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

OBJECTIVES: 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). METHODS: We derived, based on published evidence, a diagnostic algorithm for SNPT. Sputum concentration constitutes its first step. In suspects with negative results, SNPT probability is classified with a CPR as low (excluded), high (confirmed) or intermediate. For intermediate patients, sputum Middlebrook 7H9 liquid culture is performed, and they are assessed after 2 weeks. If clinically deteriorated, with still negative liquid culture, bronchoscopy is offered. Otherwise, results of Middlebrook 7H9 culture are awaited. We prospectively evaluated this algorithm against a reference standard of solid and liquid cultures in two reference hospitals in Lima, Peru. RESULTS: 670 SNPT suspects were included from September 2005 to March 2008. The prevalence of SNPT was 27% according to the reference standard. The algorithm's overall accuracy was 0.94 (95% CI 0.91-0.95), its sensitivity was 0.88 (95% CI 0.82-0.92) and its specificity, 0.96 (95% CI 0.94-0.98). Sputum concentration, the CPR, Middlebrook 7H9 sputum culture and bronchoscopic samples defined a diagnosis of SNPT according to the algorithm in 57 (37%), 25 (16%), 63 (41%) and 8(5%) of patients, respectively. 65% of patients were diagnosed within 3 weeks. CONCLUSIONS: The algorithm was accurate for SNPT diagnosis. Sputum concentration, CPR and selective Middlebrook 7H9 culture are essential components.

Diagnostic work-up and loss of tuberculosis suspects in Jogjakarta, Indonesia.

BACKGROUND: Early and accurate diagnosis of pulmonary tuberculosis (TB) is critical for successful TB control. To assist in the diagnosis of smear-negative pulmonary TB, the World Health Organisation (WHO) recommends the use of a diagnostic algorithm. Our study evaluated the implementation of the national tuberculosis programme's diagnostic algorithm in routine health care settings in Jogjakarta, Indonesia. The diagnostic algorithm is based on the WHO TB diagnostic algorithm, which had already been implemented in the health facilities. METHODS: We prospectively documented the diagnostic work-up of all new tuberculosis suspects until a diagnosis was reached. We used clinical audit forms to record each step chronologically. Data on the patient's gender, age, symptoms, examinations (types, dates, and results), and final diagnosis were collected. RESULTS: Information was recorded for 754 TB suspects; 43.5% of whom were lost during the diagnostic work-up in health centres, 0% in lung clinics. Among the TB suspects who completed diagnostic work-ups, 51.1% and 100.0% were diagnosed without following the national TB diagnostic algorithm in health centres and lung clinics, respectively. However, the work-up in the health centres and lung clinics generally conformed to international standards for tuberculosis care (ISTC). Diagnostic delays were significantly longer in health centres compared to lung clinics. CONCLUSIONS: The high rate of patients lost in health centres needs to be addressed through the implementation of TB suspect tracing and better programme supervision. The national TB algorithm needs to be revised and differentiated according to the level of care.

High prevalence of primary multidrug resistant tuberculosis in persons with no known risk factors.

INTRODUCTION: In high multidrug resistant (MDR) tuberculosis (TB) prevalence areas, drug susceptibility testing (DST) at diagnosis is recommended for patients with risk factors for MDR. However, this approach might miss a substantial proportion of MDR-TB in the general population. We studied primary MDR in patients considered to be at low risk of MDR-TB in Lima, Peru. METHODS: We enrolled new sputum smear-positive TB patients who did not report any MDR-TB risk factor: known exposure to a TB patient whose treatment failed or who died or who was known to have MDR-TB; immunosuppressive co-morbidities, ex prison inmates; prison and health care workers; and alcohol or drug abuse. A structured questionnaire was applied to all enrolled participants to confirm the absence of these factors and thus minimize underreporting. Sputum from all participants was cultured on Löwenstein-Jensen media and DST for first line drugs was performed using the 7H10 agar method. RESULTS: Of 875 participants with complete data, 23.2% (203) had risk factors for MDR-TB elicited after enrolment. Among the group with no reported risk factors who had a positive culture, we found a 6.3% (95%CI 4.4-8.3) (37/584) rate of MDR-TB. In this group no epidemiological characteristics were associated with MDR-TB. Thus, in this group, multidrug resistance occurred in patients with no identifiable risk factors. CONCLUSIONS: We found a high rate of primary MDR-TB in a general population with no identifiable risk factors for MDR-TB. This suggests that in a high endemic area targeting patients for MDR-TB based on the presence of risk factors is an insufficient intervention.

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.

[Tuberculosis incidence strata in Cuban municipalities: 1999-2002 and 2003-2006]. / Estratos de incidencia de tuberculosis en los municipios de Cuba: 1999-2002 y 2003-2006.

