Factors associated with CD4 lymphocyte counts in HIV-negative Senegalese individuals.

CD4+ lymphocytes are a primary target of the human immunodeficiency virus (HIV), and CD4 counts are one of the factors used to measure disease progression in HIV-positive individuals. CD4 counts vary in uninfected individuals and across populations due to a variety of demographic, environmental, immunological and genetic factors that probably persist throughout the course of HIV infection. This study sought to determine reference levels and identify factors that influence lymphocyte counts in 681 HIV-uninfected adults in Senegal, where residents are exposed to a variety of infectious diseases and other conditions that may affect CD4 counts. Lymphocyte counts were assessed in commercial sex workers, symptomatic men and women presenting to the University of Dakar infectious disease clinic for out-patient care and women seeking family planning services. CD4 and CD3 lymphocyte counts differed between the four study groups (P < 0.01). Men had the lowest mean CD4 count (711.6 cells/microl), while commercial sex workers had the highest levels (966.0 cells/microl). After adjustment for age and other behavioural and clinical factors, the difference in CD4 counts between the three groups of women did not remain. However, both gender and smoking were associated independently with CD4 counts, as men maintained lower mean CD4 counts (beta = -156.4 cells/microl, P < 0.01) and smokers had higher mean CD4 counts (beta = 124.0 cells/microl, P < 0.01) than non-smokers in multivariable analyses. This study is the first to explore factors that may influence CD4 levels in Senegal and to estimate baseline CD4 levels among HIV-negatives, information that may guide clinicians in interpreting CD4 counts.

Prospective analysis of Staphylococcus aureus bacteremia in nonneutropenic adults with malignancy.

PURPOSE: To determine the primary sources and secondary complications of Staphylococcus aureus bacteremia (SAB) in cancer patients, as well as predictors of outcome in cancer patients with SAB. PATIENTS AND METHODS: Fifty-two patients at Duke University Medical Center met entry criteria between September 1994 and December 1996 for this prospective cohort study involving hospitalized nonneutropenic adult cancer patients with SAB. All subjects were observed throughout initial hospitalization and were evaluated again at 6 and 12 weeks or until death. RESULTS: SAB was intravascular device-related in 42%, tissue infection-related (TIR) in 44%, and unidentifiable focus-related (UFR) in 13%. Seventeen patients (33%) were found to have metastatic infections or conditions, with eight (15%) developing infectious endocarditis (IE). Patients with TIR bacteremia were less likely than other patients to develop IE (4% v 24%, P =.06). The overall mortality rate was 38%, the SAB-related mortality rate was 15%, and the rate of SAB relapse was 12%. Methicillin resistance was not associated with adverse outcome. Inability to identify a point of entry (UFR bacteremia), however, was associated with a higher overall mortality rate (100% v 24%, P =.0006). Furthermore, a 72-hour surveillance blood culture positive for organisms was associated with an increased incidence of IE (P =.0006), metastatic infections or conditions (P =.0002), SAB relapse (P =.038), and SAB-related death (P =.038). CONCLUSION: SAB in cancer patients is associated with significant morbidity from frequent metastatic infections or conditions including IE, as well as considerable mortality. Unknown initial infection site and 72-hour surveillance cultures positive for organisms were predictive of a complicated course and poor final outcome.

Staphylococcus aureus bacteremia in the surgical patient: a prospective analysis of 73 postoperative patients who developed Staphylococcus aureus bacteremia at a tertiary care facility.

BACKGROUND: Staphylococcus aureus is a frequent cause of infection and bacteremia in the postoperative patient. Unfortunately, there have been no prospective studies evaluating these patients, so the incidence of complications, subsequent treatment algorithms, and prognosis remain undefined. The objectives of this prospective study of postoperative Staphylococcus aureus bacteremia (SAB) were to define the primary sources of bacteremia and to identify the common complications of SAB in the postoperative setting. METHODS: A registry was developed into which 309 consecutive adult patients with SAB were prospectively enrolled between September 1994 and December 1996. Seventy-three of these patients (23.6%) developed SAB in the postoperative setting. RESULTS: Analysis of the clinical features of these 73 postoperative patients revealed three important results. First, infective endocarditis is surprisingly common in postoperative patients with SAB and the classical stigmata of endocarditis are often absent. Transesophageal echocardiography was performed in 31 of 73 patients; 10 of these patients (32.3%) met Duke Criteria for definite endocarditis, but only 3 of these patients had vegetations detected by transthoracic echocardiography, and only 2 patients had peripheral stigmata of infective endocarditis. Second, the development of SAB after cardiothoracic surgery was strongly associated with underlying S. aureus mediastinitis. Twenty-one of the 23 patients who developed SAB after median sternotomy had mediastinitis (positive predictive value 91.3%). In many cases, the diagnosis of mediastinitis was not apparent when SAB was detected. Third, complications, relapses, and mortality were high in postoperative patients with SAB. Fourteen of 73 patients (19.2%) developed multiple noncardiac metastatic complications, including metastatic abscesses (5), septic emboli (3), pneumonia or empyema (2), septic arthritis (1), epidural abscess (1), and other metastatic foci (7). Twelve of 73 patients (16.4%) had recurrent staphylococcal infection after treatment of their first episode of SAB, including 8 patients (11.0%) with recurrent bacteremia. Of patients who survived, those with recurrent staphylococcal infection were more likely to have an infected surgical wound than were patients who were cured of infection (p = 0.05). Finally, mortality attributable to SAB (11.0%), and all-cause mortality (21.9%), was high. CONCLUSIONS: SAB in the postoperative setting is often a severe disease with high morbidity and mortality. A thorough diagnostic evaluation is indicated in surgical patients with S. aureus bacteremia to ensure the early detection of metastatic infections such as infective endocarditis and to define foci such as mediastinitis re quiring surgical intervention.

