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Now going ‘viral’: Novel coronavirus, SFTS virus and avian influenza A(H7N9)
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One of the most exciting and alarming aspects of infectious diseases is the continual emergence and re-emergence of new diseases.
In the past 6 years, we have seen the recognition of three new diseases caused by novel viruses, all presumably of animal origin, occurring in the Middle East and the Far East. Novel coronavirus (nCoV) in the Middle East was first recognized in September. Severe fever with thrombocytopenia syndrome (SFTS), caused by a novel bunyavirus, in the Far East (China and Japan), was first recognized in 2007. And in late February, the first-ever human outbreak of avian A(H7N9) influenza started in China.
To date, no vector or animal reservoir has been recognized for nCoV. A tick vector has been hypothesized for infection with SFTS in China, as well as transmission through blood, but no vector has been identified for SFTS in Japan. In March, cases of severe H7N9 avian influenza were first reported in China.
Donald Kaye
Novel coronavirus
Coronaviruses are associated with respiratory infections in humans and animals. The severe acute respiratory syndrome (SARS) outbreak in 2002 and 2003, which infected more than 8,000 people worldwide and killed close to 10% of those infected, was caused by a coronavirus that made a species jump from bats to humans through the intermediate host of farmed civet cats bred for human consumption in China. Now we have nCoV, which produces a syndrome similar to SARS, currently referred to as SARI (severe acute respiratory illness).
Of note is that all of the cases can be traced to exposure in the Middle East, with two patients who were close contacts of a case who developed his infection in the Middle East. The virus was first identified in a patient in Saudi Arabia who died in June 2012. Subsequently, there have been 30 confirmed cases with 18 deaths: Saudi Arabia, 14 cases (11 deaths); Jordan, two cases (two deaths); Germany, two cases (one death), one from Qatar and one from the United Arab Emirates; the United Kingdom, four patients (two deaths), one from Qatar, one who had returned from Pakistan and Saudi Arabia and two who were exposed to the patient who returned from Saudi Arabia.
It is noteworthy that one of these two latter patients had mild disease, as did one of the patients from Saudi Arabia. The mortality rate of 65% may well be too high because of lack of adequate identification of mild disease. To date, no vector for nCoV has been identified, but presumably it is a nonhuman mammal. Bats have been demonstrated to carry a very similar coronavirus, but there is no epidemiological link.
Human-to-human spread has presumably occurred, with three clusters of cases. The three clusters are: 1) a definitive one that occurred in the United Kingdom in a family in which two family members were exposed to one who had returned from the Middle East; 2) a probable cluster with ICU staff in a hospital in Jordan; 3) and a probable cluster in a family in Saudi Arabia. Thus, although limited person-to-person transmission has occurred, it has not been widespread. A mutation in the virus or a super-spreader, such as occurred with SARS, could possibly change the dynamics.
Severe fever with thrombocytopenia syndrome
SFTS is a disease with sudden onset of fever, thrombocytopenia and leucopenia, as well as elevated hepatic enzymes, vomiting and diarrhea. It was first identified in China in 2007 and is caused by a newly identified member of the genus Phlebovirus, of the family Bunyaviridae.
Rift Valley fever is the best known member of the genus Phlebovirus. Diseases caused by Bunyaviridae are generally transmitted by arthropod vectors, with the notable exception of Hantaviruses. SFTS has occurred in six rural provinces in northeast and central China, where more than 200 patients have reportedly developed the disease. SFTS is reported to have a 12% case fatality rate.
In one study, 0.8% of healthy Chinese had serological evidence of past infection, so mild disease or unapparent infection can occur. Serological studies have shown that exposure to the virus has been widespread among nonhuman mammals studied in the affected areas. Evidence of past infection was especially high in goats; 83% in one study. The ixodid tick Haemaphysalis longicornis has been postulated to carry the disease to humans as accidental hosts. More than 5% of the ticks studied in an affected area of China were found to carry the virus. Human-to-human transmission has occurred in China from exposure to blood of infected patients.
During autumn months of 2012, SFTS was first identified in Japan; 11 cases with seven deaths were reported. There have been no epidemiological links reported between the different Japanese cases and no reports of tick bites in these cases. In fact, SFTS has not been isolated from ticks in Japan. The Japanese strain of SFTS, although very similar to the Chinese strain, is genetically different.
Influenza A(H7N9)
At the end of March, we learned of three cases of life-threatening avian A(H7N9) influenza in China, the first human cases ever recorded of H7N9. The first of these became ill in late February. As of early May, there have been 130 cases; most have been critically ill and 31 have died; one of the deaths occurred in an asymptomatic child. New numbers are coming in daily.
In contrast to avian A(H5N1) influenza, in which children were commonly infected and infection was linked to exposure to backyard flocks of poultry, the great majority of H7N9 cases have been adults. Cases in children are uncommon and tend to be milder. There are no epidemiologic connections between the cases, and they have occurred in multiple provinces in China. Some of the cases had known poultry exposure and some did not. There has been no evidence of person-to-person spread. H7N9 virus has been isolated from caged chickens, ducks, and pigeons raised for food in some locations where disease has occurred in humans.
The H7N9 influenza virus is an avian influenza virus of low pathogenicity for birds. The current strain developed from genetic reassortment of influenza strains from wild birds from East Asia and chickens from East China. There is a problem in recognizing infected birds, as they do not get sick. In contrast, death of the birds is frequent with avian influenza A(H5N1).
The H7N9 strain is obviously highly pathogenic for humans, but it does not seem to be easily transmissible from person-to-person. The possibility of pandemic potential is real because there is no previous human experience with either the hemagglutinin or the neuraminidase, and a mutation(s) could make the virus more transmissible among humans. The strains that have been tested are susceptible to oseltamivir (Tamiflu, Roche) and zanamivir (Relenza, GlaxoSmithKline).
This outbreak is rapidly evolving and is alarming. In its peak year, there were only 115 cases of H5N1 worldwide, as compared with more than 75 cases of H7N9 in less than 2 months in China. The CDC is developing a candidate virus that could be used to produce a vaccine if widespread transmission occurs. If it is decided to mass produce a H7N9 vaccine, it would greatly detract from the ability to produce sufficient seasonal influenza vaccine. Furthermore, and unfortunately, the H7 antigen has been poorly immunogenic in humans and will probably have to be engineered to create higher immunogenic potential for an effective vaccine.
Stay tuned.
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Disclosure: Kaye reports no relevant financial disclosures.