Lely Solari

Microscopic observation drug susceptibility assay for tuberculosis screening before isoniazid preventive therapy in HIV-infected persons

BACKGROUND Active tuberculosis (TB) must be excluded before initiating isoniazid preventive therapy (IPT) in persons infected with human immunodeficiency virus (HIV), but currently used screening strategies have poor sensitivity and specificity and high patient attrition rates. Liquid TB culture is now recommended for the detection of Mycobacterium tuberculosis in individuals suspected of having TB. This study compared the efficacy, effectiveness, and speed of the microscopic observation drug susceptibility (MODS) assay with currently used strategies for TB screening before IPT in HIV-infected persons. METHODS A total of 471 HIV-infected IPT candidates at 3 hospitals in Lima, Peru, were enrolled in a prospective comparison of TB screening strategies, including laboratory, clinical, and radiographic assessments. RESULTS Of 435 patients who provided 2 sputum samples, M. tuberculosis was detected in 27 (6.2%) by MODS culture, 22 (5.1%) by Lowenstein-Jensen culture, and 7 (1.6%) by smear. Of patients with any positive microbiological test result, a MODS culture was positive in 96% by 14 days and 100% by 21 days. The MODS culture simultaneously detected multidrug-resistant TB in 2 patients. Screening strategies involving combinations of clinical assessment, chest radiograph, and sputum smear were less effective than 2 liquid TB cultures in accurately diagnosing and excluding TB (P<.01). Screening strategies that included nonculture tests had poor sensitivity and specificity. CONCLUSIONS MODS culture identified and reliably excluded cases of pulmonary TB more accurately than other screening strategies, while providing results significantly faster than Lowenstein-Jensen culture. Streamlining of the ruling out of TB through the use of liquid culture-based strategies could help facilitate the massive up-scaling of IPT required to reduce HIV and TB morbidity and mortality.

Performance of an algorithm based on WHO recommendations for the diagnosis of smear‐negative pulmonary tuberculosis in patients without HIV infection

Objective  To evaluate the performance of an algorithm based on WHO recommendations for diagnosis of smear‐negative pulmonary tuberculosis in HIV‐negative patients.

Validation of a clinical-radiographic score to assess the probability of pulmonary tuberculosis in suspect patients with negative sputum smears.

Background Clinical suspects of pulmonary tuberculosis in which the sputum smears are negative for acid fast bacilli represent a diagnostic challenge in resource constrained settings. Our objective was to validate an existing clinical-radiographic score that assessed the probability of smear-negative pulmonary tuberculosis (SNPT) in high incidence settings in Peru. Methodology/Principal Findings We included in two referral hospitals in Lima patients with clinical suspicion of pulmonary tuberculosis and two or more negative sputum smears. Using a published but not externally validated score, patients were classified as having low, intermediate or high probability of pulmonary tuberculosis. The reference standard for the diagnosis of tuberculosis was a positive sputum culture in at least one of 2 liquid (MGIT or Middlebrook 7H9) and 1 solid (Ogawa) media. Prevalence of tuberculosis was calculated in each of the three probability groups. 684 patients were included. 184 (27.8%) had a diagnosis of pulmonary tuberculosis. The score did not perform well in patients with a previous history of pulmonary tuberculosis. In patients without, the prevalence of tuberculosis was 5.1%, 31.7% and 72% in the low, intermediate and high probability group respectively. The area under de ROC curve was 0.76 (95% CI 0.72–0.80) and scores ≥6 had a positive LR of 10.9. Conclusions/Significance In smear negative suspects without previous history of tuberculosis, the clinical-radiographic score can be used as a tool to assess the probability of pulmonary tuberculosis and to guide the decision to initiate or defer treatment or to requesting additional tests.

