COVID-19 pandemic and lockdowns impact TB mortality

There was a significant reduction in tuberculosis (TB) testing and case detection across South Africa in the past two years, and these reductions directly coincided with each wave of the COVID-19 pandemic and the related tightening of lockdown regulations, according to recent data. This emerges as new papers involving University of Cape Town (UCT) researchers, just published in The Lancet and Lancet Respiratory Medicine, revealing vital information about the effects of the pandemic on TB detection and care.

To coincide with World TB Day on 25 March, the paper, ‘Accelerate Investment and Action to Find the Missing Patients with Tuberculosis’ in The Lancet, aims to draw attention to the “missing” TB diagnoses that occurred over the past two years.

The missing 4 million

“COVID-19 was associated with an estimated increase in the number of missing new tuberculosis diagnoses to about 4 million worldwide in 2020,” wrote the paper’s authors. “The COVID-19 pandemic has disrupted access to tuberculosis services, resulting in multi-dimensional effects, including increased tuberculosis morbidity and mortality.”

Credited among the paper’s authors is Professor Keertan Dheda, director of the Centre for Lung Infection and Immunity (CLII), a unit of the UCT Lung Institute (UCTLI).

Dheda is also an author of the paper, ‘The Intersecting Pandemics of Tuberculosis and COVID-19: Population-Level and Patient-Level Impact, Clinical Presentation, and Corrective Interventions’, which was published in Lancet Respiratory Medicine.

“The most drastic reduction showed that in May of 2020, TB testing had fallen by more than 50%, the diagnosis of drug-sensitive TB had fallen by 40%, and rifampicin-resistant TB by about 50%.”

Dr Tahlia Perumal is named as a co-author with Dheda on the Lancet Respiratory Medicine paper. A clinical researcher at the CLII, Perumal works on clinical trials specialising in TB and COVID-19, and says that data received from the National Institute For Communicable Diseases (NICD) indicates that there was a “substantial reduction” in TB testing and case detection nationwide as the country went through each of its COVID-19 waves and hard lockdowns.

“The most drastic reduction showed that in May of 2020, TB testing had fallen by more than 50%, the diagnosis of drug-sensitive TB had fallen by 40%, and rifampicin-resistant TB by about 50%. Additionally, we saw an 18% reduction in attendance of primary healthcare facilities nationwide,” confirms Perumal.

Restriction of movement over this period is attributed as a factor for the decrease in TB diagnosis and care.

“Although there may have been outside influence in reduction attributed to infection-prevention-and-control interventions put in place for COVID-19 such as mask wearing, hand hygiene and social distancing, it is widely assumed that the restrictions to access to healthcare (testing, treatment, and prevention) offsets any transmission reduction,” she added.

Perumal's keen interest in epidemiology led to her becoming familiar with COVID-19 modelling studies that described the potential effects of lockdowns on core health services.

The Lancet Respiratory Medicine paper she worked on with Dheda is a systematic review commissioned by Lancet Respiratory Medicine looking at current evidence available. Perumal noted that more than 20 people worked on it, including Dr Ali Esmail, a specialist pulmonologist and the head of the clinical trials unit at the CLII, and Dr Alex J Scott, a clinician at the CLII.

“The WHO estimates an 18% global reduction in TB case detection.”

“This was a collective from many researchers… The paper included TB experts, researchers and doctors from all over the world: representatives of the CLII, representatives from the NICD and South African Medical Research Council, and representatives from India, China, the United States and Canada.”

A massive drop in TB testing and detection

Through individual country analyses, large global reporting services like the World Health Organization (WHO) global TB reports, and national laboratory data, Perumal says they saw a massive reduction in TB testing, TB case detection and access to TB care (including treatment and prevention services) as a result of the pandemic and the associated control efforts.

“The WHO estimates an 18% global reduction in TB case detection (from 7.1 million in 2019 to 5.8 million in 2020). Major reductions were recorded in the Philippines (37%), Indonesia (31%), South Africa (26%) and India (25%). The COVID-19 pandemic has also interrupted TB prevention services, accounting for up to 60% reduction in BCG vaccination globally.”

Data shows that the reduction in TB services has lead to an increase in TB-related deaths.

“There are a wide variety of modelling studies that estimate the effects the reduction to TB services may have (had) — they all have one thing in common: significant increases in tuberculosis-associated mortality, worsened by every month taken to restore TB services.

“Analysis from the WHO and the StopTB Partnership predicted 190 000 additional deaths in 2020, and 1.4 million additional tuberculosis deaths between 2020 and 2025. Additionally, the reduction in access to BCG vaccination (delayed or missed) may account for up to 33 074 additional TB-associated paediatric deaths.

“South Africa is considered one of the top TB-burdened countries in the world — notifying [around] 200 000 cases every year.”

“This was supported by data presented to and reported by the WHO in their global TB report for 2021, showing 1.32 million tuberculosis deaths worldwide in 2020 — the first increase in TB morality in over a decade.”

Tough road ahead for curbing TB deaths

Perumal predicts a “long and winding road” ahead in addressing morbidity and mortality associated with TB and COVID-19 in South Africa. Dheda adds that “major investments into TB R&D are required by African governments, where TB sets back national GDPs by between 2 and 3%”.

“South Africa is considered one of the top TB-burdened countries in the world — notifying [around] 200 000 cases every year, including both multi and extensively drug-resistant cases.”

The paper advocates for improved funding for diagnostic, treatment, and prevention services including vaccine development, and dedication to healthcare workers and services.

“Significant improvements to the methods of diagnosis for both TB and COVID-19 are required: faster, more sensitive point-of-care testing for TB, as well as consideration into joint screening strategies for the twin pandemics.

“Investment in active case finding strategies need to be made to treat TB early and curb transmission… Improvements in the care and protection of healthcare workers and healthcare services are essential for building lasting interventions.”

As the paper is published, CLII’s work to dig deeper into TB research that could unlock breakthroughs continues. Perumal said she is project managing a trial funded by the Wellcome Trust, UK MRC and the European and Developing Countries Clinical Trials Partnership (EDCTP) called XACT-3 (with Dheda as PI), which aims to validate a scalable TB case-finding strategy.

“There is something different about working to incite change on a policy-changing level. UCT and the UCTLI give us an incredible springboard — connecting us to core research ventures and incredible people in healthcare. I really want to use our research platform to change the way we tackle infectious disease, something so often stigmatised and neglected.”

Watch the Brimstone and Groote Schuur Hospital "Dialogue on Tuberculosis 2022", featuring Professor Keertan Dheda here.