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.

Surveillance of drug-resistant tuberculosis and molecular evaluation of transmission of resistant strains in refugee and non-refugee populations in North-Eastern Kenya.

SETTING: Three refugee camp complex clinics and an adjacent non-refugee treatment centre in North-Eastern Kenya. OBJECTIVES: To use conventional and molecular epidemiology tools to determine: 1) the prevalence of drug resistance in newly diagnosed patients with smear-positive pulmonary tuberculosis in refugee and non-refugee populations; 2) risk factors for resistance in the two populations; and 3) whether IS6110 restriction fragment length polymorphism (RFLP) and spoligotyping showed similarities in DNA fingerprinting patterns of drug-resistant isolates that could infer transmission within and between the two populations. RESULTS: Of 241 isolates from the camps, 44 (18.3%) were resistant to one or more drugs, seven of which (2.9%) were multidrug-resistant TB (MDR-TB). Of 88 isolates from the non-refugees, five (5.7%) were resistant to one or more drugs without MDR-TB. Drug resistance was higher in the camps than in the non-refugee population (OR = 3.7; 95%CI 1.42-9.68; P < 0.007). Resistance was significantly higher in one camp compared with the other two, despite a comparable ethnic distribution. Unusually, females were more associated with drug resistance than their male counterparts in both populations (OR = 2.3; 95%CI 1.2-4.8; P = 0.008). There was evidence of transmission of streptomycin-resistant strains in the refugee population. DNA fingerprints of resistant strains from the non-refugee population were unique and different from those in the refugee camps. CONCLUSION: The observed high levels of drug resistance and MDR-TB, combined with evidence of transmission of strains resistant to streptomycin in the refugee population, suggest a need for strengthened TB control programmes in settings with a high risk of developing drug-resistant strains.

Tuberculosis and the HIV epidemic: increasing annual risk of tuberculous infection in Kenya, 1986-1996.

OBJECTIVES: The purpose of this study was to assess the impact of the increased incidence of tuberculosis (TB) due to HIV infection on the risk of TB infection in schoolchildren. METHODS: Tuberculin surveys were carried out in randomly selected primary schools in 12 districts in Kenya during 1986 through 1990 and 1994 through 1996. Districts were grouped according to the year in which TB notification rates started to increase. HIV prevalence in TB patients and changes in TB infection prevalence were compared between districts. RESULTS: Tuberculous infection prevalence rates increased strongly in districts where TB notification rates had increased before 1994 (odds ratio = 3.1, 95% confidence interval = 2.3, 4.1) but did not increase in districts where notification rates had increased more recently or not at all. HIV prevalence rates in TB patients were 50% in districts with an early increase in notification rates and 28% in the other study districts. CONCLUSIONS: Countries with an increasing prevalence of HIV infection will need additional resources for TB control, not only for current patients but also for the patients in additional cases arising from the increased risk of TB infection.

Altitude: a determinant for tuberculosis in Kenya?

OBJECTIVE: To determine to what extent tuberculosis incidence is associated with altitude. METHODS: Notification rates were obtained from all 41 districts in Kenya in the period 1988-1990; the mean altitude of each district was estimated. Data on indicators of socio-economic status such as literacy rate and infant mortality rate were obtained from the 1989 census, as well as data on other potential confounders such as urbanisation and median household size. RESULTS: The notification rate of new smear-positive tuberculosis was 32/100000 overall, varying between districts from 5 to 222/100000. Notification rates steeply reduced with increasing altitude (r = -0.71; 95% confidence interval [CI] -0.51 to -0.83). At altitudes of 1000 m or more the notification rates were less than 30% of those in districts at altitudes below 500 m, also after adjustment for confounding. CONCLUSION: Tuberculosis incidence in Kenya decreases strongly with increasing altitude. If the association is not due to unknown confounding factors, a range of potential biological explanations needs to be explored.

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.

Cost-effectiveness and total costs of three alternative strategies for the prevention and management of severe skin reactions attributable to thiacetazone in the treatment of Human Immunodeficiency Virus positive patients with tuberculosis in Kenya.

SETTING: Severe skin reactions due to thiacetazone (T) in Human Immunodeficiency Virus (HIV) positive tuberculosis patients have been reported in several publications, one of them from Kenya. However, the abandoning of T may not be feasible in Kenya as this may increase the cost of drugs by about three-fold per regimen. OBJECTIVE: To compare the cost-effectiveness and total cost of three strategies in which T is replaced with ethambutol (E). DESIGN: Three strategies are compared with a baseline strategy in which T is not replaced. The indicator for cost-effectiveness is the cost-per-averted-death attributable to T. RESULTS: Education of patients on the possibility of side-effects and replacement of T with E is the most cost-effective strategy at HIV prevalence rates of 1-90%. Abandonment of T and replacement with E is the most cost-effective at over 90% HIV prevalence. CONCLUSION: In Kenya, education of patients on the possibility of skin reactions should be preferred at low range HIV prevalence rates. Routine HIV testing would be the most attractive strategy in the middle range, and total replacement of T with E is to be preferred in the higher range of HIV prevalence.

PIP: In Kenya, the National Leprosy Tuberculosis Programme (NLTP) used previously reported data from Nairobi to compare the cost-effectiveness and total costs of a hypothetical strategy with three intervention strategies for the prevention and management of severe skin reactions caused by thiacetazone in treating HIV-positive patients with tuberculosis (TB). The hypothetical strategy was continued use of thiacetazone despite adverse skin reactions. The intervention strategies included patient education about possible side effects of anti-TB drugs (discontinue use if skin rash develops, report situation to clinic, replace thiacetazone with ethambutol when other skin diseases have been excluded), abandonment of thiacetazone and replacement with ethambutol, and HIV testing and pre- and post-test counseling. NLTP currently used the education strategy. It assumed a mortality rate of 5%. When the HIV prevalence rate is 1-90%, the education strategy is the most cost-effective strategy. In terms of total costs, the education strategy was also the most inexpensive strategy regardless of the HIV prevalence. At an HIV prevalence rate greater than 65%, the abandonment of thiacetazone strategy was the cheapest strategy. When the assumed mortality rate was 3%, the cost per averted death for the education strategy was reduced from about US$120 to about US$80 and the education strategy became the most cost-effective strategy over the entire range of HIV prevalence. In addition, the cost of HIV testing significantly increased the cost per averted death. Thus, the findings of this study are truly sensitive to different program conditions. Based on these findings, the authors recommended that the education strategy be applied with a range of HIV prevalence of 1-45%, that HIV testing be applied with a range of 46-72%, and that total abandonment be applied with an HIV prevalence greater than 72%.