Clinical spectrum of congenital Zika virus infection in Brazil: Update and issues for research development.

This review aimed to provide an update on the morphological and/or functional abnormalities related to congenital Zika virus (ZIKV) infection, based on primary data from studies conducted in Brazil since 2015. During the epidemic years (2015-2016), case series and pediatric cohort studies described several birth defects, including severe and/or disproportionate microcephaly, cranial bone overlap, skull collapse, congenital contractures (arthrogryposis and/or clubfoot), and visual and hearing abnormalities, as part of the spectrum of Congenital Zika Syndrome (CZS). Brain imaging abnormalities, mainly cortical atrophy, ventriculomegaly, and calcifications, serve as structural markers of CZS severity. Most case series and cohorts of microcephaly have reported the co-occurrence of epilepsy, dysphagia, orthopedic deformities, motor function impairment, cerebral palsy, and urological impairment. A previous large meta-analysis conducted in Brazil revealed that a confirmed ZIKV infection during pregnancy was associated with a 4% risk of microcephaly. Additionally, one-third of children showed at least one abnormality, predominantly identified in isolation. Studies examining antenatally ZIKV-exposed children without detectable abnormalities at birth reported conflicting neurodevelopmental results. Therefore, long-term follow-up studies involving pediatric cohorts with appropriate control groups are needed to address this knowledge gap. We recognize the crucial role of a national network of scientists collaborating with international research institutions in understanding the lifelong consequences of congenital ZIKV infection. Additionally, we highlight the need to provide sustainable resources for research and development to reduce the risk of future Zika outbreaks.

Survival and mortality profile among people living with HIV in a cohort in the Northeastern region of Brazil.

Conditions related to the acquired immune deficiency syndrome (AIDS) are still a significant cause of morbidity and mortality among people living with HIV (PLHIV). Longer survival in this population were reported to increase the risk of developing noncommunicable chronic diseases (NCDs). This study aimed to estimate the survival and causes of death according to age group and sex among PLHIV monitored at two referral centers in the Northeastern Brazil. This is a prospective, retrospective cohort with death records from 2007 to 2018, based on a database that registers causes of death using the International Classification of Disease (ICD-10), which were subsequently coded following the Coding Causes of Death in HIV (CoDe). A total of 2,359 PLHIV participated in the study, with 63.2% being men, with a follow-up period of 13.9 years. Annual mortality rate was 1.46 deaths per 100 PLHIV (95% CI: 1.33 - 1.60) with a frequency of 20.9%. Risk of death for men increased by 49% when compared to women, and the risk of death in PLHIV increased by 51% among those aged 50 years and over at the time of diagnosis. It was observed that 73.5% accounted for AIDS-related deaths, 6.9% for non-AIDS defining cancer, 6.3% for external causes, and 3.2% for cardiovascular diseases. Among the youngest, 97.2% presented an AIDS-related cause of death. Highest frequency of deaths from neoplasms was among women and from external causes among men. There is a need for health services to implement strategies ensuring greater adherence to treatment, especially among men and young people. Moreover, screening for chronic diseases and cancer is essential, including the establishment of easily accessible multidisciplinary care centers that can identify and address habits such as illicit drug use and alcoholism, which are associated with violent deaths.

Feeding characteristics and growth among children with prenatal exposure to Zika virus with and without microcephaly in the microcephaly epidemic research group pediatric cohort.

OBJECTIVE: To describe the feeding characteristics and growth of children with prenatal exposure to Zika virus (ZIKV) from birth to 48 months. DESIGN: Using data from the prospective Microcephaly Epidemic Research Group Pediatric Cohort (MERG-PC), children without microcephaly born to mothers with evidence of ZIKV infection during pregnancy (ZIKV-exposed children without microcephaly) and children with Zika-related microcephaly were compared using repeated cross-sectional analyses within the following age strata: birth; 1 to 12; 13 to 24; 25 to 36; and 37 to 48 months. The groups were compared in relation to prematurity, birth weight, breastfeeding, alternative feeding routes, dysphagia and anthropometric profiles based on the World Health Organization Anthro z-scores (weight-length/height, weight-age, length/height-age and BMI-age). RESULTS: The first assessment included 248 children, 77 (31.05%) with microcephaly and 171 (68.95%) without microcephaly. The final assessment was performed on 86 children. Prematurity was 2.35 times higher and low birth weight was 3.49 times higher in children with microcephaly. The frequency of breastfeeding was high (> 80%) in both groups. On discharge from the maternity hospital, the frequency of children requiring alternative feeding route in both groups was less than 5%. After 12 months of age, children with microcephaly required alternative feeding route more often than children without microcephaly. In children with microcephaly, the z-score of all growth indicators was lower than in children without microcephaly. CONCLUSIONS: Children with Zika-related microcephaly were more frequently premature and low birth weight and remained with nutritional parameters, i.e., weight-for-age, weight-for-length/height and length/height-for-age below those of the children without microcephaly.

