Alcohol in combination with illicit drugs among fatal injuries in Sao Paulo, Brazil: An epidemiological study on the association between acute substance use and injury.

Injury deaths have a major impact on public health systems, particularly in the Latin American region; however, little is known about how different drugs, in combination or not with alcohol, interact with each injury type. We tested an epidemiological protocol for investigating alcohol and other drug acute use among fatally injured victims taking into account the injury context for all injury causes in Sao Paulo, Brazil. Blood alcohol and drug content were fully screened and confirmed following a probability sample selection of decedents (n = 365) during 19 consecutive months (2014-2015). Drug concentrations, including benzodiazepines, cannabis, cocaine, and opioids were determined by gas chromatography-mass spectrometry (GC-MS) or liquid chromatography tandem mass spectrometry (LC-MS/MS). Toxicology data were interpreted in combination with injury context retrieved from police records regarding cause, place of injury, and victims' criminal history. More than half of all fatally injured victims studied were under the influence of at least one substance (55.3%). Alcohol was the leading substance consumed before a fatal injury event (30.1%), followed by cocaine (21.9%) and cannabis (14%). Illicit drug use (cocaine and cannabis) comprised more than two thirds of all drug-related deaths. Alcohol-positive deaths are over-represented among road traffic injuries, while drug-positive deaths are more prevalent among intentional injuries. Victims who had previous criminal convictions were significantly more likely to have used illicit drugs compared to those who did not have a criminal background. We estimated that one in every two fatal injuries in the city of Sao Paulo is associated with acute substance use by the victim. The health burden attributed to alcohol- and drug-related fatal injury events has reached significant higher levels in Latin American cities such as Sao Paulo compared globally.

Structured treatment interruptions (STI) in chronic unsuppressed HIV infection in adults.

