Tomato Flu: A New Pediatric Viral Threat - Review of Current Evidence

"Tomato flu" or "tomato fever" is derived from the fact that the disease initially appears as a tiny red blister that develops into a shape resembling a tomato. The most vulnerable population consists of kids less than five. Strong immunity against the pathogen could explain why adults seldom get tomato flu. But adults who deal with kids could be a vector for the virus. One of the most frequent viral infections, is classified as a HFMD, according to epidemiologist and Kerala State Nodal Officer Dr. Amar S. Fettle. [1] Two primary infectious agents responsible for this condition are EV-71 & CV-A16. Rising number of cases in recent years has brought HFMD's peculiar symptoms to a greater public's attention, despite the fact that the virus is mild and is associated with self-limiting clinical features; patients typically feel well within 5 to 7 days. Among young teenagers, it spreads rapidly on a global scale. [2] All inhabitants have been residing in protected indoor environments since March 2020. Now that limitations are being relaxed and life is getting back to normal. Children are now more likely to come into contact with germs and the outside world now that schools are back in session. Tomato flu is very contagious. There has been a new surge of concern, particularly among the young, over the novel tomato flu virus, which joins the ranks of the undiagnosed monkeypox and COVID-19 infections. The outbreak raised public health concerns due to its rapid spread among young children and its symptomatic similarities to other common viral infections. Despite being non-life-threatening and self-limiting in nature, tomato flu highlights the need for vigilant disease surveillance, accurate diagnosis, and appropriate preventive measures, particularly in pediatric populations. This review aims to provide a comprehensive overview of the epidemiology, clinical features, possible etiology, transmission, management, and preventive strategies related to tomato flu.

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Figure 1: Oral Ulceration in Tomato Flu [10]

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   Figure 2: Small Multiple/Round/Oval Macules & Pearly White Vesicles [10]

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Figure 3: Vesiculobullous Blister in Tomato Flu [10]

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Figure 4: Macules, Papules & Vesicles Around Mouth in HFMD [10]

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            <img alt="Maculopapular Rash on Palm in Tomato Flu.png" height="150" src="https://www.ijpsjournal.com/uploads/createUrl/createUrl-20250425203625-2.png" width="150">
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Figure 5: Maculopapular Rash on Palm in Tomato Flu [10]

Epidemiology

Tomato flu, first identified on May 6, 2022, in the Kollam district of Kerala, India, emerged as a pediatric viral illness predominantly affecting children under the age of five. By late July 2022, 82 cases were reported in Kerala, and the infection subsequently spread to other Indian states, including Tamil Nadu, Odisha, and Haryana. In Odisha, 26 cases were documented among children aged one to nine years .Amazingly, this disease can still cause a great deal of suffering with each new variation, regardless of the severity of the initial attack or the fatality rate. Despite the disease's infectious nature, the Kerala government's health department took sufficient precautions to limit public contamination and the spread of the illness. Although the government mandated isolation for infected individuals for 5-7 days with proper symptom guidance, the general public was encouraged to practise good hygiene and sanitisation and to confine the infected person and their possessions. [4-5]

Biology of Tomato Flu

According to experts, it could be a variant of HFMD. Enterovirus 71, A16, and A6 are the three most common Coxsackie viruses that cause HFMD. At risk are children younger than five years old. HFMD symptoms can begin with a fever and flu-like symptoms in the prodromal phase. Later on, red, blistering patches would appear on the buccal mucosa and tongue, making eating and drinking painful. The soles and palms of the hands could also develop a rash that is vesicular, papular, or macular in appearance. Paralysis and other symptoms such as photophobia, projectile vomiting, stiff neck, or meningoencephalitis can be caused by meningitis, which is a rare consequence. [6] Signs of tomato flu include growing rashes on the hands and feet, fatigue, vomiting, diarrhoea, fever, dehydration, swollen joints, aches and pains throughout the body, and a generalised feeling of not feeling well. [7] In order to determine the causative agent, the BMJ suggests collecting further samples from the ill children and sending them for testing. [8-9]

