H. Stott

A fourth study of case-finding methods for pulmonary tuberculosis in Kenya

Abstract This investigation is the fourth of a series of case-finding studies in Kenya. It explored in a new area (the Baragwi location of Kirinyaga), five methods of case-finding involving the examination of the sputum by smear and culture of symptomatic tuberculosis suspects in the community identified (i) by interrogation of the Elders, (ii) by interrogation of household heads, (iii) by tracing all patients registered during the previous 10 years in the District Tuberculosis Register, (iv) by the examination of all their close contacts and (v) from outpatients attending peripheral health units. The initial interrogation of the Elders yielded 123 suspects with bacteriological results, of whom seven were culture-positive, including four smear-positive. A second interrogation three to six months later produced a further 66 suspects and four more culture-positive cases (all smear-negative). The examination of a second sputum specimen after three to six months from all the suspects from both interrogations produced a further culture-positive smear-negative case. A single interrogation of household heads in a house-to-house survey yielded 867 suspects and 15 culture-positive cases, including eight smear-positive. Of 862 suspects with no history of tuberculosis, 778 (90%) claimed they had attended a medical facility for their respiratory symptoms during the previous year, the most recent visit being within the previous month in 24%. All except 1% of the total had attended on more than one occasion, the average number of attendances being 5·3. 83% said they had attended the peripheral health units and 37% had attended the Central District Hospital, yet 65% of the suspects had had neither a chest radiograph nor their sputum examined bacteriologically. Of the 114 cases of tuberculosis registered in the District Tuberculosis Register during the previous 10 years, nine were currently culture-positive, seven being smear-positive. The examination of a second sputum specimen from 105 yielded one more culture-positive case. Of 577 household contacts of the registered cases, seven were culture-positive, three being smear-positive. The examination of a second sputum specimen from 568 yielded two more culture-positive cases. During a full year, only 45 suspects were registered among out-patients attending seven health units serving the area (population 27,500), of whom four were smear-positive. This indicates a failure of the staff to take appropriate actions.

An assessment of the carcinogenicity of isoniazid in patients with pulmonary tuberculosis.

In an assessment of the carcinogenicity of isoniazid, 3,842 adult tuberculous patients admitted to 2 sanatoria in the period 1950 to 1957 (that is, in the years immediately before and after the introduction of isoniazid) have been followed up for a mean period of over 19 years. Their mortality has been compared with that expected during the same calendar period in a general population group in England and Wales with the same age and sex distribution. The relative risk of death (the observed divided by the expected number of deaths) from all malignant neoplasms in patients first starting chemotherapy in 1950 to 1952, before the general introduction of isoniazid, was 0.8 for those who received isoniazid at some time, compared with 0.5 for those who never received it; for those first starting chemotherapy in 1953 to 1957, after the general introduction of the drug, the respective risks were 1.4 and 1.8. The relative risk of death from malignant neoplasms was 2.1 in the first 4 years after starting the treatment with isoniazid; this high relative risk is unlikely to be attributable to isoniazid and largely disappears subsequently, for in successive 4-year periods it was 1.3, 0.9, 1.2 and 1.4. The relative risks of death from all malignant neoplasms for patients receiving a total dosage of less than 50, 50-99, 100-199 and 200 g or more were 1.5, 1.5, 1.0 and 1.3, respectively. For patients receiving a maximum daily dose of less than 250 g the relative risk was 1.3, and for those receiving 250 g or more it was 1.2. There was a curious and unexplained difference in the mortality from malignant neoplasms in patients first starting chemotherapy in 1950 to 1952 (relative risk 0.6) and those first starting in 1953 to 1957 (relative risk 1.5). This is being studied further. This study has provided no evidence of a carcinogenic effect of isoniazid in a period of follow-up averaging nearly 20 years. The follow-up is being continued.

