Severity of illness by pregnancy status among laboratory-confirmed SARS-CoV-2 infections occurring in reproductive-aged women in Colombia.

BACKGROUND: Multiple studies have described increased risk of severe coronavirus disease (COVID-19) among pregnant women compared to nonpregnant women. The risk in middle-income countries where the distributions of age groups and preexisting conditions may differ is less known. OBJECTIVES: To determine whether pregnant women with SARS-CoV-2 infection are at increased risk for severe COVID-19 compared to nonpregnant women in Colombia. METHODS: We analysed national surveillance data from Colombia, of women aged 15-44 years with laboratory-confirmed infection with SARS-CoV-2 by molecular or antigen testing, from 6 March 2020 to 12 December 2020. An enhanced follow-up of pregnant women with COVID-19 was established to monitor pregnancy and birth outcomes. RESULTS: Of 371,363 women aged 15-44 years with laboratory-confirmed SARS-CoV-2 infection, 1.5% (n = 5614) were reported as pregnant; among those, 2610 (46.5%) were considered a complete pregnancy for reporting purposes at the time of analysis. Hospitalisation (23.9%) and death (1.3%) occurred more frequently among pregnant symptomatic women compared to nonpregnant symptomatic women (2.9% and 0.3%, respectively). Compared to nonpregnant symptomatic women, pregnant symptomatic women were at increased risk of hospitalisation (adjusted risk ratio [RR] 2.19, 95% confidence interval [CI] 2.07, 2.32) and death (RR 1.82, 95% CI 1.60, 2.07), after adjusting for age, type of health insurance and presence of certain underlying medical conditions. Among complete pregnancies, 55 (2.1%) were pregnancy losses, 72 (2.8%) resulted in term low birthweight infants and 375 (14.4%) were preterm deliveries. CONCLUSIONS: Although pregnant women were infrequently reported with laboratory-confirmed SARS-CoV-2 infection, pregnant symptomatic women with COVID-19 were at increased risk for hospitalisation and death compared to nonpregnant symptomatic women. Almost all infections we reported on were third-trimester infections; ongoing follow-up is needed to determine pregnancy outcomes among women infected earlier in pregnancy. Healthcare providers should counsel pregnant women about preventive measures to protect from SARS-CoV-2 infection and when to seek care.

Clinical and neurodevelopmental outcomes based on brain imaging studies in a Colombian cohort of children with probable antenatal Zika virus exposure.

BACKGROUND: Our aim was to describe the neuroimaging and clinical evaluations of children with antenatal Zika-virus (ZIKV) exposure. METHODS: The Colombian National Institute of Health performed serial clinical evaluations of children with probable antenatal ZIKV exposure (i.e., born to ZIKV symptomatic mothers or born with birth defects compatible with ZIKV infection, regardless of laboratory results) over 2 years that included head circumference (HC), eye examination, and neurodevelopmental assessments. Clinical neuroimaging studies (head computed tomography and/or brain magnetic resonance imaging) were analyzed for abnormalities, two-dimensional measurements were made of the right and left frontal and occipital cortical thickness. Two abnormal patterns were defined: Pattern 1 (sum of four areas of cortex <6 cm) and Pattern 2 (sum of four areas of cortex ≥6 cm and < 10 cm). RESULTS: Thirty-one children had a neuroimaging study; in 24, cortical thickness was measured. The median age at the first visit was 8 (range: 6-9) months and 22 (range: 19-42) months at the last evaluation. In the 24 cases with cortical measurements, three were normal, 12 were in Pattern 1, and nine were in Pattern 2. Children within Pattern 1 had lower mean HC at birth and in follow-up (both p < .05) and a higher frequency of structural eye abnormalities (p < .01). A trend towards poorer neuromotor development was seen in Pattern 1, although not statistically significant (p = .06). CONCLUSION: Brain imaging classification based on cortical measurements correlate with ophthalmologic abnormalities and HC. Cortical thickness may be a marker for clinical outcomes in children with congenital ZIKV infection.

Epidemiology of cytomegalovirus Infection among mothers and infants in Colombia.