OBJECTIVE: identify Cuban municipalities with high, medium, and low incidence of tuberculosis (TB), compare incidence rates for the periods 1999-2002 and 2003-2006, and analyze distribution of the disease by population density and economic activity. METHODS: TB incidence was calculated by municipality, confidence interval (95%), and the percentage of variation for the defined strata according to population density and the predominant economic activity. The municipalities were divided into three categories based on incidence (> 10 per 100 000; > 5 per 100 000 to < 10 per 100 000, and < 5 per 100 000), and maps were plotted. RESULTS: the proportion of municipalities with an incidence of < 5 per 100 000 rose from 35.5% to 57.4% between the two periods, while the proportion of municipalities with an incidence of > 10 per 100 000 fell from 22.5% to 5.9%. National incidence fell by 28.7%-from 8.7 per 100 000 in 1999-2002 to 6.2 in 2003-2006. Municipalities that were not very densely populated and where agricultural activities predominated showed significant reductions in incidence. The rates in densely populated municipalities devoted primarily to industrial and service activities are still high. CONCLUSIONS: TB incidence is gradually and sustainably declining in the majority of municipalities. Differentiated strategies are needed to reduce TB incidence rates in municipalities where they continue to be relatively high.

Estratos de incidencia de tuberculosis en los municipios de Cuba: 1999-2002 y 2003-2006 / Tuberculosis incidence strata in Cuban municipalities: 1999-2002 and 2003-2006

OBJETIVO: Identificar los municipios cubanos de alta, mediana y baja incidencia de tuberculosis (TB), comparar las tasas de incidencia de los períodos 1999-2002 y 2003-2006, y analizar la distribución de la enfermedad según la densidad poblacional y la actividad económica. MÉTODOS: Se calculó la incidencia de TB por municipios, el intervalo de confianza (95 por ciento) y el porcentaje de variación para los estratos definidos según la densidad demográfica y la actividad económica predominante. Los municipios fueron divididos en tres categorías según su incidencia (> 10 por 100 000; > 5 por 100 000 a < 10 por 100 000, y < 5 por 100 000) y se realizaron mapas temáticos. RESULTADOS: La proporción de municipios con una incidencia < 5 por 100 000 aumentó de 35,5 por ciento a 57,4 por ciento entre ambos períodos, mientras que la proporción de municipios con incidencia > 10 por 100 000 disminuyó de 22,5 por ciento a 5,9 por ciento. La incidencia nacional cayó 28,7 por ciento -de 8,7 por 100 000 en 1999-2002, a 6,2 en 2003-2006. Los municipios no muy densamente poblados y dedicados principalmente a actividades agropecuarias registraron disminuciones de incidencia significativas. Todavía siguen altas las tasas de los municipios densamente poblados y dedicados a la industria y los servicios. CONCLUSIONES: La incidencia de TB disminuye sostenida y progresivamente en la mayoría de los municipios. Se necesitan estrategias diferenciadas para reducir las tasas de incidencia de TB en los municipios donde siguen siendo relativamente altas.

OBJECTIVE: Identify Cuban municipalities with high, medium, and low incidence of tuberculosis (TB), compare incidence rates for the periods 1999-2002 and 2003-2006, and analyze distribution of the disease by population density and economic activity. METHODS: TB incidence was calculated by municipality, confidence interval (95 percent), and the percentage of variation for the defined strata according to population density and the predominant economic activity. The municipalities were divided into three categories based on incidence (> 10 per 100 000; > 5 per 100 000 to < 10 per 100 000, and < 5 per 100 000), and maps were plotted. RESULTS: The proportion of municipalities with an incidence of < 5 per 100 000 rose from 35.5 percent to 57.4 percent between the two periods, while the proportion of municipalities with an incidence of > 10 per 100 000 fell from 22.5 percent to 5.9 percent. National incidence fell by 28.7 percent-from 8.7 per 100 000 in 1999-2002 to 6.2 in 2003-2006. Municipalities that were not very densely populated and where agricultural activities predominated showed significant reductions in incidence. The rates in densely populated municipalities devoted primarily to industrial and service activities are still high. CONCLUSIONS: TB incidence is gradually and sustainably declining in the majority of municipalities. Differentiated strategies are needed to reduce TB incidence rates in municipalities where they continue to be relatively high.

Outcomes after chemotherapy with WHO category II regimen in a population with high prevalence of drug resistant tuberculosis.

Standard short course chemotherapy is recommended by the World Health Organization to control tuberculosis worldwide. However, in settings with high drug resistance, first line standard regimens are linked with high treatment failure. We evaluated treatment outcomes after standardized chemotherapy with the WHO recommended category II retreatment regimen in a prison with a high prevalence of drug resistant tuberculosis (TB). A cohort of 233 culture positive TB patients was followed through smear microscopy, culture, drug susceptibility testing and DNA fingerprinting at baseline, after 3 months and at the end of treatment. Overall 172 patients (74%) became culture negative, while 43 (18%) remained positive at the end of treatment. Among those 43 cases, 58% of failures were determined to be due to treatment with an inadequate drug regimen and 42% to either an initial mixed infection or re-infection while under treatment. Overall, drug resistance amplification during treatment occurred in 3.4% of the patient cohort. This study demonstrates that treatment failure is linked to initial drug resistance, that amplification of drug resistance occurs, and that mixed infection and re-infection during standard treatment contribute to treatment failure in confined settings with high prevalence of drug resistance.

