Tuberculosis (TB) causes significant morbidity and mortality among the global civilian population. Historically, TB has also been responsible for a considerable burden of disease among military populations during periods of both peace and conflict. TB will continue to be of importance to the military for several reasons. Military units live and work in confined environments, personnel may deploy to areas highly endemic for TB where there is the potential to be exposed to infected local communities, and they undertake physiologically stressful activities during training and operations. These are just a few of the factors that may increase the risk of acquiring, developing and transmitting TB among military personnel. This review examines the military relevance of TB in the modern era within the context of epidemiological, pathological and clinical considerations of this ancient disease.
- Received May 25, 2013.
- Accepted May 29, 2013.
- Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions
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Tuberculosis (TB) is the second most common infectious cause of death among young adults worldwide.
Military populations have experienced a considerable burden of TB in times of peace and conflict.
Numerous host and environmental factors place military personnel at an increased risk of acquiring, developing and transmitting TB.
TB control within military units is challenging and may significantly impact on operational capability.
Introduction and military relevance
It has been estimated that a third of the world's population, more than two billion people, are latently infected with Mycobacterium tuberculosis.1 After HIV infection, tuberculosis (TB) is the most common infectious cause of death in young adults worldwide. Together with HIV, the major contributors to the resurging global TB epidemic include poverty and drug resistance.2–4
It is well recognised that infection with M tuberculosis has, and will continue to be, of particular relevance to military populations and may significantly impact on operational capability. There are several factors which place military personnel at an increased risk of acquiring, developing and transmitting TB that are related to the environment in which they serve and individual host factors.
The control of TB within communal settings such as military units represents a significant challenge due to the close quarters of operating environments and living conditions. This is exemplified within naval ships and submarines where crews live and work in crowded, enclosed spaces. Extensive transmission of TB has been described in several outbreaks aboard ships of the US Navy.5 ,6 The Royal Navy's experience of an outbreak aboard HMS Ocean in 2006 and extensive contact tracing investigation resulted in the diagnosis of active pulmonary TB in several members of the crew and over 80 cases of latent TB infection (LTBI).7 There have also been similar reports from land units overseas involving new recruits and active duty soldiers in training establishments and military camps.8–14 Of concern, there have been occasional reports of multidrug-resistant TB (MDR TB) among military populations.15
Overseas deployment places military personnel at a significantly increased risk of TB. British Armed Forces have, and will undoubtedly continue to be, deployed on operations and exercises to countries and regions highly endemic for TB. Exposures and activities at close quarters during such deployments may result in primary infection or re-activation of latent disease.16–21
Furthermore, war and armed conflicts have a negative impact on the control of infectious diseases.22–25 The incidence of TB increases during years of war and there are often rapid rises in morbidity and mortality from TB which may persist for many years after the cessation of hostilities.23 Armed conflicts, often in resource-poor regions with limited and fragile health systems, disrupt disease control programmes through the interruption of normal healthcare provision, the reduction in patients’ ability to seek medical attention and the diversion of economic resources from healthcare to military priorities.26 It is axiomatic that as the incidence of TB within a region of conflict increases, the potential risk of infection among foreign troops serving in that region increases concomitantly.
With regard to host factors, it is acknowledged that country of birth may significantly increase an individual's risk of TB. The number of individuals from current and former Commonwealth countries joining the British armed forces continues to rise. Up to 10% of soldiers in the British Army are recruited from overseas, often from countries highly endemic for infectious diseases such as TB and HIV. The young adults joining the armed forces are of the age group which typically experiences some of the highest burdens of these diseases. There have been several reports of the high incidence of LTBI among military recruits in countries with a high burden of disease, which is clearly of both individual clinical importance (to recruits and their families) and operational relevance.11–15
The 16th global report on TB by the World Health Organization (WHO), published in October 2011, estimated that in 2010 there were 8.8 million incident cases of TB with 1.4 million deaths from TB among HIV-negative people and an additional 350 000 deaths from HIV-associated TB.27 The highest incidence of disease occurred in sub-Saharan Africa (276 cases per 100 000 population), primarily attributable to HIV co-infection in this region (Figure 1). The prevalence of TB in the UK in 2010 was 15 cases per 100 000 population and there were a total of 8483 case notifications.
