“Ukatamanga weka utamangisa, tikatamanga awili, tifikapatali - When you run alone, you run fast. When you run together, you run far Zambian Proverb

UNZA-UCLMS

Research and Training Programme

HHV-6A/6B viral loads in febrile paediatric admissions with and without seizures 

Background

Seizures are common in the pediatric population worldwide. Most children never experience a recurrence but a seizure may be an initial presentation of a serious medical condition. Determining whether a seizure was provoked or unprovoked helps determine treatment options and prognosis. Common causes of provoked seizures are central nervous system (CNS) infections, metabolic derangements, high fever, head trauma and structural abnormalities. Febrile seizures (FS) are the most common seizure disorder in childhood. Occurring in 2 to 5% of children under 5 years of age with a peak age of onset being in the second year of life . (Shinnar et al., 2003. AAP 2008.). Febrile seizures are defined as seizures that occur in febrile children commonly between the ages of 6 months – 6 years without an acute central nervous system infection or insult, or history of afebrile seizures. 

Febrile status epilepticus (FSE) is a FS lasting more than 30 minutes or a series of seizures without fully regaining consciousness in-between. Common causes of fever in children with FS/FSE are acute otitis media and viral infections.These include influenza, parainfluenza, adenovirus and Human herpesvirus-6 (HHV-6) (Chung et al., 2007), with the prevalence of HHV-6 in children presenting with febrile seizures being 18-42%. (Laina et al.,2010. Hakin et al., 1998). In Western countries HHV-6B is well established as a serious cause of hospitalization due to febrile seizures in healthy children (Hall et al,1994), and both HHV-6A and HHV-6B are established as significant causes of morbidity and mortality in immune-compromised patient groups (Lusso et al, 1989, 2007). These two viruses are however severely neglected as topics for research in low-income, high HIV-burden populations such as Zambia. Children with febrile seizures are at risk of developing subsequent unprovoked seizures or epilepsy. The risk is even more in those who experience complex febrile seizures and febrile status epilepticus. It is therefore important to identify the cause of the fever for appropriate treatment and prevention where possible. Human Herpesvirus-6 (HHV-6) is one of the important causes of fever induced seizures in children. HHV-6 was first isolated in 1986 from patients with Acquired immunodeficiency syndrome (AIDS) and those with lymphoproliferative disorders in the United States of America (Salahuddin et al ., 1986). It was initially known as “Human B-lymphotropic virus” but later renamed human herpesvirus 6. The discovery of other strains from different geographic areas (including Uganda and Zaire) resulted in the classification of the virus into two variations, namely HHV-6A and HHV-6B. After several years of scientific debate, genomic sequencing confirmed that these are two separate viruses. In 2012, the International Committee on Taxonomy of Viruses (ICTV) officially recognized HHV-6A and HHV-6B as distinct viruses in the genus roseolovirus, subfamily Betaherpesvirinae, family Herpesviridae and Order Herpesvirales, (Ablashi et al.,2013. ICTV, 2012)

Objective

To determine the prevalence of HHV-6A/6B and HHV-7 in children 6 months- 6 years old with febrile seizures and febrile status epilepticus.

Specific aims

1) To compare the prevalence and viral loads of HHV-6A/6B and HHV-7 in children 6 months- 6 years old with FS/FSE and in febrile children without seizures at UTH paediatrics department.

2) To determine the percentage of children with primary HHV-6/7 and febrile seizures who are HIV positive.

3) To determine the percentage of children with primary HHV-6/7 and febrile seizures who have malaria.

Methodology

This will be a cross-sectional study over a period of 12 months. Children between the ages of 6 months- 6 years presenting with first episode of febrile seizure and those presenting with febrile illness. The study will be conducted from the paediatric emergency room and admission ward at University Teaching Hospital in Lusaka. The paediatric department has an approximate bed capacity of 350 catering for patients coming from various parts of Lusaka as well as receiving patients referrals from all parts of Zambia. Eligibility to participate in the study will be based on the study definitions of febrile seizures and febrile illness in children between the ages of 6 months to 6 years. Patients who do not fit into the definitions will not be enrolled.

Group 1 : Children aged 6 months – 6 years with first episode of febrile seizure and febrile status epilepticus presenting within 48hrs of a febrile illness.

Group 2 : Children aged 6 months – 6 years with a febrile illness presenting within 48hrs of a febrile illness without seizures.