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. 2016 May 31;11(5):e0156376. doi: 10.1371/journal.pone.0156376

Table 11. Complications reported to be associated with ZIKV infection in 35 case reports/ case series and outbreak reports.

20 reports on birth defects and microcephaly in pregnant women (2013–2016) and 24 on Guillain-Barré syndrome following ZIKV infection (probable and confirmed) during outbreaks in the Pacific Islands and the Americas (2011–2016).

Ref Country Study year Complication N ZIKV confirmed? Description of clinical findings:
Microcephaly and other birth defects potentially associated with ZIKV infection
[148] French Polynesia 2014 Birth Defects: fetal cerebral anomaly 18 4/6 amniotic fluid samples were RT-PCR positive French Polynesia has ~4000 births/year. Retrospective analysis of birth defects involving the central nervous system indicated 18 cases in 2014 (vs. 4 in 2013 and 3 in 2012) where the mothers may have been infected with ZIKV early in pregnancy. Amniotic fluid samples from standard testing procedures showed 4/6 samples were ZIKV positive. Since our search, an additional paper on this set of cases has been published.
[206] Brazil 2015 Birth defects: microcephaly 3 33% mothers had clinical symptoms. No testing done. CT scan and ocular examination showed all infants had unilateral ocular findings: gross macular pigment mottling and foveal reflex loss. Well-defined macular neuroretinal atrophy was detected in one child.
[80] Brazil 2015 Birth defects: microcephaly 8 25% positive amniotic fluid, 75% mothers had clinical symptoms during pregnancy Amniotic fluid positive fetuses (n = 2), note mother’s serum RT-PCR1 was negative: both eyes had cataracts and intraocular calcifications, and one eye was smaller than the other. Fetuses from mothers with clinical symptoms (n = 6): fetal neurosonograms showed 33% cases with cerebellar involvement and 16% with severe arthrogryposis.
[201] Brazil 2015 Birth defects: Microcephaly and ocular defects 29 29 cases 29 infants age 1–6 months. 23/29 mothers had clinical ZIKV infections: 18/29 first trimester, 4/29 second trimester, 1/29 third trimester. 6 had no symptoms of ZIKV; 10 patients had ocular findings and were presumed to have been exposed to ZIKV.
[52] Brazil 2015 Birth defects: Microcephaly 2 2 cases: first and second trimester ZIKV infections Case 1: normal ultrasound at 16wk, ZIKV at 18wk, ultrasound at 21 weeks detected microcephaly, confirmed at 27wk. Baby born at 40wks with head circumference of 30cm. Case 2: ZIKV at 10wk, 22wk ultrasound indicated fetal head <10th percentile, 25wk indicated microcephaly, term delivery neonate presented with severe ventriculomegaly, microphthalmia, cataract, and severe arthrogryposis in the legs and arms. Amniotic fluid positive at 28wks.
[55] Brazil 2015/10 Microcephaly 1 RT-PCR positive on fetal brain sample Mother had ZIKV at 13 weeks gestation. Ultrasound at 14 and 20 weeks were normal. Ultrasound at 29 and 32 weeks showed retardation of growth with normal amniotic fluid and placenta, a head circumference below the second percentile for gestation (microcephaly), moderate ventriculomegaly. Brain structures were blurred, calcifications and no other fetal structural abnormalities. Fetal, umbilical, and uterine blood flows were normal. RT-PCR1 ZIKV positive in the fetal brain sample (6.5×107 viral RNA copies per milligram of tissue).
[202] Brazil 2015/12 Birth defects: Microcephaly and ocular findings 10 10 cases 10 cases had clinical diagnosis of ZIKV vertical infection (mothers 7/10 rash, 6 in 1st trimester) and diagnosed with ophthalmological abnormalities
