Case Study: Risk Assessment and Potential Interventions for Tuberculosis in Travelers
Case Study: Risk Assessment and Potential Interventions for Tuberculosis in Travelers
By Anisha P. Kamath, Vamsi K. Kantamaneni and Maria D. Mileno, MD
Anisha P. Kamath and Vamsi K. Kantamaneni are final year medical students at Government Medical College, Miraj, India and Kasturba Medical College, Manipal, Manipal University. Dr. Maria Mileno is Associate Professor of Medicine, Division of Infectious Diseases, at Brown University, Alpert Medical School.
The authors report no financial relationships to this field of study.
Synopsis: We describe a recent case of cavitary tuberculosis (TB) occurring in a Rhode Island resident along with a review of various approaches to travelers who are at high risk of exposure and infection from TB. Travel medicine advisors and their travelers must be aware of effective and appropriate tuberculosis prevention and screening methods.
Source: Tuberculosis Prevention in travellers by Amy Neilson and Cora A Mayer reprinted from Australian Family Physician Vol.39. No.10, October 2010.
A 23-year-old woman with a past medical history of childhood asthma presented to our emergency room with cough, fever, chills and recent 5 lb. weight loss. Cough was productive of green, yellow and brown sputum for three weeks. She reported a single episode of hemoptysis (1/4-1/2 cup of bright red blood) 3 weeks previously. She smoked 10 cigarettes/day with occasional use of marijuana. Chest imaging showed cavitary lesions in the left upper lobe. (Figure 1) Sputum acid fast stains and cultures showed Mycobacterium tuberculosis complex. When asked about possible TB contacts, she mentioned that she had visited her family in South Korea 2 years ago, and noted that her uncle had a "chronic coughing illness" while she was there. She had no other known potential TB contacts. (See figures 2 and 3, Chest CTs with contrast showing a cavitating lesion in the left upper lobe,below.)
Tuberculosis transmission occurs when a contagious patient coughs, sneezes, or otherwise spreads infectious mycobacteria through droplets that can remain suspended in air for hours. Bovine TB, caused by closely related Mycobacterium bovis, can be transmitted by consumption of contaminated, unpasteurized dairy products obtained from infected cattle. Travel to Mexico represents a potential source of this infection in the western hemisphere.2
TB is a disease with worldwide prevalence, morbidity and mortality. The WHO estimates that one-third of world's population is infected with TB.4 Latent TB infection (LTBI) may progress to active TB, and untreated disease can be fatal. CDC (2012) estimates TB incidence at more than 9 million new cases globally, and nearly 2 million TB-related deaths each year.2 In the United States, the annual incidence is approximately 4 per 100,000, but in some countries in sub-Saharan Africa and Asia, the annual incidence is several hundred per 100,000.2 Many factors have hampered efforts to reduce TB transmission worldwide and they include Multi-Drug Resistance [MDR], Extensively Drug Resistant [EDR] strains, poverty, co-endemic human immunodeficiency virus infections, long standing inability of public health systems in developing countries to deal effectively with the disease, and ever increasing rates of global travel.1
MDR and XDR-TB are of particular concern among HIV-infected and other immunocompromised individuals. Nearly 500,000 new cases of MDR-TB are diagnosed each year, and in some countries the proportions are as high as 20% of TB cases.2 As of early 2010, XDR-TB had been reported in 58 countries.2 Travel medicine advisors may warn about the risks of TB in various countries, but travelers may not seek evaluation unless illness actually occurs. Tuberculosis is a worldwide disease and travelers also must be made aware of the incidence rates of TB, MDR-TB and XDR-TB in the countries they travel to.
Risk Assessment and tools available to ameliorate the risk of TB in travelers1
The risk of TB infection increases with length of travel, extent of exposure to the local population, and also among health care workers, refugees and prisoners. Travelers to highly endemic countries are at substantial risk, of similar magnitude to the average risk for the local population.6
In the Australia guidelines BCG vaccination is recommended for those whose destinationis to a high risk country, which is defined as a yearly TB incidence varying from >40/100, 000 (UK recommendation) to >100/100,0001 BCG vaccine is not routinely utilized in the US.
In terms of duration of travel the risk of latent infection [LTBI] in long-term travelers (3-12 months) to highly endemic areas is calculated from pre- and post-travel tuberculin skin testing [TST].1 It has been found that the risk of infection for longer term travelers approximated that of the local population. Healthcare workers in such geographic areas experience an even higher risk.
