Juan Echevarría

Epidemiology of Candidemia in Latin America: A Laboratory-Based Survey

Background The epidemiology of candidemia varies depending on the geographic region. Little is known about the epidemiology of candidemia in Latin America. Methods We conducted a 24-month laboratory-based survey of candidemia in 20 centers of seven Latin American countries. Incidence rates were calculated and the epidemiology of candidemia was characterized. Results Among 672 episodes of candidemia, 297 (44.2%) occurred in children (23.7% younger than 1 year), 36.2% in adults between 19 and 60 years old and 19.6% in elderly patients. The overall incidence was 1.18 cases per 1,000 admissions, and varied across countries, with the highest incidence in Colombia and the lowest in Chile. Candida albicans (37.6%), C. parapsilosis (26.5%) and C. tropicalis (17.6%) were the leading agents, with great variability in species distribution in the different countries. Most isolates were highly susceptible to fluconazole, voriconazole, amphotericin B and anidulafungin. Fluconazole was the most frequent agent used as primary treatment (65.8%), and the overall 30-day survival was 59.3%. Conclusions This first large epidemiologic study of candidemia in Latin America showed a high incidence of candidemia, high percentage of children, typical species distribution, with C. albicans, C. parapsilosis and C. tropicalis accounting for the majority of episodes, and low resistance rates.

Durability of Initial Antiretroviral Therapy in a Resource-Constrained Setting and the Potential Need for Zidovudine Weight-Based Dosing

Background:Whereas access to antiretroviral therapy (ART) for HIV-infected individuals in the developing world is increasing, data on factors impacting initial regimen durability are lacking. Methods:Retrospective review patients starting initial ART at Instituto de Medicine Tropical (Lima, Peru) April 1, 2004 to December 30, 2007. Survival methods (Kaplan-Meier, Cox proportional hazard) assessed factors associated with regimen durability including an interaction term between nucleoside reverse transcriptase inhibitor backbone and time. Results:Decreased initial regimen durability was observed with weight <60 kg [hazards ratio (HR) = 1.77; 95% confidence interval (CI) = 1.25-2.51], CD4 <200 (HR = 1.73; 95% CI = 1.03-2.91), and zidovudine (AZT) use at <120 days (HR = 2.09; 95% CI = 1.22-3.57). In contrast, after 120 days, AZT use decreased risk of discontinuation (HR = 0.52; 95% CI = 0.28-0.95). Early (<120 days) toxicity-related discontinuation of AZT containing regimens was observed in 44% of patients <50 kg at baseline vs. 14% of those >70 kg. An increased risk of early toxicity-related discontinuation of AZT-containing regimens was observed for baseline weight <60 kg (HR = 2.52; 95% CI = 1.46-4.35). Conclusions:Lower baseline weight and lower CD4 values at ART initiation were associated with decreased regimen durability. Compared with didanosine/stavudine, AZT use initially increased, then subsequently (>120 days) lowered hazards for regimen discontinuation. Weight <60 kg was associated with an increased risk of toxicity-related AZT discontinuation. As ART use expands globally, further study into maximally durable, least toxic regimens, and the role of weight-based AZT dosing is imperative.BACKGROUND Anal intraepithelial neoplasia (AIN), particularly AIN 3 is a precursor to anal cancer. Most cases of AIN are intraanal, but few treatments for intraanal AIN are currently available. Topical 85% trichloroacetic acid (TCA) is an inexpensive method used to treat perianal condyloma, a form of AIN 1, but its efficacy to treat intraanal AIN as first-line therapy is unknown. METHODS Retrospective review of medical records was performed for all patients with AIN treated at the University of California San Francisco Anal Neoplasia Clinic with TCA as the first-line therapy from January 2000 to December 2004. Clearance was defined as the absence of AIN confirmed by high-resolution anoscopy and cytology after up to 4 TCA treatments. RESULTS Thirty-five HIV-positive men and 19 HIV-negative men met the enrollment criteria. In multivariate analysis, greater clearance was seen in patients 41-48 years of age versus >49 years [odds ratio (OR): 8.4, confidence interval (CI): 1.1 to 94, P: 0.04]. Among HIV-positive men, those with 2 or fewer lesions showed greater clearance (OR: 14.3, CI: 1.5 to 662, P: 0.01). 32% of patients with AIN 2/3 cleared to no lesions. On a per lesion basis, 73% of AIN 1 and 71% AIN 2/3 cleared to no lesion or AIN 1 or less, respectively. CONCLUSIONS Topical 85% TCA was safe and well tolerated. It was more effective in younger patients and among HIV-positive patients, those with 2 or fewer lesions. A high proportion of AIN 2/3 lesions responded to TCA treatment.