BACKGROUND: Structured treatment interruptions (STI) of antiretroviral therapy (ART) have been investigated as part of novel treatment strategies, with different aims and objectives depending on the populations involved. These populations include: 1) patients who initiate ART during acute HIV infection; 2) patients with chronic HIV infection, on ART, with successfully suppressed viremia; and 3) patients with chronic HIV infection and treatment failure, with persistent viremia due to multi-drug resistant HIV (Hirschel 2001; Deeks 2002; Miller 2003). In an earlier Cochrane review (Pai 2005), we had summarized the evidence about the effects of STI in chronic suppressed HIV infection. In this review, we summarize the evidence on STI in patients with chronic unsuppressed HIV infection due to drug-resistant HIV. Unsuppressed HIV infection describes those patients who cannot suppress viremia, due to the presence of multi-drug-resistant virus. It is also referred to as treatment failure. Drug resistance is identified by the presence of resistant mutations at baseline.STI as a treatment strategy in HIV-infected patients with chronic unsuppressed viremia involves interrupting ART in controlled clinical settings, for a pre-specified duration of time. These interruptions have various aims, including the following: 1) to allow wild virus to re-emerge and replace the resistant mutant virus, with the hope of improving the efficacy of a subsequent ART regimen; 2) to halt development of drug resistance and to preserve subsequent treatment options; 3) to alleviate treatment fatigue and reduce drug-related adverse effects; and 4) to improve quality of life (Miller 2003; Montaner 2001; Vella 2000;). OBJECTIVES: The objective of our systematic review was to synthesize the evidence on the effect of structured treatment interruptions in adult patients with chronic unsuppressed HIV infection. SEARCH STRATEGY: We included all available intervention studies (randomized controlled trials and non-randomized trials) conducted in HIV-infected patients worldwide. We searched nine databases, covering the period from January 1996 to February 2006. We also scanned bibliographies of relevant studies and contacted experts in the field to identify unpublished research, abstracts and ongoing trials. In the first screen, a total of 3186 potentially eligible citations from nine databases and sources were identified, of which 2047 duplicate citations were excluded. The remaining 1139 citations were examined in detail, and we further excluded 951 citations that were modeling studies, animal studies, case reports, and opinion pieces. As shown in Figure 01, 188 citations were identified in the second screen as relevant for full-text screening. Of these, 60 basic science studies, editorials and abstracts were excluded and 128 full-text articles were retrieved. In the third screen, all full-text articles were examined for eligibility in our review. These were subclassified into three categories: 1) chronic suppressed HIV infection; 2) chronic unsuppressed HIV infection; and 3) acute HIV infection. Studies were further excluded if their abstracts did not contain enough information for inclusion in our reviews. A total of 62 studies were finally classified into chronic suppressed, acute, and chronic unsuppressed categories. Of these, 17 trials met the eligibility criteria for this review. SELECTION CRITERIA: Inclusion criteriaAll available randomized or non-randomized controlled trials investigating planned treatment interruptions among patients with chronic unsuppressed HIV infection. Early pilot non-randomized prospective studies on treatment interruptions of fixed and variable durations were also included. Relevant abstracts on randomized controlled trials were also included if they contained sufficient information. Exclusion criteriaEditorials, reviews, modeling studies, and basic science studies were excluded. Studies on STI among patients with chronic suppressed HIV infection were summarized in a separate review. Studies on STI in primary HIV infection were beyond the scope of this review. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data, evaluated study eligibility and quality. Disagreements were resolved in consultation with a third reviewer.A total of seventeen studies on STI were included in our review. However, due to significant heterogeneity across studies (i.e. in study design, populations, baseline characteristics, and reported outcomes; and in reporting of measures of effect, hazard ratios, and risk ratios), we considered it inappropriate to perform a meta-analysis. MAIN RESULTS: In early pilot non-randomized trials, a pattern was evident across studies. During treatment interruption, a decline in CD4 cell counts, increase in viral load, and a shift in the level of genotypic drug resistance towards more of a wild-type HIV virus was reported. This suggests that STI may be used to increase drug susceptibility to an optimized salvage regimen upon treatment re-initiation. These studies generated useful data and hypotheses that were later tested in randomized controlled trials. Randomized controlled trials rated high on quality. Of the eight randomized controlled trials reviewed, seven had been completed while one was ongoing and remains blinded. Of the seven completed randomized controlled trials, six have reported consistent virologic and immunologic patterns, and found no significant benefit in virologic response to subsequent ART in the STI arm, compared to the control arm. In addition, the largest completed randomized trial reported greater numbers of clinical disease progression events and evidence of prolonged negative impact on CD4 cell counts in the STI arm (Beatty 2005; Benson 2004; Deeks 2001; Lawrence 2003; Walmsley 2005; Ruiz 2003). The single RCT with divergent findings from the others (GigHAART), reporting a significant virologic and immunologic benefit due to STI, was different in prescribing a shorter STI duration and a salvage ART regimen of 8-9 drugs. There were also differences in the patient population characteristics with this study, targeting those with very advanced HIV disease (Katlama 2004). Although we await the unblinded results of the eighth RCT (OPTIMA), the evidence so far does not support STI in the setting of chronic unsuppressed HIV infection with antiretroviral treatment failure (Brown 2004; Holodniy 2004; Kyriakides 2002; Singer 2006). AUTHORS' CONCLUSIONS: The current available evidence primarily supports a lack of benefit of STI before switching therapy in patients with unsuppressed HIV viremia despite ART. There is evidence of harm in attempting STI in patients with relatively advanced HIV disease, due to the associated CD4 cell decline and the increased risk of clinical disease progression. At this time, there is no evidence to recommend the use of STI in this clinical category of patients with treatment failure.

Structured treatment interruptions (STI) in chronic suppressed HIV infection in adults.

