Novel Antiviral Activity of Ethyl 3-Hydroxyhexanoate Against Coxsackievirus B Infection.

Coxsackievirus group B (CVB) is a member of the genus Enterovirus in the family Picornaviridae. CVB infection has been implicated as a major etiologic agent of viral myocarditis, dilated cardiomyopathy, meningitis, and pancreatitis among children and young adults. Until date, no antiviral agent has been licensed for the treatment of Coxsackievirus infection. In an effort to identify antiviral agents against diseases caused by the CVB, we found that ethyl 3-hydroxyhexanoate (EHX), a volatile compound present in fruits and food additives, is a potent antiviral compound. In this study, we demonstrated that EHX treatment significantly inhibits CVB replication both in vivo and in vitro. Furthermore, EHX possesses antiviral activity at 50% effective concentration (EC50) of 1.2 µM and 50% cytotoxicity (CC50) of 25.6 µM, yielding a selective index (SI) value as high as 20.8. Insights into the mechanism of antiviral activity of EHX showed that it acts at the step of viral RNA replication. Since EHX has received approval as food additives, treatment of CVB-related infections with EHX might be a safe therapeutic option and may be a promising strategy for the development of semi-synthetic antiviral drugs for viral diseases.

Virus-Induced Cytoplasmic Aggregates and Inclusions are Critical Cellular Regulatory and Antiviral Factors.

RNA granules, aggresomes, and autophagy are key players in the immune response to viral infections. They provide countermeasures that regulate translation and proteostasis in order to rewire cell signaling, prevent viral interference, and maintain cellular homeostasis. The formation of cellular aggregates and inclusions is one of the strategies to minimize viral infections and virus-induced cell damage and to promote cellular survival. However, viruses have developed several strategies to interfere with these cellular processes in order to achieve productive replication within the host cells. A review on how these mechanisms could function as modulators of cell signaling and antiviral factors will be instrumental in refining the current scientific knowledge and proposing means whereby cellular granules and aggregates could be induced or prevented to enhance the antiviral immune response in mammalian cells.

Incidence, Remission and Mortality of Convulsive Epilepsy in Rural Northeast South Africa.

BACKGROUND: Epilepsy is one of the most common neurological conditions globally, estimated to constitute 0.75% of the global burden of disease, with the majority of this burden found in low- and middle- income countries (LMICs). Few studies from LMICs, including much of sub-Saharan Africa, have described the incidence, remission or mortality rates due to epilepsy, which are needed to quantify the burden and inform policy. This study investigates the epidemiological parameters of convulsive epilepsy within a context of high HIV prevalence and an emerging burden of cardiovascular disease. METHODS: A cross-sectional population survey of 82,818 individuals, in the Agincourt Health and Socio-demographic Surveillance Site (HDSS) in rural northeast South Africa was conducted in 2008, from which 296 people were identified with active convulsive epilepsy. A follow-up survey was conducted in 2012. Incidence and mortality rates were estimated, with duration and remission rates calculated using the DISMOD II software package. RESULTS: The crude incidence for convulsive epilepsy was 17.4/100,000 per year (95%CI: 13.1-23.0). Remission was 4.6% and 3.9% per year for males and females, respectively. The standardized mortality ratio was 2.6 (95%CI: 1.7-3.5), with 33.3% of deaths directly related to epilepsy. Mortality was higher in men than women (adjusted rate ratio (aRR) 2.6 (95%CI: 1.2-5.4)), and was significantly associated with older ages (50+ years versus those 0-5 years old (RR 4.8 (95%CI: 0.6-36.4)). CONCLUSIONS: The crude incidence was lower whilst mortality rates were similar to other African studies; however, this study found higher mortality amongst older males. Efforts aimed at further understanding what causes epilepsy in older people and developing interventions to reduce prolonged seizures are likely to reduce the overall burden of ACE in rural South Africa.

Exposure to multiple parasites is associated with the prevalence of active convulsive epilepsy in sub-Saharan Africa.

BACKGROUND: Epilepsy is common in developing countries, and it is often associated with parasitic infections. We investigated the relationship between exposure to parasitic infections, particularly multiple infections and active convulsive epilepsy (ACE), in five sites across sub-Saharan Africa. METHODS AND FINDINGS: A case-control design that matched on age and location was used. Blood samples were collected from 986 prevalent cases and 1,313 age-matched community controls and tested for presence of antibodies to Onchocerca volvulus, Toxocara canis, Toxoplasma gondii, Plasmodium falciparum, Taenia solium and HIV. Exposure (seropositivity) to Onchocerca volvulus (OR = 1.98; 95%CI: 1.52-2.58, p<0.001), Toxocara canis (OR = 1.52; 95%CI: 1.23-1.87, p<0.001), Toxoplasma gondii (OR = 1.28; 95%CI: 1.04-1.56, p = 0.018) and higher antibody levels (top tertile) to Toxocara canis (OR = 1.70; 95%CI: 1.30-2.24, p<0.001) were associated with an increased prevalence of ACE. Exposure to multiple infections was common (73.8% of cases and 65.5% of controls had been exposed to two or more infections), and for T. gondii and O. volvulus co-infection, their combined effect on the prevalence of ACE, as determined by the relative excess risk due to interaction (RERI), was more than additive (T. gondii and O. volvulus, RERI = 1.19). The prevalence of T. solium antibodies was low (2.8% of cases and 2.2% of controls) and was not associated with ACE in the study areas. CONCLUSION: This study investigates how the degree of exposure to parasites and multiple parasitic infections are associated with ACE and may explain conflicting results obtained when only seropositivity is considered. The findings from this study should be further validated.

Clinical features, proximate causes, and consequences of active convulsive epilepsy in Africa.

PURPOSE: Epilepsy is common in sub-Saharan Africa (SSA), but the clinical features and consequences are poorly characterized. Most studies are hospital-based, and few studies have compared different ecological sites in SSA. We described active convulsive epilepsy (ACE) identified in cross-sectional community-based surveys in SSA, to understand the proximate causes, features, and consequences. METHODS: We performed a detailed clinical and neurophysiologic description of ACE cases identified from a community survey of 584,586 people using medical history, neurologic examination, and electroencephalography (EEG) data from five sites in Africa: South Africa; Tanzania; Uganda; Kenya; and Ghana. The cases were examined by clinicians to discover risk factors, clinical features, and consequences of epilepsy. We used logistic regression to determine the epilepsy factors associated with medical comorbidities. KEY FINDINGS: Half (51%) of the 2,170 people with ACE were children and 69% of seizures began in childhood. Focal features (EEG, seizure types, and neurologic deficits) were present in 58% of ACE cases, and these varied significantly with site. Status epilepticus occurred in 25% of people with ACE. Only 36% received antiepileptic drugs (phenobarbital was the most common drug [95%]), and the proportion varied significantly with the site. Proximate causes of ACE were adverse perinatal events (11%) for onset of seizures before 18 years; and acute encephalopathy (10%) and head injury prior to seizure onset (3%). Important comorbidities were malnutrition (15%), cognitive impairment (23%), and neurologic deficits (15%). The consequences of ACE were burns (16%), head injuries (postseizure) (1%), lack of education (43%), and being unmarried (67%) or unemployed (57%) in adults, all significantly more common than in those without epilepsy. SIGNIFICANCE: There were significant differences in the comorbidities across sites. Focal features are common in ACE, suggesting identifiable and preventable causes. Malnutrition and cognitive and neurologic deficits are common in people with ACE and should be integrated into the management of epilepsy in this region. Consequences of epilepsy such as burns, lack of education, poor marriage prospects, and unemployment need to be addressed.