ABSTRACT
In order to maintain the polio eradication status, it has become evident that the surveillance of cases with acute flaccid paralysis and of environmental samples must be urgently supplemented with the surveillance of poliovirus excretions among individuals with inborn errors of immunity (IEI). All children with IEI were screened for the excretion of poliovirus during a collaborative study conducted by the ICMR-National Institute of Virology, Mumbai Unit, ICMR-National Institute of Immunohaematology, and World Health Organization, India. A seven-month -old male baby who presented with persistent pneumonia and lymphopenia was found to have severe combined immune deficiency (SCID) due to a missense variant in the RAG1 gene. He had received OPV at birth and at 20 weeks. Four stool samples collected at 4 weekly intervals yielded iVDPV type 1. The child's father, an asymptomatic 32-year-old male, was also found to be excreting iVDPV. A haploidentical hematopoietic stem cell transplant was performed, but the child succumbed due to severe myocarditis and pneumonia three weeks later. We report a rare case of transmission of iVDPV from an individual with IEI to a healthy household contact, demonstrating the threat of the spread of iVDPV from persons with IEI and the necessity to develop effective antivirals.
ABSTRACT
An outbreak of Hand Foot and Mouth Disease (HFMD) which occurred in August-September, 2022 in Navi Mumbai, India was prospectively investigated, to delineate the clinical manifestations and identify the etiological agent. Molecular characterization at ICMR-National Institute of Virology (NIV), Mumbai unit reported 69 (88.5%) cases out of 78 clinically diagnosed HFMD cases positive for enteroviruses. Thirty-nine (56.5%) children were positive for CVA6, 11 (15.9%) for CVA16, and one for CVA4 (1.4%). One case of co-infection (CVA16, CVA6) was reported. Fourteen (17.9%) cases had recurrent disease in the same season. CVA6 was associated with unusual extension of the rash beyond the conventional areas of hands, feet, and mouth, with involvement of body areas including face, axillae and trunk. Whole genome sequencing classified CVA6 as group D3 and CVA16 isolates as group B1c. Co-infection and recurrence of disease with atypical symptoms observed in this study highlight the need for continued vigilance of the evolutionary clinical characteristics of the enteroviruses causing HFMD.
ABSTRACT
The emergence of vaccine-derived polioviruses (VDPVs) in patients with Primary Immunodeficiency (PID) is a threat to the polio-eradication program. In a first of its kind pilot study for successful screening and identification of VDPV excretion among patients with PID in India, enteroviruses were assessed in stool specimens of 154 PID patients across India in a period of two years. A total of 21.42% of patients were tested positive for enteroviruses, 2.59% tested positive for polioviruses (PV), whereas 18.83% of patients were positive for non-polio enteroviruses (NPEV). A male child of 3 years and 6 months of age diagnosed with Hyper IgM syndrome was detected positive for type1 VDPV (iVDPV1) with 1.6% nucleotide divergence from the parent Sabin strain. E21 (19.4%), E14 (9%), E11 (9%), E16 (7.5%), and CVA2 (7.5%) were the five most frequently observed NPEV types in PID patients. Patients with combined immunodeficiency were at a higher risk for enterovirus infection as compared to antibody deficiency. The high susceptibility of PID patients to enterovirus infection emphasizes the need for enhanced surveillance of these patients until the use of OPV is stopped. The expansion of PID surveillance and integration with a national program will facilitate early detection and follow-up of iVDPV excretion to mitigate the risk for iVDPV spread.
ABSTRACT
Individuals with primary immunodeficiencies who are infected with vaccine-derived polioviruses may continue to shed poliovirus for months and go undetected by surveillance programmes of acute flaccid paralysis. These patients therefore pose a risk of initiating poliovirus outbreaks that jeopardize efforts towards global polio eradication. To identify these individuals, we designed a study protocol for the establishment of a network for surveillance of immunodeficiency-related vaccine-derived poliovirus in India. In the first step we identified recognized centres in India that could diagnose and enrol patients with primary immunodeficiency disorder into the study. Stool sample collection from study sites, culture, isolation, characterization of enteroviruses and reporting to study sites was carried out at the National Institute of Virology Mumbai Unit, as per the WHO national polio surveillance project protocol. In the first phase of the study from January 2020 to December 2021, we implemented the protocol at seven study sites at different medical institutes to determine the proportion of poliovirus infections in primary immunodeficiency disorder patients of India. We later expanded the study by including an additional 14 medical institutes across the country in the second phase running from January 2022 to December 2023. We believe this study protocol will help other countries to initiate immunodeficiency-related vaccine-derived poliovirus surveillance to identify and follow up patients who are long-term excretors of vaccine-derived poliovirus. Integration of immunodeficiency-related poliovirus surveillance with acute flaccid paralysis surveillance of the existing poliovirus network will enhance continuous screening of patients with primary immunodeficiency disorder in the future.
