Pulmonary tuberculosis is the leading cause of death in adults with HIV / AIDS (PLWHA), so early detection is needed to reduce mortality. In some countries, death occurs in 50% of patients undergoing tuberculosis treatment, usually within two months after being diagnosed with tuberculosis. Late diagnosis of tuberculosis is likely a significant cause of high mortality.

Tuberculosis Screening in People Living With HIV/AIDS

Although the administration of antiretroviral (ARV) therapy can reduce the death risk, it can cause immune-reconstitution inflammatory syndrome. To reduce mortality and increase antiretroviral therapy safety, WHO recommends tuberculosis screening at the time of HIV infection is diagnosed, before starting antiretroviral therapy and isoniazid preventive therapy, and is regularly carried out next.

To date, there are no guidelines for screening tuberculosis in HIV-infected patients that are accepted internationally and made into global health policy. Chest X-ray examination and acid resist staining are relatively insensitive for detecting tuberculosis in people with HIV / AIDS. 

Besides, many PLWHA are asymptomatic, have normal chest X-ray results, and negative smear sputum may still have positive tuberculosis sputum culture results. Many studies have been done to develop a simple method to rule out the possibility of active tuberculosis in people living with HIV. Still, problems related to the method make none of the studies actually be used as a basis for global health policy.

Tuberculose Screening

a. TB Screening in Adolescent and Adult PLWHA

The latest WHO guidelines on TB in 2011 recommend that all people with HIV be regularly screened for TB with clinical algorithms at every visit to a health facility or contact a health worker. This guideline is based on the results of a meta-analysis conducted by Getahun et al. This meta-analysis evaluates the symptom-based screening method for TB screening in PLWHA. The intended symptoms, i.e.

- Active cough
- Fever
- Night sweats
- Weight loss

PLWHA who do not have any of the four symptoms are less likely to suffer from active tuberculosis. This symptom-based screening method is the best method for screening TB in PLWHA in areas with limited resources. This screening method has a sensitivity of 79% and a specificity of 50%. In the HIV-infected population with a TB prevalence of 5%, the negative predictive value (NPV) of 97.7% (95% CI 97.4-98.0) indicates that those who screen negative are most likely not currently suffering tuberculosis so can start prophylactic therapy with isoniazid. This recommendation can be applied to all people with HIV regardless of immunosuppression degrees in PLWHA who are already on ART therapy and in PLWHA who are pregnant.

The same meta-analysis shows that the absence of abnormal images on chest radiographs and the four-symptom-based rule increase its sensitivity from 79% to 91% and a decrease in specificity from 50% to 39%.

In the HIV-infected population, with a TB prevalence of 5%, NPV increased by 1% to 98.7%. Whereas in the PLWHA population, with a TB prevalence of 20%, NPV increased by 4% to 94.3%. These results indicate that chest X-ray can be considered in addition to the symptom-based screening method in high TB ​​prevalence situations in PLWHA. 

However, increased sensitivity and NPV must be accompanied by an increase in the need for cost, work weight, infrastructure, and competent staff. Therefore, WHO recommends that the screening method based on symptoms is still be continued without regard to the chest radiographs availability. PLWHA, whose one of four symptoms (productive cough, fever, weight loss, or night sweats), has the possibility of suffering from active tuberculosis and must be evaluated for tuberculosis and other diseases according to national guidelines in each country. 

b. TB Screening in PLWHA Children

Infants and children who have HIV must also be routinely screened for tuberculosis. Diagnosis of TB in children, whether they have HIV or not, is more complicated, and clinicians must continue to have a high level of suspicion. Having a history of contact with TB sufferers at home is very important and is a strong reason for health workers to screen for TB in children and other family members. The study results showed that some scoring systems that exist to diagnose tuberculosis in children without HIV are not sufficient to use in children with HIV.

An unpublished study showed that the absence of a cough that lasted more than two weeks, fever, and failure to thrive, showed that most likely children with HIV do not have active tuberculosis and may get isoniazid prophylactic therapy. Growth failure is weight loss or very low weight (weight for age <-3 Z score) or underweight (weight for age <-2 Z score) or growth curve that tends to slope. 

