A Review on Microcephaly Associated with Zika Fever in New Born Babies


V.P.Laavanya, R. Jayasurya, N. Kavitha, G. Prabakaran, Dr. S. Jayakumari*

School of Pharmaceutical  Sciences , Vels University , Vels  Institute of  Science, Technology and Advanced Studies [VISTAS] Pallavaram, Chennai,  600 117.Tamilnadu,  India.

*Corresponding Author E-mail: nisajayaa@gmail.com



A widespread epidemic of Zika virus (ZIKV) infection was reported in 2015 in South and Central America and the Caribbean. A major concern associated with this infection is the apparent increased incidence of microcephaly in fetuses born to mothers infected with(ZIKV). In this report, it was described the case of an expectant mother who had a febrile illness with rash at the end of the first trimester of pregnancy living in Brazil. Ultrasonography performed at 29 weeks of gestation revealed microcephaly with calcifications in the fetal brain and placenta. After the mother requested termination of the pregnancy, a fetal autopsy was performed. Microcephaly (an abnormally small brain) was observed, with almost complete agyria, hydrocephalus, and multifocal dystrophic calcifications in the cortex and subcortical white matter, with associated cortical displacement and mild focal inflammation. ZIKV was found in the fetal brain tissue on reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assay, with consistent findings on electron microscopy. The complete genome of (ZIKV) was recovered from the fetal brain.


KEYWORDS: Zika virus (flavivirus) Uganda, microcephaly, reverse-transcriptase–polymerase-chain-reaction (RT-PCR)



Zika virus (ZIKV) is  transmitted  by daytime-active aedes mosquitoes, such as A.aegypti1,2. Its name comes from the zika forest of Uganda. Zika virus (ZIKV) is a member of the virus family.


Fig-1 Zika Virus Structure 


Family: Flaviviridae

Group: Group IV (+)ssRNA

Genus : Flavivirus


In1950s it has been known to occur within a narrow equatorial belt from Africa to Asia. In 2014, the virus spread eastward across the Pacific Ocean to french polynesia, then to Easter Island and in 2015 to Mexico, Central America, the Caribbean, and South America, where the Zika outbreak has reached pandemic levels. Zika virus is related to dengue,yellow fever, japanese encephalitis.3



Zika virus is envolped , icosahedral and has a nonsegmented, single-stranded, positive-sense RNA genome. It is most closely related to the spondweni virus and is one of the two viruses in the Spondweni virus clade4,5 There are two lineages of Zika virus, the African lineage and the Asian lineage.6. Phylogenetic studies indicate that the virus spreading in the Americas is most closely related to the Asian strain, which circulated in French Polynesia during the 2013 outbreak.7,8 Recent preliminary findings from sequences in the public domain uncovered a possible change in nonstructural protein 1 codon usage that may increase the viral replication rate in humans9



The vertebrate hosts of the virus were primarily monkeys with only occasional transmission to humans. Rarely, arboviruses become established as a human disease, spread in a mosquito–human–mosquito cycle, having permanently left the enzootic mosquito-monkey-mosquito cycle. Arbo viruses to have done so are the flaviviruses yellow fever and dengue, and the togavirus  chikungunya. Before the current pandemic , which began in 2007, Zika virus "rarely caused recognized 'spillover' infections in humans, even in highly  enzootic areas".10 It is spread around like Barbados, Bolivia, Brazil, Colombia, Commonwealth of Puerto Rico, USterritory, CostaRica, Curacao, Dominican Rep Ecuador, Salvador, French Guiana, Guadeloupe, Guatemala, Guyana, Haiti, Honduras, Jamaica, Martinique, Mexico, Nicaragua, Panama Paraguay, Saint Martin, uriname,U.S. Virgin Islands, Venezuela, American Samoa, Samoa, Tonga, Cape Verde 11



The most common symptoms of Zika are fever, rash, joint pain, or conjunctivitis (red eyes)12.Other common symptoms include muscle pain and headache. The incubation period (the time from exposure to symptoms) for Zika virus disease is not known, but is likely to be a few days to a week.13. The illness is usually mild with symptoms lasting for several days to a week. Zika virus usually remains in the blood of an infected person for a few days but it can be found longer in some people. Severe disease requiring hospitalization is uncommon. Deaths are rare14



The symptoms of Zika are similar to those of dengue and chikungunya, diseases spread through the same mosquitoes that transmitted zika.15 undergo blood tests to look for Zika or other similar viruses like dengue or chikungunya16



If laboratory testing is required, the following instructions should be followed:

1) IgM, IgG and PCR  test for Zika virus.