Certains individus qui présentent des immunodéficiences primaires et sont infectés par des poliovirus dérivés d'une souche vaccinale pourraient continuer à excréter le poliovirus pendant des mois sans que ce dernier ne soit détecté par le biais d'une surveillance de la paralysie flasque aiguë. Ces patients risquent donc de déclencher des épidémies de poliovirus qui mettent en péril les efforts visant à éradiquer la poliomyélite dans le monde. En vue d'identifier ces individus, nous avons élaboré un protocole d'étude pour établir, en Inde, un réseau de surveillance du poliovirus d'origine vaccinale lié à une immunodéficience. Au cours de la première étape, nous avons repéré des centres reconnus dans le pays, capables de diagnostiquer des patients atteints d'un syndrome d'immunodéficience primaire et de les recruter dans le cadre de l'étude. Le prélèvement des échantillons de selles auprès des sites participant à l'étude, la culture, l'isolement, la caractérisation des entérovirus et la communication des résultats à ces sites ont été pris en charge par le National Institute of Virology Mumbai Unit, conformément au protocole du Projet national de surveillance de la poliomyélite de l'OMS. Nous avons consacré la première phase de l'étude, qui s'est déroulée entre janvier 2020 et décembre 2021, à la mise en Åuvre du protocole au sein de différents établissements médicaux sur sept sites participants, afin de déterminer le nombre d'infections au poliovirus chez les patients souffrant d'un syndrome d'immunodéficience primaire en Inde. Nous avons ensuite, durant la deuxième phase comprise entre janvier 2022 et décembre 2023, élargi l'étude en incluant 14 établissements supplémentaires à travers le pays. Nous sommes convaincus que ce protocole d'étude aidera d'autres pays à instaurer une surveillance du poliovirus dérivé d'une souche vaccinale et lié à une immunodéficience, qui leur servira à identifier et suivre les patients responsables d'une excrétion prolongée du poliovirus d'origine vaccinale. L'intégration, au sein du réseau existant dédié au poliovirus, d'une surveillance de ce type couplée à une surveillance de la paralysie flasque aiguë améliorera le dépistage systématique des patients atteints d'un syndrome d'immunodéficience primaire à l'avenir.
Las personas con inmunodeficiencias primarias infectadas por los poliovirus de origen vacunal pueden seguir excretando poliovirus durante meses sin que la vigilancia de la parálisis flácida aguda los detecte. Por lo tanto, estos pacientes suponen un riesgo de iniciar brotes de poliovirus que pongan en peligro los esfuerzos hacia la erradicación mundial de la poliomielitis. Para identificar a estas personas, diseñamos un protocolo de estudio para el establecimiento de una red de vigilancia de poliovirus de origen vacunal relacionados con inmunodeficiencias en la India. En el primer paso identificamos centros reconocidos en la India que pudieran diagnosticar e inscribir en el estudio a pacientes con trastorno de inmunodeficiencia primaria. La recogida de muestras de heces de los centros de estudio, el cultivo, el aislamiento, la caracterización de los enterovirus y la notificación a los centros de estudio se llevaron a cabo en el Instituto Nacional de Virología, Unidad de Mumbai, según el protocolo del Proyecto Nacional de Vigilancia de la Poliomielitis de la OMS. En la primera fase del estudio, de enero de 2020 a diciembre de 2021, aplicamos el protocolo en siete centros de estudio de diferentes institutos médicos para determinar la proporción de infecciones por poliovirus en pacientes con trastorno de inmunodeficiencia primaria de la India. A continuación, ampliamos el estudio con la inclusión de otros 14 institutos médicos de todo el país en la segunda fase, de enero de 2022 a diciembre de 2023. Creemos que este protocolo de estudio ayudará a otros países a iniciar la vigilancia de poliovirus de origen vacunal relacionados con la inmunodeficiencia para identificar y hacer un seguimiento de los pacientes que son excretores a largo plazo de poliovirus de origen vacunal. La integración de la vigilancia del poliovirus asociado a la inmunodeficiencia con la vigilancia de la parálisis flácida aguda de la red de poliovirus existente mejorará el cribado continuo de pacientes con trastorno por inmunodeficiencia primaria en el futuro.