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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.

In sub-Saharan Africa, respiratory tract infections (RTI) are the leading cause of serious morbidity and mortality in HIV-infected persons. This study sought to investigate demographic, socioeconomic, and environmental risk factors for pneumonia in a cohort of HIV-infected women. The authors performed a nested case-control study in a cohort of HIV-1-infected adults followed in Nairobi, Kenya. Thirty-nine women who developed pneumonia during the follow-up period were selected as cases, and 66 women who did not develop pneumonia were randomly chosen to serve as control subjects. A questionnaire was administered in subjects' homes that assessed demographics, home environment, and socioeconomic status. Women were followed in the cohort for a median of 36.8 months (range, 27.3-39.3). Adjusting for length of follow-up period, factors associated with lower socioeconomic status (lower monthly spending [OR = 3.2; 95% CI, 1.2-8.4 per 10,000 Kenyan shilling decrease], having no savings [OR = 4.1; 95% CI, 1.4-11.9], less sturdy home construction material such as mud or cement walls [OR = 2.6; 95% CI, 1.1-5.9] or dirt floors [OR = 2.8; 95% CI, 1.0-7.6], and lack of a window in the home [OR = 5.5; 95% CI, 0.9-32.2]) and being widowed (OR = 4.3; 95% CI, 1.2-15.1) or single (OR = 3.3; 95% CI, 1.0-11.2) were associated with an increased risk of pneumonia. In multivariate analysis, widowed (AOR = 5.9; 95% CI, 1.3-26.3), single (AOR = 7.7; 95% CI, 1.6-36.4), and divorced (AOR = 4.5; 95% CI, 1.0-20.1) women, those without savings (AOR = 3.7; 95% CI, 1.2-11.7), and those living in more crowded and contagious conditions (AOR = 1.5; 95% CI, 1.1-2.1) remained at increased risk of pneumonia. If confirmed by prospective investigation, these findings could help identify persons and subpopulations of HIV-infected women with the greatest risk of pneumonia.

To evaluate the WHO (World Health Organization) algorithm for management of respiratory tract infection (RTI) in HIV-1-infected adults and determine risk factors associated with RTI, we enrolled a cohort of 380 HIV-1-seropositive adults prospectively followed for incident RTI at an outpatient clinic in Nairobi, Kenya. RTI was diagnosed when patients presented with history of worsening or persistent cough. Patients were treated with ampicillin, or antituberculosis therapy when clinically indicated, as first-line therapy and with trimethoprim/sulfamethoxazole as second-line therapy. Five hundred ninety-seven episodes of RTI were diagnosed: 177 of pneumonia and 420 of bronchitis. The WHO RTI algorithm was used for 401 (95%) episodes of bronchitis and 151 (85%) episodes of pneumonia (p <.001). Three percent of bronchitis cases versus 32% of pneumonia cases failed to respond to first-or second-line treatment (p <.0001). Being widowed (adjusted odds ratio [OR] = 2.1, 95% confidence interval [CI]: 1.0-4.4), less than 8 years of education (adjusted OR = 2.5, CI: 1.5 - 4.1), and CD4 count < 200 cells/microl (adjusted OR = 2.4, CI: 1.4-3.9) were risk factors for pneumonia. A high percentage of patients (32%) with pneumonia required a change in treatment from that recommended by the WHO guidelines. Randomized trials should be performed to determine more appropriate treatment strategies in HIV-1-infected individuals.

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.

Objectives: To determine the efficacy of isoniazid 300 mg daily for 6 months in the prevention of tuberculosis in HIV-1-infected adults and to determine whether tuberculosis preventive therapy prolongs survival in HIV-1-infected adults., Design and Setting: Randomized, double-blind, placebo-controlled trial in Nairobi, Kenya., Subjects: Six hundred and eighty-four HIV-1-infected adults., Main Outcome Measures: Development of tuberculosis and death., Results: Three hundred and forty-two subjects received isoniazid and 342 received placebo. The median CD4 lymphocyte counts at enrolment were 322 and 346 x 10(6)/l in the isoniazid and placebo groups, respectively. The overall median follow-up from enrolment was 1.83 years (range, 0-3.4 years). The incidence of tuberculosis in the isoniazid group was 4.29 per 100 person-years (PY) of observation [95% confidence interval (CI) 2.78-6.33] and 3.86 per 100 PY of observation (95% CI, 2.45-5.79) in the placebo group, giving an adjusted rate ratio for isoniazid versus placebo of 0.92 (95% CI, 0.49-1.71). The adjusted rate ratio for tuberculosis for isoniazid versus placebo for tuberculin skin test (TST)-positive subjects was 0.60 (95% CI, 0.23-1.60) and for the TST-negative subjects, 1.23 (95% CI, 0.55-2.76). The overall adjusted mortality rate ratio for isoniazid versus placebo was 1.18 (95% CI, 0.79-1.75). Stratifying by TST reactivity gave an adjusted mortality rate ratio in those who were TST-positive of 0.33 (95% CI, 0.09-1.23) and for TST-negative subjects, 1.39 (95% CI, 0.90-2.12)., Conclusions: Overall there was no statistically significant protective effect of daily isoniazid for 6 months in the prevention of tuberculosis. In the TST-positive subjects, where reactivation is likely to be the more important pathogenetic mechanism, there was some protection and some reduction in mortality, although this was not statistically significant. The small number of individuals in this subgroup made the power to detect a statistically significant difference in this subgroup low. Other influences that may have diluted the efficacy of isoniazid include a high rate of transmission of new infection and rapid progression to disease or insufficient duration of isoniazid in subjects with relatively advanced immunosuppression. The rate of drug resistance observed in subjects who received isoniazid and subsequently developed tuberculosis was low.

