Each year, the flu-like illness usually peaks in February-April and July-September in Nepal. In most cases, influenza virus testing is recommended for people who have flu-like symptoms. Among the flu-like cases, only 8-18 percent were found positive for influenza virus, from the beginning of 2023 till February 12, meaning that 82 percent of the flu-like illnesses are actually caused by non-flu viruses. In other words, unknown flu-like illnesses are widely circulating in Nepal. According to the World Health Organization (WHO) statistics report, influenza-like illnesses (non-influenza virus) are widespread across the world. The question then is: Could these mysterious flu-like illnesses or infections be capable of triggering the next pandemic?

The WHO defines influenza-like illness (ILI) as an acute respiratory infection with a fever over 38 degrees Celsius or 100.4 degrees Fahrenheit and a cough with onset within the last 10 days. Likewise, severe acute respiratory infection (SARI) is defined as an acute respiratory infection with a history of fever or measured fever of over 38 degrees Celsius or 100.4 degrees Fahrenheit and cough with onset within the last 10 days and requires hospitalisation. However, most patients with ILI symptoms are reluctant to seek medical advice or care from hospitals in Nepal. Patients with ILI symptoms are usually advised to visit healthcare centres only if fever and cough persist and last longer than two or three weeks. Patients with SARI symptoms are observed up to six times higher compared to patients with ILI symptoms. A study conducted in 2014 in Nepal showed that 87.5 percent of the patients with SARI were found negative for the flu virus, meaning unknown respiratory pathogens responsible for SARI have been circulating, perhaps for many years, in Nepal. Such unexplained flu-like illnesses are spreading all over the world. Unfortunately, they have received little attention so far. Countries are unable to understand, explain or identify the causative agent of flu-like symptoms and SARI.

Another interesting observation is that an increasing number of flu A and B viruses could not be further identified by their subtypes and lineages. There are four types of flu viruses: A, B, C, and D, with A and B being the most contagious, causing seasonal epidemics of disease in humans annually. H1N1pdm09 and H3N2, popularly known as “Swine flu” and “Hong Kong flu”, are subtypes of the flu A virus, while flu B is further divided into two lineages: Victoria and Yamagata. There is, however, a growing number of undetermined lineage(s) (neither Victoria nor Yamagata) of flu B virus detected in recent years in Nepal, notably observed just before the Covid-19 pandemic (during August-September 2019). Similarly, unknown flu subtype(s) A virus has also significantly increased globally over the past few years. It is well known that flu is an RNA (ribonucleic acid) virus with a higher mutation rate. It is, thus, possible that the flu virus is continuing to evolve rapidly, giving rise to subtypes and lineages that pose a challenge for currently available flu vaccines. This could be the main reason for the lower effectiveness of currently available flu vaccines, which needs further investigation. Vaccines are less effective when the vaccine antigen is mismatched with those of circulating virus strains.

In 2019, Nepal first reported bird flu infection, i.e. H5N1, in a 21-year-old young male, who later died of complications. Prior to this incident (a couple of days before), I had examined other suspected bird flu cases who developed the ILI after disposing of chickens (hundreds of dead chickens per day) following sudden unexplained deaths. A few days ago, Nepal reported an outbreak of H5N1 bird flu on poultry farms in Kathmandu Valley. A study conducted in Nepal found that most farmers do not wear face masks and wash their hands regularly after handling poultry. It poses a significant risk of transmission of bird flu infection to poultry farmers. Unfortunately, it is unlikely to detect bird flu infection in farmers with ILI/SARI early since laboratory testing is not widely available or accessible in Nepal. Bird flu infection may go unnoticed until complications occur, as with a young male in 2019. People-to-people H5N1 bird flu transmission is a matter of grave concern, as it is a highly pathogenic avian influenza, and the mortality rate is nearly 60 percent. However, there is no clear evidence of it easily spreading from person to person.

On November 21, 2022, the WHO launched the list of priority pathogen agents that can cause a serious international epidemic in future. It consists of several viruses, including “Disease X”. According to the WHO, “Disease X” indicates an unknown pathogen that could cause future deadly outbreaks and pandemics. The respiratory pathogen could likely be the next “Disease X” that can cause the next pandemic, as we recently experienced with Covid-19. Several other respiratory pathogens, popularly known as Spanish flu (H1N1), Swine flu(H1N1pdm09), and SARS-CoV-1, created serious international epidemics in the past. It is not easy to prevent the spread of any airborne disease (i.e., respiratory diseases) from place to place or country to country. Many countries, including Nepal, implemented travel and trade-related restrictions and strict preventive measures but failed to avert Covid-19 waves in their respective countries. Thus, ILI/SARI being airborne/droplet disease(s) or respiratory illness(es), there is a greater chance of becoming a “Disease X”, triggering the next pandemic. It is worth mentioning here that initially, Covid-19 was also presented as ILI/SARI before the World Health Organization officially named it. “Disease X” might emerge from unknown respiratory diseases, initially presenting as ILI/SARI and may cause a pandemic later.