INFECTIOUS DISEASES Tuberculosis (TB): targeting our interventions

Transcription

1 révention en pratique médicale INFECTIOUS DISEASES Tuberculosis (TB): targeting our interventions Latent tuberculosis infection (LTBI) remains asymptomatic until it evolves into disease, often in circumstances where it is more difficult to treat and where close contacts may have already become infected. This is why it is so important to detect LTBI as soon as possible. The priorities of the ministère de la Santé et des Services sociaux du Québec for tuberculosis control continue to be management and follow-up of tuberculosis disease cases and of their close contacts. Most often, these patients are followed by the Public Health Department, in collaboration with the CLSCs and specialised services. Beyond these cases, cases of LTBI are frequent. It is important to identify those with LTBI who would benefit from treatment. The importance of early TB detection to prevent outbreaks Every week, 4 new cases of tuberculosis disease are discovered in Montréal. This means that every year in Montréal, there are 180 to 200 new cases, for a rate of 11/100,000. The best way to prevent TB from spreading is to diagnose it quickly and to start treating TB disease cases without delay. The clinical features of tuberculosis disease can easily be mistaken for those of pneumonia or other respiratory diseases. More than one physician has been fooled, particularly since TB is often ruled out as a diagnosis because it seems (wrongly) so unlikely here in Montréal. Do not hesitate to refer a patient to a specialist to establish a specific diagnosis if his or her chest X-ray is abnormal and clinical signs even slightly suggest tuberculosis. The earlier the treatment starts, the sooner the risk of transmission stops. The general practitioner is essential for detecting and treating LTBI Screening for and treating latent tuberculosis infection can reduce the number of cases of tuberculosis disease and reduce future risks of transmission. It is up to general practitioners to identify individuals among their patients who belong to the groups at risk and to integrate LTBI detection into their routine practices. In Montréal, almost 80% of TB disease cases are among recent immigrants who have come from countries where TB is endemic. Individuals from certain groups should be screened for latent tuberculosis infection because they are more at risk of having been infected previously and more susceptible of developing the disease once they have been infected. Rate of TB disease in Canada by region of origin and estimates for LTBI Region Incidence Prevalence of origin of TB disease of LTBI(%) 1 (per 100,000) Born in Canada Non-Aboriginal 1.5 < 5 Aboriginal Born outside Canada Europe 5 < 10 South America Central America Asia Africa (1) estimates for young adults November

2 Who should be screened? Detecting latent TB infection (LTBI) Latent tuberculosis infection is defined as the presence of active tubercle bacilli in the body. Bacilli are usually detected by a hypersensitivity to tuberculin, as demonstrated by the tuberculin skin test (TST), also called the Mantoux test or PPD. LTBI is not contagious and is not on the list of reportable diseases. Screening for LTBI identifies people with the infection and for whom isoniazid (INH) prophylaxis will reduce the risk of progressing to the active phase of the disease (TB disease). Screening health care workers Over the last several years, it has been recommended that every new employee in health care institutions be asked to undergo a two-step TST when he or she is hired. Health science students in comprehensive schools and CEGEPs, as well as trainees in health care facilities are also asked to undergo testing. Screening people who are in a situation where they may potentially be exposed to tuberculosis on a regular basis allows us to determine the baseline level of an individual s response to the tuberculosis protein, and shows whether or not the person has ever been in contact with the tubercle bacillus. Immigrants and refugees All immigrants to Canada who had an abnormal chest X-ray suggestive of a past history of TB when evaluated in their country of origin are placed under medical surveillance by the federal government. In Montreal, the Public Health Department ensures that these people are refered to a specialised clinic within 30 days of their arrival in Canada. Refugee claimants are seen by a physician from Immigration Canada within 5 working days following their request for asylum in Canada. If an abnormal chest radiograph suggests active TB or a prior