We assessed maternal and infant cytomegalovirus (CMV) infection in Colombia. Maternal serum was tested for CMV immunoglobulin G antibodies at a median of 10 (interquartile range: 8-12) weeks gestation (n = 1501). CMV DNA polymerase chain reaction was performed on infant urine to diagnose congenital (≤21 days of life) and postnatal (>21 days) infection. Maternal CMV seroprevalence was 98.1% (95% confidence interval [CI]: 97.5%-98.8%). Congenital CMV prevalence was 8.4 (95% CI: 3.9%-18.3%; 6/711) per 1000 live births. Among 472 infants without confirmed congenital CMV infection subsequently tested at age 6 months, 258 (54.7%, 95% CI: 50.2%-59.1%) had postnatal infection.

Cohort profile: congenital Zika virus infection and child neurodevelopmental outcomes in the ZEN cohort study in Colombia.

Zika en Embarazadas y Niños (ZEN) is a prospective cohort study designed to identify risk factors and modifiers for Zika virus (ZIKV) infection in pregnant women, partners, and infants, as well as to assess the risk for adverse maternal, fetal, infant, and childhood outcomes of ZIKV and other congenital infections. ZIKV infection during pregnancy may be associated with longterm sequelae. In the ZEN cohort, 1,519 pregnant women and 287 partners were enrolled from 3 departments within Colombia between February 2017 and January 2018, as well as 1,108 infants born to the pregnant women who were followed to 6 months. The data include baseline questionnaires at enrollment; repeated symptoms and study follow-up questionnaires; the results of lab tests to detect ZIKV and other congenital infections; medical record abstractions; infant physical, eye, and hearing exams; and developmental screening tests. Follow-up of 850 mother-child dyads occurred at 9 months, 12 months, and 18 months with developmental screenings, physical exams, and parent questionnaires. The data will be pooled with those from other prospective cohort studies for an individual participant data meta-analysis of ZIKV infection during pregnancy to characterize pregnancy outcomes and sequelae in children.

Zika Virus Disease and Pregnancy Outcomes in Colombia.

BACKGROUND: In 2015 and 2016, Colombia had a widespread outbreak of Zika virus. Data from two national population-based surveillance systems for symptomatic Zika virus disease (ZVD) and birth defects provided complementary information on the effect of the Zika virus outbreak on pregnancies and infant outcomes. METHODS: We collected national surveillance data regarding cases of pregnant women with ZVD that were reported during the period from June 2015 through July 2016. The presence of Zika virus RNA was identified in a subgroup of these women on real-time reverse-transcriptase-polymerase-chain-reaction (rRT-PCR) assay. Brain or eye defects in infants and fetuses and other adverse pregnancy outcomes were identified among the women who had laboratory-confirmed ZVD and for whom data were available regarding pregnancy outcomes. We compared the nationwide prevalence of brain and eye defects during the outbreak with the prevalence both before and after the outbreak period. RESULTS: Of 18,117 pregnant women with ZVD, the presence of Zika virus was confirmed in 5926 (33%) on rRT-PCR. Of the 5673 pregnancies with laboratory-confirmed ZVD for which outcomes had been reported, 93 infants or fetuses (2%) had brain or eye defects. The incidence of brain or eye defects was higher among pregnancies in which the mother had an onset of ZVD symptoms in the first trimester than in those with an onset during the second or third trimester (3% vs. 1%). A total of 172 of 5673 pregnancies (3%) resulted in pregnancy loss; after the exclusion of pregnancies affected by birth defects, 409 of 5426 (8%) resulted in preterm birth and 333 of 5426 (6%) in low birth weight. The prevalence of brain or eye defects during the outbreak was 13 per 10,000 live births, as compared with a prevalence of 8 per 10,000 live births before the outbreak and 11 per 10,000 live births after the outbreak. CONCLUSIONS: In pregnant women with laboratory-confirmed ZVD, brain or eye defects in infants or fetuses were more common during the Zika virus outbreak than during the periods immediately before and after the outbreak. The frequency of such defects was increased among women with a symptom onset early in pregnancy. (Funded by the Colombian Instituto Nacional de Salud and the Centers for Disease Control and Prevention.).

Etiology of Microcephaly and Central Nervous System Defects during the Zika Epidemic in Colombia.

