Dataset Information

Pathologic and molecular studies of enterovirus 71 infection in a fatal case from a recent epidemic in China: A case report.

ABSTRACT:

Rationale

Enterovirus 71 (EV71) is identified as the primary cause of hand, foot, and mouth disease (HFMD) and mainly infects the young infants. Though some fatal cases have been reported, the underlying mechanisms of EV71 infection remain elusive and more further pathologic and molecular studies of EV71 infection are needed.

Patient concerns

A 26-month-old girl with a history of fever and lethargy for 3 days and intermittent seizures for 2 hours associated with rash on 4 limbs was brought to a hospital.

Diagnoses

The autopsy was performed to identify the cause of death for a medical dispute. The results of histologic examination, immunohistochemistry (IHC), nested reverse transcription polymerase chain reaction (RT-PCR), and viral isolation confirmed that this patient died of EV71 infection.

Interventions

The patient was transferred to neonatal intensive care unit and was intubated and mechanically ventilated. The other treatment included cardiopulmonary resuscitation and intravenous injection of adrenaline.

Outcomes

The patient presented persistent coma and intermittent seizures and suddenly developed respiratory arrest and died 16 hours after admission.

Lessons

Our results suggest that EV71 might invade into the central nervous system (CNS) through peripheral nerves which control the digestive tract in the early stage of infection. In addition, we successfully isolated one EV71 strain. Phylogenetic analysis showed that the isolated strain clustered in the C4a of C4 subgenotype. This case also highlights that rapid deterioration in HFMD cases is still a challenge to physicians and they must pay special attention to the infants with HFMD symptoms, particularly in EV71 epidemic areas for early diagnosis and treatment.

SUBMITTER: Xing J

PROVIDER: S-EPMC6283094 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundChina accounted for 87% (9.8 million/11.3 million) of all hand, foot, and mouth disease (HFMD) cases reported to WHO during 2010-2014. Enterovirus 71 (EV71) is responsible for most of the severe HFMD cases. Three EV71 vaccines recently demonstrated good efficacy in children aged 6-71 mo. Here we assessed the cost-effectiveness of routine pediatric EV71 vaccination in China.Methods and findingsWe characterized the economic and health burden of EV71-associated HFMD (EV71-HFMD) in China using (i) the national surveillance database, (ii) virological surveillance records from all provinces, and (iii) a caregiver survey on the household costs and health utility loss for 1,787 laboratory-confirmed pediatric cases. Using a static model parameterized with these data, we estimated the effective vaccine cost (EVC, defined as cost/efficacy or simply the cost of a 100% efficacious vaccine) below which routine pediatric vaccination would be considered cost-effective. We performed the base-case analysis from the societal perspective with a willingness-to-pay threshold of one times the gross domestic product per capita (GDPpc) and an annual discount rate of 3%. We performed uncertainty analysis by (i) accounting for the uncertainty in the risk of EV71-HFMD due to missing laboratory data in the national database, (ii) excluding productivity loss of parents and caregivers, (iii) increasing the willingness-to-pay threshold to three times GDPpc, (iv) increasing the discount rate to 6%, and (v) accounting for the proportion of EV71-HFMD cases not registered by national surveillance. In each of these scenarios, we performed probabilistic sensitivity analysis to account for parametric uncertainty in our estimates of the risk of EV71-HFMD and the expected costs and health utility loss due to EV71-HFMD. Routine pediatric EV71 vaccination would be cost-saving if the all-inclusive EVC is below US$10.6 (95% CI US$9.7-US$11.5) and would remain cost-effective if EVC is below US$17.9 (95% CI US$16.9-US$18.8) in the base case, but these ceilings could be up to 66% higher if all the test-negative cases with missing laboratory data are EV71-HFMD. The EVC ceiling is (i) 10%-14% lower if productivity loss of parents/caregivers is excluded, (ii) 58%-84% higher if the willingness-to-pay threshold is increased to three times GDPpc, (iii) 14%-19% lower if the discount rate is increased to 6%, and (iv) 36% (95% CI 23%-50%) higher if the proportion of EV71-HFMD registered by national surveillance is the same as that observed in the three EV71 vaccine phase III trials. The validity of our results relies on the following assumptions: (i) self-reported hospital charges are a good proxy for the opportunity cost of care, (ii) the cost and health utility loss estimates based on laboratory-confirmed EV71-HFMD cases are representative of all EV71-HFMD cases, and (iii) the long-term average risk of EV71-HFMD in the future is similar to that registered by national surveillance during 2010-2013.ConclusionsCompared to no vaccination, routine pediatric EV71 vaccination would be very cost-effective in China if the cost of immunization (including all logistical, procurement, and administration costs needed to confer 5 y of vaccine protection) is below US$12.0-US$18.3, depending on the choice of vaccine among the three candidates. Given that the annual number of births in China has been around 16 million in recent years, the annual costs for routine pediatric EV71 vaccination at this cost range should not exceed US$192-US$293 million. Our results can be used to determine the optimal vaccine when the prices of the three vaccines are known.