Cost-effectiveness of active case-finding of household contacts of pulmonary tuberculosis patients in a low HIV, tuberculosis-endemic urban area of Lima, Peru.

We compared the cost-effectiveness (CE) of an active case-finding (ACF) programme for household contacts of tuberculosis (TB) cases enrolled in first-line treatment to routine passive case-finding (PCF) within an established national TB programme in Peru. Decision analysis was used to model detection of TB in household contacts through: (1) self-report of symptomatic cases for evaluation (PCF), (2) a provider-initiated ACF programme, (3) addition of an Xpert MTB/RIF diagnostic test for a single sputum sample from household contacts, and (4) all strategies combined. CE was calculated as the incremental cost-effectiveness ratio (ICER) in terms of US dollars per disability-adjusted life years (DALYs) averted. Compared to PCF alone, ACF for household contacts resulted in an ICER of $2155 per DALY averted. The addition of the Xpert MTB/RIF diagnostic test resulted in an ICER of $3275 per DALY averted within a PCF programme and $3399 per DALY averted when an ACF programme was included. Provider-initiated ACF of household contacts in an urban setting of Lima, Peru can be highly cost-effective, even including costs to seek out contacts and perform an Xpert/MTB RIF test. ACF including Xpert MTB/RIF was not cost-effective if TB cases detected had high rates of default from treatment or poor outcomes.

Time to initiation of multidrug-resistant tuberculosis treatment and its relation with outcome in a high incidence district in Lima, Peru.

OBJECTIVE: To determine the time from diagnosis to start of multidrug resistant tuberculosis (MDR TB) treatment in Lima, Peru. METHODS: We studied new smear-positive TB adults that were started on MDR TB treatment or that were switched to it between June 2008 and December 2011. RESULTS: Time from the first positive smear to MDR-TB treatment was >30 days in 35% (13/37) of patients. Among the 27% (24/88) of patients that switched to MDR-TB treatment, time from the last dose of a drug-susceptible regimen was >30 days. CONCLUSION: Start of and switching to MDR TB treatment is still delayed.

Duration of cough, TB suspects' characteristics and service factors determine the yield of smear microscopy.

OBJECTIVE: To determine the efficiency of routine tuberculosis (TB) case detection by examining sputum smear positivity for acid-fast bacilli in relation to duration of cough, characteristics of TB suspects examined and health service factors. METHOD: We combined patient interviews with routine data from laboratory registers in 6 health care facilities in San Juan de Lurigancho district, Lima, Peru. A TB case was defined as a TB suspect with at least one positive sputum smear. We calculated adjusted odds ratios with 95% confidence intervals for the association between smear positivity and health service and patient's characteristics. RESULTS: Smear positivity was 7.3% (321/4376). Of the 4376 adults submitting sputa, 55.3% (2418) reported cough for <14 days. In this group, smear microscopy yielded 3.2% (78/2418) positive results vs. 12.4% (243/1958) in patients coughing for 14 or more days. Having cough for >2 weeks, being referred by health care staff, attending a secondary-level health care facility, male sex and age between 15 and 44 years were independent determinants of smear positivity. CONCLUSIONS: Routine case detection yields a low proportion of smear-positive cases because of the inclusion of a high proportion of patients without cough or coughing for <2 weeks. Adherence to the national TB control programme guidelines on the selection of TB suspects would have a positive impact on the smear positivity rate, reduce laboratory costs and workload and possibly improve the reading quality of smear microscopy.

Bodyweight gain to predict treatment outcome in patients with pulmonary tuberculosis in Peru.

