COVID-19 vaccination and breakthrough infections in patients with cancer.

BACKGROUND: Vaccination is an important preventive health measure to protect against symptomatic and severe COVID-19. Impaired immunity secondary to an underlying malignancy or recent receipt of antineoplastic systemic therapies can result in less robust antibody titers following vaccination and possible risk of breakthrough infection. As clinical trials evaluating COVID-19 vaccines largely excluded patients with a history of cancer and those on active immunosuppression (including chemotherapy), limited evidence is available to inform the clinical efficacy of COVID-19 vaccination across the spectrum of patients with cancer. PATIENTS AND METHODS: We describe the clinical features of patients with cancer who developed symptomatic COVID-19 following vaccination and compare weighted outcomes with those of contemporary unvaccinated patients, after adjustment for confounders, using data from the multi-institutional COVID-19 and Cancer Consortium (CCC19). RESULTS: Patients with cancer who develop COVID-19 following vaccination have substantial comorbidities and can present with severe and even lethal infection. Patients harboring hematologic malignancies are over-represented among vaccinated patients with cancer who develop symptomatic COVID-19. CONCLUSIONS: Vaccination against COVID-19 remains an essential strategy in protecting vulnerable populations, including patients with cancer. Patients with cancer who develop breakthrough infection despite full vaccination, however, remain at risk of severe outcomes. A multilayered public health mitigation approach that includes vaccination of close contacts, boosters, social distancing, and mask-wearing should be continued for the foreseeable future.

Public Health Implications of Changing Rodent Importation Patterns - United States, 1999-2013.

The United States imports a large volume of live wild and domestic animal species; these animals pose a demonstrated risk for introduction of zoonotic diseases. Rodents are imported for multiple purposes, including scientific research, zoo exhibits and the pet trade. Current U.S. public health regulatory restrictions specific to rodent importation pertain only to those of African origin. To understand the impacts of these regulations and the potential public health risks of international rodent trade to the United States, we evaluated live rodent import records during 1999-2013 by shipment volume and geographic origin, source (e.g. wild-caught versus captive- or commercially bred), intended purpose and rodent taxonomy. Live rodent imports increased from 2737 animals during 1999 to 173 761 animals during 2013. Increases in both the number and size of shipments contributed to this trend. The proportion of wild-captured imports declined from 75% during 1999 to <1% during 2013. Nearly all shipments during these years were imported for commercial purposes. Imports from Europe and other countries in North America experienced notable increases in volume. Gerbils and hamsters arriving from Europe and chinchillas, guinea pigs and hamsters arriving from other countries in North America were predominant taxa underlying this trend. After 2003, African-origin imports became sporadic events under the federal permit process. These patterns suggest development of large-scale captive rodent breeding markets abroad for commercial sale in the United States. While the shift from wild-captured imports alleviates many conservation concerns and risks for novel disease emergence, such consolidated sourcing might elevate exposure risks for zoonotic diseases associated with high-density rodent breeding (e.g. lymphocytic choriomeningitis or salmonellosis). A responsive border health system must periodically re-evaluate importation regulations in conjunction with key stakeholders to ensure a balance between the economic benefits of rodent trade against the potential public health risks.

Oncolytic adenoviruses: A thorny path to glioma cure.

Glioblastoma Multiforme (GBM) is a rapidly progressing brain tumor. Despite the relatively low percentage of cancer patients with glioma diagnoses, recent statistics indicate that the number of glioma patients may have increased over the past decade. Current therapeutic options for glioma patients include tumor resection, chemotherapy, and concomitant radiation therapy with an average survival of approximately 16 months. The rapid progression of gliomas has spurred the development of novel treatment options, such as cancer gene therapy and oncolytic virotherapy. Preclinical testing of oncolytic adenoviruses using glioma models revealed both positive and negative sides of the virotherapy approach. Here we present a detailed overview of the glioma virotherapy field and discuss auxiliary therapeutic strategies with the potential for augmenting clinical efficacy of GBM virotherapy treatment.

Subacute measles encephalitis in an immunocompetent adult.

