Summary:

Smear-negative pulmonary tuberculosis (SNPTB) is a problem, both for clinicians and for tuberculosis programme managers. This research project approaches SNPTB from three different perspectives: the laboratory perspective, by testing the feasibility of more valid and efficient methods for quality assurance of smear-microscopy; the clinical perspective, by testing the clinical audit cycle as a method to improve the quality management of smear-negative tuberculosis suspects and the validity of diagnostic work-up; and the health service organisation perspective, in relation to (de)centralisation of different elements of the diagnosis of smear-negative tuberculosis. This study will contrast high and low incidence, centralised and decentralised, and urban and rural settings. HIV-related aspects will be examined and special emphasis will be given to the operationalisation and dissemination of study findings.

Objectives:

The general objective is to evaluate three different strategies to improve the diagnosis of smear-negative pulmonary tuberculosis in South America. The specific objectives are:

1) Laboratory strategy: to test novel approaches for quality assurance of direct smear microscopy, in both low-incidence, and high-incidence countries
2) Clinical strategy: to evaluate the improvement in the clinical management of smear-negative TB suspects and TB patients that can be reached through the audit cycle of the existing procedures, for both HIV-infected, and HIV-uninfected patients
3) Health system strategy: to study the effects of extensive (de)centralisation of microscopy diagnosis, in both high and low TB incidence countries, and to identify the level of health services where the different diagnostic elements should be performed to guarantee adequate suspect management and laboratory quality control.

Description:

The diagnosis of pulmonary TB in developing countries relies primarily on direct microscopic examination of sputum smears. The sensitivity of this method is limited as few countries have implemented a rigorous quality assurance network. These factors result in a high number of so-called 'TB suspects' who are smear-negative. This is aggravated by the HIV pandemic, which is on the rise in Latin America. To tackle the complex problem of smear-negative pulmonary TB, one has to adapt a systems view and address the quality of microscopy examinations, as well as the quality of the clinical management of these smear-negative TB suspects and the level of (de)centralisation of diagnostic services. After a baseline assessment of the quality of diagnosis, three possible intervention strategies will be examined: a novel quality assurance method for smear microscopy, the clinical audit cycle and a strategy optimising health service organisation-related aspects. A cohort study on TB-HIV co-infection will address specific HIV related issues of the diagnostic process. The exploitable results will be:

1) Laboratory strategy: report on quality assurance method leading to an improved design, which will feed into an international TB control strategy
2) Clinical strategy: a handbook of procedures relating elements leading to process improvement

3) Health system strategy: a policy document on adequate level of centralisation/decentralisation in terms of diagnosis.

The final report of this study is expected to draw the synthesis of the three axes, and to result in a policy document for decision makers in TB control, as well as a R&D strategy.

Milestones:

a) International workshops (in months 3, 24 and 33) for protocol standardisation, sharing research findings and to assure dissemination.
b) Baseline indicators of diagnostic performance (month 12).
c) Framework for the assessment of quality of diagnostic care (month 6) and monitoring progress towards targets.
d) Context-sensitive (TB incidence, HS development, HIV prevalence) recommendations for efficient and valid QA of sputum microscopy, implementation of audit cycles and (de)centralisation of diagnosis.

Coordinator:

Partners:

Nº	Principal Scientific Participants	Official Address	Other Information
2	Antonio y Espada Faustino Torrico	IIBISMED – Universidad Mayor de San Simon Facultad de Medicine Av. Aniceto Arce N° 0371 Casilla 3119 – Cochabamba Bolivia	Tel: +591 42 31508 / 23206 Fax: +591 42 31690 E-mail: daespadat@hotmail.com ftorrico@med.umss.edu.bo
3	Eduardo y Gotuzzo Tine Verdonck	Instituto de Medicina Tropical Alexander von Humboldt Universidad Peruana Cayetano Heredia Departemento de Enfermedades Transmisibles y Dermatologicas AP 4314 Av. Honokio Delgado 430 - Urb. Ingenieria SMP Lima 100 Peru	Tel: +51 1 482 3910 Fax: +51 1 482 3404 E-mail: egh@upch.edu.pe verweven@amata.rcp.net.pe
4	Edilberto González Ochoa	Instituto ‘Pedro Kourí’ Grupo de Investigación y Vigilancia de TB e IRA PO Box 601 Marianao 13 La Habana Cuba	Tel: +53 7 202 0652 / 24 6664 Fax: +53 7 204 6051 / 220633 E-mail: ochoa@ipk.sld.cu
5	John D.Walley	Nuffield Institute for Health Senior Lecturer in Public Health TB Research Programme Director International Division, 71-75 Clarendon Rd, UK-LS2 9PL Leeds United Kingdom	Tel: +44 113 233 6963 Fax: +44 113 233 6997 E-mail: j.d.walley@leeds.ac.uk