SETTING: Tuberculosis control programmes of two health care centres in the central rainforest of Peru. OBJECTIVE: To evaluate if bodyweight gain (BWG) predicts treatment outcome in patients with pulmonary tuberculosis (PTB). DESIGN: Retrospective cohort study of adults with PTB diagnosed between 1995 and 2004. BWG was assessed after month 1 of treatment, after the initial phase and at the end of treatment. Patients were stratified into two BWG categories, < or = 5% and >5%. Failures and relapses were grouped together as unsuccessful treatment outcome. RESULTS: A total of 650 patients were included: 7.2% (n = 47) had an unsuccessful outcome. Unsuccessful outcome was associated with BWG < or = 5% at the end of treatment (RR 2.05, 95%CI 1.10-3.80), but not at the completion of month 1 (RR 0.99, 95%CI 0.52-1.88) or at completion of the initial phase (RR 1.46, 95%CI 0.82-2.57). Median BWG at completion of the initial phase was higher in cured patients (P = 0.007). BWG < or = 5% at end of treatment (RR 2.35, 95%CI 1.17-4.72), initial sputum smear 2+ (RR 2.48, 95%CI 1.14-5.31) and positive smear microscopy at month 2 (RR 4.0, 95%CI 1.30-12.31) were independent predictors of unsuccessful treatment outcome. CONCLUSION: BWG < or = 5% at the end of treatment, high bacterial load and lack of sputum conversion correlate with unsuccessful treatment outcome in this setting. New discriminative cut-offs for BWG are proposed.

HTLV-1 infection is frequent among out-patients with pulmonary tuberculosis in northern Lima, Peru.

SETTING: Tuberculosis (TB) and human T-lymphotropic virus 1 (HTLV-1) are frequent in Peru. The prevalence of HTLV-1 among Peruvian TB patients is unknown. OBJECTIVE: To determine the prevalence of HTLV-1, HTLV-2 and the human immunodeficiency virus (HIV) in out-patients with TB and to compare HTLV-1-infected patients with seronegative patients. DESIGN: Cross-sectional study including subjects aged 18-65 years diagnosed with smear-positive pulmonary TB at health centres in northern Lima from November 2004 to August 2005. HTLV and HIV screening was performed using enzyme-linked immunosorbent assay; HTLV-1 and HTLV-2 were confirmed using line immunoassay. RESULTS: There were 311 participants with a median age of 29 years; 173 (56%) were men. HTLV-1 prevalence was 5.8% (18/311, 95%CI 3.2-8.4) and HIV prevalence was 1.3% (4/304, 95%CI 0.4-3.3). HTLV-2 was not diagnosed. In comparison with HIV- and HTLV-seronegative patients, HTLV-1-infected subjects were older (median age 44 vs. 28, P < 0.001) and were more likely to have been born in the southern Andes (OR 4.4, 95%CI 1.6-11.9). They were also more likely to report a history of TB deaths in the family (OR 5.4, 95%CI 1.7-16.8) and had more sputum smear results graded as 3+ (OR 4.1, 95%CI 1.5-11.2). CONCLUSION: HTLV-1 screening among Peruvian TB patients is important. Because 3+ sputum smears are frequent and mortality is high among relatives, families of HTLV-1/TB-positive cases merit special attention.

Oxacillin-resistant and multidrug-resistant Staphylococcus aureus in Lima, Peru.

In a hospital in Lima, Peru, a review of 103 Staphylococcus aureus infections was conducted during 2002. The prevalence of oxacillin-resistant S. aureus strains was 68%; 25% of strains were resistant to multiple drugs. Previous use of antibiotics and undergoing a surgical procedure during the current hospital stay were associated with the presence of an oxacillin-resistant S. aureus strain.

Manual MGIT™ system for the detection of Mycobacterium tuberculosis: insights from a high TB burden setting.