Setting: Two Research Clinics within Nairobi, Kenya, one in the Infectious Diseases Hospital, the national referral centre for tuberculosis, and one in a community based project in Pumwani district, and the Bacterial Molecular Genetics Unit at the London School of Hygiene and Tropical Medicine., Objective: To determine whether recurrence of tuberculosis after 'adequate' treatment was due to reinfection with a different isolate of Mycobacterium tuberculosis or to relapse of the original infection., Design: A retrospective comparison by DNA fingerprinting of sets of isolates of M. tuberculosis from patients with recurrence of tuberculosis and in whom isolates from the original episode had been stored was made. Five patients with recurrence of tuberculosis two to nineteen months after adequate treatment and documented clearance of disease were studied., Results: In one patient, fingerprints of the isolates of M. tuberculosis from the recurrence were quite different to those from the original episode; in the other four, the fingerprints were identical., Conclusion: Reinfection rather than relapse was the cause of recurrence in at least one patient. The high 'relapse' rates seen in HIV-related tuberculosis in Africa may in part be due to increased susceptibility to reinfection and not to treatment failure.

There is evidence that in human immunodeficiency virus 1 (HIV-1) infected patients with tuberculosis the rate of recurrence of tuberculosis is increased in those patients treated with a standard thiacetazone-containing regimen. To assess the impact of HIV-1 on tuberculosis in Kenya, patients with tuberculosis were studied prospectively. After treatment with either a standard thiacetazone plus isoniazid regimen or a short-course thiacetazone-containing regimen, overall recurrence rate of tuberculosis was 34 times greater in 58 HIV-1-positive patients than in 138 HIV-1-negative patients (adjusted rate ratio 33.8, 95% CI 4.3-264). Recurrence in the HIV-1-positive group was strongly associated with a cutaneous hypersensitivity reaction due to thiacetazone during initial treatment (rate ratio 13.2, 95% CI 3.1-56.2). In all patients with a cutaneous hypersensitivity reaction ethambutol was substituted for thiacetazone. No significant association was found between recurrence among HIV-1-positive patients and initial resistance, initial treatment regimen, a diagnosis of AIDS (WHO definition), or poor compliance. DNA fingerprinting suggested that both relapse and new infection may have produced recurrence of tuberculosis. In patients who had a cutaneous hypersensitivity reaction, increased recurrence rate may have been related to interruption of treatment, subsequent poor compliance, or more advanced immunosuppression. Alternatively, a change to the combination of ethambutol and isoniazid in the continuation phase for 11 months only may not be adequate.

By using routinely collected data and results from research studies at the Infectious Diseases Hospital (IDH), Nairobi, we have begun to determine the scale of the increase in resource utilisation and treatment costs for tuberculosis control services caused by the HIV epidemic. New cases of tuberculosis registered annually at the IDH rose 61%, from 447 in 1985 to 720 in 1990. HIV seroprevalence among patients with tuberculosis rose from 7.5% in 1986 to 42% in 1990. The inpatient mortality rate rose from 8.4% in 1985 to 16.8% in 1989, but fell to 13.5% in 1990. HIV-positive patients were admitted to hospital on 2 or more occasions more often than HIV-negative patients (Relative risk (RR) = 2.46, 95% confidence intervals (CI), 1.1-5.7), but average duration of admission was similar for the 2 groups. Significantly more HIV-positive patients were prescribed antibiotics, antifungal agents, antidiarrhoeal agents, analgesics and corticosteroids than HIV-negative patients. Microbiological investigations, apart from those for tuberculosis, were performed more commonly among HIV-positive patients (RR = 2.0, 95% CI 1.0-4.2). Using this data, the average cost of ideal drug therapy, including antituberculosis drugs and treatment for intercurrent infections and other complications, was estimated using 1992 prices (ECHO, Coulsdon Surrey, UK). The costs were US$16.62 and US$32.94 for HIV-negative patients using 'standard' therapy (2STH/10TH) and short course therapy (2SHRZ/6TH) respectively, and US$41.18 for HIV-positive patients using a short-course regimen without thiacetazone (2EHRZ/6EH). The HIV epidemic is causing both an increase in the numbers of patients requiring treatment and an increase in the average cost of treatment per patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Retrospective studies suggest that the mortality rate from HIV-1-associated tuberculosis is greater than that from tuberculosis alone, but it is not clear if this is due to failure of antituberculosis treatment or to the complications of HIV-1 infection. We have carried out a prospective cohort study of patients with tuberculosis in Nairobi, Kenya, to compare mortality rates, risk factors, and causes of death in HIV-1 positive and HIV-1 negative patients. One hundred seven HIV-1 positive and 174 HIV-1 negative patients with tuberculosis attending two tuberculosis treatment centers in Nairobi were enrolled and followed monthly. Mortality was significantly higher in HIV-1 positive than in HIV-1 negative patients within 6 months of the start of antituberculosis treatment after adjustment for age, sex, and education (rate ratio = 3.8; 95% confidence interval, 1.7 to 8.1; p less than 0.001). Most of the excess mortality occurred after the first month of treatment and was due to nontuberculous infections. Predictors for mortality differed greatly between HIV-1 positive and HIV-1 negative patients. Mortality was greater in HIV-1 positive patients treated with a "standard" regimen for tuberculosis than in HIV-1 positive patients receiving a "short-course" regimen (p = 0.08 when adjusted for all independent risk factors). Tuberculosis control programs in developing countries need to implement "short-course" regimens and train health workers to recognize and treat nontuberculous infections to maintain their effectiveness in the face of the HIV epidemic.