Terence Chorba

Pseudomonas cepacia colonization in patients with cystic fibrosis: Risk factors and clinical outcome†

During the period of 1979 to 1983, 38 patients with cystic fibrosis (CF) at the CF center of St. Christophers Hospital for Children in Pennsylvania developed respiratory tract colonization with Pseudomonas cepacia. Seventeen (45%) of the patients with colonization died. Yearly incidence rates of P. cepacia colonization fluctuated between 1.3% and 6.1%, suggesting an endemic phenomenon. Case-control studies showed that severe underlying CF, use of aminoglycosides, and having a sibling with CF and P. cepacia colonization were significant risk factors for P. cepacia colonization. Once colonized with P. cepacia, patients with CF were likely to be hospitalized longer (P = 0.008) and to die sooner (P = 0.0001) than control patients with CF. Environmental and microbiologic studies did not identify a common source or mode of transmission of P. cepacia among patients. The results of this investigation suggest that P. cepacia colonization of patients with CF was endemic in the hospital, occurred more frequently in those with severe disease, and was associated with adverse clinical outcome.

Sensitivity and Specificity of Human Immunodeficiency Virus Rapid Serologic Assays and Testing Algorithms in an Antenatal Clinic in Abidjan, Ivory Coast

ABSTRACT To evaluate serologic testing algorithms for human immunodeficiency virus (HIV) based on a combination of rapid assays among persons with HIV-1 (non-B subtypes) infection, HIV-2 infection, and HIV-1–HIV-2 dual infections in Abidjan, Ivory Coast, a total of 1,216 sera with known HIV serologic status were used to evaluate the sensitivity and specificity of four rapid assays: Determine HIV-1/2, Capillus HIV-1/HIV-2, HIV-SPOT, and Genie II HIV-1/HIV-2. Two serum panels obtained from patients recently infected with HIV-1 subtypes B and non-B were also included. Based on sensitivity and specificity, three of the four rapid assays were evaluated prospectively in parallel (serum samples tested by two simultaneous rapid assays) and serial (serum samples tested by two consecutive rapid assays) testing algorithms. All assays were 100% sensitive, and specificities ranged from 99.4 to 100%. In the prospective evaluation, both the parallel and serial algorithms were 100% sensitive and specific. Our results suggest that rapid assays have high sensitivity and specificity and, when used in parallel or serial testing algorithms, yield results similar to those of enzyme-linked immunosorbent assay-based testing strategies. HIV serodiagnosis based on rapid assays may be a valuable alternative in implementing HIV prevention and surveillance programs in areas where sophisticated laboratories are difficult to establish.

STD screening of HIV-infected MSM in HIV clinics.

Background: National guidelines for the care of human immunodeficiency virus (HIV)-infected persons recommend asymptomatic routine screening for sexually transmitted diseases (STDs). Our objective was to determine whether providers who care for HIV-infected men who have sex with men (MSM) followed these guidelines. Methods: We abstracted medical records to evaluate STD screening at 8 large HIV clinics in 6 US cities. We estimated the number of men who had at least one test for syphilis, chlamydia (urethral and/or rectal), or gonorrhea (urethral, rectal, and/or pharyngeal) in 2004, 2005, and 2006. Urethral testing included nucleic acid amplification tests of both urethral swabs and urine. We also calculated the positivity of syphilis, chlamydia, and gonorrhea among screened men. Results: Medical records were abstracted for 1334 HIV-infected MSM who made 14,659 visits from 2004–2006. The annual screening rate for syphilis ranged from 66.0% to 75.8% during 2004–2006. Rectal chlamydia and rectal and pharyngeal gonorrhea annual screening rates ranged from 2.3% to 8.5% despite moderate to high positivity among specimens from asymptomatic patients (3.0%–9.8%) during this period. Annual urethral chlamydia and gonorrhea screening rates were higher than rates for nonurethral sites, but were suboptimal, and ranged from 13.8% to 18.3%. Conclusions: Most asymptomatic HIV-infected MSM were screened for syphilis, indicating good provider adherence to this screening guideline. Low screening rates for gonorrhea and chlamydia, especially at rectal and pharyngeal sites, suggest that substantial barriers exist for complying with these guidelines. The moderate to high prevalence of asymptomatic chlamydial and gonococcal infections underscores the importance of screening. A range of clinical quality improvement interventions are needed to increase screening, including increasing the awareness of nucleic acid amplification tests for nonurethral screening.