history of TB, they are referred to a specialised clinic for follow-up. The federal programme does not require immigrants or refugees to undergo systematic LTBI detection. Prophylaxis INH prophylaxis should be offered to people whose TST results measured in millimetres correspond to the cut-off levels defined for each risk factor (see Table LTBI: who should be treated ). If prophylaxis is refused or cannot be administered due to a contraindication, the patient should be informed of the symptoms of tuberculosis and told to consult a physician should he or she develop these symptoms. Groups at risk for whom LTBI screening is indicated Groups in which LTBI prevalence is high close contacts of patients with pulmonary tuberculosis; people born in endemic regions who immigrated to Canada within the last 5 years: Asia, Africa, India, Middle-East, Central and South America, Caribbean; Aboriginal communities. Clinical risks of developing tuberculosis disease once infected people with HIV; people with illnesses that increase the risk of developing tuberculosis once they have been infected: immunosuppression, gastrectomy, chronic renal failure, silicosis, diabetes mellitus, chronic malnutrition, injection drug use, leukaemia, or Hodgkin s disease; Clinical risk factors for LTBI developing into TB disease people with a chest radiograph showing signs of inactive tuberculosis who have not received adequate treatment. Condition Relative Annual risk Lifetime risk of developing cumulative TB disease (%) risk (%) 1 AIDS HIV infection Transplantation Pulmonary silicosis Chronic renal failure/haemodialysis LTBI for at least 2 years Carcinoma of head and neck Abnormal chest X-ray - fibronodular disease Diabetes Abnormal chest X-ray - granuloma No known risk factor The indications for screening are clear. Avoid screening if not indicated. 1 Estimates for young adults 2 Prévention en pratique médicale, November 2001

3 How to perform a TST Performing and reading a TST Only a TST can detect latent TB infection (LTBI) Chest radiography is not useful for LTBI screening. A person who has a significant reaction to a TST should undergo a medical examination and chest radiography to exclude tuberculosis disease. A person for whom a significant reaction has been documented in the past will not have to be retested in the future, whatever the circumstances. A diagnosis of LTBI The tuberculin skin test (TST) is the best method for diagnosing tuberculosis infection. It is administered by injecting intradermally a small quantity (5 TU) of purified proteine derivative (PPD) tuberculin. The injection elicits a delayed-type (cellular) hypersensitivity reaction within 48 to 72 hours. It produces induration around the site of injection and should be measured perpendicular to the long axis. However, delayed cell-mediated reaction will not be manifested immediately in persons who have been newly exposed to and become infected with tubercle bacilli (such as the close contacts of an index case). It will only develop from 3 to 8 weeks after acquisition of the infection. Nonetheless, close contacts should undergo TST immediately to document their current immunological status. For these cases, a second TST should be performed after 8 weeks if a result measures less than 5 mm. Two-step testing Tuberculin testing may elicit a mild reaction yet stimulate a secondary immune response; consequently, a subsequent TST, performed any time from 1 week to 1 year later, will elicit a much greater response. A second test performed soon after will detect this booster reaction: its value will serve as a base measurement for follow-up and for diagnosing conversion. It is important to recognise the booster reaction as it could be confused with (recent) tuberculin conversion. Two-step testing is only recommended for people who will be retested periodically, such as health care workers. If the first TST measures less than 10 mm, a second test should be done as soon as possible, a minimum of 7 days following the first test. Contraindications to the TST TST is contraindicated for the following people: anyone who has had a severe tuberculin reaction in the past (blistering abcess at injection site); anyone who has ever been treated for LTBI or tuberculosis disease in the past; anyone with a major viral infection or who has received a live-virus vaccine in the past 6 weeks (such as MMR) which can cause false-negative TST results. Other causes of false-negative reactions include: poor injection technique; immune suppression (advanced age, corticosteroids, cancer therapy agents, HIV with CD4 <500); malnutrition; tuberculosis