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BackgroundThe HIV Prevention Trials Network (HPTN) Study 073 (HPTN 073) assessed the feasibility, acceptability, and safety of preexposure prophylaxis (PrEP) for black men who have sex with men (BMSM). The purpose of this analysis was to characterize the relationship between PrEP uptake and use and incident sexually transmitted infections (STIs) among participants enrolled in HPTN 073.MethodsA total of 226 human immunodeficiency virus (HIV)-uninfected BMSM were enrolled in 3 US cities; all participants received client-centered care coordination (C4) and were offered daily oral PrEP. Participants were followed for 12 months with STI testing (rectal and urine nucleic acid amplification test for gonorrhea and chlamydia, rapid plasma reagin for syphilis) conducted at baseline, week 26, and week 52. Logistic regression was used to examine associations between STI incidence and PrEP uptake. Generalized estimating equations were used to evaluate associations between age, PrEP acceptance, sexual behaviors, and incident STIs.ResultsBaseline STI prevalence was 14.2%. Men aged

Background. Antimicrobial stewardship programs are advised to measure and risk-adjust antimicrobial use to facilitate interhospital comparisons, a process called benchmarking. The purpose of this investigation was to evaluate a new benchmarking strategy for antibacterials. Methods. Hospital-wide adult antibacterial drug use in 2009 was measured as days of therapy (DOT) and length of therapy (LOT) from billing records in 70 US academic medical centers (AMCs). Patients were assigned to 1 of 35 clinical service lines (CSL) based on their Medicare Severity Diagnosis Related Group. Expected (E) use was determined by indirect standardization and compared with observed (O) use. Results. Of 1 791 180 discharged adults, 63.7% received antibacterial drugs; the range by CSL was 14.3% (psychiatry) to 99.7% (lung transplant). Mean ± SD hospital-wide use was 839 ± 106 DOTs (range, 594-1109) and 536 ± 53.0 LOT (range, 427-684) per 1000 patient-days. The ventilator support CSL had the most DOT per discharge, 39.4±9.4 days; the LOT was 21.5±4.5 days. The hospital-wide O/E ratio range was 0.7-1.45; in 5 AMCs the ratio exceeded the 90% confidence interval (CI) and was below the 90% CI in 6. Variability in use was explained by the proportion of treated patients within each CSL and mean LOT and DOT per discharge. Conclusions. Adult antibacterial drug use was benchmarked to expected use adjusted for patient mix, and outlier hospitals were identified. Differences between expected and observed use reflect usage patterns that were benchmarked and are targets for evaluation and intervention. [ABSTRACT FROM AUTHOR]

Background. Highly active antiretroviral therapy (HAART) has improved human immunodeficiency virus (HIV)-associated morbidity and mortality. The bimodal mortality distribution in HIV-infected children makes it important to evaluate temporal effects of HAART among a birth cohort with long-term, prospective follow-up. Methods. Perinatal AIDS Collaborative Transmission Study (PACTS)/PACTS-HIV Follow-up of Perinatally Exposed Children (HOPE) study was a Centers for Disease Control and Prevention-sponsored multicenter, prospective birth cohort study of HIV-exposed uninfected and infected infants from 1985 until 2004. Mortality was evaluated for the no/monotherapy, mono-/dual-therapy, and HAART eras, that is, 1 January 1986 through 31 December 1990, from 1 January 1991 through 31 December 1996, and 1 January 1997 through 31 December 2004. Results. Among 364 HIV-infected children, 56% were female and 69% black non-Hispanic. Of 98 deaths, 79 (81%) and 61 (62%) occurred in children ≤3 and ≤2 years old, respectively. The median age at death increased significantly across the eras (P < .0001). The average annual mortality rates were 18 (95% confidence interval [CI], 11.6-26.8), 6.9 (95% CI, 5.4-8.8), and 0.8 (95% CI, 0.4-1.5) events per 100 person-years for the no/monotherapy, mono-/dual-therapy and HAART eras, respectively. The corresponding 6-year survival rates for children born in these eras were 57%, 76%, and 91%, respectively (P, .0001). Among children who received HAART in the first 6 months of age, the probability of 6-year survival was 94%. Ten-year survival rates for HAART and non-HAART recipients were 94% and 45% (P < .05). HAART-associated reductions in mortality remained significant after adjustment for confounders (hazard ratio, 0.3; 95% CI, .08-.76). Opportunistic infections (OIs) caused 31.8%, 16.9%, and 9.1% of deaths across the respective eras (P = .051). Conclusions. A significant decrease in annual mortality and a prolongation in survival were seen in this US perinatal cohort of HIV-infected children. Temporal decreases in OI-associated mortality resulted in relative proportional increases of non-OI-associated deaths. [ABSTRACT FROM AUTHOR]

Background. Chloroquine (CQ) remains the treatment of choice for Plasmodium vivax malaria. Initially confined to parts of Indonesia and Papua, resistance of P. vivax to CQ seems to be spreading, and alternative treatments are required. Methods. We conducted a randomized controlled study to compare the efficacy and the tolerability of CQ and dihydroartemisinin-piperaquine (DP) in 500 adults and children with acute vivax malaria on the Northwestern border of Thailand. Results. Both drugs were well tolerated. Fever and parasite clearance times were slower in the CQ than in the DP group (P < .001). By day 28, recurrent infections had emerged in 18 of 207 CQ recipients compared with 5 of 230 treated with DP (relative risk, 4.0; 95% confidence interval [CI], 1.51-10.58; P = .0046). The cumulative risk of recurrence with P. vivax at 9 weeks was 79.1% (95% CI, 73.5%-84.8%) in patients treated with CQ compared with 54.9% (95% CI, 48.2%-61.6%) in those receiving DP (hazard ratio [HR], 2.27; 95% CI, 1.8-2.9; P < .001). Children <5 years old were at greater risk of recurrent P. vivax infection (74.4%; 95% CI, 63.2%-85.6%) than older patients (55.3% [95% CI, 50.2%-60.4%]; HR, 1.58 [95% CI, 1.1-2.2]; P = .005). In vitro susceptibility testing showed that 13% of the tested isolates had a CQ median inhibitory concentration >100 nmol/L, suggesting reduced susceptibility. Conclusions. The efficacy of CQ in the treatment of P. vivax infections is declining on the Thai-Myanmar border. DP is an effective alternative treatment. [ABSTRACT FROM AUTHOR]

Reporting of confirmed pandemic influenza A virus (pH1N1) 2009 infection was mandatory among health care workers in Hong Kong. Among 1158 confirmed infections, there was no significant difference in incidence among clinical versus nonclinical staff (relative risk, 0.98; 95% confidence interval, 0.78-1.20). Reported community exposure to pH1N1 was common and was similar in both groups. [ABSTRACT FROM AUTHOR]

We studied 1,819 children with 2,592 peripherally inserted central venous catheters (PICCs). Independent predictors of CLABSI included prolonged catheter dwell time, pediatric ICU exposure, and administration of parenteral nutrition as indication for PICC insertion.Background. Increasingly, peripherally inserted central venous catheters (PICCs) are placed for prolonged intravenous access. Few data exist regarding risk factors for central line–associated bloodstream infection (CLABSI) complicating PICCs in hospitalized children, especially children hospitalized outside the intensive care unit (ICU).Methods. We identified all children with a PICC inserted at The Johns Hopkins Hospital (Baltimore, MD) from 1 January 2003 through 31 December 2009 and used Poisson regression models to identify risk factors for PICC-associated CLABSIs.Results. A total of 2592 PICCs were placed in 1819 children. One hundred sixteen CLABSIs occurred over 44,972 catheter-days (incidence rate [IR], 2.58 cases per 1000 catheter-days; 95% confidence interval [CI], 2.07–3.00 cases per 1000 catheter-days). Independent predictors of CLABSI in the entire cohort included PICC dwell time of ≥21 days (IR ratio [IRR], 1.53; 95% CI, 1.05–2.26), parenteral nutrition as indication for insertion (IRR, 2.24; 95% CI, 1.31–3.84), prior PICC-associated CLABSI (IRR, 2.48; 95% CI, 1.18–5.25), underlying metabolic condition (IRR, 2.07; 95% CI, 1.14–3.74), and pediatric ICU exposure during hospitalization (IRR, 1.80; 95% CI, 1.18–2.75). Risk factors for CLABSI in children without PICU exposure included younger age, underlying malignancy and metabolic conditions, PICCs inserted in the lower extremity, and a prior PICC-associated CLABSI.Conclusions. Prolonged catheter dwell time, pediatric ICU exposure, and administration of parenteral nutrition as the indication for PICC insertion are important predictors of PICC-associated CLABSI in hospitalized children. A careful assessment of these risk factors may be important for future success in preventing CLABSIs in hospitalized children with PICCs. [ABSTRACT FROM AUTHOR]

