Co-colonization by Streptococcus pneumoniae and Staphylococcus aureus in the throat during acute respiratory illnesses.

Pneumonia due to either Streptococcus pneumoniae (Sp) or Staphylococcus aureus (Sa) accounts for most mortality after influenza and acute respiratory illness (ARI). Because carriage precedes infection, we estimated Sp and Sa carriage to examine the co-colonization dynamics between Sp, Sa and respiratory viruses in the presence of ARI in the oropharynx. We tested oropharyngeal specimens of community subjects (aged ⩾2 years) with ARI for the presence of influenza A and B, 11 other common respiratory viruses, Sp and Sa, using real-time PCR. A total of 338 participants reported 519 ARI episodes of which 119 (35%) carried Sp, 52 (13%) carried Sa and 25 (7%) carried both. Thirty-five subjects tested positive for influenza, of which 14 (40%) carried Sp and six (17%) carried Sa, significantly more than in the influenza-negative group (P = 0·03 and P = 0·04, respectively). In subjects infected by any virus compared to those with no virus, Sp carriage (39·2% vs. 27·9%, P = 0·03) but not Sa carriage (11·6% vs. 14%, P = 0·6) was more frequent. For children, when Sa was present, Sp carriage tended to be less frequent than expected given the presence of viral infection, but not significantly [observed relative risk 1·14, 95% confidence interval (CI) 0·4-3·1; with a relative excess risk due to interaction of -0·11]. Independent of age, Sp carriers were more likely to return that season with subsequent ARI (odds ratio 2·14, 95% CI 1·1-4·3, P = 0·03). Both Sp and Sa carriage rates in the oropharynx increase during influenza infection in children. However, no negative interaction between Sp and Sa was observed. Sp carriers are more likely to suffer subsequent ARI episodes than non-carriers.

Oral lesions among women living with or at risk for HIV infection. HIV Epidemiology Research Study (HERS) Group.

PURPOSE: Our objectives were to compare the prevalence of oropharyngeal mucosal lesions among human immunodeficiency virus (HIV) seropositive and demographically similar seronegative women, and to determine the association of oral lesions with immunosuppression, substance abuse, use of medications, and utilization of dental services. POPULATION AND METHODS: Participants in a multicenter, longitudinal cohort study of HIV infection in women were evaluated at baseline by interview, physical examination, and laboratory studies. RESULTS: Oropharyngeal pathology was found in 40% of seropositive and 23% of seronegative women. Oral candidiasis was identified in 15% of seropositive and 3% of seronegative women. Among seropositive women, history of previous oral candidiasis, lower CD4 lymphocyte counts, and current antibiotic use were associated with oral candidiasis. Hairy leukoplakia was identified in 5% of seropositive women and was significantly associated with lower CD4 lymphocyte counts. Gingival erythema and ulcerative gingivitis were found in 23% of participants overall, but were unrelated to HIV serostatus or CD4 lymphocyte count. Substance abuse, lack of dental care, and African-American race were associated with gingival pathology. CONCLUSION: The high prevalence of oral lesions among HIV seropositive and at-risk seronegative women underscores the need for routine oral examination and targeted treatment of this population.

Ribavirin utilization and clinical effectiveness in children hospitalized with respiratory syncytial virus infection.

Ribavirin was approved in early 1986 for treatment of illness associated with respiratory syncytial virus (RSV) infection in hospitalized children; however, the value of its use remains controversial. This investigation was undertaken to describe ribavirin utilization and to evaluate the effectiveness of ribavirin in reducing the period of hospitalization. All children with laboratory-confirmed RSV infection, hospitalized over seven epidemic periods at a single institution, were identified. Characteristics from the medical records of the 768 children and their course of hospitalization were evaluated as determinants of treatment with ribavirin. Very young age as well as diagnoses of congenital heart disease, certain pulmonary conditions, and failure to thrive were all significantly related to increased likelihood of treatment. Children requiring intensive care were likely to be treated; however, the most critically ill children, those who required mechanical ventilation, were not treated. Although these results were in keeping with treatment guidelines for the use of ribavirin, actual utilization declined significantly over the course of the evaluation. The effect of ribavirin treatment on the duration of hospitalization among children with community-acquired infection was evaluated in a multivariate model, which controlled for the effects of underlying conditions, measures of illness severity, and epidemic year. This analysis failed to demonstrate a benefit for ribavirin in reducing length of stay; in fact, ribavirin treatment was significantly associated with prolonged hospitalization. It was not likely that the explanation for ribavirin's association with prolonged hospitalization was that the most seriously ill children were treated; however, it was not possible to determine whether this association was due to an adverse effect of treatment or resulted from a perceived need to complete the course of therapy.

