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
Public HealthDiagnosis of smear-negative pulmonary tuberculosis in people with HIV infection or AIDS in resource-constrained settings: informing urgent policy changes
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
References (76)
- et al.
Negative sputum smear results in HIV-positive patients with pulmonary tuberculosis in Lusaka, Zambia
Tuber Lung Dis
(1993) - et al.
Transmission of Mycobacterium tuberculosis from patients smear-negative for acid-fast bacilli
Lancet
(1999) - et al.
Lung diseases at necropsy in African children dying from respiratory illnesses: a descriptive necropsy study
Lancet
(2002) - et al.
Clinical diagnosis of smear-negative pulmonary tuberculosis in low-income countries: the current evidence
Lancet Infect Dis
(2003) - et al.
Cross-sectional survey of HIV infection among patients with tuberculosis in Nairobi, Kenya
Tuber Lung Dis
(1992) - et al.
Sputum concentration improves diagnosis of tuberculosis in a setting with a high prevalence of HIV
Trans R Soc Trop Med Hyg
(2000) - et al.
Sputum processing methods to improve sensitivity of smear microscopy for tuberculosis: a systematic review
Lancet Infect Dis
(2006) - et al.
Fluorescence versus conventional sputum smear microscopy for tuberculosis: a systematic review
Lancet Infect Dis
(2006) - et al.
Tuberculosis
Lancet
(2003) - et al.
Unrecognised Mycobacterium tuberculosis bacteraemia among hospital inpatients in less developed countries
Lancet
(1999)
Unrecognised Mycobacterium tuberculosis
Lancet
Interferon-gamma assays in the immunodiagnosis of tuberculosis: a systematic review
Lancet Infect Dis
Diagnosis of tuberculosis in South African children with a T-cell-based assay: a prospective cohort study
Lancet
Global tuberculosis control: surveillance, planning, financing
A review of the diagnosis and treatment of smear-negative pulmonary tuberculosis
Int J Tuberc Lung Dis
An approach to the problems of diagnosing and treating adult smear-negative pulmonary tuberculosis in high-HIV-prevalence settings in sub-Saharan Africa
Bull World Health Organ
‘Smear-negative’ pulmonary tuberculosis in a DOTS programme: poor outcomes in an area of high HIV seroprevalence
Int J Tuberc Lung Dis
Tuberculosis case fatality rates in high HIV prevalence populations in sub-Saharan Africa
AIDS
Treatment of Tuberculosis: guidelines for national programmes
TB/HIV research priorities in resource limited settings: report of an expert consultation WHO/HTM/TB/2005.355 and WHO/HIV/2005.3
HIV infection in patients with tuberculosis in Kinshasa, Zaire
Am Rev Respir Dis
The impact of HIV on the usefulness of sputum smears for the diagnosis of tuberculosis
Am J Public Health
Long-term outcome in patients registered with tuberculosis in Zomba, Malawi: mortality at 7 years according to initial HIV status and type of TB
Int J Tuberc Lung Dis
The scourge of HIV-related tuberculosis: a cohort study in a district general hospital in Malawi
Ann Trop Med Parasitol
Evaluation of outpatients with suspected pulmonary tuberculosis in a high HIV prevalence setting in Ethiopia: clinical, diagnostic and epidemiological characteristics
Scand J Infect Dis
Integration of tuberculosis screening at an HIV voluntary counselling and testing centre in Haiti
Aids
Seroprevalence of human immunodeficiency virus (HIV) infection among tuberculosis patients in Tamil Nadu
Indian J Med Res
Trend in HIV prevalence among tuberculosis patients in Tanzania, 1991–1998
Int J Tuberc Lung Dis
Pulmonary tuberculosis in HIV-infected patients presenting with normal chest radiograph and negative sputum smear
Infection
The epidemiological profile of tuberculosis in southern Brazil in times of AIDS
Int J Tuberc Lung Dis
Voluntary counselling, HIV testing and sexual behaviour among patients with tuberculosis in a rural district of Malawi
Int J Tuberc Lung Dis
Causes of lower respiratory infection in HIV-infected Ugandan adults who are sputum AFB smear-negative
Int J Tuberc Lung Dis
HIV and tuberculosis coinfection in the southern region of Ethiopia: a prospective epidemiological study
Scand J Infect Dis
Tuberculosis in children with human immunodeficiency virus infection
Int J Tuberc Lung Dis
Pathology and causes of death in a group of 128 predominantly HIV-positive patients in Botswana, 1997–1998
Int J Tuberc Lung Dis
Autopsy study of HIV-1-positive and HIV-1-negative adult medical patients in Nairobi, Kenya
J Acquir Immune Defic Syndr
Clinical diagnosis of mycobacterial diseases versus autopsy findings in 350 patients with AIDS
Eur J Clin Microbiol Infect Dis
How can detection of infectious tuberculosis be improved? Experience in the Somali region of Ethiopia
Int J Tuberc Lung Dis
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