Emergence of the Zika virus Asian lineage in Angola
Authors: Hill Sarah C. , Vasconcelos Jocelyne , Neto Zoraima , Jandondo Domingos , Zé-Zé Líbia , Aguiar Renato Santana , Xavier Joilson , Thézé Julien , Mirandela Marinela , Cândido Ana Luísa Micolo , Vaz Filipa , Sebastião Cruz dos Santos , Wu Chieh-Hsi , Kraemer Moritz , Melo Adriana , Schamber-Reis Bruno L.F. , de Azevedo Girlene S. , Tanuri Amilcar , Higa Luiza M. , Clemente Carina , da Silva Sara Pereira , da Silva Candido Darlan , Claro Ingra M. , Domingos Quibuco Nurse , Domingos Cristóvão , Pocongo Bárbara , Watts Alexander G. , Khan Kamran , Alcantara Luiz Carlos Junior , Sabino Ester C. , Lackritz Eve , Pybus Oliver G. , Alves Maria-João , Afonso Joana , Faria Nuno R. 
Published: January 2019

Research In ContextEvidence before this studyWe searched PubMed without language restrictions using the keywords ‘Zika’ and ‘Africa’ for papers published to October 2018. We also checked available ‘Situation Report’ publications from WHO for evidence of Zika virus (ZIKV) or congenital Zika disease in Africa. ZIKV African lineage has been detected within Africa since the mid 20th century, yet evidence for spread of the ZIKV Asian lineage within Africa is limited. Two countries in Africa (Cabo Verde and Angola) have reported ZIKV cases that are believed to be caused by a newly introduced Asian lineage virus. Sequence data are critical for confirming and understanding the spread of ZIKV Asian lineage within Africa, but these data are currently limited to a single 193bp fragment of the ZIKV NS1 gene from Angola. In addition, whilst epidemiological data on ZIKV and suspected microcephaly cases have been reported in detail from Cabo Verde, data from Angola are extremely limited.Added value of this studyWe provide a detailed report of detected ZIKV acute cases and suspected microcephaly cases in Angola. We sequence ZIKV genomes from three acutely infected cases. These represent the first three Asian lineage genomes available from Africa, one of which was acquired from a baby with confirmed microcephaly. Analysis of these sequences suggests that ZIKV may have been introduced to Angola between July 2015 and June 2016, after which it likely circulated for at least one year. This provides the first genetic confirmation of autochthonous ZIKV Asian lineage transmission within Africa. We suggest that the virus was more likely introduced to Angola directly from Brazil, rather than from Cabo Verde. Our analyses from Angola, only the second African country to report presence of the Asian virus lineage, therefore improve our understanding of the extent and clinical impact of ZIKV Asian lineage in the continent.Implications of all the available evidenceThe circulation of ZIKV Asian lineage within parts of sub-Saharan Africa is concerning given the potential for continued viral spread across much of the continent. Available evidence suggests that ZIKV has circulated and caused cases of microcephaly in Cabo Verde and in Angola. Detecting additional ZIKV transmission using only clinical data on suspected microcephaly or clusters of mild illness may be challenging in countries where systems for reporting birth defects are limited and infectious disease burden is high. Further spread of the ZIKV Asian lineage would likely not be detected unless molecular surveillance systems for ZIKV are implemented to routinely monitor ZIKV transmission in Africa. Implementation of such a surveillance system is especially important in countries that are linked by high human mobility to areas that have experienced recent or ongoing outbreaks of ZIKV.AbstractBackgroundZika virus (ZIKV) infections and suspected microcephaly cases have been recently reported in Angola, but no data are available on the origins, epidemiology, and diversity of the virus.MethodsSerum samples from 54 suspected ZIKV cases, 76 suspected microcephaly cases, and 24 mothers of infants with suspected microcephaly were received by the Angolan Ministry of Health. Computed tomographic brain imaging and serological assays (PRNT) were conducted on one microcephalic infant. All sera were tested for ZIKV by RT-qPCR. 349 samples from HIV+ patients and 336 samples from patients suspected of chikungunya virus or dengue virus infection were also tested. Portable sequencing was used to generate Angolan ZIKV genome sequences, including from a ZIKV+ neonate with microcephaly born in Portugal to an Angolan resident. Genetic and mobility data were analysed to investigate the date of introduction and geographic origin of ZIKV in Angola.FindingsFour autochthonous cases were ZIKV positive via RT-qPCR, with all positive samples collected between December 2016 and June 2017. Viral genomes were generated for two of these cases, and from the neonate with microcephaly identified in Portugal. Genetic analyses and other data indicate that ZIKV was introduced to Angola from Brazil between July 2015 and June 2016. This introduction likely initiated local ZIKV circulation in Angola that continued until June 2017. The scanned microcephaly case showed brain abnormalities consistent with congenital Zika syndrome and serological evidence for maternal ZIKV infection.InterpretationOur analyses confirm the autochthonous transmission of the ZIKV Asian lineage in continental Africa. Conducting ZIKV surveillance throughout Africa is critical in the light of presented evidence for autochthonous ZIKV transmission in Angola, and associated microcephaly cases.FundingRoyal Society, Wellcome Trust, CNPq, CAPES, ERC, Oxford Martin School, Global Challenges Research Fund, Africa Oxford, and John Fell Fund.