Influenza vaccine effectiveness in preventing hospitalization among the elderly during influenza type A and type B seasons.

BACKGROUND: Influenza vaccine effectiveness evaluations were carried out among the elderly, as part of a demonstration established to estimate the value of including influenza vaccination as a covered Medicare benefit. METHODS: Cases hospitalized with pneumonia and influenza-related diagnoses during November through April were identified and group matched to randomly selected community controls. Data were collected from cases and controls on influenza vaccination status and other factors which could have confounded the association between vaccination and hospitalization. A community-based influenza surveillance programme was conducted each year to determine the timing and aetiology of influenza activity. Logistic regression analyses were carried out to evaluate the association of influenza vaccination with the likelihood of hospitalization. RESULTS: In 1990-1991, during the peak of the influenza type B outbreak, influenza vaccination was estimated to be 31% (95% CI: 4-51%) effective in reducing the likelihood of hospitalization. In 1991-1992, during the peak of the influenza type A(H3N2) epidemic, a nearly identical point estimate for vaccine effectiveness was demonstrated (32%, 95% CI: 7-50%). Identical analyses carried out each year during the periods of low or absent influenza activity failed to demonstrate a significant effect for vaccination in preventing hospitalization. CONCLUSION: Results indicated that a significant benefit for vaccination could be expected during both type A and type B influenza seasons.

Effectiveness of inactivated influenza vaccine among nursing home residents during an influenza type A (H3N2) epidemic.

OBJECTIVES: To evaluate the use of influenza vaccine in nursing homes and its effectiveness in reducing the likelihood of influenza-like illness. DESIGN: A retrospective case-control study with active identification of influenza infection. SETTING: All nursing homes in a seven-county study area in southern lower Michigan were eligible for participation. Analyses were based on data collected from 23 homes with documented influenza transmission. PARTICIPANTS: Persons aged 65 years or older who were residents of the nursing homes under study during the influenza type A(H3N2) outbreak in 1989-1990. MEASUREMENTS: Residents were identified as cases or controls based on occurrence of febrile respiratory illness meeting a case definition. Demographic and underlying illness information were gathered as were data on the use of influenza vaccine, antibiotics, and antivirals. Characteristics of the nursing homes were also recorded. Logistic regression analyses were carried out to determine vaccine effectiveness. MAIN RESULTS: Determinants of vaccine use were different from those observed in a parallel community-based study. In a multivariate model that considered the effects of resident and nursing home characteristics, vaccinated residents were significantly less likely than those who were not vaccinated to have an influenza-like illness (OR = .58 (95% CI, .43-.78), P < .001, imputed vaccine effectiveness estimate of 42%). Vaccination was more effective in younger residents (those aged 65 to 84) then in older residents (those older than 84 years). CONCLUSIONS: Influenza vaccination was effective in reducing the likelihood of influenza-like illness in nursing home residents. Effectiveness appeared to be related to age, which may function as a surrogate for related immunologic factors. Older nursing home residents should be targeted for newer vaccines and/or potential prophylactic use of antivirals.

Influenza vaccine use among an elderly population in a community intervention.