disease (anergy). There are no contraindicatinos to the TST for the following people: anyone who has recently received killed virus vaccine; pregnant women; anyone who has received BCG vaccination in the past; anyone who says they have had a positive TST result, if this is not documented. Failed TST: when and how should it be repeated? If the papule is not clearly defined, another TST should be done on the other forearm, during the same visit. Developing a good technique for performing a TST requires much practice. If you do not perform these tests regularly, it might be preferable that you refer the patient to specialised resources. Intradermal injection of 0.1 ml (Tubersol) into the inner surface of the forearm (needle bevel facing upward). Formation of a papule (texture of an orange peel). Delimitation of the zone to measure (48-72 hours after the injection): - push the tip of a medium ballpoint pen held at a 45 o angle towards the site of injection, perpendicular to the axis of injection; - make a mark where the tip stops, which will be at the edge of the induration; - repeat on the other side. Measure the distance between the two marks in millimetres. BCG and interpreting TST results Persistant reactions > 10 mm are seen in 10% to 25% of people vaccinated with the Calmette- Guérin (BCG) bacillus vaccine after the age of 2. Among non-native Quebecers and immigrants from industrialised countries who received BCG vaccination after 2 years of age and have no other risk factors, BCG vaccination would likely be the cause of a positive test that true infection. Therefore, we do not recommend LTBI screening for these groups. However, previous BCG vaccination should be disregarded among the following groups, no matter the age at which the individual received the vaccine: immigrants from TB-endemic countries; Native Canadians; close contacts of a case of tuberculosis disease; individuals at risk of developing the disease if they are infected. Pré vention en pratique mé dicale, November

4 The epidemiology of tuberculosis Globally, tuberculosis continues to be a major health problem. The World Health Organisation (WHO) estimates that over a third of the world s population is infected with Mycobacterium tuberculosis. In addition, over 8 million new cases of tuberculosis and about 2 million deaths occur each year. In 1993, the spread of human immunodeficiency virus (HIV) and the growing number of drugresistant strains led the WHO to declare tuberculosis a global emergency, a statement that still holds true today. Canada and Québec have one of the lowest rates of tuberculosis in the world (about 6 cases/100,000 inhabitants). However, since 1985 in Montréal, there have been around 180 to 200 new cases of tuberculosis per year, raising the rate of TB disease to over 11 cases/100,000 inhabitants. This figure accounts for almost 60% of the total number of cases in Québec. The face of tuberculosis has changed significantly in Québec over the last 20 years. Cases in urban centres are younger that before, and 80% are among recent immigrants originating from countries where tuberculosis is endemic. The geographical distribution of cases is consistent with the preference of these populations for settling in certain neighbourhoods in Montréal. Montréal s multiethnic character often brings us face to face with issues related to cultural (stigma associated with TB), language, and socio-economic questions, which represent major obstacles to an effective TB prevention programme. LTBI and tuberculosis disease in nursing homes Throughout Québec, the number of cases of tuberculosis disease in nursing homes is no higher than among people of the same age group living in the community. Therefore, it is not indicated to initiate screening for LTBI in this population. However, any case of tuberculosis reported in a nursing home should be followed-up quickly and close contacts given a chest radiography to rule out active tuberculosis. TST should only be performed if it will help clinical decisionmaking. The rate of positive TST results in persons aged 65 and over A world traveller Koch s bacillus the name given to Mycobacterium tuberculosis following its discovery by the German physican Robert Koch in 1882 has travelled widely. The spread of the disease and deaths due to tuberculosis have been under control in most Western countries since the latter half of the 20th century when antibiotics (streptomycin in 1944, isoniazid in 1952, and rifampicin in 1966) were introduced. However, with the increase in international travel and intercontinental migration, tuberculosis has