Background. A number of observational studies and a few small or open randomized clinical trials suggest that the American cranberry may decrease incidence of recurring urinary tract infection (UTI).Methods. We conducted a double-blind, placebo-controlled trial of the effects of cranberry on risk of recurring UTI among 319 college women presenting with an acute UTI. Participants were followed up until a second UTI or for 6 months, whichever came first. A UTI was defined on the basis of the combination of symptoms and a urine culture positive for a known uropathogen. The study was designed to detect a 2-fold difference between treated and placebo groups, as was detected in unblinded trials. We assumed 30% of participants would experience a UTI during the follow-up period.Results. Overall, the recurrence rate was 16.9% (95% confidence interval, 12.8%–21.0%), and the distribution of the recurrences was similar between study groups, with the active cranberry group presenting a slightly higher recurrence rate (20.0% vs 14.0%). The presence of urinary symptoms at 3 days, 1–2 weeks, and at ≥1 month was similar between study groups, with overall no marked differences.Conclusions. Among otherwise healthy college women with an acute UTI, those drinking 8 oz of 27% cranberry juice twice daily did not experience a decrease in the 6-month incidence of a second UTI, compared with those drinking a placebo. [ABSTRACT FROM AUTHOR]

Background. To determine the rate of seroconversion after 2 doses of a novel split virion, inactivated, adjuvanted pandemic H1N1 influenza vaccine (A/California/7/2009) in human immunodeficiency virus type 1 (HIV-1)–infected patients (ClinicalTrials.gov NCT01017172).Methods. Diagnostic study of adult HIV-1–infected patients scheduled for H1N1 influenza A vaccination. Blood samples where taken before and 21 days after the first dose and 21 days after the second dose of the vaccine. Antibody (AB) titers were determined by hemagglutination inhibition assay. Seroconversion was defined by either an AB titer ≤1:10 before and ≥1:40 after or ≥1:10 before and a ≥4-fold increase in AB titer 21 days after vaccination.Results. One hundred thirty-five patients received 2 doses of the H1N1 vaccine and were analyzed. The rate of seroconversion was 68.2% (95% confidence interval, 59.6–75.9) after the first dose and 91.9% (95% confidence interval, 85.9–95.9) after the second dose. Patients who did not seroconvert had a lower mean nadir CD4 cell count (±standard deviation; 81 ± 99 vs 190 ± 148 cells/μL; P = .006), had a longer duration of HIV infection (±standard deviation; 13.1 ± 5.9 vs 8.8 ± 6.8 years; P = .04), and were more likely to have an AB titer ≥1:40 before vaccination (4% vs 55%; P < .001) when compared with patients with seroconversion. No other differences were found between the 2 groups, including AIDS status, highly active antiretroviral therapy status, HIV RNA - polymerase chain reaction load <50 copies/mL, CD4 cell count, sex, body mass index, and chronic hepatitis.Conclusion. Among HIV-infected patients, the rate of seroconversion after the first dose of an adjuvanted H1N1 influenza A vaccine was 68% and increased to 92% after a second doses. [ABSTRACT FROM AUTHOR]

Background. Factors involved in the development of resistance to sulphadoxine-pyrimethamine (SP) by Plasmodium falciparum, particularly in the context of intermittent preventive treatment during pregnancy (IPTp), are not well known. We aimed to determine the impact of IPTp and human immunodeficiency virus (HIV) infection on molecular markers of SP resistance and the clinical relevance of resistant infections.Methods. SP resistance alleles were determined in peripheral (n = 125) and placental (n = 145) P. falciparum isolates obtained from pregnant women enrolled in a randomized, placebo-controlled trial of IPTp in Manhiça, Mozambique.Results. Prevalence of quintuple mutant infections was 12% (23 of 185 isolates) in pregnant women who received placebo and 24% (20 of 85 isolates) in those who received SP (P = .031). When the last IPTp dose was administered at late pregnancy, mutant infections at delivery were more prevalent in placental samples (7 [23%] of 30, samples) than in peripheral blood samples (2 [7%] of 30 samples; P = .025), more prevalent in women who received IPTp-SP than in those who received placebo (odds ratio [OR], 8.13; 95% confidence interval [CI], 1.69–39.08), and more prevalent in HIV-positive women than in HIV-negative women (OR, 5.17; 95% CI, 1.23–21.66). No association was found between mutant infections and increased parasite density or malaria-related morbidity in mothers and children.Conclusions. IPTp with SP increases the prevalence of resistance markers in the placenta and in HIV-infected women at delivery, which suggests that host immunity is key for the clearance of drug-resistant infections. However, this effect of IPTp is limited to the period when blood levels of SP are likely to be significant and does not translate into more-severe infections or adverse clinical outcomes. [ABSTRACT FROM AUTHOR]

Background. Ventilator-associated pneumonia (VAP), the most common hospital-acquired infection in intensive care units, increases mortality and health care costs. We describe the long-term impact of a multifaceted program for decreasing VAP rates that markedly improved compliance with 8 targeted preventive measures. Methods. We compared VAP rates during a 45-month baseline period and a 30-month intervention period in a cohort of patients who received mechanical ventilation for 148 h. VAP was diagnosed on the basis of quantitative cultures of distal specimens. VAP incidence density rates were expressed as total VAP episodes over totalmechanical ventilation duration and as first VAP episodes over mechanical ventilation duration at VAP or hospital discharge. We used segmented regression analysis and a Cox proportional hazard model to assess the impact of the program on first VAP occurrence. Results. Baseline and intervention VAP rates were 22.6 and 13.1 total VAP episodes over total mechanical ventilation duration per 1000 ventilation-days, respectively, and 26.1 and 14.9 first VAP episodes over mechanical ventilation duration at VAP or hospital discharge per 1000 procedure-days, respectively (P < .001). VAP rates decreased by 43% in both statistical analyses and remained significant after adjustment for confounders (Cox adjusted hazard ratio, 0.58; 95% confidence interval, 0.46-0.72; P < .001). Daily VAP hazard rates on ventilation days 5, 10, and 15 were 2.6%, 3.5%, and 3.4%, respectively, during the baseline period and 1.4%, 2.3%, and 2%, respectively, during the intervention period. Conclusion. Our preventive program produced sustained VAP rate decreases in the long term. However, VAP rates remained substantial despite high compliance with preventive measures, suggesting that eliminating VAP in the intensive care unit may be an unrealistic goal. [ABSTRACT FROM AUTHOR]

Background. Congenital cytomegalovirus (CMV) is a leading cause of disability, including sensorineural hearing loss, developmental delay, and mental retardation. Although the seroprevalence of CMV and associated exposure and behavioral risk factors have been reported in adolescent females, few data exist about males. Methods. Serum samples were obtained from males aged 12-17 years from June 2006 through July 2007 in Cincinnati, Ohio; Galveston, Texas; and Nashville, Tennessee. The samples were tested for CMV immunoglobulin G antibody with a commercial assay. Participants completed a computer-assisted screening interview to assess 7 risk categories. Results. A total of 397 adolescent males were screened, and 165 (47%) were seropositive. African American race, older age, and exposure to children ⩾3 years of age in the home were significant predictors of CMV infection in the univariate analysis. Hispanic ethnicity, group living situations, saliva-sharing behaviors, and intimate sexual contact were not associated with CMV infection. However, among those with a history of sexual contact, the number of life-time partners was associated with CMV. In the final multivariate model, CMV seroprevalence was significantly higher in African American subjects (odds ratio [OR], 1.93; 95% confidence interval [CI], 1.27-2.95) and subjects ⩾14 years of age (OR, 1.1; 95% CI, 1.0-1.28). With each additional risk factor, males had a 1.6 times increased risk of CMV. Conclusions. CMV infections are common in adolescent males and are associated with African American race and increasing age. Further study is needed to understand these risk factors in preparation for a CMV vaccine targeted at both adolescent males and females. [ABSTRACT FROM AUTHOR]

Background. On the basis of meta-analyses, concern has been raised regarding a possible signal of increased mortality associated with the use of cefepime versus other b-lactam antibiotics. To further investigate this possible signal, we accessed findings and data from published and unpublished cefepime clinical trials. Methods. We performed meta-analyses using trial- and patient-level data from comparative trials. Trial-level analyses were performed using summary data from all patients in the trials, and patient-level analyses were performed on trials for which patient-level data were available. Thirty-day, all-cause mortality was analyzed using the Mantel-Haenszel adjusted risk difference (ARD) method. Results. The trial-level meta-analysis was based on 88 trials (9467 cefepime patients and 8288 comparator patients). The 30-day, all-cause mortality rates were 6.21% (588/9467) for the cefepime patients and 6.00% (497/ 8288) for comparator patients (ARD per 1000 population, 5.38; 95% confidence interval [CI], -1.53 to 12.28). In the patient-level analysis (35 trials, 5058 cefepime patients, and 3976 comparator patients), 30-day, all-cause mortality rates were 5.63% (285/5058) for cefepime patients and 5.68% (226/3976) for comparator patients (ARD per 1000 population, 4.83; 95% CI, -4.72 to 14.38). A sensitivity analysis based solely on the 24 febrile neutropenia trials did not show a statistically significant increase in mortality with cefepime use (ARD per 1000 population, 9.67; 95% CI, -2.87 to 22.21). Conclusions. In both trial-level and patient-level meta-analyses, we did not identify a statistically significant increase in mortality among cefepime-treated patients, compared with those treated with other antibacterials. [ABSTRACT FROM AUTHOR]

