Measuring antibody titres following rabies postexposure prophylaxis in immunosuppressed patients: a norm rather than the exception

We present a case of a 51-year-old immunosuppressed man with underlying chronic lymphoproliferative leukaemia (CLL), who presented to us in emergency with breathlessness, hydrophobia, anxiety and restlessness. He had a history of category 3 dog bite 2 months ago and had received a full course of rabies immunoglobulin and antirabies vaccine (ARV) as per the national schedule. As there were frank clinical reports of rabies, the patient was managed according to Milwaukee regimen. The patients died within a week of the appearance of symptoms. The brain autopsy revealed Negri bodies conforming the mortality due to rabies.Immunosuppressed patients, like our patient who had CLL have low antibody formation after rabies prophylaxis. Antibody titres in immunosuppressed patients need to be measured after the 2–4 weeks of the last injection of ARV to decide whether a booster of ARV needs to be administered or not.

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Acute Measles Encephalitis in Children With Immunosuppression

PEDIATRICS ◽

10.1542/peds.59.2.232 ◽

1977 ◽

Vol 59 (2) ◽

pp. 232-239

Author(s):

Jean Aicardi ◽

Francoise Goutieres ◽

Maria-Leonor Arsenio-Nunes ◽

Pierre Lebon

Keyword(s):

Measles Virus ◽

Subacute Sclerosing Panencephalitis ◽

Immunosuppressive Drugs ◽

Prominent Feature ◽

Epilepsia Partialis Continua ◽

Fatal Course ◽

Immunosuppressed Patients ◽

History Of ◽

The Central Nervous System ◽

The Brain

Four cases of encephalitis occurring in children treated for lymphatic malignancies by immunosuppressive drugs are reported. Measles virus was isolated from the brain in one case and identified immunologically in another. Nucleocapsids identical to those seen in subacute sclerosing panencephalitis were demonstrated in three cases. Severe immunosuppression was evidenced in two patients by failure of rosette formation and low phytohemagglutinin tests. Pathologically, the inflammatory reaction was absent in one brain and moderate in two. Clinically, epilepsia partialis continua was a prominent feature in three patients. A history of measles or of contact was elicited in three cases, five weeks to three months before onset. All cases ran an acute fatal course. Measles virus can behave as an opportunistic invader of the central nervous system in children and the diagnosis of measles encephalitis should be considered in immunosuppressed patients.

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THE HEXOSAMINE CONTENT OF THE ORBIT IN RELATION TO ANTI-THYROTROPHIN ANTIBODY TITRES IN SERA OF THYROTROPHIN-TREATED RABBITS WITH AND WITHOUT CORTISONE ADMINISTRATION

Acta Endocrinologica ◽

10.1530/acta.0.0410474 ◽

1962 ◽

Vol 41 (3) ◽

pp. 474-480 ◽

Cited By ~ 2

Author(s):

Otto Wegelius ◽

E. J. Jokinen

Keyword(s):

Connective Tissue ◽

Guinea Pigs ◽

Antibody Formation ◽

Direct Proof ◽

Significant Rise ◽

Extraocular Muscles ◽

Concomitant Treatment ◽

Antibody Titres ◽

Hexosamine Content ◽

Synergetic Action

ABSTRACT In all previous investigations on experimental exophthalmos, heterologous thyrotrophic pituitary extracts have been used. These protein hormones stimulate antihormone formation in the test animals. Cortisone has been reported to effectively block antibody formation. In addition, it has been shown to potentiate TSH-induced exophthalmos in guinea-pigs. With rabbits as test animals, the hexosamine content of the orbital tissues was determined and used as an index of exophthalmos development and at the same time the antibody titres in the sera were followed. TSH injections for six weeks led to a highly significant accumulation of hexosamine in the retrobulbar connective tissue and in the extraocular muscles, i. e. an increase of up to 400% as compared with the control animals. At the same time a significant rise in antihormonal titres was detectable in the sera. Concomitant treatment with cortisone brought about an equal or higher accumulation of hexosamine but significantly lower antibody titres. The known opposite peripheral actions of TSH and cortisone can be reconciled with the synergy in producing experimental exophthalmos by attributing the synergetic action of cortisone to the blocking of antihormone formation. If less antihormones are produced, the effect of TSH is enhanced. Our experiments do not provide direct proof for this hypothesis. High hexosamine values in the orbit and low antihormone titres in the serum are, however, concomitant phenomena.

