Allen W. Hightower

Epidemic Listeriosis — Evidence for Transmission by Food

The bacterium Listeria monocytogenes is a motile, gram-positive coccobacillus that can frequently be isolated from soil, water, and vegetation. It is a common cause of meningoencephalitis and abort...

The emergence of methicillin-resistant Staphylococcus aureus infections in United States hospitals. Possible role of the house staff-patient transfer circuit.

Infections with methicillin-resistant strains of Staphylococcus aureus appear to be occurring with increasing frequency in some U.S. hospitals about a decade after a similar increase in Britain and other countries. In the United States, clustered methicillin-resistant S. aureus infections reported in scientific journals and in three hospital surveys have been almost entirely in large, tertiary referral hospitals affiliated with medical schools. Among 63 hospitals regularly reporting infections from 1974 to 1981 in the National Nosocomial Infections Study, the increase in methicillin-resistant S. aureus infections was entirely due to substantial increases in only four hospitals, all of which were large, tertiary referral centers affiliated with medical schools. The predominance of methicillin-resistant S. aureus infections in these large hospitals may be due to the large numbers of patients at high risk of infection and to the interhospital spread of the organism by the transfer of infected patients and house staff from similar hospitals or from nursing homes.Abstract Infections with methicillin-resistant strains ofStaphylococcus aureusappear to be occurring with increasing frequency in some U.S. hospitals about a decade after a similar increase in Brit...

Enteric Viruses and Diarrhea in HIV-Infected Patients

BACKGROUND Diarrhea occurs frequently among persons with the acquired immunodeficiency syndrome, but the cause often remains unknown. We used a group of diagnostic assays to determine which viruses were etiologic agents of diarrhea in a group of persons infected with the human immunodeficiency virus (HIV). METHODS Stool and serum specimens were obtained from HIV-infected patients enrolled in a longitudinal study in Atlanta. Fecal specimens from patients with diarrhea and from control patients without diarrhea were screened by electron microscopy, polyacrylamide-gel electrophoresis, and enzyme immunoassays for rotaviruses, enteric adenoviruses, caliciviruses, picobirnaviruses, and astroviruses. Paired serum samples were tested for antibody responses to Norwalk virus and picobirnavirus. RESULTS Viruses were detected in 35 percent of 109 fecal specimens from patients with diarrhea but in only 12 percent of 113 specimens from those without diarrhea (P < 0.001). Specimens from patients with diarrhea were more likely than those from patients without diarrhea to have astrovirus (12 percent vs. 2 percent, P = 0.003); picobirnavirus (9 percent vs. 2 percent, P = 0.017); caliciviruses, including small round structured viruses (6 percent vs. 1 percent, P = 0.062); and adenoviruses (9 percent vs. 3 percent, P = 0.047). They were also more likely to have a mixed viral infection (6 percent vs. 0 percent, P = 0.006). With the use of polyacrylamide-gel electrophoresis to analyze concentrated RNA extracts from stool, picobirnavirus was detected in fecal specimens from 6 of the 65 patients with diarrhea and was associated with prolonged viral shedding and chronic diarrhea. No rotaviruses, enteric adenoviruses, or instances of seroconversion to positivity for Norwalk virus were observed. CONCLUSIONS Novel enteric viruses such as astrovirus and picobirnavirus may be more important etiologic agents of diarrhea in HIV-infected patients than previously recognized and may be more common than either bacterial or parasitic enteropathogens.

Cryptosporidiosis: An Outbreak Associated with Drinking Water Despite State-of-the-Art Water Treatment