Sexual behavior of international travelers visiting Peru

Background Sexual behavior of travelers to Latin America and the sexual behavior of US travelers in general are poorly characterized. Goal The goal of the study was to evaluate sexual risk factors of travelers to Peru. Study Design Anonymous written questionnaires were administered to 442/507 (87%) of the individuals approached in the international departures area of the Lima airport. Results Of the 442 respondents, 54 (12.2%) had new sex partners during their stay. Sex with a local partner (35/52; 67.3%) was more frequent than sex with other travelers (18/52; 34.6%) or with sex workers (4/52; 7.7%). Risk factors for a new sex partner included male sex (relative risk, 1.94), single marital status (relative risk, 2.59), duration of stay longer than 30 days (relative risk, 5.05), traveling alone or with friends (relative risk, 2.88), and bisexual orientation (relative risk, 4.94). Frequency of sexual activity among US travelers was greater than that among travelers from other countries (15.2% [22/145] versus 10.6% [30/282]; NS). Condoms were consistently used by 12/50 (24%) and sometimes used by 10/50 (20%), including 8/20 United States travelers and 13/29 travelers from other countries. Conclusion Behaviors and risk factors are similar to those described for travelers to Africa, Asia, and Eastern Europe. Behavior of US travelers did not differ from that of other travelers.

Efficacy of Sodium Stibogluconate Alone and in Combination with Allopurinol for Treatment of Mucocutaneous Leishmaniasis

A randomized, open, controlled clinical trial was designed to evaluate the efficacy, tolerance, and safety of sodium stibogluconate plus allopurinol and sodium stibogluconate alone as treatment of patients with mucocutaneous leishmaniasis. In phase 1 of the study, all 22 patients with severe disease had improvement of their lesions, but only two had clinical cure (both of these patients received sodium stibogluconate alone). In phase 2, which included 59 patients with moderate disease, the cure rate among sodium stibogluconate recipients was 75% (21 of 28) compared with 63.6% (14 of 22) among the sodium stibogluconate plus allopurinol recipients. The rates of clinical adverse events were similar among both groups. Thrombocytopenia was more frequent in the sodium stibogluconate plus allopurinol recipients, but the difference was not statistically significant. Eight patients (two sodium stibogluconate recipients and six sodium stibogluconate plus allopurinol recipients) withdrew from the study because of severe thrombocytopenia. In this study, the addition of allopurinol to sodium stibogluconate provided no clinical benefit as treatment of mucocutaneous leishmaniasis.

Sexual behavior in travelers visiting Cuzco.

BACKGROUND In South America, little is known about sexual behavior and risk factors for acquiring sexually transmitted diseases (STDs) among travelers and among local people sexually interacting with travelers. There is evidence that, in Peru, significant sexual interaction between these groups exists. METHOD An anonymous written questionnaire was administered to travelers in the airport and bus stations before they left Cuzco. RESULTS Of the travelers,5.6% engaged in sexual activity with a new partner during their stay in Cuzco. Sexual intercourse with other travelers was most common (76/140, 54.3%), followed by sex with local partners (57/140, 40.7%), and with commercial sex workers (3/140, 2.15%). Consistent condom use was reported by 97/140 (69.3%). In the multivariate analysis, the following variables were independently associated with casual sex: male gender, single marital status, age between 15 and 35 years, non-United States travelers (NUSTs), traveling alone or with friends, length of stay more than 30 days, homosexual or bisexual orientation, and expectation of having sex before traveling. Homosexual and bisexual travelers had 3 or more new sexual partners more frequently than heterosexual travelers (4/8, 18/129, OR=6.17 (1.16<OR<33.5)). NUSTs received more pretravel advice (698/1587, 210/718, OR=1.86 (1.54<OR<2.24)) and engaged in more sexual activity (100/1,587, 25/722, OR=1.86 (1.20<OR<2.93)) than United States travelers (USTs). CONCLUSION Travelers visiting Cuzco engage in sexual activities that put them at risk of acquiring STD and transmitting it, both in their home country and in Peru. We recommend the inclusion of Peru and possibly other Latin American countries in the list of destinations where there is substantial risk of transmission of STD and the provision of pretravel advice regarding this issue to travelers to Peru.

