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Objective: To assess the impact of prophylactic oral co-trimoxazole in reducing mortality in HIV positive Zambian adults being treated for pulmonary tuberculosis., Design: Double blind placebo controlled randomised clinical trial., Participants: Two groups of antiretroviral treatment naive adults with HIV infection: patients newly diagnosed as having tuberculosis and receiving tuberculosis treatment either for the first time or for retreatment after relapse; previously treated patients not receiving treatment., Intervention: Oral co-trimoxazole or matching placebo daily. Primary outcome measures Time to death and occurrence of serious adverse events related to study drug., Results: 1003 patients were randomised: 835 (416 co-trimoxazole, 419 placebo) were receiving treatment for tuberculosis, 762 (376 co-trimoxazole, 386 placebo) of them newly diagnosed previously untreated patients and 73 (40 co-trimoxazole, 33 placebo) receiving a retreatment regimen; 168 (84 co-trimoxazole, 84 placebo) were not on treatment but had received treatment in the past. Of 835 participants receiving tuberculosis treatment, follow-up information was available for 757, with a total of 1012.6 person years of follow-up. A total of 310 (147 co-trimoxazole, 163 placebo) participants died, corresponding to death rates of 27.3 and 34.4 per 100 person years. In the Cox regression analysis, the hazard ratio for death (co-trimoxazole:placebo) was 0.79 (95% confidence interval 0.63 to 0.99). The effect of co-trimoxazole waned with time, possibly owing to falling adherence levels; in a per protocol analysis based on patients who spent at least 90% of their time at risk supplied with study drug, the hazard ratio was 0.65 (0.45 to 0.93)., Conclusions: Prophylaxis with co-trimoxazole reduces mortality in HIV infected adults with pulmonary tuberculosis. Co-trimoxazole was generally safe and well tolerated., Trial Registration: Current Controlled Trials ISRCTN15281875.

Background: A national survey of tuberculosis was conducted in England and Wales in 1998 to obtain detailed information on the occurrence of the disease and recent trends. This survey also piloted the methodology for enhanced tuberculosis surveillance in England and Wales and investigated the prevalence of HIV infection in adults with tuberculosis., Methods: Clinical and demographic data for all cases diagnosed during 1998 were obtained, together with microbiological data where available. Annual incidence rates in the population were estimated by age, sex, ethnic group, and geographical region using denominators from the 1998 Labour Force Survey. Incidence rates in different subgroups of the population were compared with the rates observed in previous surveys. The tuberculosis survey database for 1998 was matched against the Communicable Disease Surveillance Centre HIV/AIDS database to estimate the prevalence of HIV co-infection in adult patients with tuberculosis., Results: A total of 5658 patients with tuberculosis were included in the survey in England and Wales (94% of all formally notified cases during the same period), giving an annual rate of 10.93 per 100 000 population (95% CI 10.87 to 10.99). This represented an increase of 11% in the number of cases since the survey in 1993 and 21% since 1988. In many regions case numbers have remained little changed since 1988, but in London an increase of 71% was observed. The number of children with tuberculosis has decreased by 10% since 1993. Annual rates of tuberculosis per 100 000 population have continued to decline among the white population (4.38) and those from the Indian subcontinent, although the rate for the latter has remained high at 121 per 100 000. Annual rates per 100 000 have increased in all other ethnic groups, especially among those of black African (210) and Chinese (77.3) origin. Over 50% of all patients were born outside the UK. Recent entrants to the UK had higher rates of the disease than those who had been in the country for more than 5 years or who had been born in the UK. An estimated 3.3% of all adults with tuberculosis were co-infected with HIV., Conclusions: The epidemiology of tuberculosis continues to change in England and Wales and the annual number of cases is rising. More than one third of cases now occur in young adults and rates are particularly high in those recently arrived from high prevalence areas of the world. The geographical distribution is uneven with urban centres having the highest rates. The increase in the number of cases in London is particularly large. Tuberculosis in patients co-infected with HIV makes a small but important contribution to the overall increase, particularly in London. To be most effective and to make the most efficient use of resources, tuberculosis prevention and control measures must be based on accurate and timely information on the occurrence of disease. A new system of continuous enhanced tuberculosis surveillance was introduced in 1999, based on the methodology developed in this national survey.

The pattern of tuberculosis in Indian, Pakistani and Bangladeshi patients in Blackburn (1978-1987) was compared with that for England and Wales (MRC Survey), with particular reference to the proportion with parenchymal lung disease, by a generalized linear model allowing for age, ethnic group and time since first entry. In Blackburn, the proportion with lung disease was higher in Pakistani/Bangladeshi (46%) compared with 28% in Indians, although in both groups this increased with age. In the MRC Survey, the proportions with lung disease were similar (Pakistani/Bangladeshi 36.5%, Indians 34%) but there was an increase in lung disease with age and year since first entry in the Indian ethnic group only. The reasons for the differences, and their implications are discussed.

