Azole resistance among clinical isolates of Aspergillus fumigatus in Lima-Peru.

Azole resistance among Aspergillus fumigatus isolates, which is mainly related to mutations in the cyp51A gene, is a concern because it is rising, worldwide disseminated, and associated with treatment failure and death. Data on azole resistance of aspergillus from Latin American countries is very scarce and do not exist for Peru. Two hundred and seven Aspergillus clinical isolates collected prospectively underwent mycology and molecular testing for specie identification, and 143 isolates were confirmed as A. fumigatus sensu stricto (AFSS). All AFSS were tested for in vitro azole susceptibility, and resistant isolates underwent PCR amplification and sequencing of the whole cyp51A gene and its promoter. The in vitro susceptibility showed a minimal inhibitory concentration (MIC) range, MIC50 and MIC90 of 0.125 to >16, 0.25, and 0.5 µg/ml for itraconazole; 0.25 to 2, 0.5, and 0.5 µg/ml for voriconazole; and 0.003 to 1, 0.06, and 0.125 µg/ml for posaconazole. Three isolates (2%) showed resistance to itraconazole and exhibited different mutations of the cyp51A gene. One isolate harbored the mutation M220K, while a second one exhibited the G54 mutation plus a modification in the cyp51A gene promoter. The third isolate, from an azole naive patient, presented an integration of a 34-bp tandem repeat (TR34) in the promoter region of the gene and a substitution of leucine 98 by histidine (L98H). The three source patients had a diagnosis or suspicion of chronic pulmonary aspergillosis.

Prevention of sexually transmitted infections in urban communities (Peru PREVEN): a multicomponent community-randomised controlled trial.

BACKGROUND: Previous community-randomised trials of interventions to control sexually transmitted infections (STIs) have involved rural settings, were rarely multicomponent, and had varying results. We aimed to assess the effect of a multicomponent intervention on curable STIs in urban young adults and female sex workers (FSWs). METHODS: In this community-randomised trial, baseline STI screening was done between August, and November, 2002, in random household samples of young adults (aged 18-29 years) and in FSWs in Peruvian cities with more than 50,000 inhabitants. Geographically separate cities were selected, matched into pairs, and randomly allocated to intervention or control groups with an S-PLUS program. Follow-up surveys of random samples were done after 2 years and 3 years. The intervention comprised four modalities: strengthened STI syndromic management by pharmacy workers and clinicians; mobile-team outreach to FSWs for STI screening and pathogen-specific treatment; periodic presumptive treatment of FSWs for trichomoniasis; and condom promotion for FSWs and the general population. Individuals in control cities received standard care. The composite primary endpoint was infection of young adults with Chlamydia trachomatis, Trichomonas vaginalis, or Neisseria gonorrhoeae, or syphilis seroreactivity. Laboratory workers and the data analyst were masked, but fieldworkers, the Peruvian study team, and participants in the outcome surveys were not. All analyses were done by intention to treat. This trial is registered, ISRCTN43722548. FINDINGS: We did baseline surveys of 15,261 young adults in 24 Peruvian cities. Of those, 20 geographically separate cities were matched into pairs, in each of which one city was assigned to intervention and the other to standard of care. In the 2006 follow-up survey, data for the composite primary outcome were available for 12,930 young adults. We report a non-significant reduction in prevalence of STIs in young adults, adjusted for baseline prevalence, in intervention cities compared with control cities (relative risk 0·84, 95% CI 0·69-1·02; p=0·096). In subgroup analyses, significant reductions were noted in intervention cities in young adult women and FSWs. INTERPRETATION: Syndromic management of STIs, mobile-team outreach to FSWs, presumptive treatment for trichomoniasis in FSWs, and condom promotion might reduce the composite prevalence of any of the four curable STIs investigated in this trial. FUNDING: Wellcome Trust and Burroughs Wellcome Fund, National Institutes of Health, Center for AIDS Research, CIPRA, and USAID-Peru.

Studying complex interactions among determinants of healthcare-seeking behaviours: self-medication for sexually transmitted infection symptoms in female sex workers.

