More than 2 billion people (about one-third of the world population) are estimated to be infected with tuberculosis.1 The global incidence of TB peaked around 2003 and now appears to be declining slowly. In 2006, the WHO estimated the prevalence of active infection to be 14.4 million and the incidence of new cases 9.2 million; 12 of the 15 countries with the highest estimated TB incidence were reported to be in Africa.

Developed nations including the USA and parts of Southeast Asia report an estimated 380 million persons infected with Mtb; about 80% of infected persons in Europe are 50 years of age or older.3

In the USA, TB prevails among the foreign-born and minorities. From 1985 to 1992, TB incidence increased among all ethnic groups except non-Hispanic whites and Native Americans/Alaskan Natives. From 1992 to the present, the overall incidence of TB in the USA declined by over 45%, largely because of improved funding resources channelled into TB control programmes, which allowed for the implementation of directly observed therapy (DOT). However, the percentage of cases among foreign-born persons increased disproportionately from 27% in 1992 to 46% in 2000.4 In 2009, the CDC reported 11 540 TB cases; the TB rate was 3.8 cases per 100 000 population, a decrease of 11.4% from the rate of 4.2 per 100 000 reported for 2008.5 The 2009 rate demonstrated the greatest single-year decrease ever recorded and was the lowest recorded rate since national TB surveillance began in 1953. TB case counts and rates decreased substantially among both foreign-born and US-born persons, although foreign-born persons and racial/ethnic minorities continued to have TB disease disproportionate to their respective populations, and nearly 11 times higher than in US-born persons. The rates among Hispanics and blacks were approximately eight times higher than among non-Hispanic whites and rates among Asians were nearly 26 times higher. The large decrease in reported cases during 2009 might represent a decrease in TB disease resulting from changes in population demographics or improved TB control.

TB also occurs with disproportionate frequency among the elderly.6, 7 Elders living in communal settings such as nursing homes or other long-term care facilities have a TB incidence rate approximately four times greater than the general population.8 The aggregate TB incidence rate for nursing home residents is 1.8 times higher than the rate seen in community-dwelling elderly.9 The enhanced efficiency of TB transmissibility within congregate settings such as prisons, nursing facilities (nursing homes), chronic disease facilities and homeless shelters has raised concerns about TB infection and disease in the institutionalized elderly.10, 11 Positive tuberculin reactivity associated with prolonged stay among residents of long-term care facilities for the elderly has been demonstrated, implying an increasing risk of TB infection.

The pathogenesis of TB infection and disease begins in most cases with the inhalation of the tubercle bacilli.12 The usual inoculum is no more than 1–3 organisms, which are taken up by alveolar macrophages and carried to regional lymph nodes. Spread may occur via the lymphohaematogenous route with dissemination to multiple organs. From 2 to 8 weeks after infection, cell-mediated immunity (CMI) and delayed-type hypersensitivity (DTH) responses develop, leading to the characteristic reactive tuberculin test and to the containment of infection. Chemoattractants cause monocytes to enter the area and become transformed into histiocytes forming granulomas. Although the bacilli may persist within macrophages, additional multiplication and spread is curtailed. Healing usually follows with calcification of the infected focus. Caseous necrosis may result secondary to the immune response. Erosion into a bronchiole causes cavity formation where bacilli can multiply and spread. Solid necrosis can result from production of hydrolases from inflammatory cells causing tissue liquefaction and creating a prime medium for microbial replication, generating up to 10 billion bacilli per millilitre. Individuals who develop active disease either fail to contain the primary infection or develop reactivation as a result of relative or absolute immune suppression at a point remote from primary infection. This is most likely to occur in immunocompetent adults within the first 3 years after exposure. Factors related to progression of disease reflect a weakened immune status and include physiological states, for example, normal ageing; associated intercurrent disease—particularly diabetes mellitus, malignancies causing primary immunosuppression or requiring toxic chemotherapy or corticosteroid-dependent diseases such as asthma or collagen vascular disease; poor nutritional status particularly related to alcohol and drug abuse; smoking and HIV infection. Although it is likely that the increased frequency of TB in the elderly could partly be due to CMI that is impaired by senescence (shown in murine models), other concomitant age-related diseases (diabetes mellitus, malignancy), chronic kidney disease and renal insufficiency, poor nutrition and immunosuppressive drugs may also contribute to this increase.13 In the elderly, approximately 90% of TB disease cases are due to reactivation of primary infection. Persistent infection without disease may occur in 30–50% of individuals. Some elderly persons previously infected with Mtb may eventually eliminate the viable tubercle bacilli and revert to a negative tuberculin reactor state. These individuals are therefore at risk of new infection (reinfection) with Mtb. There are therefore three subgroups of older persons potentially at risk for TB: one subgroup never exposed to TB that may develop primary TB disease, a second subgroup with persistent and latent primary infection that may reactivate and a third subgroup that is no longer infected and consequently at risk for reinfection.