The risk of tuberculous infection in uganda, derived from the findings of national tuberculin surveys in 1958 and 1970☆

Abstract The World Health Organization made a tuberculin survey in Uganda in 1958 as part of an assessment of the prevalence of tuberculosis in that country. This paper describes a second tuberculin survey made in Uganda in 1970-71, to assess changes in the situation. The second survey was made deliberately in the same ten randomly chosen geographical areas as were surveyed in 1958, using the same techniques for registration and testing of the population, the same tuberculin, and employing as tester and reader the same WHO tuberculin testing nurse as had made and read the majority of the tests in 1958. Very few BCG vaccinations had been made in the interim in these areas. In 1970–1971 a total of 7,912 subjects (91·4 per cent of the registered population of the areas) completed the tuberculin test. This total included 2,038 subjects who had also been tested in the 1958 survey, and were still alive and resident in the area. The distribution of the diameters of induration in the tests was closely similar in the two surveys, the mode of the larger reactions being at 17 mm in both. The same criterion for the percentage with tuberculous infection could therefore be used in 1970–1971 as in 1958, namely the percentage with reactions of 17 mm or more, multiplied by two. For studying the changes in the prevalence of tuberculous infection, test results were available for 5,719 subjects in 1958, and for 6,875 subjects (258 of whom were tuberculin negative and had been given BCG vaccine at the 1958 survey) living in the identical geographical areas in 1970–1971. To obtain unbiased estimates of the percentages infected in the whole population in 1970–1971, it was necessary to estimate the numbers of infections which would have occurred by 1970–1971 in the 258 subjects, if they had not been vaccinated in 1958. The findings for the percentages infected at different ages at the two surveys have been used to estimate the annual risks of tuberculous infection during the period from about 1940 to 1970, and the association of the risk of infection with age of the subject. Based on the findings up to age 30 years, it is estimated that the annual risk of infection (at age 10) was 2·8 per cent in 1940, 2·6 per cent in 1950, 2·4 per cent in 1960 and 2·3 per cent in 1970. The slight decrease (amounting each year to less than 1 per cent of the risk) is not statistically significant. There does, however, appear to be a definite increase in the risk with age. The estimates of the risks at ages 5, 10 and 15 years in 1970 were 1·9, 2·3 and 2·8 per cent (amounting to a rise of 4 per cent of the risk with each year of age). It is concluded that the tuberculosis situation in Uganda has shown little improvement during the 1212 years between the two surveys, and that there is still a substantial risk of tuberculous infection there. There is thus considerable scope in Uganda for benefit from BCG vaccination and other modern methods of tuberculosis control which include simplified case finding and chemotherapy.

A Third Study Of Case-finding Methods For Pulmonary Tuberculosis In Kenya, Including The Use Of Community Leaders

Five methods of identifying tuberculosis suspects were investigated in the Machakos District of Kenya by: (1) 3-monthly interrogation of the Community Elders, (2) interrogation of household heads, (3) identifying suspects amongst outpatients attending local health units, (4) examination of patients registered during the previous 10 years in the District Tuberculosis Register and also (5) their close contacts. Sputum was bacteriologically examined by smear and culture from suspects found by all the methods. The initial interrogation of the Elders yielded 216 suspects, of whom 9 were culture-positive, including 6 smear-positive. Reinterrogating the Elders 4 times at 3-monthly intervals produced a further 114 suspects including 4 culture-positive cases (3 being smear-positive). The examination of a second sputum specimen from suspects after a 3-month interval yielded 4 further culture-positive cases (all smear-negative) but the examination of a third specimen after a further 3 months yielded no further cases. A single interrogation of 1093 household head suspects yielded 22 culture-positive cases, including 11 smear-positive. The response in 5 health units covering a population of about 24 500 was poor. During a 2-year period only 109 suspects were recorded; 7 were culture-positive, including 3 smear-positive. Of 61 cases of tuberculosis registered during the previous 10 years, 8 were currently culture-positive, 5 being smear-positive. Of 318 household contacts of these cases, 6 were culture-positive cases, 2 being smear-positive. The problems presented by different active case-finding methods are discussed, identifying those that appear promising and those unpromising.

Studies of case-finding for pulmonary tuberculosis in outpatients at 4 district hospitals in Kenya.