Of considerable concern was the estimated prevalence of MDR TB of 650 000 cases in 2010, reflecting just 16% of the estimated total number of cases that would be identified if all new cases were tested for resistance.
There are two predominant groups of risk factors for TB disease: host factors that determine the probably of developing disease following infection and environmental factors that influence the likelihood of becoming infected in the first instance.
Age and gender are important host factors. In the developing world, TB is typically a disease of the young, affecting those aged 25–44 years and likely to reflect primary transmission in this group. This is also the case in Western Europe in individuals who are immigrants from those endemic countries while in the USA the highest rates of TB are found in the elderly, probably reflecting reactivation of latent TB with waning host immunity.28
The influence of immunocompromise, and in particular the role of HIV infection in driving the TB epidemic, cannot be emphasised enough. It is the most important biological host risk factor for developing disease and the degree of this risk is probably dependent upon the degree of HIV-induced immunosuppression.29–33 The risk of acquiring TB among HIV-positive individuals is 9–16 times greater than those who are of HIV-negative; however, this risk decreases with initiation of appropriate antiretroviral therapy.30–33 The control of the TB epidemic will only be achieved with control of HIV. Other groups with relative immunocompromise and thus at greater risk of TB include those receiving systemic glucocorticoid therapy, tumour necrosis factor-α inhibitors and transplant patients.34–37
This is also the case for those with chronic systemic conditions including diabetes mellitus, renal disease, coeliac disease, gastric surgery, malignancy (particularly haematological malignancies and solid head and neck tumours) and silicosis.38–43
Nutritional status is another important biological factor and malnourished individuals (body mass index<18.5) have an almost threefold increased risk for TB.44 ,45 There has been much recent interest in the role of vitamin D in TB infection which is known to be involved in macrophage activation. Hypovitaminosis is also associated with an increased risk of TB, which is particularly relevant to immigrants from high-incidence countries.46–48 Increased serum iron concentrations may also increase host susceptibility to TB infection.49
Finally, behavioural risk factors and substance abuse are also associated with higher rates of TB including intravenous and non-intravenous drug use, cigarette smoking (both active and passive) and excess alcohol consumption.50–56
Among the social and environmental factors identified, close (generally household) contact with an individual with smear-positive pulmonary TB is the most important risk factor for acquiring TB infection.28 ,57 The severity of disease in the infected individual (and hence increased inoculum size), the greater the duration of exposure to that individual and the more intimate the contact, the greater the risk. This is also the case in community settings of high TB endemicity in which there may be increased transmission due to crowded living conditions and poor ventilation such as hospitals, prisons, nursing homes and homeless shelters.58–62 Similarly, birth in a TB-endemic area carries an increased risk of TB which is the highest in the first 5 years after immigration, but remains higher than many native populations for up to 20 years after arrival.63
Finally, TB is traditionally associated with populations of low socioeconomic status and the impoverished where multiple factors (crowding, poor nutrition, poor access to health services, unemployment and low education) are likely to contribute to increased risk of TB infection and subsequent disease.64
The genus Mycobacterium comprises of aerobic, non-motile, acid-alcohol-fast, Gram-positive, rod-shaped bacilli that may be classified into one of four groups on the basis of microbiological, clinical and epidemiological characteristics. M tuberculosis, the pathogenic organism responsible for the majority of human tuberculous infection, is a member to the Mycobacterium tuberculosis complex, together with Mycobacterium bovis, Mycobacterium africanum, Mycobacterium microti, Mycobacterium canetti, Mycobacterium caprae and Mycobacterium pinnipedii, all of which share considerable genetic homology (Table 1). The term TB is commonly used to describe the spectrum of clinical diseases resulting from infection with M tuberculosis, and to a lesser degree, M bovis.