Cellular Human Immunodeficiency Virus (HIV)–Protective Factors: A Comparison of HIV-Exposed Seronegative Female Sex Workers and Female Blood Donors in Abidjan, Côte d’Ivoire

Cellular factors that may protect against human immunodeficiency virus (HIV) infection were investigated in 27 HIV-exposed seronegative (ESN) female sex workers (FSWs) and 27 HIV-seronegative female blood donors. Compared with blood donors, ESN FSWs had significantly decreased expression levels of C-X-C chemokine receptor 4 (CXCR4), but not of C-C chemokine receptor 5, on both memory (P<.001) and naive (P=.041) CD4(+) T cells. CXCR4 down-regulation was associated with prolonged duration of commercial sex work by ESN FSWs. CD38 expression on CD8(+) T cells was significantly increased among ESN FSWs, compared with that among blood donors (P=.017). There were no differences in HLA-DR and CD62L expression between blood donors and ESN FSWs. Proportions of T cells producing the beta-chemokines RANTES (regulated on activation, normally T cell-expressed and -secreted), macrophage inflammatory protein (MIP)-1alpha, and MIP-1beta or the cytokines interleukin (IL)-2, IL-4, interferon-gamma, and tumor necrosis factor-alpha, were similar in the 2 groups. These data indicate that ESN FSWs differ from HIV-seronegative female blood donors with respect to immunological factors that have no clear protective potential against HIV transmission.

Acute viral hepatitis morbidity and mortality associated with hepatitis E virus infection: Uzbekistan surveillance data

BackgroundIn Uzbekistan, routine serologic testing has not been available to differentiate etiologies of acute viral hepatitis (AVH). To determine the age groups most affected by hepatitis E virus (HEV) during documented AVH epidemics, trends in AVH-associated mortality rate (MR) per 100,000 over a 15-year period and reported incidence of AVH over a 35-year period were examined.MethodsReported AVH incidence data from 1971 to 2005 and AVH-associated mortality data from 1981 to 1995 were examined. Serologic markers for infection with hepatitis viruses A, B, D, and E were determined from a sample of hospitalized patients with AVH from an epidemic period (1987) and from a sample of pregnant women with AVH from a non-epidemic period (1992).ResultsTwo multi-year AVH outbreaks were identified: one during 1975–1976, and one during 1985–1987. During 1985–1987, AVH-associated MRs were 12.3–17.8 per 100,000 for the general population. Highest AVH-associated MRs occurred among children in the first 3 years of life (40–190 per 100,000) and among women aged 20–29 (15–21 per 100,000). During 1988–1995 when reported AVH morbidity was much lower in the general population, AVH-associated MRs were markedly lower among these same age groups. In 1988, AVH-associated MRs were higher in rural (21 per 100,000) than in urban (8 per 100,000) populations (RR 2.6; 95% CI 1.16–5.93; p < 0.05). Serologic evidence of acute HEV infection was found in 280 of 396 (71%) patients with AVH in 1987 and 12 of 99 (12%) pregnant patients with AVH in 1992.ConclusionIn the absence of the availability of confirmatory testing, inferences regarding probable hepatitis epidemic etiologies can sometimes be made using surveillance data, comparing AVH incidence with AVH-associated mortality with an eye to population-based viral hepatitis control measures. Data presented here implicate HEV as the probable etiology of high mortality observed in pregnant women and in children less than 3 years of age in Uzbekistan during 1985–1987. High mortality among pregnant women but not among children less than 3 years has been observed in previous descriptions of epidemic hepatitis E. The high mortality among younger children observed in an AVH outbreak associated with hepatitis E merits corroboration in future outbreaks.

Comparative Tuberculosis (TB) Prevention Effectiveness in Children of Bacillus Calmette-Guérin (BCG) Vaccines from Different Sources, Kazakhstan