2) Acute serum (taken within 5 days of symptom onset) and convalescent serum (2–3 weeks later) should be taken. The two samples are important to rule out false positive tests due to cross reactivity with similar viruses such as Dengue17

3) Provide overseas travel details and clinical history including the onset day and patient’s DHB.  Onset date is extremely important to ensure that the most appropriate test is performed.18

4) The local laboratory will forward samples to ESR who will arrange testing at an Australian Arbovirus Reference Laboratory (no labs in NZ currently test for Zika virus).Note: there is currently no particular action expected following Zika virus confirmation. 19



To eliminate and control the mosquito, it is recommended to:

1)   Avoid allowing standing water in outdoor containers (flower pots, bottles, and containers that collect water) so that they do not become mosquito breeding sites.

2)   Cover domestic water tanks so that mosquitoes cannot get in.

3)   Avoid accumulating garbage: Put it in closed plastic bags and keep it in closed containers.

4)   Unblock drains that could accumulate standing water21.

5)   Use screens and mosquito nets in windows and doors to reduce contact between mosquitoes and people. To prevent mosquito bites, it is recommended that people who live in areas where there are cases of the disease, as well as travelers and, especially, pregnant women should:

6)   Cover exposed skin with long-sleeved shirts, trousers, and hats

7)   Use repellents recommended by the health authorities (and apply them as indicated on the label)

8)   leep under mosquito nets.

9)   People with symptoms of Zika, dengue, or chikungunya should visit a health center22.



Zika virus disease is usually relatively mild and requires no specific treatment. People sick with Zika virus should get plenty of rest, drink enough fluids, and treat pain and fever with common medicines. If symptoms worsen, they should seek medical care and advice. There is currently no vaccine available23


New Link Between Zika Virus and Microcephaly:

some of the evidence  was  identified that there is a direct link between the debilitating birth defect and the Zika virus24 .Researchers here tested the spinal fluid of 12 babies with microcephaly, all of whom were born to mothers who reported having symptoms of Zika early in their pregnancies25 .Brazilian researchers later found traces of the virus in the amniotic fluid and the brain tissue of a small number of microcephaly babies26. if a baby had been infected with the Zika virus by looking for a specific antibody in the baby’s cerebral-spinal fluid27 They tested samples of 12 babies whose spinal fluid had been collected shortly after birth. They all tested positive.28 .This test works better than others because it is looking for an antibody called immunoglobulin M, the largest antibody humans produce. It is too large to pass from mother to child, so researchers can be confident that it is an antibody produced by the baby — and can therefore infer that the baby was infected with Zika while en utero.29 .It indicates the virus is making its way into the nervous system, and the baby’s immune system is battling it there30 .And second, while immunoglobulin M disappears from the blood stream within weeks of an infection, it remains present in the cerebrospinal fluid for months or longer. This means the antibody can be detected at birth31 that the virus attack stem cells during early brain development while also causing the general destruction of other brain tissue.


Two ways to Prevent Zika Virus:

The first uses strands of DNA that belong to the Zika virus32. While these so-called recombinant DNA vaccines are easier to create, they don’t always produce a strong enough immune response.33.The second is an inactivated version of the Zika virus, which means the virus is unable to replicate and cause infection, but it is still able to trigger an immune response. Experts believe that this type of vaccine stands a better chance of sucess 34



The Zika virus vaccine developed by Bharat Biotech International Limited, Hyderabad goes well beyond the prime minister's catchy slogans as it is truly a 'made in India'35 by Indians moment and the patent on the product is also Indian .Ella's company also partnered with Indian government to make the first-ever Indian-made vaccine called 'Rotavac', a vaccine against an infectious diarrhoea disease caused by Rota virus that afflicts children36. Bharat Biotech's vaccines now christened 'Zikavac' are ready for pre-clinical trials, this makes these two vaccines head and shoulders ahead of the other international efforts which are still literally efforts on the drawing board.37



The overall review about the microcephaly link between the new born babies are consist of it is spread rapidly in southern America and also spreading all over the world. The most common symptoms are fever,joint paint,rashes .And this can be diagnoised by IgM,IgG, PCR test.



 Spreading of Zika virus can be controlled only by prevention.since there is no vaccine scientist of bharath biotechnology in Hyderabad was invented two vaccines called ‘Rotavac’ and “Zikavac”.these are the two vaccine that prevent the zika vaccines.



1.     "Zika Virus". Division of Vector-Borne Diseases (DVBD), National Center for Emerging and Zoonotic Infectious Diseases (NCEZID). Centers for Disease Control and Prevention. 19 January 2016.