BACKGROUND: Although antiretroviral treatment (ART) has led to a decline in morbidity and mortality of HIV-infected patients in developed countries, it has also presented challenges. These challenges include increases in pill burden; adherence to treatment; development of resistance and treatment failure; development of drug toxicities; and increase in cost of HIV treatment and care. These issues stimulated interest in investigating the short-term and long-term consequences of discontinuing ART, thus providing support for research in structured treatment interruptions (STI). Structured treatment interruptions of antiretroviral treatment involve taking supervised breaks from ART. STI are defined as one or more planned, timing pre-specified, cyclical interruptions in ART. STI are attempted in monitored clinical settings in eligible participants. STI have generated hopes of reducing drug toxicities, decreasing costs and total time on treatment in HIV-positive patients. The first STI was attempted in the case of a patient in Germany, who later permanently discontinued treatment. This successful anecdotal case report led to several trials on STI worldwide. OBJECTIVES: The objective of this systematic review was to assess the effects of structured treatment interruptions (STI) of antiretroviral therapy (ART) in the management of chronic suppressed HIV infection, using all available high-quality studies. SEARCH STRATEGY: Nine databases covering the time period from January 1996 to March 2005 were searched. Bibliographies were scanned and experts contacted in the field to identify unpublished research and ongoing trials. Two reviewers independently extracted data, and evaluated study eligibility and quality. Disagreements were resolved in consultation with a third reviewer. Data from 33 studies were included in the review. SELECTION CRITERIA: STI is a planned, timing pre-specified experimental intervention. In our review, we decided to include all available intervention trials in HIV-infected patients, with or without control groups. We reviewed evidence from 18 randomized and non-randomized controlled trials, and 15 single arm trials. Single arm trials were included because these pilot studies made significant contribution to the early development and refutation of hypotheses in STI. DATA COLLECTION AND ANALYSIS: Trials included in this review varied in study participants, methodology and reported inconsistent measures of effect. Due to this heterogeneity, we did not attempt to meta-analyse them. Results were tabulated and a qualitative systematic review was done MAIN RESULTS: For the purpose of this review, STI strategies were classified either as a timed-cycle STI strategy or a CD4-guided STI strategy. In timed-cycle STI strategy, a predetermined period of fixed duration (e.g. one week, one month) off ART was attempted followed by resumption of ART, while closely monitoring changes in CD4 levels and viral load levels. Predetermined criteria for interruption and resumption were laid out in this strategy. Timed-cycle STI fell out of favor due to reports of development of resistance in many studies. Moreover, there were no significant immunological and virological benefits, and no reduction in toxicities, reported in these studies. In CD4-guided STI strategy, ART was interrupted for variable durations guided by CD4 levels. Participants with high nadir CD4 levels qualified for this approach. A reduction in costs of ART, a reduction in mutation, and a better tolerability of this CD4-guided STI strategy was reported. However, concerns about long-term safety of this strategy on immunological, virological, and clinical outcomes were also raised. AUTHORS' CONCLUSIONS: Timed-cycle STI have not been proven to be safe in the short term. Although CD4-guided STI strategy has reported favorable outcomes in the short term, the long-term safety, efficacy and tolerability of this strategy has not been fully investigated. Based on the studies we reviewed, the evidence to support the use of timed-cycle STI and CD4-guided STI cycles as a standard of care in the management of chronic suppressed HIV infection is inconclusive.

Tuberculosis among immigrants and refugees.

BACKGROUND: Overseas screening of immigrants and refugees applying for a visa to the United States identifies foreign-born individuals who are at high risk for tuberculosis (TB) or who have active TB. The system's effectiveness relies on further medical evaluation and follow-up of foreign-born individuals after their arrival in the United States. METHODS: Retrospective cohort study of 893 immigrants and refugees who arrived in the United States from July 1, 1992, through December 31, 1993, with a destination of San Francisco, Calif, and a referral for further medical evaluation. MAIN OUTCOME MEASURES: Time to report to the local health department after arrival and the yield of active and preventable cases of TB from follow-up medical evaluations. RESULTS: Median time from arrival in the United States to seeking care in San Francisco was 9 days (range, 1-920 days). Of 745 immigrants and refugees (83.4%) who sought further medical evaluation, 51 (6.9%) had active TB and 296 (39.7%) were candidates for preventive therapy. Being a refugee was an independent predictor of failure to seek further medical evaluation in the United States. Class B-1 disease status based on overseas TB screening (odds ratio, 3.5; 95% confidence interval, 2.0-6.2) and being from mainland China (odds ratio, 4.4; 95% confidence interval, 1.9-9.9) were independent predictors of TB diagnosed in San Francisco. CONCLUSIONS: Timely, adequate medical evaluation and follow-up care of immigrants and refugees has a relatively high yield and should be a high priority for TB prevention and control programs.

Evaluation of effectiveness of the 23-valent pneumococcal capsular polysaccharide vaccine for HIV-infected patients.