Evaluation of Clinical Prediction Rules for Respiratory Isolation of Inpatients with Suspected Pulmonary Tuberculosis

BACKGROUND In the framework of hospital infection control, various clinical prediction rules (CPRs) for respiratory isolation of patients with suspected pulmonary tuberculosis (PTB) have been developed. Our aim was to evaluate their performance in an emergency department setting with a high prevalence of PTB. METHODS We searched the MEDLINE and OVID databases to identify CPRs to predict PTB. We used a previously collected database containing clinical, radiographical, and microbiological information on patients attending an emergency department with respiratory complaints, and we applied each CPR to every patient and compared the result with culture for Mycobacterium tuberculosis as the reference standard. We also simulated the proportion of isolated suspects and missed cases for PTB prevalences of 5% and 30%. RESULTS We withheld 13 CPRs for evaluation. We had complete data on 345 patients. Most CPRs achieved a high sensitivity but very low specificity and very low positive predictive value. Mylottes score, which includes results of sputum smear as a predictive finding, was the best-performing CPR. It attained a sensitivity of 88.9% and a specificity of 63.9%. However, at a 30% PTB prevalence, 498 of 1000 individuals with suspected PTB would have to be isolated; 267 of these cases would be true PTB cases, and 33 cases would be missed. Two consecutive sputum smears had a sensitivity of 75.6% and a specificity of 99.7%. CONCLUSIONS In a setting with a high prevalence of PTB, only 1 of the 13 assessed CPRs demonstrated high sensitivity combined with satisfactory specificity. Our results highlight the need for local validation of CPRs before their application.

Análisis de costos de los métodos rápidos para diagnóstico de Tuberculosis multidrogorresistente en diferentes grupos epidemiológicos del Perú

Objectives.To evaluate the costs of three methods for the diagnosis of drug susceptibility in tuberculosis, and to compare the cost per case of Multidrug-resistant tuberculosis (MDR TB) diagnosed with these (MODS, GRIESS and Genotype MTBDR plus ®) in 4 epidemiologic groups in Peru. Materials and methods.In the basis of programmatic figures, we divided the population in 4 groups: new cases from Lima/Callao, new cases from other provinces, previously treated patients from Lima/Callao and previously treated from other provinces. We calculated the costs of each test with the standard methodology of the Ministry of Health, from the perspective of the health system. Finally, we calculated the cost per patient diagnosed with MDR TB for each epidemiologic group. Results. The estimated costs per test for MODS, GRIESS, and Genotype MTBDR plus® were 14.83. 15.51 and 176.41 nuevos soles respectively (the local currency, 1 nuevos sol=0.36 US dollars for August, 2011). The cost per patient diagnosed with GRIESS and MODS was lower than 200 nuevos soles in 3 out of the 4 groups. The costs per diagnosed MDR TB were higher than 2,000 nuevos soles with Genotype MTBDR plus ® in the two groups of new patients, and lower than 1,000 nuevos soles in the group of previously treated patients. Conclusions. In high-prevalence groups, like the previously treated patients, the costs per diagnosis of MDR TB with the 3 evaluated tests were low, nevertheless, the costs with the molecular test in the low- prevalence groups were high. The use of the molecular tests must be optimized in high prevalence areas.

Revisión sistemática de evaluaciones económicas de fármacos antivirales para el tratamiento de la hepatitis B crónica

Objective. To revise the available evidence on the cost-effectiveness of antiviral regimens for treatment of chronic hepatitis B. Material and methods. We performed a systematic revision on MEDLINE, LILACS NICE and COCHRANE databases, searching for economic evaluations of antiviral regimens for treatment of chronic hepatitis B. We included original studies, systematic revisions and management guidelines including information on the cost-effectiveness of this treatment. We registered the characteristics and results of the retrieved documents. Results. We obtained 29 original papers, 4 revision articles and 4 management guidelines. Most of these publications have been done in the last 5 years. There was conflict of interest in 73% of original articles, due to authors working for the pharmaceutical industry. 93% of articles that evaluate the cost-effectiveness of giving treatment for chronic hepatitis B against management of its complications find that it is indeed cost-effective to give antiviral treatment. 3/6 studies that evaluate lamivudine against other drugs find it as a dominant strategy, 3/5 find entecavir as the dominant strategy, 1/1 find tenofovir dominant, ¼ find conventional interferon as dominant and none of them find adefovir or pegylated interferon as dominant strategies. Conclusions. We consider that the available evidence suggests that to give antiviral treatment for chronic hepatitis B is a cost-effective intervention for many health systems, including ours. It has varying indexes of cost-effectiveness according to the evaluated regimens. Ideally , we should perform local economic evaluations in this issue.

