The effect of BCG revaccination on all-cause mortality beyond infancy: 30-year follow-up of a population-based, double-blind, randomised placebo-controlled trial in Malawi.

BACKGROUND: Trials of BCG vaccination to prevent or reduce severity of COVID-19 are taking place in adults, some of whom have been previously vaccinated, but evidence of the beneficial, non-specific effects of BCG come largely from data on mortality in infants and young children, and from in-vitro and animal studies, after a first BCG vaccination. We assess all-cause mortality following a large BCG revaccination trial in Malawi. METHODS: The Karonga Prevention trial was a population-based, double-blind, randomised controlled in Karonga District, northern Malawi, that enrolled participants between January, 1986, and November, 1989. The trial compared BCG (Glaxo-strain) revaccination versus placebo to prevent tuberculosis and leprosy. 46 889 individuals aged 3 months to 75 years were randomly assigned to receive BCG revaccination (n=23 528) or placebo (n=23 361). Here we report mortality since vaccination as recorded during active follow-up in northern areas of the district in 1991-94, and in a demographic surveillance follow-up in the southern area in 2002-18. 7389 individuals who received BCG (n=3746) or placebo (n=3643) lived in the northern follow-up areas, and 5616 individuals who received BCG (n=2798) or placebo (n=2818) lived in the southern area. Year of death or leaving the area were recorded for those not found. We used survival analysis to estimate all-cause mortality. FINDINGS: Follow-up information was available for 3709 (99·0%) BCG recipients and 3612 (99·1%) placebo recipients in the northern areas, and 2449 (87·5%) BCG recipients and 2413 (85·6%) placebo recipients in the southern area. There was no difference in mortality between the BCG and placebo groups in either area, overall or by age group or sex. In the northern area, there were 129 deaths per 19 694 person-years at risk in the BCG group (6·6 deaths per 1000 person-years at risk [95% CI 5·5-7·8]) versus 133 deaths per 19 111 person-years at risk in the placebo group (7·0 deaths per 1000 person-years at risk [95% CI 5·9-8·2]; HR 0·94 [95% CI 0·74-1·20]; p=0·62). In the southern area, there were 241 deaths per 38 399 person-years at risk in the BCG group (6·3 deaths per 1000 person-years at risk [95% CI 5·5-7·1]) versus 230 deaths per 38 676 person-years at risk in the placebo group (5·9 deaths per 1000 person-years at risk [95% CI 5·2-6·8]; HR 1·06 [95% CI 0·88-1·27]; p=0·54). INTERPRETATION: We found little evidence of any beneficial effect of BCG revaccination on all-cause mortality. The high proportion of deaths attributable to non-infectious causes beyond infancy, and the long time interval since BCG for most deaths, might obscure any benefits. FUNDING: British Leprosy Relief Association (LEPRA); Wellcome Trust.

High mortality associated with retreatment of tuberculosis in a clinic in Kampala, Uganda: a retrospective study.

The World Health Organization recommends for tuberculosis retreatment a regimen of isoniazid (H), rifampicin (R), ethambutol (E), pyrazinamide (Z), and streptomycin (S) for 2 months, followed by H, R, E, and Z for 1 month and H, R, and E for 5 months. Using data from the National Tuberculosis and Leprosy Program registry, this study determined the long-term outcome under programmatic conditions of patients who were prescribed the retreatment regimen in Kampala, Uganda, between 1997 and 2003. Patients were traced to determine their vital status; 62% (234/377) patients were found dead. Having ≤ 2 treatment courses and not completing retreatment were associated with mortality in adjusted analyses.

Incidence and predictors of mortality and the effect of tuberculosis immune reconstitution inflammatory syndrome in a cohort of TB/HIV patients commencing antiretroviral therapy.

