Determinants of tuberculosis diagnosis and the role of counselling.

OBJECTIVE: To study patient determinants that may affect completion of the diagnostic process in tuberculosis control, highlighting the role of counselling. DESIGN: Cross-sectional study. SUBJECTS: TB patients. SETTING: Rhodes Chest Clinic, Nairobi, City Council. RESULTS: Ninety five percent of the suspects delivered three sputum samples but only 27% consented to a HIV test; several determinants for none consenting were mentioned. On average US$2.27 was spent for one clinic visit and U.S. $8.62 for following the entire diagnostic process. Cost factors included transport, loss of income and food. CONCLUSION: Individual pre-test counselling seems important for obtaining three sputum specimens. It takes time and for settings with a large number of suspects, alternative methods may be required. To obtain consensus for a HIV test in a TB clinic is complicated. Costs spent on transport and loss in income are important determinants and may contribute to poor patient adherence to the diagnostic process.

The role and performance of chest X-ray for the diagnosis of tuberculosis: a cost-effectiveness analysis in Nairobi, Kenya.

BACKGROUND: The objective of this study was to establish 1) the performance of chest X-ray (CXR) in all suspects of tuberculosis (TB), as well as smear-negative TB suspects and 2) to compare the cost-effectiveness of the routine diagnostic pathway using Ziehl-Neelsen (ZN) sputum microscopy followed by CXR if case of negative sputum result (ZN followed by CXR) with an alternative pathway using CXR as a screening tool (CXR followed by ZN). METHODS: From TB suspects attending a chest clinic in Nairobi, Kenya, three sputum specimens were examined for ZN and culture (Lowenstein Jensen). Culture was used as gold standard. From each suspect a CXR was made using a four point scoring system: i: no pathology, ii: pathology not consistent for TB, iii: pathology consistent for TB and iv: pathology highly consistent for TB. The combined score i + ii was labeled as "no TB" and the combined score iii + iv was labeled as "TB". Films were re-read by a reference radiologist. HIV test was performed on those who consented. Laboratory and CXR costs were used to compare for cost-effectiveness. RESULTS: Of the 1,389 suspects enrolled, for 998 (72%) data on smear, culture and CXR was complete. 714 films were re-read, showing a 89% agreement (kappa value = 0.75 s.e.0.037) for the combined scores "TB" or "no-TB". The sensitivity/specificity of the CXR score "TB" among smear-negative suspects was 80%/67%. Using chest CXR as a screening tool in all suspects, sensitivity/specificity of the score "any pathology" was 92%, respectively 63%. The cost per correctly diagnosed case was for the routine process 8.72 dollars, compared to 9.27 dollars using CXR as screening tool. When costs of treatment were included, CXR followed by ZN became more cost-effective. CONCLUSION: The diagnostic pathway ZN followed by CXR was more cost-effective as compared to CXR followed by ZN. When cost of treatment was also considered CXR followed by ZN became more cost-effective. The low specificity of chest X-ray remains a subject of concern. Depending whether CXR was performed on all suspects or on smear-negative suspects only, 22%-45% of patients labeled as "TB" had a negative culture. The introduction of a well-defined scoring system, clinical conferences and a system of CXR quality control can contribute to improved diagnostic performance.

Cost-effectiveness of polymerase chain reaction versus Ziehl-Neelsen smear microscopy for diagnosis of tuberculosis in Kenya.

BACKGROUND: Laboratory services, particularly in large sub-Saharan cities, are overstretched, and it is becoming difficult both for patients and health staff to adhere to the diagnostic procedures for tuberculosis. Alternative techniques would be welcome. The polymerase chain reaction (PCR) has the potential to be cost-effective. We compared the cost-effectiveness of two diagnostic strategies, Ziehl-Neelsen (ZN) on three specimens followed by chest X-ray (CXR), and AMPLICOR MTB PCR on the first specimen only. METHODS: Three sputum samples were collected from tuberculosis (TB) suspects attending the Rhodes Chest Clinic, Nairobi. All samples were subjected to ZN, PCR and Löwenstein-Jensen culture used as gold standard. CXR was used to diagnose smear-negative TB. Cost analysis included health service and patient costs. RESULTS: Costs per correctly diagnosed case were US dollar 41 and dollar 67 for ZN and PCR, respectively. When treatment costs were included, including treatment of culture-negative cases, PCR was more cost-effective: dollar 382 vs. dollar 412. CONCLUSION: PCR may be an alternative in settings with many patients. PCR is patient friendly, CXR is not necessary and, unlike ZN, its performance is hardly affected by the human immunodeficiency virus. PCR can handle large numbers of specimens, with results becoming available on the same day.