The results are reported of the application of a short-course regimen for pulmonary tuberculosis in routine service in three districts in Kenya. All patients were treated in hospital for one month receiving Streptomycin, Isoniazid, Rifampicin and Pyrazinamide daily and followed by Rifampicin and Isoniazid daily on outpatient basis for five months. There was no failure of chemotherapy among 194 patients with pre-treatment sensitive strains at the end of chemotherapy. Six (3.9%) had a doubtful status but none relapsed during follow-up. Among 123 patients assessed after completion of follow-up only one (0.8%) relapsed and 16 of 22 patients with pretreatment resistant strains had a favourable response at the end of chemotherapy and follow-up. The therapeutic results achieved are excellent under programme conditions though of necessity with some amount of supervision that is not routinely available. Considering the advantages of short course regimens, a case for the choice of an appropriate short regimen to be used nationwide in the near future is made.

This investigation is the fifth in a series of case-finding studies in Kenya. It explores the potential for case-finding by the identification of persons with suspected tuberculosis (persons with a cough for 1 month or more) through careful screening of general outpatients attending a district hospital. Of 601 suspects identified among 20,756 new outpatients attending hospital during a period of 11 wk, 5.6% were considered by an independent assessor to have active pulmonary tuberculosis (2.2% with sputum positive on both smear and culture, 1.2% on culture only, and 2.2% negative sputum but radiographically active lesions). A further 2.0% were considered to have inactive tuberculosis. This method of case-finding appears to be uniformly effective within a radius of approximately 9 miles of the hospital, becoming less effective outside this range. There were certain important diagnostic pointers. There was an excess of tuberculosis cases in males, in those with weight loss, in those with a history of cough of less than a year, in those with a history of hemoptysis, and in those 35 yr of age or older. This investigation provides additional support to our previous studies, which demonstrated serious problems of case-finding in the peripheral health units and suggests that unless the infrastructure of primary health care at the periphery can be improved, the policy should be to diagnose tuberculosis in the district hospital and to operate a simple referral system for persons with suspected tuberculosis from the periphery.

This investigation is the sixth in a series of case-finding studies in Kenya. It explores the potential for case-finding by the identification of tuberculosis suspects (individuals with a cough for 1 month or more) through careful screening of general outpatients attending 4 district hospitals for the first time. Of 2299 suspects identified among 87 845 new outpatients attending the hospitals, 4.7% had culture-positive pulmonary tuberculosis, 3.6% having sputum positive on smear as well. In the 3 hospitals with radiographic facilities, 1.3% of suspects (whose sputum was negative on culture) were considered on review of their clinical history and chest radiograph by an independent assessor to have radiographically active tuberculous lesions and a further 2.5% to have inactive lesions. The proportion of bacteriologically positive cases per 1000 of the general population aged 6 years or more decreased as the distance of their homes from the hospital increased (P less than 0.001 for the trend). However, the proportion of cases per 1000 of the suspects identified increased as the distance of their homes from the hospital increased (P less than 0.001 for the trend). History of cough for between 1 and 12 months was the most useful factor for the identification of cases of tuberculosis among the suspects, and would have identified 92% of the smear-positive cases from the examination of 70% of the suspects; a history of weight loss identified 84% of the smear-positive cases from the examination of 64% of the suspects. A history of weight loss and/or a history of cough for between 1 and 12 months would have detected all the smear-positive cases from the examination of 89% of the suspects. The proportion of bacteriologically positive cases in the younger suspects aged 9-32 years (who had been eligible for a mass BCG campaign) was greater among the non-vaccinated than among the vaccinated suspects, 4.9% and 2.3% respectively (P=0.04), implying protection from vaccination of the order of 50%.

Patients with pulmonary tuberculosis who were failures of primary chemotherapy with strains resistant to isoniazid or to isoniazid and streptomycin were allocated at random to receive a regimen of rifampicin and ethambutol for 6 (4RE) or 9 months (7RE), supplemented in both treatment series by streptomycin plus pyrazinamide for the first 2 months. The patients were treated in hospital for the first 2 months and thereafter treatment was supervised on a daily basis in the nearest health institution by an appointed member of staff or at home by responsible members of the community. A total of 306 patients was admitted and 226 patients remained for analysis at the end of chemotherapy, 179 with a strain resistant to isoniazid alone and 47 with a strain resistant to isoniazid and streptomycin. There were only two failures at the end of chemotherapy, one in the 6-month series who had resistance to both isoniazid and streptomycin pretreatment, and one in the 9-month series who had resistance to isoniazid alone. For the 144 patients with initial resistance to isoniazid alone assessed up to 30 months, the relapse rates were low in both series: 4% for the 72 patients in the 6-month series and 3% for the 72 patients in the 9-month series. However, for the 34 patients with resistance to both drugs, three of the 14 in the 6-month but none of 20 in the 9-month series relapsed.

