First two cases of Monkeypox virus infection in travellers returned from UAE to India, July 2022

doi:10.21203/rs.3.rs-1927719/v1

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First two cases of Monkeypox virus infection in travellers returned from UAE to India, July 2022

https://doi.org/10.21203/rs.3.rs-1927719/v1

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We report the first two confirmed cases of Monkeypox in foreign returnees from United Arab Emirates who presented with fever, myalgia, and vesicular lesions on the genital area with cervical lymphadenopathy. The oropharyngeal & nasopharyngeal swab, EDTA blood, serum, urine, lesion samples from multiple sites (lesion fluid, lesion roof and lesion base) were collected from both the cases on ninth post onset day of illness. The clinical specimens of both the cases were tested with real time PCR for Orthopoxvirus, Monkeypox virus (MPXV), West African clade specific MPXV. The specimens oropharyngeal & nasopharyngeal swab, urine, lesion samples from multiple sites (lesion fluid, lesion roof and lesion base) were tested positive for MPXV. The complete genome sequences obtained from skin lesions of case 1 and 2 showed similarity of 99.91 and 99.96% respectively with MPXV_USA_2022_FL001 West African clade. Phylogenetic analysis revealed that the two cases were infected with Monkeypox virus strain A.2 which belong to hMPXV-1A lineage of clade 3.

Virology

Monkeypox

Imported case

UAE

West African Clade

Genome characterization

India

The Monkeypox virus (MPXV), belongs to Orthopoxvirus genus and Poxviridae family which is endemic in Central and West Africa since 1970¹ and now has been reported from various non-endemic countries in 2022.² On 23 July, the World Health Organization declared MPXV as a Public Health Emergency of International Concern (PHEIC) considering the global outbreaks in all the six regions in multiple countries. The cases found to occur mainly due to the imported infections from endemic countries and due to further community transmission.³

The MPXV infection starts with a febrile illness with average incubation of 5–13 days with lymphadenopathy, myalgia, and headache, followed by deep-seated umbilicated vesicular/pustular rashes. The rash primarily starts from face (oral), genital or perianal region and then distributed in centrifugal manner to other parts of the body and progresses over time to scab.^4,5 The primarily infection is of zoonotic origin through contact with infected animals. It is followed by secondary human-to-human transmission that occurs by direct contact with infected body fluids or lesions, via infectious fomites, or through respiratory droplets. The secondary transmission has been reported amongst close contacts through fomites (e.g., beddings, linens, clothes, etc.).⁵

The West African and Central Africa (Congo Basin) are the two known clades of the MPXV, of which Congo Basin strain causes more severe illness, 0–11% mortality and increased transmissibility.⁶ The West African clade is found to be circulating in the current ongoing outbreaks of 2022 in non-endemic countries.³

Here, we report the detection and genomic characterization of first two cases of MPXV infection with travel history from United Arab Emirates (UAE) to India during month of July 2022.

Case 1, a 35-year, male, resident of UAE had developed low-grade fever and myalgia on 5 July 2022. On the next day, he developed multiple vesicular rashes in the oral cavity and lips followed by single lesion on the genital organ [Figure-1A]. The lesions were umbilicated with the size 0.5 to 0.8 cm. Subsequently, the upper lip became edematous and then he developed umbilicated vesicular lesions in right infra-mammary, right tragus, right temple, and right deltoid region [Figure-1B]. He also had maculopapular rashes on both hands. With these complaints, he visited a medical facility on 9 and 11 July 2022. [Figure-1A]. Upon consultation, he revealed history of similar lesions amongst his friends and contact with suspected Monkeypox cases (denied sexual contact), a week prior to onset of symptoms. The clinician had advised the screening for MPXV and prescribed tablet Acyclovir.

However, he travelled from UAE to his hometown Kerala, India on 12 July 2022. On his return, he developed sore throat along with worsening of oral lesions for which he visited a hospital in Kerala. Considering his history of contact with suspected Monkeypox case and pustular lesions, he was referred to Government Medical College Thiruvananthapuram [GMCT][Figure-1A]. The patient had no known co-morbidities but gave history of self-limiting genital lesions eighteen months ago. During clinical evaluation, multiple cervical and inguinal lymph nodes were palpable, which raised a high suspicion of MPXV infection. The initial hematological and biochemical profile on the same day showed haemoglobin-14.1 gm%, leukocytosis [14,600/L], platelets-2,29,000/µL and random blood sugar level of 100 mg/dl. Serological investigations for Syphilis and HIV were non-reactive.

Case 2, a 31-year, male in Dubai, UAE had developed dysuria and genital swelling on July 8, 2022. On the next day, he developed fever with chills, myalgia, backache and headache. Subsequently, he developed multiple vesicular rashes on the genital organ and on both hands on July 10, 2022. [Figure-1A]. He travelled from Dubai to his hometown Kerala state, India on July 13, 2022. The lesions progressed and later spread to face, back, neck and forearm with cervical lymphadenopathy by July 15, 2022 [Figure-1C]. He visited government hospital locally and on the suspicion as Monkeypox case, he was isolated on July 16, 2022 He did not have any co-morbidity and denied any sexual or physical contact with suspected or confirmed MPXV case.

