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.

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.

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.

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.

Rotavirus infection in New Zealand.

Rotavirus infection is commonly found in young infants admitted to hospital with gastroenteritis. An enzyme-linked immunosorbent assay (ELISA) for virus diagnosis is described and the results of testing stool specimens from 497 children with gastroenteritis, 192 neonates and 247 asymptomatic six month old infants are presented. Rotavirus infection was found in 45 percent of all children with gastroenteritis but only in 4.7 percent of neonates and 2 percent of asymptomatic infants. These results do not support the proposal that children in our community have a high incidence of subclinical infections.

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.

Rotavirus infection in Otago: a serological study.

A method for measuring rotavirus antibody in human sera has been established using enzyme-linked immunosorbent assay (ELISA). A Simian strain of rotavirus (SA11) was used as the antigen. Serum eluted from dried blood spots on good quality chromatography paper was found suitable for analysis. Paired serum samples from children with gastroenteritis have shown a brisk antibody response in association with the presence of rotavirus in the faeces. Community studies indicate that although all older children and adults tested have detectable antibodies to rotavirus, there is a significant rise in the number of individuals with high titre antibody in the child bearing age group, after which the levels diminish. This finding suggests that repeated infections occur throughout childhood and early adult life.

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.

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.

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.

Inflammatory fibroid polyp of the stomach in a child.

A large inflammatory fibroid polyp of the stomach with endo-exophylic growth is described in a 5-year-old. CT and UGI demonstrate the lesion.

The development and evaluation of an ELISA for the detection of antibodies to caprine arthritis-encephalitis virus in goat sera.

An enzyme-linked immunosorbent assay (ELISA) was developed for the detection of antibodies to caprine arthritis encephalitis virus (CAEV) in goat sera. The system was evaluated using some 1500 sera from flocks of known clinical history. From this data the interpretation limits of the system were determined. The ELISA system was compared with a gel precipitin test using 5800 sera. Of the positive sera, ELISA detected 97.3% and AGPT 61%. Further evaluation was made using 60 sera of known CAEV reactivity from the USA, and results agreed 100%. Indications are that antibody to the envelope glycoprotein gp135 is being detected. The ELISA system is more sensitive than the precipitin test and is presently being used in a CAEV flock accreditation scheme.

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.