OBJECTIVE: To evaluate the diagnostic performance of manual MGIT™ (MMGIT) compared to the gold standard, Löwenstein-Jensen (LJ), in the diagnosis of pulmonary tuberculosis (TB) in a high-burden setting. METHODS: Individuals with suspected TB enrolled in parallel diagnostic trials during 2007-2011 were included. Two samples were obtained from each patient and inoculated into MMGIT and LJ medium. Diagnostic tests were performed, and the incremental yield of a second test and time to detection (TTD) were calculated. Analyses were performed per patient and per sample. Gold standard was based on LJ culture. RESULTS: In the per patient and per sample analysis, we evaluated 1436 patients and 4142 samples. The sensitivity and specificity for smear and MMGIT per sample were respectively 89.9%/92.2% and 97.1%/98.9%. Contamination was observed in 1.4% of samples on MMGIT. The mean TTD (days) was 11.8 for MMGIT and 22.9 for LJ. The sensitivity and specificity for smear and MMGIT per patient were respectively 89.9% and 92.2% and 97.1% and 98.3%. A second MMGIT culture had an incremental yield of 1.6%. CONCLUSIONS: MMGIT has high sensitivity and specificity, regardless of smear result, with a 50% reduction in TTD compared to LJ. These features make MMGIT an acceptable TB diagnostic method for use in resource-limited settings.

Practical guidelines for the treatment of cholera.

Cholera is a dramatic clinical illness that requires rapid diagnosis and aggressive therapy. Clinical signs and symptoms of mild, moderate and severe dehydration must be determined, before beginning fluid therapy. Fluid therapy has 2 phases: rehydration (first 3 to 4 hours to correct deficits) and maintenance (to match continuing losses). The route and speed of fluid administration will depend on the degree of dehydration. Patients with severe dehydration should be treated intravenously, as should those patients who do not tolerate oral rehydration solution (ORS). Ringer's lactate is the preferred intravenous solution, although normal saline may be used along with ORS. For most patients with cholera, an ORS using one of the higher sodium-containing solutions and plain water optimally provide the fluid and salt needed. Close monitoring of intake, outputs and hydration status should be performed for all patients. Antimicrobial therapy should be given to moderately and severely ill patients in order to decrease the volume of fluids lost and to shorten the period of excretion of vibrios.

Cholera. Lessons from the epidemic in Peru.

It is not known why the cholera epidemic, which affected all other continents, has not affected Latin America in the past 30 years. In addition, it is unclear why cholera appeared in Peru in 1991. Improvements in scientific knowledge and technology have occurred in Peru during the last 30 months. While it is impossible to summarize in only one article all these concepts, this article presents a few of the most important issues and recent developments in the treatment and prevention of cholera.

New insights on the emergence of cholera in Latin America during 1991: the Peruvian experience.

After a century of absence, in late January 1991, Vibrio cholerae invaded the Western Hemisphere by way of Peru. Although a number of theories have been proposed, it is still not understood how that invasion took place. We reviewed the clinical records of persons attending hospital emergency departments in the major coastal cities of Peru from September through January of 1989/1990 and 1990/1991. We identified seven adults suffering from severe, watery diarrhea compatible with a clinical diagnosis of cholera during the four months preceding the cholera outbreak, but none during the previous year. The patients were scattered among five coastal cities along a 1,000 km coastline. We postulate that cholera vibrios, autochthonous to the aquatic environment, were present in multiple coastal locations, and resulted from environmental conditions that existed during an El Nino phenomenon. Once introduced into the coastal communities in concentrations large enough for human infection to occur, cholera spread by the well-known means of contaminated water and food.

Clinical features, antimicrobial susceptibility and toxin production in Vibrio cholerae O139 infection: comparison with V. cholerae O1 infection.

We prospectively compared the clinical features of cholera due to Vibrio cholerae O1 and V. cholerae O139 in 242 men 18-60 years of age, with a history of diarrhoea of 24 h or less, and moderate or severe dehydration. The antimicrobial susceptibility of all of the V. cholerae strains isolated from these patients was determined, and in vitro cholera toxin production determined for 68 isolates. On admission, the 110 patients infected with V. cholerae O1 significantly more often had body temperature < 36 degrees C (85% vs. 66%, P < or = 0.05), faecal leucocyte count > 50/high power microscope field (40% vs. 12%), and lower mean faecal chloride content (94 vs. 103 mmol/L) than did the 132 patients infected with V. cholerae O139. Patients infected with V. cholerae O1 also initially had significantly higher median volumes of stool (13 vs. 11 mL per kg body weight per h), vomitus (1 mL/kg/h vs. nil), and intravenous fluid requirements (23 vs. 21 mL/kg/h). All V. cholerae O1 and O139 isolates were susceptible to ciprofloxacin, all but one were susceptible to doxycycline and erythromycin, and the majority of both serogroups were resistant to co-trimoxazole (95% and 97%, respectively). V. cholerae O1 and O139 susceptibilities differed for tetracycline (58% vs. 100%) and furazolidone (27% vs. 93%) (P < 0.001 in both cases). The amount of cholera toxin produced in vitro by strains of V. cholerae O1 and O139 was similar, and did not correlate with stool volume. The results demonstrated that V. cholerae O139 does not cause more severe, or more invasive, disease than V. cholerae O1, as had been previously suggested, but that clinically important differences in antimicrobial susceptibility do exist among strains isolated in Bangladesh.

