Pulmonary Arterial Hypertension:
Tuberculosis Through Time: Historic Burden, Modern Challenges
Global respiratory leaders at the CHEST 2024 annual meeting underscored the ongoing clinical burden of tuberculosis, emphasizing that it remains a significant global health challenge that requires ongoing attention and awareness.
Despite being often thought of as a disease of the past, tuberculosis (TB) continues to pose a global health challenge, as emphasized by leaders at the CHEST 2024 annual meeting in Boston, Massachusetts.1
Global respiratory leaders at CHEST 2024 underscored the ongoing clinical burden of tuberculosis, emphasizing that it remains a significant global health challenge that requires attention and awareness.Image Credit: tashatuvango - stock.Adobe.Com
History of TBTB is an infectious disease caused by bacteria that spread through the air when infected people cough, sneeze, or spit2; it most often affects the lungs. TB has affected humans for thousands of years, with evidence of it in ancient Egyptian mummies dating back over 4000 years.3 From the 1600s through the 1800s, it caused 25% of all deaths in Europe; similar numbers also occurred in the US.
Before Robert Koch in 1882 discovered Mycobacterium tuberculosis, the bacteria that causes TB, many thought the disease was hereditary.2 It has also been known as phthisis, white plague, consumption, and wasting disease. Before the discovery of antibiotics, a TB diagnosis was considered a death sentence, with treatment limited to warmth, rest, and good food. Many patients were housed in TB sanatoriums to reduce the chance of the disease spreading to their families. By 1953, there were 839 sanatoriums with a capacity for 136,000 patients. Other treatments used in the early 1800s included vinegar massages, cod liver oil, and inhaling hemlock or turpentine.
Today, TB is known to be an airborne infectious disease, and its names indicate where it is (pulmonary or extrapulmonary) and how to treat it (drug resistant, drug susceptible, multidrug resistant, and extensively drug resistant). Also, it is primarily treated using antibiotics, namely Isoniazid, pyrazinamide, ethambutol, and rifampin.
After the discovery of antibiotics, the number of TB cases and deaths began to drop dramatically in the US. In 1992, there were 26,673 TB cases in the US, which decreased to 7174 in 2020; the US has one of the lowest TB case rates worldwide.
TB Diagnosis and TreatmentAlthough about 25% of the global population has been infected with TB bacteria, only about 5% to 10% will eventually get symptoms and develop the disease.
Those with latent TB infection are not contagious and do not feel sick, but patients who develop TB will experience symptoms like prolonged cough, fatigue, weight loss, and chest pain. Patients' symptoms depend on where in the body TB becomes active, as it can affect the lungs, brain, spine, skin, and kidneys.
Patients with diabetes or weakened immune systems, along with those who are malnourished or use tobacco, are at increased risk for TB. However, Patients with HIV are 16 times more likely to fall ill with TB. It is the leading cause of death among this population, as HIV and TB speed up the other's progress. Therefore, without proper treatment, nearly all people who have HIV and TB will die.
All persons with TB signs and symptoms are initially advised to use rapid molecular diagnostic tests. A tuberculin skin test (TST) and an interferon-gamma release assay (IGRA) can also identify TB infection.
Treatment is recommended for both TB infection and active disease through antibiotics. These medications must be taken daily for 4 to 6 months, and it is considered dangerous to stop earlier or without medical advice. Prematurely stopping medications can allow TB to become drug resistant. After becoming unresponsive to standard drugs, patients with drug-resistant TB require more toxic treatment with different medicines.
Similarly, multidrug-resistant TB is caused by bacteria that do not respond to isoniazid and rifampicin, the 2 most effective first-line TB drugs. This is treatable and curable by using second-line drugs, which are more expensive and toxic.
Bacille Calmette-Guerin (BCG) is a TB vaccine that helps prevent children from contracting severe disseminated TB or TB meningitis. Many countries with a high TB prevalence vaccinate infants with BCG as part of their pediatric TB control efforts. Conversely, it is not generally recommended in the US due to the low overall risk of TB infection.
TB TodayDespite significant advancements in the identification and treatment of TB, the disease remains a global challenge, with varying prevalence across different regions. It is the second leading infectious killer worldwide after COVID-19, with over 80% of cases and deaths occurring in low- and middle-income countries.
In 2022, most new TB cases occurred in the World Health Organization's South-East Asian region (46%), followed by the African (23%) and Western Pacific (18%) regions. Of these cases, about 87% occurred in the 30 high TB-burden countries,4 with more than two-thirds of the global total in China, Bangladesh, India, Indonesia, the Democratic Republic of Congo, Nigeria, Pakistan, and the Philippines.3
During a session at the CHEST 2024 annual meeting earlier this month, Adrian Rendon, MD, PhD, president of the Latin American Thoracic Association, discussed the impact of the COVID-19 pandemic on TB within Central and South American countries.1 He noted there was a huge underdiagnosis of TB cases since resources were more focused on COVID-19 during the pandemic.
Consequently, there was a significant increase in TB cases and deaths, with the death toll rising from 1.4 million in 2019 to 1.5 and 1.6 million in 2020 and 2021, respectively. Rendon added that this increase in TB cases and deaths post pandemic also occurred in the US.
"TB doesn't know barriers," he said. "TB travels around the world very easily with people. We were talking about pollution, climate change, all of these are fuel for TB because they increase the economic crisis and promote migration; TB uses those factors to move around the world."
Also, John Buckley, MD, MPH, president of the American College of Chest Physicians highlighted the stark contrast between the declining prevalence of TB in high-income countries and its continued burden in other parts of the world. He expressed concerns that young US professionals may not be aware of the ongoing TB epidemic.
