By Carol A. Kemper, MD, FACP
Clinical Associate Professor of Medicine, Stanford University, Division of Infectious Diseases, Santa Clara Valley Medical Center
Dr. Kemper reports no financial relationships relevant to this field of study.
Circulation of a Novel Vaccinia Virus in Brazilian Equids
SOURCE: Borges IA, Reynolds MG, McCollum AM, et al. Serological evidence of Orthopoxvirus circulation among equids, southeast Brazil. Front
The origin of vaccinia virus (VACV), used for vaccination against smallpox, has long been debated, although for years the virus has been recognized as not being specifically a cowpox virus of lore. Complicating matters, various smallpox vaccines were manufactured in different countries and remained in use for more than a century before the World Health Organization (WHO) standardized the vaccine in 1967 using four different strains of VACV. In a 2017 New England Journal of Medicine publication, which was reviewed in Infectious Disease Alert one year ago, researchers observed that a recently discovered sample of 1902 smallpox vaccine, manufactured by an American company in Philadelphia, most closely resembled natural horsepox virus and not cowpox virus.1 DNA extracted from that vaccine was submitted to whole genome amplification and compared with 65 other published genome Orthopoxvirus sequences. The 1902 VACV strain most closely resembled horsepox virus (99.7%), using different phylogenetic algorithms, although deletions found at each end of the vaccine strain were not observed in either natural cowpox or horsepox viruses but were similar to current vaccinia strains.
Formerly, Orthopox viruses were classified on the basis of morphology and the affected animal species. The genus includes vaccinia, variola, cowpox, horsepox, buffalopox, camelpox, catpox, elephantpox, rabbitpox, monkeypox, alastrim, and ectromelia (mousepox), and has been delineated by genomics. In reality, these viruses may cross-infect different animal species, with varying disease severity, and all of these strains are genetically similar. Horsepox virus reportedly no longer exists in nature, although scientists in the United States published the sequence of horsepox virus in 2006, derived from a wild strain recovered 40 years earlier from horses in Mongolia.
Following the WHO’s campaign to eradicate smallpox (1966-1980), VACV emerged as a zoonosis in India, Pakistan, and Brazil, mostly in dairy cattle. Outbreaks of VACV were reported in 1999 in Brazil, affecting both dairy cattle and the humans who milked them. Since then, it has become largely an occupational disease of milkers, and is referred to as “bovine vaccinia.” Subsequently, an outbreak of vaccinia occurred in a horse-breeding facility in 2008 — and further outbreaks were reported in equids in Brazil in 2011 and 2014. However, none of these outbreaks in equids seemed to affect humans.
Borges and colleagues performed a serologic survey of 621 equids in Brazil, including 478 randomly selected horse samples collected and banked for various purposes since 2003, 74 sera from the outbreak in 2011, and 69 other randomly selected serologic equid samples. Remarkably, 128 (20.6%) of the samples were seropositive for antibody to “Orthopoxvirus” by either ELISA or PRNT. According to the owners, none of these horses had shown clinical evidence of vaccinia. Samples collected as early as 2003-2004 were positive — even before the recognized outbreak in 2008. Seropositivity varied by region (from 4.8% to 29.4%), and clustering in certain farms and areas was evident.
Since no Orthopoxvirus other than VACV has been found in circulation in Brazil, the authors presumed their serologic data was evidence of long-standing circulation of VACV in horses and donkeys in their country. In more recent years, equid cases of vaccinia have been reported in the neighboring South American countries Uruguay, Argentina, and Columbia. However, this virus has not yet been sequenced, and it remains a mystery why this strain of “vaccinia pox” has not caused clinical disease in humans. This low-level virus, whatever it is, in fact may be unrelated to the WHO smallpox campaign in 1966-1980. Since many countries used horses for replication of VACV for human use for decades, it is conceivable equids have evolved their own strain of vaccinia pox, derived from one of those original horse-derived vaccine strains.
- Schrick L, Tausch SH, Dabrowski PW, et al. An early American smallpox vaccine based on horsepox. N Engl J Med 2017;377:1491-1492.
