Multipathogen testing an essential part of Test-Target-Treat strategy for respiratory illnesses

At a recent webinar, experts discussed the paradigm shift in respiratory illnesses and treatment practices as the COVID-19 pandemic transitions to an endemic phase. The late Dr Mohan Ravuru, Physician Researcher and former Asia Pacific Medical Director, Abbott, Dr Johnny Sinon, Senior Emergency Physician from Makati Medical Center, Philippines, and Associate Professor Nuntra Suwantarat, Infectious Disease Specialist, from Chulabhorn International College of Medicine, Thammasat University, Thailand, delivered informative presentations and engaged the audience through a stimulating panel discussion.

Among the topics covered were the ‘immunity debt’ phenomenon leading to potential epidemics, challenges in the differential diagnosis of COVID-19 and influenza, and the importance of point-of-care, multipathogen testing as a part of the Test-Target-Treat strategy in respiratory diseases.

‘Immunity debt’ post-COVID-19
During the COVID-19 pandemic, nonpharmaceutical interventions (NPIs) such as social distancing, hand hygiene, and mask wearing have reduced the incidence of viral and bacterial infections, including respiratory infections. However, disruptions to the seasonal transmission patterns of these diseases may have consequences for the timing and severity of future outbreaks. [Proc Natl Acad Sci USA 2020;117:30547-30553]

“An ‘immunity debt’ can happen when people who have not been exposed to normal levels of viruses and bacteria experience a surge in infections upon contact with a virus,” explained Ravuru.

“The longer the periods of low-exposure to viral or bacterial infections, the greater the likelihood of larger, future epidemics. This is due to a growing proportion of susceptible people and the decline in herd immunity,” he added.

“There has been emerging evidence of rebound non-COVID-19 infections,” noted Ravuru. “Surveillance studies in France recorded uncommon trends and a significant rebound of enteroviral infections, bronchiolitis, gastroenteritis, and otitis in 2021. A near-absence of influenza was observed between April 2020 and November 2021 until a resurgence occurred in early 2022. [Lancet Reg Health Eur 2022;22:100497]

Preliminary results for modelling influenza suggest that outbreaks may occur outside of the typical season, and there is a possibility of a significant antigenic drift with the rebound. Vaccine efficacy may be compromised, as a lack of viral patterns increases the risk of antigenic mismatch between the vaccine and the circulating virus strain. These factors, coupled with lowered population immunity, could make seasonal influenza more severe than usual.

The co-circulation of influenza and COVID-19, may be on a trajectory for collision, cautioned Ravuru. The threat of a “twindemic” — two epidemics at the same time—looms large in Southeast Asia and could potentially burden vulnerable populations and healthcare systems. Co-infections with multiple viruses simultaneously add complexity to clinical diagnosis, treatment, and patient management, he added.

“As NPIs are relaxed, healthcare systems may need to prepare for future outbreaks of non–COVID-19 infections, which may occur several years later. Monitoring population immunity levels should be a part of the public health toolbox,” he advised.

Role of point-of-care testing in the differential diagnosis of COVID-19 and influenza
“There is a considerable symptom overlap between influenza and COVID-19. Fever/chills, cough, shortness of breath, fatigue, sore throat, runny nose/congestion, muscle/body pains, headache, and change or loss of taste or smell may occur in either condition. It is difficult to confirm the diagnosis based on clinical symptoms alone,” said Sinon.

Multipathogen testing, also called syndromic or panel testing, quickly distinguishes pathogens when clinical presentation is similar. These include antigen or molecular-based tests. Antigen tests detect viral proteins and are faster than molecular tests, whereas molecular tests detect nucleic acid and are more accurate than antigen tests. Molecular point-of-care tests, which offer rapid turn-around times, are generally preferred in emergency departments (Table 1).

“Confirmatory testing for respiratory diseases can guide clinical judgement, impact infection control protocols, and facilitate therapeutic decisions (Table 2). It also enables physicians to inform and counsel patients on prognosis and the risk of worsening. Moreover, diagnostic stewardship is an integral part of antibiotic stewardship efforts to optimize antibiotic use and improve patient outcomes,” Sinon elaborated.

“Severely immunocompromised and critically ill patients, and those with respiratory infections benefit the most from multipathogen testing,” he added.

Test-Target-Treat strategy in respiratory infections
The Test-Target-Treat strategy empowers healthcare workers to use rapid diagnostics to identify specific pathogens that cause respiratory infections, allowing faster, more effective, and more targeted treatment decisions. This, in turn, reduces inappropriate antimicrobial use and the spread of resistance.

Test
The WHO defines influenza-like illness (ILI) as an acute respiratory infection with a measured fever of ≥38°C and cough, with onset within the past 10 days. [https://www.who.int/teams/global-influenza-programme/surveillance-and-monitoring/case-definitions-for-ili-and-sari]

“As ILI is a syndrome, it is difficult to diagnose the exact aetiology based on clinical presentation,” said Suwantarat. “Rapid antigen tests or rapid PCR tests are very helpful for definitive diagnosis.”

The WHO Guidelines support testing for both influenza and SARS-CoV-2. [https://www.who.int/publications/i/item/WHO-2019-nCoV-Influenza-readiness-COVID-19-2020.1]

“Patients with severe acute respiratory illnesses may be also tested for co-infections with respiratory syncytial virus (RSV), mycoplasma pneumoniae, nosocomial pathogens, and multidrug-resistant pathogens,” said Suwantarat. “In tropical countries, tests for nonrespiratory diseases such as dengue, chikungunya, scrub typhus, leptospirosis, and malaria, may also be considered.”

“However, we rarely identify the final diagnosis for patients with mild upper respiratory tract infections, most often caused by rhinovirus or enterovirus, as these are usually managed with supportive treatments,” she added.

Target population
The target for testing are individuals at high risk for severe respiratory illness, such as infants and young children, pregnant women, the elderly (≤65 years of age), and those with comorbidities such as compromised immunity, diabetes, obesity, and cardiovascular disease. [CDC 2022; https://www.cdc.gov/flu/highrisk/index.htm; Accessed 21 September 2022]

Treatment options
Importantly, rapid point-of-care testing enables treatment to be given in a timely manner. Many therapeutic options require administration soon after the disease onset for optimal outcomes (Table 2).