On 23rd of June, Cape Verde’s Ministry of Health reported that there had been 11 cases of Zika virus-linked microcephaly on the small African nation [1]. This count is a significant jump from the previously reported three cases as of the beginning of June [2]. The first case in Cape Verde, confirmed on 15th March in the area of Praia [3], was diagnosed while much about Zika virus and its suspected-to-be-associated microcephaly remained unknown. It was not until the end of March 2016 that the World Health Organization (WHO) announced that there was enough evidence to scientifically link Zika virus and microcephaly in infants exposed to the virus in utero [4].
The confirmation of Zika virus-linked microcephaly cases in Cape Verde is of particular importance due to the location and timing of the outbreak. Zika virus outbreaks have been confirmed in African countries since it was serologically confirmed in humans in Uganda in 1948 [5]. The virus was confirmed by serological evidence in multiple locations in Asia, but it was not until 2007 on Yap Island that it was confirmed as a clinical illness outbreak outside of Africa [5]. From there, outbreaks were then confirmed in French Polynesia and other Pacific Islands [6]. Genetic studies of the virus from the affected populations revealed three distinct Zika virus strains or genotypes: one from West Africa, one from East Africa, and one from Asia [6]. Given Cape Verde’s location, 350 miles off the coast of West Africa, there was little debate or speculation as to what strain its outbreak belonged – the focus remained on the 7500 suspected cases in the country and the outbreak swiftly spreading through the Americas.
Prior to the outbreak in the Americas, Zika virus was considered a ‘nuisance disease’ – causing only a short/mild illness. It was not until the cases of microcephaly, Guillain Barre Syndrome (GBS) and other neurological complication emerged, that the disease became of greater concern [7]. The first cases of GBS appearing in conjunction with Zika virus infection occurred in French Polynesia between 2013 and 2014 [8]. During that outbreak, the largest of its time, 42 patients were diagnosed with GBS – a retrospective case control study provided the evidence necessary to link Zika infection with the neurological condition [8].
Genetic sequencing revealed that the strain of Zika virus to blame for the outbreak in the Americas was the Asian strain – closely resembling the virus at its state during the French Polynesian outbreak [9]. The study authors, from the University of California at Los Angeles (UCLA), highlight the dangerous developments in the virus during this outbreak: “We don’t know why Zika infection was not associated with serious human disease, especially in newborns, until recently … We hoped that taking a closer look at the virus’ genetic changes over time would reveal clues to this mystery” [9]. Significant mutations were found, further segregating the Asian strain from the African strains, and mutations have had other effects on its clinical disease. The author of the study explains, “We suspect these mutations could help the virus replicate more efficiently, evade the body’s immune response or invade new tissues that provide a safe harbor for it to spread” [9]. These mutations may explain why the ‘serious human disease’ of the outbreak in the Americas may have suddenly cropped up.
On 20th of May, it was confirmed that it was Asian strain of Zika virus responsible for the outbreak and cases of microcephaly in Cape Verde – the first time the strain responsible for ‘serious human disease’ has been reported in Africa [10]. This makes sense, given its recent reports of microcephaly – approximately nine months after the first reports of infection, in late September of 2015 [11]. Much uncertainty remains regarding a mother’s Zika virus infection timing and its risk to the unborn fetus – some studies report that there is no risk during the third trimester, others report that there has been a connection to increased rates of sudden miscarriage [12, 13]. Much of these unknowns are a result of the fact that we do not yet know the breadth of the Zika-virus syndrome in newborns exposed in utero. Research now suggests “serious joint problems, seizures, vision impairment, trouble feeding and persistent crying can be added to the list of risks from Zika exposure in the womb” [14]. It may be months or years before we understand all complications, both congenital and developmental, in this cohort of newborns.
It remains unclear why we are only now seeing these severe outcomes from the Asian strain of the Zika virus. Early findings, published in Nature Immunology, suggest that previous exposure to the vectorborne dengue virus may increase the potency of Zika [15]. The mechanism for this increased potency is suggested to be a result of “some dengue antibodies can recognize and bind to Zika due to the similarities between the two viruses, but that these antibodies may also amplify Zika infection in a phenomenon called antibody-dependent enhancement” [15]. It is proposed that this may be why this outbreak is resulting in ‘serious human disease’ – it’s occurring in regions previously affected by dengue outbreaks.
When we think of dengue virus outbreaks – we typically think of Southeast Asia and South America, primarily Brazil. So what about Cape Verde? Does the previous-dengue-infection-exacerbating-Zika-virus theory hold up? In 2009, the Cape Verde Ministry of Health reported over 13,000 suspected cases of dengue [16]. The outbreak was the first dengue outbreak for the country and, at the time, the biggest outbreak recorded in Africa [16]. Given Cape Verde’s previous exposure to dengue, it is plausible that the new theory on Zika virus infection for the current outbreak holds up – and might explain the new cases of microcephaly being reported. Only time will tell what can be done to mitigate risks and outcomes.
[1] http://www.rtp.pt/noticias/mundo/cabo-verde-regista-11-casos-de-microcefalia-associados-ao-virus_n928516
[2] http://www.rtp.pt/noticias/mundo/cabo-verde-regista-tres-casos-de-microcefalia-por-causa-do-virus-zika_n923634
[3] http://www.rtp.pt/noticias/mundo/cabo-verde-regista-primeiro-caso-de-microcefalia-associado-ao-virus_n903864
[4] http://www.npr.org/sections/thetwo-way/2016/03/31/472607576/health-agencies-confirm-zika-is-linked-with-microcephaly
[5] http://wwwnc.cdc.gov/eid/article/15/9/09-0442_article
[6] http://wwwnc.cdc.gov/eid/article/22/5/16-0065_article
[7] http://www.usnews.com/news/politics/articles/2016-04-11/us-officials-the-more-we-learn-about-zika-scarier-it-is
[8] http://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(16)00562-6.pdf
[9] http://newsroom.ucla.edu/releases/ucla-scientists-unravel-the-genetic-evolution-of-zika-virus
[10] http://reliefweb.int/report/cabo-verde/who-confirms-zika-virus-strain-imported-americas-cabo-verde
[11] http://www.who.int/csr/don/21-december-2015-zika-cape-verde/en/
[12] http://www.nejm.org/doi/full/10.1056/NEJMoa1604037
[13] http://www.nytimes.com/interactive/2016/health/what-is-zika-virus.html
[14] http://www.scientificamerican.com/article/list-of-possible-zika-birth-defects-grows-longer/?WT.mc_id=SA_TW_HLTH_NEWS
[15] http://www.reuters.com/article/us-health-zika-dengue-idUSKCN0Z921O
[16] http://www.doctorswithoutborders.org/news-stories/field-news/cape-verde-msf-responds-africas-biggest-recorded-dengue-fever-outbreak