"I want to keep reminding my young colleagues, my young learners, that just because we don't see it [TB] in our daily practice doesn't mean it's not an extraordinarily important issue," Buckley said.
References
1. McCormick B. Global respiratory leaders call for collaboration, advocacy to tackle key health challenges. AJMC®. October 8, 2024. Accessed October 24, 2024. Https://www.Ajmc.Com/view/global-respiratory-leaders-call-for-collaboration-advocacy-to-tackle-key-health-challenges
2. Tuberculosis. World Health Organization. Accessed October 24, 2024. Https://www.Who.Int/news-room/fact-sheets/detail/tuberculosis
3. TB 101 for health care workers. CDC. Accessed October 24, 2024. Https://www.Cdc.Gov/tb/webcourses/tb101/page2621.Html
4. High burden countries for tuberculosis. Stop TB Partnership. Accessed October 24, 2024. Accessed October 24, 2024. Https://www.Stoptb.Org/securing-quality-tb-care-all/high-burden-countries-tuberculosis
Goa's 100% Molecular Testing Helps Early TB Detection
Goa: For more than two years now, Goa has been providing 100% upfront molecular testing for tuberculosis detection. Molecular testing is more accurate than sputum microscopy, which has been the mainstay of the TB control programme for decades. This has ensured that Goa's peripheral health centres are detecting TB and helping patients to start treatment early.
Sputum microscopy simply means looking for the rod-like TB bacteria under the microscope. This method is fast and cheap but has very low sensitivity (40-60%) as it requires a higher number of bacilli to be detected. This means that about half the cases are not detected. It also has lower sensitivity for TB in children, and patients with HIV and extrapulmonary TB.
Nucleic Acid Amplification tests (NAATs), on the other hand, are rapid tests that can identify the genetic material of the TB bacteria and are more than 90% sensitive and accurate. These tests can also detect resistance to rifampicin, one of the major TB drugs. For NAAT testing, Indian public health systems have GeneXpert from US-based Cepheid or Truenat from Goa-based Molbio Diagnostics.
Before Goa started upfront NAAT testing, they used to diagnose most of the TB cases in the medical college, said Manish Gaunekar, Goa state TB officer. The use of NAAT testing has improved detection at the peripheral centres, from less than 50% of all cases in 2019 to 62% in 2023.
Source: Goa TB department
Goa, which started ramping up molecular testing in 2020, is the only state with 100% NAAT testing, as per the 2024 India TB report. Ladakh (93%) and Meghalaya (81%) follow.
Goa has four GeneXpert systems and 17 Truenat systems in its public health facilities. Truenat runs on a portable, battery-operated platform and can be taken to peripheral health centres situated at difficult terrains with irregular electric supply.
Universal access to World Health Organization (WHO)-recommended rapid tests for all is one of the new targets set by WHO's Director-General's flagship initiative to end TB by 2027. As per the India TB report 2024, only 21% of presumptive TB tests were used doing NAT.
Presumptive TB Examination Rates In India
Figures are in tests per 100,000 population
Reduces delay in diagnosis
Researchers model the TB care cascade to estimate gaps, as IndiaSpend reported in May 2023. The number of patients with incident TB who did not access TB tests constitute gap 1, patients who did not get diagnosed constitute gap 2, those who did not register for treatment constitute gap 3, those who were not successfully cured comprise gap 4, and those who relapsed or died even after being treated constitute gap 5.
India's most significant gap in the cascade of care in TB is diagnosis of the disease itself, we had reported. As per the National TB Prevalence Study, 2019-21, a majority of the symptomatic population--about 64%--did not seek healthcare services. The reasons are either they ignore the symptoms, or they don't recognise the symptoms as TB or they cannot afford to seek care. So it is imperative that the patients who do seek care should be tested and diagnosed as soon as possible so that they do not fall off the TB care net.
Before 2020, if a patient from Goa was symptomatic, they would first undergo sputum microscopy. If this was negative--which happens about 50% of the time even if the patient has TB--they would have to go to a higher centre such as a district hospital or medical college, losing at least about one-and-a-half to two months, said Gaunekar.
"Our patients are mostly migrant workers or old people," said Smita Parsekar, health officer at Ponda's primary health centre. Ponda is about 32 km from Goa Medical College, in Panaji. "They used to waste a lot of time in big hospitals for getting TB tests where one has to spend a whole day in the hospital and even come for follow up."
"By this time the bacilli would rise and the patient would become more infectious," said Gaunekar. "The microscopy would be able to pick it up the second or third time. Now what is happening is that infection is being picked right in the beginning at the primary healthcare facility itself."
In the National TB Prevalence Survey, 33% of cases were exclusively diagnosed based on the NAAT test. Exclusive sputum microscopy only yielded 7.9% of cases. The Survey recommends prioritising molecular test coverage.
Easier follow up
The availability of a quick testing method helps increase TB notification and in collecting data that can be used by TB officers to analyse the issues in the population. Goa has a higher TB death rate--about 8.3% in 2022 as opposed to the all India mortality rate figure of 3.9%, as IndiaSpend reported on October 22. In 2023, this climbed to 9.6%.
"Since we audit TB deaths, we have realised that people are dying within five days of admission," said Govind Desai, South Goa TB officer. "Because we are diagnosing them sooner, we can record them as TB deaths."
The availability of a superior testing method in the primary health centres has also resulted in private doctors sending their patients for TB testing there. "In my area, that is Ponda, we have about 3-4 villages around the PHC," said Parsekar. "Many private doctors here are referring their patients with TB symptoms to the PHC
Even follow up of patients has become faster. If the diagnosis is done in hospitals, for them to inform the primary health centre or sub-centre that directly follows up with patients--with home visits and doorstep treatment--can take at least a week if not more," she said.
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