BACKGROUND: Tuberculosis-HIV (TB-HIV) coinfection remains an important cause of mortality in antiretroviral therapy (ART) programs. In a cohort of TB-HIV-coinfected patients starting ART, we examined the incidence and predictors of early mortality. METHODS: Consecutive TB-HIV-coinfected patients eligible for ART were enrolled in a cohort study at the Mulago National Tuberculosis and Leprosy Program clinic in Kampala, Uganda. Predictors of mortality were assessed using Cox proportional hazards analysis. RESULTS: Three hundred and two patients [median CD4 count 53 cells/µL (interquartile range, 20-134)] were enrolled. Fifty-three patients died, 36 (68%) of these died within the first 6 months of TB diagnosis. Male sex [hazard (HR): 2.19; 95% confidence interval (CI): 1.19 to 4.03; P = 0.011], anergy to tuberculin skin test [HR: 2.59 (1.10 to 6.12); P = 0.030], a positive serum cryptococcal antigen result at enrollment (HR: 4.27; 95% CI: 1.50 to 12.13; P = 0.006) and no ART use (HR: 4.63; 95% CI: 2. 37 to 9.03; P < 0.001) were independent predictors of mortality by multivariate analysis. Six (10%) patients with TB immune reconstitution inflammatory syndrome died, and in most, an alternative contributing cause of death was identified. CONCLUSIONS: Mortality among these TB-HIV-coinfected patients was high particularly when presenting with advanced HIV disease and not starting ART, reinforcing the need for timely and joint treatment for both infections. Screening for a concomitant cryptococcal infection and antifungal treatment for patients with cryptococcal antigenemia may further improve clinical outcome.

A situação epidemiológica da tuberculose na República da Guiné-Bissau, 2000 - 2005 / The epidemiological situation of tuberculosis in the Republic of Guinea-Bissau, 2000-2005

INTRODUÇÃO: A tuberculose na República da Guiné-Bissau não apresenta bons indicadores de saúde, assim como na maioria dos países em vias de desenvolvimento. OBJETIVO: Estudar na República da Guiné-Bissau e nas suas Províncias, a situação epidemiológica da doença no período de 2000 a 2005. MÉTODO: Realizou-se levantamento de dados secundários junto ao Programa Nacional de Luta Contra Lepra e Tuberculose, no período de 2000 a 2005, e análise de relatórios anuais da Capital e das Províncias da Guiné-Bissau, para o cálculo de coeficientes e taxas dos indicadores. RESULTADOS: O número de casos de tuberculose manteve-se estável no período de 2000 (1.959 casos) a 2005 (1.888 casos). O percentual de casos pulmonares variou de 96,0 a 98,8 por cento, dos quais 55 por cento eram bacilíferos. Em 2005 o coeficiente de prevalência foi de 142,4/100.000, o de incidência 131,3/100.000 e o de mortalidade, 16,8/100.000 habitantes. A maior concentração de casos ocorreu na região da Capital. A taxa de cura variou entre 46,5 por cento em 2000 e 69,6 por cento em 2005, e a de abandono de tratamento de 29,8 por cento em 2000 para 12,1 por cento em 2005. CONCLUSÃO: Os indicadores do Plano Estratégico Nacional devem ser melhorados, sobretudo no que diz respeito à busca ativa de casos, à descentralização do atendimento aos doentes, à implantação da estratégia DOTS e à necessidade de um sistema de informação e notificação eficientes.

INTRODUCTION: Tuberculosis does not present good health indicators in the Republic of the Guinea-Bissau, like most other developing countries. OBJECTIVE: To study the epidemiological status of the illness in the 2000-2005 period in the Republic of the Guinea-Bissau and its Provinces. METHOD: Secondary data were collected from the National Fight Against Leprosy and Tuberculosis Program, in the period from 2000 to 2005, and annual reports of the Capital and the Provinces were analyzed to calculate coefficients and indicators. RESULTS: The number of tuberculosis cases remained stable in the period from 2000 (1,959 cases) to 2005 (1,888 cases). The percentage of pulmonary cases ranged from 96.0 to 98.8 percent, of which 55 percent had positive smears. The coefficients of prevalence, incidence and mortality, in 2005 were 142.4/100,000, 131.3/100,000 and 16.8/100,000 inhabitants, respectively. The main concentration of cases occurred in the region of the Capital. Cure rates varied between 46.5 percent in 2000 and 69.6 percent in 2005 and treatment interruption rates were 29.8 percent in 2000 and 12.1 percent in 2005. CONCLUSION: The indicators of the National Strategic Plan must improve, particularly with regard to active case search, decentralization of patient care, implementation of the DOTS strategy, and the need for an efficient information and reporting system.

SCORTEN: does it need modification?