Cryptosporidium parvum is transmitted through the ingestion of oocysts excreted in human or animal feces. Commonly recognized modes of spread include person-to-person and animal-to-person contact, exposure to contaminated objects, and ingestion of contaminated food or water [1-3]. The March 1993 outbreak of cryptosporidiosis in Milwaukee, Wisconsin, which affected more than 400 000 persons [4], heightened awareness about waterborne transmission of C. parvum. The Milwaukee water utility, like those associated with the previously recognized outbreaks caused by waterborne C. parvum in the United States [4-6], had met all existing state and federal standards for drinking water. We report an outbreak of cryptosporidiosis that occurred in 1994 in Clark County, Nevada, a county of about 1 million residents, most of whom live in Las Vegas. The outbreak was associated with drinking water, despite a state-of-the-art water treatment plant and water quality that was much better than that noted during the outbreak in Milwaukee. Cryptosporidium infection has been reportable in Nevada since 1992; physicians and laboratories are required to report stool specimens that test positive for the organism to their county health departments. Three cases of Cryptosporidium infection in residents of Clark County were reported by the state health department in 1992, and 23 were reported in 1993; 1 of the 1992 cases (33%) and 18 of the 1993 cases (78%) were known to have occurred in persons infected with the human immunodeficiency virus (HIV). In contrast, more than 70 cases of cryptosporidiosis were reported in the first 4 months of 1994, and most of these were in HIV-infected persons. We conducted an investigation to identify the magnitude and cause of this increase and to determine whether many cases had occurred in persons who were not infected with HIV. This outbreak (which was documented, in part, because the community was one of the few in the United States in 1994 that had a surveillance system for cryptosporidiosis) raises the question of how often outbreaks caused by waterborne C. parvum are unrecognized in the United States. Methods Case Ascertainment and Confirmation All testing of specimens from county residents for Cryptosporidium is done by two laboratories in Clark County and one at the Nevada state health department; testing is done only at the request of a physician. We reviewed the records from laboratory A, which does more than 95% of this testing, and the surveillance records at the county health department to identify all cases of Cryptosporidium infection newly diagnosed during the 4-month study period (1 January through 30 April 1994). We also reviewed the death certificates of persons who had had laboratory-confirmed cryptosporidiosis to determine whether cryptosporidiosis or Cryptosporidium was listed as an immediate or contributing cause of death. Case-Control Study of Adults with HIV Infection A case-patient was defined as an HIV-infected adult ( to 18 years of age) living in Clark County in whom laboratory-confirmed cryptosporidiosis was diagnosed for the first time during the study period. Each case-patient was matched by primary physician or clinic with three HIV-infected adult controls from the county; one control in each of three CD4+ cell count categories (< 100 cells/mm3, 100 to 199 cells/mm3, and more than or equals to 200 cells/mm3) was selected. Stool specimens from controls were not tested for Cryptosporidium. Telephone interviews were done using a standardized questionnaire in May and June 1994. The exposure period for case-patients was defined as the 4 weeks before the case-patients became ill; matched controls were asked about exposures during this period and about illness in the 4 months before their interviews. Study participants were asked whether they had been exposed to persons who may have been infected with Cryptosporidium (whether they lived in the same household with or visited or cared for a person who had diarrhea); whether they lived in a household in which someone attended or worked in a child-care setting or in which a child wore diapers; whether they had changed a childs diaper; and whether they had had any type of sexual activity or had engaged in high-risk sexual activity (anal-oral intercourse). Participants were asked about contact with newborn animals (< 4 months of age) and about visits to farms, pet stores, animal shows, animal pounds, petting zoos, and veterinarians; about restaurant patronage and consumption of uncooked and cold foods, unpasteurized dairy products, health foods, and dietary supplements; about exposure to recreational water (in a pool, whirlpool bath, hot tub, lake, or river); and about types of drinking water used at home and work (for example, tap water, tap water filtered at its point of use, bottled water, or well water). Study patients were asked whether they had immunosuppressive medical conditions other than HIV infection, whether they took immunosuppressive medications, and whether they had used nontraditional therapy for HIV infection; they were also asked about miscellaneous exposures, such as travel outside of Clark County and attendance at bars, clubs, and social functions. Case-Control Study of Immunocompetent Children In a casecontrol study of children that was similar to the study of adults described above, each case-patient who had laboratory-confirmed cryptosporidiosis was matched with three controls by age ( 3 years), primary physician or clinic, and week of medical evaluation; parents were interviewed. In contrast to the study of HIV-infected adults, no questions were asked about sexual activity and attendance at bars, and additional questions were included (for example, about attendance at child-care facilities, diaper use, and extracurricular activities). Community Health Survey A questionnaire was distributed in June 1994 to all employees at two Clark County agencies (agencies A and B) to determine whether they had had diarrheal illness during the study period and to identify their sources of drinking water. Employees were asked only about water drunk at home; however, the agencies did not provide bottled water, and tap water at the agencies was not filtered at its point of use. Water Quality Analysis and Environmental Survey Data on water quality for source water (Lake Mead) were reviewed for a 50-month period (1 March 1990 through 30 April 1994); data on water quality for finished (treated) water were reviewed for a 28-month period (1 January 1992 through 30 April 1994). The water treatment plant that serves all of Clark County was inspected. We reviewed the treatment procedures and the log of malfunctions and repairs at the plant and in the pipes that distribute water throughout the county. Statistical Analysis We used conditional logistic regression (SAS version 6.10 for Windows [PROC PHREG] [SAS Institute, Cary, North Carolina]) to calculate matched odds ratios for the casecontrol studies, and we used the chi-square test (Epi-Info version 5.1 [Centers for Disease Control and Prevention, Atlanta, Georgia, and the World Health Organization, Geneva, Switzerland]) to compare proportions for the community health survey. The Wilcoxon two-sample test was used to compare the ranked distributions of ordinal variables. We report two-tailed P values. Results Case Ascertainment and Confirmation We identified 78 persons in whom laboratory-confirmed Cryptosporidium infection was diagnosed during the study period (Figure 1). No procedural or personnel changes had been made that affected diagnosis or reporting. At laboratory A, the mean percentage of stool specimens per month that tested positive for Cryptosporidium had increased from 4% in 1993 to 21% in the first quarter of 1994. Figure 1. Number of cases of Cryptosporidium infection reported to the Clark County District Health Department by month of diagnosis, January 1993 to December 1994 (n = 148). Cryptosporidium Sixty-one of the 78 persons with cryptosporidiosis (78.2%) were HIV-infected adults Figure 2, and more than 90% of the 61 had CD4+ cell counts less than 100 cells/mm3 (Table 1). Four of the 78 (5.1%) were adults without HIV infection; 1 of these was receiving corticosteroid therapy for renal transplantation, and another was receiving chemotherapy for testicular cancer. Two of the 78 (2.6%) were HIV-infected children, and 11 (14.1%) were immunocompetent children. Figure 2. Flow diagram of the review of laboratory records, the casecontrol studies, and the community health survey. Table 1. CD4+ Cell Count Distribution of Adults with Human Immunodeficiency Virus (HIV) Infection and Laboratory-Confirmed Cryptosporidiosis and of All HIV-Infected Residents of Clark County Persons who had laboratory-confirmed cryptosporidiosis lived throughout Clark County (Figure 3, top), in four of the five geographic areas served by the water treatment plant (all except Nellis Air Force Base [Figure 3, bottom]). The epidemic curves of the dates of onset of illness for the HIV-infected adults and the immunocompetent children are similar (Figure 4). These epidemic curves and that for the month of diagnosis of the cases reported to the health department (Figure 1) show that the outbreak apparently began in December 1993 (when the first infected persons reported onset of illness) and extended through June 1994 (after which the number of reported cases notably decreased). The total number of laboratory-confirmed cases associated with the outbreak period was 103 (78 during the study period, 16 in May, and 9 in June). Figure 3. Maps of Clark County showing the residences of persons with cryptosporidiosis and the water distribution system. Top. n Bottom. Figure 4. Month of onset of diarrhea among adults with human immunodeficiency virus (HIV) infection and cryptosporidiosis, immunocompetent children with cryptosporidiosis, and county employees with diarrheal illness: Clark County, December 1993 to April 1994.

