enterovirus 71

Enterovirus 71 Vaccine Is Safe and Efficacious.

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Two doses of an enterovirus 71 vaccine had an efficacy of 80% against EV71-associated disease in Chinese children.

 

Enterovirus 71 (EV71) is associated with hand, foot, and mouth disease (HFMD) and other, more-serious conditions. Infants and young children are most affected; epidemics have been especially severe in Asia (JW Infect Dis Jan 30 2013).

Investigators (with partial manufacturer support) recently conducted a multicenter, double-blind, phase III trial of an inactivated alum-adjuvanted EV71 vaccine based on genotype C4, the predominant strain in mainland China. Healthy children in that country, aged 6 to 35 months, were randomized to receive vaccine or placebo (alum adjuvant), administered on days 0 and 28. Of 10,245 enrollees, 96% received both doses.

During active surveillance (from day 56 to month 14), vaccine efficacy in the per-protocol population was 80% against EV71-associated disease and 90% against EV71-associated HFMD. Among 52 participants with laboratory-confirmed EV71-associated disease, 51 were seronegative; all EV71 isolates were genotype C4. Eight placebo-group and no vaccine-group participants were hospitalized for EV71-associated disease. Most participants with clinical HFMD were infected with Coxsackie A virus 16 or other enteroviruses; only 2.1% of episodes were associated with EV71. In the subset studied for immunogenicity, antibody titer was significantly higher in vaccine-group than placebo-group participants. The rate of serious adverse events was similar between groups (1.2% and 1.5%, respectively).

Comment: The authors caution that although EV71 vaccine could help to prevent severe cases of EV71-associated disease, its role in reducing the overall incidence of hand, foot, and mouth disease might be limited because EV71 is only one cause of this syndrome. They also note the need to assess whether the vaccine’s immunogenicity and efficacy are affected by concomitantly administered routine vaccines. Editorialists observe that future studies should examine cross-protection against other genotypes and — because neonatal EV71 infection can be particularly severe — vaccination of infants aged <6 months. Cost-effectiveness analyses can help in setting priorities among the several new vaccines that are efficacious and have acceptable safety profiles.

 

Source: Journal Watch Infectious Diseases

Outbreak of Illness and Death Among Children in Cambodia.

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The outbreak appears to have been caused by enterovirus 71.

In early July 2012, an outbreak of severe illness with high mortality was reported by the Ministry of Health in Cambodia. According to a WHO report dated July 13, 78 cases in 14 provinces had been identified since April, mostly in children aged ❤ years.

Investigation focused on the 61 children who met the case definition, of whom 54 had died. Illness manifestations included respiratory symptoms, fever, and generalized neurological abnormalities; children who died usually did so within 24 hours after hospital admission. Samples from 31 patients were tested for a variety of pathogens by Institut Pasteur du Cambodge, and “most” tested positive for enterovirus 71 (EV-71); a few also tested positive for dengue virus or Streptococcus suis. On July 15, 2012, authorities announced that no additional cases had been noted in Cambodia. Investigators believed that the use of steroids, which can suppress the immune system, worsened the illness in many of the patients.

Comment: EV 71 — a member of the picornavirus family — was first isolated in the late 1960s. It has been associated with outbreaks worldwide, most recently in Asia. Infection with EV 71, like that with other enteroviruses, ranges from asymptomatic to lethal and can manifest as rashes, diarrhea, respiratory symptoms, meningitis, hand-foot-mouth disease (HFMD), or myocarditis. Less commonly, it has been associated with acute flaccid paralysis, encephalitis, Guillain-Barré syndrome, and pulmonary edema and hemorrhage.

HFMD is most often caused by coxsackievirus A16 (another enterovirus) but is also caused by EV 71. According to the WHO, HFMD usually begins with fever, poor appetite, malaise, and sore throat. One or 2 days after fever onset, painful sores develop on the tongue, gums, and inside of the cheeks, beginning as small red blistering spots and then often becoming ulcers. A nonitchy skin rash develops over 1 or 2 days, with flat or raised red spots that may blister. Usually located on the palms of the hands and soles of the feet, the rash can also appear on the buttocks or genitals. Generally, HFMD is spread from person to person by direct contact with nose or throat discharges, saliva, fluid from blisters, or stool of infected persons. Transmissibility is greatest during the first week of the illness but can last for several weeks. No vaccine or antiviral agent has proven effective in preventing or treating EV 71 infection.

Source: Journal Watch Infectious Diseases

 

 

Virology, epidemiology, pathogenesis, and control of enterovirus 71

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First isolated in California, USA, in 1969, enterovirus 71 (EV71) is a major public health issue across the Asia-Pacific region and beyond. The virus, which is closely related to polioviruses, mostly affects children and causes hand, foot, and mouth disease with neurological and systemic complications. Specific receptors for this virus are found on white blood cells, cells in the respiratory and gastrointestinal tract, and dendritic cells. Being an RNA virus, EV71 lacks a proofreading mechanism and is evolving rapidly, with new outbreaks occurring across Asia in regular cycles, and virus gene subgroups seem to differ in clinical epidemiological properties. The pathogenesis of the severe cardiopulmonary manifestations and the relative contributions of neurogenic pulmonary oedema, cardiac dysfunction, increased vascular permeability, and cytokine storm are controversial. Public health interventions to control outbreaks involve social distancing measures, but their effectiveness has not been fully assessed. Vaccines being developed include inactivated whole-virus, live attenuated, subviral particle, and DNA vaccines.