BACKGROUND: Toxic epidermal necrolysis (TEN) is a drug induced acute life threatening condition with mortality ranging from about 15 to 60%. A 'severity of illness' score termed as SCORTEN has been developed to predict mortality in TEN cases at the time of admission. It is calculated by giving one point for each of predetermined seven variables, evaluated during first 24 hours of admission. Total score ranging from 1-7 predicts a probability of mortality from 0.03 to 0.90. AIM: A prospective study was conducted to analyze efficacy of 'SCORTEN' in TEN cases to predict mortality during their management. METHODS: All cases of TEN reporting for management to the hospital were assessed using 'SCORTEN' on day one and day five to predict probable mortality, this data was then compared with ultimate outcome. RESULTS: During the study period, we treated 10 cases of TEN, all induced by drugs, patient's age ranging from 03 to 70 years and body surface area (BSA) involvement from 10 to 95%. Three cases succumbed to death. These cases were analyzed with SCORTEN to predict probability of mortality at the time of admission and day five. We encountered some variations from the original study. It was observed that if patients are analyzed with SCORTEN on a daily/alternate day basis, it will serve as a better predictor of mortality. CONCLUSION: Body surface area (BSA) involvement and age probably need more weightage in calculations. Besides malignancy, tuberculosis and pre-existing diabetes also need to be included while predicting mortality.

Genetic susceptibility to mycobacterial disease in humans.

Mycobacterial disease remains a serious global health problem. Tuberculosis causes more than 2 million deaths a year, and leprosy is still a cause of severe disability in many parts of the world. As a result of the study of individuals with marked susceptibility to usually nonpathogenic mycobacteria, as well as case-control studies with candidate genes and genome-wide screens of affected populations, there is substantial evidence for the role of genetic factors in the susceptibility to mycobacterial disease. These studies have defined immunological processes essential for the control of mycobacteria infections in humans.

Epidemiology of tuberculosis and leprosy, Sabah, Malaysia.

The objectives in this epidemiology review are to measure and report the extent of morbidity and mortality due to tuberculosis (TB), the proportion of new sputum smear positive cases in districts and the status of cohort analysis as of 1999. As for leprosy, the main objective is to determine morbidity and the treatment outcomes of Multiple Drug Therapy (MDT). Based on the results obtained, a comprehensive action plan for prevention, control and monitoring of tuberculosis and leprosy cases and patients is being produced and implemented throughout the state. The analysis concentrated on patients diagnosed at all out-patient units and admitted in all of the state's hospitals. The patient particulars were recorded using a standardized format based on TB and Leprosy Health Management Information System (TB HMIS). TB was the second highest by notification of communicable diseases in Malaysia in 2001. 29% or about one-third of the national TB cases are from Sabah. However, it has been noted that there was an average decline of 2.6% in annual notification since 10 years ago to date. There was also a reduction of 11.4% in 2001 as compared to annual notification in 2000. Immigrants contribute more than 24% in detection of new cases since 1990. Treatment success rate in term of completion of treatment to date is 82%. Mortality rate has steadily declined from 14 deaths to 7 deaths per 100,000 population. Leprosy in Sabah also contributes to 30% of the yearly total caseload of Malaysia and has the highest notification rate of 2 per every 100,000 population as compared to other states. The average registered leprosy cases over the past 5 years are 239 cases and the prevalence rate is 0.7/10,000 population. The state has successfully achieved its goal to decrease leprosy as per the World Health Organization (WHO) goal of yearly overall prevalence rate of less than 1 case for every 10,000 population. However, the districts of Kudat, Tawau, Lahad Datu, Kota Kinabalu and Semporna are still within the prevalence rate of more than one per 10,000 population. This review highlights some interesting findings which can be incorporated into the State and Districts action plans and strategies. It is also noted that in order to translate National Plans and Strategies into effective action at the community level, health workers need relevant up-to-date knowledge of the pattern of health and disease, and of their determinants, in each district. The Sabah Health Department continues to organize and support programs related to management and control of tuberculosis and leprosy to progressively reduce the incidence of these diseases in the community by breaking the chain of transmission of Mycobacterium tuberculosis and M. leprae, respectively.

Tuberculosis in leprosy patients detected between 1902 and 1991 in French Polynesia.