Clinicians must be aware that frail older persons with TB disease may not demonstrate the overt and characteristic clinical features of TB such as fever, night sweats or haemoptysis. They may exhibit atypical and subtle clinical manifestations of ‘failure to thrive’ with loss of appetite, functional decline and low-grade fever or weight loss.13 Although several published works have attempted to delineate clear differences between younger and older TB patients, such studies have provided variable findings. In a meta-analysis of published studies, comparing pulmonary TB in older and younger patients, evaluating the differences in the clinical, radiological and laboratory features of pulmonary TB, no differences were found in the prevalence of cough, sputum production, weight loss, fatigue/malaise, radiographic upper lobe lesions, positive acid-fast bacilli (AFB) in sputum, anaemia or haemoglobin level and serum aminotransferases.14 A lower prevalence of fever, sweating, haemoptysis, cavitary disease and positive purified protein derivative (PPD), and also lower levels of serum albumin and blood leukocytes, were noticed among older patients. In addition, the older population had a greater prevalence of dyspnoea and some underlying comorbid conditions, such as cardiovascular disorders, chronic obstructive pulmonary disease, diabetes mellitus, gastrectomy history and malignancies. This meta-analytical review identified some subtle differences in clinical presentations of older TB patients compared with their younger TB counterparts. However, most of these differences can be explained by the already known physiological changes that occur during ageing. The majority of older TB patients (75%) with Mtb disease manifest active disease in their lungs.14 Extrapulmonary TB in the elderly is similar to that in younger persons and may involve the meninges, bone and joint and genitourinary systems or disseminate in a miliary pattern.15–19 Infection of lymph nodes, pleura, pericardium, peritoneum, gall bladder, small and large bowel, the middle ear and carpal tunnel have been described in the literature. Because TB can involve virtually any organ in the body, this infection must be kept in the differential diagnosis of unusual presentations of diseases, especially in the elderly. Thus, TB has been aptly described as ‘the great masquerader’ of many diseases.

Clinicians caring for the elderly must maintain a high index of suspicion for TB when possible, in order to recognize and treat infected individuals promptly.

Tuberculin Skin Testing

The Mantoux method of tuberculin skin testing using the Tween-stabilized purified protein derivative (PPD) antigen is one of the diagnostic modalities readily available to screen for TB infection, despite its potential for false-negative results.20 In the elderly, because of the increase in anergy to cutaneous antigens, the two-step tuberculin test is suggested as part of the initial geriatric assessment to avoid overlooking potentially false-negative reaction.21 The American Geriatrics Society routinely recommends two-step tuberculin testing as part of the baseline information for all institutionalized elderly.22 The two-step tuberculin skin test involves initial intradermal placement of five tuberculin units of PPD and the results are read at 48–72 h. Patients are retested within 2 weeks after a negative response (induration of less than 10 mm). A positive ‘booster effect’, and therefore a positive tuberculin skin test reaction, is a skin test of 10 mm or more and an increase of 6 mm or more over the first skin test reaction. It is important to distinguish the booster phenomenon from a true tuberculin conversion. The booster effect occurs in a person previously infected with Mtb