emerged in places where we thought it had disappeared, especially when combined with AIDS. A disease that is getting tougher The capacity of tuberculosis to mutate is just as worrying as its ability to travel worldwide. Over the last few years, new antibiotic-resistant strains have appeared. Although still rare in Québec, these new strains are a clear reminder of the importance of keeping an eye out for new cases and monitoring compliance to treatment. Multiresistance In Montreal, over 84% of Mycobacterium tuberculosis strains respond to all medications. Multiresistance (minimally to INH and Rifampin) is stable and is less than 2%. can be as high as 40%. However, a negative test result does not exclude the possibility of tuberculosis disease. Therefore, it is not indicated to have elderly residents in nursing homes undergo routine TST. Moreover, the number of medications these people already have to take, and their cardiac, respiratory, and hepatic functions should be given particular, case-by-case attention before considering LTBI prophylaxis. TB-HIV co-infection HIV infection is the main factor in about 10% of new cases of tuberculosis in Montréal. It is found especially among patients originating from countries where tuberculosis and HIV are endemic. Children About 5% of cases of tuberculosis in Montréal are children under 15 years of age. We estimate that close to one-third of these cases could have been prevented since the infection was most probably acquired in Québec. Increased vigilance would result in physicians identifying a case of tuberculosis more quickly. This action would reduce the risk of the disease spreading to close contacts of patients, including children, and provide increased protection against peadiatric forms of TB (meningitis or miliary) that can develop rapidly (in a few months) following recent infection. révention en pratique médicale A publication of the Direction de la santé publique de Montréal-Centre in collaboration with the Association des médecins omnipraticiens de Montréal, as part of the Prévention en pratique médicale programme coordinated by Doctor Jean Cloutier. This issue is produced by the Infectious Disease Unit. Head of the unit: Doctor John Carsley Editor-in-chief: Doctor Monique Letellier Editor: Blaise Lefebvre Graphic design: Manon Girard Translation: Sylvie Gauthier Texts by: Doctor Paul Brassard Contributor: Doctor Jean-Pierre Villeneuve Doctor Martin Champagne 1301 Sherbrooke East, Montréal, Québec H2L 1M3 Telephone: (514) l: blefebvr@santepub-mtl.qc.ca Legal deposit 4 th trimestre 2001 Bibliothèque nationale du Québec National library of Canada ISSN: Agreement number: Association des Médecins Omnipraticiens de Montréal 4

5 Practice tips Latent TB infection: whom and how to treat Whom to treat for latent tuberculosis infection? Risk factors TST sensitivity cut-off rates when considering treatment < 5mm > 5 mm < 10 mm >10 mm Children < 5 years with recent close contact with TB disease* treat treat treat HIV infection with recent close contact with TB disease* treat treat treat Immunosuppression with recent close contact with TB disease* treat treat treat HIV infection do not treat treat treat Immunosuppression do not treat treat treat Recent close contact with case of infectious TB disease do not treat treat treat Radiological evidence of old TB not previously treated do not treat treat treat Recent immigration from highly endemic country do not treat do not treat treat (1) Residents and staff at health institutions do not treat do not treat treat No High-risk clinical factors gastrectomy, chronic renal failure, silicosis, diabetes mellitus, chronic malnutrition, injection drug use, do not treat do not treat treat leukaemia or Hodgkin s disease No risk factors (TST not indicated) * These people should have a TST immediately. Even if their TST result is 0 mm, they should be treated. A second TST should be performed 8 weeks after the last contact with the infectious case. If a healthy child s second TST continues to be 0 mm, treatment can be stopped. TST conversion: a tuberculin reaction that has increased 6 mm or more over the size of the last TST (within 2 years) and is greater than 10 mm should be considered a TST conversion and indicates a recent infection. (1) Consider age and other risk factors. How to treat latent tuberculosis infection? Medication Interval Dose Criteria for Comments and duration (maximum) completion Isoniazid daily adults: 5 mg/kg (300 mg) 270 doses Regimen generally recommended for all (INH) 9 months children: mg/kg (300 mg) within 12 months 100 and 300 mg tablets Isoniazid daily