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L2HGDH Missense Variant in a Cat with L-2-Hydroxyglutaric Aciduria

Genes ◽

10.3390/genes12050682 ◽

2021 ◽

Vol 12 (5) ◽

pp. 682

Author(s):

Matthias Christen ◽

Nils Janzen ◽

Anne Fraser ◽

Adrian C. Sewell ◽

Vidhya Jagannathan ◽

...

Keyword(s):

Current Knowledge ◽

Genetic Defect ◽

Clinical Signs ◽

Missense Variant ◽

Microcytic Anemia ◽

Abnormal Behavior ◽

Functional Candidate Gene ◽

History Of ◽

The Brain ◽

Hydroxyglutaric Acid

A 7-month-old, spayed female, domestic longhair cat with L-2-hydroxyglutaric aciduria (L-2-HGA) was investigated. The aim of this study was to investigate the clinical signs, metabolic changes and underlying genetic defect. The owner of the cat reported a 4-month history of multiple paroxysmal seizure-like episodes, characterized by running around the house, often in circles, with abnormal behavior, bumping into obstacles, salivating and often urinating. The episodes were followed by a period of disorientation and inappetence. Neurological examination revealed an absent bilateral menace response. Routine blood work revealed mild microcytic anemia but biochemistry, ammonia, lactate and pre- and post-prandial bile acids were unremarkable. MRI of the brain identified multifocal, bilaterally symmetrical and T2-weighted hyperintensities within the prosencephalon, mesencephalon and metencephalon, primarily affecting the grey matter. Urinary organic acids identified highly increased levels of L-2-hydroxyglutaric acid. The cat was treated with the anticonvulsants levetiracetam and phenobarbitone and has been seizure-free for 16 months. We sequenced the genome of the affected cat and compared the data to 48 control genomes. L2HGDH, coding for L-2-hydroxyglutarate dehydrogenase, was investigated as the top functional candidate gene. This search revealed a single private protein-changing variant in the affected cat. The identified homozygous variant, XM_023255678.1:c.1301A>G, is predicted to result in an amino acid change in the L2HGDH protein, XP_023111446.1:p.His434Arg. The available clinical and biochemical data together with current knowledge about L2HGDH variants and their functional impact in humans and dogs allow us to classify the p.His434Arg variant as a causative variant for the observed neurological signs in this cat.

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Cancer immunotherapy in special challenging populations: recommendations of the Advisory Committee of Spanish Melanoma Group (GEM)

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-001664 ◽

2021 ◽

Vol 9 (3) ◽

pp. e001664

Author(s):

Maria Gonzalez-Cao ◽

Teresa Puertolas ◽

Mar Riveiro ◽

Eva Muñoz-Couselo ◽

Carolina Ortiz ◽

...

Keyword(s):