Sex-specific performance of routine TB diagnostic tests.

SETTING: City Council Chest Clinic, Nairobi, Kenya. OBJECTIVE: To determine to what extent the performance of smear microscopy is responsible for sex differences in notification rates. METHODOLOGY: Three sputum samples from TB suspects were subjected to smear microscopy with Ziehl-Neelsen (ZN) and auramine (FM) staining. Lowenstein-Jensen culture was used as the gold standard. RESULTS: Of 998 suspects, 600 (60%) were men and 398 (40%) women. The odds of detecting culture-positive patients with ZN was lower for women (OR 0.67). By examining the first spot specimen, ZN detected 35% of culture-positive males and 26% of culture-positive females. These proportions increased to respectively 63% and 53% when examining three specimens, and to 79% and 74% when using FM. The sex difference reduced and became non-significant (P = 0.19) when adjusted for HIV; however, the numbers involved for HIV stratification were low. CONCLUSION: The performance of a diagnostic tool contributes to sex differences in notification rates and influences male/female ratios. Women were less likely to be diagnosed (P = 0.08), and when ZN was used they were less likely to be labelled as smear-positive TB (P < 0.01). The application of more sensitive diagnostic tools such as FM is to the advantage of women.

A comprehensive comparison of Ziehl-Neelsen and fluorescence microscopy for the diagnosis of tuberculosis in a resource-poor urban setting.

SETTING: Nairobi City Council Chest Clinic, Kenya. OBJECTIVES: To establish the efficiency, costs and cost-effectiveness of six diagnostic strategies using Ziehl-Neelsen (ZN) and fluorescence microscopy (FM). DESIGN: A cross-sectional study of 1398 TB suspects attending a specialised chest clinic in Nairobi subjected to three sputum examinations by ZN and FM. Lowenstein-Jensen culture was used as the gold standard. Cost analysis included health service and patient costs. RESULTS: Of 1398 suspects enrolled, 993 (71%) had a complete diagnostic work-up involving three sputum specimens for ZN and FM, culture and chest X-ray (CXR). Irrespective of whether ZN or FM was used on one, two or three smears, the overall diagnostic process detected 92% culture-positive cases. Different strategies affected the ratio of smear-positive to smear-negative TB; however, FM was more sensitive than ZN (P < 0.001). FM performance was not affected by the patient's HIV status. The cost per correctly diagnosed smear-positive case, including savings, was 40.30 US dollars for FM on two specimens compared to 57.70 US dollars for ZN on three specimens. CONCLUSION: The FM method used on one or two specimens is more cost-effective and shortens the diagnostic process. Consequently, more patients can be put on a regimen for smear-positive TB, contributing to improved treatment and reducing transmission.

A comprehensive study of the efficiency of the routine pulmonary tuberculosis diagnostic process in Nairobi.

Tuberculosis (TB) suspects from Rhodes Chest Clinic, Nairobi, Kenya, were subjected to three sputum smear microscopy (Ziehl-Neelsen) examinations and a chest X-ray (CXR). Results were compared with Löwenstein-Jensen culture as the gold standard to establish the efficiency of the routine diagnostic process. All laboratory tests and the CXR were available for 993 (71%) of the 1,398 enrolled suspects. Of these, 554 (56%) were culture-positive. The routine diagnostic process was very sensitive, able to detect 92% of culture-positive cases but missing 8%. The specificity was low (66%), and 23% of the patients started on treatment were culture-negative, mainly due to the low specificity of the CXR. It may be possible to increase the efficiency of the diagnostic process by specifying better criteria for CXR examination, improving the quality of CXR reading and counselling patients to return when complaints persist.