OBJECTIVE: To estimate the prevalence of microcephaly and central nervous system (CNS) defects during the Zika virus (ZIKV) epidemic in Colombia and proportion attributable to congenital ZIKV infection. STUDY DESIGN: Clinical and laboratory data for cases of microcephaly and/or CNS defects reported to national surveillance between 2015 and 2017 were reviewed and classified by a panel of clinical subject matter experts. Maternal and fetal/infant biologic specimens were tested for congenital infection and chromosomal abnormalities. Infants/fetuses with microcephaly and/or CNS defects (cases) were classified into broad etiologic categories (teratogenic, genetic, multifactorial, and unknown). Cases classified as potentially attributable to congenital ZIKV infection were stratified by strength of evidence for ZIKV etiology (strong, moderate, or limited) using a novel strategy considering birth defects unique or specific to ZIKV or other infections and laboratory evidence. RESULTS: Among 858 reported cases with sufficient information supporting a diagnosis of microcephaly or CNS defects, 503 were classified as potentially attributable to congenital ZIKV infection. Of these, the strength of evidence was considered strong in 124 (24.7%) cases; moderate in 232 (46.1%) cases; and limited in 147 (29.2%). Of the remaining, 355 (41.4%) were attributed to etiologies other than ZIKV infection (syphilis, toxoplasmosis, rubella, cytomegalovirus, herpes 1 and herpes 2 viruses only, n = 32 [3.7%]; genetic, n = 16 [1.9%]; multifactorial, n = 42 [4.9%]; unknown, n = 265 [30.9%]). CONCLUSIONS: Fifty-eight percent of cases of microcephaly and/or CNS defects were potentially attributable to congenital ZIKV infection; however, the strength of evidence varied considerably. This surveillance protocol might serve as a model approach for investigation and etiologic classification of complex congenital conditions.

Zika virus detection in amniotic fluid and Zika-associated birth defects.

BACKGROUND: Zika virus infection during pregnancy can cause serious birth defects, which include brain and eye abnormalities. The clinical importance of detection of Zika virus RNA in amniotic fluid is unknown. OBJECTIVE: The purpose of this study was to describe patterns of Zika virus RNA testing of amniotic fluid relative to other clinical specimens and to examine the association between Zika virus detection in amniotic fluid and Zika-associated birth defects. Our null hypothesis was that Zika virus detection in amniotic fluid was not associated with Zika-associated birth defects. STUDY DESIGN: We conducted a retrospective cohort analysis of women with amniotic fluid specimens submitted to Colombia's National Institute of Health as part of national Zika virus surveillance from January 2016 to January 2017. Specimens (maternal serum, amniotic fluid, cord blood, umbilical cord tissue, and placental tissue) were tested for the presence of Zika virus RNA with the use of a singleplex or multiplex real-time reverse transcriptase-polymerase chain reaction assay. Birth defect information was abstracted from maternal prenatal and infant birth records and reviewed by expert clinicians. Chi-square and Fisher's exact tests were used to compare the frequency of Zika-associated birth defects (defined as brain abnormalities [with or without microcephaly, but excluding neural tube defects and their associated findings] or eye abnormalities) by frequency of detection of Zika virus RNA in amniotic fluid. RESULTS: Our analysis included 128 women with amniotic fluid specimens. Seventy-five women (58%) had prenatally collected amniotic fluid; 42 women (33%) had amniotic fluid collected at delivery, and 11 women (9%) had missing collection dates. Ninety-one women had both amniotic fluid and other clinical specimens submitted for testing, which allowed for comparison across specimen types. Of those 91 women, 68 had evidence of Zika virus infection based on detection of Zika virus RNA in ≥1 specimen. Testing of amniotic fluid that was collected prenatally or at delivery identified 39 of these Zika virus infections (57%; 15 [22%] infections were identified only in amniotic fluid), and 29 infections (43%) were identified in other specimen types and not amniotic fluid. Among women who were included in the analysis, 89 had pregnancy outcome information available, which allowed for the assessment of the presence of Zika-associated birth defects. Zika-associated birth defects were significantly (P<.05) more common among pregnancies with Zika virus RNA detected in amniotic fluid specimens collected prenatally (19/32 specimens; 59%) than for those with no laboratory evidence of Zika virus infection in any specimen (6/23 specimens; 26%), but the proportion was similar in pregnancies with only Zika virus RNA detected in specimens other than amniotic fluid (10/23 specimens; 43%). Although Zika-associated birth defects were more common among women with any Zika virus RNA detected in amniotic fluid specimens (ie, collected prenatally or at delivery; 21/43 specimens; 49%) than those with no laboratory evidence of Zika virus infection (6/23 specimens; 26%), this comparison did not reach statistical significance (P=.07). CONCLUSION: Testing of amniotic fluid provided additional evidence for maternal diagnosis of Zika virus infection. Zika-associated birth defects were more common among women with Zika virus RNA that was detected in prenatal amniotic fluid specimens than women with no laboratory evidence of Zika virus infection, but similar to women with Zika virus RNA detected in other, nonamniotic fluid specimen types.