Type of Travel and Potential Contacts: No cases of active TB resulting from transmission during air travel have been reported thus far.7,8,9 Long distance aircraft generally have high efficacy particulate air filtration systems which reduce risk by filtering bacteria larger than 0.3 microns thereby removing Mycobacterium tuberculosis.7 Also, aircraft cabins undergo air exchanges in excess of 15 times per hour - more than are employed in negative pressure isolation rooms for MDR-TB cases.7 The WHO recommends that passengers known to have infectious TB avoid travel.7,8,9
One modeling study estimated the risk of infection, given a potential source, to be 1 in 1000. 7 The probability that a person transmits tuberculosis is determined by a number of factors including sputum-smear status, duration and nature of contact, shared air space or ventilation, susceptibility of exposed people and the infectiveness of the traveler with TB.7
The latest WHO international guidelines for the control of tuberculosis in relation to air travel require—after a risk assessment—tracing of passengers who sat for longer than 8 hours in nearby rows adjacent to people with pulmonary tuberculosis who were either smear positive or smear negative.8,9 These guidelines are based on limited research about risk of TB associated with air travel. Also, the true benefit of tracing and screening passengers and crew members is currently unknown.9 A further recommendation is that all commercial air travel should be prohibited until the infected person has two consecutive negative sputum smears for drug-susceptible tuberculosis or two consecutive cultures for multidrug-resistant tuberculosis.8 Ibrahim Abubakar, from the University of East Anglia, chaired the European Centre for Disease Prevention and Control (ECDC) working group on tuberculosis and air travel. He reviewed the evidence from thirty-nine studies looking at transmission of tuberculosis during commercial air travel, to verify if current international recommendations are justifiable.8,9 In all, thirteen studies involving more than 4,328 passengers from 6 countries were analysed. The majority of studies found no evidence of TB transmission. Only two studies reported reliable evidence of transmission.8,9 Contrary to the latest WHO guidelines, for the control of tuberculosis in relation to air travel, a recent study published in The Lancet, March 2010 has reported little risk of tuberculosis transmission via air travel.8,9 The analysis suggests that there is reason to doubt the value of actively screening air passengers for infection with Mycobacterium tuberculosis and that the resources used might be better spent addressing other priorities for the control of tuberculosis.8,9
Societal factors that affect TB transmission include: poverty, urbanization, overcrowding, high population density, migration, reduced health literacy, less autonomy to act upon health recommendations, reduced access to health services, malnutrition and exposure to indoor air pollution. Personal infectivity is dependent upon the number of bacilli present in sputum, the intensity and frequency of coughing and existence of cavitation on chest readiography.
Infants and childrenl ess than 4 years of age are at greatest risk of developing active disease following primary tuberculosis. Risk then declines between the ages 5-10 years, before climbing during adolescence (age 15-19 years) to a second peak at 20-30 years of age. The elderly are at even higher risk.
Health factors that significantly increase the risk of developing active TB include poor nutrition, smoking, diabetes, alcohol misuse, silicosis, malignant disease, chronic systemic illnesses and immunosuppressive therapy. HIV is an important risk factor for acquiring TB infection. Hence the general underlying health of the traveler may impact their risk of infection.
Personal Protective Equipment (PPE) equipment is recommended for travelers who are at higher risk of exposure to patients with active TB, such as healthcare workers. CDC guidelines recommend professionally fitted N-95 respirators with appropriate training regarding their use. WHO advises particular caution during procedures with high risk of TB transmission such as bronchoscopy or sputum induction, and when providing healthcare to patients who may have MDR- or XDR-TB.1 There are no studies to suggest that travelers in planes or buses derive any benefit from PPE.1
BCG Vaccine is used in countries where TB is endemic. The principal use of BCG vaccine is for the prevention of the severe consequences of active TB in young children.2 The vaccines have variable protective efficacy1 (0-80%) with estimate of 50% for BCG vaccines across all age groups. Factors that contribute to this variability are:
a) Host factors: age at vaccination, nutrition status, genetics, HIV status.
b) Vaccine factors: different strains of vaccine, including both phenotype and genotype.
c) Geographical factors: latitude
d) Epidemiological factors: local prevalence of non-tuberculous mycobacteria.