Surveillance of bacterial pathogens associated with acute diarrhea in Lima, Peru.

OBJECTIVES: A study was conducted in Lima, Peru, from January to April 1995, to determine the bacterial pathogens associated with acute diarrhea in adults, their susceptibility to common antimicrobials, the risk factors involved in cholera transmission, and the best clinical predictors of cholera. METHODS: A random sample of adult patients with acute diarrhea was studied. Epidemiologic and clinical data and risk factors to acquire diarrheal diseases were evaluated. Identification of bacteria and susceptibility to antimicrobials were determined. RESULTS: The study included 336 patients. Vibrio cholerae O1 (52.7%), Shigella spp. (4. 8%), and Salmonella spp (2.7%) were the pathogens most commonly isolated. No resistance to antimicrobials was observed. Patients with cholera had less access to municipal water (P = 0.0018) and were less likely to have homes connected to a sewage system (P = 0. 0003) or to have indoor toilet facilities (P = 0.0001) than those without cholera. Liquid stools (odds ratio [OR] = 16.51; confidence interval [CI] = 13.71-19.02; P = 0.003), severe dehydration (OR = 2. 48; CI = 1.57-3.38; P = 0.0083), generalized cramps (OR = 4.63; CI = 3.10-6.17, P < 0.0001), and washerwoman's hands (OR = 2.45; CI = 1. 55-3.34; P = 0.017) were the best clinical predictors of cholera in this setting. CONCLUSIONS: Cholera is still prevalent in Lima, and people living in environments with low sanitary conditions are especially at risk. Clinical signs of severe dehydration and liquid stools were the best predictors of cholera.

Geographic predictors of primary multidrug-resistant tuberculosis cases in an endemic area of Lima, Peru.

SETTING: Peru reports among the highest multidrug-resistant tuberculosis (MDR-TB) rates in the Americas, with a growing proportion in previously untreated tuberculosis (TB) cases. The identification of clusters of primary MDR-TB compared with drug-susceptible TB (DS-TB) could help prioritize interventions. OBJECTIVE: To examine the clustering of primary MDR-TB case residences and their proximity to high-risk locations in San Juan de Lurigancho District, Lima, Peru. DESIGN: Enrolled primary MDR-TB and primary DS-TB cases were interviewed and their primary residence was recorded using handheld Global Positioning System devices. Kuldorff's spatial scan statistic was used for cluster detection (SaTScan(TM), v. 9.1.1). Identified clusters were visualized in Quantum Geographic Information Systems software (v1.8.0). The following cluster centers were tested: a health centre with the highest TB and MDR-TB rates (Clinic X), a hospital and two prisons. Using regression analyses, we examined predictors of primary MDR-TB cases. RESULTS: A statistically significant cluster of primary MDR-TB cases was identified within a 2.29 km radius around Clinic X. Proximity to Clinic X remained a significant predictor of primary MDR-TB in adjusted regression analyses. CONCLUSION: We identified a hotspot of primary MDR-TB cases around Clinic X in a TB-endemic area. Causes of this clustering require investigation; targeted interventions for this high-risk area should be considered.

Metabolic syndrome in HIV-infected patients receiving antiretroviral therapy in Latin America.

