Asian lineage of Zika virus confirmed in a microcephaly case from Angola

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Thursday, 9 August 2018

A case of a newborn with microcephaly and other characteristic abnormalities associated with congenital Zika virus syndrome was linked by laboratory tests (a positive nucleic acid test) to Zika virus (Asian lineage) infection for the first time in Angola.

In Africa, some cases of microcephaly due to congenital Zika virus infection were previously reported in the islands of Cape Verde (in a large outbreak that occurred in 2015-2016). A few more cases were suspected in Guinea-Bissau in 2016, without having, nevertheless, any diagnostic confirmation.

Aedes Aegypti mosquito during blood meal © James Gathany, Wikimedia Commons

Therefore, to our knowledge, this is the first case of confirmed congenital Zika syndrome caused by a strain belonging to the Asian lineage in continental Africa.

What is a confirmed congenital Zika syndrome?

Zika virus infection is most frequently transmitted by Aedes mosquitoes and less frequently by other non-vector-borne pathways (sexual, transfusion, maternal-foetal).

Although clinically, most people infected with Zika virus present mild or no symptoms, Zika virus infection during pregnancy can be transmitted vertically and cause several birth defects in foetuses and infants, as microcephaly and other severe foetal brain abnormalities such as intracranial calcifications and eye lesions.

Detection of Zika virus nucleic acids in an infant’s body fluid with neurological complications confirms congenital Zika syndrome.

The importance of confirming Zika virus infection in cases of infants with neurological complications

The real impact of Zika virus infection during pregnancy is still unknown, as only a small percentage of suspected cases are laboratory confirmed and the range of effects can be beyond the abnormalities detected at birth. The follow-up of pregnancies and infants with laboratory evidence of Zika virus infection is essential to define public health measures.

Limitations in Zika virus laboratory tests

The laboratory diagnostic of Zika virus presents several limitations. Zika virus is a flavivirus, as dengue, West Nile, Japanese Encephalitis and Yellow Fever viruses.  

All flavivirus have RNA genomes, and upon infection, the virus’s RNA is only transitorily present in body fluids.

3D Zika virus © Manuel Almagro Rivas

Thus, a positive nucleic acid test is only possible for a period of time (that depends on the analysed sample) and a negative result, does not rule out infection.

On the other hand, serologic tests (when we look for the antibodies produced by our immune system against the virus) also depend on the sample collection time (after infection) and there are cross-reactions between antibodies produce against different flavivirus that can induce false positive results.

The interpretation of serologic tests can be extremely complicated in geographic regions where several flavivirus co-circulate.

Thus, confirming suspected congenital Zika syndromes, namely microcephaly cases, is not easy.

Since Zika virus RNA and specific antibodies that confirm recent infections (IgM antibodies) levels decrease over time, laboratory testing of infants should be ideally performed in the first days of life, and in several samples.

The impact of Zika virus Asian lineage circulation in continental Africa

Zika virus is endemic in Africa and was primarily isolated in 1947 from a febrile sentinel rhesus monkey in Uganda. The following decades was considered a relatively benign pathogen, with few detections and isolations from mosquitoes and humans in Africa and Asia, of viruses belonging to only one lineage, the African lineage.

In 2007 an epidemic in Micronesia and then French Polynesia (2013-2014) started a turnover, with the expansion of its epidemic potential, virulence and geographic range, associated with strains belonging to a new lineage, the Asian lineage (responsible for the large outbreak in the Americas, with a huge cluster of microcephaly cases in Brazil).

Several neurological complications have since then been associated with Zika virus (Asian lineage) infection, including Guillain–Barré syndrome and congenital Zika syndrome.

The epidemic potential and virulence recognized to the Asian lineage strains of Zika virus is much higher than the “older” endemic African Zika virus strains, raising the concern of a large outbreak in continental Africa.

As of November 2017, Angola (along with Guinea-Bissau) was identified as a World Health Organization (WHO) category 1 country (meaning ‘area with new introduction or re-introduction with ongoing transmission’), but no confirmed cases of Zika virus infection of Asian or African lineage have been reported, previously.

Zika virus after WHO declaration as a Public Health Emergency of International Concern

In February 2016, the World Health Organization (WHO) declared the Zika virus epidemic a Public Health Emergency of International Concern (PEIC), prompting an international research effort to understand Zika virus infection and impact.

Although the major outbreaks seem to be over, its geographic range is still growing, and the real impact of the virus is still unknown.

The long-term neurodevelopment impact of microcephaly and other neonatal complications associated with congenital Zika virus infection, will still take several years of follow-up studies to be fully understood.

Read the full publication 

About the authors

Madalena Sassetti, Department of Paediatrics, Hospital Garcia de Orta, Almada, Portugal

Líbia Zé-Zé, National Institute of Health Dr. Ricardo Jorge, Centre for Vectors and Infectious Diseases Research, Águas de Moura, Portugal and Biosystems and Integrative Sciences Institute (BioISI), Edificio TecLabs, Lisbon, Portugal