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Background: Human immunodeficiency virus (HIV)-associated tuberculosis deaths have decreased worldwide over the past decade. We sought to evaluate the effect of HIV status on tuberculosis mortality among patients undergoing treatment for tuberculosis in Lima, Peru, a low HIV prevalence setting., Methods: We conducted a prospective cohort study of patients treated for tuberculosis between 2005 and 2008 in two adjacent health regions in Lima, Peru (Lima Ciudad and Lima Este). We constructed a multivariate Cox proportional hazards model to evaluate the effect of HIV status on mortality during tuberculosis treatment., Results: Of 1701 participants treated for tuberculosis, 136 (8.0%) died during tuberculosis treatment. HIV-positive patients constituted 11.0% of the cohort and contributed to 34.6% of all deaths. HIV-positive patients were significantly more likely to die (25.1 vs. 5.9%, P < 0.001) and less likely to be cured (28.3 vs. 39.4%, P = 0.003). On multivariate analysis, positive HIV status (hazard ratio [HR] = 6.06; 95% confidence interval [CI], 3.96-9.27), unemployment (HR = 2.24; 95% CI, 1.55-3.25), and sputum acid-fast bacilli smear positivity (HR = 1.91; 95% CI, 1.10-3.31) were significantly associated with a higher hazard of death., Conclusions: We demonstrate that positive HIV status was a strong predictor of mortality among patients treated for tuberculosis in the early years after Peru started providing free antiretroviral therapy. As HIV diagnosis and antiretroviral therapy provision are more widely implemented for tuberculosis patients in Peru, future operational research should document the changing profile of HIV-associated tuberculosis mortality.

Background: Lost, delayed or incorrect laboratory results are associated with delays in initiating treatment. Delays in treatment for Multi-Drug Resistant Tuberculosis (MDR-TB) can worsen patient outcomes and increase transmission. The objective of this study was to evaluate the impact of a laboratory information system in reducing delays and the time for MDR-TB patients to culture convert (stop transmitting)., Setting: 78 primary Health Centers (HCs) in Lima, Peru. Participants lived within the catchment area of participating HCs and had at least one MDR-TB risk factor. The study design was a cluster randomized controlled trial with baseline data. The intervention was the e-Chasqui web-based laboratory information system. Main outcome measures were: times to communicate a result; to start or change a patient's treatment; and for that patient to culture convert., Results: 1671 patients were enrolled. Intervention HCs took significantly less time to receive drug susceptibility test (DST) (median 11 vs. 17 days, Hazard Ratio 0.67 [0.62-0.72]) and culture (5 vs. 8 days, 0.68 [0.65-0.72]) results. The time to treatment was not significantly different, but patients in intervention HCs took 16 days (20%) less time to culture convert (p = 0.047)., Conclusions: The eChasqui system reduced the time to communicate results between laboratories and HCs and time to culture conversion. It is now used in over 259 HCs covering 4.1 million people. This is the first randomized controlled trial of a laboratory information system in a developing country for any disease and the only study worldwide to show clinical impact of such a system., Trial Registration: ClinicalTrials.gov NCT01201941.

We conducted a case-control study to examine associations between parasite infection, including protozoa infection, and tuberculosis (TB) in children in Lima, Peru. We enrolled 189 matched-pairs. In multivariable conditional logistic regression analyses, Blastocystis hominis infection (rate ratio = 0.30, 95% confidence interval = 0.14-0.64, P = 0.002) was strongly associated with a lower risk of TB. We observed a statistically significant inverse linear dose-response relationship between Blastocystis hominis infection and TB. These findings should be confirmed in future prospective studies.

We conducted a case-control study among children in Lima, Peru to identify factors associated with tuberculosis disease. Known close contact with someone with tuberculosis disease, prior hospitalization, and history of anemia were associated with a higher tuberculosis disease rate. Consumption of fruits/vegetables ≥5 days/week was associated with a lower rate. Isoniazid uptake was low among children with a known contact.