From 1902 onward, notification and follow up of leprosy patients has been systematic in French Polynesia. Since 1960, a tuberculosis control program and a register has also been implemented. From 1902 to 1959, 673 cases of leprosy were detected [346 multibacillary (MB), 138 paucibacillary (PB), and 179 unclassified due to the loss of medical files by the time of classification which was done during the 1980s]. Of these 673 cases, 89 (13.2%) died from tuberculosis, giving a mean annual death rate of tuberculosis in leprosy patients of 232 per 100,000. Mortality from tuberculosis in leprosy patients detected between 1901 and 1930 was 20.7%, and decreased to 8.04% in patients detected from 1931 to 1959. In total, it was estimated that 26.4% of the leprosy cases had developed tuberculosis. From 1960 to 1991, 350 new cases of leprosy were detected (141 MB, 209 PB). Of them, 12 (3.4%) developed tuberculosis (7 before detection of leprosy, 5 after detection of leprosy). The dramatic decrease of the proportion of leprosy patients who developed tuberculosis between the periods 1902-1959 (26.4%) and 1960-1991 (3.4%) might be related to the important decline of the tuberculosis situation since 1960. From 1902 to 1959, mortality from tuberculosis occurred significantly more frequently in MB patients (13%) than in PB patients [4%, relative risk (RR) = 3.21, p = 0.003]. From 1960 to 1991, the incidence of tuberculosis seemed more frequent in MB patients (RR = 2.96, p = 0.07) whatever the sequence of detection of the two diseases. Our study suggests that lepromatous patients could share factors of susceptibility to mycobacterial diseases with patients developing tuberculosis.

The epidemiological transition in an overseas territory: disease mapping in French Polynesia.

During the last 200 years in French Polynesia the people have experienced several dramatic changes in the pathological scene. First the discovery of Tahiti and the surrounding islands at the end of the eighteenth century caused the spread of diseases previously unknown, usually in the form of epidemic outbreaks. In contrast, from the 1860s to soon after the end of the Second World War, health amelioration in French Polynesia was slowly occurring. This constituted a first epidemiological transition in which infectious disease mortality was sharply reduced. The distribution of vaccines, hygiene education and legislation stemmed the long period of some 100 years of demographic disaster and at last the population was able to increase. However for a long time infectious or parasitic diseases remained the main causes of morbidity and mortality. Only from the end of the 1950s has the situation evolved to the present state where morbidity and mortality of the circulatory system and cancer are similar in prevalence to industrialized countries. Diachronistic mapping of some of the most noteworthy diseases is presented to illustrate this last and most important phase of the epidemiological transition.

Cancer and other causes of death among leprosy patients.

A follow-up study was done on the mortality from 1956 to 1975 among 2,383 Japanese patients with leprosy who were admitted to a leprosarium in Japan. The leprosy was classified into two types: lepromatous and tuberculoid. Irrespective of the type of leprosy or the sex of leprosy patient, mortalities were increased from tuberculosis, pneumonia and bronchitis, nephritis and nephrosis, and from total causes. The suicide rate was high among female patients. Deaths from total malignant neoplasms were higher than expected among patients with lepromatous leprosy for both sexes (49 observed vs. 44.02 expected), whereas they were lower than expected among patients with tuberculoid leprosy (35 observed vs. 36.83 expected); however, the differences were not statistically significant. Mortalities from cancers of the cervix and the esophagus among females with lepromatous leprosy were significantly higher. The risk of lymphoreticular cancers was not increased.

Causes of death in a subarctic population.

Some of the main causes of death prior to 1900 are mentioned, including disastrous epidemics of high mortality such as plague, smallpox and the so-called hunger epidemics. Also discussed are two chronic diseases remarkable for Iceland in old times i.e., leprosy and hydatid disease. In the first third of the 20th century, infectious diseases still were the main cause of death in Iceland. The importance of tuberculosis in this connection is stressed. The very high infant mortality up to the beginning of this century is stressed. The changes in the main causes of death in the last decades are described and the growing influence of degenerative vascular diseases and cancer in that connection pointed out. Last, the remarkable fall in the infant mortality and increasing life expectancy from the beginning of this century with growing prosperity of the nation is stressed.