Health Professionals

Travel Health Information Sheets

Tuberculosis

Last updated: November 2007

 

Introduction

Epidemiology

Risk for travellers

Transmission

Signs and symptoms

Treatment

Prevention

Vaccine information

References

Reading list

Links

Introduction

The causative bacterial organisms for tuberculosis (TB) are included in the genus Mycobacterium. Mycobacterium tuberculosis is the most frequent cause of TB worldwide and affects only humans. Mycobacterium bovis, primarily a cattle organism, also can cause disease in humans.

TB is a disease of worldwide importance, and in 1993 the World Health Organization (WHO) declared TB a ‘Global Emergency’ [1].  TB has afflicted the humans since the beginning of recorded history and today is the second leading cause of death from communicable disease [2].  TB and HIV/AIDS co-infection leads to substantial morbidity and mortality.

Epidemiology

Global Epidemiology

TB is responsible for the death of nearly two million people worldwide each year [3].  sub-Saharan Africa has the highest incidence per capita (350 cases per 100,000), but the most number of cases occurs in the South and South East Asia regions [3]. Here there are an estimated 3 million new cases and 600,000 deaths annually, with the majority of cases in Bangladesh, India, Indonesia, Myanmar and Thailand [4]. A global rise in TB incidence is attributed to increasing global population and the vulnerability of those with HIVHHIV to TB infection, especially in Africa [3]. TB can enhance the progression of HIV, and vice versa, and is the leading cause of death amongst HIV positive individuals in low income regions of the world [3].

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Risk for Travellers

The majority (>70%) of cases of TB reported in the UK occur in those born abroad, with most cases occurring in people born in sub-Saharan Africa and Asia. It is likely that many of these cases acquired infection in their country of origin. However, the complex natural history of TB means that the exact time and place of infection often cannot be determined, making it extremely difficult to estimate the incidence of TB as a travel related disease. The risk for travellers to highly endemic countries (TB incidence of ³40 cases/100,000 population) is likely to be increased, particularly when the traveller undertakes activities such as health care work or where there is prolonged close contact with the local population such as travel for visiting friends and relations [5,6].

There has been concern about transmission of communicable diseases including TB during air flights. The Centers for Disease Control and Prevention (CDC) studied six separate incidents of airplane travel by a person subsequently found to be suffering from TB [7]. Evidence of transmission was found in two of these investigations [7,8,9]. In the first case, transmission took place between an infected flight attendant and other cabin crew, where the cumulative flight time exposure was greater than 12 hours [8]. In a second case TB was transmitted during a long flight to passengers seated in close proximity to the index case [9]. The WHO have also evaluated the risk of TB during air travel [10]. The CDC and WHO have concluded that the risk of TB transmission on an aircraft does not appear to be greater than in other confined spaces [7,10].

Transmission

Almost all TB infections are transmitted through inhalation of infected respiratory droplets passed on when a person with open pulmonary tuberculosis is coughing. Prolonged exposure to the infective organism is usually required and brief contact carries little risk.

Uncommonly TB can be contracted through consumption of milk or food contaminated with M. bovis.

Laboratory personnel and pathologists are at risk of inoculation of bacilli through cuts and scratches. 

Signs and symptoms

In most cases, primary TB infection is either asymptomatic or a febrile respiratory illness of short duration. The infection is usually contained by the host’s immune system and becomes dormant, termed latent tuberculosis infection (LTBI). Therefore, the vast majority (90%) of immunocompetent people infected will never develop disease. Development of disease is most likely to occur in the first few years after infection; those most at risk are young children and persons with an underlying medical condition (e.g. poorly controlled diabetes, renal failure, transplantion, malignant disease or HIV infection and AIDS), or with other predisposing risk factors such as malnutrition.

LTBI can reactivate many years after the initial exposure. Reactivation often occurs in settings of advanced age or immune compromise such as corticosteroid therapy, cancer treatment or HIV infection.