OBJECTIVES: To describe the frequency and determinants of self-medication for symptoms of sexually transmitted infections (STI) in a female sex worker (FSW) population. To present a methodology exploring the best predictors as well as the interactions between determinants of self-medication. METHODS: A cross-sectional survey of 4153 FSW carried out in Peru. The prevalence of self-medication was estimated from the subsample of participants who had experienced symptoms of STI in the past 12 months (n=1601), and used successive logistic regression models to explore the determinants. RESULTS: Self-medication prevalence for a reported symptomatic episode during the past 12 months was 32.1% (95% CI 29.8 to 34.6). It was negatively correlated with work in brothels (adjusted odds ratio (OR) 0.51, 95% CI 0.28 to 0.93; p=0.028) and awareness of STI services available for FSW (adjusted OR 0.49, 95% CI 0.29 to 0.81; p=0.006). Other determinants were organised at different levels of proximity to the outcome creating pathways leading to self-medication. CONCLUSIONS: The importance of the staggered analysis presented in this study resides in its potential to improve the understanding of associations between determinants and, consequently, the targeting of interventions. The awareness of STI services available for FSW increases access to health care, which in turn decreases self-medication. In addition, the sharing of information that takes place between brothel-based FSW was also related to a diminishing prevalence of self-medication. These two main predictors provide an opportunity for prevention programmes, in particular those designed to be led by peers.

Sexually transmitted infection screening uptake and knowledge of sexually transmitted infection symptoms among female sex workers participating in a community randomised trial in Peru.

This study aims to evaluate condom use, sexually transmitted infection (STI) screening, and knowledge of STI symptoms among female sex workers in Peru associated with sex work venues and a community randomised trial of STI control. One component of the Peru PREVEN intervention conducted mobile-team outreach to female sex workers to reduce STIs and increase condom use and access to government clinics for STI screening and evaluation. Prevalence ratios were calculated using multivariate Poisson regression models with robust standard errors, clustering by city. As-treated analyses were conducted to assess outcomes associated with reported exposure to the intervention. Care-seeking was more frequent in intervention communities, but differences were not statistically significant. Female sex workers reporting exposure to the intervention had a significantly higher likelihood of condom use, STI screening at public health clinics, and symptom recognition compared to those not exposed. Compared with street- or bar-based female sex workers, brothel-based female sex workers reported significantly higher rates of condom use with last client, recent screening exams for STIs, and HIV testing. Brothel-based female sex workers also more often reported knowledge of STIs and recognition of STI symptoms in women and in men. Interventions to promote STI detection and prevention among female sex workers in Peru should consider structural or regulatory factors related to sex work venues.

Sporotrichosis: a forgotten disease in the drug research agenda.

Potassium iodide was discovered in the 19th century and still remains as one of the more effective and most prescribed treatments for sporotrichosis. No new drugs have been evaluated in large randomized clinical trials in comparison with standard or alternative treatments for sporotrichosis during the last decades. The emergence of disseminated sporotrichosis in AIDS patients has uncovered the need for more effective treatments. Sporotrichosis is only a public health problem in a few geographical areas, mostly located in developing countries; and its usually harmless history could explain the limited investment in sporotrichosis treatment research. Better understanding of the virulence factors, such as the melanization process, could reveal new potential drug targets.

Reaching the unreachable: providing STI control services to female sex workers via mobile team outreach.

BACKGROUND: As part of a community-randomized trial of a multicomponent intervention to prevent sexually transmitted infections, we created Mobile Teams (MTs) in ten intervention cities across Peru to improve outreach to female sex workers (FSW) for strengthened STI prevention services. METHODS: Throughout 20 two-month cycles, MTs provided counseling; condoms; screening and specific treatment for Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT), and vaginal Trichomonas vaginalis (TV) infections; and periodic presumptive metronidazole treatment for vaginal infections. RESULTS: MTs had 48,207 separate encounters with 24,814 FSW; numbers of sex work venues and of FSW reached increased steadily over several cycles. Approximately 50% of FSW reached per cycle were new. Reported condom use with last client increased from 73% to 93%. Presumptive metronidazole treatment was accepted 83% of times offered. Over 38 months, CT prevalence declined from 15.4% to 8.2%, and TV prevalence from 7.3% to 2.6%. Among participants in ≥ 9 cycles, CT prevalence decreased from 12.9% to 6.0% (p <0.001); TV from 4.6% to 1.5% (p <0.001); and NG from 0.8% to 0.4% (p = 0.07). CONCLUSIONS: Mobile outreach to FSW reached many FSW not utilizing government clinics. Self-reported condom use substantially increased; CT and TV prevalences declined significantly. The community-randomized trial, reported separately, demonstrated significantly greater reductions in composite prevalence of CT, NG, TV, or high-titer syphilis serology in FSW in these ten intervention cities than in ten matched control cities.

Improved STD syndrome management by a network of clinicians and pharmacy workers in Peru: The PREVEN Network.

