Poliovirus surveillance in patients with primary immunodeficiencies, India.

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 œuvre 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.

Autoimmune acute liver failure and seronegative autoimmune liver disease in children: Are they different from classical disease?

OBJECTIVES: Presentation as autoimmune acute liver failure (AI-ALF) and seronegative autoimmune liver disease (SN-AILD) represents two uncommon variants of AILD. We compared the clinical profile and outcome of AI-ALF with autoimmune-non-acute liver failure (AI-non-ALF) and also SN-AILD with seropositive autoimmune liver disease (SP-AILD). MATERIALS AND METHODS: Children managed as AI-ALF and AI-non-ALF including SN-AILD and SP-AILD were enrolled and compared. AI-non-ALF was diagnosed by simplified diagnostic criteria and AI-ALF by Pediatric Acute Liver Failure Study Group criteria with positive autoantibody, exclusion of other etiologies, elevated immunoglobulin G and histology when available. RESULTS: Seventy children [AI-ALF=15 and AI-non-ALF=55 (SN-AILD=11, SP-AILD=44)] were evaluated. Age at presentation [7 (1.2-16) vs. 9 (2-17) years] percentage of female patients (67 vs. 62%), and AILD type (type II, 53 vs. 31%) were similar in AI-ALF and AI-non-ALF patients], respectively. 8/15 AI-ALF cases were treated with steroids (improved-4, liver transplant-1, and death-3) and 7/15 died before initiation of therapy. Hepatic encephalopathy (100 vs. 16.3%; P<0.001), massive hepatic necrosis (60 vs. 0%; P<0.001), and higher pediatric end-stage liver disease [n=53, 29.9 (13.1-56.9) vs. 9.8 (-10-28.7) P<0.001], model for end-stage liver disease [n=17, 38.5 (24-46) vs. 18 (6-24); P=0.005], and Child-Turcotte-Pugh [n=70, 13 (8-13) vs. 9 (5-13); P<0.001] scores were features of AI-ALF. Poorer response to immunosuppression (4/8 vs. 48/55; P=0.02) and higher mortality (11/15 vs. 4/55; P=0.0001) were seen in AI-ALF than in AI-non-ALF patients. Clinicolaboratory profile, therapeutic response, and outcome were similar in SN-AILD and SP-AILD. CONCLUSION: AI-ALF is characterized by poorer liver function, lower response to immunosuppression, and higher mortality compared with SP or SN AI-non-ALF, which are similar.

Budd-Chiari syndrome in children: clinical features, percutaneous radiological intervention, and outcome.

OBJECTIVES: 'Radiological intervention' to restore venous patency is the preferred therapy in adults with Budd-Chiari syndrome (BCS). The published literature on pediatric BCS is scarce. This study evaluated the clinical profile and role of a therapeutic radiological intervention in children with BCS. PATIENTS AND METHODS: Forty-six BCS children [29 boys, median age 10.5 (2-16) years] were enrolled. Standard medical therapy was administered to all. A radiological intervention, angioplasty [hepatic vein (HV) (n=3)], stenting [HV (n=18), inferior vena cava (IVC) (n=5)], transjugular intrahepatic portosystemic shunt (TIPS) (n=3), was performed in 25 cases. Clinical, biochemical, and radiological follow-up was carried out. RESULTS: Doppler ultrasonography was diagnostic in 95% of cases. All patients had chronic BCS, with ascites in 82.6%, hepatomegaly in 84.8%, splenomegaly in 69.6%, prominent abdominal veins in 69.6%, and variceal bleed in 34.8% cases. The most common site of block was HV (n=33), followed by combined HV and IVC block (n=11), and isolated IVC block (n=2). Eight of 12 (75%) cases had abnormal procoagulant workup. Radiological intervention was technically successful in 100%. Clinical and biochemical improvement was observed in the intervention group. Complications included neck hematoma and hemorrhagic ascites in one patient each. One child in the intervention group (post-TIPS sudden cardiac event) and two children in the nonintervention group [end-stage liver disease (n=1), head injury (n=1)] died. Stent was patent in 15/20 (75%) children over a median follow-up of 6.5 months. CONCLUSION: HV block and a chronic presentation are most common in BCS children. Doppler ultrasonography establishes the diagnosis in 95% of cases. Radiological intervention is an effective and safe therapeutic modality for children with BCS.

Significance of histopathological features in differentiating autoimmune liver disease from nonautoimmune chronic liver disease in children.

OBJECTIVES: Autoimmune liver disease (AILD) requires a constellation of clinical, serological, biochemical, and histological findings for diagnosis. Liver biopsy forms the cornerstone for the definite diagnosis of AILD, despite histological features not being pathognomonic. Liver biopsies of AILD and nonautoimmune chronic liver disease (NACLD) were reviewed blindly to assess the role of typical histological findings in differentiating AILD from NACLD in a pediatric population. PARTICIPANTS AND METHODS: Twenty-five liver biopsies of AILD and 34 liver biopsies of NACLD were reviewed retrospectively without knowledge of the final diagnosis. RESULTS: The typical histology comprising all four features, interface hepatitis, portal lymphoplasmacytic infiltrate, rosette formation, and emperipolesis, was observed in 56% of AILD. Rosette formation and emperipolesis were associated significantly with the diagnosis of AILD. Rosette formation alone or in combination with emperipolesis or lymphoplasmacytic infiltrate had high specificity (96.2% each) but low sensitivity (68, 60, and 60%, respectively) for AILD. The diagnostic accuracy of typical histology comprising of a combination of at least three of four features, rosette formation, emperipolesis, and lymphoplasmacytic infiltrate, was 76.9%, with a positive predictive value of 93.3% and a negative predictive value of 70.2%. CONCLUSION: Characteristic patterns of liver injury comprising typical histological features on liver biopsy may strongly suggest the diagnosis of AILD irrespective of other laboratory parameters in children. Rosette formation was the only independent significant histological factor to predict AILD. High specificity and predictability of typical histological features may be helpful in diagnosing seronegative AILD among cases of cryptogenic liver disease in the absence of other supportive findings.

Shwachman-Diamond Syndrome: are we missing many?

Shwachman-Diamond Syndrome (SDS) is a rare inherited disorder characterized by pancreatic insufficiency, bone marrow dysfunction and skeletal abnormalities. It is the most common cause of pancreatic insufficiency in children after cystic fibrosis. We report a child with classical SDS who presented to us predominantly with chronic diarrhea along with delayed growth and neutropenia.

Intractable ascites as a manifestation of Wolman's disease: report of two sibs.

Wolman disease (WD) is a rare, inherited, rapidly fatal condition presenting in early infancy. The disease manifests in the first month of life with failure to thrive, vomiting, diarrhea, abdominal distension, hepatosplenomegaly and bilateral adrenal calcification and is nearly always fatal before the age of 1 year. Barring a case report of isolated fetal ascites, there is no report of intractable ascites as the presentation of WD till date. We report two siblings with WD who both had intractable ascites and required therapeutic paracentesis, albumin infusion, and diuretics to control tense ascites. Although rare, WD should be considered in the differential diagnosis of infantile ascites.