Influence of HIV-1 and/or HIV-2 infection and CD4 count on cervical HPV DNA detection in women from Senegal, West Africa.

BACKGROUND: HIV infection is associated with greater risk of precancerous lesions and cervical cancer in women. However, several factors remain unclarified regarding the association between HIV infection and HPV detection, especially among those with HIV type 2 versus type 1 infection and severely immunocompromised persons. OBJECTIVES: To evaluate HPV overall and type-specific detection among HIV-infected and uninfected women in Senegal. STUDY DESIGN: Detection of HPV DNA for 38 genotypes in cervical swabs using PCR-based methods was evaluated in HIV-positive (n=467) and HIV-negative (n=2139) women participating in studies in Senegal. Among HIV-1 and/or HIV-2 positive women, CD4 counts were assessed. Adjusted multivariable prevalence ratios (PR) were calculated. RESULTS: The prevalence of any HPV DNA and multiple HPV types was greater among HIV-infected individuals (78.2% and 62.3%, respectively) compared with HIV-negative women (27.1% and 11.6%). This trend was also seen for HPV types 16 and 18 (13.1% and 10.9%) compared to HIV-negative women (2.2% and 1.7%). HIV-infected women with CD4 cell counts less than 200 cells/µl had a higher likelihood of any HPV detection (PRa 1.30; 95% CI 1.07-1.59), multiple HPV types (PRa 1.52; 95% CI 1.14-2.01), and HPV-16 (PRa 9.00; 95% CI 1.66-48.67), but not HPV-18 (PRa 1.20, 95% CI 0.45-3.24) compared to those with CD4 counts 500 cells/µl or above. CONCLUSION: HIV-infected women, especially those most severely immunocompromised, are more likely to harbor HPV. Measures to prevent initial HPV infection and subsequent development of cervical cancer through focused screening efforts should be implemented in these high risk populations.

Trends of HIV-1, HIV-2 and dual infection in women attending outpatient clinics in Senegal, 1990-2009.

We assessed trends in the relative prevalences of HIV-1, HIV-2 and dual HIV-1/HIV-2 infection in 10,321 women attending outpatient clinics in Senegal between 1990 and 2009. The relative prevalence of HIV-1 (defined as the proportion of seropositive subjects having HIV-1) rose sharply from 38% in 1990 until 1993 (P < 0.001), whereupon it continued to rise, but at a slower rate, reaching 72% of HIV infections in 2009. As compared with HIV-1, the relative prevalence of HIV-2 decreased sharply from 54% in 1990 until 1993 (P < 0.001) and continued to decrease at a slower rate through 2009. The relative prevalence of dual infection, as compared with HIV-1, was stable from 1990 to 1993, but decreased slightly thereafter (P < 0.001). These study findings indicate that during the early 1990s, the relative prevalence of HIV-1 increased markedly, while the relative prevalence of HIV-2 decreased and the relative prevalence of dual infection remained stable in Senegal. From 1993 to 2009, the relative prevalence of HIV-1 increased at a slower rate, while the relative prevalences of HIV-2 and dual infection decreased. These results confirm trends in HIV prevalence observed in other West African populations and provide a critical update on HIV transmission risk among women in Senegal.

UV photoaffinity labeling of Tn3 transposase--DNA complexes: identification of DNA binding domains.

The prokaryotic transposon Tn3 requires the transposase protein, as well as the cis-acting terminal inverted repeats (IRs), for transposition. The first step in the transposition process requires transposase binding to the IRs, as well as target site selection for element insertion. The primary aim of this study is to define the relationship between the structure of Tn3 transposase and its DNA binding functions. We have defined, by UV cross-linking, two broad regions of transposase that interact with DNA: a 70-kDa N-terminal domain and a 30-kDa C-terminal domain. The 70-kDa N-terminal domain encompasses the IR sequence specific binding domain, as well as a nonspecific DNA binding domain that has been previously described. We have also defined, by UV cross-linking, a region in the nonspecific DNA binding domain centered at amino acids 376 and 381 that is in contact with DNA. We have used site-directed mutagenesis of amino acids 376 and 381 to help delineate the function of this region of the transposase protein. Mutations in this region reduce transposition frequency to 30-40% of the wild type. These mutations reduce nonspecific DNA binding three- to four-fold but do not appear to affect specific binding to the IR. Transposition immunity is unaffected by mutations in the nonspecific DNA binding domain. This suggests that this region may be involved in target site selection.