BACKGROUND: Sexually Transmitted diseases (STD) syndrome management has been one cornerstone of STD treatment. Persons with STD symptoms in many countries, especially those with limited resources, often initially seek care in pharmacies. The objective of the study was to develop and evaluate an integrated network of physicians, midwives and pharmacy workers trained in STD syndromic management (The PREVEN Network) as part of a national urban community-randomized trial of sexually transmitted infection prevention in Peru. METHODS AND FINDINGS: After a comprehensive census of physicians, midwives, and pharmacies in ten intervention and ten control cities, we introduced seminars and workshops for pharmacy workers, and continuing education for physicians and midwives in intervention cities and invited graduates to join the PREVEN Network. "Prevention Salespersons" visited pharmacies, boticas and clinicians regularly for educational support and collection of information on numbers of cases of STD syndromes seen at pharmacies and by clinicians in intervention cities. Simulated patients evaluated outcomes of training of pharmacy workers with respect to adequate STD syndrome management, recommendations for condom use and for treatment of partners. In intervention cities we trained, certified, and incorporated into the PREVEN Network the workers at 623 (80.6%) of 773 pharmacies and 701 (69.6%) of 1007 physicians and midwives in private practice. Extremely high clinician and pharmacy worker turnover, 13.4% and 44% respectively in the first year, dictated continued training of new pharmacy workers and clinicians. By the end of the intervention the Network included 792 pharmacies and 597 clinicians. Pharmacies reported more cases of STDs than did clinicians. Evaluations by simulated patients showed significant and substantial improvements in the management of STD syndromes at pharmacies in intervention cities but not in control cities. CONCLUSIONS: Training pharmacy workers linked to a referral network of clinicians proved feasible and acceptable. High turn-over was challenging but over come.

Prevalences of sexually transmitted infections in young adults and female sex workers in Peru: a national population-based survey.

BACKGROUND: We assessed prevalences of seven sexually transmitted infections (STIs) in Peru, stratified by risk behaviours, to help to define care and prevention priorities. METHODS: In a 2002 household-based survey of the general population, we enrolled randomly selected 18-29-year-old residents of 24 cities with populations greater than 50 000 people. We then surveyed female sex workers (FSWs) in these cities. We gathered data for sexual behaviour; vaginal specimens or urine for nucleic acid amplification tests for Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis; and blood for serological tests for syphilis, HIV, and (in subsamples) herpes simplex virus 2 (HSV2) and human T-lymphotropic virus. This study is a registered component of the PREVEN trial, number ISRCTN43722548. FINDINGS: 15 261 individuals from the general population and 4485 FSWs agreed to participate in our survey. Overall prevalence of infection with HSV2, weighted for city size, was 13·5% in men, 13·6% in women, and 60·6% in FSWs (all values in FSWs standardised to age composition of women in the general population). The prevalence of C trachomatis infection was 4·2% in men, 6·5% in women, and 16·4% in FSWs; of T vaginalis infection was 0·3% in men, 4·9% in women, and 7·9% in FSWs; and of syphilis was 0·5% in men, 0·4% in women, and 0·8% in FSWs. N gonorrhoeae infection had a prevalence of 0·1% in men and women, and of 1·6% in FSWs. Prevalence of HIV infection was 0·5% in men and FSWs, and 0·1% in women. Four (0·3%) of 1535 specimens were positive for human T-lymphotropic virus 1. In men, 65·0% of infections with HIV, 71·5% of N gonorrhoeae, and 41·4% of HSV2 and 60·9% of cases of syphilis were in the 13·3% who had sex with men or unprotected sex with FSWs in the past year. In women from the general population, 66·7% of infections with HIV and 16·7% of cases of syphilis were accounted for by the 4·4% who had been paid for sex by any of their past three partners. INTERPRETATION: Defining of high-risk groups could guide targeting of interventions for communicable diseases-including STIs-in the general Peruvian population. FUNDING: Wellcome Trust-Burroughs Wellcome Fund Infectious Disease Initiative and US National Institutes of Health.

Design and implementation of Cell-PREVEN: a real-time surveillance system for adverse events using cell phones in Peru.

With more clinical trials involving evaluations of new drugs or vaccines, monitoring for early detection of adverse events is essential. The overall goal of this study was to develop an interactive-computer system using cell phones for real-time collection and transmission of adverse events related to metronidazole administration among female sex workers (FSW) in Peru. We developed an application for cell phones in Spanish, called Cell-PREVEN, based on a system from Voxiva Inc. We used cell phones to enter data collected by interviewers from FSW in three communities. Information was stored in an online database, where it could be immediately accessed worldwide and exported over a secure Internet connection. E-mail and text messages sent to mobile devices alerted key personnel to selected symptoms. This pilot project has demonstrated that it is feasible to develop a public-health-surveillance system based on cell phones to collect data in real-time in Peru (http://www.prevenperu.org).

