Dear Christophe, your concern is a concern of many scientists and public health personnel the world over. Apparently  the gold standard diagnostic technique for MTB is culture. This makes the screening of TB a complicated phenomena because someone has to wait for longer periods before the results are known. And make matters worse the group of people you are interested in is a group of immunosuppressed persons whereby the test might have reduced sensitivity.

However, that said in the USA there is a programme of screening all immigrants for incidence tuberculosis using the "Culture-based Algorithm" which in fact can be a better approach for you to try out on a public health point of view. Reference:(http://www.labmedica.com/microbiology/articles/294757941/screening_strategy_reduces_incidence_of_immigrationrelated_tuberculosis.html)

In conclusion I think scientist still have a challenge to come up with a quick, specific and easy to perform screening test other than TST for Tuberculosis. 

http://www.ncbi.nlm.nih.gov/pubmed/25265757

At our centre, we usually encounter many HIV patients that have history of pulmonary and extra pulmonary tuberculosis, who are on ATT or completed ATT  and even many cases who are diagnosed Tuberculosis years after ATT.

Christophe, I believe that screening is going to depend on the locations that you are seeing patients as well as their level of immunosuppression. In resource limited locales, many patients diagnosed with both infections will be highly suppressed. In this case chest radiography may not show typical patterns but the burden of organisms will be high. There may be utility in screening by urine based LAM assay in association with sputum analyzed by genExpert. In locales with less resource constraint, patients may be diagnosed with HIV before they are very suppressed by aggressive screening and in that case TB screening by CXR and standard PPD or IGRA may be more appropriate. Still much work to be done, especially in pediatrics. Hope this helps. Marc

Hello Christophe,

Unfortunately, TB skin testing is not a good screening tool for immunocompromised individuals. Do you have access to IGRA testing? Of the two available tests,              T-Spot.TB is more sensitive than QuantiFERON TB Gold but either is preferred over TBST in immunicompromised individuals. We use the T-Spot.TB test for TB screening of our foreign born students that arrive from TB endemic countries. We do HIV testing on all of our students that have positive T-Spots. We also do T-Spots on HIV positive individuals. It is just as important to know the HIV status of IGRA positive individuals as it is to know the TB status of HIV positive individuals.

From the CDC:   HIV Infection

After the initiation of antiretroviral therapy (ART), repeat testing for LTBI is recommended for HIV-infected persons previously known to have negative TST or IGRA results. This is because the immune response may be restored by ART.

http://www.cdc.gov/tb/publications/ltbi/diagnosis.htm 

Regards,

Lyn

this question is a major concern in our center, since Brazil shows a high incidence of MTB infection. Of course MTB culture  is the gold standard technique, but its sensitivity is very low. Both IGRA and skin tests showed not to be useful in severe immunodepressed individuals. Better results are achieved with the association of urine LAM tests with genExpert sputum analyses.

Tuberculosis is very common among HIV positive in our center we used to screen all HIV positives by cross referral to TB unit. We apply all available tools to screen HIV Patients

Short answer: integration of TB and HIV services under one roof, use of electronic medical records, and consistent implementation of the WHO TB screening algorithm plus chest X ray and Xpert MTB/RIF in symptomatic patients if available in your setting.

We have effectively implemented this strategy in a rural Tanzanian clinic: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0123275 

I hope this helps.

No straight forward approach to this but it will depend on Clinical setting(Resource rich Vs Resource LTD), and whether you are looking out for Latent TB (LTB)or active TB. Current Diagnostic tests for LTB are TST and IGRAs both with pros and cons but cost effectiveness being a big factor. Both tests are affected by immune suppresion but a meta analysis shows IGRA(particulary the T-SPOT TB assay)  to be less affected compared to TST but this difference is small and it varied across patients[1] IGRAs is also reported to be more specific[2]

Resource Rich for LTB

For example, many countries (eg, Portugal, Slovakia, Netherlands, South Korea, Croatia, and United Kingdom) support an approach of simultaneous testing with both TST and IGRA  to overcome suboptimal sensitivity of the two tests in immune suppresion[ link 1].

Other countries (eg, Canada, Italy, Ireland, Saudi Arabia, and Spain) recommend IGRA testing only if the initial TST is negative [link 2]

USA, the recommendations from the CDC and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America state that the predictive value of dual testing is uncertain and it would be more expensive and less feasible. Hence, routine use of both TST and IGRA to screen for LTBI is not recommended in the United States [link 3].

Resource LTD for LTB

WHO recommends LTB screening but it is non committal on which test to use. Much as the TST is comparable to IGRAs in detecting LTB and  cheaper compared to IGRAs, its is not preferred over IGRAs by WHO!! [link 4]

Neither do I recommend a TST. There is a danger of failing to rule out active TB and patients being treated with Isoniazid monotherapy yet they have underlying active TB giving way to MDR/X-DR!