Among tuberculosis patients, timely diagnosis of human immunodeficiency virus (HIV) co-infection and early antiretroviral treatment are crucial, but are hampered by a myriad of individual and structural barriers. Community-based models to provide counseling and rapid HIV testing are few but offer promise. During November 2009-April 2010, community health workers offered and performed HIV counseling and testing by using the OraQuick Rapid HIV-1/2 Antibody Test to new tuberculosis cases in 22 Ministry of Health establishments and their household contacts (n = 130) in Lima, Peru. Refusal of HIV testing or study participation was low (4.7%). Intervention strengths included community-based approach with participant preference for testing site, use of a rapid, non-invasive test, and accompaniment to facilitate HIV care and family disclosure. We will expand the intervention under programmatic auspices for rapid community-based testing for new tuberculosis cases in high incidence establishments. Other potential target populations include contacts of HIV-positive persons and pregnant women.

Aim: To describe the incidence of extensive drug-resistant tuberculosis (XDR-TB) reported in the Peruvian National multidrug-resistant tuberculosis (MDR-TB) registry over a period of more than ten years and present the treatment outcomes for a cohort of these patients., Methods: From the Peruvian MDR-TB registry we extracted all entries that were approved for second-line anti-TB treatment between January 1997 and June of 2007 and that had Drug Susceptibility Test (DST) results indicating resistance to both rifampicin and isoniazid (i.e. MDR-TB) in addition to results for at least one fluoroquinolone and one second-line injectable (amikacin, capreomycin and kanamycin)., Results: Of 1,989 confirmed MDR-TB cases with second-line DSTs, 119(6.0%) XDR-TB cases were detected between January 1997 and June of 2007. Lima and its metropolitan area account for 91% of cases, a distribution statistically similar to that of MDR-TB. A total of 43 XDR-TB cases were included in the cohort analysis, 37 of them received ITR. Of these, 17(46%) were cured, 8(22%) died and 11(30%) either failed or defaulted treatment. Of the 14 XDR-TB patients diagnosed as such before ITR treatment initiation, 10 (71%) were cured and the median conversion time was 2 months., Conclusion: In the Peruvian context, with long experience in treating MDR-TB and low HIV burden, although the overall cure rate was poor, a large proportion of XDR-TB patients can be cured if DST to second-line drugs is performed early and treatment is delivered according to the WHO Guidelines.

Patients treated in Peru for multidrug-resistant tuberculosis (MDR-TB) were followed-up for a median of 67 months. Among 86 patients considered cured after completion of treatment, 97% remain healthy; 1 patient relapsed. Employment increased from 34% before treatment to 71%. We observed favorable long-term outcomes among MDR-TB patients.

Multidrug-resistant tuberculosis (MDR-TB) is a global public health problem affecting women of childbearing age. Little is known, however, about the safety of the drugs used to treat MDR-TB during pregnancy. We describe 7 patients who were treated for MDR-TB during pregnancy. These patients had chronic tuberculosis that had caused extensive parenchymal damage and had high-grade resistance to antituberculous drugs. All patients received individualized antituberculous therapy prior to delivery of healthy term infants. Neither obstetrical complications nor perinatal transmission of MDB-TB was observed. One patient experienced treatment failure, and another abandoned therapy. The other 5 patients are currently cured or in treatment and have culture-negative status. In each of these 7 cases, excellent treatment outcomes were obtained for the women and their children. Under certain circumstances, MDR-TB can be successfully treated during pregnancy.

Debate persists about monitoring method (culture or smear) and interval (monthly or less frequently) during treatment for multidrug-resistant tuberculosis (MDR-TB). We analysed existing data and estimated the effect of monitoring strategies on timing of failure detection. We identified studies reporting microbiological response to MDR-TB treatment and solicited individual patient data from authors. Frailty survival models were used to estimate pooled relative risk of failure detection in the last 12 months of treatment; hazard of failure using monthly culture was the reference. Data were obtained for 5410 patients across 12 observational studies. During the last 12 months of treatment, failure detection occurred in a median of 3 months by monthly culture; failure detection was delayed by 2, 7, and 9 months relying on bimonthly culture, monthly smear and bimonthly smear, respectively. Risk (95% CI) of failure detection delay resulting from monthly smear relative to culture is 0.38 (0.34–0.42) for all patients and 0.33 (0.25–0.42) for HIV-co-infected patients. Failure detection is delayed by reducing the sensitivity and frequency of the monitoring method. Monthly monitoring of sputum cultures from patients receiving MDR-TB treatment is recommended. Expanded laboratory capacity is needed for high-quality culture, and for smear microscopy and rapid molecular tests.