OBJECTIVE: To evaluate the prevalence of and the associated factors for metabolic syndrome (MS) among Latin American HIV-infected patients receiving antiretroviral therapy (ART) using baseline data from the RAPID II study. METHODS: A longitudinal study to evaluate the metabolic profile, cardiovascular disease (CVD) risk and associated treatment practices to reduce this risk has been conducted in seven Latin American countries (the RAPID II study). Adult HIV patients with at least six months of RT were enrolled. MS was defined following ATP-III criteria. Demographic and anthropometric data, serum biochemical and clinical parameters were compared in patients with and without MS using bivariate and multivariate analysis. RESULTS: A total of 4,010 patients were enrolled, 2,963 (74%) were males. Mean age (SD) was 41.9 (10.0) years. The prevalence of MS was 20.2%. Females had higher prevalence of MS than males (22.7% vs. 19.4%, p = 0.02). MS was driven by high triglycerides, low HDL-cholesterol and high blood pressure (HBP). Patients with MS had higher 10 year CVD risk: 22.2% vs. 7.4%, p < 0.001. Age (OR: 1.05 per year), female gender (OR: 1.29), family history of CVD (OR: 1.28), CD4 cell count (OR: 1.09 per 100 cell increase), and protease inhibitor based-ART (OR: 1.33) correlated with MS in the multivariate analysis. CONCLUSIONS: Prevalence of MS in this setting was similar to that reported from developed countries. MS was driven by high triglycerides, low-HDL and HBP, and it was associated with higher risk of CVD. Traditional risk factors, female gender, immune reconstitution, and protease inhibitor based-ART correlated with MS.

Metabolic profile and cardiovascular risk factors among Latin American HIV-infected patients receiving HAART.

OBJECTIVE: Determine the prevalence of metabolic abnormalities (MA) and estimate the 10-year risk for cardiovascular disease (CVD) among Latin American HIV-infected patients receiving highly active anti-retroviral therapy (HAART). METHODS: A cohort study to evaluate MA and treatment practices to reduce CVD has been conducted in seven Latin American countries. Adult HIV-infected patients with at least one month of HAART were enrolled. Baseline data are presented in this analysis. RESULTS: A total of 4,010 patients were enrolled. Mean age (SD) was 41.9 (10) years; median duration of HAART was 35 (IQR: 10-51) months, 44% received protease inhibitors. The prevalence of dyslipidemia and metabolic syndrome was 80.2% and 20.2%, respectively. The overall 10-year risk of CVD, as measured by the Framingham risk score (FRF), was 10.4 (24.7). Longer exposure to HAART was documented in patients with dyslipidemia, metabolic syndrome and type 2 diabetes mellitus. The FRF score increased with duration of HAART. Male patients had more dyslipidemia, high blood pressure, smoking habit and higher 10-year CVD than females. CONCLUSIONS: Traditional risk factors for CVD are prevalent in this setting leading to intermediate 10-year risk of CVD. Modification of these risk factors through education and intervention programs are needed to reduce CVD.

Metabolic profile and cardiovascular risk factors among Latin American HIV-infected patients receiving HAART

OBJECTIVE: Determine the prevalence of metabolic abnormalities (MA) and estimate the 10-year risk for cardiovascular disease (CVD) among Latin American HIV-infected patients receiving highly active anti-retroviral therapy (HAART). METHODS: A cohort study to evaluate MA and treatment practices to reduce CVD has been conducted in seven Latin American countries. Adult HIV-infected patients with at least one month of HAART were enrolled. Baseline data are presented in this analysis. RESULTS: A total of 4,010 patients were enrolled. Mean age (SD) was 41.9 (10) years; median duration of HAART was 35 (IQR: 10-51) months, 44 percent received protease inhibitors. The prevalence of dyslipidemia and metabolic syndrome was 80.2 percent and 20.2 percent, respectively. The overall 10-year risk of CVD, as measured by the Framingham risk score (FRF), was 10.4 (24.7). Longer exposure to HAART was documented in patients with dyslipidemia, metabolic syndrome and type 2 diabetes mellitus. The FRF score increased with duration of HAART. Male patients had more dyslipidemia, high blood pressure, smoking habit and higher 10-year CVD than females. CONCLUSIONS: Traditional risk factors for CVD are prevalent in this setting leading to intermediate 10-year risk of CVD. Modification of these risk factors through education and intervention programs are needed to reduce CVD.