Randomized controlled trial of zinc supplementation for persistent diarrhea in adults with HIV-1 infection.

Background:In children, zinc supplementation reduces the incidence and severity of diarrhea. Methods:HIV-infected adults with ≥7 days of diarrhea recruited at 3 tertiary hospitals in Lima, Peru, received a zinc sulfate capsule containing 50 mg of elemental zinc twice daily or an identical placebo for 14 days. Outcomes included persistence of diarrhea at day 14 and time until cessation of diarrhea. Results:The 81 subjects randomized to zinc and 78 randomized to placebo were comparable at baseline, except for higher prevalences of certain enteric pathogens in the zinc group; complete follow-up rates were 62% and 69%, respectively. Zinc concentrations were consistent with zinc deficiency at follow-up in 94% of placebo recipients and 66% of zinc recipients (P = 0.01). Persistence of diarrhea at day 14 according to follow-up interview (60% for zinc-treated patients and 57.4% for placebo-treated patients) or to patient diary (42.2% vs. 31.9%) did not differ significantly. Adjusting for enteric pathogens and CD4 count, the hazard ratio (HR) for zinc supplementation and cessation of diarrhea (according to the diaries) was 0.91 (95% confidence interval [CI]: 0.50 to 1.64). Conclusion:Supplemental zinc had no significant effect on the duration or remission of diarrhea in HIV-infected adults.

Pretravel Health Advice among International Travelers Visiting Cuzco, Peru

BACKGROUND Cuzco, a Peruvian city of historical interest located 3,326 m above sea level, is a frequent destination for tourists. We conducted a descriptive study to assess the extent and sources of pretravel health advice received by international travelers before their arrival to Cuzco. METHODS Data were collected as part of a health survey among travelers. Between August and November 2002, travelers between 15 and 65 years old were invited to fill out a questionnaire in the departing area of Cuzcos international airport. RESULTS A total of 5,988 travelers participated. The mean age was 35.4 years (SD 11.4 yr); 50.6% were female and 50.8% were single. Tourism was the reason for traveling in 90.2% of the participants, and 89.3% of them were traveling with companions. Pretravel health information was received by 93.6%. The median number of information sources was two, with books (41.5%), travel medicine clinics (38.8%), the Internet (23.3%), and general practitioners (22.7%) as the main sources. Most frequently received recommendations were about safe food and water consumption (85%), use of insect repellents (66.0%), sunburn protection (64.4%), and condom use (22%). Only 16.5% took medication to prevent altitude sickness, and 14.2% took medication to prevent travelers diarrhea. Variables independently associated with receiving pretravel health information from a health care professional were female gender, country of residence other than the United States, length of stay in Cuzco > 7 days, length of stay in other Peruvian cities > 7 days, tourism as the main reason for visiting Cuzco, traveling with companions, and consulting of more than one source of information. CONCLUSIONS Most travelers arriving to Cuzco had received pretravel health information, and the majority obtained it from more than one source. Recommendations addressed for specific health risks, such as altitude sickness prophylaxis, were received by few travelers.

A diagnostic accuracy study of Xpert®MTB/RIF in HIV-positive patients with high clinical suspicion of pulmonary tuberculosis in Lima, Peru.

Background Diagnosis of pulmonary tuberculosis (TB) among human immunodeficiency virus (HIV) patients remains complex and demands easy to perform and accurate tests. Xpert®MTB/RIF (MTB/RIF) is a molecular TB diagnostic test which is rapid and convenient; the test requires minimal human resources and reports results within two hours. The majority of performance studies of MTB/RIF have been performed in high HIV burden settings, thus TB diagnostic studies among HIV patients in low HIV prevalence settings such as Peru are still needed. Methodology/Principal Findings From April 2010 to May 2011, HIV-positive patients with high clinical suspicion of TB were enrolled from two tertiary hospitals in Lima, Peru. Detection of TB by MTB/RIF was compared to a composite reference standard Löwenstein-Jensen (LJ) and liquid culture. Detection of rifampicin resistance was compared to the LJ proportion method. We included 131 patients, the median CD4 cell count was 154.5 cells/mm3 and 45 (34.4%) had TB. For TB detection among HIV patients, sensitivity of MTB/RIF was 97.8% (95% CI 88.4–99.6) (44/45); specificity was 97.7% (95% CI 91.9–99.4) (84/86); the positive predictive value was 95.7% (95% CI 85.5–98.8) (44/46); and the negative predictive value, 98.8% (95% CI 93.6–99.8) (84/85). MTB/RIF detected 13/14 smear-negative TB cases, outperforming smear microscopy [97.8% (44/45) vs. 68.9% (31/45); p = 0.0002]. For rifampicin resistance detection, sensitivity of MTB/RIF was 100% (95% CI 61.0–100.0) (6/6); specificity was 91.0% (95% CI 76.4–96.9) (30/33); the positive predictive value was 66.7% (95% CI 35.4–87.9) (6/9); and the negative predictive value was 100% (95% CI 88.7 –100.0) (30/30). Conclusions/Significance In HIV patients in our population with a high clinical suspicion of TB, MTB/RIF performed well for TB diagnosis and outperformed smear microscopy.