BACKGROUND: We conducted a retrospective case-control study to evaluate effectiveness of pneumococcal vaccine against invasive disease among adults with human immunodeficiency virus (HIV) infection in San Francisco, Calif, and Atlanta, Ga. METHODS: Case patients were 18- to 55-year-old subjects with HIV infection who were admitted to selected hospitals in Atlanta or San Francisco from February 1992 to April 1995 from whom Streptococcus pneumoniae was isolated from a normally sterile site. Controls were HIV-infected patients of similar age matched to cases by hospital of admission and CD4 lymphocyte count (<0.20, 0.20-0.499, >/=0.50 x 10(9)/L [<200, 200-499, >/=500 cells/mm(3)]) or clinical stage of acquired immunodeficiency syndrome. Case and control subjects were restricted to persons known to have HIV infection before hospital admission. Analysis used matched univariate and conditional logistic regression. RESULTS: One hundred seventy-six case patients and 327 controls were enrolled. By univariate analysis, persons with pneumococcal disease were more likely to be black, be current smokers, and have close contact with children. Adjusted for these factors and CD4 cell count, pneumococcal vaccine effectiveness was 49% (95% confidence interval [CI], 12%-70%). Adjusting for all variables and key interaction terms, vaccine effectiveness among whites was 76% (95% CI, 35%-91%), whereas effectiveness among blacks was 24% (95% CI, -50% to 61%). Among controls, vaccination was significantly less common among blacks (29% vs 45%; P<.005). CONCLUSIONS: Pneumococcal vaccine demonstrated protection against invasive pneumococcal infections among white but not black HIV-infected adults. Failure to demonstrate effectiveness among blacks may be due to limited power because of low use of the vaccine in this population, immunization at more advanced stages of immunosuppression, or unmeasured factors. These data support current recommendations for use of pneumococcal vaccine in HIV-infected persons and highlight a clear need for strategies to improve vaccine-induced protection.

Young people and the structure of sexual risks in Lima.

OBJECTIVES: (1) To describe psychosocial variables related to sexual activity and the prevalence of contextual factors (e.g. coercion, paid sex and drug/alcohol use) and various sexual experiences among young men and women in Lima; and (2) to assess the relationship between psychosocial, contextual and behavioral factors on one hand and negative sexual health events such as unplanned pregnancies and sexually transmitted diseases (STDs) on the other hand. DESIGN: A cross-sectional serosurvey complemented with focus groups and in-depth interviews. SUBJECTS AND METHODS: A total of 611 adolescents (16-17 years old) and 607 young adults (19-30 years old) were recruited randomly from among those registering for military service (adolescents) or seeking work/study permits (young adults). These subjects were asked to fill out a self-administered questionnaire with detailed information on sexual experiences and psychosocial variables. The response rates were 98% (adolescents) and 82% (young adults). A subsample of 858 subjects provided blood specimens, which were analyzed for antibodies to HIV-1, the hepatitis B virus and syphilis. The relationship between the main study variables and sociodemographic indicators was also assessed, and multivariate analysis was used to identify those variables associated with sexual health problems. A preliminary qualitative phase helped in the questionnaire design and in interpreting survey findings. RESULTS: Thirty-four percent of adolescents and 75% of young adults were sexually experienced. The prevalence of bisexual behavior was high, particularly among males (12%). The males often reported paid sex (47%) and the females often reported sexual coercion (47%). Among the heterosexually active, only 11% reported consistent use of condoms. While 22% of the heterosexually active reported an unplanned pregnancy in self (females) or partner (males), 18% of the sexually active reported a history of STD symptoms or diagnoses. Among the sexually active who gave a blood sample, 0.2% were positive for HIV, 6.7% for hepatitis B and 1.5% for syphilis. Those who experienced an unplanned pregnancy or STD symptoms or, for the subsample, were seropositive for HIV or other STDs, were more likely to perceive social norms as restricting condom use to casual sex, to be older, to combine sex with alcohol or drugs and to report a history of sexual coercion or of having paid or been paid for sex. For females only, engaging in sex at a younger age was a risk marker, while engaging in any homosexual activity was protective. CONCLUSIONS: Cultural norms that restrict condoms to casual sex may place many young people in Lima at risk of an unplanned pregnancy or STDs. Sexual behavior may be especially risky in a context of sexual coercion and paid sex, when sex is combined with drugs and alcohol, and when engaged in by younger females. Sexual health education should work to change such cultural norms and these risky contexts.

