The Next Big One: Drug-Resistant Airborne Tuberculosis

(Posted on Friday, October 29, 2021)

Even prior to the Covid-19 pandemic, there has been much discussion of what will be the next big pandemic and how do we prepare for it. New research has found that tuberculosis bacteria can spread via airborne and asymptomatic transmission similarly to SARS-CoV-2. This finding upends the conventional wisdom that coughing was the main route of transmission. It is these two characteristics that make SARS-CoV-2 so dangerous. Therefore I believe the next big pandemic might well be drug-resistant tuberculosis.

The pre-print study from South Africa has found that greater than 90 percent of tuberculosis bacteria released from an infected person may be carried in aerosols that are expelled when a person breathes out. Aerosols released from normal breathing will also linger in the air for longer than droplets released from coughs. Study co-author Ryan Dinkele told the New York Times “if an infected person breathes 22,000 times per day while coughing up to 500 times, then coughing accounts for as little as 7 percent of the total bacteria emitted by an infected patient”.

Tuberculosis is caused by a bacterium called Mycobacterium tuberculosis, which usually attacks the lungs. The researchers were concerned about how diagnosis and treatment of tuberculosis had changed very little over the decades and sought a better understanding of how Mycobacterium tuberculosis aerosolizes and transmits. With South Africa (a high burden tuberculosis country) reporting that nearly 60% of individuals with bacteriologically confirmed pulmonary tuberculosis were asymptomatic. The researchers were particularly intrigued by how transmission occurs in these asymptomatic cases that were cough-independent.

The researchers developed a platform combining non-invasive bioaerosol capture technology and fluorescence microscopy to accurately measure the viable Mycobacterium tuberculosis released by confirmed tuberculosis patients. They created three separate respiratory scenarios for comparison, including Tidal Breathing, otherwise known as restful breathing, Forced Vital Capacity, in which the person takes the maximum inhale and exhale they can and Cough. Viable Mycobacterium tuberculosis bacilli were detected in 66%, 70%, and 65% of Tidal breathing, Forced Vital Capacity, and Cough samples respectively. While coughing increases particle aerosolization compared to Tidal breathing, this was not associated with increased Mycobacterium tuberculosis aerosolization. Instead, Tidal breathing produces more Mycobacterium tuberculosis per particle than coughing. If we assume the number of viable Mycobacterium tuberculosis organisms detected provides an accurate measure of patient infectiousness, Tidal breathing could be considered the main route of tuberculosis transmission.

These results should have a significant impact on the public health, diagnostic and medical guidelines for tuberculosis. We should be implementing some of the methods used to limit Covid transmission such as high-quality masks and ventilation and encouraging outdoor gatherings and events to limit tuberculosis transmission in countries with a high volume of cases.

The results also cause concern for transmission of tuberculosis during air travel and the continual seeding of cases globally. While this is presently not reported as a common occurrence it is possible. From 1992 to 1994, the CDC worked with state and local health departments, conducted contact investigations for seven index cases of infectious tuberculosis.

When investigating close contacts they found evidence of transmission of tuberculosis infection during a flight in two of the seven index cases. In one event, transmission from a cabin flight attendant was detected in 2 of 212 crew members who had worked in close proximity with the index case during a 6-month period. Both of those infected were exposed to the infectious source for at least 12 hours. In the other event, there was a probable transmission from an infectious case to 4 passengers (seated in close proximity to the index case in the same cabin section), out of a total of 257 passengers tested on a flight longer than 8 hours.

Specifically, multidrug-resistant tuberculosis remains a public health crisis and a health security threat. Only about one in three people with drug-resistant tuberculosis accessed treatment in 2020 and from 2018 to 2019, the rate of drug-resistant tuberculosis infections increased by approximately 10%.

We need to seriously reevaluate the way we diagnose and screen for tuberculosis. The Covid pandemic disrupted access to health care and supply chains around the globe. Lockdowns often prevented people from accessing care and in many countries, human, financial, and other resources were diverted from tuberculosis to the Covid-19 response. As a result, 5.8 million people were diagnosed with tuberculosis in 2020, yet a WHO report estimates that about 10 million people were infected and more than 1.5 million died from tuberculosis, the first increase in a decade.

With the increase in asymptomatic cases, many may be unwittingly infecting others. Instead of waiting for patients with symptoms to seek out care, we should be screening entire populations as some countries have successfully done with Covid. As the pandemic continues to rage, we must not continue to delay or ignore public health screenings. A recent Lancet study reports nearly half (47%) of the global population has limited or no access to key tests and services that are essential for diagnosing common diseases, such as diabetes, hypertension, HIV, and tuberculosis, or basic tests for pregnant women such as hepatitis B and syphilis.

Egypt’s 100 Million Healthy Lives initiative provides an example of how we could screen entire populations. Egypt previously had the highest rate of Hepatitis C in the world. In 2018, Egypt launched the 100 Million Healthy Lives program. The goal was to screen all Egyptians over the age of 12 for active hepatitis C virus replication along with other chronic conditions such as hypertension, diabetes, and obesity. Treatment was offered for free in government clinics for those who tested positive for hepatitis C, hypertension, and diabetes; free counseling was available for those considered obese.

Approximately 4 million people with active hepatitis C were identified and treated with the antiviral medication Sovaldi (sofosbuvir), a nucleotide analogue that inhibits the polymerase enzyme of hepatitis C and blocks its replication, effectively eliminating hepatitis C from Egypt.  Once initiated, the program was completed in 18 months. The cost to the Egyptian government was about $45 per 3-month treatment. Patients electing to receive treatment at a private clinic paid $75. The program was primarily funded by a World Bank loan of $530 million. About half of the loan was to expand screening and treatment and the remainder was for health system strengthening.

A similar program could be put in place to control tuberculosis in almost any country. Countries that can not presently afford the cost, can seek out similar loans or grants. Implementing these screening and treatment programs could save millions of lives in the immediate future and avoid the global disruption Covid has caused. As we have learnt from Covid, no one is safe from infection and disease until we are all safe

Read the full article on Forbes 

Originally published on Forbes on Oct 28, 2021