[234] Brazil 2015/08–2015/10 Birth defects: Microcephaly 35 35 cases. 25/35 severe microcephaly, 17/35 at least one neurologic abnormality. 26/35 mothers recalled a rash during pregnancy: first trimester 21/26 and 5/26 in the second trimester. Pathology: Computed tomography scans and transfontanellar cranial ultrasounds showed a consistent pattern of widespread brain calcifications, ventricular enlargement secondary to cortical/subcortical atrophy, excessive and redundant scalp skin in 11 (31%) cases, also suggests acute intrauterine brain injury, indicating an arrest in cerebral growth.
[235] Brazil up to 2015/11/21 Birth defects: Microcephaly 739 739 cases (1 death) Nov 7, 2015: case definition revised from <33cm to <32cm.
[4,172] Brazil up to 2015/11/30 Birth defects: Microcephaly 1248 1,248 cases (7 deaths) 1,248 cases equates to 99.7/100,000 live births have microcephaly. Brazil noted many affected women appear to have been infected with ZIKV in first trimester (no data)
[236] Brazil up to 2015/12/05 Birth defects: Microcephaly 1761 1761 cases (19 deaths)
[170, 237] Brazil up to 2016/01/31 Birth defects: Microcephaly or CNS malformation 4783 4783 cases (76 deaths) 5/76 deaths were ZIKV positive. Historic average 163/year.
[116,117,238] Brazil 2015/11–2016/02/13 Birth defects: Microcephaly or other CNS involvement 5280 5280 cases (108 deaths) Brazil 2001 to 2014 had an average of 163 microcephaly cases/year. Validation of 1345 cases of microcephaly is complete: 837 discarded, 508 confirmed by 421/462 cases radiological findings and 41/462 ZIKV confirmed infection.
[48] Brazil 2016 Birth defects: Microcephaly 1 1 case 20 year old mother: microcephaly detection at 18 weeks, pregnancy terminated at 32 weeks. Fetal tissues: cerebral cortex, medulla oblongata and cerebrospinal and amniotic fluid ZIKV RT-PCR positive.
[116, 239] Hawaii 2016/01/08 Birth defects: Microcephaly 1 Case of microcephaly, confirmed ZIKV The mother likely acquired ZIKV in Brazil (May 2015) and her newborn acquired the infection in utero.
[240] USA 2015/08/01–2016/02/07 Birth defects: Microcephaly, miscarriage 9 3/9 fetuses ZIKV positive.9/9 mothers ZIKV confirmed. 1st trimester (6/9): 2 miscarriages, 2 terminations, 1 microcephaly case, one not born yet. Trimester 3 (3/9): 3 apparently healthy infants. Travel to American Samoa, Brazil, El Salvador, Guatemala, Haiti, Honduras, Mexico, Puerto Rico. In USA 151/257 pregnancies tested for ZIKV, 8 IgM positive.
Guillain-Barré syndrome (GBS) or other neurological complications potentially associated with ZIKV infection
[116, 117, 170, 172,241,242] Brazil 2015/11 GBS 7 7/10 GBS patients were ZIKV positive 1708 GBS cases (2015) vs. 1439 cases (2014).
[4,116, 117,170,172,237,242] Brazil 2015/05/01–2015/07/13 GBS 42 62% (26/42) were ZIKV positive  
[173] Brazil 2015/02/15-2015/06/25 GBS 24 24 cases of suspect GBS were reported during an outbreak of 14,835 cases of “indeterminate acute exanthematous illness” in Salvador, Brazil (3rd largest city). Confirmation tests not done for ZIKV, chikungunya or dengue.
[116,117, 175,237] Colombia 2015/12/27–2016/01/31 GBS 86 86 cases in 2 months Historic average is 242 GBS /year (20 cases /month).
[117,178,237,242, 243] El Salvador 2015/12–2016/01/09 GBS 46 46–118 GBS cases in 5 weeks (2 deaths) 2014 average was 169 cases/year. Case series 12/22 GBS patients had ZIKV within the 15 days prior to GBS.