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%.

A second study of the use of community leaders in case-finding for pulmonary tuberculosis in Kenya

This is the second study of case-finding activities for tuberculosis suspects undertaken in 2 locations of Machakos District. Three methods were investigated, namely (1) the requestioning of the Community Elders 1 year or more after a first questioning in the original study, (2) the examination of patients registered in the District Tuberculosis Register from 1969--1974 and (3) the examination of their close contacts. Requestioning the Elders produced a total of 421 suspects, 129 (31%) of whom had not been identified a year previously. The yield of freshly identified smear-positive, culture-positive cases was 0.7 per 100 suspects examined and of all culture-positive cases was 1.7. However, all the smear-positive and 1.0 per 100 of the culture-positive cases were old patients who had previously been registered in the District Tuberculosis Register. Of the 181 patients with tuberculosis in the Register bacteriological results were available for 97; of these 6 were smear-positive, 9 culture-positive--yields of 6.2 smear-positive, culture-positive cases per 100 registered persons examined. The corresponding yields for the 63 persons who had been registered as having pulmonary disease were 9.5 and 14.3. Of the 9 culture-positive, 7 had strains resistant to isoniazid, but all were sensitive to streptomycin. The examination of the 628 close contacts of the registered patients produced only 3 culture-positive cases, none of whom was smear-positive--a yield of 0.5 culture-positive cases per 100 contacts examined. All 3 strains were sensitive to isoniazid and streptomycin.

A two-year follow-up of patients with quiescent pulmonary tuberculosis following a year of chemotherapy with an intermittent (twice-weekly) regimen of isoniazid plus streptomycin or a daily regimen of isoniazid plus pas

Summary In the main analysis of a years study of twice-weekly high dosage isoniazid plus streptomycin (SHTW) in comparison with a standard daily regimen of isoniazid plus PAS (PH) under domiciliary conditions, 66 SHTW and 53 PH patients had attained bacteriologically quiescent disease at one year. All the patients have now been followed-up over a two-year period. Of these, 66 SHTW and 52 PH patients had been allocated at random to treatment the second year with isoniazid alone or with placebo. No patient was prescribed antituberculosis drugs for the third year. The condition of the patients in the two series was broadly similar, both at the time of their original admission to treatment and also at the start of the period of follow-up. There were five deaths (four SHTW, one PH) in the follow-up period, all in the second year and all from non-tuberculous causes; all five patients produced only negative cultures in the second year and for at least six months immediately before death. The radiographic progress was similar for the two series in the second and third years, the majority of patients in both series showing little change. The patients were under intensive bacteriological investigation, an average of 14 cultures being examined per patient in the second year and nine in the third year. A bacteriological relapse occurred in five (8%) SHTW and six (12%) PH patients. In one and two patients respectively this was associated with a serious radiographic deterioration. An isolated positive culture was produced by 17% of the SHTW and 27% of the PH patients. Four of the SHTW patients had a relapse with streptomycin- and isoniazid-sensitive cultures and four of the PH patients with isoniazid-sensitive cultures. It is concluded that bacteriological quiescence following a year of twice-weekly isoniazid plus streptomycin is at least as stable, over a two-year period of follow-up, as that attained following a year of a standard daily oral regimen of isoniazid plus PAS.

A controlled comparison of streptomycin plus pyrazinamide and streptomycin plus PAS in the retreatment of patients excreting isoniazid-resistant organisms