Metabolic syndrome in HIV-infected patients receiving antiretroviral therapy in Latin America

OBJECTIVE: To evaluate the prevalence of and the associated factors for metabolic syndrome (MS) among Latin American HIV-infected patients receiving antiretroviral therapy (ART) using baseline data from the RAPID II study. METHODS: A longitudinal study to evaluate the metabolic profile, cardiovascular disease (CVD) risk and associated treatment practices to reduce this risk has been conducted in seven Latin American countries (the RAPID II study). Adult HIV patients with at least six months of RT were enrolled. MS was defined following ATP-III criteria. Demographic and anthropometric data, serum biochemical and clinical parameters were compared in patients with and without MS using bivariate and multivariate analysis. RESULTS: A total of 4,010 patients were enrolled, 2,963 (74 percent) were males. Mean age (SD) was 41.9 (10.0) years. The prevalence of MS was 20.2 percent. Females had higher prevalence of MS than males (22.7 percent vs. 19.4 percent, p = 0.02). MS was driven by high triglycerides, low HDL-cholesterol and high blood pressure (HBP). Patients with MS had higher 10year CVD risk: 22.2 percent vs. 7.4 percent, p < 0.001. Age (OR: 1.05 per year), female gender (OR: 1.29), family history of CVD (OR: 1.28), CD4 cell count (OR: 1.09 per 100 cell increase), and protease inhibitor based-ART (OR: 1.33) correlated with MS in the multivariate analysis. CONCLUSIONS: Prevalence of MS in this setting was similar to that reported from developed countries. MS was driven by high triglycerides, low-HDL and HBP, and it was associated with higher risk of CVD. Traditional risk factors, female gender, immune reconstitution, and protease inhibitor based-ART correlated with MS.

Efficacy and tolerability of ciprofloxacin prophylaxis in adult household contacts of patients with cholera.

We conducted a randomized double-blinded study in Lima, Peru, to assess the tolerability and efficacy of a single 250-mg dose of ciprofloxacin in preventing diarrhea and Vibrio cholerae O1 infection among household contacts of bacteriologically confirmed index cases. Adult household contacts with negative baseline stool cultures were included. A total of 213 household contacts were evaluable. The study drugs were well tolerated in both groups. Ciprofloxacin did not prevent the acquisition of V. cholerae O1 infection nor the development of diarrhea. However, in a subgroup of 30 household contacts with positive baseline stool cultures a reduction in the bacterial load and a trend toward prevention of diarrhea were observed among ciprofloxacin recipients. When all household contacts were evaluated, a trend toward prevention of diarrhea was observed with the prophylactic regimen. Ciprofloxacin failed to prevent V. cholerae O1 infections during a period of low transmissibility.

Ciprofloxacin for the treatment of cholera: a randomized, double-blind, controlled clinical trial of a single daily dose in Peruvian adults.

We conducted a randomized, double-blind clinical trial to compare ciprofloxacin (250 mg once a day for 3 days) with tetracycline (500 mg four times a day for 3 days) in terms of efficacy and safety in the treatment of moderate-to-severe cholera in Peruvian adults. The baseline characteristics of the groups were similar. A total of 202 patients (102 in the tetracycline group and 100 in the ciprofloxacin group) were included in the efficacy analysis. The clinical and bacteriologic efficacies of the two regimens were similar. The study drugs were well tolerated. We conclude that ciprofloxacin given once a day is as effective as the standard tetracycline regimen for the treatment of cholera in adults. The ciprofloxacin regimen may represent an alternative to the standard treatment in areas where Vibrio cholerae O1 strains that are resistant to commonly used antimicrobials are prevalent.