High Susceptibility for Enterovirus Infection and Virus Excretion Features in Tunisian Patients with Primary Immunodeficiencies

Driss, Nadia; Ben‐Mustapha, Imen; Mellouli, Fethi; Yahia, Ahlem Ben; Touzi, Henda; Béjaoui, Mohamed; Ghorbel, Mohamed Ben; Triki, Henda; Barbouche, Mohamed‐Ridha

doi:10.1128/cvi.00293-12

Cited by 32 publications

(26 citation statements)

References 25 publications

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“…Based on several reports showing that not only patients with primary antibody deficiencies but also combined immunodeficiencies are very susceptible to persistent polio and non-polio enterovirus (NPEV) infections (4, 12), this multicenter study has been designed to determine the prevalence of iVDPV in patients with both types of immunodeficiencies and characterize the genetic properties of associated virus strains.…”

Section: Introductionmentioning

confidence: 99%

Patients with Primary Immunodeficiencies Are a Reservoir of Poliovirus and a Risk to Polio Eradication

Aghamohammadi¹,

Abolhassani²,

Kütükçüler³

et al. 2017

Front. Immunol.

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Immunodeficiency-associated vaccine-derived polioviruses (iVDPVs) have been isolated from primary immunodeficiency (PID) patients exposed to oral poliovirus vaccine (OPV). Patients may excrete poliovirus strains for months or years; the excreted viruses are frequently highly divergent from the parental OPV and have been shown to be as neurovirulent as wild virus. Thus, these patients represent a potential reservoir for transmission of neurovirulent polioviruses in the post-eradication era. In support of WHO recommendations to better estimate the prevalence of poliovirus excreters among PIDs and characterize genetic evolution of these strains, 635 patients including 570 with primary antibody deficiencies and 65 combined immunodeficiencies were studied from 13 OPV-using countries. Two stool samples were collected over 4 days, tested for enterovirus, and the poliovirus positive samples were sequenced. Thirteen patients (2%) excreted polioviruses, most for less than 2 months following identification of infection. Five (0.8%) were classified as iVDPVs (only in combined immunodeficiencies and mostly poliovirus serotype 2). Non-polio enteroviruses were detected in 30 patients (4.7%). Patients with combined immunodeficiencies had increased risk of delayed poliovirus clearance compared to primary antibody deficiencies. Usually, iVDPV was detected in subjects with combined immunodeficiencies in a short period of time after OPV exposure, most for less than 6 months. Surveillance for poliovirus excretion among PID patients should be reinforced until polio eradication is certified and the use of OPV is stopped. Survival rates among PID patients are improving in lower and middle income countries, and iVDPV excreters are identified more frequently. Antivirals or enhanced immunotherapies presently in development represent the only potential means to manage the treatment of prolonged excreters and the risk they present to the polio endgame.

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Section: Introductionmentioning

confidence: 99%

Patients with Primary Immunodeficiencies Are a Reservoir of Poliovirus and a Risk to Polio Eradication

Aghamohammadi¹,

Abolhassani²,

Kütükçüler³

et al. 2017

Front. Immunol.

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“…Regardless of the clinical presentation, enterovirus infection in patients with primary immunodeficiencies was frequently reported as chronic infection (4,8,10). In our case patient, the first virus detected was a Sabin-like poliovirus type 1; it was excreted during a period exceeding 4 months, from D1 to D134.…”

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confidence: 70%

“…This may suggest the possible role of this treatment in preventing severe forms of enterovirus infections, although it seems that this treatment does not protect against the infection itself. In fact, the very high susceptibility of our patient to enteroviral infections is remarkable, especially if we consider the relatively low endemicity of enterovirus infection in Tunisia; according to the national enterovirus surveillance data, regularly conducted since 1991, enterovirus shedding was found in only 4 to 5% of acute flaccid paralysis cases and their healthy contacts during the last decade (4,6). We have previously noted high susceptibility to enterovirus infections in a cohort of patients with various types of PIDs: 13.4% (11 of 82) of all patients and 20.7% (11 of 53) of those with humoral or combined immunodeficiency had enterovirus-positive specimens (4).…”