Background. Adequate zinc is critical for immune function; however, zinc deficiency occurs in >50% of human immunodeficiency virus (HIV)-infected adults. We examined the safety and efficacy of long-term zinc supplementation in relation to HIV disease progression. Methods. A prospective, randomized, controlled clinical trial was conducted involving 231 HIV-infected adults with low plasma zinc levels (<0.75 mg/L), who were randomly assigned to receive zinc (12 mg of elemental zinc for women and 15 mg for men) or placebo for 18 months. The primary end point was immunological failure. HIV viral load and CD4+ cell count were determined every 6 months. Questionnaires, pill counts, and plasma zinc and C-reactive protein levels were used to monitor adherence to study supplements and antiretroviral therapy. Intent-to-treat analysis used multiple-event analysis, treating CD4+ cell count !200 cells/mm3 as a recurrent immunological failure event. Cox proportional hazard models and the general-linear model were used to analyze morbidity and mortality data. Results. Zinc supplementation for 18 months reduced 4-fold the likelihood of immunological failure, controlling for age, sex, food insecurity, baseline CD4+ cell count, viral load, and antiretroviral therapy (relative rate, 0.24; 95% confidence interval, 0.10-0.56; P< .002). Viral load indicated poor control with antiretroviral therapy but was not affected by zinc supplementation. Zinc supplementation also reduced the rate of diarrhea by more than half (odds ratio, 0.4; 95% confidence interval, 0.183-0.981; P =.019), compared with placebo. There was no significant difference in mortality between the 2 groups. Conclusions. This study demonstrated that long-term (18-month) zinc supplementation at nutritional levels delayed immunological failure and decreased diarrhea over time. This evidence supports the use of zinc supplementation as an adjunct therapy for HIV-infected adult cohorts with poor viral control. [ABSTRACT FROM AUTHOR]

Background. Robust long-term estimates of the risk of development of drug resistance are needed for human immunodeficiency virus (HIV)-infected patients starting combination antiretroviral therapy (cART) regimens currently used in routine clinical practice. Methods. We followed a large cohort of patients seen in 1 of 11 HIV clinics in the United Kingdom after starting cART with nucleoside reverse-transcriptase inhibitors and either a nonnucleoside reverse-transcriptase inhibitor (NNRTI) or a ritonavir-boosted protease inhibitor (PI/r). Survival analysis was employed to estimate the incidence of virological failure and of detected drug resistance. Results. Seven thousand eight hundred ninety-one patients were included; 6448 (82%) started cART with an NNRTI and 1423 (17%) with a PI/r. The cumulative risk of virological failure by 8 years was 28%. The cumulative probabilities of detecting any mutation, ⩾1 major nucleoside reverse-transcriptase inhibitor International AIDS Society-United States of America (IAS-USA) mutation, ⩾1 major NNRTI IAS-USA mutation (in those starting an NNRTI), and ⩾1 major PI IAS-USA mutation (in those starting a PI) were 17%, 14%, 15%, and 7%, respectively, by 8 years. The probability of detecting PI mutations in people who started PI/r-based regimens was lower than that of detecting NNRTI mutations in those starting NNRTI-based regimens (adjusted relative hazard, 0.36; 95% confidence interval, 0.26-0.50; P < .001). The risk of detecting nucleoside resistance did not vary according to whether an NNRTI or a PI/r was used in the regimen (adjusted relative hazard, 1.00; 95% confidence interval, 0.80-1.26; P=.98). Conclusions. In patients who started modern cART in clinical practice in the United Kingdom, virological failure by 8 years was relatively common and was paralleled by an appreciable risk of resistance detection, although the detection rate of class-specific resistance was lower for those who started a PI/r-based regimen. [ABSTRACT FROM AUTHOR]

The incidence of and predictors of acquired immunodeficiency syndrome-defining malignancies (ADMs) and non- ADM (NADMs) were evaluated in a large Italian cohort. The incidence of ADM and NADM was 5.0 cases per 1000 personyears of follow-up (95% confidence interval, 4.3-5.8 cases per 1000 person-years of follow-up) and 2.4 cases per 1000 person-years of follow-up (95% confidence interval, 1.9-3.1 cases per 1000 person-years of follow-up), respectively. Lower current CD4 cell count was an independent predictor of developing malignancies, with the association being stronger for ADM than for NADM. [ABSTRACT FROM AUTHOR]

Background. Before 7-valent pneumococcal conjugate vaccine (PCV7) introduction, invasive pneumococcal disease (IPD) rates among Navajo were several-fold those of the general US population. Only 50% of IPD cases in children involved PCV7 serotypes. Methods. We conducted active, population-based surveillance for IPD for the period 1995-2006. We documented case characteristics and serotyped the isolates. Results. Over 12-year period, we identified 1508 IPD cases, 447 of which occurred in children aged <5 years. Rates of IPD due to vaccine serotypes among children aged <1 year, 1 to <2 years, and 2 to <5 years decreased from 210, 263, and 51 cases per 100,000 population, respectively in 1995-1997 to 0 cases in 2004-2006 (P<.001). Among adults aged ⩾65 years, rates of IPD due to vaccine serotypes decreased 81% (95% confidence interval, -98% to -9%; P=.02). Rates of nonvaccine serotype IPD were unchanged in all age strata except for persons aged 18 to <40 years, among whom the rate decreased by 35% from 27 to 18 cases per 100,000 population (95% confidence interval, -57% to -1%; P=.03). Conclusions. Vaccine-serotype IPD has virtually been eliminated in the PCV7 era among Navajo of all ages. Overall rates of nonvaccine-serotype IPD have not increased, although increases have occurred for some individual types. Rates of all-serotype IPD among Navajo children remain 3-5-fold greater than in the general US population. [ABSTRACT FROM AUTHOR]

Background. No systematic studies exist on sex and gender differences across a broad range of travel-associated diseases. Methods. Travel and tropical medicine GeoSentinel clinics worldwide contributed prospective, standardized data on 58,908 patients with travel-associated illness to a central database from 1 March 1997 through 31 October 2007. We evaluated sex and gender differences in health outcomes and in demographic characteristics. Statistical significance for crude analysis of dichotomous variables was determined using x 2 tests with calculation of odds ratios (ORs) and 95% confidence intervals (CIs). The main outcome measure was proportionate morbidity of specific diagnoses in men and women. The analyses were adjusted for age, travel duration, pretravel encounter, reason for travel, and geographical region visited. Results. We found statistically significant (P < .001) differences in morbidity by sex. Women are proportionately more likely than men to present with acute diarrhea (OR, 1.13; 95% CI, 1.09-1.38), chronic diarrhea (OR, 1.28; 95% CI, 1.19-1.37), irritable bowel syndrome (OR, 1.39; 95% CI, 1.24-1.57), upper respiratory tract infection (OR, 1.23; 95% CI, 1.14-1.33); urinary tract infection (OR, 4.01; 95% CI, 3.34-4.71), psychological stressors (OR, 1.3; 95% CI, 1.14-1.48), oral and dental conditions, or adverse reactions to medication. Women are proportionately less likely to have febrile illnesses (OR, 0.15; 95% CI, 0.10-0.21); vector-borne diseases, such as malaria (OR, 0.46; 95% CI, 0.41-0.51), leishmaniasis, or rickettsioses (OR, 0.57; 95% CI, 0.43-0.74); sexually transmitted infections (OR, 0.68; 95% CI 0.58-0.81); viral hepatitis (OR, 0.34; 95% CI, 0.21-0.54); or noninfectious problems, including cardiovascular disease, acute mountain sickness, and frostbite. Women are statistically significantly more likely to obtain pretravel advice (OR, 1.28; 95% CI, 1.23-1.32), and ill female travelers are less likely than ill male travelers to be hospitalized (OR, 0.45; 95% CI, 0.42-0.49). Conclusions. Men and women present with different profiles of travel-related morbidity. Preventive travel medicine and future travel medicine research need to address gender-specific intervention strategies and differential susceptibility to disease. [ABSTRACT FROM AUTHOR]

Background. Stavudine-containing antiretroviral regimens are widely used in developing countries. Stavudineassociated lipodystrophy commonly occurs, without a clear predictable pattern owing to the unknown interaction between stavudine and the host, among patients who received this regimen. The aim of this study was to determine the clinical risk factors and human leukocyte antigen (HLA) alleles associated with stavudine-associated lipodystrophy. Methods. A case-control, cross-sectional study was conducted for HIV-infected patients receiving stavudinecontaining antiretroviral regimens. Clinical assessments for lipodystrophy by physical examination, anthropometry, and dual-energy X-ray absorptiometry were obtained. On the basis of their clinical assessment, the patients were classified into 2 groups: the case group (moderated to severe lipodystrophy) and the control group (absent to mild lipodystrophy). The clinical characteristics and allelic distribution of HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1, and HLA-DPB1 were compared between the case group and the control group, to determine the possible association with stavudine-associated lipodystrophy. Results. There were 103 patients; 55 patients were in the case group, and 48 patients were in the control group. By use of forward stepwise logistic regression, the presence of HLA-B*4001 (odds ratio [OR], 14.05; 95% confidence interval [CI], 2.57-76.59; P=.002) and a longer duration of stavudine treatment (OR, 1.02; 95% CI, 1.00-1.04; P=.02) were significantly associated with stavudine-associated lipodystrophy, whereas a higher body mass index during treatment (OR, 0.73; 95% CI, 0.61-0.86; P < .001) was associated with a lower risk for lipodystrophy. HLA-B*4001 has a high specificity (95.8%) and a positive predictive value (88.9%) for lipodystrophy. Conclusions. HLA-B*4001 is a strong genetic risk factor for stavudine-associated lipodystrophy in HIV-infected patients in Thailand. HLA-B*4001 may be used as a genetic marker to predict which patients will develop stavudine-associated lipodystrophy, to avoid or shorten the duration of stavudine use. This finding needs to be confirmed in further replication studies. [ABSTRACT FROM AUTHOR]