Summary A controlled comparison has been made of streptomycin plus pyrazinamide (46 patients) and streptomycin plus PAS (36 patients) in the retreatment of patients with pulmonary tuberculosis. The patients had either failed to attain bacteriological quiescence on isoniazid alone or had relapsed bacteriologically after attaining quiescence; all were excreting strains of tubercle bacilli resistant to isoniazid but sensitive to streptomycin and PAS at the start of the trial. The disease status at 1 year was assessed in 41 patients on pyrazinamide and 24 on PAS, and of these, 29 (71%) and 12 (50%), respectively, had bacteriologically quiescent disease. Seven patients (2 on pyrazinamide, 5 on PAS) had their treatment terminated for toxicity, 1 due to a pyrazinamide polyarthritis, 2 on account of hypersensitivity to PAS, and 4 (1 on pyrazinamide, 3 on PAS) because of streptomycin toxicity. Nine patients (2 on pyrazinamide, 7 on PAS) became unco-operative and stopped treatment, and 2 patients (on pyrazinamide) died, 1 of a non-tuberculous condition. Thus, streptomycin plus pyrazinamide was slightly more effective therapeutically than streptomycin plus PAS and was not more toxic or less acceptable to the patients.

A study of the use of community leaders in case-finding for pulmonary tuberculosis in the machakos district of Kenya

Abstract The purpose of the study was to investigate the potential value of identifying cases of pulmonary tuberculosis in the community by interrogation of community Elders and of household heads. A survey was undertaken in two locations, comprising 11 sublocations and 59 sections, in the Machakos district of Kenya. A complete census undertaken specially for the survey showed that there were 6090 households in the area occupied by 41 287 persons of whom 29 508 were aged 6 years or more. At a special interrogation, the section Elders named 363 persons (suspects) age 6 years or more whom they said had had pulmonary tuberculosis or currently had symptoms suggestive of the disease. Sputum specimens were collected for smear and culture, and results were available for 351 (97 %). The yield of smear-positive culture-positive cases was 1.7 per 100 suspects and of all culture-positive cases (whether smear-positive or negative) it was 2.3 per 100. Every household in the survey area was visited and 1716 suspects were identified by interrogation of the household heads (172 had also been identified by the Elders). Sputum examination results were available for 1697 (99 %). The yield of smear-positive culture-positive cases was 0.8 per 100 suspects examined and of all culture-positive cases (whether smear-positive or negative) it was 1 .5. A random sample of 20 % of the households in the area was drawn. There were 5919 inhabitants aged 6 years or more and sputum specimens were collected and results were available for 5798 (98 %). Of these 344 had already been identified by the Elders and/or household heads as suspects and the remaining 5575 had neither a previous history nor current symptoms of tuberculosis. From this 20 % sample the prevalence of smear-positive cases in the community was estimated to be 6.9 (95 % confidence limits of 3.9 to 9.9) per 10 000 persons aged 6 years or more and of all culture-positive cases 17.5 (95 % confidence limits of 10:8 to 24.2). Of the total suspects identified by the Elders and/or by household heads, 124 had a previous history of tuberculosis of whom 64 were identified in the Machakos District Central Tuberculosis Register and 60 were not; 10 and 1 respectively were culture-positive including 6 and 1 respectively who were also smear-positive. A total of 1450 with chronic chest symptoms but no previous history of tuberculosis reported that they had attended a medical facility for their symptoms on at least one occasion, but had not been diagnosed as having tuberculosis; of these 13 were culture-positive including 7 who were smear-positive in the present survey.

A controlled comparison of cycloserine plus ethionamide with cycloserine plus thiacetazone in patients with active pulmonary tuberculosis despite prolonged previous chemotherapy

Summary Twenty-seven patients with chronic pulmonary tuberculosis who had failed to respond to two previous chemotherapeutic regimens were allocated to treatment with cycloserine plus ethionamide (14 patients), or with cycloserine plus thiacetazone (13 patients). All had isoniazid-resistant strains and all but one had streptomycin-resistant strains at the start of the study. At the end of a year nine of 14 patients in the ethionamide series compared with three of 13 in the thiacetazone series had bacteriologically quiescent disease, one and three. respectively, had bacteriologically active disease; during the year, two patients (one in each series) deteriorated and had their chemotherapy changed and two patients (both on thiacetazone) died of tuberculosis. The difference in the proportions of unfavourable response attained statistical significance. There was one case of peripheral neuropathy due to ethionamide. Definite toxicity to thiacetazone was not observed. One of nine patients excluded from the main analysis had had intractable vomiting due to cycloserine.