Tuberculosis Previous and Present Millennium

Tuberculosis: Previous and Present Millennium. TB before advent of chemotherapy  TB in 1950 - 2000  Morbidity, Mortality & Elimination of TB. Censina R. Apap, Pulmonologist.  Introducing Myself Respiratory specialist since 1983  Working in the Netherlands since 1977  Special interests include Tuberculosis, Asthma, COPD, and Oncology.  Tuberculosis, a fascinating topic.  Introduction to the lecture Natural history of TB  Much morbidity and mortality before the advent of antibiotics  HIV, MDR-TB and relaxation of TB control programs present new public health problems  Tuberculosis in the past: Phtisis Phtisis renamed Tuberculosis in 1837  Congenital / infectious disease?  Known to be infectious in 1865  Cause of TB discovered by Koch in 1882  Subdivision: open / closed TB  TB R/ in the pre-antibiotica era. Conservative, directed at relief of symptoms. Sanatorium R/ introduced in Germany by Brehmer resulted in 25% sputum conversion within 6 mo. 50% of smear positive cases died of disease within 5 years. How was TB treated in 1937?  “Upon the permanence of closure of a tuberculous cavity depends the future development of the disease.The tuberculous cavity is the disease itself, the one feature which controls and regulates the course and outcome of the pulmonary lesion and the fate of the patient.” Coryllos. 1200 1000 800 600 400 Total patie % deaths Sanatorium Hospital Home / 1026 152 55 86 347 83 Total patients No of deaths 200 0 Total patients No of deaths Sanatorium 1026 565 Hospital 152 131 Home R/ 347 288 From W.A. Griep Deaths (fall off rate) due to TB. % of deaths After 1 year After 5 years Infectious TB Noninfectious TB 23.8% 0.9% 66.5% 11.2% After 10 years 74% 16.5% Active R/ of TB.  • Collapse R/  Artificial pneumothorax, Forlanini in 1888;  Phrenicus paralysis;  Thoracoplasty;  Closed suction of lung cavities (Monaldi); Lung resection. Complications of Thoracoplasty Thorax cage instability with paravertebral thoracoplasty  Empyema and wound infections with plombage  In the case of selective thoracoplasty and resection of first rib:  Air emboli  Trauma to the brachial plexus and thoracic duct • Postoperative complications included: • Shock  Aspiration pneumonia, atelectasis  Cardiac complications  Natural course of TB infection  Mycobacteria inhaled -> phagocytosis by alveolar macrophages-> 2 possibilities:  No infection  Infection (early / late) Transmission of TB Source case with open TB of lungs / larynx -> transmission through cough /sneeze -> infection: early 5-10%, late in 5%. -> result: recovery (possible morbidity) / death.  Positive tuberculin test reflects infected contacts.  Progression to early / late infection  Possible new source cases provided  Introduction of Antibiotics 1944 In 1944, Waksman makes Streptomycin.  PAS is available in 1946, INH in 1952 and Rifampicin in 1965.  Improved socio-economic factors and availability of effective chemotherapy-> radical change in R/  Ambulant and in outpatient setting, unless otherwise indicated.  TB R/ in the antibiotic era. Role of chemotherapy: permanent cure without development of resistance  Lack of success herein due to various factors: - Improper use of antibiotics - Increased transmission - Priority of disease control less imminent  Risk -> outbreak  Terminology Rates are expressed per 100,000 inhabitants TB mortality = number of deaths from TB TB lethality = deaths from TB at a certain point of time expressed as % of incidence  TB prevalence = number of TB cases at a point in time  Infection prevalence = % of population infected with TB  TB incidence = number of TB cases infected in a defined year  Infection incidence = number of new cases (re-) infected with TB in a certain year  Tuberculin index = % of a defined age-group of a defined population developing a positive tuberculin test at a given point in time    Terminology     Bacterial resistance = 1% of TB bacilli population insensitive to chemotherapy Resistance: mono / multiple INH = 5-10%, RMP rare Resistance: primary / secondary MDR-TB -> resistant to both INH + RMP Blessing or threat? TB is rare in industrialized countries  If undetected, increased morbidity follows  Outbreak to the general population may be the result  Current situation in the Netherlands (NL). Mortality rate = 2 / 100,000  Morbidity rate = 20 – 50 / 100,000  1n 1987, 1229 cases recorded  Current problems -> emergence of drug resistance and HIV-infection.  100% 80% 60% 40% 20% 0% 1981 1984 1987 1990 1994 Total Immigrants Dutch Prognostic factors.        Extent of the disease Cavernous lung disease Family history of tuberculosis Social factors Nutrition status Immune state R/ TB in the year 2000 TB -> still a leading cause of death in developing countries  TB -> kills 3 million people a year worldwide  3 current epidemics -> HIV, resurgence of TB, MDR-TB  AIDS + MDR-TB (super bug) -> alliance of error  HIV attributable TB In 1990 -> 4%  In 2000 -> 14%, of which 40% in subSaharan Africa, another 40% in South East Asia  Global mortality from TB associated with HIV in 1990 -> 116,000  TB in HIV-positive subjects  M. Tuberculosis:  Prevalence is higher than in HIVnegative subjects;  Often preceeds the diagnosis of AIDS, is commonly a reactivation of a latent infection;  Other mode of presentation than in HIVnegative individuals. TB variance in HIV + and HIV subjects. Features Age incidence Fever Caseation AFB’s Tuberculin test Calcification Hilaradenopathy Cavitation Extrapulmonary sites HIV + 20 – 50 years Common Minimal Present, often extracellular Negative in 60% Absent Bilateral Rare In 50% HIV – 50 + years Common Present Present, usually intracellular Positive in most Present Unilateral Common Rare Atypical TB in HIV-postives.  Atypical TB:  MAIS- complex, exposure difficult to escape;  Late manifestation of HIV disease, an expression of severe immunosuppression;  Is usually widely disseminated, lung is not the primary organ affected;  Heaps of intracellular AFB’s;  Is to be seen as a harbinger of death. Prevention and control of TB  2 basic strategies of paramount importance:  Timely identification and effective treatment  Effective and timely screening of close contacts Contact tracing Ring 1 = high contact, 20% risk of infection  Ring 2 = moderate contact, 4% risk  Ring 3 = little contact, 0,3% risk  Positive case finding in an inner ring, influences testing in an outer ring  Summary (1) Past R/ ineffective -> high morbidity and mortality  Chemotherapy and improved socioeconomic conditions -> a radical change in R/ -> ambulant and in out-patient setting  Result -> TB, a rare disease in industrialized countries  Summary (2)    In 1980+ : relaxation / dismantling of TB control network HIV epidemic causes TB resurgence Drug resistance leads to MDR-TB in  Sub-Saharan Africa and South East Asia  Some states of the USA  Might become a problem in W. Europe  A 3rd epidemic with MDR-TB should be avoided at all costs Recommended literature Styblo K.  Brudney et al  Ryan Fr.  Dolin PJ et al  Gyselen A.  Recommended sites New York’s Health department  Global netwerk TB control  Centers for disease control & prevention  John Hopkin’s  National Institute of Allergy & Infectious Diseases  Tuberculosis testing  Discuss global TB program  Further links Search for TB articles  Personal stories, support groups  National Library of Medicine  World Health Organization  Tuberculosis control in NL  Tuberculosis control in Belgium 