A community intervention program was carried out to promote influenza immunization among an elderly population, as part of a demonstration established to estimate the value of including influenza immunization as a Medicare-covered benefit. Potential recipients were informed of reasons for receiving vaccine and its availability at no cost, and physicians and others administering it were provided with educational materials and cost reimbursement. Data collected for annual evaluations of influenza vaccine effectiveness were used to evaluate the impact of the community intervention program on influenza immunization status and to determine the effects of age, gender, chronic health conditions, and smoking status on the likelihood of immunization. Results indicated that the intervention program had a statistically significant impact on increasing the likelihood of immunization among the elderly population living in the targeted area. The existence of certain chronic health conditions also predicted immunization, while the effect of current smoking on immunization was strongly negative. During the three years of vaccine promotion, use in those 65 years and older who resided in the intervention area increased from approximately 40% in 1989-1990 to over 56% in 1991-1992. With various incentives, including cost reimbursement through Medicare, influenza immunization can be markedly increased among elderly beneficiaries.

Severity of illness models for respiratory syncytial virus-associated hospitalization.

The objective of this investigation was to examine the feasibility of multivariate severity of illness models for pediatric patients hospitalized with respiratory syncytial virus (RSV) infection. From a preexisting retrospective cohort study database, all infants and children 2 yr of age or younger with community-acquired RSV infection admitted to the University of Michigan's C. S. Mott Children's Hospital during nine epidemics were examined. The study group consisted of 802 hospitalized patients younger than 2 yr of age with community-acquired RSV infection; 182 (23%) patients had prolonged hospital length of stay defined as 7 d or greater. Multivariate logistic regression modeling of nine variables measurable during the first hospital day was strongly associated with prolonged hospitalization (p < 0.0001). Receiver operator characteristic curve analysis resulted in an area under the curve of 0.894, indicating excellent model discrimination. Goodness-of-fit testing indicated excellent model calibration for observed versus predicted outcomes (p = 0.216). We conclude that severity of illness models for RSV-associated hospitalization with excellent predictive properties in terms of classification, discrimination, and calibration are possible. Further study is required to determine if such models are generalizable across multiple centers and epidemics.

Respiratory syncytial virus in a community population: circulation of subgroups A and B since 1965.

Respiratory syncytial viruses were isolated from residents of Tecumseh, MI, with illnesses of all severities during the periods 1965-1971 and 1976-1981. These isolates were grouped using one monoclonal antibody specific for each subgroup. All were identified as either subgroup A or B. Subgroup A predominated in most years. No differences in age distribution or illness characteristics could be found between the subgroups. This study demonstrated that the currently recognized subgroups have been present in a single community since 1965, and their behavior in the past is similar to that currently described.

Vaccine use and the risk of outbreaks in a sample of nursing homes during an influenza epidemic.

This study was conducted in nursing homes in a seven-county area of lower Michigan. Seventy percent of the 83 nursing homes in the study area provided data on vaccine use. Significantly higher rates of vaccination were found in smaller vs larger nursing homes; a requirement of written informed consent lowered the frequency of vaccination among residents. Among a subset of 45 homes that collected weekly prospective illness data during the confirmed epidemic of influenza A(H3N2), 17 (38%) experienced an influenza outbreak. In bivariate analyses, both greater size of nursing home and lower frequency of vaccination were significant predictors of outbreak status, suggesting a role for indirect protection or herd immunity.

Influenza vaccine effectiveness among elderly nursing home residents: a cohort study.

Outbreaks of influenza in nursing homes still occur, even when a large portion of residents have been inoculated with inactivated vaccine. Data were collected in 1991--1992 from 83 eligible skilled nursing homes located in southern Lower Michigan to determine the effectiveness of inactivated influenza vaccine in preventing influenza-like illness and influenza-associated pneumonia. Surveillance was conducted to identify the occurrence of influenza in the homes and, at the end of the season, specific data were gathered on all residents of homes with influenza activity. Age- and sex-adjusted estimates of vaccine effectiveness were calculated using Cox proportional hazards models for each nursing home. Estimates were pooled using precision-based weights calculated from data for each home. Vaccine was found to be 33% effective in preventing total respiratory illness (influenza-like illness and clinically diagnosed pneumonia). In prevention of pneumonia alone, vaccine was 43% effective. The estimate for prevention of pneumonia rose to 55% if the period under consideration was limited to the time of peak influenza activity. Given the number of eligible homes and the cohort methodology used, the results support continuation of current policy, encouraging use of vaccine in all nursing home residents.