Background. Comparative cohort studies are often conducted to identify novel therapeutic strategies or prognostic factors for ventilator-associated pneumonia (VAP). We aimed to evaluate the power of such studies to provide clinically and statistically significant conclusions with regard to mortality differences. Methods. We searched in PubMed and Scopus for comparative cohort studies that evaluated mortality in patients with VAP. We calculated the central estimates and corresponding 95% confidence intervals (CIs) for mortality differences between compared patient groups. We also calculated the statistical power of the included studies to detect a difference in mortality that corresponds to a risk ratio of 0.80. Results. We identified 39 (20 prospective) comparative cohort studies on VAP as eligible for inclusion in this analysis. The median absolute risk difference in mortality between compared groups was 10% (interquartile range [IQR], 5%-18%), and the median width of the 95% CI of the absolute risk difference in mortality was 34% (IQR, 28%-42.5%). The median power of the included studies to detect a risk ratio for mortality of 0.80 was 14.7% (IQR, 10.6%-21.8%). Conclusions. There is considerable uncertainty around the central estimate of comparative cohort studies on VAP with regard to mortality differences. For a wiser use of resources allocated to research, we emphasize the need to conduct cohort studies with larger sample size so that potential differences between the compared groups are more likely to be shown. [ABSTRACT FROM AUTHOR]

Background. Despite poor primary health care systems, free antiretroviral therapy (ART) has been available in China for >5 years. Virologic outcomes in Chinese patients receiving ART have not been described on a national level. Methods. A multistage cluster design was used in 8 provinces to randomly select patients who had been receiving first-line ART for at least 6 months, who were stratified into 3 treatment-duration groups. Viral load testing and patient interviews were conducted, and data were linked with national treatment database information. Collected data were analyzed for association with viral suppression by means of multivariate modeling. Adequate viral suppression was defined as a viral load of <400 copies/mL. Results. Of 5256 patients receiving ART, 3894 met the eligibility criteria, among whom 1153 were analyzed. Overall, 72% demonstrated viral suppression, and 82%, 73%, and 67% of the participants receiving ART for 6-11, 12-23, and ⩾24 months, respectively, experienced viral suppression (P < .001). In a multivariate model, treatment given at locations other than county-level hospitals was less likely to achieve viral suppression, with greater odds for inadequate virologic response found at village clinics (odds ratio [OR], 5.4; 95% confidence interval [CI], 2.9-10.1), township health centers (OR, 3.1; 95% CI, 1.7-5.6), and public health clinics (OR, 3.1; 95% CI, 1.7- 5.6). Patients receiving didanosine-based regimens were more likely to experience an inadequate virologic response than were those receiving lamivudine-based regimens (OR, 3.9; 95% CI, 2.7-5.7). Conclusions. China's national ART program is largely successful at suppressing viral load. Care received outside of hospitals and regimens containing didanosine were associated with less favorable virologic outcomes. [ABSTRACT FROM AUTHOR]

Background. Surface-active antiseptics, such as chlorhexidine, are increasingly being used as part of intervention programs to prevent methicillin-resistant Staphylococcus aureus (MRSA) transmission, despite limited evidence and potential for resistance. We report on the effect of an antiseptic protocol on acquisition of both endemic MRSA and an outbreak strain of MRSA sequence type 239 (designated TW). Methods. Interrupted time-series data on MRSA acquisitions in two 15-bed intensive care units were analyzed using segmented regression models to estimate the effects of sequential introduction of an educational campaign, cohorting, and a chlorhexidine-based antiseptic protocol on transmission of TW and non-TW MRSA strains. Representative TW and non-TW MRSA strains were assessed for carriage of qacA/B genes and antiseptic susceptibility. Results. The antiseptic protocol was associated with a highly significant, immediate 70% reduction in acquisition of non-TW MRSA strains (estimated model-averaged incidence rate ratio, 0.3; 95% confidence interval, 0.19-0.47) and an increase in acquisition of TW MRSA strains (estimated model-averaged incidence rate ratio, 3.85; 95% confidence interval, 0.80-18.59). There was only weak evidence of an effect of other interventions on MRSA transmission. All TW MRSA strains (21 of 21 isolates) and <5% (1 of 21 isolates) of non-TW MRSA strains tested carried the chlorhexidine resistance loci qacA/B. In vitro chlorhexidine minimum bactericidal concentrations of TW strains were 3-fold higher than those of non-TW MRSA strains, and in vivo, only patients with non-TW MRSA demonstrated a reduction in the number of colonization sites in response to chlorhexidine treatment. Conclusion. A chlorhexidine-based surface antiseptic protocol can interrupt transmission of MRSA in the intensive care unit, but strains carrying qacA/B genes may be unaffected or potentially spread more rapidly. [ABSTRACT FROM AUTHOR]

Background. Among patients with multidrug-resistant human immunodeficiency virus type 1 (HIV-1) infection, salvage regimens including enfuvirtide have demonstrated sustained efficacy. Because of reluctance to use subcutaneous injections, raltegravir may be an alternative to replace enfuvirtide within a suppressive regimen. We conducted a prospective, randomized, open-label trial to compare the antiviral efficacy and safety of a switch to raltegravir with the efficacy and safety of continuing enfuvirtide. Methods. A total of 170 patients with multidrug-resistant HIV-1 infection and plasma HIV-1 RNA levels <400 copies/mL who were receiving enfuvirtide-based regimens were randomized 1:1 to maintain enfuvirtide or to switch to raltegravir. The primary efficacy end point was the cumulative proportion of patients with virologic failure, defined as a confirmed plasma HIV-1 RNA level ≥400 copies/mL, over 24 weeks. The secondary end points mainly involved safety. Results. The switch to raltegravir was non-inferior to the maintenance of enfuvirtide, with virologic failure rates of 1.2% in both treatment arms in the intention-to-treat analysis (δ = 0.01%; 95% confidence interval, -6.7 to 6.8) and 1.2% and 0%, respectively, in the on-treatment analysis (δ = 1.22%; 95% confidence interval, -5.6 to 8.1). At week 24, 88%-89% of patients in both arms had plasma HIV-1 RNA levels <50 copies/mL. No significant CD4 cell count changes occurred in either arm. Grade 3-4 adverse events and laboratory abnormalities were uncommon and were not different between the treatment arms. Conclusion. A switch to raltegravir was safe, well tolerated, and virologically non-inferior to the maintenance of enfuvirtide in patients infected with multidrug-resistant HIV-1 infection who were receiving suppressive antiretroviral therapy. [ABSTRACT FROM AUTHOR]

Background. The natural history of congenital cytomegalovirus (CMV) infection is scarcely known in populations with high maternal CMV seroprevalence. This study evaluated the birth prevalence, clinical findings at birth, and hearing outcome in CMV-infected children from such a population. Methods. Consecutively born infants were screened for the presence of CMV in urine and/or saliva specimens during the first 2 weeks after birth. Neonatal clinical findings were recorded, and CMV-infected children were tested to document hearing function during follow-up. A subset of mothers of CMV-infected infants were prenatally tested for the presence of anti-CMV immunoglobulin G antibodies. Results. Congenital CMV infection was confirmed in 87 (1.08%; 95% confidence interval [CI], 0.86%-1.33%) of 8047 infants. Seven infants (8.1%; 95% CI, 3.3%-15.9%) had at least 1 clinical finding suggestive of CMV infection, and 4 (4.6%; 95% CI, 1.3%-11.3%) had 13 findings of systemic disease. Sensorineural hearing loss was found in 5 (8.6%; 95% CI, 2.9%-19.0%) of 58 children tested at a median age of 21 months. Bilateral profound hearing loss was observed in 2 children, and the hearing threshold was 160 decibels in all 5 children with hearing loss, including 2 children born to mothers with probable nonprimary CMV infection. Conclusions. The results of this large newborn screening study in a population with high CMV seroimmunity provide additional evidence that congenital CMV disease occurs in populations with high seroprevalence rates, with a similar incidence of CMV-related hearing loss to that reported in the offspring of women from populations in developed countries with lower rates of seroimmunity to CMV. [ABSTRACT FROM AUTHOR]