This screening method has an NPV of 99% with a 90% sensitivity and a 90% specificity. To increase the detection of tuberculosis in children suffering from HIV, WHO recommends the duration of cough not be taken into account and only assess whether the child has a cough complaint or not, the same as recommendations in adults. This recommendation is only based on experts' and clinicians' opinions to expand the possibility of a differential diagnosis that can cause children with HIV to have these symptoms. In conclusion 2011, WHO guidelines recommend the TB screening method in children with HIV by looking for the following symptoms:
- Stunted growth,
- Fever and
- Active cough, regardless of duration

Children with HIV who do not experience any of these symptoms are most likely not suffering from active tuberculosis and should receive isoniazid prophylactic therapy. Correspondingly, HIV-infected children who have one of the following symptoms, failure to thrive, fever, active cough, and contact with TB sufferers, may suffer from active TB and must undergo further evaluation.

Problems related to Early Detection of Tuberculosis in PLWHA

A challenge in using screening methods based on symptoms is the reduced sensitivity in HIV patients who get antiretroviral therapy even though TB ​​screening must be done every time PLWHA meets with health workers.  It might be caused by an increase in the immune system of PLWHA, thus masking the symptoms present in tuberculosis. Therefore, other screening methods are recommended to increase the screening for tuberculosis in PLWHA who are already on ARV treatment.

In a study conducted by Khan et al., chest X-ray as an additional TB screening method for PLWHA who had already taken ARV treatment increased sensitivity by about 25% to 76.7%. Nevertheless, it decreased its specificity due to the many abnormal chest X-ray images in PLWHA even though it is not currently suffering from active tuberculosis.

The TB screening method's sensitivity in PLHIV based on symptoms was also lower in pregnant women and was also lower, at only 42.9%. It may be due to tuberculosis symptoms that are less common in women than men, and pregnancy can mask tuberculosis symptoms because it is related to physiological changes in pregnancy. A study conducted by LaCourse et al. showed the result that TB screening by adding questions about the presence of TB symptoms in family members living together increased sensitivity to 71.4% by not decreasing the specificity value. The same study showed that rapid diagnostic methods, such as Xpert, also have low sensitivity in pregnant women.

The implementation of TB screening in people living with HIV varies significantly around the world. When PLHIVs are categorized as presumptive tuberculosis, they must undergo the diagnostic TB. However, this is still a big problem in the early detection of tuberculosis programs in PLWHA. A study in Kenya showed that only less than 15% of the presumptive group of people living with TB who underwent further examinations for TB diagnosis. It may be due to several factors, namely the low level of referral to higher health services or sufferers who have difficulty undergoing recommended evaluation procedures, which may be caused by difficulties in transportation costs or diagnostic examinations themselves.

1. Cain KP, et al. An algorithm for tuberculosis screening and diagnosis in people with HIV. NEJM. 2010; 362 (8): 707-16
2. World Health Organization. Guidelines for intensified tuberculosis case finding and isoniazid preventive therapy for people living with HIV in resource-constrained settings. Geneva, Switzerland. WHO; 2011
3. Getahun H, et al. Development of a standardized screening rule for tuberculosis in people living with HIV in resource-limited settings: individual data meta-analysis of observational studies. PLoS Med. 2011; 8(1): 1-14
4. Khan FA, et al. performance of symptom-based tuberculosis screening among people living with HIV: not as great as hoped. AIDS. 2014; 28 (10): 1463-72
5. LaCourse SM et al.Tuberculosis case finding in HIV-infected pregnant women in Kenya reveals the poor performance of symptom screening and rapid diagnostic tests. J Acquir Immune Defic Syndr. 2016; 71 (2): 219-27
6. Date A, Modi S. TB screening among people living with HIV/AIDS in resource-limited settings. J Acquir Immune Defic Syndr. 2015; 68: S270-3

2. picture: http://www.zdravlje.eu/wp-content/uploads/2011/05/Tuberkuloza.jpg