TB disease can affect any part of the body. Primary TB infection most commonly occurs in the mid and lower lung, with regional spread to the hilar lymph nodes. Reactivation pulmonary disease often occurs with cavitation in the upper lung zones. Disease may also be extrapulmonary. The most common sites are the lymph nodes, pleura, genitourinary system, bones and joints, and central nervous system (CNS); disseminated or military disease also occurs. CNS involvement includes inflammation of the meninges (TB meningitis) or space occupying lesions of the brain (tuberculoma).


Patients with pulmonary TB may have a productive cough with purulent sputum, breathlessness and chest wall pain. Additional symptoms are often non-specific: weight loss, malaise and night sweats. However, some patients even those with extensive disease may have no symptoms at all. Diagnosis is made by radiological examination and sputum smear microscopy. Those with pulmonary TB are infectious for as long as the bacteria remain in the sputum. 

Extra pulmonary disease can present in a variety of ways depending upon the site (e.g. CNS symptoms include cranial nerve palsies, motor and sensory defects, seizures and coma), though weight loss and malaise are often key features. Diagnosis may require tissue sampling. Those with extrapulmonary TB are generally not infectious to others.

Treatment

The standard initial treatment of TB is the use of first-line anti-TB medications: isoniazid, rifampicin, pyrazinamide and ethambutol [11]. TB that is resistant to isoniazid and rifampicin is defined as multi-drug resistant TB (MDR-TB) and second-line drugs are required. In the late 1980s and early 1990s low income countries as well as the United States and Europe had outbreaks of MDR-TB [12]. More recently, extensively drug resistant strains of TB (XDR-TB) have emerged globally, and present a serious public health threat [12,13]. Most cases of XDR-TB have occurred in eastern Europe, western Asia and South Africa. Vulnerable groups include the immunocompromised, particularly those living with HIV [14] and those living in poverty. In response to the emergence of XDR-TB, the WHO has published recommendations for its prevention and control [15].

In 1991 the World Health Organization (WHO) implemented the Directly Observed Treatment Short Course (DOTS) strategy for treatment and control of TB globally [16]. This strategy aims to maximise completion of treatment and reduce the incidence of drug resistant strains. The strategy’s recommendations include government commitment to TB control, prompt case detection by sputum smear microscopy, and a standardised treatment regime with directly observed treatment for at least the first two months. Although there have been successes with the DOTS strategy, in areas with high HIV prevalence the approach has been less effective and additional strategies are needed to achieve a reduction in tuberculosis morbidity and mortality [17].

Drug treatment needs to be continued for several months; usually six months for pulmonary TB and often longer for bone or meningeal TB. Lack of compliance with medications is a major contributing factor to development of drug resistant strains of TB, a problem that the DOTS strategy aims to reduce.

Prevention

Primary prevention against tuberculosis is by vaccination with BCG (Bacillus Calmette-Guérin) vaccine. In the United Kingdom, vaccination against TB (BCG vaccine) forms part of the UK national immunisation programme and is targeted to high risk individuals that includes some travellers [18].

In addition to vaccination, those caring for TB infected individuals should be advised to adhere to local protocols, that may include isolation and barrier nursing procedures. The use of FFP3 masks is recommended for healthcare workers where risk of infection is high (i.e. during cough–inducing procedures such as intubation or suction on individuals with active, untreated TB) and when they are caring for patients MDR-TB for as long as the patient remains infectious [11,18,19].

Vaccine Information

Tuberculin skin testing prior to BCG vaccination – Mantoux test

In the UK, tuberculin skin testing (TST or Mantoux) is used either prior to BCG, in order to determine whether there has been previous infection with Mycobacterium tuberculosis (BCG should not be given if TST indicates previous exposure), or as an aid to diagnosis [18,20].

TST testing prior to BCG is necessary for:

  • Those aged 6 years and over
  • Children aged under 6 years who have lived in a country with an annual TB incidence of 40/100,00 or greater for longer than 3 months
  • Close contacts with a known TB case
  • Those with a family history of TB infection in the last 5 years

Bacillus Calmette-Guérin (BCG) 

Indications for use of vaccine

BCG vaccine offers protection in children against the most severe forms of the disease, including meningeal and miliary TB [21]. 