Background. Infection due to Salmonella species causes an estimated 1.4 million illnesses and 400 deaths annually in the United States. Orange juice is a known vehicle of salmonellosis, for which regulatory controls have recently been implemented. We investigated a nationwide outbreak of Salmonella infection to determine the magnitude of the outbreak and to identify risk factors for infection. Methods. We identified cases through national laboratory-based surveillance. In a case-control study,we defined a case as infection with Salmonella serotype Typhimurium that demonstrated the outbreak pulsed-field gel electrophoresis pattern in a person with illness onset from 1 May through 31 July 2005; control subjects were identified through random digit dialing. Results. We identified 152 cases in 23 states. Detailed information was available for 95 cases. The median age of patients was 23 years; 46 (48%) of the 95 patients were female. For 38 patients and 53 age-group matched control subjects in 5 states, illness was associated with consuming orange juice (90% vs. 43%; odds ratio, 22.2; 95% confidence interval, 3.5-927.5). In a conditional logistic regression model, illness was associated with consuming unpasteurized orange juice from company X (53% vs. 0%; odds ratio, 38.0; 95% confidence interval, 6.5-infinity). The US Food and Drug Administration found that company X was noncompliant with the juice Hazard Analysis and Critical Control Point regulation and isolated Salmonella serotype Saintpaul from company X's orange juice. Conclusions. Unpasteurized orange juice from company X was the vehicle of a widespread outbreak of salmonellosis. Although the route of contamination is unknown, noncompliance with the juice Hazard Analysis and Critical Control Point regulation likely contributed to this outbreak. Pasteurization or other reliable treatment of orange juice could prevent similar outbreaks. [ABSTRACT FROM AUTHOR]

Background. Tuberculosis (TB) immune reconstitution inflammatory syndrome (IRIS) is emerging as an important early complication of combination antiretroviral therapy in patients with TB in developing countries. The differential diagnosis of TB IRIS includes deterioration caused by other human immunodeficiency virus--related morbidities and drug-resistant TB. Methods. We prospectively evaluated consecutive patients with suspected TB IRIS from February 2005 through July 2006 at a community-based secondary hospital in Cape Town, South Africa, by means of clinical case definitions for TB IRIS. Specimens were sent for TB culture and susceptibility testing, and a rapid test (FASTplaque-Response) was performed to expedite determination of rifampin susceptibility. Results. One hundred patients with suspected TB IRIS were evaluated, 26 of whom were being retreated for TB. IRIS symptoms developed a median of 14 days (interquartile range, 7-25 days) after the initiation of combination antiretroviral therapy. In 7 patients, an alternative opportunistic disease was diagnosed. Rifampin-resistant TB was present in 13 patients, 9 of whom received a diagnosis after study entry (7 of 9 had multidrug-resistant TB). Undiagnosed rifampin-resistant TB was thus present in 10.1% of patients (95% confidence interval, 3.9%-16.4%) who presented with TB IRIS, once those with alternative diagnoses and TB with known rifampin resistance were excluded. In the remaining 80 patients, TB IRIS without rifampin resistance was the final diagnosis. Conclusions. TB IRIS that is clinically indistinguishable from TB IRIS that occurs in the context of drug-susceptible disease may occur in patients with undiagnosed multidrug-resistant TB. Antitubercular drug resistance should be excluded in all cases of suspected TB IRIS, and corticosteroids should be used with caution for patients with presumed TB IRIS until the result of drug-susceptibility testing is known. [ABSTRACT FROM AUTHOR]

Background: The benefits of breast-feeding for the prevention of infection in infants and young children have been widely recognized, but epidemiologic studies regarding the role of breast-feeding in protecting against Helicobacter pylori infection have produced conflicting results. Methods: We performed a systematic review of relevant epidemiologic studies conducted during the period 1984-2007 after abstracting data from articles that met our inclusion criteria. Study quality was assessed using the Newcastle-Ottawa scale. With use of the random effects model, we calculated the summary odds ratios (ORs) and 95% confidence intervals (CIs) for H. pylori infection according to history of breast-feeding. Results: For the 14 studies that met inclusion criteria, the summary OR for H. pylori infection was 0.78 (95% CI, 0.61-0.99; 1-sided ). Nine of the 14 studies reported ORs of !1.0, and 6 of these studies reportePp.02 d statistically significant protective effects. Only 1 study reported a statistically significant OR of 11.0. In studies in which the subjects resided in middle- or low-income nations, the summary OR was 0.55 (95% CI, 0.33-0.93; P = .01), compared with 0.93 (95% CI, 0.73-1.19; P = .28) in studies in which subjects resided in high-income nations. The summary OR for studies that use the 13C-urea breath test was 0.67 (95% CI, 0.32-1.39), compared with 0.91 (95% CI, 0.74-1.11) for studies that used the H. pylori IgG serologic test. We found no statistically significant dose-dependent protective effect against H. pylori associated with increasing duration of breast-feeding. Conclusions: Breast-feeding is protective against H. pylori infection, especially in middle- and low-income nations. [ABSTRACT FROM AUTHOR]

Background. Dramatic increases in the number of patients requiring linkage to treatment for human immunodeficiency virus (HIV) infection are anticipated in response to updated Centers for Disease Control and Prevention HIV testing recommendations that advocate routine, opt-out HIV testing. Methods. A retrospective analysis nested within a prospective HIV clinical cohort study evaluated patients who established initial outpatient treatment for HIV infection at the University of Alabama at Birmingham 1917 HIV/ AIDS Clinic from 1 January 2000 through 31 December 2005. Survival methods were used to evaluate the impact of missed visits during the first year of care on subsequent mortality in the context of other baseline sociodemographic, psychosocial, and clinical factors. Mortality was ascertained by query of the Social Security Death Index as of 1 August 2007. Results. Among 543 study participants initiating outpatient care for HIV infection, 60% missed a visit within the first year. The mortality rate was 2.3 deaths per 100 person-years for patients who missed visits, compared with 1.0 deaths per 100 person-years for those who attended all scheduled appointments during the first year after establishing outpatient treatment ( P=.02). In Cox proportional hazards analysis, higher hazards of death were independently associated with missed visits (hazard ratio, 2.90; 95% confidence interval, 1.28-6.56), older age (hazard ratio, 1.58 per 10 years of age; 95% confidence interval, 1.12-2.22), and baseline CD4+ cell count !200 cells/mm3 (hazard ratio, 2.70; 95% confidence interval, 1.00-7.30). Conclusions. Patients who missed visits within the first year after initiating outpatient treatment for HIV infection had more than twice the rate of long-term mortality, compared with those patients who attended all scheduled appointments. We posit that early missed visits are not causally responsible for the higher observed mortality but, rather, identify those patients who are more likely to exhibit health behaviors that portend increased subsequent mortality. [ABSTRACT FROM AUTHOR]

Background. Risk factors and treatment outcomes under program conditions for isoniazid (INH)-monoresistant tuberculosis have not been well described. Methods. Medical charts were retrospectively reviewed for all cases of culture-confirmed, INH-monoresistant tuberculosis ( ) reported n=137 to the San Francisco Department of Public Health Tuberculosis Control Section from October 1992 through October 2005, and those cases were compared with a time-matched sample of drugsusceptible tuberculosis cases (n=274). Results. In multivariate analysis, only a history of treatment for latent tuberculosis (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.5-6.4; P=.003) or for active tuberculosis (OR, 2.7; 95% CI, 1.4-5.0; P=.002) were significantly associated with INH-monoresistant tuberculosis. Of the 119 patients who completed treatment, 49 (41%) completed a 6-month treatment regimen. Treatment was extended to 7-12 months for 53 (45%) of the patients and to 112 months for 17 (14%). Treatment was most commonly extended because pyrazinamide was not given for the recommended 6-month duration (35 patients [29%]). Despite variation in treatment regimens, the combined end point of treatment failure or relapse was uncommon among patients with INH-monoresistant tuberculosis and was not significantly different for patients with drug-susceptible tuberculosis (1.7% vs. 2.2%; P=.73). Conclusions. A history of treatment for latent or active tuberculosis was associated with subsequent INH monoresistance. Treatment outcomes for patients with INH-monoresistant tuberculosis were excellent and were no different from those for patients with drug-susceptible tuberculosis. However, new, short-course regimens are needed because a small proportion of patients completed the 6-month treatment regimen recommended by the American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society ofAmerica, primarily because of pyrazinamide intolerance. [ABSTRACT FROM AUTHOR]

Background. Since 2005, an increase in the prevalence of Clostridium difficile infection (CDI) due to polymerase chain reaction ribotype 078 has been noticed in The Netherlands. This strain has also been identified as the predominant strain in pigs and calves. Methods. CDI caused by type 078 was studied in relation to CDI caused by the hypervirulent type 027 and by types other than 027 and 078. Human and porcine isolates were further investigated and characterized by multilocus variable number tandem repeat analysis. Results. From February 2005 through February 2008, the incidence of type 078 among isolates obtained from 1687 patients increased from 3% to 13%. Compared with patients infected with type 027, patients infected with type 078 were younger (67.4 vs. 73.5 years; P < .01) and more frequently had community-associated disease (17.5% vs. 6.7%; odds ratio, 2.98; 95% confidence interval, 2.11-8.02); rates of severe diarrhea (38.9% vs. 40.0%) and attributable mortality (3.8% vs. 4.0%) were similar in both groups. Compared with patients infected with other types, patients infected with type 078 more frequently received fluoroquinolone therapy (29.4% vs. 19.8%; odds ratio, 2.17; 95% confidence interval, 1.06-4.44). Type 078 isolates contained genes for toxin A, toxin B, binary toxin, and a 39-base pair deletion in toxin regulator gene (tcdC), as well as a point mutation at position 184, resulting in a stop codon. Multilocus variable number tandem repeat analysis of 54 human and 11 porcine isolates revealed 4 clonal complexes containing both porcine and human isolates. Conclusions. CDI due to type 078 and CDI due to type 027 present with similar severity, but CDI due to type 078 affects a younger population and is more frequently community associated. C. difficile type 078 isolates from humans and pigs are highly genetically related. [ABSTRACT FROM AUTHOR]