Subacute sclerosing panencephalitis (SSPE) and subacute measles encephalitis (SME) are both rare complications of measles virus infection. SSPE typically affects immunocompetent children, has an insidious onset and follows a steadily progressive course. SME mainly occurs in immunosuppressed children and has a rapidly progressive course. We describe a 43 year old immunocompetent man who presented with a rapidly progressive fatal encephalopathy. Histological examination of the brain showed a meningoencephalitis with inclusion bodies. Complement fixing antibody to measles virus was present in his serum and CSF. Measles virus RNA was found in the brain, spinal cord and eye, but not in the CSF. Analysis of the nucleoprotein gene isolated from this patient did not show similarity to SSPE strains of the measles virus. This patient demonstrates that subacute encephalitis secondary to measles virus infection can develop in an immunocompetent adult host.

Detection and characterisation of swine hepatitis E virus in New Zealand.

The objectives of the present study were to establish the presence of hepatitis E virus (HEV) in New Zealand pigs, first by testing for HEV antibody in pig herds throughout New Zealand to measure the herd prevalence, then by attempting to amplify HEV genomic sequences by PCR. Antibody was measured by two independently designed ELISA serology tests. HEV RNA fragments were amplified by RT-PCR of nucleic acid extracted from faeces of 10-12-week-old piglets using primers targeting ORF1, ORF2, and ORF2/3. PCR products were subject to phylogenetic analysis. Antibody to HEV was found throughout New Zealand pig herds as well as in the different age groups within the herds. Twenty herds from 22 tested were positive for HEV antibody (91% herd prevalence). Phylogenetic analysis of the amplified sequences placed this New Zealand strain of HEV closest to the human European strain It-1 (AF 110390) and U.S. swine strain (AF 082843) with 88% and 83% similarity respectively in ORF1. It was concluded that HEV is widely distributed in the New Zealand pig population. Phylogenetic analysis shows that this is a new HEV strain, grouping most closely with the United States/European cluster, which includes HEV strains of both human and swine origin.

Prevalence and phylogenetic characterisation of TT-virus in the blood donor population of Auckland, New Zealand.

TT-virus (TTV, patient initials: T.T.), a novel DNA virus, was first isolated in Japan in 1997 from serum of a patient with post-transfusion hepatitis of unknown aetiology. To date, the contribution of TTV to liver disease remains doubtful. The potential for transmission via blood and blood products makes it essential to establish the prevalence of TTV viraemia in the blood donor population. 413 blood donor serum samples were chosen randomly, the DNA was extracted and TTV-specific DNA amplified by nested polymerase chain reaction (PCR). TTV infection was present in 13 out of 413 (3.15%) blood donors in the Auckland region of New Zealand using a set of primers targeting open reading frame (ORF) 1. These 13 amplification products (264 bp) were sequenced and TTV genotypes determined. Alignment with published TTV sequences showed that seven (53.8%) of the thirteen positive serum samples belonged to genotype 1, five (38.5%) belonged to genotype 2 and one (7.7%) could not be classified as either genotype 1 or 2. One hundred twenty-seven blood donor serum samples were retested with a second set of primers targeting the 5' region of the TTV genome in a single round PCR. Forty-three samples were positive for TTV DNA with these primers resulting in a prevalence of 37%. The data demonstrate that TTV is present among New Zealand blood donors and support the need for further investigation into the natural history of TTV infection.

No evidence of infection with porcine endogenous retrovirus in recipients of encapsulated porcine islet xenografts.

Transplantation of pig tissues into humans has the potential for cotransferring pig infections. Knowledge of the epidemiology of pig infections transmissible to humans allows the development of risk limitation strategies at the source herd level, but potentially infectious pig endogenous retrovirus (PERV) is ubiquitous in all domestic pigs and therefore is not avoidable. Using a specific and sensitive RT-PCR and nested PCR for PERV nucleic acids with primers, the screening of pigs from New Zealand herds for the presence and expression of the PERV was conducted. The presence of PERV proviral DNA (pol and env region) and viral RNA was demonstrated in all tested pig tissues including pancreas, liver, spleen, brain, heart, and PBMC. Using the same assays it was established that different tissues (liver, spleen, and heart) of nude and nonobese diabetic (NOD) mice previously transplanted with nonencapsulated pig islets were PERV DNA and RNA negative. Alginate polylysine capsules prepared with encapsulated pig islets were tested for possible leakage of viral particles or viral nucleic acids. RNA was extracted from the supernatant of viable encapsulated pig islet cells grown in culture for 2 months. No evidence of PERV RNA or of cellular nucleic acids could be found. Two adult type I diabetic subjects were transplanted with 1 x 10(6) neonatal pig islets encased in alginate capsules into the peritoneal cavity. One patient was immunosuppressed. Both showed evidence of graft function (up to 34% reduction in insulin dose, corresponding increase in serum pig C-peptide) for up to 2 years. DNA and RNA were extracted from PBMC and blood plasma of both patients at 19 months posttransplant. No evidence of PERV proviral DNA or RNA could be detected. Piglet islets contain PERV DNA and RNA, but this does not traverse the capsules used or produce any evidence of infection in nude and nonobese diabetic (NOD) mice or humans.