Issues for BCG Vaccination:5
Contraindications: HIV infection, pregnancy, serious illness, impaired immunity, generalized skin diseases with potential for sepsis, previous history of TB or >5 mm tuberculin reaction, significant febrile illness in the preceding month.1
Tuberculin Skin Testing (TST) versus Interferon Gamma Release Assays (IGRAs):6
IGRA (Interferon Gamma Release Assay)3 is an important addition to the diagnosis and control of TB. Interferon gamma is released in response to in vitrostimulation of sensitised T-cells with specific Mycobacterium tuberculosis antigens. These antigens are absent in BCG vaccine strains and most other Mycobacterial species except M.kansasii, marinum and szulgai. CDC recommends TST (and/or QFT-G) testing 8-10 weeks post travel.1 The BMC (Biomedcentral) states that available studies on cost-effectiveness provide strong evidence in support of use of IGRAs in screening high risk groups. In general, the higher unit cost of the IGRAs compared to the TST is compensated for by cost savings through the more targeted performance of chest radiographs and chemoprevention. If increasing evidence that IGRA-positive subjects have a higher probability of progression to active TB holds true, the IGRA-only screening strategy may prove to be a more cost-effective test.
Updated Guidelines for Nucleic Acid Amplification (NAA) Tests for the diagnosis of TB: 10
These tests reliably detect Mycobacterium tuberculosis in specimens one or more weeks earlier than do cultures. Earlier laboratory confirmation of TB can lead to earlier treatment initiation, improved patient outcomes, increased opportunities to interrupt transmission and more effective public health interventions. These are confirmatory tests. CDC recommends that NAA testing be performed on at least one respiratory specimen from each patient with signs and symptoms of pulmonary TB for whom a diagnosis of TB is being considered, but has not yet been established, and also for those in whom the test result would alter case management or TB control activities, such as contact investigation.
Prophylaxis and Treatment for Converters include:
Chemoprophylaxis with 12 months of isoniazid is recommended for those who convert to a positive TB test. WHO recommends preventive therapy with isoniazid for people with HIV who are at risk of TB. They may also benefit from early Highly Active Antiretroviral Therapy (HAART) and close post-travel TST or IGRA testing.1
American Thoracic Society (ATS)/CDC Guidelines for treatment of LTBI2 recommend 9 months of isoniazid as the preferred treatment and 4 months of Rifampin as an alternative. Active TB is treated with a variety of regimens dependent upon the potential for MDR- or XDR-TB in a patient who acquires TB during travel, and whether pregnancy is an issue. For active TB during pregnancy, isoniazid, rifampin and ethambutol are given for 9 months with close monitoring for hepatotoxicity during pregnancy and 3 months postpartum.
Education about TB should be included in a pre-travel visit and travelers can be invited back for post-travel screening.
Eight to ten weeks after travel represents a good time frame for post-travel screening. Travel clinics should also consider annual screening TB among regular travelers whose risk factors warrant it.
What travelers should be tested for TB?6
- Corporate travelers and expatriates traveling to endemic regions for >3months.
- Healthcare workers, including students, working or volunteering in high TB prevalence areas.
- Individuals working in high-risk situations such as refugee and transit camps.
- Individuals with travel-related TB exposure such as known exposures at health facilities.
- Long term tourists and travelers (>3months) who work or reside in regions with a high prevalence of TB.
- International visa requirements: many countries require testing for refugees, immigrants and asylum seekers.
- Tuberculosis Prevention in travellers by Amy Neilson and Cora A Mayer reprinted from Australian Family Physician Vol.39. No.10, October 2010.
- CDC, 2012, http://wwwnc.cdc.gov/travel/yellowbook/2012/chapter-3-infectious-diseases-related-to-travel/tuberculosis.htm
- BMC Health Services Research 2011, http://www.biomedcentral.com/1472-6963/11/247.
- Public Health Agency of Canada 2011, http://www.phac-aspc.gc.ca/tmp-pmv/info/tubercul-eng.php
- Tuberculosis Travel Health Advice New Zealand 2011, http://www.travel-essentials.co.nz/tuberculosis.asp
- QuantiFeron -TB Gold (Cellestis, www.cellestis.com).
- www.thelancet/infection Vol. 10 March 2010.
- Abubakar I. Tuberculosis and air travel: a systematic review and analysis of policy Lancet Infect Dis 2010; 10:176-183
- Tuberculosis And Commercial Air Travel: Inefficient Tracing And Screening Of Airline Passengers: http://www.medicalnewstoday.com/articles/179902.php
- CDC. Updated Guidelines for the Use of Nucleic Acid Amplification Tests in the Diagnosis of Tuberculosis MMWR 2009;58(01):7-10
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