Background. The optimal medical or surgical therapy and outcome of enterococcal prosthetic joint infection are unknown. Method. We performed a retrospective cohort study involving all patients with enterococcal total hip or knee arthroplasty infection treated at our institution from 1969 through 1999. The outcome for patients treated with combination systemic antimicrobial therapy (a cell wall-active agent and an aminoglycoside) versus monotherapy with a cell wall-active agent was analyzed. Results. Fifty episodes of prosthetic joint infection due to enterococci occurred in 47 patients. The median duration of follow-up was 1253 days (range, 29-4610 days). The median age at the time of diagnosis was 70 years (range, 32-89 years). Fifty percent of episodes (25 of 50 episodes) occurred in male patients; 48% (24 of 50 episodes) involved total hip or knee arthroplasty. The estimate of 2-year survival free of treatment failure was 94% (95% confidence interval [CI], 83%-100%) for patients treated with 2-stage exchange, 76% (95% CI, 58%-100%) for patients treated with resection arthroplasty, and 80% (95% CI, 51.6%-100%) for patients treated with debridement and retention of the components (P=.9). The overall rate of 2-year survival free of treatment failure was 88% (95% CI, 77%-100%) for patients treated with monotherapy and 72% (95% CI, 54%-96%) for patients treated with combination therapy (P=.1). The development of cranial nerve VIII toxicity was significantly more common among patients receiving combination therapy (P=.002). Nephrotoxicity was more frequent in the combination therapy group (occurring in 26% of episodes; P=.09). Conclusions. Enterococcal prosthetic joint infection is uncommon at our institution. Patients receiving combination therapy and those receiving monotherapy did not differ with respect to outcome. There were more cases of ototoxicity in the combination therapy group than there were in the monotherapy group. [ABSTRACT FROM AUTHOR]

Background. Streptococcus pneumoniae is the most common cause of bacterial pneumonia in children. Despite the use of the 7-valent pneumococcal conjugate vaccine, the incidence of pneumococcal necrotizing pneumonia (PNP) has been increasing. Our objectives were to describe temporal trends in PNP and to evaluate pneumococcal serotypes associated with PNP in Utah. Methods. We performed a retrospective review of all children <18 years of age who were cared for at a tertiary care children's hospital and who had blood, lung tissue, broncheoalveolar lavage, or pleural fluid cultures that grew S. pneumoniae, as well as radiographic evidence of pneumonia, from January 1997 through March 2006. All S. pneumoniae isolates were typed. Results. A total of 124 children with pneumococcal pneumonia were identified, and 33 (27%) of these children had radiographic evidence of PNP. During the period 1997-2000, 5 (13%) of 39 cases of culture-confirmed pneumococcal pneumonia were associated with PNP. In contrast, during the period 2001-2006, 28 (33%) of 85 pneumococcal pneumonia cases were complicated by PNP (odds ratio, 3.34; 95% confidence interval, 1.11-12.03). Non-7-valent pneumococcal conjugate vaccine serotypes comprised 49% of the isolates during 1997-2000 and 88% of isolates during 2001-2006 (odds ratio, 7.89; 95% confidence interval, 2.91-21.90). Pneumonia due to serotype 3 was most often associated with PNP. Eleven (79%) of 14 cases of serotype 3-associated pneumonia were associated with PNP. When compared with all other serotypes, serotype 3 was strongly associated with necrosis (odds ratio, 14.67; 95% confidence interval, 3.39-86.25). Conclusions. PNP is a serious and increasingly common complication of S. pneumoniae pneumonia in Utah. Infection with serotype 3 is associated with an increased risk of developing PNP. The increase in the incidence of infection due to nonvaccine serotypes reported worldwide and the changing epidemiology of invasive pneumococcal disease should be considered when developing vaccine strategies. [ABSTRACT FROM AUTHOR]

Background. Plasmodium falciparum infection exerts a considerable burden on pregnant women, but less is known about the adverse consequences of Plasmodium vivax infection. Methods. In Papua, Indonesia, where multiple drug resistance to both species has emerged, we conducted a cross-sectional hospital-based study to quantify the risks and consequences of maternal malaria. Results. From April 2004 through December 2006, 3046 pregnant women were enrolled in the study. The prevalence of parasitemia at delivery was 16.8% (432 of 2570 women had infections), with 152 (35.2%) of these 432 infections being associated with fever. The majority of infections were attributable to P. falciparum (250 [57.9%]); 146 (33.8%) of the infections were attributable to P. vivax, and 36 (8.3%) were coinfections with both species. At delivery, P. falciparum infection was associated with severe anemia (hemoglobin concentration, <7 g/dL; odds ratio [OR], 2.8; 95% confidence interval [95% CI], 2.0-4.0) and a 192 g (95% CI, 119-265) reduction in mean birth weight (P< .001). P. vivax infection was associated with an increased risk of moderate anemia (hemoglobin concentration, 7-11 g/dL; OR, 1.8; 95% CI, 1.2-2.9; P = .01) and a 108 g (95% CI, 17.5-199) reduction in mean birth weight (P = .019). Parasitemia was associated with preterm delivery (OR, 1.5; 95% CI, 1.1-2.0; P = .02) and stillbirth (OR, 2.3; 95% CI, 1.3-4.1; P = .007) but was not associated with these outcomes after controlling for the presence of fever and severe anemia, suggesting that malaria increases the risk of preterm delivery and stillbirth through fever and contribution to severe anemia rather than through parasitemia per se. Conclusions. These observations highlight the need for novel, safe, and effective treatment and prevention strategies against both multidrug-resistant P. falciparum and multidrug-resistant P. vivax infections in pregnant women in areas of mixed endemicity. [ABSTRACT FROM AUTHOR]

Background. Invasive pulmonary aspergillosis (IPA) is a significant problem in patients with chemotherapy-induced prolonged neutropenia. Because pulmonary deposition of conidia is the first step in developing IPA, we hypothesized that inhalation of liposomal amphotericin B would prevent IPA. Methods. We performed a randomized, placebo-controlled trial of patients with hematologic disease with expected neutropenia for ≥10 days. Patients were randomized to receive liposomal amphotericin B or placebo inhalation twice a week, using an adaptive aerosol delivery system, until neutrophil counts increased to 1300 cells/mm3. In subsequent neutropenic episodes, the assigned treatment was restarted. The primary end point was the occurrence of IPA according to European Organization for Research and the Treatment of Cancer-Mycoses Study Group definitions. Kaplan-Meier curves were compared with log-rank tests for intent-to-treat and on-treatment populations. Results. A total of 271 patients were studied during 407 neutropenic episodes. According to the intent-to-treat analysis, 18 of 132 patients in the placebo group developed IPA versus 6 of 139 patients in the liposomal amphotericin B group (odds ratio, 0.26; 95% confidence interval, 0.09-0.72; P = .005). According to the on-treatment analysis, 13 of 97 patients receiving placebo versus 2 of 91 receiving liposomal amphotericin B developed IPA (odds ratio, 0.14; 95% confidence interval, 0.02-0.66; P = .007). Some adverse effects, but none serious, in the liposomal amphotericin B group were reported, most frequently coughing (16 patients vs. 1 patient; P = .002). Conclusion. In high-risk patients, prophylactic inhalation of liposomal amphotericin B significantly reduced the incidence of IPA. [ABSTRACT FROM AUTHOR]

Background. Galactomannan is an Aspergillus-specific polysaccharide released during aspergillosis and is detected by the quantitative serum galactomannan index (GMI) test. Preclinical and preliminary clinical reports have suggested a good correlation between GMI and aspergillosis outcome. Methods. We reviewed the literature to assess the strength of correlation between GMI and aspergillosisoutcome using the κ correlation coefficient. We included 27 studies that enrolled patients with hematological cancer and proven or probable aspergillosis and that used sequential GMI testing. We examined the 3 following outcomes: survival (survival vs. death), global outcome (survival vs. death [including autopsy findings]), and autopsy outcome (autopsy findings only). Results. Overall, 257 patients fulfilled criteria for proven or probable aspergillosis and were eligible for outcome evaluation. Correlation between GMI (within ≤1 week before outcome) and defined outcomes was excellent, with κ correlation coefficients of 0.8737 (95% confidence interval, 0.8140-0.9333; P < .001) and 0.9123 (95% confidence interval, 0.8617-0.9629; P < .001) for survival and global outcome, respectively. Most importantly, the κ correlation coefficient for autopsy outcome was high (0.8498; 95% confidence interval, 0.5608-1.000; P < .001). Furthermore, the κ correlation coefficient for all outcomes was comparable across age groups (pediatric and adult patients) and treatment modalities, including allogeneic transplantation. This strong correlation is also supported by extensive preclinical data and recent clinical reports. Conclusions. We conclude that serum GMI is a good marker of aspergillosis outcome. [ABSTRACT FROM AUTHOR]