Geriatric complex offers options from housing to skilled nursing.

A not-for-profit geriatric complex offers comprehensive services and care ranging from independent living, with limited supportive services, in apartment units, to an intermediate level of care in a health-related facility, to skilled nursing and intensive care in an accredited long-term care facility. Thus, the elderly residents and patients are provided with ready access to progressive patient care in either direction whenever needed. The complex includes newly constructed and recycled apartment and medical care buildings.

Candida dubliniensis fungemia in a solid organ transplant patient: case report and review of the literature.

We report a case of Candida dubliniensis fungemia in a solid organ transplant patient, which, to our knowledge is the first such case in this patient population. C. dubliniensis is a recently described, emerging fungal pathogen, thus far, found in AIDS and a limited number of other immunosuppressed patients. It is of interest and concern because it can be misidentified as C. albicans and it may be resistant to azole antifungal agents. This case illustrates the need to be aware of emerging pathogens in new host populations and that new techniques used to identify yeast species may provide more accurate identification.

Recurrent Staphylococcus aureus bacteremia: pulsed-field gel electrophoresis findings in 29 patients.

To identify risk factors for relapse among 309 prospectively identified cases of Staphylococcus aureus bacteremia, patients with recurrent S. aureus bacteremia were identified, and pulsed-field gel electrophoresis (PFGE) was performed on isolates from both episodes. PFGE banding patterns from both isolates were identical in 23 patients, consistent with relapsed infection. Patients with PFGE-confirmed relapse were more likely by both univariate and multivariate analyses to have an indwelling foreign body (odds ratio [OR]=18.2, 95% confidence interval [CI]=7. 6-43.6; P<.001), to have received vancomycin therapy (OR=4.1, 95% CI=1.5-11.6; P=.008), or be hemodialysis-dependent (OR=4.1, 95% CI=1. 8-9.3; P=.002) than patients who did not develop recurrent bacteremia. These results suggest that recurrent episodes of S. aureus bacteremia are primarily relapses and are associated with an indwelling foreign body, receiving vancomycin therapy, and hemodialysis dependence.

Comparison of human immunodeficiency virus (HIV)-specific T-cell responses in HIV-1- and HIV-2-infected individuals in Senegal.

Human immunodeficiency virus type 2 (HIV-2) infection is typically less virulent than HIV-1 infection, which may permit the host to mount more effective, sustained T-cell immunity. We investigated antiviral gamma interferon-secreting T-cell responses by an ex vivo Elispot assay in 68 HIV-1- and 55 HIV-2-infected Senegalese patients to determine if differences relate to more efficient HIV-2 control. Homologous HIV-specific T cells were detected in similar frequencies (79% versus 76%, P = 0.7) and magnitude (3.12 versus 3.08 log(10) spot-forming cells/10(6) peripheral blood mononuclear cells) in HIV-1 and HIV-2 infection, respectively. Gag-specific responses predominated in both groups (>/=64%), and significantly higher Nef-specific responses occurred in HIV-1-infected (54%) than HIV-2-infected patients (22%) (P < 0.001). Heterologous responses were more frequent in HIV-1 than in HIV-2 infection (46% versus 27%, P = 0.04), but the mean magnitude was similar. Total frequencies of HIV-specific responses in both groups did not correlate with plasma viral load and CD4(+) T-cell count in multivariate regression analyses. However, the magnitude of HIV-2 Gag-specific responses was significantly associated with lower plasma viremia in HIV-1-infected patients (P = 0.04). CD4(+) T-helper responses, primarily recognizing HIV-2 Gag, were detected in 48% of HIV-2-infected compared to only 8% of HIV-1-infected patients. These findings indicate that improved control of HIV-2 infection may relate to the contribution of T-helper cell responses. By contrast, the superior control of HIV-1 replication associated with HIV-2 Gag responses suggests that these may represent cross-reactive, higher-avidity T cells targeting epitopes within Gag regions of functional importance in HIV replication.

Infective endocarditis due to Staphylococcus aureus: 59 prospectively identified cases with follow-up.

Fifty-nine consecutive patients with definite Staphylococcus aureus infective endocarditis (IE) by the Duke criteria were prospectively identified at our hospital over a 3-year period. Twenty-seven (45.8%) of the 59 patients had hospital-acquired S. aureus bacteremia. The presumed source of infection was an intravascular device in 50.8% of patients. Transthoracic echocardiography (TTE) revealed evidence of IE in 20 patients (33.9%), whereas transesophageal echocardiography (TEE) revealed evidence of IE in 48 patients (81.4%). The outcome for patients was strongly associated with echocardiographic findings: 13 (68.4%) of 19 patients with vegetations visualized by TTE had an embolic event or died of their infection vs. five (16.7%) of 30 patients whose vegetations were visualized only by TEE (P < .01). Most patients with S. aureus IE developed their infection as a consequence of a nosocomial or intravascular device-related infection. TEE established the diagnosis of S. aureus IE in many instances when TTE was nondiagnostic. Visualization of vegetations by TTE may provide prognostic information for patients with S. aureus IE.