Rhinovirus infections in Tecumseh, Michigan: frequency of illness and number of serotypes.

We studied rhinovirus-associated illnesses from 1976 to 1981 among residents of the community of Tecumseh, Michigan, in a continuation of similar studies done in 1966-1971. Rhinoviruses were the most frequently isolated respiratory pathogen in all age groups, including young children. The pattern of age-specific isolation rates was similar to that for total respiratory illness. Rhinovirus-associated illnesses were generally mild but of relatively long duration; restriction of daily activity was frequent, especially in certain age groups. Typing of all isolates has been completed; with high-quality antisera nearly all isolates could be typed. Thus, new serotypes are probably not evolving, and most have already been identified. Differences in frequency of occurrences of different serotypes were evident, but ranking in order of importance was difficult based on existing data.

Medical practice-based influenza surveillance: viral prevalence and assessment of morbidity.

Regular surveillance of influenza virus activity and associated illness is necessary to monitor changes in circulating strains. As part of a demonstration project, medical practices in a seven-county area in southern lower Michigan were recruited as sentinel surveillance sites. The practices were asked to collect specimens for virus isolation and/or data on age-specific frequency of respiratory illnesses that met a case definition. Data were used to establish periods of influenza virus activity for vaccine effectiveness determinations. Over three study periods, 1989-1992, there were documented outbreaks of influenza type A(H3N2), type A(H1N1), and type B. The incidence of influenza-like illness increased during these outbreaks, with variation in age-specific frequency from year to year. Recovery of virus was not affected during the winter season by long delays in specimen receipt by the laboratory. Results indicated that medical practices can be successfully recruited as surveillance sites to provide information on the timing, etiology, and intensity of acute respiratory illness.

Effectiveness of ribavirin in otherwise well infants with respiratory syncytial virus-associated respiratory failure. Pediatric Critical Study Group.

OBJECTIVE: To examine ribavirin's effectiveness in otherwise well infants with respiratory syncytial virus (RSV)-associated respiratory failure. DESIGN: Prospective multicenter cohort study. SETTING: Pediatric critical care units affiliated with the Pediatric Critical Care Study Group; 38 centers from the United States and Canada participated. PATIENTS: Infants with RSV-associated respiratory failure undergoing mechanical ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data collected included demographic information; dates of hospitalization, intensive care, and mechanical ventilation; all patient diagnoses; reason for tracheal intubation; dates of ribavirin use before and during mechanical ventilation; time in hours after intubation until ribavirin administration; Pediatric Risk of Mortality (PRISM) score; and outcome. A total of 439 patients received mechanical ventilation for RSV-associated respiratory failure; 223 were classified as previously well and met entry criteria. Ninety-one infants (41%) received ribavirin during mechanical ventilation. The PRISM scores during the initial 24 hours of intensive care and blood gas measurements before intubation were similar for patients who received ribavirin versus those who did not. Use of ribavirin during mechanical ventilation was associated with prolonged duration of mechanical ventilation (p < 0.01) in a multivariate model that controlled for patient age, gender, prematurity status, and use of ribavirin before intubation. Subgroup analysis of mechanical ventilation days for previously well patients was 5.0 +/- 4.2 in the no-ribavirin group versus 6.4 +/- 5.0 in the ribavirin group (p < 0.05) and for well premature infants was 6.3 +/- 4.9 in the no-ribavirin group versus 9.0 +/- 6.3 in the ribavirin group (p < 0.01). The mortality rates for the term and the premature groups were similar for treated and untreated patients. CONCLUSIONS: Ribavirin administration during mechanical ventilation to previously well infants with RSV infection was not associated with reductions in either mortality rates or duration of mechanical ventilation. Additional clinical effectiveness studies are required to define specific groups in which the use of aerosolized ribavirin is indicated.

Safety and efficacy of long-term use of rimantadine for prophylaxis of type A influenza in nursing homes.