Background. To prepare for national introduction of a pneumococcal conjugate vaccine of restricted valency, we studied nasopharyngeal carriage of Streptococcus pneumoniae in Gambian infants. Methods. We studied 236 infants in 21 villages. We collected nasopharyngeal swab samples at birth, twice per month for 6 months, and every second month until 1 year of age. We studied time to acquisition and duration of pneumococcal carriage according to serotype. Results. All infants carried S. pneumoniae at some point. Sixty-five serotypes were found, and the 5 most common serotypes (6B, 19F, 6A, 14, and 23F) accounted for 51% of isolates. The mean age at first acquisition of carriage was 33 days (95% confidence interval, 29-36 days). There were no significant differences in acquisition rates between the 6 most common serotypes (P = .067) or between vaccine serotypes, vaccine-related serotypes, or nonvaccine serotypes (P = .317). However, the duration of carriage differed significantly between the 6 most common serotypes (P = .004). The rate of reacquisition of carriage and the duration of carriage did not differ significantly between the 6 most common serotypes (P = .229 and P = .699 respectively). However, nonvaccine types were acquired faster (P = .004) and were carried for a shorter duration (P< .001) than were vaccine serotypes. A previous episode of serotype 14 carriage was associated with delayed reacquisition of this serotype (P = .005) and longer duration of carriage (P = .017). Conclusions. The data provided in this study regarding time to acquisition and duration of pneumococcal carriage in Gambian infants provide an important baseline for evaluating the impact of the introduction of a pneumococcal conjugate vaccine in The Gambia and elsewhere in Africa. [ABSTRACT FROM AUTHOR]

Background. The incidence of Clostridium difficile-associated disease (CDAD) is increasing. There are few data on the short-term and long-term attributable costs of CDAD. The objective of this study was to determine the acute and 180-day attributable inpatient costs of CDAD. Methods. We performed a retrospective cohort study of all patients without operating room costs who were admitted for ⩾48 h to Barnes-Jewish Hospital, a tertiary care hospital in St. Louis, Missouri, 1 January 2003-3 1 December 2003 (n = 24,691). Attributable costs of CDAD were determined by multivariable linear regression and propensity-score matched-pairs analyses (n = 684) for the hospitalization in which CDAD occurred and per patient over a 180-day period, including the initial hospitalization. Results. CDAD was associated with $2454 (95% confidence interval, $2380-$2950; increase in cost, 41%) attributable costs per CDAD episode by linear regression and with $3240 attributable costs (P < .001; increase in cost, 33%) by propensity-score matched-pairs analysis. CDAD was associated with $5042 (95% confidence interval, $3797-$6481; increase in cost, 53%) attributable inpatient costs over 180 days by linear regression and with $7179 attributable costs for inpatient care (P < .001; 48% increase in costs) by propensity-score matched-pairs analysis. Conclusions. CDAD was associated with a significant increase in costs for inpatient care and increased costs at 180 days after the initial hospitalization when the CDAD episode occurred. [ABSTRACT FROM AUTHOR]

Background. In the African meningitis belt, Neisseria meningitidis serogroup W135 has emerged as a cause of epidemic disease. The establishment of W135 as the predominant cause of endemic disease has not been described. Methods. We conducted national laboratory-based surveillance for invasive meningococcal disease during 2000-2005. The system was enhanced in 2003 to include clinical data collection of cases from sentinel sites. Isolates were characterized by pulsed field gel electrophoresis and multilocus sequence typing. Results. A total of 2135 cases of invasive meningococcal disease were reported, of which 1113 (52%) occurred in Gauteng Province, South Africa. In this province, rates of disease increased from 0.8 cases per 100,000 persons in 2000 to 4.0 cases per 100,000 persons in 2005; the percentage due to serogroup W135 increased from 7% (4 of 54 cases) to 75% (221 of 295 cases). The median age of patients infected with serogroup W135 was 5 years (interquartile range, 2-23 years), compared with 21 years (range, 8-26 years) for those infected with serogroup A (). The incidence of W135 disease increased in all age groups. Rates were highest among infants (age, <1 year), increasing from 5.1 cases per 100,000 persons in 2003 to 21.5 cases per 100,000 persons in 2005. Overall case-fatality rates doubled, from 11% in 2003 to 22% in 2005. Serogroup W135 was more likely to cause meningococcemia than was serogroup A (82 [28%] of 297 cases vs. 11 [8%] of 141 cases; odds ratio, 8.9, 95% confidence interval, 2.2-36.3). A total of 285 (95%) of 301 serogroup W135 isolates were identified as 1 clone by pulsed-field gel electrophoresis; 7 representative strains belonged to the ST-11/ET-37 complex. Conclusions. Serogroup W135 has become endemic in Gauteng, South Africa, causing disease of greater severity than did the previous predominant serogroup A strain. [ABSTRACT FROM AUTHOR]

Background. Bloodstream infections (BSIs) are an ever-present concern for clinicians evaluating ill-appearing pediatric patients with central venous catheters (CVCs) in the ambulatory care setting. Methods. We performed a case-control study of a cohort of 200 pediatric patients who were evaluated in the ambulatory care setting and who were found to have laboratory-confirmed BSI in the context of a CVC. This study sought to compare patients with polymicrobial versus monomicrobial BSIs to identify potential risk factors for polymicrobial BSI. Results. Of the 200 patients enrolled in the study, 73 (37%) had a polymicrobial BSI. Patients with polymicrobial BSI were more likely than those with monomicrobial BSI to be younger (P = .002) and less likely to have been recently discharged from the hospital (P .01). The odds of a polymicrobial BSI were >4 times greater for patients aged <3 years than for those aged ⩾3 years (odds ratio, 4.54; 95% confidence interval, 1.68-12.29), and the odds were 50% lower for those discharged from the hospital in the prior 7 days than for those without recent hospi- talization (odds ratio, 0.46; 95% confidence interval, 0.22-0.95) after controlling for an underlying cancer diagnosis and the time of year during which a patient presented. Recent antibiotic use, recent BSI, duration that the CVC had been in place, and underlying gastrointestinal dysfunction were not associated with a risk of polymicrobial BSI. Conclusions. Younger children and those who had not recently been discharged from the hospital had an increased risk of developing catheter-related polymicrobial BSI. Special consideration should be given to the increased likelihood of polymicrobial BSIs in these pediatric patients when initiating empirical antimicrobial therapy. [ABSTRACT FROM AUTHOR]

Background. The aim of this study, conducted in Ivory Coast, was to evaluate the prevalence and evolution of viral hepatitis in children coinfected with human immunodeficiency virus type 1 (HIV-1). Methods. Hepatitis B virus (HBV) and hepatitis C virus (HCV) markers were retrospectively and longitudinally assessed among 280 HIV- 1-infected children enrolled in the Agence Nationale de Recherches sur le SIDA et les Hépatites Virales B et C 1244/1278 cohort. Among these, 173 (61.8%) received highly active antiretroviral therapy (HAART), including lamivudine (3TC) for 122 children. Detection of the hepatitis B s antigen (HB5Ag) was performed on specimens collected at inclusion and 6 months later. If results of both tests were positive, hepatitis B e antigen (HBeAg)/hepatitis B e antibody (HBeAb) and HBV DNA levels were measured at inclusion and during follow-up. A fourth-generation HCV enzyme immunoassay was used for HCV screening at inclusion. Results. In our pediatric cohort, no patients were infected with HCV, but the prevalence of HB5Ag at inclusion was 12.1% (34 of 280; 95% confidence interval [CI], 8.6-16.6). Among the HBV-HIV-1-coinfected children, a high rate of positive HBeAg chronic hepatitis B (CHB) was noted at inclusion (82.4% [28 of 34]; 95% CI, 65.5%- 93.2%) and after a median follow-up of 18 months (78.3%; 95% CI, 45.5%-92.7%), with no significant difference between children treated with HAART (with or without 3TC) and untreated ones. These children showed high HBV DNA levels (usually >8.0 log10 copies/mL) and viral population consisting of nearly exclusively wild-type HBeAg-positive HBV strains, strongly suggesting that most of them were in the initial immunotolerant phase of chronic hepatitis B. Conclusion. In sub-Saharan Africa, children with chronic hepatitis B and who are treated with 3TC-based HAART are at risk of developing 3TC resistance. Further studies are required to guide the management of HBV- HIV- 1-coinfected children. [ABSTRACT FROM AUTHOR]