2.     "Zika virus". NCBI Taxonomy Browser. 64320.

3.     Schmaljohn, Alan L.; McClain, David (1996). "54. Alphaviruses (Togaviridae) and Flaviviruses (Flaviviridae)". In Baron, Samuel. Medical Microbiology (4th ed.). ISBN 0-9631172-1-1. NBK7633.Zika Virus – Centers for Disease Control and Prevention

4.     http://www.nbcdfw.com/news/health/Zika-Virus-Confirmed-in-Dallas-County-Spread-Through-Sexual-Contact-Dallas-County-Health-367395911.html

5.     http://www.dallascounty.org/department/hhs/press/documents/PR2-2-16DCHHSReportsFirstCaseofZikaVirusThroughSexualTransmission.pdf

6.     Knipe, David M.; Howley, Peter M. (2007). Fields' Virology (5th ed.). Lippincott Williams and Wilkins. pp. 1156, 1199. ISBN 978-0-7817-6060-7.

7.     Faye, Oumar; Freire, Caio C. M.; Iamarino, Atila; Faye, Ousmane; de Oliveira, Juliana Velasco C.; Diallo, Mawlouth; Zanotto, Paolo M. A.; Sall, Amadou Alpha; Bird, Brian (9 January 2014).

8.     "Molecular Evolution of Zika Virus during Its Emergence in the 20th Century".PLoS Neglected Tropical Diseases (1): e2636.doi:10.1371/journal.pntd.0002636. PMC 3888466.PMID 24421913.

9.     Freire, Caio Cesar de Melo; Iamarino, Atila; Neto, Daniel Ferreira de Lima; Sall, Amadou Alpha; Zanotto, Paolo Marinho de Andrade (25 November 2015)."Spread of the pandemic Zika virus lineage is associated with NS1 codon usage adaptation in humans" (PDF).BioRxiv: 032839. doi:10.1101/032839.

10.   World Health Organization Zika Virus Fact Sheet.

11.   Grard G, Caron M, Mombo IM, Nkoghe D, Mboui Ondo S, Jiolle D, Fontenille D, Paupy C, Leroy EM. Zika virus in Gabon (Central Africa)--2007: a new threat from Aedes albopictus? PLoS Negl Trop Dis. 2014 Feb 6; 8(2):e2681. doi: 10.1371/journal.pntd.0002681. eCollection 2014.

12.   Zammarchi L, Stella G, Mantella A, Bartolozzi D, Tappe D, Günther S, Oestereich L, Cadar D, Muñoz-Fontela C, Bartoloni A, Schmidt-Chanasit J. Zika virus infections imported to Italy: clinical, immunological and virological findings, and public health implications. J Clin Virol. 2015 Feb;63:32-5. doi: 10.1016/j.jcv.2014.12.005.(subscription required)

13.   Kraemer, Moritz UG; Sinka, Marianne E.; Duda, Kirsten A.; Mylne, Adrian QN; Shearer, Freya M.; Barker, Christopher M.; Moore, Chester G.; Carvalho, Roberta G.; Coelho, Giovanini E. (7 July 2015). "The global distribution of the arbovirus vectors Aedes aegypti and Ae. albopictus". ELife 4: e08347. doi:10.7554/eLife.08347.PMC 4493616. PMID 26126267

14.   Foundation, Thomson Reuters. "FACTBOX – Zika virus spreads rapidly through Latin America, Caribbean". news.trust.org. Retrieved26 January 2016.

15.   "Mosquitoes capable of carrying Zika virus found in Washington, D.C.". University of Notre Dame. 2016.

16.   Foundation, Thomson Reuters. "FACTBOX – Zika virus spreads rapidly through Latin America, Caribbean". news.trust.org. Retrieved26 January 2016.

17.   Zika virus infection in a traveller returning from the Maldives, June 2015.Korhonen EM, Huhtamo E, Smura T, Kallio-Kokko H, Raassina M, VapalahtiO.Euro Surveill. 2016 Jan 14;21(2). doi: 10.2807/1560-7917.ES.2016.21.2.30107. PMID:26764427

18.   Autophagy and viral diseases transmitted by Aedes aegypti and Aedes albopictus.Carneiro LA, Travassos LH. Microbes Infect. 2016 Jan 14. pii: S1286-4579(16)00004-6. doi: 10.1016/j.micinf.2015.12.006. [Epub ahead of print] PMID:26774331.