Long-term outcomes of Guillain-Barré syndrome possibly associated with Zika virus infection.

BACKGROUND: This prospective cohort investigation analyzed the long-term functional and neurologic outcomes of patients with Zika virus-associated Guillain-Barré syndrome (GBS) in Barranquilla, Colombia. METHODS: Thirty-four Zika virus-associated GBS cases were assessed a median of 17 months following acute GBS illness. We assessed demographics, results of Overall Disability Sum Scores (ODSS), Hughes Disability Score (HDS), Zung Depression Scale (ZDS), and Health Related Quality of Life (HRQL) questionnaires; and compared outcomes indices with a normative sample of neighborhood-selected control subjects in Barranquilla without GBS. RESULTS: Median age at time of acute neurologic onset was 49 years (range, 10-80); 17 (50%) were male. No deaths occurred. At long-term follow-up, 25 (73%) patients had a HDS 0-1, indicating complete / near complete recovery. Among the group, HDS (mean 1.4, range 0-4), ODSS (mean 1.9, range 0-9) and ZDS score (mean 34.4, range 20-56) indicated mild / moderate ongoing disability. Adjusting for age and sex, Zika virus-associated GBS cases were similar to a population comparison group (n = 368) in Barranquilla without GBS in terms of prevalence of physical or mental health complaints, though GBS patients were more likely to have an ODSS of ≥ 1 (OR 8.8, 95% CI 3.2-24.5) and to suffer from moderate / moderate-severe depression (OR 3.89, 95% CI 1.23-11.17) than the comparison group. CONCLUSIONS: Long-term outcomes of Zika virus-associated GBS are consistent with those associated with other antecedent antigenic stimuli in terms of mortality and ongoing long-term morbidity, as published in the literature. Persons with Zika virus-associated GBS more frequently reported disability and depression after approximately one year compared with those without GBS.

Use of the Staged Development Tool for Assessing, Planning, and Measuring Progress in the Development of National Public Health Institutes.

The Staged Development Tool (SDT) was created to help national public health institutes (NPHIs) assess their current capacity and develop roadmaps for achieving a higher level of functioning. This article discusses the current use of the SDT by national public health institutes to establish baseline capacity and inform strategic planning and its proposed use in a 3-step sequence for measuring the impact of capacity-building interventions over time. The article also includes descriptions of how national public health institutes have been using the SDT to assess their baseline capacity in management issues and core public health functions. The first use of the SDT by a national public health institute provides essential baseline information on their capacities and levels of functioning and plans for addressing gaps. By repeating the SDT after time for the plans to be implemented, the SDT can be used to evaluate changes in capacity and the effectiveness of the interventions made. Because the SDT is built to be complementary to existing assessments and public health strengthening tools and guidelines, implementing the SDT provides concrete, complementary information that can help countries achieve global health security goals and address current and future threats to public health.

Zika virus disease-associated Guillain-Barré syndrome-Barranquilla, Colombia 2015-2016.