Cancer Immunotherapy ◽

Multidisciplinary Approach ◽

Checkpoint Inhibitors ◽

Solid Organ Transplantation ◽

Latent Tuberculosis ◽

Solid Organ ◽

Chronic Infections ◽

Immunosuppressed Patients ◽

History Of ◽

Evidence Based Guidelines

Cancer immunotherapy based on the use of antibodies targeting the so-called checkpoint inhibitors, such as programmed cell death-1 receptor, its ligand, or CTLA-4, has shown durable clinical benefit and survival improvement in melanoma and other tumors. However, there are some special situations that could be a challenge for clinical management. Persons with chronic infections, such as HIV-1 or viral hepatitis, latent tuberculosis, or a history of solid organ transplantation, could be candidates for cancer immunotherapy, but their management requires a multidisciplinary approach. The Spanish Melanoma Group (GEM) panel in collaboration with experts in virology and immunology from different centers in Spain reviewed the literature and developed evidence-based guidelines for cancer immunotherapy management in patients with chronic infections and immunosuppression. These are the first clinical guidelines for cancer immunotherapy treatment in special challenging populations. Cancer immunotherapy in chronically infected or immunosuppressed patients is feasible but needs a multidisciplinary approach in order to decrease the risk of complications related to the coexistent comorbidities.

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Molecular evolutionary analysis of human primary microcephaly genes

BMC Ecology and Evolution ◽

10.1186/s12862-021-01801-0 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Nashaiman Pervaiz ◽

Hongen Kang ◽

Yiming Bao ◽

Amir Ali Abbasi

Keyword(s):

Evolutionary History ◽

Genetic Basis ◽

Brain Size ◽

Primate Species ◽

Evolutionary Analysis ◽

Australopithecus Afarensis ◽

Primary Microcephaly ◽

Modern Humans ◽

History Of ◽

The Brain

Abstract Background There has been a rapid increase in the brain size relative to body size during mammalian evolutionary history. In particular, the enlarged and globular brain is the most distinctive anatomical feature of modern humans that set us apart from other extinct and extant primate species. Genetic basis of large brain size in modern humans has largely remained enigmatic. Genes associated with the pathological reduction of brain size (primary microcephaly-MCPH) have the characteristics and functions to be considered ideal candidates to unravel the genetic basis of evolutionary enlargement of human brain size. For instance, the brain size of microcephaly patients is similar to the brain size of Pan troglodyte and the very early hominids like the Sahelanthropus tchadensis and Australopithecus afarensis. Results The present study investigates the molecular evolutionary history of subset of autosomal recessive primary microcephaly (MCPH) genes; CEP135, ZNF335, PHC1, SASS6, CDK6, MFSD2A, CIT, and KIF14 across 48 mammalian species. Codon based substitutions site analysis indicated that ZNF335, SASS6, CIT, and KIF14 have experienced positive selection in eutherian evolutionary history. Estimation of divergent selection pressure revealed that almost all of the MCPH genes analyzed in the present study have maintained their functions throughout the history of placental mammals. Contrary to our expectations, human-specific adoptive evolution was not detected for any of the MCPH genes analyzed in the present study. Conclusion Based on these data it can be inferred that protein-coding sequence of MCPH genes might not be the sole determinant of increase in relative brain size during primate evolutionary history.

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Streptococcus pluranimalium meningoencephalitis in a horse

Journal of Veterinary Diagnostic Investigation ◽

10.1177/10406387211023465 ◽

2021 ◽

pp. 104063872110234

Author(s):

Dah-Jiun Fu ◽

Akhilesh Ramachandran ◽

Craig Miller

Keyword(s):

Ribosomal Rna ◽

Cross Sections ◽

Nucleotide Sequencing ◽

Formalin Fixed Paraffin ◽

Quarter Horse ◽

Formalin Fixed Paraffin Embedded ◽

History Of ◽

The Brain ◽

Gram Positive Cocci ◽

Formalin Fixed

A 3-y-old, female Quarter Horse with a history of acute neurologic signs was found dead and was submitted for postmortem examination. Areas of petechial and ecchymotic hemorrhage were present on cross-sections of the cerebrum, cerebellum, and brainstem. Histologic examination of the brain revealed severe, purulent meningoencephalitis and vasculitis with a myriad of intralesional gram-positive cocci. Streptococcus pluranimalium was identified from formalin-fixed, paraffin-embedded tissue obtained from sites with active lesions by PCR and nucleotide sequencing of bacterial 16S ribosomal RNA. S. pluranimalium should be considered as a cause of meningoencephalitis in a horse.