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confidence: 84%

Sequential Asymptomatic Enterovirus Infections in a Patient with Major Histocompatibility Complex Class II Primary Immunodeficiency

et al. 2014

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Patients with primary immunodeficiencies are usually susceptible to enterovirus infections and have higher risks to develop severe clinical forms. We report a unique description of a boy with major histocompatibility complex class II (MHC-II) deficiency infected by 9 different enterovirus serotypes during a 2-year period, with very mild clinical symptoms, probably due to the immunoglobulin therapy he was receiving. CASE REPORTT he case patient is the older child of Tunisian consanguineous healthy parents. He was born in 2002 with, apparently, no neonatal pathology. Breastfed for 20 months, he had a history of multiple episodes of upper respiratory infections and diarrhea with failure to thrive (Ϫ2 standard deviations in weight and size). At the age of 3 months, he developed a chronic diarrhea (6 to 7 stools per day) which required hospitalization. He was hospitalized again at 4 years of age for diarrhea and dehydration; the diagnoses of mucovicidosis and of celiac disease were ruled out based on negative sweat testing and the results of duodenal fibroscopy and biopsy, respectively. At 5 years of age, because of multiple respiratory infections, a computed tomography thoracic scan was performed and found a diffuse bronchiectasis. His vaccination history against poliomyelitis included four doses of trivalent oral poliovirus vaccine (OPV) administered at 3, 4, 5, and 18 months of age; he received another dose of OPV at 4 years of age during a subnational polio mass vaccination campaign. In December 2007, major histocompatibility (MHC) class II deficiency was diagnosed based on the defect of expression of MHC class II molecules on the surface of resting peripheral blood mononuclear cells, with confirmation by expression study on phytohemagglutinin-activated blast cells, as assessed by flow cytometry. A severe CD4 lymphopenia (6%) was found, along with abnormal immunoglobulin titers of 644 mg/dl for IgG (normal, 929 Ϯ 228 mg/dl), 74 mg/dl for IgA (normal, 56 Ϯ 18 mg/dl), and 132 mg/dl for IgM (normal, 93 Ϯ 27 mg/dl) (1). Subsequently, he was treated on a monthly basis with substitutive intravenous immunoglobulins and was regularly followed by the expert physicians and nurses of the Bone Marrow Transplantation Center in Tunisia, specialized in managing and providing care for these patients. Bone marrow transplantation could not be performed due to the unavailability of a compatible donor. The molecular analysis did not show the presence of the recurrent 752delG26/RFXANK gene mutation that is observed in most MHC class II-deficient Maghrebian patients (2). At each visit and prior to immunoglobulin transfusion, a blood sample was collected for residual immunoglobulin titration. A complete medical examination was performed; all clinical symptoms present at the day of the visit and those that occurred during the previous month were recorded and appropriate treatment prescriptions were provided.In , approximately 15 months of followup) were previously published in a paper summarizing the study results for the whole cohort (...

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“…Patients with primary immunodeficiency disorders (PIDs) have a high susceptibility to microbial infections, particularly to enteric viral infections [22-25]. Reports on HCoSV infection in PID patients are very scarce.…”

Section: Introductionmentioning

confidence: 99%

Iterative Excretion of Human Cosaviruses from Different Genotypes Associated with Combined Immunodeficiency Disorder

et al. 2018

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Background: Human cosaviruses (HCoSVs) are newly discovered enteric viruses in the Picornaviridae family. They have been described in non-polio acute flaccid paralysis, diarrheal patients, and healthy individuals. They remain rarely documented in immunodeficient patients. Objectives: This study reports iterative excretion of HCoSVs in a patient with major histocompatibility complex (MHC) class II combined immunodeficiency, a relatively common primary immunodeficiency in consanguineous settings. Methods: A total of 35 samples were collected from a patient followed for oral polio vaccine strains detection in stool samples during a 57-month period. Detection of HCoSVs in stools was performed by nested RT-PCR in the 5′ noncoding region. The genotype identification and screening for recombinant strains was performed by sequencing in the VP1 and 3D genomic regions followed by phylogenetic analysis. Results: The patient was infected with HCoSVs twice at a 3-year interval. The excreted viruses belonged to 2 different genotypes with 2 probable recombinant viruses. During HCoSV infections, the patient was also excreting Sabin-related polioviruses. Conclusions: This study describes excretion kinetics and genetic characteristics of HCoSVs in a patient with combined immunodeficiency due to MHC class II expression defect. The patient did not have concomitant symptoms related to the HCoSV infection.

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High Susceptibility for Enterovirus Infection and Virus Excretion Features in Tunisian Patients with Primary Immunodeficiencies

Cited by 32 publications

References 25 publications

Patients with Primary Immunodeficiencies Are a Reservoir of Poliovirus and a Risk to Polio Eradication

Patients with Primary Immunodeficiencies Are a Reservoir of Poliovirus and a Risk to Polio Eradication

Sequential Asymptomatic Enterovirus Infections in a Patient with Major Histocompatibility Complex Class II Primary Immunodeficiency

Iterative Excretion of Human Cosaviruses from Different Genotypes Associated with Combined Immunodeficiency Disorder

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