Vaccination requires intra-dermal injection and should be carried out by healthcare professionals skilled in this technique.

In the UK, vaccination against TB forms part of the UK national immunisation programme and is targeted to high risk individuals [18]. BCG vaccination is recommended for:

  • All infants (aged 0-12 months) living in areas of the UK where the annual incidence of TB is 40 cases/100,000 population or greater
  • All infants (aged 0-12 months) with a parent or grandparent who was born in a country where the annual incidence of TB is 40/100,000 or greater
  • Previously unvaccinated children aged one to five years with a parent or grandparent who was born in a country where the annual incidence of TB is 40/100,000 or greater
  • Previously unvaccinated, tuberculin-negative children aged from six to under sixteen years of age with a parent or grandparent who was born in a country where the annual incidence of TB is 40/100,000 or greater
  • Previously unvaccinated tuberculin-negative contacts of cases of respiratory TB (following recommended contact management advice) [11,18]
  • Previously unvaccinated, tuberculin-negative new entrants under 16 years of age who were born in or who have lived for a prolonged period (at least 3 months) in a country with an annual TB incidence of 40/100,000 or greater

In addition, TB vaccination is recommended for the following two groups of travellers:

  • Previously unvaccinated tuberculin-negative travellers under 16 years of age, going to live or work with local populations for three or more months in a country where the annual incidence is 40/100,000 or greater
  • Individuals at occupational risk including healthcare workers aged less than 35 years of age, irrespective of duration of stay. 

There is a little evidence of vaccine efficacy in adults (i.e. those aged 16 years and older) and vaccination is only recommended for such individuals in special circumstances [18,22]. Repeated BCG vaccination is not recommended as there is no evidence that re-vaccination confers additional protection [18].

Pre and post travel screening for tuberculosis

For travellers for whom BCG vaccination is not an option, pre and post travel tuberculin skin testing may be considered, either as a screening test for latent or recent infection or as an aid to diagnosis of active disease [11,22]. 

The measurement of interferon gamma (IFN-gamma), as means to identify active or LTBI, may be used as an alternative to TST in some countries [23,24].  In the UK, the acceptability and efficacy of IFN-gamma testing is still under evaluation [11,25]. 

Availability of vaccine

BCG vaccine contains a live attenuated strain of the tuberculin bacillus (Danish strain 1331). BCG Vaccine manufactured by the Statens Serum Institute (SSI) is the only vaccine available in the UK.

BCG Vaccine

Vaccine

Manufacturer

Schedule

Age range

BCG Vaccine “SSI”

Statens Serum Institut

Single dose following negative tuberculin testing*

Infants below 12 months: 0.05ml

Children aged 12 months and over and adults: 0.1ml

Tuberculin PPD SSI

Tuberculin

Manufacturer

Schedule

Age range

Tuberculin PPD

2TU per 0.1ml

solution for injection

Statens Serum Institut

Single test for tuberculin skin testing

Repeat testing should be avoided within one year

Not specified in SmPC

Refer to Green Book for guidance regarding  indication for testing

* Full details of tuberculin testing and interpretation can be found in the Department of Health publications [18,20].

The specific Summary of Product Characteristics (SmPC) for should be consulted prior to the administration of any vaccine [26,27].

Vaccine schedules

BCG vaccine is administered as a single intradermal dose. Although immunity may wane over time, reinforcing doses are not recommended due to uncertainty about their efficacy and the risk of adverse reactions [18].

Contraindications

BCG vaccination should not be given to:

  • Those who have evidence of a previous BCG vaccination
  • Those with a past history of TB
  • Those with an induration of 6mm or more following TST or Mantoux (SSI)
  • Those with confirmed anaphylaxis to an component of the vaccine
  • Pyrexia or generalised infected skin conditions
  • Neonates in a household where an active TB case is suspected or confirmed
  • Immune suppression including systemic corticosteroid therapy, radiotherapy, malignant conditions, known or suspected HIV infection

Precautions

  • Postpone in those who are acutely unwell
  • Pregnancy. Although the risk of vaccination is theoretical, it is advisable to delay vaccination until after delivery [18].