Mycolic acid is the major constituent of the mycobacterial cell envelope, accounting for >50% by weight, defining the genus and is responsible for its characteristic staining properties. Mycobacteria stain positive with Gram's stain and the mycolic acids resist destaining by acid-alcohol after staining with certain aniline dyes (hence acid-alcohol fast bacilli, AAFB). Many of the 4000 genes within the M tuberculosis genome encode enzymes for lipid biosynthesis and metabolism.65 ,66
Natural history and pathogenesis
Infection with TB is by droplet transmission and occurs when an individual with active pulmonary disease expels aerosol droplets 1–5 mµ in diameter, each containing up to six bacilli, into the environment by coughing, sneezing or speaking.67 ,68 Droplet nuclei may remain airborne for prolonged periods until undergoing surface deposition, dilution or inactivation. The infectious dose of TB in humans is very low (ID50<10 bacilli; infectious dose 50 is the median dose that will infect 50% of an exposed population), and inhalation and deposition in the pulmonary alveolar space of infectious bacilli may result in one of a number of possible outcomes: immune-mediated clearance of the organism (the majority of cases) or established infection which may result in rapidly progressive active disease (primary disease, 5%–10%) or chronic (latent) infection (90% of those with persisting infection) and active disease due to endogenous re-activation after initial infection (post-primary pulmonary disease, 5%) (Figure 2). Over 90% of TB infections do not result in TB disease, with a lifetime risk of active TB disease of 5%–10%.28 This is in stark contrast to an annual risk of 5%–15% in patients with HIV co-infection.70
The probability of transmission of bacilli may be affected by the severity of disease in the index case, proximity and duration of exposure, humidity, ventilation and the presence of ultraviolet light (which inactivates bacilli).71
Over half of infected individuals who develop primary disease, frequently young adults, will do so within the first 2–3 years after infection. Following deposition in the alveoli, macrophages ingest the bacilli which undergo intracellular replication and eventually cause cell lysis and release of further bacilli. If the host immune response does not eliminate the tubercle bacilli there is further ingestion by, and proliferation within, alveolar macrophages and subsequent cell apoptosis. The production and release of cytokines and chemokines by macrophages result in the recruitment of other phagocytic cells (monocytes and more alveolar macrophages) and neutrophils, eventually resulting in the formation of a nodular granulomatous structure called the Ghon focus. Further replication of the bacilli and the involvement of regional draining lymph nodes produces the Ghon (or primary) complex (a Ranke complex consists of a healed and calcified peripheral lung lesion with an associated calcified lymph node).72 ,73
An effective T lymphocyte-mediated Th1 immune response, typically within the first several weeks following infection, will result in quiescent infection. Failure by the host to mount such a response leads to progressive destruction of the lung. Progressive proliferation of bacilli may result in haematogenous spread and the development of disseminated disease (eg, miliary TB in which disseminated disease results in lesions resembling millet seeds). Local spread by erosion of caseating lesions through the pulmonary parenchyma and into adjacent airways may occur resulting in expectoration of bacilli and infectiousness of the host to others. There is significant mortality associated with such individuals if untreated.74
Reactivation of quiescent or latent infection occurs when persisting bacilli suddenly proliferate. The lifetime risk of reactivation of latent TB acquired in childhood or adolescence is 10% which increases with numerous immunosuppressive conditions. Reactivated disease is often localised with scant regional lymph node involvement and less caseation. The lung apices are usually affected and disseminated disease is unusual, except in severe immunosuppression.
The spectrum of clinical manifestations of TB ranges from asymptomatic latent infection to fulminant pulmonary disease and is generally divided into pulmonary and extrapulmonary forms.
Pulmonary TB (defined in the UK as including the lung parenchyma, pleura and mediastinal lymph nodes) is the predominant form of the disease and accounts for up to 80% of all cases in HIV-negative individuals. Pulmonary TB typically has an insidious progression over weeks or months except in some patients with HIV co-infection or severe immunosuppression of another aetiology in whom a rapidly progressive disease, often accompanied with extensive dissemination, may occur over several weeks. Untreated pulmonary TB has an associated mortality of 50%, with 25% of patients developing chronic disease and the remainder recovering spontaneously.75 ,76
Constitutional symptoms typical of pulmonary TB include fever, night sweats, weight loss and malaise.77 However, only 50%–75% of patients with a confirmed diagnosis have a recorded fever and therefore this is an unreliable feature of the disease. Sub-acute respiratory infection is characterised by an initially dry cough which often progresses to sputum production and occasionally haemoptysis. Dyspnoea may reflect extensive parenchymal disease, significant pleural effusion, endobronchial obstruction or pneumothorax. Chest pain is most frequently observed in patients with pleural disease and is generally pleuritic in nature. Physical findings on clinical examination are often few and are of limited value in diagnosing pulmonary TB. Lymphadenopathy and hepatomegaly may occur in disseminated TB but this not a typical presentation.