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A Rare Case of Spontaneous Arachnoid Cyst Rupture Presenting as Right Hemiplegia and Expressive Aphasia in a Pediatric Patient

Children ◽

10.3390/children8020078 ◽

2021 ◽

Vol 8 (2) ◽

pp. 78

Author(s):

Anne Bryden ◽

Natalie Majors ◽

Vinay Puri ◽

Thomas Moriarty

Keyword(s):

Cognitive Processing ◽

Arachnoid Cyst ◽

Memory Loss ◽

Acute Onset ◽

Word Finding ◽

Outpatient Visits ◽

The Family ◽

History Of ◽

Cyst Rupture ◽

The Brain

This study examines an 11-year-old boy with a known history of a large previously asymptomatic arachnoid cyst (AC) presenting with acute onset of right facial droop, hemiplegia, and expressive aphasia. Shortly after arrival to the emergency department, the patient exhibited complete resolution of right-sided hemiplegia but developed headache and had persistent word-finding difficulties. Prior to symptom onset while in class at school, there was an absence of reported jerking movements, headache, photophobia, fever, or trauma. At the time of neurology consultation, the physical exam showed mildly delayed cognitive processing but was otherwise unremarkable. The patient underwent MRI scanning of the brain, which revealed left convexity subdural hematohygroma and perirolandic cortex edema resulting from ruptured left frontoparietal AC. He was evaluated by neurosurgery and managed expectantly. He recovered uneventfully and was discharged two days after presentation remaining asymptomatic on subsequent outpatient visits. The family express concerns regarding increased anxiety and mild memory loss since hospitalization.

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Reactivation of BK Polyomavirus in Urine Cytology Is Not Associated with Urothelial Cell Carcinoma

Viruses ◽

10.3390/v12121412 ◽

2020 ◽

Vol 12 (12) ◽

pp. 1412

Author(s):

Faisal Klufah ◽

Ghalib Mobaraki ◽

Axel zur Hausen ◽

Iryna V. Samarska

Keyword(s):

Cell Carcinoma ◽

Urine Cytology ◽

Urothelial Cell ◽

The Other ◽

Urothelial Cell Carcinoma ◽

Tissue Samples ◽

Bk Polyomavirus ◽

Ffpe Tissues ◽

Immunosuppressed Patients ◽

History Of

BK polyomavirus (BKPyV) has been associated with some high-grade and special urothelial cell carcinoma (UCC) subtypes in immunosuppressed patients. Here, we evaluated the relationship of BKPyV-positive urine cytology specimens (UCS) with UCC. A large single-institution database was retrospectively searched for UCS positive for decoy cells, suggesting BKPyV infection. These were tested for the presence of BKPyV by PCR and immunohistochemistry (IHC) in urine sediments and formalin-fixed paraffin-embedded (FFPE) tissue samples of UCC. Decoy cells were reported in 30 patients out of the database with 22.867 UCS. Of these 30 patients, 16 (53.3%) had no history of UCC. Six patients out of these 16 had a history of transplantation, 4 had a history of severe chronic medical conditions, and 6 had no chronic disease. The other fourteen patients were diagnosed with either in situ or invasive UCC of the urinary bladder (14/30; 46.6%) prior to the detection of decoy cells in the urine. Nine of these UCC patients received intravesical treatment (BCG or mitomycin) after the first presentation with UCC. However, the clinical data on the treatment of the other five UCC patients was lacking. IHC identified BKPyV-positivity in the urine samples of non-UCC and UCC patients, while no BKPyV positivity was found in FFPE tissues of primary UCCs and metastases. In addition, BKPyV-PCR results revealed the presence of BKPyV DNA in the urine of the UCC cases, yet none in the UCC tissues itself. These data strongly indicate that BKPyV reactivation is not restricted to immunosuppression. It can be found in UCS of the immunocompetent patients and may be related to the intravesical BCG or mitomycin treatment of the UCC patients.

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