Rationale: A better understanding of the composition of optimal treatment regimens for multidrug-resistant tuberculosis (MDR-TB) is essential for expanding universal access to effective treatment and for developing new therapies for MDR-TB. Analysis of observational data may inform the definition of an optimized regimen. Objectives: This study assessed the impact of an aggressive regimen–one containing at least five likely effective drugs, including a fluoroquinolone and injectable–on treatment outcomes in a large MDR-TB patient cohort. Methods: This was a retrospective cohort study of patients treated in a national outpatient program in Peru between 1999 and 2002. We examined the association between receiving an aggressive regimen and the rate of death. Measurements and Main Results: In total, 669 patients were treated with individualized regimens for laboratory-confirmed MDR-TB. Isolates were resistant to a mean of 5.4 (SD 1.7) drugs. Cure or completion was achieved in 66.1% (442) of patients; death occurred in 20.8% (139). Patients who received an aggressive regimen were less likely to die (crude hazard ratio [HR]: 0.62; 95% CI: 0.44,0.89), compared to those who did not receive such a regimen. This association held in analyses adjusted for comorbidities and indicators of severity (adjusted HR: 0.63; 95% CI: 0.43,0.93). Conclusions: The aggressive regimen is a robust predictor of MDR-TB treatment outcome. TB policy makers and program directors should consider this standard as they design and implement regimens for patients with drug-resistant disease. Furthermore, the aggressive regimen should be considered the standard background regimen when designing randomized trials of treatment for drug-resistant TB. [ABSTRACT FROM AUTHOR]

The Peruvian National Tuberculosis Control Program issued guidelines in 2006 specifying criteria for culture and drug-susceptibility testing (DST), including district-level rapid DST. All patients referred for culture and DST in 2 districts of Lima, Peru, during January 2005-November 2008 were monitored prospectively. Of 1,846 patients, 1,241 (67.2%) had complete DST results for isoniazid and rifampin; 419 (33.8%) patients had multidrug-resistant (MDR) TB at the time of referral. Among patients with new smear-positive TB, household contact and suspected category I failure were associated with MDR TB, compared with concurrent regional surveillance data. Among previously treated patients with smear-positive TB, adult household contact, suspected category II failure, early relapse after category I, and multiple previous TB treatments were associated with MDR TB, compared with concurrent regional surveillance data. The proportion of MDR TB detected by using guidelines was higher than that detected by a concurrent national drug-resistance survey, indicating that the strategy effectively identified patients for DST. [ABSTRACT FROM AUTHOR]

Background: Despite the prevalence of multidrug-resistant tuberculosis in nearly all low-income countries surveyed, effective therapy has been deemed too expensive and considered not to be feasible outside referral centers. We evaluated the results of community-based therapy for multidrug-resistant tuberculosis in a poor section of Lima, Peru. Methods: We describe the first 75 patients to receive ambulatory treatment with individualized regimens for chronic multidrug-resistant tuberculosis in northern Lima. We conducted a retrospective review of the charts of all patients enrolled in the program between August 1, 1996, and February 1, 1999, and identified predictors of poor outcomes. Results: The infecting strains of Mycobacterium tuberculosis were resistant to a median of six drugs. Among the 66 patients who completed four or more months of therapy, 83 percent (55) were probably cured at the completion of treatment. Five of these 66 patients (8 percent) died while receiving therapy. Only one patient continued to have positive cultures after six months of treatment. All patients in whom treatment failed or who died had extensive bilateral pulmonary disease. In a multiple Cox proportional-hazards regression model, the predictors of the time to treatment failure or death were a low hematocrit (hazard ratio, 4.09; 95 percent confidence interval, 1.35 to 12.36) and a low body-mass index (hazard ratio, 3.23; 95 percent confidence interval, 0.90 to 11.53). Inclusion of pyrazinamide and ethambutol in the regimen (when susceptibility was confirmed) was associated with a favorable outcome (hazard ratio for treatment failure or death, 0.30; 95 percent confidence interval, 0.11 to 0.83). Conclusions: Community-based outpatient treatment of multidrug-resistant tuberculosis can yield high cure rates even in resource-poor settings. Early initiation of appropriate therapy can preserve susceptibility to first-line drugs and improve treatment outcomes. N Engl J Med 2003;348:119-28. [ABSTRACT FROM AUTHOR]

