Infectious Disease Alert Updates
December 1, 2022
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By Carol A. Kemper, MD, FACP
Clinical Associate Professor of Medicine, Stanford University, Division of Infectious Diseases, Santa Clara Valley Medical Center
Animal Reservoirs for Human Infection
SOURCE: Madhusoodanan J. Animal reservoirs — Where the next SARS-CoV-2 variant could arise. JAMA 2022;328:696-698.
This insightful article explores the dilemmas posed by zoonotic reservoirs of infection and future risks for novel infection in humans. For example, horseshoe bats may have been the origin of the current SARS-CoV-2 pandemic, with likely transmission to humans through one or more intermediate hosts, such as raccoon dogs and pangolins (scaly anteaters), possibly in two or more separate events in 2019. This makes SARS-CoV-2 one of more than 900 zoonotic infections that have made the leap from animals to humans, an event that biologists refer to as “spill-over.” But transmission to humans is not just a one-way event. We are the source for animal infection in many instances, and the COVID-19 pandemic now has spread from humans back into previously uninfected animal species. As of this May, more than 30 countries around the globe have reported SARS-CoV-2 infections in 23 animal species, including white-tailed deer in Canada and the northeastern United States, domestic cats and dogs, mink, otters, anteaters, manatees, hamsters, hippopotamuses, etc. Human to animal transmission has been responsible for COVID-19 infections in zoo animals, resulting in the death of a tiger at the Columbus, OH, zoo in June 2022.
Infection in secondary populations often is a one-off, unable to sustain transmission in a novel host, but occasionally can establish a new reservoir of infection, allowing the virus to propagate more or less “silently” for long periods of time. As viruses adapt and evolve in their new animal host, they theoretically could serve as a breeding ground for infections with more lethal mutations to humans (as likely occurred with distemper virus and rubeola hundreds of years ago).
For example, an increased mutation rate was observed in SARS-CoV-2 virus when it appeared in the mink population. Another study identified 14 different strains of virus in domestic cats and dogs, including six new mutations in spike protein. Tremendous diversity has been identified in SARS-CoV-2 virus in the white-tailed deer population in Ontario and the United States. While sampling in white-tailed deer is largely opportunistic (i.e., roadkill and hunting specimens), infection in this deer species was documented early on in the human pandemic (as early as January through March 2020), and by 2021 was observed in 40% of specimens in four U.S. states. A broad survey of 17 wildlife species in Ontario in 2021 found SARS-CoV-2 in wood rats, skunks, white-tailed deer, and deer mice, but house mice, rabbits, and raccoons appeared to be unaffected.
It is hoped that as viruses adapt to better infect and replicate in their new nonhuman host, they become less infectious to humans. For example, experiments involving MERS-CoV in bats demonstrated that multiple passages of virus in bats improved their potential for bat-to-bat transmission (with improved binding to bat host receptors) but presumably diminished their affinity for human receptors.
In March 2022, the World Health Organization and the United Nations’ Food and Agriculture Organization called for efforts to reduce transmission of SARS-CoV-2 between humans and animals. But since we really have no idea how transmission occurs for many animal species, it is not clear how this goal can be achieved. Transmission from humans to zoo animals and domestic cats and dogs may be more obvious, but how human infection spread so quickly and extensively to the white-tailed deer population is impressively mysterious. Possible modes of transmission include airborne, wastewater, and fomites, with virions in wastewater being an obvious concern for wildlife reservoirs.
Clearly there needs to be better surveillance of animal populations for new and emerging diseases that could affect humans. Which animals to survey and how to gain access to them is part of the dilemma, let alone what to watch out for. Increasing surveillance of wastewater, especially in countries bordering wilderness populations, may be helpful. As population density increases in critical areas of Africa and Asia, pandemics may emerge quickly and involve large numbers of people. Further, global warming may propel certain populations to newer, cooler locations, altering their “ecology” and bringing them closer to forested areas and new animal populations.
Novel Rat-Derived HEV Infection in Humans
SOURCE: Sridhar S, Yip CCY, Lo KHY, et al. Hepatitis E virus species C infection in humans, Hong Kong. Clin Infect Dis 2022;75:288-296.
Hepatitis E virus is a diverse group of viruses divided between two genera: Orthohepevirus and Piscihepevirus. Within the Orthohepevirus genera, four species, A-D, have been identified. Previous to 2017-2019, only HEV-A was believed to infect humans. HEV-A genotypes 1 and 2 were found in human infections, while genotypes 3 and 4 were more commonly found in swine and generally infected humans who ingested undercooked pork. But in 2017-2019, human infection from HEV-C1 was identified in residents of Hong Kong. HEV-C1 is a divergent variant of HEV-C and is commonly found in ordinary street rats throughout the world — and as such is probably much more common than previously recognized.