Distribution of HIV-1 subtypes seen in an AIDS clinic in Sao Paulo City, Brazil.

OBJECTIVE: To determine the distribution of HIV-1 subtypes in Sao Paulo, Brazil. METHODS: Samples were obtained from 80 consecutive HIV-1-infected individuals attending the Immunodeficiency Clinic at the University of Sao Paulo in 1993. Peripheral blood mononuclear cells (PBMC) were separated by Ficoll-Hypaque gradient and a portion was used for routine CD4 counts; the remainder were frozen. PBMC were proteinase-K-digested and DNA-purified by organic extraction. Samples were amplified for the env region of HIV, and envelope sequence subtypes determined by heteroduplex mobility analysis using prototypic subtypes as references. A subset of these were also sequenced through the C2-V3 region of env. RESULTS: A total 69 of 80 samples yielded env polymerase chain reaction product enabling subtype determination; samples that did not amplify were those with low DNA yields. Among 12 injecting drug users (IDU) or sexual partners of IDU, four were typed as clade F and eight as clade B. Forty-three homosexual men or female sexual partners of bisexual men were typed as clade B. The 14 additional cases without known risk factors were typed as clade B. CONCLUSION: These data suggest that subtype F is related to injecting drug use in Brazil.

PIP: Serum samples from 80 consecutive HIV-1-infected individuals presenting to the Immunodeficiency Clinic at the University of Sao Paulo in 1993 were analyzed to determine the distribution of HIV-1 subtypes in the city. Peripheral blood mononuclear cells (PBMC) were separated using Ficoll-Hypaque gradient, a portion was used for routine CD4 counts, and the rest were frozen. PBMC were proteinase-K-digested and DNA-purified by organic extraction. The samples were amplified for the env region of HIV, and envelope sequence subtypes determined by heteroduplex mobility analysis using prototypic subtypes as references. A subset was also sequenced through the C2-V3 region of env. 69 samples yielded env polymerase chain reaction product enabling subtype determination. The samples which did not amplify had low DNA yields. Among 12 IV-drug users or their sex partners, four were typed as clade F and eight as clade B. 43 homosexual men or female sex partners of bisexual men were typed as clade B. The 14 additional cases with no known risk factor were typed as clade B.

Risk factors associated with a school-related outbreak of serogroup C meningococcal disease.

An outbreak of Neisseria meningitidis sero-group C disease occurred in four eighth grade students and in a younger sibling of another eighth grade student attending an intermediate school (seventh and eighth grades) in Santa Clara County, CA. Four cases had onset within 3 days in January, 1989, with the fifth case occurring approximately 10 days later. A case-control study was performed to determine risk factors associated with serogroup C meningococcal infection (disease or carriage) in this eighth grade class. Students were more likely to be infected if they had had a preceding viral-like respiratory illness characterized by fever (odds ratio (OR) 5.3, P = 0.03) or cough (OR 5.1, P = 0.048). A ski trip (OR 6.3, P = 0.01) and a poster-making session for a school dance (OR 3.7, P = 0.08) were identified as possible settings for a common exposure. Spending time with two specific students during lunchtime or outside of school was associated with an increased risk of infection (OR 7.0, P = 0.054; OR 5.8, P = 0.04).

AIDS incidence and survival in a hospital-based cohort of asymptomatic HIV seropositive patients in São Paulo, Brazil.