Evaluation of alpha interferon for the treatment of chronic hepatitis B infection in Christchurch.

AIM: To evaluate alpha interferon for the treatment of chronic replicative hepatitis B infection in Christchurch patients. METHODS: Ten patients were divided into two groups depending upon whether their average pretreatment ALT levels were greater than twice the upper limit of normal (group 1, 6 subjects) or less than twice the upper limit of normal (group 2, 4 subjects). Interferon alpha-2a (4.5 mega units) was administered three times a week for 24 weeks with the addition of a preceding priming course of prednisone in group 2. RESULTS: At 6 months post treatment only one patient in group 1 had seroconverted (HBeAg to anti-HBe), however, the remaining five patients seroconverted from 18-32 months after therapy. This response was associated with normalisation of the transaminases and in 5/6 subjects a fall in the HBV DNA levels. In group 2 one subject seroconverted by 6 months despite a shortened course of Interferon. A delayed seroconversion (18 months) was observed in one patient and another had a partial response with the development of anti-HBe but associated with persistence of HBeAg. The remaining patient has not responded. CONCLUSIONS: Interferon alpha-2a was effective in promoting a seroconversion HBeAg to anti-HBe in patients with chronic hepatitis B and transaminases elevated to twice the upper limit of normal, although in most cases this response was delayed. Larger studies will be required to determine the role of steroid priming in those with less active disease.

Specific sequence amplification of bovine viral diarrhoea virus nucleic acid.

Bovine viral diarrhoea virus (BVDV) causes infection of cattle worldwide and is a common contaminant of cell cultures in the laboratory. Methods of diagnosis for BVDV are time-consuming and inconsistent. We describe the development of an in vitro test based on enzymatic DNA amplification with Thermus aquaticus DNA polymerase of sequences of BVDV cDNA reverse transcribed from viral RNA. Specific sequences were amplified from infected cell cultures and clinical material using laboratory and field strains of BVDV including both cytopathic and non-cytopathic isolates. Both plus and minus strands of viral RNA can act as suitable templates for cDNA synthesis prior to sequence amplification. Internal restriction digest of amplified sequences and the co-amplification of multiple sequences increased the specificity of the reaction. The significance of the technique in relation to the diagnosis and understanding of strain differences is also discussed.

The gastric bubble: roentgen observations.

The appearance of the stomach bubble provides many clues to underlying thoracoabdominal disorders. Illustrated in this article are (1) the major complications of large hiatal hernias: intrathoracic gastric volvulus and ulceration; (2) diaphragmatic abnormalities including inversion of the hemidiaphragm and intrathoracic displacement of abdominal contents because of diaphragmatic laceration or congenital herniation; (3) extrinsic displacement of the stomach bubble by splenomegaly (the occurrence of which in association with radiographic abnormalities in the chest--cardiomegaly, interstitial lung disease, mediastinal or hilar adenopathy--helps form a differential diagnosis); and (4) situs abnormalities for the analysis of which a simplified schema is presented.

Chest-wall collapse as a complication of atelectasis.

A case of chest-wall collapse following atelectasis of the lung is reported. The presumed mechanism is abnormal compliance of the chest wall.

Upper lobe lung disease: physiologic correlates. Review.

Preferential localization of pathologic conditions in the upper lobes of the lung might seem unexpected, considering that both blood flow and ventilation predominate in the lower lobes. The erect lung is marked by striking regional non-uniformity in perfusion, ventilation, lymphatic flow, metabolism, and mechanics. These regional disparities form the foundation for a physiologic approach to the evaluation of diffuse lung disease. The pathologic-physiologic correlations in apical lung disease are examined, and a differential diagnosis is offered. Analysis of diffuse lung disease on the basis of radiologic-physiologic correlation is suggested as an aid in radiographic interpretation.