The safety and efficacy of rimantadine for long-term prophylaxis of influenza A (H3N2) infection were evaluated among elderly residents in 10 nursing homes. Within each nursing home, participating residents were randomly assigned to receive placebo or rimantadine at 100 or 200 mg/day. Residents were evaluated daily for symptoms and significant health events as possible side effects, as well as for influenza-like illness. The study medications were administered to 328 residents for up to 8 weeks, with no statistically significant differences in the frequencies of gastrointestinal or central nervous system symptoms between the groups. However, residents in the active medication groups were more likely to withdraw from the study and to experience various health events including death; some but not all of these differences were statistically significant. Efficacy evaluations were carried out on the 68 vaccinated residents in the two nursing homes with demonstrated influenza virus activity. Rimantadine appeared to provide an additional protective effect beyond vaccination in reducing the risk of clinical and laboratory-confirmed influenza-like illness; however, the efficacy estimates were never statistically significant. The efficacies of the 100- and 200-mg/day dosages were generally similar. When data for the 100- and 200-mg/day dosage groups were combined and compared with data for the group receiving placebo, the efficacy of rimantadine in reducing the risk of clinical influenza-like illness was estimated to be 58 percent (P = 0.079). The results suggest the relative safety and clinical efficacy of using rimantadine for influenza prophylaxis among vaccinated elderly individuals and support the recommendation for a dosage reduction to 100 mg/day in this population.

Perceived need for and use of mental health services by women living with or at risk of human immunodeficiency virus infection.

OBJECTIVES: To determine prevalence of and factors associated with perceived need for and use of mental health services and use of psychotherapeutic medications among women in the Human Immunodeficiency Virus Epidemiology Research Study (HERS). METHODS: We interviewed 871 HIV-seropositive and 439 demographically and behaviorally similar seronegative women at baseline regarding demographics, psychosocial measures, substance use, medical history, and use of health care services and medications. RESULTS: Thirty-eight percent of HIV-seropositive women and 35% of seronegative women (p = 0.33) reported needing mental health services in the prior six months. Women who were older, were white or Latina (compared with African American), had some college education, had less social support, and reported recent negative life events or had CES-D scores higher than 15 (suggesting depression) were more likely to report needing mental health services. Sixty-seven percent of seropositive and 65% of seronegative women who reported needing services (p = 0.69) reported obtaining services. Women who were white (compared with Latina or African American) and had more education, more social support, and health insurance were more likely to obtain services. Eighteen percent of seropositive and 13% of seronegative women (p = 0.006) reported current use of psychotherapeutic medications, especially antidepressants and antianxiety medications. Women who reported use of medications were more likely to report recent negative life events; were older, white, or Latina; had more education, less social support, CES-D scores higher than 15, and health insurance. CONCLUSION: Women both living with or at risk of HIV perceived a need for and used mental health services in association with negative life events, social isolation, and depressive symptoms. Need for and use of services differed by race/ethnicity, education, and availability of social support.

The evolution of Candida species and fluconazole susceptibility among oral and vaginal isolates recovered from human immunodeficiency virus (HIV)-seropositive and at-risk HIV-seronegative women.

Antifungal agents can effectively treat mucosal candidiasis; however, their use can lead to colonization with less susceptible species and to resistance among normally susceptible strains. Oral and vaginal Candida isolates obtained at 3 points over 2 years from human immunodeficiency virus (HIV)-seropositive and at-risk HIV-seronegative women were identified by species and were evaluated for in vitro fluconazole susceptibility. Prevalence of non-C. albicans strains increased over time, and these strains were more likely among women reporting current antifungal use. Among C. albicans isolates, resistance was rare, with no evidence for progressive reduction in susceptibility over time. Among non-C. albicans isolates, reduced susceptibility occurred frequently and increased with time. HIV-seropositive women were more likely to have non-C. albicans isolates with reduced susceptibility as were women reporting current antifungal use. This evolution and section of mucosa-colonizing Candida species with reduced susceptibility could play a critical early role in the development of antifungal resistance among C. albicans isolates responsible for refractory candidiasis.

Influenza vaccine effectiveness in preventing hospitalization for pneumonia in the elderly.