This investigation is the seventh in a series of case-finding studies in Kenya. It explores the potential value of questioning mothers attending maternity and child welfare (M & CW) clinics to identify tuberculosis suspects (individuals aged 6 years or more with a cough for 1 month or more or hemoptysis) living in their households. The study was carried out in all the eight M & CW clinics in two divisions (populations 86,000 and 112,000) of two different districts. The mothers were asked to give a standard letter, which explained the possible importance of a chronic cough, to each suspect they identified and invited the suspect to attend the district hospital chest clinic. Each suspect attending the clinic was entered in a special register and two sputum specimens were collected. For those who failed to attend, the specimens were collected at a home visit. Of the total of 342 suspects living in the two study areas who were registered at the M & CW clinics during 1 year, 261 were identified by the mothers but 19 denied having received the standard letter. The remaining 81 had not been identified by mothers but had attended the M & CW clinics on their own initiative. Of the 242 suspects who received the letter, 89 (39%) attended the hospital chest clinic, 74% within a week of the letter being issued from the M & CW clinic. The main reasons given for not attending the hospital chest clinic by the remaining suspects were financial or because their cough had improved or disappeared. Sputum was collected from 238 suspects and examined bacteriologically: in six (2.5%) it was positive for tubercle bacilli on smear and culture and in a further two (0.8%) the sputum was positive on culture only. Of those attending the hospital chest clinic 2.9% were smear- and culture-positive and 4.7% were culture positive. This method of case-finding has yielded disappointing results, for only 4% of the estimated annual incidence of smear-positive cases was detected.

In a survey of the chemotherapy prescribed for 1312 adult patients of white or Indian subcontinent ethnic origin with pulmonary tuberculosis only, notified in the 6 months from October 1978 to March 1979, it was found that 163 (12%) patients died before they had completed chemotherapy. Of the 163 patients who died 96% were of white ethnic origin; 15% of the 1022 white patients died compared with 2% of the 290 Indian subcontinent patients. According to the death certificate, approximately half the white patients died from tuberculosis, and in a further 31% tuberculosis was a contributory factor. Death from tuberculosis most frequently occurred in the older age groups, accounting in part for the different findings in these two ethnic groups, because of the excess of older white patients. In a step-wise multivariate discriminant analysis death from tuberculosis was found to be significantly associated in the white patients with the radiographic extent of disease before treatment, and with age, extent of cavitation and a positive sputum smear result, but not sex. Most of the deaths from tuberculosis occurred early, 38% before the end of the first week of chemotherapy and 69% by the end of 4 weeks. There was a further group of 51 adult patients with pulmonary tuberculosis notified in the same 6-month period in whom the diagnosis was not made until after death, 25 of them dying from tuberculosis. It is concluded that there is still a substantial risk of death from tuberculosis in patients with extensive disease in the older age groups.

This study has compared a daily 6-month short-course chemotherapy regimen and a daily 12-month standard duration regimen in the treatment of smear positive pulmonary tuberculosis in a rural area of Algeria where the population contains a relatively high proportion of nomads. The 6-month regimen (6M) was isoniazid and rifampicin throughout with ethambutol and pyrazinamide in addition for the first 2 months, and the 12-month regimen (12M) was isoniazid and ethambutol supplemented by streptomycin during the first month. All the 601 patients admitted had one or more sputum smears positive on examination in the local laboratory and 70% had a positive culture in the reference laboratory in Algiers. Most patients were admitted to hospital initially for one or two months where chemotherapy was fully supervised and subsequently it was self-administered. In both nomads and settled residents known to have fully sensitive strains of tubercle bacilli pretreatment the 6-month regimen was highly effective with no failures during chemotherapy and only 3% relapses after stopping chemotherapy in 126 patients compared with a combined failure rate during chemotherapy and relapse rate of 21% in the 152 patients receiving the 12-month regimen (P less than 0.001). The results in patients with isoniazid-resistant strains pretreatment were also significantly better for the 6-month than for the 12-month regimen, one of 15 and 8 of 17 patients respectively being classified as failures or relapses (P = 0.03). To assess the results which might be achieved by these regimens under programme conditions the outcome at 3 years was also assessed in all patients admitted to the study irrespective of whether the disease was confirmed in the reference laboratory or at independent assessment and whether or not the allocated chemotherapy was modified or further courses of chemotherapy were given. At 3 years, 82% of the 6M and 80% of the 299 12M patients had achieved a favourable status and only one 6M patient and 4 12M patients were still known to have active disease with a positive culture. A further 23 6M and 22 12M patients were known to have died, 11 in each series probably or definitely from tuberculosis. The remaining 28 6M and 34 12M patients were lost from follow-up, but 24 and 22 respectively had completed their allocated chemotherapy before defaulting. It was estimated that, overall, 272 (94%) of the 6M and 263 (91%) of the 12M patients had a favourable status at 3 years.(ABSTRACT TRUNCATED AT 400 WORDS)