Chopin’s Brandied Heart
SOURCE: Witt M, Szklener A, Marchwica W, Dobosz. Disease not genetic but infectious: Multiple tuberculomas and fibrinous pericarditis as symptoms pathognomonic for tuberculosis of Frederic Chopin. J Appl Genet 2018;59:471-473.
It is a macabre tale: Many believe that Frederic Chopin, the great Polish pianist and composer, died from progressive tuberculosis in Paris in 1849. However, the exact cause of his death is not known. He had been exiled from his beloved home country for years, and, on his deathbed, he allegedly whispered to his sister, Ludwika, that he wished for his heart to rest in Poland. And so, while his body was buried in France, she smuggled his heart in a glass jar, past border guards, to her home in Warsaw. The heart ostensibly was preserved in cognac or brandy, since that was the only alcohol of sufficient strength at the time. The heart then passed through the hands of various relatives before it was enshrined in a pillar at Holy Cross Church in Warsaw. It briefly fell into the hands of Nazis during World War II, but then was returned to Holy Cross Church on Oct. 17, 1945, on the 96th anniversary of Chopin’s death. For years, relatives consistently declined requests to analyze the jar’s contents.
However, in April 2014, the family allowed access to the specimen — only because of concerns about the amount of liquid preservative remaining in the jar. In the dark of night, completely in secret, the heart was removed from its hiding place for inspection. Only 13 individuals were present, including one forensic scientist and the Archbishop, who stood by, praying. Only nondestructive specimens were going to be allowed, such as samples of the liquid for genetics. The heart appeared to be in excellent condition, floating within an amber liquid — and remained fully submerged. So, in the end, only a superficial inspection and about 1,000 photos were allowed before the jar was sealed with beeswax and replaced within its crypt. The secret investigation was not revealed for another five months.
Dr. Tadeusz Dobosz, the forensic scientist on the team, was allowed to visually inspect the heart within the jar (photos are available on the internet), and described a generally enlarged heart, completely coated with a thickened white “tapestry” of fibrous tissue, and studded with shiny white pearls of glossy tissue. These are believed to be consistent with tuberculomas, and the white coating consistent with a diffuse, organizing inflammatory process, or what is referred to in the pathological literature as a “frosted heart.” The heart also had areas of nodular hyalinization and “organizing serosanguineous effusions” consistent with granulomatous caseation, predominantly involving the right side of the heart. All of this is very different from the post-mortem crystalline precipitates that can be seen in other types of preserved specimens. Dr. Dobosz believes the appearance of the heart is consistent with a diagnosis of tuberculous pericarditis, which likely contributed to more rapid downhill course at the end of Chopin’s chronic illness.
The Scent of Malaria
SOURCE: Lindsay S, Pinder M, Squires C, et al. Can medical-detection dogs identify people with malaria parasites? Abstract #32. American Society for Tropical Medicine and Hygiene Annual Meeting; New Orleans: Oct. 29, 2018.
Quick and easy, noninvasive diagnostic tools are always welcome, especially in poor and rural areas. These researchers had the ingenious idea that if scent dogs can be trained to detect drugs, cheese, fruit, and vegetables at ports of entry, could they be trained to detect the odor of malaria infection? Researchers obtained blood samples from 600 children ages 5 to 13 years in the upper river region of Gambia in West Africa and assessed for malaria. The children then received socks to take home and wear in bed at night. A total of 175 socks were collected, including socks from 30 children with positive blood smears and 145 without malaria. The socks were frozen and shipped to England. After four months of training, two dogs (a Labrador and a Labrador-golden retriever cross) performed a “blinded” study. The dogs correctly identified 70% of socks from children with malaria, and 90% of socks from children without the disease.
The use of scent dogs could prove of tremendous benefit in the more rapid identification of individuals carrying malaria, since generally only those people with symptoms are screened. The alternative is to screen everyone in a community with blood smears, which simply is not practical. The real question is, how much better would the dogs perform in real time if the socks weren’t frozen?