Programs implementing community-based directly observed therapy (DOT) have demonstrated success in the treatment of patients with tuberculosis. However, given complexities in the management and treatment of patients infected with multidrug-resistant tuberculosis (MDR-TB), the utilization of community-based DOT to treat MDR-TB patients has only recently been successfully attempted. We describe the first such program and highlight the crucial components and most critical challenges to creating a successful community-based MDR-TB treatment program. [Copyright &y& Elsevier]

Treatment for pulmonary tuberculosis (TB) is drug-based but the emergence of drug-resistance has decreased its therapeutic efficacy. Pulmonary surgery is an important beneficial adjuvant strategy for MDR TB treatment in this context. Objectives. To describe the clinical characteristics results and complications in a series of 304 patients with MDR TB submitted to surgical therapy. Material and methods. Between May of 1999 and January of 2007 a total of 336 surgical interventions were performed on 304 patients from the National Program of TB Control who, were operated by a surgical team of the Ministry of Health in the Hipolito unanue National Hospital and in a Private Center in Lima. Results. Most cases were male (60%) and the mean age was 28 years. Patients were resistant to a median of 5 drugs. Cavitary lesions were the most common (91.8%) and lobectomy was the most commonly performed surgical procedure (68.4%). Postoperative morbidity and mortality occurred in 12.8% and 2% respectively. Patients were followed post-operatively for a maximum time of 79.3 months and healing was reached in the 77.2% of cases. Conclusions. Pulmonary adjuvant surgery on MDR TB patients is an effective alternative for cure. This strategy should be included as part of treatment programs for MDR TB. [ABSTRACT FROM AUTHOR]

Background: Extensively drug-resistant tuberculosis has been reported in 45 countries, including countries with limited resources and a high burden of tuberculosis. We describe the management of extensively drug-resistant tuberculosis and treatment outcomes among patients who were referred for individualized outpatient therapy in Peru. Methods: A total of 810 patients were referred for free individualized therapy, including drug treatment, resective surgery, adverse-event management, and nutritional and psychosocial support. We tested isolates from 651 patients for extensively drug-resistant tuberculosis and developed regimens that included five or more drugs to which the infecting isolate was not resistant. Results: Of the 651 patients tested, 48 (7.4%) had extensively drug-resistant tuberculosis; the remaining 603 patients had multidrug-resistant tuberculosis. The patients with extensively drug-resistant tuberculosis had undergone more treatment than the other patients (mean [±SD] number of regimens, 4.2±1.9 vs. 3.2±1.6; P<0.001) and had isolates that were resistant to more drugs (number of drugs, 8.4±1.1 vs. 5.3±1.5; P<0.001). None of the patients with extensively drug-resistant tuberculosis were coinfected with the human immunodeficiency virus (HIV). Patients with extensively drug-resistant tuberculosis received daily, supervised therapy with an average of 5.3±1.3 drugs, including cycloserine, an injectable drug, and a fluoroquinolone. Twenty-nine of these patients (60.4%) completed treatment or were cured, as compared with 400 patients (66.3%) with multidrug-resistant tuberculosis (P=0.36). Conclusions: Extensively drug-resistant tuberculosis can be cured in HIV-negative patients through outpatient treatment, even in those who have received multiple prior courses of therapy for tuberculosis. N Engl J Med 2008;359:563-74. [ABSTRACT FROM AUTHOR]