The oropharyngeal (OPS) & nasopharyngeal swab (NPS), EDTA blood, serum, urine, lesion samples from multiple sites (lesion fluid, lesion roof and lesion base) of both the cases were collected on ninth post onset day of illness i.e., July 13, 2022 and July 16, 2022 respectively. Further, they were referred to the World Health Organization Collaborating Centre for emerging and re-emerging diseases, ICMR-National Institute of Virology, Pune, India for the MPXV diagnosis.

The laboratory diagnosis on the clinical samples of both the cases (OPS, NPS, EDTA blood, serum, urine, lesion fluid, lesion roof and lesion base) was carried out using real time PCR for Orthopoxvirus, MPXV, West African clade specific MPXV.^7,8 All the clinical samples of two cases were positive for MPXV, except the EDTA blood and serum of case 2. The clinical specimens of case 1 showed viral load (Copy number/ml) in the NPS (7.4×10⁵/ml), OPS (3.4 ×10⁶/ml), urine (3.4 ×10⁶/ml), serum (1.8 ×10⁶/ml), EDTA blood (6.8 ×10⁴/ml), lesion roof (1.1 ×10⁸/ml), lesion fluid (6.3 ×10⁶/ml) and lesion base (2.3×10⁸/ml). Similarly for the clinical specimens of case 2 had the viral DNA copy number/ml in NPS/OPS (5.9×10⁷/ml), urine (3.4 ×106/ml), lesion roof (8.4 ×10⁸/ml), lesion fluid (2.1 ×10⁷/ml) and lesion base (5.5 ×10⁸/ml).

Further, the skin lesions of both the cases were sequenced with next generation sequencing using Illumina platform.⁹ The complete MPXV genome was retrieved for both the cases and analyzed using CLC Genomic Workbench 22.0. The Maximum likelihood tree has been generated in IQ-TREE software with 1000 bootstrap replications.^10–12 The sequence analysis of case 1 and case 2 revealed similarity of 99.91% and 99.96% respectively with Monkeypox virus isolate MPXV_USA_2022_FL001, complete genome [GenBank accession no. ON674051]. The retrieved sequences [GenBank accession no. EPI_ISL_13953611 and EPI_ISL_13953610] from the clinical specimens of confirmed Monkeypox cases in India belonged to the A.2 descendent lineage of hMPXV-1A lineage of clade 3 (West African clade) (Fig. 2). It has significant 34472 nucleotide mutation of allele T. (https://github.com/nextstrain/monkeypox/blob/master/config/clades.tsv).

The two close contacts [Mother and brother] of the case-I showed symptoms of sore throat, were screened negative for the MPXV. Considering the surge in COVID-19, cases globally and in India, these cases were screened and brother of the case-patient was found positive for SARS-CoV-2. The three close contacts of case 2 were asymptomatic in observation period.

Recently Happi et al., proposed a novel classification of MPXV which grouped into three monophyletic clades (Clade 1: Central Africa 1970–2017, Clade 2: Various countries 1970–2017, Clade 3: 2017–2022). All MPXV genomes from the 2022 outbreak belong to new latter clade hMPXV-1A and the newly classified lineages: A.1, A.1.1, A.2 and B.1.¹³

The clinico-epidemiological history and laboratory analysis of two confirmed Monkeypox cases in India suggest travel-associated introduction of MPXV infection in the country. The genome of both the cases matched closely with the A.2 lineage of clade 3. Recently, Gigante et al., demonstrated highest similarity of two MPXV sequences from 2022 outbreak in USA (USA_2022_FL001 and USA_2022_VA001) with MPXV sequences from a 2021 (ON676707), a travel-associated case from Nigeria to Texas which belongs to lineage A.2. The current Monkeypox outbreak in USA represents the circulation of MPXV lineage A.2 from 2021 which has evolved from lineage A that caused the Nigeria outbreak in 2017–2018.¹⁴ The MPXV genome retrieved from confirmed Monkeypox cases with travel history from UAE to India also demonstrated the circulation of A.2 lineage in UAE. Unfortunately, no epidemiological data is available for the introduction of MPXV to UAE.

An increase in the number of Monkeypox cases with low mortality rate has been observed with B.1. Its estimated time of emergence in the European continent has been predicted to have occurred in as early as March 2022. The B.1 lineage has significant 77383 nucleotide mutation of allele A.¹⁵ However, there is no information available which can differentiate between the transmission pattern of A.2 and B.1 lineage.