Classical radiographic abnormalities include pulmonary infiltrates, nodules, cavitation, mediastinal or hilar lymphadenopathy, pleural effusions and atelectasis (often involving the right middle lobe)78–80 (Figure 3). TB has a predilection for the upper zones of the lungs where both the infiltrates and cavities of active disease may be observed and where latent infection often reactivates.81 ,82 However, while these features are suggestive of, they are not specific for, TB. Furthermore, up to 5% of patients with active culture-positive pulmonary TB may have normal chest radiography.83
Pleural fluid analysis may help establish the diagnosis of pleural TB (an acidic exudate with normal or low glucose, predominant lymphocytosis and elevated lactate dehydrogenase and adenosine deaminase) and percutaneous pleural biopsies may give both histological (granulomatous inflammatory changes in 80% of cases) and microbiological (culture positive in 50% of cases) evidence of TB infection.69
While extrapulmonary TB occurs in 15%–20% of immunocompetent individuals, it is identified in >50% of HIV-positive patients. Extrapulmonary disease may be a presentation of either primary or reactivated TB and includes lymphatic, genitourinary, bone and joint, central nervous system, abdominal and disseminated infection and site-specific investigations are often required to aid diagnosis and assessment (Table 2).84
TB lymphadenitis classically involves the cervical and supraclavicular lymph nodes in HIV-negative patients and more commonly the axillary, inguinal, mesenteric and retroperitoneal nodes in those with HIV infection. Mediastinal and hilar lymphadenopathy occur in primary pulmonary and disseminated disease. Other than painless swelling, symptoms are few and lymph node biopsy for culture and histology is the typical means of diagnosis.69
In the context of HIV co-infection, the frequency of pulmonary cavitation becomes progressively less common with declining immunity while the risk of developing extrapulmonary TB (typically involving lymph nodes and the pleura) and disseminated disease increases.85 ,86 The diagnosis of pulmonary TB in HIV-infected individuals may be hindered for a number of reasons. Such patients are more likely to have atypical radiographic findings including non-cavitary pulmonary infiltrates sparing the lung apices.85 ,86 One consequence of the lower frequency of pulmonary cavitation in HIV infection is that patients are more likely to have smear-negative pulmonary disease, although this is also the case for those with extrapulmonary TB.87 ,88 The value of tuberculin skin testing (TST) in patients with HIV is limited due to high false negative rates and in advanced immunosuppression a negative test does not exclude a diagnosis of TB.89
Non-specific investigations such as radiological imaging, biochemistry and histology are cumulatively useful in the diagnosis of TB. However, definitive diagnosis relies upon specific studies including mycobacterial culture, microscopy and staining, molecular methods or, for latent infection, tests assessing cell-mediated immunity.
Staining and microscopy
Mycobacterial staining of smear specimens and subsequent light microscopy is the most commonly used method to diagnose TB worldwide and is rapid, relies upon simple technology and is inexpensive.
The traditional Ziehl-Neelsen staining has a limit of sensitivity of 104 bacilli per mL of sputum and up to 50% of sputum positive TB cultures may have a negative smear.90 This is of particular issue in patients with non-cavitary pulmonary disease. Auramine O staining and fluorescent microscopy increases the sensitivity and improves the yield by 10% over traditional methods (Figure 4).
Early morning sputum samples have a higher yield and the examination of three samples increases the yield still further (the first smear identifies 70%–80% of patients, the second a further 10%–15% and the third another 5%–10%).