BACKGROUND: An outbreak of Guillain-Barré syndrome (GBS), a disorder characterized by acute, symmetric limb weakness with decreased or absent deep-tendon reflexes, was reported in Barranquilla, Colombia, after the introduction of Zika virus in 2015. We reviewed clinical data for GBS cases in Barranquilla and performed a case-control investigation to assess the association of suspect and probable Zika virus disease with GBS. METHODS: We used the Brighton Collaboration Criteria to confirm reported GBS patients in Barranquilla during October 2015-April 2016. In April 2016, two neighborhood and age range-matched controls were selected for each confirmed GBS case-patient. We obtained demographics and antecedent symptoms in the 2-month period before GBS onset for case-patients and the same period for controls. Sera were collected for Zika virus antibody testing. Suspected Zika virus disease was defined as a history of rash and ≥2 other Zika-related symptoms (fever, arthralgia, myalgia, or conjunctivitis). Probable Zika virus disease was defined as suspected Zika virus disease with laboratory evidence of a recent Zika virus or flavivirus infection. Conditional logistic regression adjusted for sex and race/ethnicity was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: We confirmed 47 GBS cases. Incidence increased with age (10-fold higher in those ≥60years versus those <20years). We interviewed 40 case-patients and 79 controls. There was no significant difference in laboratory evidence of recent Zika virus or flavivirus infection between case-patients and controls (OR: 2.2; 95% CI: 0.9-5.1). GBS was associated with having suspected (OR: 3.0, 95% CI: 1.1-8.6) or probable Zika virus disease (OR: 4.6, CI: 1.1-19.0). CONCLUSIONS: Older individuals and those with suspected and probable Zika virus disease had higher odds of developing GBS. KEY POINTS: We confirmed a Guillain-Barré syndrome (GBS) outbreak in Barranquilla, Colombia, during October 2015-April 2016. A case-control investigation using neighborhood controls showed an association of suspected and probable Zika virus disease with GBS.

Severe Neurologic Disorders in 2 Fetuses with Zika Virus Infection, Colombia.

We report the results of pathologic examinations of 2 fetuses from women in Colombia with Zika virus infection during pregnancy that revealed severe central nervous system defects and potential associated abnormalities of the eye, spleen, and placenta. Amniotic fluid and tissues from multiple fetal organs tested positive for Zika virus.

Guillain-Barré Syndrome Associated with Zika Virus Infection in Colombia.

BACKGROUND: Zika virus (ZIKV) infection has been linked to the Guillain-Barré syndrome. From November 2015 through March 2016, clusters of cases of the Guillain-Barré syndrome were observed during the outbreak of ZIKV infection in Colombia. We characterized the clinical features of cases of Guillain-Barré syndrome in the context of this ZIKV infection outbreak and investigated their relationship with ZIKV infection. METHODS: A total of 68 patients with the Guillain-Barré syndrome at six Colombian hospitals were evaluated clinically, and virologic studies were completed for 42 of the patients. We performed reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assays for ZIKV in blood, cerebrospinal fluid, and urine, as well as antiflavivirus antibody assays. RESULTS: A total of 66 patients (97%) had symptoms compatible with ZIKV infection before the onset of the Guillain-Barré syndrome. The median period between the onset of symptoms of ZIKV infection and symptoms of the Guillain-Barré syndrome was 7 days (interquartile range, 3 to 10). Among the 68 patients with the Guillain-Barré syndrome, 50% were found to have bilateral facial paralysis on examination. Among 46 patients in whom nerve-conduction studies and electromyography were performed, the results in 36 patients (78%) were consistent with the acute inflammatory demyelinating polyneuropathy subtype of the Guillain-Barré syndrome. Among the 42 patients who had samples tested for ZIKV by RT-PCR, the results were positive in 17 patients (40%). Most of the positive RT-PCR results were in urine samples (in 16 of the 17 patients with positive RT-PCR results), although 3 samples of cerebrospinal fluid were also positive. In 18 of 42 patients (43%) with the Guillain-Barré syndrome who underwent laboratory testing, the presence of ZIKV infection was supported by clinical and immunologic findings. In 20 of these 42 patients (48%), the Guillain-Barré syndrome had a parainfectious onset. All patients tested were negative for dengue virus infection as assessed by RT-PCR. CONCLUSIONS: The evidence of ZIKV infection documented by RT-PCR among patients with the Guillain-Barré syndrome during the outbreak of ZIKV infection in Colombia lends support to the role of the infection in the development of the Guillain-Barré syndrome. (Funded by the Bart McLean Fund for Neuroimmunology Research and others.).