A suspected case of tomato flu from an endemic region. Credit: Prakasini Satapathy

In May 2022, there was an outbreak of a rash affecting children in Kerala in south India. The rash developed into small tomato-like blisters, earning it the name ‘tomato flu’.

Within three months the infection was reported in children from Tamil Nadu, Odisha, Haryana and Punjab. Health authorities monitored Kerala-Karnataka border districts including Kannada, Udupi, Kodagu, Chamarajanagar and Mysuru1. By July 26, 82 cases had been reported in Kerala2 among children under 5. Twenty-six children from the age of one to 9 were diagnosed with tomato flu in Bhubaneswar, Odisha, indicating that children over 5 were also at risk of the infection2.

Initially considered a new viral infection, the possibility soon emerged of it being a new variant of the common viral hand, foot, and mouth disease (HFMD) 2, 3, an infection mostly in children aged 1–5 years and immunocompromised adults. Studies confirmed tomato flu as a possible HFMD variant by excluding common viral illnesses such as dengue, chikungunya, zika, varicella-zoster and herpes by molecular and serological tests in children. These children were reporting symptoms of fatigue, nausea, vomiting, diarrhoea, fever, dehydration, swelling of joints, body aches, and common influenza-like symptoms. The hypothesis of a new virus was thus proven wrong. Tomato flu was established as a variant of HFMD caused by the coxsackievirus A-16 of the enterovirus family3. HFMD’s peak transmission is during summer and fall4.

By August, a blog on the Infectious Diseases Society of America (IDSA) site claimed tomato flu was named incorrectly, criticising the use of the term ‘new virus’ to describe it. It noted that HFMD due to the coxsackievirus A-16 was likely the cause of the outbreak in India. It also noted that the atypical symptoms were due to the coxsackie A16 variant, which was confirmed by viral sequencing in the UK from skin lesions in two children returning from Kerala.

Tomato flu as a popular reference to HFMD may be acceptable, but to declare it a new variant needs genetic characterization, sequence similarities and phylogeny. Biological and environmental conditions coupled with active disease surveillance is needed to establish it as a clinical variant.

HDFD symptoms in children are similar to those of chikungunya, which include high fever, rashes, and intense pain in joints. But the rash pointed to HFMD and varicella.

HFMD is mostly a localized eruption limited to painful oral erosion after 1 to 2 days of fever followed by appearance of typical greyish vesicles with surrounding erythema on the palms and soles, buttocks and genital area 4,5. But the most prominent feature is the eruption of red and painful blisters throughout the body that gradually enlarge to the size of a small tomato. In varicella-zoster, vesicular eruption spreads from the face to the trunk. Varicella lesions are polymorphous eruptions — rose-coloured macules that rapidly progress to papules, vesicles, pustules and crusts4.

While HFMD is highly contagious, it is relatively mild lasting 7 to 10 days and caused by multiple enterovirus (EV) serotypes mainly coxsackievirus A6 (CVA6), coxsackievirus A16(CVA16) and enterovirus 71 (EV71) in India6.

HFMD due to CVA6 serotype is typically mild or asymptomatic and has rarely needed clinical attention. The disease has been in focus since 2008 given increasing evidence that the clinical, epidemiologic and etiologic characteristics of HFMD are currently different from those initially thought.

In 2011, 170 children reportedly died in Vietnam due to an HFMD outbreak associated with enterovirus-A71 infection7.

Several studies reported differences in symptomatology from HFMD disease arising from CVA16 and EV71 infections. CVA6-associated atypical HFMD is frequently associated with crusted lesions, eczema-type rash on arms, trunk, buttocks and legs; onychomadesis and a greater disease severity than HFMD is associated with other EV-A serotypes8.

The current outbreak in India attributed to tomato flu only demonstrates the role played by virus recombination mutations, which lead to emergence of new enteroviral strains and altered presentation of the disease clinically. Urgent laboratory testing and genotyping are therefore needed to confirm the cause.

In the absence of antiviral drugs or vaccines to treat or prevent HFMD, efforts should be made to repurpose existing drugs. Follow-up of cases and active surveillance will also help understand outcomes and future consequences of the disease.

Prakasini Satapathy is with the Department of Virology; Postgraduate Institute of Medical Education and Research, Chandigarh, India; Ranjit Sah is at the Tribhuvan University Teaching Hospital, Institute of Medicine, Kathmandu, Nepal.