Tomato Flu in India: A confluence of resurgence and mutation?

Dear Editor, Several states in India are reeling from a recent outbreak of tomato-flu or tomato-fever, amid the mounting cases of monkeypox and COVID-19. This self-limiting flu has been reported in patients aged 5 years or under and is non-life-threatening in its current endemic state [1]. The symptoms, mode of transmission, prevention and mitigation are illustrated in Fig. 1.Fig. 1.: The symptoms, mode of transmission, prevention and mitigation strategies against Tomato-flu.In the Lancet Respiratory Medicine, Chavda et al. presented an interesting discussion on the emergence of the tomato-flu virus, first reported on May 6, 2022 [1]. However, its first reports dated back to early 2000, in patients previously infected with Chikungunya [2,3]. The disease has been recurring since then, during September–October, following the rainy season in Kerala. The BMJ validates the same by reporting statements from medical practitioners in Kerala who have observed and reported these cases as early as 2001 [3]. Tomato-flu may be an aftermath of dengue, or more possibly, chikungunya. However, as suggested by the same team, it could also suggest the emergence of a new variant of the viral hand, foot, and mouth disease (HFMD) [1] caused by enteroviruses (EV) such as Coxsackie A6 (CA6), Coxsackie A16 (CA16), Coxsackie B, EV A71, and other Echo viruses, infecting children aged 5 or under [4]. Most patients of tomato-flu are aged 1–5 years [5,6], and in some cases up to 9 years [7]. There is a possible tendency to spread the disease from children to immunocompromised adults [8], and ultimately to immunocompetent adults [1,9]. Tang et al. reported similar vesicular rashes in siblings, male (5 years) and female (13 months), who manifested after their Kerala vacation. Though neither child developed fever or other systemic symptoms, painful oral lesions (with excessive drooling) manifested in the female. The lesions healed completely without scarring on days 6 and 16 for the male- and female-child, respectively. Polymerase chain reaction (PCR) was positive for EV and negative for monkeypox. Phylogenetic analysis of the tomato-flu virus included partial CA16 sequences resembling a clade from China (2011–2014) [10]. Furthermore, Sasidharan et al. who were the pioneers in documenting the prevalence of HFMD in India, reported 81 cases of the same and determined Enterovirus-71 (EV-71) as its causative in 2005 [11]. The authors also regarded the disease as mild that did not require hospital admissions, and it was self-limiting and the patients recovered within two weeks [3]. In 2008, Singapore witnessed one of the largest outbreaks of HFMD, with more than 30,000 cases reported [12]. However, experts believed that the actual cases in India are far more than the reported figures, owing to under-reporting resulting from a lack of surveillance and reporting matrix or system in India [3]. These findings corroborate the possibility of a resurgence and/or variant of the HFMD virus, with an increased recovery time of 8–10 days [5]. Since its first outbreak in 2001, healthcare providers have witnessed the evolution of the virus, which has brought about changes in its clinical characteristics. While the initial outbreaks majorly affected children aged below 5 years, there has been a gradual shift when symptoms have been reported in adolescents and adults too. The lesions now are predominant in the trunk area, which earlier was majorly confined to the palms and soles [3]. The tomato-flu diagnostic regimen should be rational and directed, contrary to the sero-immunological testing for a spectrum of viral illnesses to subsequently ruling them out. Alternatively, common methods such as PCR could identify the causative and devise a diagnostic regimen. Until then, symptomatic treatments including antipyretics, antihistamines, and local anesthetics for lesions should be recommended. Since medical practitioners may potentially confuse these symptoms with varicella, which causes chickenpox, the antiviral acyclovir may be overly prescribed [3]. However, this can be limited by laboratory confirmation of samples and concurrent, training, and education of physicians. Non-infected states could use this time to conduct research, train medical professionals, develop diagnostic kits, repurpose pre-approved drugs, and create standard operating procedures (SOPs). A dedicated reporting and monitoring system must be institutionalized and reinforced to prevent this outbreak from straining the already overburdened healthcare system. Ethical approval Not applicable/Not required. This article does not require any human/animal subjects to acquire such approval. (This submission is a Correspondence. It is not a clinical or experimental study and does not involve human participants and/or research studies.) Sources of funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Author contribution Ryan Varghese: Conceptualization, Resources, Data Curation, Writing-Original Draft, Writing-Reviewing and Editing, Visualization, Project Administration, Dileep Kumar: Writing-Reviewing and Editing, Resources, Data Curation, Visualization, Project Administration, Rohit Sharma: Writing-Reviewing and Editing, Resources, Data Curation, Visualization, Project Administration. Conflicts of interest The authors declare that there is no conflict of interest. Research registration Unique Identifying number (UIN) Name of the registry: Not applicable/Not required [Please note that this submission is a Correspondence article which discusses the Outbreak of Tomato Flu. It is not a research study/clinical trial/systematic review, and therefore does not require any Registry number.] Unique Identifying number or registration ID: Not applicable/Not required Hyperlink to your specific registration (must be publicly accessible and will be checked): Not applicable/Not required Guarantor Rohit Sharma (Corresponding author). Data statement The data in this correspondence article is not sensitive in nature and is accessible in the public domain. The data is therefore available and not of a confidential nature. Provenance and peer review Not commissioned, internally peer-reviewed. Ryan Varghese Dileep Kumar Rohit Sharma 1Poona College of Pharmacy, Bharati Vidyapeeth (Deemed to Be) University, Pune, Maharashtra, 411038, India 3Department of Entomology, University of California, Davis, One Shields Ave, Davis, CA, 95616, USA 4Department of Rasa Shastra and Bhaishajya Kalpana, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005, Uttar Pradesh, India E-mail addresses:[email protected]; [email protected]