BACKGROUND: In spite of the high incidence of AIDS in Brazil, few studies have tried to evaluate the prognosis of asymptomatic HIV seropositive Brazilian patients. METHODS: A hospital outpatient facility-based cohort of HIV seropositive asymptomatic subjects was followed to determine their probability of remaining AIDS-free at 2 and 4 years of follow-up, as well as the one-year estimated cumulative probability of survival for the AIDS incident cases. The cohort was made up of all asymptomatic HIV seropositive subjects referred to the Immunology Branch of a large university hospital in São Paulo, Brazil, between 1985 and June 1997. RESULTS: The cumulative probability of remaining free from AIDS was 79% (+/- 3.7% SE) at 2 years, and 64.4% (+/- 5.1% SE) at 4 years after first known positive anti-HIV serology. Women had a marginally significant better probability of remaining AIDS-free after both 2 and 4 years of known seropositivity, as compared with men. There were no significant differences in the prognosis of the infection by age; the only single parameter associated with better prognosis was an initial CD4+ count > or =350/microl. The probability of survival one year after the diagnosis of AIDS was 78%, and the 50% estimated probability of survival was 19 months. Older patients (aged > or =35 years) had a better prognosis, as suggested by their longer survival estimates (P = 0.06). CONCLUSIONS: The probability of survival with AIDS observed in this study was higher than in the few previously published estimates for Brazil. However, since the time frame was so wide, it may not be entirely comparable with earlier studies. Some likely explanations for this possibly better prognosis could include more efficient prophylaxis for opportunistic diseases, as well as an increase in the availability of anti-retroviral drugs. The 8% incidence of AIDS at 2 years observed in this study for those individuals whose initial CD4+ count was > or =350/ml was close to that found in a large international epidemiological study of seroconverters.

Detection of meningitis epidemics in Africa: a population-based analysis.

Portions of sub-Saharan Africa are subject to major epidemics of meningococcal meningitis that require early detection and rapid control. We evaluated the usefulness of weekly meningitis rates derived from active surveillance data in Burkina Faso for detecting a meningitis epidemic. By analysing the rates of disease in 40 x 40km2 areas within a study region of Burkina Faso, we found that a threshold of 15 cases/100,000/week averaged over 2 weeks was 72-93% sensitive and 92-100% specific in detecting epidemics exceeding 100 cases/100,000/year. During epidemic periods, the positive predictive value of this threshold approached 100% for detecting local epidemics. Additionally, meningitis incidence was proportional to village size, with villages greater than 8000 having the highest disease rates during a major group A meningococcal epidemic in 1983-1984. Despite the rudimentary nature of surveillance data available in many developing countries, these data can be used to detect the early emergence of meningitis epidemics. Additional studies are needed to determine the relevance of this approach for detecting epidemics.

Drug-resistant tuberculosis in the Dominican Republic: results of a nationwide survey.

SETTING: The Dominican Republic. OBJECTIVE: To assess the extent of drug-resistant tuberculosis (TB) following the guidelines of the World Health Organization (WHO)/International Union Against Tuberculosis and Lung Disease (IUATLD) new global surveillance project on drug resistance in TB. METHODS: Using a multi-step proportional weighted approach, a sample of 688 sequential cases of smear positive pulmonary TB diagnosed between April 1994 and April 1995 was studied in six of the country's eight health regions. Pre-treatment sputum samples were cultured on Loewenstein-Jensen medium and drug susceptibility tests were performed using the economic variant of the proportion method. RESULTS: Of 420 cases with drug susceptibility results, resistance to one or more drugs was observed in 43.8%; resistance was found in 52.1% of 117 TB cases with a history of previous antituberculosis treatment and in 40.6% of 303 new TB cases. In five of the six health regions surveyed, > or = 41% of strains were resistant to one or more drugs. Multidrug resistance (MDR) to isoniazid and rifampicin with or without resistance to other drugs was found in 43 (10.2%) of 420 cases, including 6.6% of new TB cases. In five of the six health regions > or = 8% of strains were classified as MDR. Independent predictors of MDR-TB included being in the age group 25 to 44 years (odds ratio [OR] = 4.2, 95% confidence interval [Cl] 1.5, 11.6; P = 0.005), being aged 45 years and over (OR = 4.5, 95% CI 1.4, 14.4; P = 0.009), and having a prior history of TB (OR = 3.7, 95% CI 1.9, 7.4; P = 0.0001). CONCLUSION: The proportion of Mycobacterium tuberculosis strains resistant to one or more anti-TB drugs in the Dominican Republic is among the highest observed world-wide. The severity of the problem urgently requires the full implementation of TB control strategies endorsed by the WHO and the IUATID, which include political commitment to a National TB Program, case detection utilizing sputum-smear microscopy, directly observed treatment, regular drug supply, and standardised recording and reporting systems. Also, the sale of TB drugs in the private market should be controlled.