After detecing LTB, active TB should be ruled out and still Resource rich Vs LTD has a role to play

Resource rich for Active TB -CXR, XPER/RIF[link 5]

Resource LTD for Active TB -follow WHO Guideline[link 4]. Radiography plus sputum examinations if available. Good clinical skills, high index of suspicion may make a big difference

1. Brock I, Ruhwald M, Lundgren B, et al. Latent tuberculosis in HIV positive, diagnosed by the M. tuberculosis specific interferon-gamma test. Respir Res 2006; 7:56.

2. Menzies D, Pai M, Comstock G. Meta-analysis: new tests for the diagnosis of latent tuberculosis infection: areas of uncertainty and recommendations for research. Ann Intern Med 2007; 146:340.

http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5905a1.htm?s_cid=rr5905a1_e

http://www.phac-aspc.gc.ca/publicat/ccdr-rmtc/10pdf/36-acs-5.pdf

http://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf

http://www.who.int/hiv/pub/tb/9789241500708/en/

http://apps.who.int/iris/handle/10665/44586

To manage efficently HIV infected patient, they should be tested for three tests: tuberculosis (baciloscopy), HBV (HBsAg) and HCV (Ab/Ag EIA test).

Tuberculosis (TB) is difficult to diagnose in HIV-positive patients because they form poor granulomas resulting in lower concentrations of Mycobacterium tuberculosis (MTB) in lesions.Culture which has higher sensitivity is time consuming and not readily available. In line with the recent WHO recommendation on the use of GeneXpert, Nigeria reviewed its diagnostic algorithm to reflect the use of GeneXpert as first screening test for HIV-infected persons showing symptoms of TB. 

i must say that with the new algorithm, increased number of HIV-infected persons are being screened for TB and appreciable number are coming out positive for not only susceptible TB but also the drug resistant strains. 

Knowledge Health Organization -Geneva has made the following recommendations:

DIAGNOSTIC APPROACH The highest priority in TB control is the identification and treatment of infectious cases, which are patients with PTBC positive sputum discoloration. For this reason, all patients (regardless of HIV status) with clinical characteristics suggesting PTBC must submit sputum to sputum diagnostic microscopy. Most susceptible persons on TB (people with symptoms or signs suggesting TB) are mobile. Therefore, PTBC diagnosis is usually based on external patients. Some of the suspect TB patients are severely ill and / or tied to bed, and should therefore be examined as outpatients. A symptom assessment clinically identifies suspect PTBCs among patients who come to a healthcare facility. The most desirable method of detecting TBC cases among suspected PTBCs in the countries where it prevails is through sputum microscopy. A suspicious person (a suspense) having a positive sputum disc has a PTBC positive sputum disc. Local TB (DTO) registers a patient with TB and treatment begins. For most positive PTBC scavengers, X-ray film scavenging is not required. Sometimes the patient may be negative on sputum microscopy, and there is no broad spectrum antibiotic enhancement. If you still suspect TB, evaluate your patient again and make CXR. If CXR is typical for PTBC, register the patient at DTO and start treatment for TB. If you think about CXR diagnosis on TB, ie if CXR shows non-specific pulmonary infiltrates, give the patient a second dose of antibiotics. If there is no clinical improvement or if you just cough shortly and return, repeat the microscopy of the sputum disc. If you still suspect that a patient might have TB, despite a still negative sputum, re-evaluate the patient and do the CXR. Then decide whether the diagnosis is TB or not. In cases where diagnostic paralysis does not cease, sputum culture may be beneficial if appropriate capacities are available. In populations dominated by TB, tuberculin skin test is not of high value for TB diagnosis in adults. Positive tuberculin skin test does not in itself distinguish M. tuberculosis from TBC disease. Earlier exposure to mycobacteria from the environment may also result in false positive test results. In contrast, tuberculin skin test may be negative, even if the patient has TB. Conditions that are often associated with false negative tuberculin skin tests include HIV infection, severe malnutrition and billionth of TB.