Cost-effectiveness of the polymerase chain reaction versus smear examination for the diagnosis of tuberculosis in Kenya: a theoretical model.

SETTING: A major out-patient tuberculosis clinic in Nairobi, Kenya. OBJECTIVE: To ascertain the cost-effectiveness of the polymerase chain reaction (PCR) for the diagnosis of tuberculosis in an urban setting in a developing country. DESIGN: A cost-effectiveness analysis of PCR and direct smear microscopy examination based on theoretical modelling. The cost-effectiveness was expressed in costs per correctly diagnosed tuberculosis patient for each of the two diagnostic techniques. Data were obtained from the literature, from the staff and the register at the health facility and from structured interviews with patients. Assumptions were made when no data were available. RESULTS: The PCR is expected to be more specific and sensitive than the routine procedure for diagnosis, but it is also more costly. The routine procedure based on direct smear microscopy turned out to be 1.8 times as cost-effective as PCR. CONCLUSION: It is concluded that the PCR method can potentially be a cost-effective screening procedure for tuberculosis, provided that the largest contributing cost component, the costs of the PCR-kit, can be reduced substantially.

Clinical and immunological markers in Kenyan pulmonary tuberculosis patients with and without HIV-1.

Amongst newly diagnosed pulmonary tuberculosis patients, 44% were co-infected with human immunodeficiency virus (HIV). Pulmonary tuberculosis patients with HIV-1 presented more frequently with lymphadenopathy and diarrhoea than those without HIV-1. Peripheral blood CD4+ counts were significantly lower in patients with pulmonary tuberculosis with HIV-1 than those with pulmonary tuberculosis alone, P = 0.0292. CD4+ lymphocyte counts, lymphadenopathy and BCG scar could serve as indicators of HIV-1 infection in pulmonary tuberculosis (PTB) patients.

PIP: 87 newly diagnosed pulmonary tuberculosis (PTB) patients at the Infectious Diseases Hospital, Nairobi, Kenya, were recruited into the study. Only patients with acid fast bacilli on stained smears of expectorated sputum were considered to have PTB. Cases were presumed PTB when a negative sputum smear was obtained in a patient with clinical and radiographic features consistent with PTB. Heparinized peripheral venous blood from each patient was tested for antibodies to HIV-1 with the Dupont HTLV 111 and the Wellcozyme Diagnostics ELISA. Only samples seropositive with both ELISAs were considered HIV-1 seropositive. T-lymphocyte subpopulation was separated from mononuclear cells by centrifugation on a Ficoll-Hypaque gradient. There were approximately equal numbers of males and females (25 males and 24 females) in the HIV-1 negative group but as many as 26 males compared to 12 females in the HIV-1 positive group. The sex ratio in the HIV-1 negative was M/F; 1:0.96 and M/F; 1:0.5 in the HIV-1 positive group. The mean age of patients with HIV-1 (33.4 +or- 7.22) was significantly higher than those without HIV-1 (28.70 +or- 11.20; p0.001). The overall prevalence of HIV-1 was 44%; higher in men (30%) than in women (14%). The hemoglobin (12.0 +or- 2.6 gm HIV-1 negative; 12.0 +or- 1.4.0 gm HIV-1 positive) and total lymphocyte counts (2451.6 +or- 1036.7/cubic mm HIV-1 negative; 2020.9 +or- 1258.6/cubic mm HIV-1 positive) were not significantly different between the 2 groups. However, the white blood cell count was significantly higher in HIV-1 seronegative group (7273.5 +or- 4700/cubic mm) than in the HIV-1 seropositive group (5094.8 +or- 3494/cubic mm); p0.05). Patients with HIV-1 presented more often with lymphadenopathy, diarrhea and weight loss, whereas cough and fever were as common in HIV-1 positive as HIV-1 negative patients. Even though CD3, CD4, and CD8 counts were significantly lower in HIV-1 positive patients, the ratio of CD4/CD8 was not significantly different between the 2 groups.