adults: 5 mg/kg (300 mg) 180 doses Not optimal regimen (INH) 6 months children: mg/kg (300 mg) within 9 months Not indicated if HIV+ or fibrotic lesions 100 and 300 mg tablets Not recommended for children Rifampin (RMP) daily adults: mg/kg (600 mg) 120 doses Indicated if contact of active case 300 mg tablets 4 months children: mg/kg (600 mg) within 6 months resistant to INH and sensitive to Rifampin or cannot tolerate INH Watch for drug interactions. Rifampin (RMP) adult: mg/kg (600 mg) 300 mg tablet daily children: mg/kg (600 mg) 60 doses Consider for patients with HIV and 2 months within 3 months - not recommended for children Pyrazinamide (PZA) adult: mg/kg (2.0 g) - frequent adverse effects (1) 500 mg tablets children: mg/kg (2.0 g) Watch for drug interactions. * The patient should take the number of doses equal to the number prescribed for the duration of treatment, even if treatment must be prolonged due to non-compliance. A medical evaluation is indicated before re-starting any medication once the patient has stopped for more than 2 consecutive months. (1) Close clinical follow-up, consult a specialist before starting this treatment. No matter what regimen is chosen, add mg pyridoxine (vitamin B-6) daily if patient suffers from alcoolism, malnutrition, or peripheral neuropathy Supplément Prévention en pratique médicale, November 2001

6 Practice tips Managing latent TB infection (LTBI) treatment Monitoring LTBI treatment All patients: initial clinical evaluation including a chest X-ray to rule out the possibility of tuberculosis disease; remind the patient to notify his or her physician or a nurse as soon as the first symptoms of gastrointestinal upset or jaundice appear; medical visit at onset of treatment and at 1 month, and then every 2 or 3 months. People aged years: monitor transaminase levels at onset of treatment and at 1 month. People aged 50 years and over: monitor transaminase levels at onset of treatment, 1 month, and then every 2 nd month. Clinical evaluation of the liver at each visit for patients with: chronic hepatitis HIV infection risk of increased liver disease such as taking other hepatotoxic medications (e.g.anticonvulsants) Medication should be stopped and the patient reevaluated if: transaminase > 3x normal levels and the patient is symptomatic; transaminase > 5x normal levels and patient is not symptomatic. When should a specialist be consulted? When there are complications or drug interactions. When treating LTBI in pregnant women. When treating LTBI in HIV+ patients on antiretroviral therapy. When treating LTBI in a contact of an active case carrying a resistant strain of TB. When diagnosing and managing a case of tuberculosis disease, including interpretating laboratory results. What if a patient with LTBI refuses or cannot take the treatment? No clinical or radiographical follow-up is necessary. Tell the patient to consult if he or she develops symptoms of TB disease. Free medication Since 7 February 1997, all 2L anti-tuberculosis drugs (including pyridoxine) are included in a RAMQ 2k programme providing free medications. Medications are absolutely free for all people presenting their health insurance card. The prescription should indicate: 2k for someone with tuberculosis disease 2L for treatment of latent tuberculosis infection. Resources Montreal Public Health Department Ms. Sylvianne Manseau, TB coordinator Doctor Paul Brassard, TB medical officer Tel.: Hospitals with out-patient clinics specialising in tuberculosis For adults: Montréal Chest Institute Tel.: , extension 2588 Hôpital Maisonneuve-Rosemont Clinique de tuberculose Tel.: , extension 4807 Jewish General Hospital Tuberculosis clinic Tel.: , extesion 1359 Hôpital du Sacré-Cœur Clinique de tuberculose Tel.: , extension 2704 For children: Hôpital Sainte-Justine Tel.: , extension 3900 Montreal Children s Hospital Tel.: Other references Management of Tuberculosis in the United States. Small P, Fujiwara P. N Engl J Med 2001; 345(3): Canadian Tuberculosis Standards, 5 th Edition, R. Long editor, Canadian Lung Association 2000 ISBN , 253pp. (Available through the Quebec Lung Assocation), and as a PDF file on its web site: Epidemiology of Tuberculosis in Montreal. Rivest P, Bédard L, Tannenbaum TN. CMAJ 1998; 158:605-9 Internet International Union Against Tuberculosis and Lung Disease: World Health Organisation: National Tuberculosis Center at Harlem Hospital: New Jersey Medical School National Tuberculosis Center: Canadian guidelines [...] Canada Communicable Disease Report, Vol. 27, No 19, 1 October Prévention en pratique médicale Supplement, November 2001