This is the preferred laboratory method for diagnosing TB and has other valuable roles including mycobacterial speciation and drug susceptibility testing. Samples are decontaminated with mucolytics and numerous artificial solid culture media are available in which colonies of M tuberculosis may be identified after 3–6 weeks.93
Several recently developed systems using liquid or broth-based media, or a combination, are more rapid and sensitive techniques.94 These generally rely upon radiometric, fluorometric or colorimetric methods to detect growth.95 ,96 Such systems may identify samples positive for mycobacteria within several days as opposed several weeks of traditional culture. Unfortunately, the high costs associated with equipment and reagents are often prohibitive for the use of these systems in areas with the highest incidences of TB.
Drug susceptibility testing is crucial to guide patient management and inform public health policies. Drug-resistant TB includes M tuberculosis that is resistant to one of the first-line anti-tuberculous drugs: isoniazid, rifampicin, pyrazinamide or ethambutol. MDR TB includes M tuberculosis resistant to at least isoniazid and rifampicin, and possibly additional agents. M tuberculosis exhibiting resistance to at least isoniazid and rifampicin as well as at least one of three injectable second-line drugs (capreomycin, kanamycin and amikacin) and a fluoroquinolone is termed extensively drug-resistant (XDR) TB.69
Nucleic acid amplification testing (NAAT) can rapidly identify mycobacteria within 24–48 h and may identify TB in 50%–80% of smear negative sputum samples which are eventually positive by culture.97 NAATs require as few as 1–10 organisms/mL and the sensitivity and specificity are 95% and 98% (respectively) in smear positive sputum samples and up to 88% and 95% (respectively) in smear negative samples.98–101 While smear positivity and a positive NAAT are grounds for a diagnosis of TB, a negative NAAT is not sufficient to exclude such a diagnosis.
A fully automated, highly sensitive, rapid molecular diagnostic tool for TB case detection and drug resistance testing has been described following development through a public–private partnership.102 The GeneXpert platform integrates sample processing with a real-time polymerase chain reaction assay to amplify an M tuberculosis-specific sequence of the rpoB gene which is subsequently probed with molecular beacons for mutations within the rifampicin-resistance determining region.103 ,104 The device uses a disposable cartridge and the entire process from bacterial lysis and nucleic acid extraction to amplification and amplicon detection is self-contained.105 Results are available within 2 h. Such point-of-care tests have the potential to revolutionise the detection of TB and drug resistance in resource-poor settings; however, there are considerable implications in terms of costs and requirements for infrastructure and trained personnel.106
Treatment of active TB
There are four main objectives of effective TB treatment:
To reduce the duration and severity of disease in individuals and thus morbidity and mortality
To reduce the bacillary burden in respiratory secretions and hence prevent the transmission of infection to others
To prevent the emergence of drug resistance with the use of multidrug regimens
To eradicate both actively replicating and persisting bacterial populations to prevent relapse.
Regimens of multiple drugs are recommended in order to target the whole bacillary population and therefore prevent the development of resistant organisms. During the initial, intensive phase of chemotherapy a minimum of three drugs are administered concurrently to reduce the burden of rapidly dividing bacilli, while a minimum of two drugs are used during the continuation phase to sterilise lesions containing slowly dividing bacilli. The use of monotherapy for treating TB is not advised.84 ,107
Generally, there are first- and second-line drugs used for the treatment of TB. The former group includes those of ready availability and in common use for fully susceptible TB. The latter group are typically of greater toxicity and reduced potency (except for the fluoroquinolones) and typically have a role in the treatment of drug-resistant infections. The management of MDR and XDR TB is a highly specialised area and invariably requires prolonged complex drug regimens with potentially significant toxicities. Discussion of such regimens is beyond the scope of this review and specialist advice should be sought.
First-line anti-tuberculous drugs include isoniazid, rifampicin, pyrazinamide and ethambutol. Rifampicin is bactericidal against all populations of (sensitive) bacilli and is a mainstay of treatment. It causes discolouration of body fluids, inducing an orange colour in urine, sweat and tears (a valuable independent marker of compliance). Rifampicin is a potent hepatic cytochrome P450 enzyme inducer (eg, CYP3A4 and CYP2C9) and may cause hepatotoxicity, characteristically cholestasis. It may also produce thrombocytopenia, anaemia and hypersensitivity reactions including fever, rash and joint swelling.
