native (AI/AN) children and the general US population of children aged <5 years.nnnSTUDY DESIGNnThis was a retrospective analysis of trends and hospitalization rates for LRTI-associated hospitalizations in 1998-2008 among AI/AN children aged <5 years using the Indian Health Service direct/contract inpatient data, and also among the general population of US children aged <5 years using the Nationwide Inpatient Sample.nnnRESULTSnThe 2006-2008 LRTI-associated hospitalization rate for AI/AN children aged <5 years (21.8 per 1000/year) was 32% lower than the 1998-1999 rate, and 1.6-fold higher than the general US children rate (13.8 per 1000/year; 95% CI, 12.8-14.8). Higher rates were seen in AI/AN children aged <5 years in the Alaska and the Southwest regions of the United States (41.2 and 28.0 per 1000/year, respectively). In infants, these rates were 136.4 and 82.4 per 1000/year, respectively, exceeding the rate in the general US infant population (37.1 per 1000/year; 95% CI, 34.3-40.0). The greatest disparity in the LRTI-associated hospitalization rate between AI/AN infants and the general US infant population was seen for pneumonia, with a 3-fold higher rate in AI/AN infants (36.2 per 1000/year vs 12.7 per 1000/year; 95% CI, 11.8-13.6).nnnCONCLUSIONnThe LRTI-associated hospitalization rate is higher in AI/AN children, particularly infants from Alaska and the American Southwest, compared with the general US child population. Closing this gap will require addressing housing and sanitation inequities and ensuring high immunization rates and access to care.

Venous thromboembolism hospitalizations among American Indians and Alaska Natives

Cardiovascular disease (CVD) has been reported to be on the increase in the American Indian/Alaska Native (AI/AN) population. The Indian Health Service (IHS) hospital discharge database was used to describe venous thromboembolism (VTE)-associated hospitalizations among patients receiving IHS-reported medical care in the United States from 1980 through 1996. The average overall VTE-associated hospitalization rate in the AI/AN population during 1980-1996 was 33.1 per 100,000, however, the rate significantly decreased from 38.4 per 100,000 AI/ANs in 1980-1982 to 33.2 in 1994-1996. The average age at hospitalization was 50.4 years, which was consistent during the 17-year period. The overall annual VTE hospitalization rate was higher for females than for males (38.0 versus 27.7 per 100,000). The female VTE hospitalization rates decreased significantly from 46.1 per 100,000 in 1980-1982 to 36.7 per 100,000 in 1994-1996 (risk ratio: RR=1.3; 95% confidence interval: CI=1.1-1.4), while the rates for males remained unchanged. The VTE hospitalization rates also varied by geographic region. The hospitalization rate was highest in the East region (52.2 per 100,000) and lowest in the Alaska region (16.1 per 100,000). These data indicate that the overall VTE rate for AI/ANs may not have only decreased, but appears lower than the reported rate for Caucasians.

Progressive multifocal leukoencephalopathy deaths in the USA, 1979-2005.

Background: Progressive multifocal leukoencephalopathy (PML) is a neurological disease most often seen among immunosuppressed patients. The incidence of PML increased with an increasing incidence of HIV/AIDS. We describe recent trends and the epidemiology of PML-associated death in the era of highly active antiretroviral therapy (HAART). Methods: National multiple-cause-of-death data for the USA were used to identify records with PML listed as a cause of death during 1979–2005. Age-adjusted PML-associated death rates were calculated overall and by sex, race, region and HIV status. Results: The PML-associated death rates peaked in the mid-1990s and decreased from 2.76 deaths per 1 million persons in 1992–1995 to 0.66 in 2002–2005. This decrease was mainly due to a decreasing death rate among PML decedents with HIV diagnosis, males and those aged 20–49 years at death. A decline in death rate was also seen among PML decedents without HIV diagnosis, although this trend was not significant. Decedents in the latter time period were more often female, and older. The proportion of HIV-associated deaths from PML decreased between 1992–1995 (1.4%) and 2002–2005 (1.0%). Conclusion: PML mortality has decreased significantly since 1996 when HAART became the standard of care in the USA. This decline likely reflects increased survival among HIV-positive persons who receive HAART.

Trends in non-Hodgkin lymphoma (NHL) and HIV-associated NHL deaths in the United States.

Since a significant number of lymphomas have been associated with the human immunodeficiency virus (HIV), the purpose of this study was to describe the impact of HIV infection on non‐Hodgkins lymphoma (NHL) mortality trends and demographics. Multiple‐cause‐of‐death data for the United States from 1979 through 1996 were obtained from the National Center for Health Statistics, Centers for Disease Control and Prevention. Annual NHL deaths rates for the United States were calculated as the number of NHL deaths per 100,000 persons, based on estimates of the U.S. resident population. The time periods 1979–1982, 1986–1989, and 1993–1996 were examined for changes over time. To describe NHL and HIV infection mortality, the characteristics of NHL deaths with HIV infection listed anywhere on the death records were examined beginning in 1987. This study found that despite reports of a lower incidence rate of NHL among blacks with HIV/AIDS, death rates from lymphomas associated with HIV/AIDS have markedly increased in black males and females over time. It was also noted that in agreement with other studies, this study documented a decrease in NHL/HIV mortality in 1996. Am. J. Hematol. 66:159–166, 2001. Published 2001 Wiley‐Liss, Inc.