Background. Polysaccharide pneumococcal vaccine (PPV) is recommended among human immunodeficiency virus (HIV)-infected patients, although its effect in reducing the incidence of pneumonia or invasive pneumococcal disease is not well established. Our objective was to determine the effectiveness of 23-valent PPV in HIV-infected adults and the risk factors for pneumococcal pneumonia or invasive pneumococcal disease. Methods. We performed a retrospective case-control study in 4 Spanish hospitals for the period from January 1995 through December 2005 using the HIV database from each hospital to identify case patients with Streptococcus pneumoniae disease and control subjects without a history of pneumococcal infection. Results. A total of 184 case patients and 552 control subjects were identified. The factors associated with pneumococcal disease in bivariate analysis were active injection drug use (odds ratio [OR], 3.33; 95% confidence interval [CI], 2-5.55), alcoholism (OR, 3.03; 95% CI, 1.86-4.91), chronic obstructive pulmonary disease (OR, 2.58; 95% CI, 1.3-5.1), cirrhosis (OR, 6.05; 95% CI, 3.2-11.4), antiretroviral therapy (OR, 0.23; 95% CI, 0.16- 0.32), trimethoprim-sulfamethoxazole prophylaxis (OR, 0.66; 95% CI, 0.45-0.97), viral load <5000 copies/mL (OR, 0.38; 95% CI, 0.26-0.54), and previous PPV (OR, 0.39; 95% CI, 0.24-0.65). Risk factors for pneumococcal disease in multivariate analysis were cirrhosis (OR, 5.64; 95% CI, 2.53-12.53), chronic obstructive pulmonary disease (OR, 2.90; 95% CI, 1.21-6.94), and alcoholism (OR, 2.15; 95% CI, 1.11-4.19), whereas protective factors were receipt of antiretroviral therapy (OR, 0.23; 95% CI, 0.14-0.36) and receipt of pneumococcal vaccine (OR, 0.44; 95% CI, 0.22-0.88), even in patients with CD4 lymphocyte counts <200 cells/μL. Conclusions. Antiretroviral therapy and PPV have a significant, independent protective effect against pneumococcal disease, regardless of CD4 lymphocyte count; thus, all patients with HIV infection should be vaccinated with PPV to prevent pneumococcal disease. [ABSTRACT FROM AUTHOR]

Dosage adjustments are often used to manage HIV drug interactions, but little is known about their clinical significance. We examined patients from the Ontario HIV Cohort Study to assess the effects of dosage adjustments on plasma viral load. A significant reduction (0.67 log10 copies/mL) in viral load was associated with adjustments to manage efavirenz-based interactions (95% confidence interval, -1.33 to -0.01) but was not observed after adjustments to manage rifabutin-based (difference in viral load, 0.03 log10 copies/mL; 95% confidence interval, -0.71 to 0.77) or nevirapinebased interactions (difference in viral load, 0.09 log10 copies/mL; 95% confidence interval, -0.83 to 1.01). [ABSTRACT FROM AUTHOR]

Background. Interferon-γ release assays (IGRAs) are attractive alternatives to the tuberculin skin test (TST) for detecting Mycobacterium tuberculosis infection. However, the inability to definitively confirm the presence of most M. tuberculosis infections hampers assessment of IGRA accuracy. Although IGRAs are primarily indicated for the detection of latent tuberculosis infection, we sought to determine the sensitivity of the TST and 2 whole- blood IGRAs (QuantiFERON-TB assay [QFT] and QuantiFERON-TB Gold assay [QFT-G]) in situations in which infection is confirmed by recovery of M. tuberculosis by culture. Methods. We conducted a prospective, multicenter, cross-sectional comparison study in which 148 persons suspected to have tuberculosis were tested simultaneously with the TST, QFT, and QFT-G. Results. M. tuberculosis was cultured from samples from 69 (47%) of 148 persons suspected to have tuberculosis; the TST induration was ⩾5 mm for 51(73.9%) of the 69 subjects (95% confidence interval [CI], 62.5%-82.8%). The QFT indicated tuberculosis infection for 48 (69.6%) of the 69 subjects (95% CI, 57.9%-79.2%) and was indeterminate for 7 (10.1%). The QFT-G yielded positive results for 46 (66.7%) of the 69 subjects (95% CI, 54.9%-76.7%) and indeterminate results for 9 subjects (13.0%). If subjects with indeterminate QFT-G results were excluded, 46 (76.7%) of 60 subjects (95% CI, 64.6%-85.6%) had positive TST results, and the same number of subjects had positive QFT-G results. HIV infection was associated with false-negative TST results but not with false-negative QFT-G results. Conclusions. The TST, QFT, and QFT-G have similar sensitivity in persons with culture-confirmed infection. As with the TST, negative QFT and QFT-G results should not be used to exclude the diagnosis of tuberculosis in persons with suggestive signs or symptoms. [ABSTRACT FROM AUTHOR]

Background. Several host- and procedure-related factors have been reported to increase the risk of permanent pacemaker (PPM) infection on the basis of descriptive analyses of case series. The purpose of this study is to assess the risk factors for PPM infection using case-control study methods. Methods. All patients who had a PPM implanted at our institution from January 1991 to December 2003 were retrospectively reviewed. Each patient who experienced a PPM infection was matched with 2 control subjects by age, sex, year of implantation, and duration of follow-up. Univariate and multivariable analyses were performed to identify significant risk factors for PPM infection. Results. Twenty-nine case patients and 58 control subjects met inclusion criteria. The majority (83%) of case patients presented with a pocket infection; a minority (10%) had PPM-related endocarditis. Staphylococcus species (69%) were the most common pathogens. On univariate analysis, previous PPM infection, malignancy, long-term corticosteroid use, multiple device revisions, a permanent central venous catheter, the presence of >2 pacing leads, and a lack of antibiotic prophylaxis at the time of PPM placement were associated with an increased risk of PPM infection. A multivariable logistic regression model identified long-term corticosteroid use (odds ratio [OR], 13.90; 95% confidence interval [CI], 1.27-151.7; P = .03) and the presence of >2 pacing leads versus 2 leads (OR, 5.41; 95% CI, 1.44-20.29; P = .01) as independent risk factors for PPM infection. In contrast, use of antibiotic prophylaxis prior to PPM implantation had a protective effect (OR, 0.087; 95% CI, 0.016-0.48; P = .005). Conclusions. These findings should assist clinicians in identifying patients who are at increased risk of PPM infection, as well as in developing strategies to minimize the modifiable risks. [ABSTRACT FROM AUTHOR]

Background. We obtained estimates of the incidence of tuberculosis (TB) among patients receiving HAART and identified determinants of the incidence. Methods. We analyzed the incidence of TB during the first 3 years after initiation of HAART among 17,142 treatment-naive, AIDS-free persons starting HAART who were enrolled in 12 cohorts from Europe and North America. We used univariable and multivariable Poisson regression models to identify factors associated with the incidence. Results. During the first 3 years (36,906 person-years), 173 patients developed TB (incidence, 4.69 cases per 1000 person-years). In multivariable analysis, the incidence rate was lower for men who have sex with men, compared with injection drug users (relative rate, 2.46; 95% confidence interval [CI], 1.51-4.01), heterosexuals (relative rate, 2.42; 95% CI, 1.64-3.59), those with other suspected modes of transmission (relative rate, 1.66; 95% CI, 0.9 1-3.06), and those with a higher CD4+ count at the time of HAART initiation (relative rate per log2 cells/μL, 0.87; 95% CI, 0.84-0.91). During 28,846 person-years of follow-up after the first 6 months of HAART, 88 patients developed TB (incidence, 3.1 cases per 1000 person-years of follow-up). In multivariable analyses, a low baseline CD4+ count (relative rate per log2 cells/μL, 0.89; 95% CI, 0.83-0.96), 6-month CD4+ count (relative rate per log2 cells/μL, 0.90; 95% CI, 0.81-0.99), and a 6-month HIV RNA level >400 copies/mL (relative rate, 2.21; 95% CI, 1.3 3-3.67) were significantly associated with the risk of acquiring TB after 6 months of HAART. Conclusion. The level of immunodeficiency at which HAART is initiated and the response to HAART are important determinants of the risk of TB. However, this risk remains appreciable even among those with a good response to HAART, suggesting that other interventions may be needed to control the TB epidemic in the HIV- infected population. [ABSTRACT FROM AUTHOR]

Background. Pentavalent antimony is the agent recommended for treatment of cutaneous leishmaniasis (CL). Its use is problematic, because it is expensive and because of the potential for drug-associated adverse effects during a lengthy and painful treatment course. Methods. We tested the efficacy of thermotherapy for the treatment of CL due to Leishmania tropica in a randomized, controlled trial in Kabul, Afghanistan. We enrolled 401 patients with a single CL lesion and administered thermotherapy using radio-frequency waves (1 treatment of &ges; 1 consecutive application at 50°C for 30 s) or sodium stibogluconate (SSG), administered either intralesionally (a total of 5 injections of 2-5 mL every 5-7 days, depending on lesion size) or intramuscularly (20 mg/kg daily for 21 days). Results. Cure, defined as complete reepithelialization at 100 days after treatment initiation, was observed in 75 (69.4%) of 108 patients who received thermotherapy, 70 (75.3%) of 93 patients who received intralesional SSG, and 26 (44.8%) of 58 patients who received intramuscular SSG. The OR for cure with thermotherapy was 2.80 (95% confidence interval [I], 1.45-5.41), compared with intramuscular SSG treatment (P = .002). No statistically significant difference was observed in the odds of cure in comparison of intralesional SSG and thermotherapy treatments. The OR for cure with intralesional SSG treatment was 3.75 (95% CI, 1.86-7.54), compared with intramuscular SSG treatment (P < .001). The time to cure was significantly shorter in the thermotherapy group (median, 53 days) than in the intralesional SSG or intramuscularly SSG group (median, 75 days and >100 days, respectively; P = .003). Conclusions. Thermotherapy is an effective, comparatively well-tolerated, and rapid treatment for CL, and it should be considered as an alternative to antimony treatment. [ABSTRACT FROM AUTHOR]