Isoniazid is also highly bactericidal and is more hepatotoxic than rifampicin, resulting in an idiosyncratic hepatocellular injury and an asymptomatic transient transaminitis in 10%–20% of patients and a more severe clinical hepatitis in up to 1% of patients. Risk factors associated with isoniazid-induced hepatotoxicity include increasing age, chronic liver disease, concomitant use of other hepatotoxic drugs (eg, rifampicin) and slow acetylation genotype. Furthermore, isoniazid is an inhibitor of the hepatic cytochrome P450 enzyme system and may cause a sensory neuropathy due to disruption of pyridoxine (vitamin B6) metabolism and therefore co-administration of pyridoxine with isoniazid is recommended.
Pyrazinamide is primarily bacteriostatic but may be bacteriocidal on actively replicating bacilli. It may cause hepatotoxicity; however, the most common side effect is arthralgia (1% of patients) together with hyperuricaemia and gout. Renal-adjusted dosing is required in patients with impaired renal function.
Ethambutol is a bacteriostatic agent active against proliferating bacilli and its most significant side effect, while rare, is a dose-dependent optic (retrobulbar) neuritis which may result in impairment of visual acuity and colour vision. Early changes are reversible but permanent impairment may occur without prompt cessation of the drug. As with pyrazinamide, renal-adjusted dosing may be required. The value of these last two drugs is mainly in preventing the emergence of drug resistance.
Prior to the initiation of TB therapy liver function testing, complete blood count, serum creatinine, uric acid, visual acuity and colour discrimination should be performed and only repeated during the course of treatment if initially abnormal or clinically indicated. Routine monitoring is not advised. In addition, testing for HIV infection should be performed together with hepatitis B and C in patients with epidemiological risk factors.84 ,107
In the UK, the ‘standard recommended regimen’ for the management of active pulmonary (fully sensitive) TB consists of a 6-month fixed-dose combination regimen initially of four drugs for the first 2 months (isoniazid, rifampicin, pyrazinamide and ethambutol) followed by a 4-month continuation phase of two drugs (isoniazid and rifampicin). This is also the regimen of choice for treating sensitive extrapulmonary TB with the exception of central nervous system (meningeal) TB which requires 12 months of treatment and occasionally bone and joint TB which may also need a prolonged regimen. Together with daily dosing regimens, an intermittent (thrice-weekly) regimen is also available which may be considered for patients receiving directly observed therapy.84
While drug regimens for the management of TB in HIV positive individuals are in principle the same as for those who are HIV-negative, concomitant therapy is complicated by several factors including anti-retroviral and anti-TB drug–drug interactions and toxicities, reduced tolerance of high pill burdens and thus adherence to multidrug regimens and the risk of inducing immune reconstitution inflammatory syndrome (a paradoxical worsening of a pre-existing infectious process following anti-retroviral therapy-associated immune recovery and corresponds to a clinical deterioration).108 ,109
Monitoring the effectiveness of treatment in patients with smear-positive pulmonary TB should be by repeat sputum smear examination after 2 months, 4 months and on completion of a standard 6-month regimen. The majority (>95%) of patients with fully sensitive TB are smear-negative after completing 2 weeks of effective short-course chemotherapy.110 Patients may be considered negative after at least three negative microscopic smears on separate occasions over a 14-day period. If sputum smears remain positive the initial phase of treatment is extended. For patients who remain smear- or culture-positive after 4 months of therapy, ‘treatment failure’ should be considered. In individuals with smear-negative pulmonary and extrapulmonary TB, response to treatment is assessed by monitoring improvements in clinical indicators (eg, defervescence, improvement of cough and appetite, and weight gain).