Predisposition to invasive pneumococcal illness following parainfluenza type 3 virus infection in chimpanzees.

An outbreak of invasive disease, including pneumococcal bacteremia, meningitis, and pneumonia, involved 17 of 83 (20.5%) chimpanzees at a primate rehabilitation unit. Invasive disease was more common in splenectomized than in nonsplenectomized animals (42.9% vs 18.4%), but the difference was not statistically significant. The outbreak followed closely an outbreak of upper respiratory tract infection (URTI) that occurred with equal frequency in splenectomized and nonsplenectomized chimpanzees. Those with URTI were 5.7 times as likely to develop invasive disease than those without URTI (P less than 0.005). Fourteen of 20 (70%) chimpanzees with recent URTI and serologically examined had a 4-fold or greater rise in titer to parainfluenza type 3 virus. The outbreak of invasive disease occurred despite the fact that most of the chimpanzees had been vaccinated with pneumococcal vaccine. Efficacy of pneumococcal vaccine could not be demonstrated among any segment of the chimpanzee population, and testing of sera from 23 vaccinated chimpanzees against 4 pneumococcal serotypes (3, 6, 8, and 14) failed to show a meaningful immune response. The findings demonstrated that viral URTI can predispose primates to invasive infections and suggested that pneumococcal vaccine is not protective in chimpanzees.

Developing evidence-based immunization recommendations and GRADE.

The Strategic Group of Advisory Experts (SAGE) on immunization is an independent advisory committee with a mandate to advise the World Health Organization (WHO) on the development of vaccine and immunization related policies. SAGE working groups are established on a time-limited basis to review and provide evidence-based recommendations, together with their implications, for open deliberation and decision-making by SAGE. In making its recommendations, SAGE takes into consideration: the epidemiologic and clinical characteristics of the disease; vaccine and immunization characteristics; economic analysis; health system considerations; the existence of and interaction with other intervention and control strategies; costing and social impacts; and legal and ethical concerns. Since 1998, WHO has produced evidence-based vaccine position papers for use primarily by national public health officials and immunization programme managers. Since April 2006 all new or updated position papers have been based on SAGE recommendations. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach has been adopted by WHO and, since 2008, GRADE tables that rate the quality of evidence have been produced in support of key recommendations. SAGE previously expressed concern that GRADE was not ideally suited to many immunization-specific issues such as the vaccine population level effect and the inclusion of surveillance system data, particularly for vaccine safety. Extensive productive interactions with various advisory groups including the US Advisory Committee on Immunization Practices, the European Centres for Disease Control, the German Standing Committee on Vaccination (STIKO), WHO's Global Advisory Committee on Vaccine Safety and the GRADE working group resulted in key enhancements to accommodate vaccine-relevant evidence. This facilitated integration and acceptability of the GRADE approach in the development of immunization related SAGE and WHO recommendations. Ongoing utilisation should result in further fine-tuning of the approach to ensure that recommendations are based on the full range of appropriate evidence.

Prevalence and correlates of bacterial vaginosis among young women of reproductive age in Mysore, India.

PURPOSE: Bacterial vaginosis (BV) is the most common cause of abnormal vaginal discharge among women of childbearing age and is associated with STI/HIV and adverse birth outcomes. The objective of this study was to determine the prevalence and correlates of BV among young women of reproductive age in Mysore, India. METHODS: Between October 2005 and December 2006, 898 sexually active women of 15-30 years of age were enrolled from two reproductive health clinics in Mysore. The women underwent an interview followed by physical examination, HSV-2 serologic testing, endocervical culture for Neisseria gonorrhoeae , and vaginal swabs for diagnosis of BV, Trichomonas vaginalis infection and candidiasis. Statistical analyses included conventional descriptive statistics and multivariable analysis using logistic regression. RESULTS: Of the 898 women, 391 (43.5%) were diagnosed with >or=1 endogenous reproductive tract infection and 157 (17.4%) with >or=1 sexually transmitted infection. Only 863 women had Gram-stained vaginal smears available, out of which 165 (19.1, 95% confidence interval [CI]: 16.3%-22.2%) were found to have BV and 133 (15.4, 95% CI: 12.9%-18.3%) were in the 'intermediate' stage. BV was related to concurrent infections with T. vaginalis (odds ratio [OR]=4.07, 95% CI: 2.45-6.72) and HSV-2 seropositivity (OR=2.22, 95% CI: 1.39-3.53). CONCLUSIONS: In this population, the prevalence of BV at 19% was relatively low. Coinfection with T. vaginalis , however, was common. BV was independently associated with concurrent T. vaginalis infection and partner's alcohol use. Muslim women had reduced odds of BV as compared to non-Muslim women. Further research is needed to understand the role of T. vaginalis infection in the pathogenesis of BV and the sociocultural context surrounding the condition in India.