Adverse events

The expected reaction to a successfully administered BCG vaccine is induration at the vaccine site followed by development of a lesion that may ulcerate before it heals, leaving a small, round, flat scar.

No other vaccines should be administered in the arm used for BCG vaccination for 3 months due to the risk of regional lymphadenitis.

BCG vaccine should be administered strictly intradermally at the insertion of the deltoid muscle, or lateral thigh. Inadvertent subcutaneous administration or administration higher on the arm has been associated with an increased risk of local reaction and keloid formation.

Undesirable adverse events include:

  • Uncommon: headache, fever, enlargement of regional lymph node, ulceration with discharge at the site of vaccination
  • Rare (<1/1,000): Disseminated BCG complications including osteomyelitis or osteitis, allergic reactions including anaphylaxis, lymphadenitis, abscess formation

References

1. Dolin PJ, Raviglione MC, Lpcjo A. A review of current epidemiological data and estimation of future tuberculosis incidence and mortality. World Health Organization 1993. WHO/TB/93.173. Available at http://www.who.int/tb/publications/1993/en/index.html [Accessed 27 November 2007]

2. Frieden TR, Sterling TR, Munsiff SS et al. Tuberculosis. Lancet 2003;362:887-99.

3. World Health Organization. Tuberculosis Fact Sheet No 104, revised March 2007.  Available at http://www.who.int/mediacentre/factsheets/fs104/en/ [Accessed 1 December 2006]

4. World Health Organization. Regional Office for South East Asia. Communicable Diseases: Tuberculosis. Available at http://www.searo.who.int/en/Section10/Section2097.htm [Accessed 3 May 2007]

5. Health Protection Agency. Migrant Health: Infectious diseases in non-UK born populations in England, Wales and Northern Ireland. A baseline report – 2006. London: Health Protection Agency.

6. Cobelens FG, van Deutekom H, Draayer-Jansen IW et al.  Risk of infection with Mycobacterium tuberculosis in travellers to areas of high tuberculosis endemicity. Lancet 2000;356:461-5.

7. Centers for Disease Control and Prevention. Exposure of passengers and flight crew to Mycobacterium tuberculosis on commercial aircraft, 1992-1995. Morb Mortal Wkly Rep. 1995;44:137-40.

8. Driver CR, Valway SE, Morgan WM et al. Transmission of M. Tuberculosis associated with air travel. JAMA 1994;272:1031-5.

9. Kenyon TA, Valway SE, Ihle WW et al. Transmission of multidrug-resistant Mycobacterium Tuberculosis during a long airplane flight. N Engl J Med 1996;334: 933-8.

10. World Health Organization. Tuberculosis and Air Travel: Guidelines for prevention and control. Second Edition. World Health Organization 2006. Available at http://whqlibdoc.who.int/hq/2006/WHO_HTM_TB_2006.36

3_eng.pdf [Accessed 21 November 2007]

11. The National Collaborating Centre for Chronic Conditions. Tuberculosis: Clinical diagnosis and management of tuberculosis and measures for its prevention and control. NICE guideline - second consultation. 13 September, 2005 London. The Royal College of Physicians.

12. Centers for Disease Control and Prevention. Emergence of Mycobacterium tuberculosis with Extensive Resistance to Second-Line Drugs Worldwide, 2000-2004. MMWR March 24 2006,55,11:301-305 Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5511a2.htm

13. World Health Organization. Frequently asked questions – XDR-TB. 17 October 2007. Available at http://www.who.int/tb/xdr/faqs/en/index.html [Accessed 21 November 2007]

14. Gandhi NR, Moll A, Sturm AW, et al. Extensively drug-resistant tuberculosis as a cause of death in patients co-infected with tuberculosis and HIV in a rural area of South Africa. Lancet 2006;368:1575-80.