Reasons for failure of patients to improve clinically include poor adherence to treatment, the presence of drug-resistant TB or an alternative diagnosis to TB. Poor compliance causes treatment failure, early relapses and promotes the emergence of drug resistance. The introduction of directly observed therapy and fixed-dose combination drugs are two interventions that improve adherence to TB treatment.111 ,112
If admitted to hospital, patients with pulmonary TB should be separated from immunocompromised patients. Masks, gowns and barrier nursing measures are not required for healthcare workers caring for people with TB unless MDR TB is suspected or aerosol-generating procedures are being performed (eg, bronchoscopy, sputum induction or nebuliser treatment). In-patients with smear-positive pulmonary TB should wear a surgical mask whenever they leave their room until they have completed 2 weeks of appropriate multiple drug therapy.84
Latent TB—diagnosis and treatment
The identification and treatment of individuals with LTBI may reduce the risk of development of active disease by 60%–90% and are beneficial to the individual and have important public health implications by reducing potential sources of infection.113 ,114
The primary indications for LTBI testing are to identify individuals who are at risk of new infection (close contacts of patients with active pulmonary TB) and those at an increased risk of reactivation of latent disease (eg, HIV infection, transplant patients) who would benefit from treatment. Such targeted testing and treatment of LTBI are fundamental to TB control and elimination strategies in many high-income, low TB prevalence countries.115 ,116 While the annual risk of developing active TB among healthy individuals with LTBI is 0.1%, this may be as high as 10% in those with HIV co-infection or other conditions causing immunocompromise.117
The diagnosis of LTBI relies upon tests that evaluate cell-mediated immunity to mycobacterial antigens and include the century-old Tuberculin skin test (TST) and the novel interferon gamma release assays (IGRAs), both of which have well-described limitations, further discussion of which is beyond the scope of this review.118–123 While significant advances have been made in recent years in LTBI diagnostics, the greatest methodological limitation in assessing the performance of IGRAs is the lack of a gold-standard reference test for LTBI, which has made the direct quantification of the sensitivity and specificity of the new tests difficult.120 ,121
UK national guidelines advise that contact tracing in the event of possible human-to-human transmission should be undertaken at the earliest opportunity and not delayed until notification. Screening should be offered to the household contacts of any person with active TB, irrespective of the site of infection. Screening includes an IGRA, TST or chest X-ray, depending upon age, Bacille Calmette-Guerin (BCG) status and infectiousness of the index case, and consideration of BCG vaccination or treatment for LTBI should be offered once active TB has been excluded. Other close contacts of sputum smear positive TB should also be assessed which may include workplace associates.84
There are no specific guidelines concerning contact tracing within a military community, and clearly the nature of the unit (eg, marine or land), its geographical location (eg, UK or overseas) and activities (eg, training or operational deployment) will significantly influence the organisation and execution of any subsequent contact tracing investigation that may be required. Advice from a Service communicable disease consultant, with the involvement of public health, infectious disease or respiratory physicians should be sought at the earliest opportunity to ensure an appropriate and coordinated response.
When considering the merits of treating an individual for LTBI, the potential risk of developing active TB must be balanced against the risk of adverse drug reactions, treatment adherence and completion. Treatment for LTBI should be considered in close contacts of individuals with (non-MDR) pulmonary TB and those with immunocompromise. In the UK, standard treatment regimens for LTBI include either 6 months of isoniazid monotherapy or 3 months of combined rifampicin and isoniazid, depending upon age, HIV status and contacts of those with isoniazid-resistant TB.84 More recently, a once-weekly regimen of rifapentine and isoniazid for 3 months has been shown to be highly efficacious and better tolerated than standard regimens.124–127
TB is an ancient disease and affects a significant number of the global civilian population in terms of both morbidity and mortality. TB has, and will continue to be, of considerable relevance to military populations for several reasons. The confined living and working environments of military units, the deployment of personnel to areas highly endemic for TB, the nature of such deployments and potential for exposure to infected local communities, and host factors including individuals originating from countries with a high burden of TB and the stressful activities of training and operations all increase the risk of acquiring, developing and transmitting TB. It is the duty of physicians charged with the care of military personnel to be alert to the possibility of such infections in those presenting to them and to investigate, refer and treat as appropriate. Specialist advice in available and should be sought.
- Received May 25, 2013.
- Accepted May 29, 2013.
Contributors Initial concept, DW. Co-authorship, MKO and DW.
Competing interests None.
Provenance and peer review Not commissioned; internally peer reviewed.
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