Surveillance of Candida spp bloodstream infections: epidemiological trends and risk factors of death in two Mexican tertiary care hospitals.

Introduction Larger populations at risk, broader use of antibiotics and longer hospital stays have impacted on the incidence of Candida sp. bloodstream infections (CBSI). Objective To determine clinical and epidemiologic characteristics of patients with CBSI in two tertiary care reference medical institutions in Mexico City. Design Prospective and observational laboratory-based surveillance study conducted from 07/2008 to 06/2010. Methods All patients with CBSI were included. Identification and antifungal susceptibility were performed using CLSI M27-A3 standard procedures. Frequencies, Mann-Whitney U test or T test were used as needed. Risk factors were determined with multivariable analysis and binary logistic regression analysis. Results CBSI represented 3.8% of nosocomial bloodstream infections. Cumulative incidence was 2.8 per 1000 discharges (incidence rate: 0.38 per 1000 patient-days). C. albicans was the predominant species (46%), followed by C. tropicalis (26%). C. glabrata was isolated from patients with diabetes (50%), and elderly patients. Sixty-four patients (86%) received antifungals. Amphotericin-B deoxycholate (AmBD) was the most commonly used agent (66%). Overall mortality rate reached 46%, and risk factors for death were APACHE II score ≥16 (OR = 6.94, CI95% = 2.34–20.58, p<0.0001), and liver disease (OR = 186.11, CI95% = 7.61–4550.20, p = 0.001). Full susceptibility to fluconazole, AmBD and echinocandins among C. albicans, C. tropicalis, and C. parapsilosis was observed. Conclusions The cumulative incidence rate in these centers was higher than other reports from tertiary care hospitals from Latin America. Knowledge of local epidemiologic patterns permits the design of more specific strategies for prevention and preemptive therapy of CBSI.

High Prevalence of Sexually Transmitted Infections Among Young Peruvians Who Have Sexual Intercourse With Foreign Travelers in Cuzco

BACKGROUND Sexual networking in popular tourist destinations is a problem worldwide. In Peru, locals sexually interacting with travelers bridge high-risk groups, the general population, and travelers. METHODS A cross-sectional study was conducted in Cuzco about sexual behavior among young Peruvians who admitted having sex with travelers. A subgroup of the participants had serologic testing for Chlamydia trachomatis, Herpes simplex virus (HSV) type 2, and Treponema pallidum. RESULTS Eighty-eight subjects volunteered for blood sampling. Their mean age was 22.9 years (+/-4.1) and 53.4% were male. The majority were single (86.2%), but 12.6% had a stable relationship. The median number of sexual partners in the 3 months prior to the study was 2 [interquartile range (IQR): 1-4]. During that period, 43.1% reported foreign partners, 28.4% reported foreign and Peruvian partners, 17% reported Peruvian partners, and the remaining 11.5% reported combinations of Peruvian, foreign, and sex workers partners. The median number of foreign partners in the 12-month period prior to the study was 4 (IQR: 2-8). Only 25.3% reported consistent condom use. Alcohol (69%) and drugs (36.8%) were commonly used before sexual activity. Seventy-eight percent tested positive for HSV type 2, 25% for C trachomatis, and 1.1% for T pallidum. CONCLUSIONS The core group of young Peruvians we report on demonstrated a high-risk sexual behavior and a high prevalence of sexually transmitted infections. Our results underscore the need for education on safer sex practices among this group and among travelers.