Etiology

China, Japan, Singapore, Malaysia, and other Asian Pacific nations have occasionally connected HFMD outbreaks to Cv-A16. The respiratory droplets, direct contact, and fecal- oral routes are the primary vectors for its transmission. One component of good hygiene that has been shown to lower the incidence of HFMD is washing one's hands often. Vaccines and other prophylactic measures against Cv-A16 can only be developed after the virus's cause is known. Although there is no specific antiviral treatment for Cv-A16 at this time, preventative strategies include immunisation, hospital infection control, and excellent personal cleanliness. It has been proposed that immunisations, particularly inactivated ones, be administered to children in order to boost immunity and mitigate the impact of epidemics. [10] Initially, tomato flu was speculated to be a sequela of viral infections like dengue or chikungunya, due to overlapping symptoms such as fever, rash, and joint pain. However, further clinical evaluations and virological testing did not confirm any association with these arboviruses. Instead, the disease presentation and transmission patterns strongly align with enteroviral infections. The coxsackie virus, which causes HFMD, was identified in the youngsters by Julian Tang and colleagues at the University of Leicester in the UK. Children in India often get HFMD, a common but mild illness, which is likely to blame for the so-called tomato flu. [12]

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Figure 6: 'Tomato Flu' Causative Agent, Coxsackievirus [10]

Clinical Features

Tomato flu is believed to be a side effect of treating dengue or chikungunya due to their similar symptoms, although there is currently no evidence or data to support this. They are all characterised by a lack of fluids in the body, a high temperature, and the appearance of big, red blisters on different areas of the body. Myalgia, skin rashes, skin pain, etc. Symptoms may include a lack of energy, stomach aches and cramps, painful and swollen joints, and changes in skin tone that manifest as discolouration of the lips, hands, feet, buttocks, and knees. [13] There is currently no evidence to suggest a relationship between dengue, chikungunya, and tomato flu, despite the fact that they overlap symptoms. [14] The aggressiveness of the virus responsible for the recent global tomato flu epidemics has been linked to a number of clinical features. Like dengue and chikungunya, high-grade fever causes rashes and terrible joint pain. One to two days after the fever goes away, you can see little red spots all over your body. They'll eventually turn into blisters and then ulcers. [2] Another theory is that the virus represents a new variation of the common infectious disease hand, foot, and mouth, which disproportionately affects young people and those with weakened immune systems. [15]

Diagnosis

Molecular and serological testing should be conducted on children who show symptoms to rule out herpes, dengue, chikungunya, zika, and varicella-zoster viruses. Following elimination of various viral infections, the presence of tomato virus is confirmed. [16] Laboratory Tests: - In order to investigate an outbreak, samples of stool, skin, and throat are collected. - Within 48 hours of encephalitis patients, samples of cerebrospinal fluid (CSF) are taken. [17] High temperature, joint discomfort, and a rash are the most common clinical signs used to diagnose tomato flu. [10] Serological Studies: Serological studies can measure neutralising antibody titres that are specific to the serotype. When titres quadruple, it is considered significant. Serology can be used to track healing; however, it is less sensitive. [17] Viral Isolation—The diagnosis of HFMD, which includes Tomato Flu, is often considered to be the gold standard when it comes to viral isolation.  The Vero Rhabdomyosarcoma and MRC 5 monolayers are subjected to isolation. Immunofluorescence testing validates the suspicion of enterovirus when cytopathic effect is present. [10] RT-PCR is a tool in molecular diagnostics that can be used for laboratory confirmation. It uses the 5'-UTR region for characterisation & VPI region for genotyping. [17] Additional Molecular Investigations - To learn more about a particular strain and its traits, genotyping is a useful tool. [10]

Transmission

Children exhibiting symptoms should undergo molecular and serological testing to eliminate the possibility of herpes, dengue, chikungunya, zika, and varicella-zoster viruses. The existence of tomato virus is established after multiple viral infections have been eliminated. [16]

