Japanese Encephalitis: Estimating Future Trends in Asia

Julia Metelka; Colin Robertson; Craig Stephen; Julia Metelka; Colin Robertson; Craig Stephen

doi:10.3934/publichealth.2015.4.601

AIMS Public Health

2015, Volume 2, Issue 4: 601-615. doi: 10.3934/publichealth.2015.4.601

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Research article Special Issues

Japanese Encephalitis: Estimating Future Trends in Asia

1.
Department of Geography & Environmental Studies, Wilfrid Laurier University, Waterloo, ON, Canada;
2.
Canadian Wildlife Health Cooperative, Saskatoon, Canada

Received: 25 February 2015 Accepted: 17 August 2015 Published: 31 August 2015

Limited surveillance programs and lack of diagnostic laboratory testing capacity in many low and middle income Asian countries have made it difficult to validate epidemiological patterns and anticipate future changes in disease risk. In this study, we consider the case of Japanese Encephalitis in Asia and examine how populations of human hosts and animal reservoirs are expected to change over the next three decades. Growth was modelled at the sub-national level for rural and urban areas to estimate where high-density, susceptible populations will potentially overlap with populations of the virus' amplifying host. High-risk areas based on these projections were compared to the current distribution of Japanese Encephalitis, and known immunization activities in order to identify areas of highest priority for concern. Results indicated that mapping JE risk factors at the sub-national level is an effective way to contextualize and supplement JE surveillance data. New patterns of risk factor change occurring in Southeast Asia were identified, including around major urban areas experiencing both urbanization and growth in pig populations. A hotspot analysis of pig-to-population ratio found a significant spatial cluster extending northward through Southeast Asia and interior China. Mapping forecasted changes in risk factors for JE highlights regions vulnerable to emerging zoonoses and may be an important tool for developing effecting transnational health policies.

Keywords:

Citation: Julia Metelka, Colin Robertson, Craig Stephen. Japanese Encephalitis: Estimating Future Trends in Asia[J]. AIMS Public Health, 2015, 2(4): 601-615. doi: 10.3934/publichealth.2015.4.601

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Abstract

1. Introduction

The risk of cerebral palsy (CP) is inversely correlated with gestational age at birth [1]. CP is accompanied with life-long consequences for the child, its family and society as a whole.Meta-analyses haveindicated that magnesium sulphate may be neuroprotective for the preterm infant, when the drug is given to women at high risk of preterm birth [2,3]. However, this was recently questioned by a trial sequential analysis (TSA), a statistical method which adjusts for risk of random errors [4]. The TSA demonstrated that additional data are needed before accepting magnesium sulphateas evidence-based therapy for women in preterm labour.

Our aim is toinvestigate if antenatal magnesium sulphate administrated to women at risk of preterm birth can protect their children against CP.

2. Materials and methodology:

This trial is ongoing and is performed as a double-blinded, randomized, controlled, multicenter clinical trial. A study population consisting of 500 women, who are at risk of preterm birth at 24 to 32 weeks of gestation, are randomized to receive either intravenous magnesium sulphate or placebo with saline. The women are recruited from 14 obstetrics departments in Denmark. The children are followed up after 18 months of age by a questionnaire (The Ages & Stages Questionnaire), which is a standardized, validated questionnaire containing questions that can reveal signs of CP [5]. The trial is approved by the Scientific Ethics Committee of the Capital Region of Denmark (H-4-2011-024), the Danish Data Protection Agency (HVH-2011-41-6007) and is registered at ClinicalTrials.gov (no. NCT01492608).

Inclusion criteria are: maternal age ≥ 18 years, gestational age 24+0 to 31+6 weeks, singleton or twin pregnancy, preterm rupture of membranes at 24+0 to 31+6 weeks with contractions and expected birth within 2-24 hours, or preterm contractions and expected birth within 2-24 hours and finally anticipated delivery within 2-24 hours of other reasons (for example fetal growth restriction).

Exclusion criteria are major fetal abnormalities, maternal contraindication to magnesium sulphate (e.g. allergy, myasthenia gravis, kidney failure and heart disease), magnesium sulphate administrated for other reasons (e.g. for prevention of eclampsia) and lack of the ability to understand and speak Danish.

2.1. Administration of magnesium sulphate:

Magnesium sulphate is administrated as a loading dose of five grams infused for 20-30 minutes, followed by a maintenance dose of one gram per hour. Placebo is given in identical appearing doses. The maintenance infusion will be continued until delivery appears, or for 24 hours if delivery does not occur or no longer is considered imminent. The doses that are used in this project are similar to those used in Denmark for prevention of eclampsia. Blood pressure, pulse rate, respiration rate and reflexes are being controlled throughout the period. Also the fetal heart is monitored closely.

2.2. Follow-up of the children:

The children are followed up after 18 months of age. A questionnaire will be sent to the parents. If signs of CP are revealed from the questionnaire, the children will be examined neurologically by a pediatrician. The effect will be assessed blinded to the treatment.

3. Power calculation:

A total sample size of 500 patients would allow us to detect or reject a difference in CP of 25% or more with a 5% type 1 error risk. The present trial will with a power of only 13%, not in itself have the power to detect a significant difference between magnesium and placebo treatment. Instead, when the trial is completed, the results will be added to the existing data in a cumulative meta-analysis, in order to ‘close the gap of evidence’ in a TSA, and determine whether magnesium sulphate has an effect. The power of the new meta-analysis will be 63%. We used a one-sided test as a harmful effect of magnesium sulphate on CP seems unlikely according to previous data.

4. Current status and future perspectives:

To date more than 380 women have been included in the trial. We expect the inclusion period to end in December 2016. Positive results of this trial will support a change of the clinical guidelines concerning the treatment of women with threatening preterm birth.

Conflict of Interest

No conflict of interests.

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