19.   Zika virus: a previously slow pandemic spreads rapidly through the Americas.Gatherer D, Kohl A.J Gen Virol. 2015 Dec 18. doi: 10.1099/jgv.0.000381. [Epub ahead of print] PMID:26684466

20.   Zika virus information from the World Health Organization.

21.   Factsheet for health professionals - European Centre for Disease Prevention and Control.

22.   Zika Virus Outside Africa - Centers for Disease Control and Prevention.

23.   "Mosquitoes capable of carrying Zika virus found in Washington, D.C.". University of Notre Dame. 2016.

24.   Foy, B. D.; Kobylinski, K. C.; Foy, J. L. C.; Blitvich, B. J.; Travassos Da Rosa, A.; Haddow, A. D.; Lanciotti, R. S.; Tesh, R. B. (2011)."Probable Non–Vector-borne Transmission of Zika Virus, Colorado, USA". Emerging Infectious Diseases 17 (5): 880–

25.   Ophthalmological findings in infants with microcephaly and presumable intra-uterus Zika virusinfection Ventura CV, Maia M, Ventura BV, Linden VV, Araújo EB, Ramos RC, Rocha MA, Carvalho MD, Belfort R Jr, Ventura LO.Arq Bras Oftalmol. 2016 Feb;79(1):1-3. doi: 10.5935/0004-2749.20160002.PMID: 26840156.

26.   Zika virus intrauterine infection causes fetal brain abnormality and microcephaly: tip of the iceberg?Oliveira Melo AS, Malinger G, Ximenes R, Szejnfeld PO, Alves Sampaio S, Bispo de Filippis AM.Ultrasound Obstet Gynecol. 2016 Jan;47(1):6-7. doi: 10.1002/uog.15831. No abstract available. PMID:26731034.

27.   Zika virus in Brazil and macular atrophy in a child with microcephaly.Ventura CV, Maia M, Bravo-Filho V, Góis AL, Belfort R Jr. Lancet. 2016 Jan 16;387(10015):228. doi: 10.1016/S0140-6736(16)00006-4. Epub 2016 Jan 8. No abstract available. PMID:26775125.

28.   Interim Guidelines for the Evaluation and Testing of Infants with Possible Congenital Zika VirusInfection - United States, 2016.

 Staples JE, Dziuban EJ, Fischer M, Cragan JD, Rasmussen SA, Cannon MJ, Frey MT, Renquist CM, Lanciotti RS, Muñoz JL, Powers AM, Honein MA, Moore CA.MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):63-7. doi: 10.15585/mmwr.mm6503e3. PMID:26820387.

29.   Interim Guidelines for Pregnant Women During a Zika Virus Outbreak - United States, 2016. Petersen EE, Staples JE, Meaney-Delman D, Fischer M, Ellington SR, Callaghan WM, Jamieson DJ.MMWR Morb Mortal Wkly Rep. 2016 Jan 22;65(2):30-3. doi: 10.15585/mmwr.mm6502e1. PMID:26796813.

30.   Interim Guidelines for the Evaluation and Testing of Infants with Possible Congenital Zika VirusInfection - United States, 2016.

 Staples JE, Dziuban EJ, Fischer M, Cragan JD, Rasmussen SA, Cannon MJ, Frey MT, Renquist CM, Lanciotti RS, Muñoz JL, Powers AM, Honein MA, Moore CA.MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):63-7. doi: 10.15585/mmwr.mm6503e3. PMID:26820387.

31.   Vogel, Gretchen (3 December 2015). "Fast-spreading virus may cause severe birth defects". Science News. AAAS.doi:10.1126/science.aad7527

32.   Maron, Dina Fine (February 2, 2016). "First Case of U.S. Transmission in Ongoing Zika Outbreak Announced in Texas".Scientific American. Retrieved 2016-02-03.

33.   Vogel, Gretchen (3 December 2015). "Fast-spreading virus may cause severe birth defects". Science News. AAAS.doi:10.1126/science.aad7527.

34.   "Epidemiological update: Outbreaks of Zika virus and complications potentially linked to the Zika virus infection". European Centre for Disease Prevention and Control. Retrieved 18 January 2016.

35.   "For Health Care Providers: Clinical Evaluation and Disease". Zika Virus. DVBD, NCEZID, Centers for Disease Control and Prevention. 19 January 2016.

36.   "WHO – ratio of zika virus in infants. World Health Organization.

37.   articles.economictimes.indiatimes.com › Collections › Virus






Received on 16.08.2016          Modified on 12.09.2016

Accepted on 12.10.2016        © RJPT All right reserved

Research J. Pharm. and Tech. 2017; 10(1): 337-340.

DOI: 10.5958/0974-360X.2017.00068.3