Primary invasive Haemophilus influenzae type b disease: A population-based assessment of risk factors

We performed a population-based case-control study of risk factors for primary invasive Haemophilus influenzae type b (Hib) disease in metropolitan Atlanta from July 1, 1983, through June 30, 1984. Active surveillance identified 102 cases in children less than 5 years of age, 89 of whom lived in households with telephones. We used random digit dialing to select 530 controls who were postmatched to cases by age. Multivariate analysis showed a significant association between Hib disease and two independent exposure factors, household crowding (odds ratio (OR) 2.7, 95% confidence limits (CL) 1.3 to 5.6) and day-care attendance. For day-care attendance, relative risk was highest in 2- to 5-month-old infants (OR 17.7, 95% CL 5.8 to 54.4) and declined to 9.4 (4.3 to 20.9) at ages 6 to 11 months, 5.0 (2.7 to 9.3) at 12 to 23 months, 2.7 (1.3 to 5.5) at 24 to 35 months, and 1.4 (0.5 to 4.0) in 36- to 59-month-old children. Fifty percent of all invasive Hib disease that occurred during the study period was attributable to exposure to day-care; the attributable risk for household crowding was 18%. Dose-response effects were observed for hours per week of day-care attendance and extent of household crowding. Breast-feeding was protective for infants less than 6 months of age (OR 0.08, 95% CL 0.01 to 0.59). After controlling for socioeconomic and other confounding factors, we could demonstrate no effect of black race on cumulative risk of invasive Hib disease. Our study defines high-risk groups and provides a population-based model of the interrelationship between risk factors associated with invasive Hib disease.

Risk factors for kala-azar in Bangladesh

Since 1990, South Asia has experienced a resurgence of kala-azar (visceral leishmaniasis). To determine risk factors for kala-azar, we performed cross-sectional surveys over a 3-year period in a Bangladeshi community. By history, active case detection, and serologic screening, 155 of 2,356 residents had kala-azar with onset from 2000 to 2003. Risk was highest for persons 3–45 years of age, and no significant difference by sex was seen. In age-adjusted multivariable models, 3 factors were identified: proximity to a previous kala-azar patient (odds ratio [OR] 25.4, 95% confidence interval [CI] 15–44 within household; OR 3.2 95% CI 1.7–6.1 within 50 m), bed net use in summer (OR 0.7, 95% CI 0.53–0.93), and cattle per 1,000 m2 (OR 0.8, 95% CI 0.70–0.94]). No difference was seen by income, education, or occupation; land ownership or other assets; housing materials and condition; or keeping goats or chickens inside bedrooms. Our data confirm strong clustering and suggest that insecticide-treated nets could be effective in preventing kala-azar.