Topics

. TBC associated with HIV 1.3.1 HIV coinfection epidemiology and M. tuberculosis 37 TBC / HIV: CLINICAL MANUAL By the end of 2000, around 11.5 million people worldwide infected with HIV were simultaneously infected with M.tuberculosis . 70% of the fatalities were in sub-Saharan Africa, 20% in South-East Asia and 4% in Latin America and the Caribbean. Number of infected adults (15 to 49 years) in WHO regions by the end of 2002 WHO Region Number of people infected with TB and HIV (in thousands)% of total population Africa 7979 70 Si J.America 468 4 Eastern Mediterranean 163 1 Europe 133 1 South East Asia 2269 20 West Pacific 427 4 Total 11440 100 1.3.2. HIV infection and TB risk HIV probably increases susceptibility to M. tuberculosis infection. HIV increases the risk of developing M.tuberculosis infection in the direction of TBC disease. This risk is increased by increasing immunosuppression. HIV increases not only the risk but also the rate of advancement of recent or latent M.tuberculosis infection in the disease. The table below shows the effect of HIV infection on the life-threatening risk that an individual infected with M.tuberculosis develops TB. HIV Status Lifelong TB Risk Negative Positive 5 - 10% 50% FOR PRACTICE HIV is the most powerful known factor that increases the risk of TB. 1.3.3. TBC during HIV progression TB can occur at any point during the progression of HIV infection. The risk of developing TBC 38 is rapidly increasing by weakening immune status. 1.3.4. Consequences of HIV co-infection / M.tuberculosis Compared to a person who is not infected with HIV, a person infected with HIV has a tenfold higher risk of developing TB. Information on TBCs is higher in populations where HIV infection and M.tuberculosis infection are common. For example, in some parts of Podsahar Africa over the past decade, there has been an increase in information on the number of TB cases 3 to 5 times. The seroprevalence of HIV in these tuberculosis patients is up to 75%. In Sub-Saharan Africa, one third of people or more HIV-infected can develop TB. 1.3.5. Influence of HIV on TB Control The principles of TB control are the same even where there are many HIV / TB patients. However, in populations where HIV / TBC is common, health services are struggling to deal with large and growing numbers of tuberculosis patients. Consequences include: Excessive TBD diagnosis with negative plaque smear detection (due to difficulty diagnosing); Too small a diagnosis of pulmonary TB with positive saliva (due to overworked workload); Insufficient monitoring of TBC chemotherapy; Low healing rates; High morbidity during treatment; High rates of mortality during treatment; High standard rates due to adverse drug reactions; High rates of TB return; Increased transmission of drug-resistant strains in patients infected with HIV in a common environment. 1.3.6. HIV-associated TBC patterns How HIV infection progresses, the number and function of CD4 + T-lymphocyte decreases. These cells play an important role in defending the TBC. In this way, the immune system becomes less capable of preventing growth and local spread of M. tuberculosis. Disease and disability is more common. Pulmonary TB Even in patients infected with HIV, lung TB is the most common form of TB.

iPresentation depends on the level of immunosuppression. The table below shows how the clinical picture, the results of spotting and appearance of breast rendenograms, often differ in early and late HIV infection. How does pulmonary TBC differ in early and late HIV infection PTBC Characteristics Stage of HIV infection Early Late Clinical Image Very Common to Postprimer PTBC Often Likeness to Primary PTBC Result of Spasm Often Positive Frequently Negative Visualization of Liver Disease Frequent Caverns Often infiltrates without a Cavity TBC The most common forms of outbreaks of TB are: pleural effusion, lymphadenopathy, pericardial illness, myocardial disease, meningitis, disseminated TB (with mycobacterium). TBC associated with HIV in children As in adults, the natural history of TBC in children infected with HIV depends on the stage of HIV infection. At an early stage, when the immunity is good, TBs are similar to those in a child who does not infect HIV. As HIV infection progresses and immune attenuates, the TBC disinfection becomes more common. Tuberculous meningitis, millions of TB and widespread tuberculous lymphadenopathy occur. 1.3.7 Influence of TB in HIV In HIV-infected persons, the presence of other infections including TB can lead to a faster multiplication of HIV, which can lead to faster development of HIV disease RECOMMENDATIONS FOR ADDITIONAL READING Crofton J, Horne N, Miller F Clinical Tuberculosis, 2nd Edition. London, MacMillan Press Limited, 1999. Schlossberg D, ed. And non-tuberculous mycobacterial infections. Fourth edition. Philadelphia, WB Saunders, 1998 International Tobacco and Lung Disease Union. Tuberculosis Guide for Low Countries. Fifth Edition. Paris, 2000. Reider HL. Epidemiological basis of tuberculosis control .. Paris, International Tobacco and Lung Disease, 1999 World Health Organization. Tuberculosis Manual, Geneva, 1998, (WHO / TBC / 98.253). World Health Organization. Global TB control: surveillance, planning, financing. Report WHO 2003 Geneva, 2003 (WHO / CDS / TB / 2003.316). HIV / AIDS Fauci AS. AIDS epidemic. Questions for the 21st Century. New England Journal of Medicine, 1999, 341: 1046-1050. Royce RA, Sena A, Cates Jr., W Cohen, MS. Sexual Transmission of HIV New England Journal of Medicine, 1997, 336: 1072-1078. 40 Recommendations for further reading: United Nations Program on HIV / AIDS (UNAIDS), Global HIV / AIDS Epidemic Report, Geneva, July 2002 (contains specific country estimates). United Nations Program on HIV / AIDS (UNAIDS), New AIDS Epidemic Data,: Geneva, December 2002 HIV CLINICAL STAGE SYSTEMS AND HIV-RELATED HIV SYSTEMS World Health Organization, Relatively Increased Antiretroviral Therapy in Resource Restricted