15. World Health Organization. Extensively drug-resistant tuberculosis (XDR-TB): recommendations for prevention and control. Weekly Epidemiological Record. 2006:81:425-32. Available at: http://www.who.int/wer/2006/wer8145/en/index.html

16. World Health Organization Global Tuberculosis Programme. An expanded DOTS framework for effective tuberculosis control. WHO/CDS/TB2002.297. WHO 2002. Available at http://www.who.int/tb/publications/expanded_dots_framework

/en/index.html [Accessed 27 November 2007]

17. Laserson KF, Wells CD. Reaching the targets for tuberculosis control: the impact of HIV. Bull World Health Organ 2007;85:377-81)

18. Immunisation against infectious disease Department of Health. Tuberculosis. Chapter 32 In: Immunisation against infectious disease. 2006. Available at: http://www.dh.gov.uk/en/Policyandguidance/Healthandsocial

caretopics/Greenbook/DH_4097254

19. Health and Safety Executive. Respiratory protective equipment at work: a practice guide. London: HSE, 2005

20. The Department of Health. The Mantoux test: Administration, reading and interpretation. NHS. The Department of Health Publications. Available at http://www.immunisation.nhs.uk/files/mantouxtest.pdf

21. Rodrigues LC, Diwan VK, Wheeler JG. Protective effect of BCG against tuberculous meningitis and military tuberculosis: a meta-analysis. Int J Epidemiol 22:1154-8

22. Department of Health. Joint Committee on Vaccination and Immunisation. BCG Statement. 23 July, 2007. Department of Health Available at http://webarchive.nationalarchives.gov.uk/20130107105354/

http://www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets

/@dh/@ab/documents/digitalasset/dh_094742.pdf

23. MMWR. Guidelines for using Quantiferon ® TB Gold Test for detecting Mycobacterium tuberculosis infection. United States. Dec 16, 2005 /54 (RR15;49-55. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5415a4.htm

24. Drobniewski F, Cobelens F, Zellweger JP. Use of Gamma-interferon assays in low and medium prevalence countries in Europe: a consensus statement of a Wolfheze Workshop organised by KNCV/Euro TB, Vilnus. September 2006

25. Health Protection Agency Position Statement on the use of Interferon Gamma Release Assay (IGRA) tests for tuberculosis (TB). Draft Interim Guidance. HPA Tuberculosis Programme Board. October 2007

26. Summary of Product Characteristics: BCG SSI. Statens Serum Institute. Denmark. Available online at http://www.ssi.dk/sw10375.asp

27. Core Summary of Product Characteristics. Tuberculin PPD. Statens Serum Institute. Denmark. Available at http://www.ssi.dk/sw46139.asp. [Accessed 21 November 2007].

Reading list

Grange JM, Zumla A. Tuberculosis. In Cook GC, Zumla Z (eds.) Manson’s Tropical Diseases 21st edition. 2003, Elsevier Science Ltd.

WHO. Global Tuberculosis Control: Surveillance, Planning, Financing. WHO Report 2006. Geneva, WHO/HTM/TB/2006.362. See http://www.who.int/tb/publications/global_report/

Links

Health Protection Agency http://www.hpa.org.uk/infections/topics_az/tb/menu.htm

Word Health Organization, WHO country data: estimated burden of TB. Available at

http://www.hpa.org.uk/infections/topics_az/tb/epidemiology/

who_table1.htm

World Health Organization, Global Health Atlas. Available at http://www.who.int/globalatlas/dataQuery/default.asp

World Health Organization, Emergence of XDR-TB. Available at http://www.who.int/mediacentre/news/notes/2006/np23/en

/index.html

World Health Organization. Frequently asked questions XDR-TB. Available at http://www.who.int/tb/xdr/faqs/en/index.html

Tuberculosis: Guidelines, Reviews, Statements, Recommendations, Standards. Geneva Foundation for Medical Education and Research. Available at http://www.gfmer.ch/Guidelines/Tuberculosis/Tuberculosis_

mt.htm