Since the detection of Monkeypox cases in India, the containment measures have been taken by Department of Health Research, Ministry of Health and Family Welfare. This includes the isolation of case and contacts, quick screening of all the symptomatic contacts, strict adherence to the personal protective equipment and hand hygiene, hospital infection control practices and intense health education in the community. India has demonstrated quick and continuous vigilance and preparedness to detect the first two MPXV cases within a day of entry of the case in the country. This emphasized the alertness of the all stakeholders including airport authority and the clinicians to be alert for the patients who have rash like illness with international travel irrespective of age, gender or sexual orientation. The surveillance of suspected Monkeypox cases could be strengthened by screening the at-risk population such as men who have sex with men (MSM) and female sex workers (FSW) by National AIDS Control Organization, India. Besides this, adhering to the COVID-19 protocol during the air travel would be beneficial for reducing the transmission amongst the co-passengers and crews through respiratory droplets.

Ethical approval

The study was approved by the Institutional Human Ethics Committee of ICMR-NIV, Pune, India under the project ‘Providing diagnostic support for referred samples of viral hemorrhagic fever and other unknown etiology and outbreak investigation’. The written informed consents were obtained from both the cases.

Author Contributions

PDY, RRS contributed to study design, data analysis, interpretation and writing and critical review. ARS, SK, AMS, AR, PVK, RB, SSSM, SM, DYP, AEG, RR, MS, AU, GNS, MR, SS, PJ, SMJcontributed to data collection, interpretation, writing and critical review. PDY, RRS, ARS, DYP, PA, NG, NV contributed to the critical review and finalization of the paper.

Conflicts of Interest

Authors do not have a conflict of interest among themselves.

Financial support & sponsorship

The grant was provided from ICMR-National Institute of Virology, Pune for conducting this study.

Acknowledgement

Authors extend gratitude to Smt. Veena George [Hon’ble Minister for Health and Family Welfare, Kerala], for her exemplary leadership and efficient coordination of the Monkeypox virus disease control activities, and “The Team Kerala Health,” the district administration, press, media, and people for their efforts in streamlining the public health responses. We would also extend our gratitude towards Mrs. Tinku Biswal, Principal secretary for Health Kerala and Dr. Asha Thomas, Additional Chief secretary Medical Education. The author also extend gratitude to Dr. Thomas Mathew Director of Medical Education; Dr. Preetha PP Director of Health services; Dr. Kala Kesavan P, Principal, Government Medical college Thiruvananthapuram [GMCT]; Dr. Nizarudeen A, Medical superintendent GMCT; Dr. PrathapSomanath, Principal, Government Medical College Kannur; and Dr. Meenakshi V State Surveillance Officer, Dr. Sandhya, District Surveillance Officer, Kollam, Additional director of public Health, Kerala for their immense support. The authors are thankful to Dr. Venugol M, Professor and Head of ENT; and Dr. Anil Kumar TV, Professor and Head of Psychiatry GMCT; Dr. Kirankumar VS and Dr Athul Gurudas Assistant Professors of Infectious diseases at GMCT for their role in patient care. Dr. Aiswarya Babu Heera Junior resident dermatology; Dr. Praveen RK, Junior resident Internal Medicine; Dr Teny George Pallipadan and Dr. Ajithalekshmi A S, Junior residents of community medicine GMCT for being part of the treatment team. The authors are thankful to Dr. Anuja M, Associate professor and all members of State Prevention of epidemic and infectious diseases cell for their role in contact tracing. The authors are thankful to Mrs. Sabitha T.S, Chief Nursing officer GMCT and entire nursing and infection control team for their role in treatment of the patient. Authors are thankful to Miss. Vidya M, Research assistant VRDL, GMCT; Miss Annie CS VRDL GMCT and MrAvin VA, Lab Technician VRDL GMCT for their help in transporting and packing the samples collected. Authors acknowledge Dr. Ajay Krishnan MD, Consultant dermatologist at N.S. Memorial Institute of Medical sciences Kollam for initially suspecting monkeypox and for timely referral to GMCT. The authors are thankful to Prof. Balram Bhargava, Former Secretary Department of Health Research and Director General, ICMR for his encouragement and support. Authors are also thankful for the staff of the Administration section, ICMR-NIV, Pune for their support during the outbreak response. We also acknowledge the excellent technical support from Mrs. Triparna Majumdar, Mrs. Savita Patil, Dr. Raklaxmi Jain, Ms. Jyoti Yemul, Ms. Pranita Gawanade, Ms. Pratiksha Vedhpathak, Mrs. Shubhangi Sathe, Ms. Vaishnavi Kumari, Ms. Nandini Shende, Mr. Raj Hawale, Mr. Ajay Kumar, Mr. Yash Joshi, Dr. Abhinendra Kumar for the diagnosis and data management.

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First two cases of Monkeypox virus infection in travellers returned from UAE to India, July 2022

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Abstract

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Introduction

Clinical Presentation Of Cases

Laboratory Analysis

Discussion

Declarations

References

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