Monkeypox and Hand-Foot-Mouth Disease Outbreak in india: A Double Trouble?

Amidst the coronavirus disease pandemic


inTRODuCTiOn
Amidst the COVID-19 pandemic, the recent concurrent surge in cases of Hand-Foot-Mouth Disease (HFMD) and monkeypox in India has been a major cause of public health concern. 1 Since both HFMD and monkeypox are viral diseases having similar signs and symptoms, it is difficult to distinguish between the two clinically. 2 Improper diagnosis will lead to incorrect treatment of the disease, thus adding the burden of the disease on society. 3Therefore, it is the need of the hour to sensitize the medical fraternity towards the differences between the two viral diseases based on the etiology, epidemiology, transmission, and signs and symptoms so that the diagnosis and management can be done effectively.

etiology and epidemiology HFMD
HFMD or tomato fever is a viral infection commonly caused by coxsackievirus A16 and enterovirus A71. 4 HFMD is found to affect both genders equally.However, according to the available epidemiological data, the occurrence is slightly higher in males.It has also been noted that HFMD affects children (mostly below 10yrs of age) more as compared to adults. 4Studies have reported that the outbreak is common in summer and early autumn.In a few studies, it has been reported that close contacts are at risk of developing the disease since the virus is shed from the stools of the infected person for many weeks. 5

Monkeypox
Monkeypox virus, belonging to the Poxviridae family, is the causative agent for monkeypox. 6Monkeypox is endemic to Central and Western Africa.Recent studies suggest that the virus is commonly found in African rodents.Two genetically distinct clades (Central and West African clade) exist currently. 7The Central African clade (Congo Basin) shows propensity for human transmission. 7The possible risk factors include inhabiting rural and forested areas of Africa, preparing bushmeat, looking after monkeypox-infected people, and lack of smallpox vaccination.The infection has been reported to showcase a male predilection, possibly due to constant contact with wild animals during frequent hunting. 8,9rrent status of the outbreaks in india HFMD The first case of HFMD in 2022 was first reported in Kerala on 6 th August 2022 and as of 22 nd August 2022, more than eighty-two children below the age of 5 years have been infected. 10amil Nadu and Odisha have also reported an outbreak of some cases. 10As of now, no mortality has been reported in India due to HFMD.

Monkeypox
In India, the first case of monkeypox was reported on 15 th July 2022 in a 35-year-old man who had returned from the Middle East. 11As of 15 th August 2022, India has reported ten confirmed cases and 8 suspected cases of monkeypox.The confirmed cases are from Kerala 12 and Delhi 13 and the suspected cases are from Telangana, 14 Uttar Pradesh, 15 Bihar, 16 and Delhi.The first monkeypoxrelated death in India was reported on 1 st August 2022 in Kerala. 17he Indian government health officials have declared both these diseases as highly infectious, and have issued a warning regarding their spread to other states as well.

Mode of Transmission HFMD
HFMD spreads by direct contact through saliva, nasal, and throat secretions, blister fluid, and stool of infected persons. 18The virus may spread by unwashed or virally-contaminated hands, and by contact with contaminated surfaces.People infected with the virus are highly contagious during the first week of illness.However, the infection can still be transmitted to other people even if the infected person becomes asymptomatic. 18Some people may also act as carriers (people infected and excreting the virus but not showing any symptoms).The disease is not transmitted through animals or pets. 18

Monkeypox
According to the CDC, monkeypox spreads through direct contact with respiratory secretions, rash, scabs, body fluids, or touching fomites that have been used by the infected individual. 19Direct contact involves physical or intimate contact, or prolonged face-to-face contact with an infected person. 19According to the WHO, some of the cases of the current outbreak have been reported in homosexual and bisexual communities.Transgender people may also be vulnerable to the disease. 20

Signs and symptoms
H F M D a n d m o n ke y p ox c a n b e differentiated based on the following signs and symptoms 21 (Table 1).

Diagnosis HFMD
The diagnosis of HFMD is usually made clinically.Shedding of the virus from the oropharynx starts within 4 weeks of infection; however, the virus is detectable in the stool for about 6 weeks post-infection. 22Microscopic examination of biopsies and swabs from vesicles can help differentiate HFMD from Varicella Zoster virus and Herpes Simplex Virus infections. 22Serum IgG levels can be used to monitor the recovery from HFMD, but they are not very specific. 23In certain cases, serological tests have been useful in differentiating HFMD from Enterovirus infection.However, RT-PCR has been a gold standard diagnostic tool for the final confirmatory diagnosis of HFMD. 23

Monkeypox
Visual diagnostic methods like electron microscopy, immunohistochemistry and serum studies using IgG and IgM are sufficient for the diagnosis of Monkeypox infection. 24However, the use of patient specimens for isolation of the virus in a culture medium, or amplification of the viral DNA using RT-PCR can be confirmatory. 24

HFMD
HFMD is a self-limiting disease that resolves on its own within 7-10 days. 25anagement should aim at lowering fever, pain relief, and adequate oral hydration.Enterovirus 71-induced HFMD has shown severe neurological complications.No drug has been approved for treating the same; however, novel agents such as translation inhibitors, molecular decoys, replication inhibitors, and receptor antagonists have shown promising results. 25Pleconaril, a novel Gargle using a mixture of liquid ibuprofen and liquid diphenhydramine.This mixture coats the ulcers and helps in reducing the pain Severe cases Ribavirin, amantadine, and quinacrine of enterovirusinduced HFMD antiviral agent has been effective in the treatment of enterovirus-induced HFMD. 25 The supportive management of HFMD 26,27 has been discussed in Table 2.

Monkeypox
At present, there is no clinically proven management existing for monkeypox.However, certain preventive measures like isolation of infected patients, wearing surgical masks, and covering the lesions until their crusts naturally fall off, may prevent the further spread of the disease. 28rior vaccination against smallpox was reported to be 85% effective in preventing monkeypox infection. 29n certain cases, post-exposure vaccination with a modified vaccine has been recommended.The Ankara vaccine is a live, modified vaccine.It is a two-dose vaccine, administered at an interval of four weeks.It has a greater safety profile, and stimulates antibody production in immunocompromised patients.It also does not invoke skin lesions or any local or distant spread of infection. 28 o s t -e x p o s u r e v a c c i n a t i o n i s recommended in high-risk exposure patients with contact between broken skin or mucous membrane and body fluids.According to the CDC, initiating vaccination within 4 days of infection may prevent disease onset, while severity of the disease can be decreased by vaccinating within 14 days of infection. 28djunctive management of monkeypox, 30 has been discussed in Table 3.

COnCluSiOn
While the country is still combating the COVID-19 pandemic, the outbreak of these two viral diseases simultaneously is a significant public health threat.Moreover, the sparsity of available data on the two diseases may underestimate the severity of the infections.It is, therefore, imperative to distinguish the two disease entities to ensure that an accurate diagnosis is made and prompt management is initiated.The Government needs to standardize the treatment protocol and issue appropriate guidelines to curb the further outbreak of these infections in the country.

Table 1 .
Signs and symptoms of monkeypox and HFMD

Table 2 .
Supportive management of HFMD

Table 3 .
Adjunctive therapy for monkeypox