Intra-African Ethnicity May for Be Important for Drug Choices in Epilepsy Care

Epilepsy care in African countries continues to rely largely upon older antiepileptic agents, so new findings in Acta Tropica by Motshoge and colleagues are of interest to physicians working in the region1. They evaluated the prevalence of CYP2C8*2, a slow drug metabolism allele, in San and Bantu populations in Botswana and found 17.5% amongst the San compared to 8.5% in the Bantu. The authors credit the differing evolutionary pressures on hunter-gatherers (the San). CYP2C8*2 is particularly important in the metabolism of carbamazepine and is virtually absent outside of African populations.2 Prior studies have indicated the San are also more likely to be slow acetylators3 and have lower CYP2D6 activity as well.4

Emerging Viral Pandemics: More Bad News for Neurology

The growing insights evolving from the Zika story continue to get grimmer and grimmer. An exposure-control study published in NEJM reports that even in pregnant women with mild disease, ~a third have antenatal ultrasound evidence of significant fetal neurologic abnormalities and problems are not limited to microcephalic fetuses.5 The impact of acute Zika infections on the nervous systems of neonates and infants is unknown, but on February 26th, the World Health Organization issued a report recommending that women, including women with confirmed active Zika infection, should continue to breastfeed. Then on March 1st, Lancet published a case report in which a high Zika viral load (39 million RNA copies per mL) was measured in the breast milks of an acutely infected woman 3 days post-partum.6 As the summer Olympics approaches, Brazilian authorities are reassuring the public that vector control measures will be in place to mitigate risks, but de Silva Augusto and colleagues point out that these measures have failed against dengue in the region.

As Zika rages across Latin America, Chikungunya (CHIK) continues remains a problem particularly in El Salvador and Colombia.7 In addition to the chronic fatigue syndrome phenomena that can occur post-infectiously, CHIK can cause myelitis, encephalitis, and radiculitis8-11. Still, the absolute numbers of CHIK cases in Latin America are down this year possibly because the first pass of the infection through the population provided sufficient herd immunity to squelch subsequent major outbreaks.

That which does not kill you may still be detrimental to your nervous system. Dr. Lauren Bowen with the NINDS will present her findings of neurologic complaints and exam abnormalities in Ebola survivors at the 2016 American Academy of Neurology Annual Meeting in Vancouver next month. Six months after recovery from infection, most Ebola survivors suffer from headaches, memory loss, mood disorders and muscle pains with exam abnormalities notable for tremors, eye movement abnormalities and abnormal reflexes. The neurologic status of unexposed controls with no history of Ebola infection but who nonetheless survived the Ebola epidemic remains to be seen.

There is some good news on the viral front. The WHO now recommends that people with HIV should be placed on treatment as soon as possible. This differs from many country-level treatment guidelines that mandate CD4 count thresholds or evidence of invasive disease to initiate treatment. Since lower CD4 nadir and longer duration of immune suppression are both risk factors for CNS opportunistic infections, HIV-associated neurocognitive disorders, and IRIS, earlier initiation of treatment could result in a global decrease in HIV-associated neurologic morbidity and mortality. Low-income countries may struggle to adopt these recommendations given the economic costs.

References

  1. Motshoge T, Tawe L, Muthoga CW, et al. Cytochrome P450 2C8*2 allele in Botswana: Human genetic diversity and public health implications. Acta tropica 2016;157:54-58.
  2. Dai D, Zeldin DC, Blaisdell JA, et al. Polymorphisms in human CYP2C8 decrease metabolism of the anticancer drug paclitaxel and arachidonic acid. Pharmacogenetics 2001;11:597-607.
  3. Jenkins T, Lehmann H, Nurse GT. Public health and genetic constitution of the San (“Bushmen”): carbohydrate metabolism and acetylator status of the Kung of Tsumkwe in the North-western Kalahari. British medical journal 1974;2:23-26.
  4. Sommers DK, Moncrieff J, Avenant J. Metoprolol alpha-hydroxylation polymorphism in the San Bushmen of southern Africa. Human toxicology 1989;8:39-43.
  5. Brasil P, Pereira JP, Jr., Raja Gabaglia C, et al. Zika Virus Infection in Pregnant Women in Rio de Janeiro – Preliminary Report. The New England journal of medicine 2016.
  6. Dupont-Rouzeyrol M, Biron A, O’Connor O, Huguon E, Descloux E. Infectious Zika viral particles in breastmilk. Lancet 2016.
  7. ProMED-Mail. Chikunguyna in the Americas. 2016.
  8. Bank AM, Batra A, Colorado RA, Lyons JL. Myeloradiculopathy associated with chikungunya virus infection. Journal of neurovirology 2016;22:125-128.
  9. Ganesan K, Diwan A, Shankar SK, Desai SB, Sainani GS, Katrak SM. Chikungunya encephalomyeloradiculitis: report of 2 cases with neuroimaging and 1 case with autopsy findings. AJNR American journal of neuroradiology 2008;29:1636-1637.
  10. Gerardin P, Couderc T, Bintner M, et al. Chikungunya virus-associated encephalitis: A cohort study on La Reunion Island, 2005-2009. Neurology 2016;86:94-102.
  11. Robin S, Ramful D, Le Seach F, Jaffar-Bandjee MC, Rigou G, Alessandri JL. Neurologic manifestations of pediatric chikungunya infection. Journal of child neurology 2008;23:1028-1035.
Gretchen L. Birbeck, MD, MPH

Gretchen L. Birbeck, MD, MPH

Gretchen Birbeck is a neurologist who divides her time between the US and Africa. Her US academic home is the University of Rochester where she is the Rykenboer Professor of Neurology and Research Director for the Strong Epilepsy Center with adjunct appointments in the Center for Human Experimental Therapeutics and the Department of Public Health. Her additional skills in epidemiology, health services research, and tropical medicine are brought to bear during the 6-months annually she spends in Africa where she serves as Director for the Chikankata Epilepsy Care Team in rural Mazabuka, Zambia, an Honorary Lecturer at the University of Zambia and a consultant for the Paediatric Research Ward at Queen Elizabeth Central Hospital in Blantyre, Malawi. Gretchen’s research programs are aimed at identifying opportunities to prevent or ameliorate the medical and social morbidities of common neurologic conditions in low-income, tropical settings with the ultimate goal of developing successful interventions feasible for scale up and broad implementation. She has been recognized as an Ambassador for Epilepsy by the International League against Epilepsy, a Global Health Research Ambassador by the US Paul Rogers Society, a National Outreach Scholar by the WK Kellogg Foundation and a Leader in Medicine by the American Medical Students Association.

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