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

Abstract

Dear Editor, Recently, Orviz et al., reported the clinical and virological aspects of Monkeypox cases in Spain during May-June 2022.1Orviz E Negredo A Ayerdi O et al.Monkeypox outbreak in Madrid (Spain): clinical and virological aspects.Journal of Infection. 2022 Jul 10; Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar Since 1970, the Monkeypox virus (MPXV), belonging to Orthopoxvirus genus and Poxviridae family, has been endemic in Central and West Africa.2Parker S Nuara A Buller RM et al.Human monkeypox: an emerging zoonotic disease.Future Microbiol. 2007; 2: 17-34Crossref PubMed Scopus (155) Google Scholar It has now have shown the emergence in various non-endemic countries in 2022 due to the importation from endemic countries due to further community transmission.3WHODisease outbreak news; multi-country monkeypox outbreak in non-endemic countries. World Health Organization, 2022https://www.who.int/emergencies/disease-outbreak-news/item/2022-DON385Google Scholar On 23 July the World Health Organization declared Public Health Emergency of International Concern considering the global monkeypox outbreaks all the six regions affecting multiple countries. The West African and Central Africa (Congo Basin) are the two known clades of the MPXV. The Congo Basin strain causes more severe illness, 0-11% mortality and increased transmissibility.4Bunge EM Hoet B Chen L Lienert F Weidenthaler H Baer LR Steffen R. The changing epidemiology of human monkeypox—A potential threat? A systematic review.PLoS neglected tropical diseases. 2022; 16e0010141Crossref PubMed Scopus (305) Google Scholar The West African clade is been circulating in the ongoing 2022 outbreaks.5WHO. Multi-country outbreak of monkeypox. https://cdn.who.int/media/docs/default-source/2021-dha-docs/20220706_monkeypox_external_sitrep_final.pdf?sfvrsn=1b580b3d_4&download=true. Accessed on July 19, 2022.Google Scholar. Here, we report the detection and genomic characterization of first two MPXV cases travelled from United Arab Emirates (UAE) to India during July 2022. Case 1, a 35-year, male, engineer and 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 [Fig. 1A]. The lesions were umbilicated with the size 0.5 to 0.8 cm. Subsequently, the upper lip became oedematous and then he developed umblicated vesicular lesions in right infra-mammary, right-tragus, right-temple, and right-deltoid region [Fig. 1B]. He also had maculopapular rashes on both hands. With these complaints, he visited a medical facility on 9 and 11 July 2022 [Fig. 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 on 12 July 2022. On his return, he developed sore throat 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 immediately to Government Medical College Thiruvananthapuram [GMCT] [Fig. 1A]. The patient had no known comorbidities 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%, leucocytosis [14,600/L], platelets-2,29,000/µL and random blood sugar level of 100 mg/dl. Investigations for HSV-1/2, Syphilis and HIV were negative. Case 2, a 31-year, male, from UAE had developed dysuria and genital swelling on 8 July 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 10 July 2022. [Fig. 1B]. He travelled from UAE to his hometown in Kerala on 13 July 2022. The lesions progressed and later spread to face, back, neck and forearm with cervical lymphadenopathy by 15 July 2022 [Fig. 1C]. He visited government hospital locally , he was isolated on 16 July 2022 [Fig. 1A]. 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 infection i.e. 13 and 16 July 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.6Li Y Olson VA Laue T Laker MT Damon IK Detection of monkeypox virus with real-time PCR assays.Journal of Clinical Virology. 2006; 36: 194-203Crossref PubMed Scopus (129) Google Scholar,7Li Y Zhao H Wilkins K et al.Real-time PCR assays for the specific detection of monkeypox virus West African and Congo Basin strain DNA.J. Virol Methods. 2010; 169: 223-227Crossref PubMed Scopus (94) Google Scholar 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.8Yadav PD Nyayanit DA Shete AM et al.Complete Genome Sequencing of Kaisodi Virus Isolated from Ticks in India Belonging to Phlebovirus Genus, Family Phenuiviridae.Ticks Tick Borne Dis. 2019; 10: 23-33Crossref PubMed Scopus (28) Google Scholar The complete MPXV genome was retrieved from 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. 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 lineage of 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, the World Health Organization has proposed novel classification for the MPXV genome, where the former Congo Basin (Central African) clade designated as Clade one (I) and West African clade as Clade two (II) with two sub-clades IIa and IIb. All MPXV genomes from the 2022 outbreak belong to West African clade.9WHO Monkeypox: experts give virus variants new names.https://www.who.int/news/item/12-08-2022-monkeypox--experts-give-virus-variants-new-namesDate accessed: August 15, 2022Google Scholar 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. 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 2017–2018.10Gigante CM Korber B Seabolt MH et al.Multiple lineages of Monkeypox virus detected in the United States, 2021-2022.bioRxiv. 2022; https://doi.org/10.1101/2022.06.10.495526Crossref Scopus (0) Google Scholar 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.11Luna N Ramírez AL Muñoz M et al.Phylogenomic analysis of the monkeypox virus (MPXV) 2022 outbreak: Emergence of a novel viral lineage?.Travel Medicine and Infectious Disease. 2022; 49PubMed Google Scholar 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 public health department. 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. 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. PDY, RRS contributed to study design, data analysis, interpretation and writing and critical review. ARS, SK, AMS, AR, PVK, RB, SSM, SM, DYP, AK, AEG, RR, MS, AU, GNS, MR, SS, PJ, SMJ contributed to data collection, interpretation, writing and critical review. PDY, RRS, ARS, AMS, DYP, PA, NG, NV contributed to the critical review and finalization of the paper. The grant was provided from ICMR-National Institute of Virology, Pune for conducting this study. Authors do not have a conflict of interest among themselves. 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. Prathap Somanath, Principal, Government Medical College Kannur; and Dr. Meenakshi V State Surveillance Officer, Additional director of public Health, and Dr. Sandhya, District Surveillance Officer, Kollam 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 Mr Avin 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. Rajlaxmi Jain, Ms. Jyoti Yemul, Ms. Pranita Gawande, Ms. Pratiksha Vedpathak, Mrs. Shubhangi Sathe, Ms. Vaishnavi Kumari, Ms. Nandini Shende, Mr. Raj Hawale, Mr. Ajay Kumar, Mr. Yash Joshi for the diagnosis and data management.