Role of legionellae in acute infections of the lower respiratory tract.

The genus Legionella currently comprises 24 species and multiple serogroups. Despite the continuing development and increasing availability of new and improved laboratory tests for diagnosing legionella infections, the incidence of such infections remains poorly defined. The most frequently cited estimate of 25,000 to 50,000 cases of legionella pneumonia per year in the United States is based on a single study with a number of methodologic limitations. While numerous studies of the etiology of pneumonia have been published, it is usually not possible to calculate incidence from these investigations. The proportion of pneumonia cases attributable to legionella species has ranged from less than 1% to greater than 30%. Differences in the diagnostic methods employed in various studies and questions concerning the representativeness of the patients studied make it difficult to determine how much of the observed variation is due to true geographic and temporal differences in the incidence of legionella pneumonia. Further studies are needed to define the incidence of acute lower respiratory tract infections due to Legionella.

Toxic shock in the United States of America: epidemiology.

Toxic-shock syndrome (TSS), a severe multisystem febrile illness caused by S. aureus, occurs in a wide variety of clinical settings. Although the majority of reported cases in the United States continue to be associated with menstruation and tampon use, TSS also occurs in postpartum women and in patients with infected surgical wounds, cutaneous and subcutaneous infections, and infections at other body sites. Well documented cases of TSS have now been reported from countries around the world.

Toxic shock syndrome: an update.

Since late 1979 to early 1980, when toxic shock syndrome achieved notoriety, a substantial body of data has demonstrated that vaginal Staphylococcus aureus infections, particularly those occurring during menstruation, account for most cases of toxic shock syndrome in women of reproductive age. Among those patients with onset during menstruation, tampon use has been identified as the most important risk factor. Although menstrually associated cases have been observed among users of all brands and styles of tampons, the use of selected "super absorbent" brands and styles has been associated with an increased risk of toxic shock syndrome. Although the tampon characteristics responsible for the associated risk of toxic shock syndrome remain poorly understood, both absorbency and chemical composition appear to be important variables in this relationship. In response to studies demonstrating this relationship and legal pressures, tampon manufacturers have removed chemical constituents previously used to enhance absorbency, such as polyester foam, carboxymethylcellulose, and polyacrylate rayon, and have markedly reduced tampon absorbency. Coinciding with these changes, the reported number of menstrually related cases of toxic shock syndrome has dropped substantially, although they continue to account for 50% to 70% of all cases of toxic shock syndrome in women of reproductive age.

Outbreak investigations--a perspective.

Outbreak investigations, an important and challenging component of epidemiology and public health, can help identify the source of ongoing outbreaks and prevent additional cases. Even when an outbreak is over, a thorough epidemiologic and environmental investigation often can increase our knowledge of a given disease and prevent future outbreaks. Finally, outbreak investigations provide epidemiologic training and foster cooperation between the clinical and public health communities.

Recent trends in the incidence of toxic shock syndrome in northern California.

The incidence of toxic shock syndrome in women members of a large prepaid medical care program in Northern California was 1.5 cases per 100,000 in a period after removal of tampons containing polyacrylate rayon and reductions in tampon absorbency. This rate was lower, but not significantly lower, than the rate of 2.2 per 100,000 in the prior interval. It was higher, but not significantly higher, than the rate of 0.4 per 100,000 in the era before "superabsorbent" materials were introduced into tampons. The incidence in men has been stable at about 0.1 cases per 100,000 for the 15-year period from 1972 though 1987.