Algorithm for the diagnosis of smear-negative pulmonary tuberculosis in high-incidence resource-constrained settings

Diagnosis of smear‐negative pulmonary tuberculosis (SNPT) remains a challenge, particularly in resource‐constrained settings. We evaluated a diagnostic algorithm that combines affordable laboratory tools and a clinical prediction rule (CPR).

Incremental yield of bronchial washing for diagnosing smear-negative pulmonary tuberculosis

OBJETIVO Avaliar o aumento do rendimento do diagnostico de tuberculose pulmonar mediante cultura de lavado bronquico em comparacao ao rendimento da cultura de escarro. METODOS Estudo realizado com 61 adultos da cidade de Lima, Peru, a partir de janeiro de 2006 a dezembro de 2007. Foi comparado o rendimento de culturas de escarro com o de esfregaco de bacilos acido-resistentes e cultura de amostras de lavado bronquico para diagnostico de tuberculose pulmonar, em casos suspeitos de tuberculose clinica, com esfregaco de escarro de bacilos acido-resistentes negativo. RESULTADOS Vinte e sete (IC95% 32;58) dos casos foram diagnosticados com tuberculose pulmonar de baciloscopia negativa. As amostras de lavabo bronquio detectaram 23 (95%; IC95% 72;99) dos casos de tuberculose pulmonar de baciloscopia negativa, comparados com 15 (IC95% 37;74) de cultura de escarro (p = 0.02). O diagnostico da tuberculose pulmonar mediante o uso do esfregaco de bacilos acido-resistentes e da cultura de lavado bronquico tiveram um rendimento adicional de 44% (IC95% 25;65) em relacao a cultura de escarro. CONCLUSOES Em funcao do contexto epidemiologico e dos recursos disponiveis, a broncoscopia deve ser adotada como parte de trabalho abrangente que otimize o diagnostico de tuberculose pulmonar de baciloscopia negativa e minimize riscos e custos.OBJECTIVE To assess the increased diagnostic yield for pulmonary tuberculosis using bronchial washing cultures compared with sputum cultures. METHODS Study conducted with 61 adults in Lima, Peru, from January 2006 to December 2007. The yield of sputum cultures was compared with the yield of acid-fast bacilli smears and cultures of bronchial washing for diagnosing pulmonary tuberculosis in suspected cases of clinical tuberculosis with negative acid fast bacilli sputum smears. RESULTS Twenty seven (95%CI 32;58) of the cases were eventually diagnosed with smear-negative pulmonary tuberculosis. Bronchial washing samples detected 23 (95%CI 72;99) of the smear-negative pulmonary tuberculosis cases compared with 15 (95%CI 37;74) for sputum cultures (p = 0.02). The incremental diagnostic yield of acid fast bacilli smear and culture of bronchial washing specimens over sputum culture was 44% (95%CI 25;65). CONCLUSIONS In function of the epidemiological context and the resources available, bronchoscopy should be deployed as part of a comprehensive work up that optimizes smear-negative pulmonary tuberculosis diagnosis and minimizes risk and costs.

Performance of clinical prediction rules for diagnosis of pleural tuberculosis in a high-incidence setting

Diagnosis of pleural tuberculosis (PT) is still a challenge, particularly in resource‐constrained settings. Alternative diagnostic tools are needed. We aimed at evaluating the utility of Clinical Prediction Rules (CPRs) for diagnosis of pleural tuberculosis in Peru.

Development of a clinical prediction rule for tuberculous meningitis in adults in Lima, Peru

Diagnosis of tuberculous meningitis (TM) is a challenge in countries with a high burden of the disease and constrained resources and clinical prediction rules (CPRs) could be of assistance. We aimed at developing a CPR for diagnosis of TM in a Latin American setting with high tuberculosis incidence and a concentrated HIV epidemic.