Elsevier

The Lancet

Volume 369, Issue 9578, 16–22 June 2007, Pages 2042-2049
The Lancet

Public Health
Diagnosis of smear-negative pulmonary tuberculosis in people with HIV infection or AIDS in resource-constrained settings: informing urgent policy changes

https://doi.org/10.1016/S0140-6736(07)60284-0Get rights and content

Summary

The HIV epidemic has led to large increases in the frequency of smear-negative pulmonary tuberculosis, which has poor treatment outcomes and excessive early mortality compared with smear-positive disease. We used a combination of systematic review, document analysis, and global expert opinion to review the extent of this problem. We also looked at policies of national tuberculosis control programmes for the diagnosis of smear-negative pulmonary tuberculosis to assess their coverage, identify the diagnostic difficulties, and find ways to improve the diagnosis of this type of tuberculosis, with a focus on resource-constrained settings with high HIV infection rates. We propose that the internationally recommended algorithm for the diagnosis of smear-negative pulmonary tuberculosis should be revised to include HIV status, severity of AIDS and tuberculosis, and early use of chest radiography in the decision tree. Increased use of promising methods of diagnosis such as sputum liquefaction and concentration and increased availability of fluorescence microscopy should be explored and encouraged. Culturing of sputum in resource-constrained settings with high HIV infection rates should also be encouraged, existing facilities should be made full use of and upgraded, and effective quality-assurance systems should be used. Innovative ways to address human resources issues involved in addressing the diagnostic difficulties are also needed. The development of rapid, simple, and accurate tuberculosis diagnostic tools with applicability at point of care and remote location is essential. To achieve these goals, greater political commitment, scientific interest, and investment are needed.

Section snippets

Frequency of smear-negative pulmonary tuberculosis

Of the 120 reports reviewed and assessed for inclusion in this review, only 15 studies met the selection criteria. All included studies were institution-based and the purpose of most (11/15) studies was to describe the pattern of HIV prevalence in tuberculosis patients, although one study described the cause of lower-respiratory-tract infections in HIV-positive patients. In the remaining three studies the distribution of type of tuberculosis in HIV-positive patients was obtained from secondary

Algorithms for diagnosis

As much as possible, patients should be correctly diagnosed and treated for smear-negative pulmonary tuberculosis, but treatment of those without the disease should be avoided. Many countries adapted the WHO guidelines6 and included an algorithm for the diagnosis of smear-negative pulmonary tuberculosis in their national guidelines. Table 2 compares diagnostic algorithms of selected countries. Examination of up to nine sputum smears is recommended before the diagnosis of smear-negative

Smear microscopy for acid-fast bacteria

Microscopy for the detection of acid-fast bacilli is rapid, low cost, and specific and detects the most infectious cases of tuberculosis, but needs maintenance of equipment, consistent supply of reagents, and proper training in interpretation of the slides.37 For a smear to be positive, there must be at least 5000–10 000 acid-fast bacilli per mL sputum, but these bacilli could be released only intermittently from cavities. The overall positive rate of a single smear microscopy ranges between

What needs to be done?

There is an urgent need to develop rapid, simple, and accurate tuberculosis diagnostic tools. Although such tests are under development and validation, policy and clinical practice should be modified to improve the diagnosis and management of smear-negative pulmonary tuberculosis. Rapid diagnosis and treatment of smear-negative pulmonary tuberculosis in settings with high HIV prevalence are important73 because the HIV epidemic is driving a large increase in the proportion of patients with

Conclusion

Extensive basic research to develop rapid, simple, and accurate tuberculosis diagnostic tools that can be used in laboratories and remote locations is essential. Increased political commitment, greater scientific interest, and massive investment are needed. At the same time, innovative means need to be sought to address the human resources issues in the diagnosis problem, such as strategic efforts to train adequate and efficient laboratory staff at all levels. Strong advocacy and activism

Search strategy and selection criteria

We used a combination of systematic review, document analysis, and global expert opinion to prepare this paper. We searched PubMed for combinations of the search terms “tuberculosis” and “HIV” with “pulmonary”, “smear negative”, and “diagnosis”. We included reports of studies published in English, between 1985, and May, 2005. 120 reports were reviewed and assessed by one investigator (HG) for appropriateness for inclusion. Studies were included in the review if they reported on tuberculous

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