Infants with HHV-6B seizures are 15X more likely to develop febrile status epilepticus

A large prospective study in Africa adds weight to the argument that HHV-6B infection is an important cause of febrile status epilepticus (FSE).

The study was carried out as a collaborative initiative of the HerpeZ medical research organization based in Zambia, which aims to generate knowledge on a range of infectious diseases that will ultimately improve diagnostics and treatment in sub-Saharan Africa and beyond. During the course of the study, 102 children between the ages of 6 and 60 months with febrile seizures (FS) and FSE were recruited, as were 95 children with febrile illness in the same age range who did not have FS nor FSE. Children with signs and symptoms of central nervous system (CNS) infection were excluded.

HHV-6B was detected in the plasma of 10 (10.5%) febrile children without seizures (the controls) and 6 (5.8%) of those with FS/FSE. HHV-6A was not detected at all. While HHV-6B was detected in fewer samples from children with FS than from febrile controls, and HHV-6B was not independently associated with FS, the prevalence of the virus among those with FSE was considerably higher than in either of the other groups. The rate of active HHV-6B infection among the FSE subgroup was 40%, and although there were only 5 cases of FSE total, the association between FSE and HHV-6 infection was significant (OR 15; 95% CI, [1.99-120]; p=0.009). The two HHV-6B+ patients who developed FSE represented 12.5% of the total (16) HHV-6B+ cases, indicating a high risk of FSE during active HHV-6 infection in Zambian children. The investigators note that most of the positive cases likely resulted from viral reactivation instead of primary infection, as only 3 positive samples were obtained from children under 1 year of age, and primary infection tends to occur before the age of 1 in Zambia.

FSE, which is characterized by prolonged or recurrent seizures, has been associated with a heightened risk of developing mesial temporal lobe epilepsy (MTLE) (Shinnar 2003). Complex seizures have been previously associated with HHV-6 in immunocompetent and immunocompromised adults as well as in children. HHV-6 DNA has also been detected in the brain tissue of 28% of refractory MTLE patients (Li 2011) and about 55% of patients with TLE and a history of encephalitis (Niehusmann 2010). Similarly, Fotheringham et al. reported finding HHV-6B in 62.5% of MTLE patients but zero controls (Fotheringham 2007), and HHV-6B has also been linked to mesial temporal sclerosis, which leads to MTLE (Kawamura 2015). Moreover, the development of symptomatic generalized epilepsy has been documented following HHV-6-associated post-transplant acute limbic encephalitis (Raspall-Chaure 2013, Howell 2012).

Although a previous study (Epstein 2012) showed that 32% of febrile status epilepticus patients suffer from active HHV-6B infection, FSE infants are rarely tested for HHV-6B or treated with antivirals.

The consequences of CNS involvement during childhood infections may be more extensive in sub-Saharan Africa than in developed countries due to the higher disease burden during childhood. In fact, epilepsy is two times more prevalent in sub-Saharan Africa than in Asia, North-America, and Europe (Ba-Diop 2014).

Find the full paper here: Tembo 2018.