Background Except during a 1-year period when BCG vaccine was not routinely administered, annual coverage of infants with Bacillus Calmette-Guérin (BCG) in Kazakhstan since 2002 has exceeded 95%. BCG preparations from different sources (Japan, Serbia, and Russia) or none were used exclusively in comparable 7-month time-frames, September through March, in 4 successive years beginning in 2002. Our objective was to assess relative effectiveness of BCG immunization. Methods/Findings We compared outcomes of birth cohorts from the 4 time-frames retrospectively. Three cohorts received vaccine from one of three manufacturers exclusively, and one cohort was not vaccinated. Cohorts were followed for 3 years for notifications of clinical TB and of culture-confirmed TB, and for 21 months for TB meningitis notifications. Prevention effectiveness based on relative risk of TB incidence was calculated for each vaccinated cohort compared to the non-vaccinated cohort. Although there were differences in prevention effectiveness observed among the three BCG vaccines, all were protective. The Japanese vaccine (currently used in Kazakhstan), the Serbian vaccine, and the Russian vaccine respectively were 69%, 43%, and 22% effective with respect to clinical TB notifications, and 92%, 82%, and 51% effective with respect to culture confirmed TB. All three vaccines were >70% effective with respect to TB meningitis. Limitations Potential limitations included considerations that 1) the methodology used was retrospective, 2) multiple risk factors could have varied between cohorts and affected prevention effectiveness measures, 3) most cases were clinically diagnosed, and TB culture-positive case numbers and TB meningitis case numbers were sparse, and 4) small variations in reported population TB burden could have affected relative risk of exposure for cohorts. Conclusions/Significance All three BCG vaccines evaluated were protective against TB, and prevention effectiveness varied by manufacturer. When setting national immunization policy, consideration should be given to prevention effectiveness of BCG preparations.

Differences in HIV-2 plasma viral load and immune activation in HIV-1 and HIV-2 dually infected persons and those infected with HIV-2 only in Abidjan, Côte D'Ivoire.

Objective: To determine whether blood plasma levels of HIV-2 RNA viral loads and immune activation markers differ between persons infected with HIV-2 only and those dually infected with HIV-1 and HIV-2. Methods: Between September 1996 and February 2000, we collected, analyzed and compared levels of HIV-2 RNA in plasma and immune activation markers among 52 persons infected with HIV-2 alone and 75 with confirmed dual infection. We also compared viral load and immune activation in patients who were infected with HIV-1 only and those who were dually infected. Results: When we conducted a CD4 T-cell count-stratified multivariate analysis of HIV-2 viral load, controlling for difference in CD4 T-cell counts, age and sex: at < 200 × 106 CD4 T cells/l, HIV-2 viral load was 2.0 log10 copies/ml lower in dually infected patients than in HIV-2 only patients (P < 0.0001). At CD4 T-cell counts between 200 × 106 and 500 × 106/l, HIV-2 viral load was 0.3 log10 copies/ml lower in dually infected patients (P = 0.45). However, at CD4 T-cells counts > 500 × 106/l, HIV-2 viral load was 0.9 log10 copies/ml higher in dually infected patients (P < 0.0001). Dually infected persons with undetectable HIV-2 viral loads had significantly higher median levels of CD8 T cells expressing CD38 (P < 0.001) and HLA-DR (P = 0.01) than HIV-2 only infected patients. Conclusion: These results suggest that in dual infection, the level of HIV-2 replication depends on the immune status of the patients, with HIV-1 out-replicating HIV-2 as disease progress.

Cost savings associated with increased safety belt use in Iowa, 1987–1988

Although safety belt use increases after passage of a safety belt law, the statewide direct and indirect cost savings associated with increased safety belt use after a belt use law has been enacted is not known. We analyzed a subset of data from the Iowa Safety Restraint Assessment consisting of 997 injured motor vehicle occupants treated at any of 11 Iowa hospitals from throughout the state between November 1987 and March 1988. We found that injuries were more serious and that more deaths and cases of permanent disability occurred among persons who did not wear safety belts. Failure to use safety belts was independently associated with higher payments to hospitals by health care insurers and individuals in nearly all age, sex, and vehicle speed categories. Lifetime direct and indirect cost savings associated with Iowas safety belt law for persons injured in one year were estimated to be

Sexually transmitted diseases and managed care: an inquiry and review of issues affecting service delivery.

69.5 million.

Assessment of the infectious diseases surveillance system of the Republic of Armenia: an example of surveillance in the Republics of the former Soviet Union

To understand the potential role of managed care organizations (MCOs) in prevention and control of sexually transmitted diseases (STDs), we conducted a systematic review of articles on STDs and managed care and sought qualitative information from MCOs on STD-related activities. The review focused on prevention, risk assessment, patient education, counseling, screening, and costs of care, but revealed relatively few published articles. Barriers to STD service delivery included competing priorities, lack of time or supporting organizational structures, and differing mandates of health departments and MCOs. Facilitators included collaboration between health departments and MCOs, regulatory and performance incentives, buy-in from key stakeholders, availability of infrastructure to support data collection, and inclusion of chlamydia screening in the Health Employer Data and Information Set to monitor plan performance. Because of the shift of STD service delivery from the public to private sector, incentives need to maximize interest and cooperation of patients, clinicians, and MCOs in STD prevention.