Laboratory Testing: - When looking into an epidemic, it's common practice to get samples of bodily fluids such as stool, skin, and throat. Patients with encephalitis are required to have cerebrospinal fluid (CSF) samples obtained within 48 hours. - Samples are collected using viral transfer medium within 48 hours after the onset of sickness. [17] The majority of cases of tomato flu are diagnosed by looking for a rash, joint pain, and high temperature. [10] Serological Studies: Serological studies can measure serotype-specific neutralising antibody titres. It is noteworthy when titres quadruple. Healing can be monitored using serology; however it is not as sensitive as other methods. [17] As far as viral isolation goes, the diagnosis of HFMD (which includes Tomato Flu) is generally thought to as the pinnacle. Each monolayer, including the Vero Rhabdomyosarcoma and the MRC 5, is carefully separated. When cytopathic effect is observed, immunofluorescence testing confirms the suspicion of enterovirus. [10] It genotypes using the VPI region and characterises using the 5'-UTR region. [17] More Molecular Studies – One component of molecular studies could involve genotyping the Vp4 and Vp1 genes with viral capsid subunit proteins (VCSP). Genotyping is an effective method for studying a specific strain and its characteristics. [10]

Management Treatment of Tomato Flu

Symptoms often subside within a week to ten days since the virus is self-remitting. A medical history and physical exam are used for clinical diagnosis in areas where epidemics are taking place. Non-Medical Approach to Treatment: According to doctors, this illness is manageable and the mortality rate is quite low. So, there are ways to avoid getting sick that don't include drugs, such as being clean, staying away from people who seem to be sick, and drinking enough of water and juice. You can lessen the severity of tomato flu symptoms in the long run by avoiding touching blisters, increasing your intake of hot water, and getting enough of sleep. [22]

Medications for Treatment -: The lack of an effective treatment, as well as antiviral drugs and vaccinations, is due to the fact that the disease resolves on its own. According to the Lancet study, the most common drugs used to treat fever, bodyaches & other symptoms are ibuprofen and paracetamol. Although HFMD does not have an antiviral treatment available at this time, oseltamivir & acyclovir have demonstrated some improvement in symptom severity. Use of immunoglobulins in HFMD has also been associated with a reduction in mortality and an acceleration of clinical recovery. [23] At this time, there is no vaccination available to treat it. Although the number of defendants is low. Oseltamivir and acyclovir have demonstrated potential in reducing the intensity of TF symptoms, while there isn't a specific antiviral medication for controlling HFMD. Immunoglobulins are useful in the treatment of heart failure because they lessen the risk of death, alleviate symptoms, and speed up the healing process. The prevention of In order to reduce and control hazards, it is critical to handle the unexpected eccentric illness pandemic properly with certain prevention measures. Basic Safety Measures: Keeping oneself clean is the first line of protection against tomato flu and any other sickness. Preventing the spread of germs by sanitising and washing hands before eating, and shielding children from polluted water and uncooked or leftover food. It is important to regularly clean and sanitise toys and other common household items. If you or someone you know has tomato flu, stay away from them. First, immunisations: Vaccination is the best and safest way to avoid getting sick. The EV-A71 inactivated vaccine, which protects against EV-A71 infections, is now available for children aged six months to five years. The conventional schedule for vaccination is for two doses, each given at least one month apart. Vaccinating infants before the age of twelve months helps them develop a stronger immune system. [1] Infection Prevention in Healthcare Facilities: Healthcare facilities, including hospitals, should actively work to control and prevent the spread of infection. All necessary safety measures should be put in place, including the isolation and quarantining of sick individuals. Counselling the patient is the most effective method for keeping their mind under control when they are sick. Hygienic procedures and regular space and object sanitisation are common preventative measures that hospitals should employ. It may be worth looking at disinfectants that include chlorine or bromine. Traditional disinfectants like 5% Lysol or 75% ethanol are ineffective against enterovirus. [25] Here are some things you can do to be healthy and not get tomato flu: Sick individuals should be quarantined for five to seven days. To avoid transferring tomato fever from patient to host, it is vital to refrain from scratching blisters. This is because the infection is highly contagious. Stay away from infectious patients at all costs. Defences are strengthened by practices of sanitation and cleanliness. To maintain personal cleanliness. Dehydration is dangerous for children. Preserving and improving immunity requires sticking to a healthy, balanced diet. [1, 26]

Table 1: Comparative Representation of Diseases