Prediction, Assessment of the Rift Valley Fever Activity in East and Southern Africa 2006-2008 and Possible Vector Control Strategies

Historical outbreaks of Rift Valley fever (RVF) since the early 1950s have been associated with cyclical patterns of the El Niño/Southern Oscillation (ENSO) phenomenon, which results in elevated and widespread rainfall over the RVF endemic areas of Africa. Using satellite measurements of global and regional elevated sea surface temperatures, elevated rainfall, and satellite derived-normalized difference vegetation index data, we predicted with lead times of 2-4 months areas where outbreaks of RVF in humans and animals were expected and occurred in the Horn of Africa, Sudan, and Southern Africa at different time periods from September 2006 to March 2008. Predictions were confirmed by entomological field investigations of virus activity and by reported cases of RVF in human and livestock populations. This represents the first series of prospective predictions of RVF outbreaks and provides a baseline for improved early warning, control, response planning, and mitigation into the future.

Risk factors for primary invasive Haemophilus influenzae disease: Increased risk from day care attendance and school-aged household members

From November 1, 1981, through April 30, 1982, we performed a case-control study of primary invasive Haemophilus influenzae infections in children in Colorado. Information was collected for 121 (83%) of 146 children with positive cultures and for 196 (67%) of 292 age-matched controls selected at random from birth certificates. Infected children were more likely to have attended a day care center or nursery (DCC/N) and to have an elementary school-aged household member. For attendance at DCC/N, the relative risk was significantly increased only for children 12 months of age or older, and increased with the size of the DCC/N. After controlling for DCC/N attendance and school-aged siblings, children younger than 6 months of age with infection were significantly less likely to have been breast-fed, suggesting a protective effect of breast-feeding. We identified DCC/N attendees, especially those older than 1 year of age, to be at increased risk of primary H. influenzae disease. They could benefit from immunization.

Profile: The KEMRI/CDC Health and Demographic Surveillance System—Western Kenya

The KEMRI/Centers for Disease Control and Prevention (CDC) Health and Demographic Surveillance System (HDSS) is located in Rarieda, Siaya and Gem Districts (Siaya County), lying northeast of Lake Victoria in Nyanza Province, western Kenya. The KEMRI/CDC HDSS, with approximately 220 000 inhabitants, has been the foundation for a variety of studies, including evaluations of insecticide-treated bed nets, burden of diarrhoeal disease and tuberculosis, malaria parasitaemia and anaemia, treatment strategies and immunological correlates of malaria infection, and numerous HIV, tuberculosis, malaria and diarrhoeal disease treatment and vaccine efficacy and effectiveness trials for more than a decade. Current studies include operations research to measure the uptake and effectiveness of the programmatic implementation of integrated malaria control strategies, HIV services, newly introduced vaccines and clinical trials. The HDSS provides general demographic and health information (such as population age structure and density, fertility rates, birth and death rates, in- and out-migrations, patterns of health care access and utilization and the local economics of health care) as well as disease- or intervention-specific information. The HDSS also collects verbal autopsy information on all deaths. Studies take advantage of the sampling frame inherent in the HDSS, whether at individual, household/compound or neighbourhood level.

HIV prevalence and associated risk factors among individuals aged 13-34 years in Rural Western Kenya.

Objectives To estimate HIV prevalence and characterize risk factors among young adults in Asembo, rural western Kenya. Design Community-based cross-sectional survey. Methods From a demographic surveillance system, we selected a random sample of residents aged 13-34 years, who were contacted at home and invited to a nearby mobile study site. Consent procedures for non-emancipated minors required assent and parental consent. From October 2003 - April 2004, consenting participants were interviewed on risk behavior and tested for HIV and HSV-2. HIV voluntary counseling and testing was offered. Results Of 2606 eligible residents, 1822 (70%) enrolled. Primary reasons for refusal included not wanting blood taken, not wanting to learn HIV status, and partner/parental objection. Females comprised 53% of 1762 participants providing blood. Adjusted HIV prevalence was 15.4% overall: 20.5% among females and 10.2% among males. HIV prevalence was highest in women aged 25-29 years (36.5%) and men aged 30-34 years (41.1%). HSV-2 prevalence was 40.0% overall: 53% among females, 25.8% among males. In multivariate models stratified by gender and marital status, HIV infection was strongly associated with age, higher number of sex partners, widowhood, and HSV-2 seropositivity. Conclusions Asembo has extremely high HIV and HSV-2 prevalence, and probable high incidence, among young adults. Further research on circumstances around HIV acquisition in young women and novel prevention strategies (vaccines, microbicides, pre-exposure prophylaxis, HSV-2 prevention, etc.) are urgently needed.