Managing tuberculosis in primary care
Dr Indumathi Venkatachalam, a consultant at the Department of Infectious Diseases, Singapore General Hospital, speaks to Roshini Claire Anthony on how GPs can help ensure early detection of tuberculosis (TB).
According to data from the Ministry of Health (MOH), Singapore, the age-standardized incidence rate of TB in Singapore was 38.7 per 100,000 persons in 2016, a figure which included Singapore citizens, permanent residents, and long- and short-staying foreigners. A total of 3,294 cases of TB were notified in Singapore in 2016, comprising 3,100 new and 194 relapsed cases. [https://www.moh.gov.sg/docs/librariesprovider5/resources-statistics/reports/other-diseases]
TB can affect any organ but involves the lungs about 80 percent of the time. Extrapulmonary TB commonly affects lymph nodes, pleura, and osteoarticular areas. The risk for extrapulmonary TB increases with advancing immunosuppression. While it is more common in individuals infected with the human immunodeficiency virus (HIV) regardless of the CD4 count, clinical presentation is not very different from that in individuals without HIV infection. Disseminated TB with or without meningitis is associated with a higher mortality. Apart from mortality, central nervous system TB can also cause significant morbidity as a result of severe neurological sequelae. [BMC Infectious Diseases 2014;14:5; Clin Microbiol Rev 2008;21:243-271;
In Singapore in 2016, a majority (83.5 percent) of cases were pulmonary TB (with or without extra-pulmonary disease), with the remainder (16.5 percent) exclusively extrapulmonary TB. [https://www.moh.gov.sg/docs/librariesprovider5/resources-statistics/reports/other-diseases]
By being aware of (i) the community prevalence of TB, (ii) patients with a higher risk of developing active TB, and (iii) the common clinical manifestations, GPs can be alerted to the possibility of TB in their patients. MOH recommendations for the diagnosis of TB are as follows:
· To consider pulmonary TB in patients presenting with unexplained cough for more than 3 weeks – these patients should have a chest X-ray.
· GPs are urged to refer suspected TB cases to the Tuberculosis Control Unit (TBCU) or specialists with experience in TB management.
[MOH, Singapore, Clinical practice guidelines 1/2016. Prevention, diagnosis, and management of tuberculosis, March 2016]
GPs should be aware of individual and group risk factors for TB to ensure early diagnosis. Patients with chronic cough for more than 3 weeks, especially persons in the risk categories below, should be screened with a chest x-ray and if abnormal, referred to the TBCU or a specialist with experience in TB management for further evaluation.
Almost 50 percent of new TB cases in Singapore were detected in foreigners. Screening for TB in the migrant population, especially international students and foreign workers from countries with high TB incidence, has led to early detection and reduced infectiousness. The risk of developing TB is higher in persons:
(i) with HIV and other immunocompromised conditions (eg, post-transplant, on immunosuppressive agents)
(ii) on immunomodulators (eg, tumour necrosis factor [TNF] alpha inhibitors)
(iii) exposed to individuals with sputum smear positive pulmonary TB
(iv) with diabetes mellitus
(v) with chronic kidney disease
(vi) with gastrectomy or jejunoileostomy
(vii) in institutional settings including healthcare workers.
Chronic cough and weight loss are the predominant symptoms in patients with pulmonary TB. Only 25 percent of patients with pulmonary TB have haemoptysis and 5–14 percent of patients are asymptomatic at presentation. [MOH, Singapore, Clinical practice guidelines 1/2016. Prevention, diagnosis, and management of tuberculosis, March 2016] For adults and adolescents with HIV, the World Health Organization recommends regular screening based on symptoms of current cough, fever, weight loss, or night sweats. If any of these symptoms are present, the patient should be evaluated for TB.
TB can affect any organ in the body and hence can present in myriad ways depending on the organ/s involved. In general, TB in adults presents as a subacute or chronic illness and can be in the differential for an infection that is unresponsive to standard empirical treatment.
Only pulmonary TB is infectious. As such, early diagnosis of pulmonary TB is crucial for TB control in the community. Awareness of patient categories at higher risk for the condition and the predominant symptoms of pulmonary TB would help alert GPs to the possibility of underlying TB.
Undiagnosed persons with active pulmonary TB in the community act as reservoirs leading to ongoing transmission. A sputum smear positive patient can cause 15–20 transmission events per year. Strategies that identify and treat TB patients in ≤28 days could prevent 1–2 transmission events per infectious case. [S Afr Respir J 2016;22:93-98] GPs play a crucial role in early detection and diagnosis of patients with TB through which they reduce risk of community transmission.
As recommended by MOH, GPs should refer patients with TB to the TBCU or to specialists experienced in treating TB. Patients should be referred when TB is suspected based on risk factors, symptoms, and in the case of pulmonary TB, chest x-ray findings.
First-line anti-tuberculous drugs are isoniazid, rifampicin, ethambutol, pyrazinamide, and streptomycin. Standard treatment for drug-susceptible TB involves a 6-month regimen comprising a 2-month intensive phase of daily isoniazid, rifampicin, pyrazinamide, and ethambutol followed by a 4-month continuation phase with isoniazid and rifampicin.
Drugs to treat TB are associated with several toxicities, in particular hepatotoxicity and neurotoxicity, and may also interact with other medications the patients may be taking. The initial anti-tuberculous drug regimen is selected based on baseline risk assessment, taking into account factors such as age, comorbidities, and concomitant drug use. Once on treatment, patients are closely monitored for development of toxicities, through regular clinical reviews and laboratory tests as indicated. When isoniazid is used in the regimen, pyridoxine (vitamin B6) is co-administered to reduce the risk of isoniazid-associated neurotoxicity.
Correct doses have to be given for an adequate period to cure the infection and reduce the risk of development of drug resistance. Directly observed therapy (DOT) reduces the risk of relapse and the development of drug resistance. In Singapore, outpatient DOT is carried out at 18 polyclinics nation-wide and at the TBCU. DOT should be standard of care for all infectious TB cases.
Multidrug-resistant TB (MDR TB) is defined by resistance to the two most effective of the four first-line drugs, isoniazid and rifampicin. Treatment of MDR TB is complicated by the need for an injectable drug with a longer duration of treatment (18–24 months). MDR TB is associated with higher morbidity and mortality compared with drug susceptible TB with mortality exceeding 10 percent. [PLoS One 2009;4:e6914]
Although TB incidence in Singapore declined between 1997 and 2007, the trend reversed in 2008. There is ongoing transmission of TB in the community from undiagnosed symptomatic patients. GPs, our front-line healthcare professionals, play a crucial role in TB prevention and control by being alert to the possibility of TB in their patients and aiding early diagnosis.
MOH (Singapore) Clinical Practice Guidelines 1/2016. Prevention, diagnosis, and management of tuberculosis [Singapore Med J 2016;57:118-124]
US Centers for Disease Control and Prevention (CDC)
American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America Clinical Practice Guidelines: Treatment of Drug-Susceptible Tuberculosis. [Clin Infect Dis 2016;63:e147-e195]