Prompted by this discovery, the Public Health Laboratory Services Branch (PHLSB) in Hong Kong began systematically testing available blood and stool specimens for HEV-C infection by reverse-transcriptase polymerase chain reaction (RT-PCR). From August 2019 to December 2020, an additional eight cases of HEV-C1 infection were identified, raising the total number of HEV-C1 cases in the city to 16, including the earlier cases. These additional eight cases were identified three different ways: the main hospital facility in Hong Kong received 229 requests for HEV testing, and five (2.2%) tested positive for HEV by RT-PCR, including two HEV-A and three HEV-C1 cases; all potential organ donors were screened; and 139 individuals with + HEV IgM serology were referred to the PHLSB for testing, and 40 (28.8%) were positive for HEV-A and three (2.2%) were positive for HEV-C1. In addition, direct testing of various clinical samples yielded five additional cases, including two additional HEV-C1 cases.
These eight newly identified HEV-C1 strains were compared with earlier strains from 2017-2019. Four of the new cases (50%) occurred in severely immunocompromised (IC) individuals (including three transplant patients and a patient with CML). Two of four of these IC individuals tested negative for both HEV IgM and IgG, and the other two tested positive for one or the other antibody but not both. Seven of eight infections resulted in persistent infection, with documented viremia > 3 months duration. Although two patients died before they could be treated, three patients achieved sustained viral suppression with ribavirin, and one patient achieved sustained viral suppression with repeated courses of ribavirin.
Concerted surveillance was able to detect small numbers of novel HEV-C1 infection in residents of Hong Kong, making up ~2% of all HEV infections. Seven of eight strains were closely related, and phylogenetic analysis revealed these to be derived from rat strains of HEV-C1 infection. Since HEV-C1 infection appears to be ubiquitous in street rats throughout the world, it is likely that human infection with this zoonosis is under-recognized. Persistent HEV-C1 infection occurred in 87.5% of patients, three of whom were severely IC, and sustained infection did not resolve with a reduction in immunosuppression. Notably, humoral responses were weak or lacking in many of these patients.
Household Contamination with Monkeypox
SOURCE: Pfeiffer JA, Collingwood A, Rider LE, et al. High-contact object and surface contamination in a household of persons with monkeypox virus infection – Utah, June 2022. MMWR Morb Mortal Wkly Rep 2022;71:1092-1093.
To determine the degree of surface contamination of household objects in persons with monkeypox (MP) infection, investigators broadly sampled household items for MP deoxyribonucleic acid (DNA) by real-time polymerase chain reaction (PCR). Both qualitative PCRs for nonvariola Orthopoxvirus and specific West African monkeypox virus were performed. Cultures were performed if qualitative PCRs were positive.
Two people with MP infection lived in the household. Both patients had relatively mild infections with multiple small lesions in multiple locations, including the penis, lips, scalp, chest, legs, and feet. The lesions were described as “pimple-like.” The patients had developed prodromal symptoms about 22 and 30 days prior to sampling and had been isolated at home for 20 days. They had been given written instructions on personal hygiene and household cleaning and decontamination. During isolation, the patients showered one to two times a day, washed their hands ~10 times per day, laundered their linens weekly, and regularly mopped and wiped down surfaces throughout the household with a multipurpose spray (not specified).
Twenty-one of 30 specimens (70%) were positive by PCR, including all three porous surfaces sampled (including a blanket and cloth furniture). PCRs were also positive from 17 of 25 (68%) nonporous surfaces, including a table and handles. None of the cell cultures yielded viable virus for any of these positive specimens.
It is not surprising that molecular footprints of MP virus were found throughout this household — and it is conceivable that sampling earlier in the course of infection may have identified viable virus, or that simple household cleaning might have deactivated live virus. A similar 2021 study also found extensive MP DNA contamination (90%) of both porous and nonporous household surfaces about 15 days after a patient with MP had left a household.1 But in this study, viable MP virus was observed in 22% of the specimens, including 6/10 samples from porous surfaces (60%) and 1/21 samples (5%) from nonporous surfaces. However, live virus was present in such small amounts as to likely be noninfectious.
- Morgan CN, Whitehill F, Doty JB, et al. Environmental persistence of monkeypox virus on surfaces in household of person with travel-associated infection, Dallas, Texas, USA, 2021. Emerg Infect Dis 2022;28:1982-1989.
Animal Reservoirs for Human Infection; Novel Rat-Derived HEV Infection in Humans; Household Contamination with Monkeypox
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