Pulmonary tuberculosis case detection through fortuitous cough screening during home visits.

OBJECTIVE: To compare the yield of active tuberculosis (TB) case detection among risk groups during home visits with passive detection among patients at health services. METHODS: In April 2004, in a first phase, we introduced, active screening for coughing among all family members of patients that were visited at home by their family doctor or nurse for other reasons. Subsequently, from October 2004 onwards, active screening was restricted to family members belonging to groups at risk of TB. RESULTS: The overall detection rate of TB increased from 6.7/100,000 during passive detection at health services before the intervention to 26.2/100,000 inhabitants when passive detection was complemented by active case finding. Active screening among risk groups yielded 35 TB cases per 1000 persons screened compared to 20 TB cases per 1000 persons passively screened at health services. Active case finding was particularly efficient in those coughing for 3 weeks or more (107/1000 screened). CONCLUSION: This study demonstrates that active case finding in groups at risk during home visits increases the case detection rate in the population and permits the identification of cases that may not be detected through passive case finding at health facility level.

Integrating tuberculosis and HIV care in the primary care setting in South Africa.

BACKGROUND: In many countries including South Africa, the increasing human immunodeficiency virus (HIV) and tuberculosis (TB) epidemics have impacted significantly on already weakened public health services. This paper reviews the scope, process and performance of the HIV and TB services in a primary care setting where antiretroviral therapy is provided, in Khayelitsha, South Africa, in order to assess whether there is a need for some form of integration. METHODS: The scope and process of both services were assessed through observations of the service and individual and group interviews with key persons. The performance was assessed by examining the 2001-2002 reports from the health information system and clinical data. RESULTS: The TB service is programme oriented to the attainment of an 85% cure rate amongst smear-positive patients while the HIV service has a more holistic approach to the patient with HIV. The TB service is part of a well-established programme that is highly standardized. The HIV service is in the pilot phase. There is a heavy load at both services and there is large degree of cross-referral between the two services. There are lessons that can be learnt from each service. There is an overlap of activities, duplication of services and under-utilization of staff. There are missed opportunities for TB and HIV prevention, diagnosis and management. CONCLUSIONS: The study suggests that there may be benefits to integrating HIV and TB services. Constraints to this process are discussed.

Strong general health care systems: a prerequisite to reach global tuberculosis control targets.

We argue that tuberculosis control cannot reach its proposed global targets without investment in an adequate network of accessible, effective and comprehensive health services. Lessons from the past are reviewed. They underscore that passive case-detection and adequate case management is the central technical strategy for tuberculosis control. There is no compelling evidence to support active case-detection in the general population. We elaborate on why a strong health care system is a prerequisite in the framework of case-detection and treatment. The necessity to improve quality and accessibility of general health services for ensuring early detection and subsequent cure is demonstrated. It is argued why the need for strong public health care system becomes even more eminent in the light of the tuberculosis/HIV dual epidemics and of the rapid growth of unregulated private-for-profit services. We finally examine the financial gaps for tuberculosis control and discuss the need for allocating more resources to the strengthening of general health care systems.

Decentralization of the DOTS programme within a Russian penitentiary system. How to ensure the continuity of tuberculosis treatment in pre-trial detention centres.

BACKGROUND: In Kemerovo region (Siberia), three pre-trial detention centres (SIZO; Ministry of Justice) serve as the gateway to the penitentiary system, comprised of 23 prisons and 30,000 detainees. The follow-up for tuberculosis (TB) patients released into civil society is unreliable. Due to varying detention times and frequent transfers to temporary detention centres (IVS; Ministry of Internal Affairs) for investigation and trial, and concerns about continuity of treatment, SIZOs were not included in the revised TB control programme initiated during 1996. METHODS: To investigate the feasibility of DOTS (Directly Observed Therapy, Short-Course) expansion into SIZOs, general detainee release was studied by examining 10% of files from detainees admitted during 1998 (SIZOs 1,2,3). Then, 5% of general files from SIZO 1 were examined to determine SIZO-IVS flow; 224 TB patient files from SIZO 3 were evaluated to determine the pattern of release/transfer. RESULTS: TB patients in SIZO 3 have less chance of release before six months of detention than non-TB detainees (14/224, 6.3% versus 774/2276, 34%; p < 0.001). Among detainees not released, 60% are not moved during the first six months of detention. For those who move, the mean stay in IVS was 9.5 (+/- 6) days. The incidence of active disease detected upon entry to SIZO 3 was 4,560/100,000, the subsequent rate during the same year of detention 880/100,000. CONCLUSION: Despite frequent detainee movements between institutions, DOTS should be introduced into the earliest stages of detention to prevent case mismanagement, and links to the civilian programme should be developed.