Multidrug-resistant Mycobacterium tuberculosis in HIV-infected persons, Peru.

During 1999 to 2000, we identified HIV-infected persons with new episodes of tuberculosis (TB) at 10 hospitals in Lima, Peru, and a random sample of other Lima residents with TB. Multidrug-resistant (MDR)-TB was documented in 35 (43%) of 81 HIV-positive patients and 38 (3.9%) of 965 patients who were HIV-negative or of unknown HIV status (p<0.001). HIV-positive patients with MDR-TB were concentrated at three hospitals that treat the greatest numbers of HIV-infected persons with TB. Of patients with TB, those with HIV infection differed from those without known HIV infection in having more frequent prior exposure to clinical services and more frequent previous TB therapy or prophylaxis. However, MDR-TB in HIV-infected patients was not associated with previous TB therapy or prophylaxis. MDR-TB is an ongoing problem in HIV-infected persons receiving care in public hospitals in Lima and Callao; they represent sentinel cases for a potentially larger epidemic of nosocomial MDR-TB.

Prevention of sexually transmitted diseases (STDs) in female sex workers: prospective evaluation of condom promotion and strengthened STD services.

BACKGROUND: In Perú, a previous study of government-sponsored periodic examinations of female sex workers (FSWs) found no significant impact on rates of sexually transmitted diseases (STDs). GOAL: This study assessed the impact of technically improved periodic STD services on STD prevalence and on consistent condom use (CCU). STUDY DESIGN: The study involved monthly follow-up of 917 FSWs at two STD clinics, with evaluations before and during implementation of strengthened STD services, which included periodic screening and treatment for gonorrhea, chlamydial infection, trichomoniasis, bacterial vaginosis (BV), and syphilis; counseling; and supply of condoms. Outcome analyses were adjusted for participation bias. RESULTS: During 7908 person-months of observation, the prevalences of gonorrhea, chlamydial infection, trichomoniasis, and BV declined significantly and CCU increased significantly, with similar trends in both clinics. During follow-up, gonorrhea, chlamydial infection, trichomoniasis, and BV were negatively associated with follow-up after screening. BV also was positively associated with use of an intrauterine device and negatively with douching. CCU during follow-up was associated with significantly decreased risk of gonorrhea, chlamydial infection, and trichomoniasis. CONCLUSIONS: Strengthened periodic screening for and treatment of confirmed STD, in addition to condom promotion and provision, represent feasible, effective interventions in commercial sex, and time series analyses can provide a useful approach to evaluating new interventions.

The etiology and management of genital ulcers in the Dominican Republic and Peru.

BACKGROUND: Clinical diagnosis of genital ulcers is difficult, and diagnostic tests are least available in settings where rates of disease are highest. The World Health Organization (WHO) has developed protocols for the syndromic management of genital ulcers in resource-poor settings. However, because risk factors, patterns and causes of disease, and antimicrobial susceptibilities differ from region to region and over time, they must be adapted to local situations. GOAL: The goal of this study was to determine etiologic factors, evaluate syndromic management, and compare polymerase chain reaction (PCR) testing with other diagnostic alternatives for genital ulcers among patients attending sexually transmitted disease clinics in the Dominican Republic and Peru. STUDY DESIGN: Eighty-one men with genital ulcers in the Dominican Republic and 63 in Peru underwent identical interviews and identical multiplex PCR (M-PCR) tests of genital lesion specimens for etiologic diagnoses. Algorithms for managing genital ulcers were developed. RESULTS: In the Dominican Republic, 5% were M-PCR-positive for, 26% for, and 43% for herpes simplex virus (HSV); in Peru, 10%, 5%, and 43%, respectively, were positive. The WHO algorithm for treating syphilis and chancroid had a sensitivity of 100%, a positive predictive value (PPV) of 24%, and an overtreatment rate of 76%. A modified algorithm for treating only those without vesicular lesions had 88% sensitivity and a 27% PPV, and the overtreatment rate was reduced to 58%. CONCLUSION: HSV caused 43% of genital ulcers in these populations. The modified algorithm had lower sensitivity but a reduced overtreatment rate. M-PCR testing was more sensitive than standard tests and more specific and sensitive than clinical diagnosis.