During the winter of 1989-1990, influenza type A(H3N2) circulated widely, causing excess morbidity and mortality nationwide. From November through April, 1989-1990, hospitalized cases of pneumonia and influenza occurring among noninstitutionalized individuals 65 or more years of age were identified by 20 acute care hospitals in southern lower Michigan. These cases were group matched on age, sex, race, and zip code to randomly sampled, community-based controls from a comprehensive listing of Medicare beneficiaries residing in the study area. Self-reported data were collected from cases and controls on influenza vaccine status for the 1989-1990 season and on a number of other factors which could have influenced vaccination status or outcome. Questionnaires were completed by 1,907 individuals, 449 of whom were cases, resulting in an overall response rate of 76%. A community-based influenza surveillance system was implemented to determine the timing and intensity of viral activity and influenza-like illness. Vaccine effectiveness in preventing overall pneumonia and influenza hospitalizations was estimated by logistic regression. During the 3-month period of surveillance-confirmed peak influenza type A(H3N2) circulation, vaccine effectiveness was 45% (95% confidence interval 14-64, p = 0.009). However, during the 3-month period of low or absent virus activity, identical methodology and model specification resulted in an effectiveness estimate of 21% that was not statistically different from zero (p = 0.36). The effectiveness determined during the peak period of virus circulation is felt to be a conservative estimate, since agents other than influenza are responsible for pneumonia and influenza hospitalizations, even during times of peak influenza activity.

Mucosal candidal colonization and candidiasis in women with or at risk for human immunodeficiency virus infection. HIV Epidemiology Research Study (HERS) Group.

The epidemiology of mucosal candidal colonization and candidiasis was studied in a multicenter cohort of 871 human immunodeficiency virus (HIV)-seropositive and 439 demographically and behaviorally similar HIV-seronegative women. Cross-sectional analyses at baseline revealed that oropharyngeal colonization with Candida species was more prevalent among seropositive women and among women reporting recent cigarette smoking and injection drug use. Oropharyngeal candidiasis was also more prevalent among seropositive women. Both oropharyngeal colonization and candidiasis were significantly associated with a lower median CD4 lymphocyte count among seropositive women. Vaginal candidal colonization was more prevalent among seropositive women and among those reporting recent injection drug use and current insulin or oral antihyperglycemic therapy. Vaginal candidiasis was equally likely to be diagnosed in seropositive and seronegative women and was not significantly related to recent sexual contact. Neither vaginal colonization nor candidiasis was significantly related to a lower median CD4 lymphocyte count among seropositive women. Baseline evaluation indicated differences in the epidemiology of oropharyngeal and vaginal candidal colonization and candidiasis in HIV-seropositive women and suggested possible variation in pathogenesis of candidal infection at these two mucosal sites.

Effect of HIV infection on menstrual cycle length.

HIV serostatus and menstrual function were examined using prospectively collected menstrual data from 802 HIV-seropositive and 273 HIV-seronegative women, ages 20 to 44, enrolled in two cohort studies of HIV infection in North American women. The associations between HIV serostatus and the probabilities of having a cycle lasting >40 days (n = 541 cycles), >90 days (n = 67 cycles), <18 days (n = 316 cycles) and mean length and variability of 18 to 40 day cycles (n = 3,634) were assessed. After adjustment for demographic characteristics, body mass index, and substance use, seropositivity increased the odds of having a very short cycle (< 18 days, odds ratio [OR], 1.45; 95% confidence interval [CI], 1.00-2.11) and a very long cycle (>90 days, OR, 1.32; 95% CI, 0.68-2.58) slightly, although the latter CIs include one. Seropositivity did not increase the odds of having a moderately long cycle (>40 days, OR, 1.14) or affect mean cycle length or variability (beta, 0.30 +/- 0.20; between-woman standard deviation [SD], 2.2 days [HIV-seronegative] and 1.9 days [HIV-seropositive]; within-woman SD, 3.5 days for both). Although seropositivity may slightly increase the probability of very short cycles, HIV serostatus has little overall effect on amenorrhea, menstrual cycle length, or variability. Among HIV-seropositive women, higher viral loads and lower CD4+ counts were associated with increased cycle variability and polymenorrhea.