Methicillin-Resistant Staphylococcus aureus-Associated Hospitalizations among the American Indian and Alaska Native Population

BACKGROUNDnAmerican Indians and Alaska Natives (AI/ANs) have had documented outbreaks of methicillin-resistant Staphylococcus aureus (MRSA) infection but, to our knowledge, no studies have examined MRSA infection among this population nationally. We describe MRSA-associated hospitalizations among the approximately 1.6 million AI/ANs who receive care at Indian Health Service health care facilities nationwide.nnnMETHODSnWe used hospital discharge data from the Indian Health Service National Patient Information Reporting System to determine the rate of MRSA-associated hospitalizations among AI/ANs who used Indian Health Service health care in 1996-2005 and in the comparison periods 1996-1998 and 2003-2005. Hospitalization rates among AI/ANs were examined by year, age group, sex, and region. MRSA-associated diagnoses were also examined. Rate comparisons were performed using Poisson regression analysis. Comparison of rates to those of the general United States population was made for 2003-2005 by means of the Nationwide Inpatient Sample.nnnRESULTSnBetween comparison periods, the rate of MRSA-associated hospitalization increased from 4.6 to 50.6 hospitalizations per 100,000 AI/ANs (P<.01), with increases in both sexes, all age groups, and all regions. By 2005, MRSA was the causative organism for the majority (52%) of all S. aureus-associated hospitalizations. The most common associated diagnosis was skin and soft-tissue infection, which accounted for 59% of MRSA-associated diagnoses. In 2003-2005, the age-adjusted rate among AI/ANs was 58.8 hospitalizations per 100,000 persons, compared with 84.7 hospitalizations per 100,000 persons in the general US population.nnnCONCLUSIONSnMRSA-associated hospitalizations have increased significantly among AI/ANs served by Indian Health Service health care facilities. Clinicians should have a high index of suspicion for MRSA infection in AI/ANs, especially in those with a diagnosis of skin and soft-tissue infection.

Increasing trend in the rate of infectious disease hospitalisations among Alaska Native people

Objectives To examine the epidemiology of infectious disease (ID) hospitalisations among Alaska Native (AN) people. Methods Hospitalisations with a first-listed ID diagnosis for American Indians and ANs residing in Alaska during 2001–2009 were selected from the Indian Health Service direct and contract health service inpatient data. ID hospitalisations to describe the general US population were selected from the Nationwide Inpatient Sample. Annual and average annual (2007–2009) hospitalization rates were calculated. Results During 2007–2009, IDs accounted for 20% of hospitalisations among AN people. The 2007–2009 average annual age-adjusted ID hospitalisation rate (2126/100,000 persons) was higher than that for the general US population (1679/100,000; 95% CI 1639–1720). The ID hospitalisation rate for AN people increased from 2001 to 2009 (17%, p<0.001). Although the rate during 2001–2009 declined for AN infants (<1 year of age; p=0.03), they had the highest 2007–2009 average annual rate (15106/100,000), which was 3 times the rate for general US infants (5215/100,000; 95% CI 4783–5647). The annual rates for the age groups 1–4, 5–19, 40–49, 50–59 and 70–79 years increased (p<0.05). The highest 2007–2009 age-adjusted average annual ID hospitalisation rates were in the Yukon-Kuskokwim (YK) (3492/100,000) and Kotzebue (3433/100,000) regions; infant rates were 30422/100,000 and 26698/100,000 in these regions, respectively. During 2007–2009, lower respiratory tract infections accounted for 39% of all ID hospitalisations and approximately 50% of ID hospitalisations in YK, Kotzebue and Norton Sound, and 74% of infant ID hospitalisations. Conclusions The ID hospitalisation rate increased for AN people overall. The rate for AN people remained higher than that for the general US population, particularly in infants and in the YK and Kotzebue regions. Prevention measures to reduce ID morbidity among AN people should be increased in high-risk regions and for diseases with high hospitalisation rates.

Evaluation of seasonal patterns of Kawasaki Syndrome- and rotavirus-associated hospitalizations in California and New York, 2000-2005

BackgroundKawasaki Syndrome (KS) is an uncommon childhood disease with unknown etiology. It has been suggested that rotavirus infection may play a causative role in the development of KS.MethodsTo examine potential temporal associations between KS and rotavirus infection, seasonal patterns of KS- and rotavirus-associated hospitalizations among children in California and New York during 2000-2005 were compared.ResultsRotavirus hospital admissions were markedly winter seasonal, with very few summer hospitalizations. KS hospitalizations occurred year-round but also peaked slightly during winter and spring.ConclusionThe strong winter seasonal pattern of rotavirus clearly differed from the year-round pattern of KS hospitalizations. While the present study cannot completely rule out rotavirus as having a role in the development of KS, other agents must be involved in the etiology of KS.

Hodgkin disease mortality in the United States: 1979-1988.

Mortality trends for Hodgkin disease in the United States were examined from 1979 to 1988 with the use of mortality data for multiple causes of death, which were obtained from the National Center for Health Statistics. A progressive decrease in the death rate from Hodgkin disease was observed over this period. The decrease in death rate was greatest among white patients. Patients who were 55 years or older had the highest death rate. Analysis by geographic region showed decreases in each of the regions, with no significant difference among groups of states with high and low incidences of acquired immune deficiency syndrome. However, the decrease in the South was approximately 35% greater than that in the Northeast. In 1988 the most significant difference in death rates between male and female patients was in the 35‐54‐year age group, whereas a significant difference in death rates between white and black patients was seen only in patients who were 55 years of age or older. In summary, although there has been a significant reduction in deaths resulting from Hodgkin disease between 1979 and 1988, the decreases observed have varied between sexes and among age groups, racial groups, and geographic regions.