[116,117,137,138, 144147, 172,242,244,245] French Polynesia Nov 2013-Feb 2014 GBS 42   42 cases of GBS and increased incidence of neurological complications were reported associated with the ZIKV outbreak in the Pacific Islands. 37/42 GBS cases reported having a viral syndrome 6 (4–10) days before the onset of GBS. GBS symptoms peaked at 6 (4–9) days and by 3 months after discharge, 24 (57%) patients were able to walk without assistance. All GBS patients were hospitalized, median 11days (7–20) (N = 42) and 51 days (16–70) for ICU patients (n = 10).Symptoms: Clinical presentation at hospital admission included generalised muscle weakness (74%), inability to walk (44%), facial palsy (64%), 39 (93%) patients had increased (>0·52 g/L) protein concentration in their CSF, 16 (38%) patients were admitted to ICU and 12 (29%) required respiratory assistance. All cases (100%) received immunoglobulin treatment and one (2%) had plasmapheresis.
[245] French Polynesia Nov 2013-Feb 2014 GBS 42 Case control study: If the ZIKV attack rate in French Polynesia was 66%, the risk of GBS was 0·24/1000 Zika virus infections. Patient and control samples drawn at several time points were examined by RT-PCR, IgM / IgG and PRNT2 reaction. 98% of GBS patients were IgM or IgG positive, 19% cross-reacted with dengue, but 100% were confirmed ZIKV positive by PRNT. Compared to a control group of hospitalized patients, the odds of a GBS patient being ZIKV positive was 59·7 (95% CI 10·4 –+∞); p<0·0001. And for PRNT the odds was 34·1 (95% CI 5·8 –+∞) p<0·0001. No association was detected for dengue test results and GBS.
[223] French Polynesia 2013 GBS 1 Case report, sero-positive Polynesian woman, early 40s had ZIKV symptoms 7 days before neurological symptoms. No past medical history except acute articular rheumatism. Day 0: evaluated for paraesthesia of the four limb extremities. Day 1: admitted to hospital, paraesthesia had evolved into ascendant muscular weakness suggestive of GBS. Day 3: developed tetraparesis predominant in the lower limbs, with paraesthesia of the extremities, diffuse myalgia, and a bilateral, but asymmetric peripheral facial palsy. Deep tendon reflexes absent. No respiratory or deglutition disorders. Chest pain developed related to a sustained ventricular tachycardia, and orthostatic hypotension, both suggestive of dysautonomia. Electromyogram confirmed a diffuse demyelinating disorder, with elevated distal motor latency, elongated F-wave, conduction block and acute denervation, without axonal abnormalities. Day 13: discharged with paraparesis requiring the use of a walking frame, and the facial palsy slowly disappeared. Day 40, able to walk without help and muscular strength score was 85/100.
[181, 237] Martinique 2016/01/21 GBS 6 6/6 GBS cases were ZIKV positive  
[246] New Caledonia 2011/01/01–2014/12/31 GBS 42 42 cases of GBS between 2011–2014 investigated. 42 cases of GBS: incidence 2011 = 2.6 (0.66–4.54)/100000 vs. 2014 = 5.09 (2/49-7.56)/100000 = NOT a significant difference. 13 (30%) cases occurred between March and July 2014 (during ZIKV outbreak), 6 in April 2014. These patients indicated 2 confirmed and 2 suspect ZIKV cases and 4 dengue cases preceded GBS.
[189] Puerto Rico 2015/11/23-2016/01/28 GBS 1 1 ZIKV positive case developed GBS  
[116, 117,170] Suriname 2015/12–2016/01/21 GBS 13 10 GBS (2015) and 3 GBS (2016) Historic average is 4/year. 2/10 2015 cases were ZIKV confirmed.
[214] Suriname 2016/01 immune-mediated thrombocytopenia 1 ZIKV positive patient Developed normal clinical symptoms of ZIKV, and on day 29 diagnosed immune-mediated thrombocytopenia.
[117, 170,175,237] Venezuela 2016/01/01–2016/02/10 GBS and other neurological symptoms 252 252 GBS (3 confirmed) Up to 76% of patients reported clinical symptoms of ZIKV. 65% had comorbidities. 3 cases with other neurological symptoms were ZIKV positive.

1 RT-PCR = reverse transcription-polymerase chain reaction,

2 PRNT = plaque reduction neutralization test