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Latent TB – What is latent TB? symptoms of latent TB, latent TB treatment

What is latent TB? What are the symptoms of latent TB?

Latent TB & TB disease

Latent TB & TB disease

Latent TB occurs when a person has the TB bacteria within their body, but the bacteria are present in very small numbers. They are kept under control by the body’s immune system. So a person with latent TB does not have any symptoms.

People with latent TB do not feel sick and are not infectious. They cannot pass the bacteria on to other people. In addition they will usually have a normal chest x-ray and a negative sputum test. It is often only known that someone has latent TB because they have had a TB test, such as the TB skin test.

Testing for latent TB

There are two types of test that can be used. These are the TB skin test (TST) and the newer IGRA blood test. In countries where there is a high level of TB (such as the high burden TB countries) the majority of people may have latent TB.

Latent TB treatment

It is not recommended that everyone with latent TB infection (LTBI) should have TB treatment. Rather it is recommended that certain “target” groups should receive treatment. The main “target” groups considered by the World Health Organisation (WHO) to be most at risk from progressing from latent to active TB include people in low TB burden countries:

  • who have had recent contact with an infectious patient;
  • with silicosis;
  • infected with both TB and HIV;
  • who have been or who are in prison;
  • who are immigrants to a low burden country from a high burden country;
  • who are homeless;
  • who are an illicit drug user;
  • who have certain clinical conditions, or conditions which compromise their immune system, such as people with diabetes, and people with chronic renal failure.

In high TB burden countries the populations that are most strongly recommended for treatment are people living with HIV, and children under five who are household contacts of pulmonary TB cases.1“Global Tuberculosis Report”, WHO, 2016, http://www.who.int/tb/publications/global_report/en/

Treatment regimens

Isionazid is one of the drugs used to treat latent TB

Isionazid is one of the drugs used to treat latent TB

Since the 1950s many studies have been carried out to assess the effectiveness of the TB drug isoniazid in treating latent TB. In some of the trials the people taking part took the drug for six months, whilst in other trials the drug was taken for twelve months. There were also trials with people taking the drug daily being compared with people taking the drug five times a week.

Any adverse effects of taking the drug were also noted and compared. There was then a long period of follow up to see who developed active TB.2Cruz, Andrea T. “Treatment of Latent Tuberculosis in Children”, Journal of the Pediatric Infectious Diseases Society, 2013, https://academic.oup.com/jpids/article/2/3/248/1018973/Treatment-of-Latent-Tuberculosis-Infection-in

The initial human studies of isoniazid  preventative therapy established that prolonged therapy with isoniazid was effective in reducing subsequent active TB infections. The optimum length of treatment was however unclear but the most common recommendation was for a treatment length of nine months.

Currently the American CDC recommends one of the following three regimens for the treatment of latent TB.3“Treatment regimens for latent TB infection”, CDC,  https://www.cdc.gov/tb/topic/treatment/ltbi.htm

  • Isoniazid daily or twice weekly for nine months
  • Isoniazid plus rifapentine once weekly for 12 weeks
  • Rifampicin (or rifabutin) daily for 4 months (with this regimen dots must be used)

The WHO also recommends two other regimens of 3 or 4 months of isoniazid plus rifampicin daily and six months of isoniazid daily.

Treatment study results in 2018 ACTG 5279

In 2018 the results were announced of the ACTG 5279 study.4R Chaisson, “One month tuberculosis prophylaxis as effective as nine month regimen for people living with HIV”, 2018 Conference on Retroviruses and Opportunistic Infections (CROI) https://www.nih.gov/news-events/news-releases/one-month-tuberculosis-prophylaxis-effective-nine-month-regimen-people-living-hiv This was a phase 3 clinical study which showed that a one month regimen to prevent latent TB developing into active TB was at least as effective as the current recommended regimens of nine months for people living with HIV. Also, adults and adolescents in the trial were more likely to complete the short course regimen.

The short course regimen consisted of daily doses of the drugs rifapentine and isoniazid.

Among people with latent TB infection, HIV infection is the greatest risk fact for progression from latent TB to active TB disease.

It was said that:

“These results have the potential to dramatically change clinical practice by offering people living with HIV who are at risk of developing active tuberculosis an additional, shorter duration prevention option that is safe, effective and more convenient. This study also will inform future research on prevention of tuberculosis disease among HIV negative people at risk for developing active tuberculosis” NIAID Director Anthony Fauci

Global progress with TB treatment as prevention

Globally in 2015 there were an estimated 1.2 million children aged under 5 who were household contacts of bacteriologically confirmed pulmonary TB cases. These children were all eligible for TB preventative treatment. However, only 87,236 children in this age group (7.1%) were reported to have been started on TB preventative treatment based on the data that WHO received from 88 countries.

A total of 910,124 HIV positive people who were newly enrolled in HIV care were started on TB preventative treatment in 2015. This was based on data from 58 countries. South Africa accounted for the largest share (45%) of the total in 2015 as in previous years, followed by Malawi, Mozambique and Kenya. Ten countries reported data for the first time including Kenya.

Latent TB in South Africa

It is estimated that 80% of the population of South Africa had latent TB in 2011. The highest prevalence, estimated at 88%, occurred among people in the age group 30-39 in township situations and informal settlements. Townships and informal settlement conditions are characterised by overcrowding and low socio-economic status, all of which provide fertile ground for TB infection and disease.5“National Strategic Plan on HIV, STIs and TB 2012-2016”, South African National AIDS Council, 2011 www.gov.za/documents/national-strategic-plan-hiv-stis-and-tb-2012-2016 There is more about TB in South Africa.

Latent TB in India

It is estimated that 40% of the population of India has latent TB.6Mahmood,T, “40% of India’s population play host to the TB bacillus as a latent TB”, 2016, www.oneindia.com/feature/40-percent-of-india-s-population-play-host-the-tb-bacillus-as-latent-tuberculosis-2049544.html There is more about TB in India.

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References

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1. “Global Tuberculosis Report”, WHO, 2016, http://www.who.int/tb/publications/global_report/en/
2. Cruz, Andrea T. “Treatment of Latent Tuberculosis in Children”, Journal of the Pediatric Infectious Diseases Society, 2013, https://academic.oup.com/jpids/article/2/3/248/1018973/Treatment-of-Latent-Tuberculosis-Infection-in
3. “Treatment regimens for latent TB infection”, CDC,  https://www.cdc.gov/tb/topic/treatment/ltbi.htm
4. R Chaisson, “One month tuberculosis prophylaxis as effective as nine month regimen for people living with HIV”, 2018 Conference on Retroviruses and Opportunistic Infections (CROI) https://www.nih.gov/news-events/news-releases/one-month-tuberculosis-prophylaxis-effective-nine-month-regimen-people-living-hiv
5. “National Strategic Plan on HIV, STIs and TB 2012-2016”, South African National AIDS Council, 2011 www.gov.za/documents/national-strategic-plan-hiv-stis-and-tb-2012-2016
6. Mahmood,T, “40% of India’s population play host to the TB bacillus as a latent TB”, 2016, www.oneindia.com/feature/40-percent-of-india-s-population-play-host-the-tb-bacillus-as-latent-tuberculosis-2049544.html