The trajectories of CD4 T lymphocytes over time in patients who have defaulted on treatment for tuberculosis in a cohort of people living with HIV, Recife/PE.

BACKGROUND: The CD4 T lymphocyte count in people living with HIV (PLHIV) is a predictor for the progression of the disease (AIDS), survival and response to antiretroviral treatment (ART). A CD4 T lymphocyte count of less than 200 cells/mm3 is indicative of a greater risk for the onset of opportunistic diseases and death. Defaulting on treatment for tuberculosis (TB) may impact immune recovery in PLHIV who are taking ART. The aim of this study was to investigate an association of the CD4 lymphocyte with TB treatment Trajectory and with death. METHODS: A cohort of PLHIV over eighteen years of age and who were taking ART and who had defaulted on pulmonary TB treatment. Latent Class analysis was used to identify different trajectories of CD4 T lymphocyte counts over time. RESULTS: Latent class 1 (High CD4 trajectory) grouped individuals together who were characterized as maintaining a low probability (0 to 29%) of a CD4 count ≤ 200 cells/mm3over time, while latent class 2 (Low CD4 trajectory) grouped individuals together with a high probability (93% to 60%), and latent class 3 (Fluctuating CD4 trajectory), grouped individuals with a fluctuating probability (66% to 0%). The chance of defaulting on treatment earlier (≤ 90 days) was four times higher in latent class 2 (Low CD4 trajectory). Although there was no statistical significance, there was a higher frequency of deaths in this same latent class. CONCLUSION: Individuals with a high probability of a CD4 count ≤ 200 cells/ mm3 should be monitored in order to avoid treatment default and thereby prevent death. New studies should be conducted with a larger sample size and a longer follow-up time in PLHIV who initiated ART treatment early so as to support clinical decisions for a better understanding of immune behavior.

Clinical spectrum of congenital Zika virus infection in Brazil: Update and issues for research development

ABSTRACT This review aimed to provide an update on the morphological and/or functional abnormalities related to congenital Zika virus (ZIKV) infection, based on primary data from studies conducted in Brazil since 2015. During the epidemic years (2015-2016), case series and pediatric cohort studies described several birth defects, including severe and/or disproportionate microcephaly, cranial bone overlap, skull collapse, congenital contractures (arthrogryposis and/or clubfoot), and visual and hearing abnormalities, as part of the spectrum of Congenital Zika Syndrome (CZS). Brain imaging abnormalities, mainly cortical atrophy, ventriculomegaly, and calcifications, serve as structural markers of CZS severity. Most case series and cohorts of microcephaly have reported the co-occurrence of epilepsy, dysphagia, orthopedic deformities, motor function impairment, cerebral palsy, and urological impairment. A previous large meta-analysis conducted in Brazil revealed that a confirmed ZIKV infection during pregnancy was associated with a 4% risk of microcephaly. Additionally, one-third of children showed at least one abnormality, predominantly identified in isolation. Studies examining antenatally ZIKV-exposed children without detectable abnormalities at birth reported conflicting neurodevelopmental results. Therefore, long-term follow-up studies involving pediatric cohorts with appropriate control groups are needed to address this knowledge gap. We recognize the crucial role of a national network of scientists collaborating with international research institutions in understanding the lifelong consequences of congenital ZIKV infection. Additionally, we highlight the need to provide sustainable resources for research and development to reduce the risk of future Zika outbreaks.

Survival and mortality profile among people living with HIV in a cohort in the Northeastern region of Brazil

ABSTRACT Conditions related to the acquired immune deficiency syndrome (AIDS) are still a significant cause of morbidity and mortality among people living with HIV (PLHIV). Longer survival in this population were reported to increase the risk of developing noncommunicable chronic diseases (NCDs). This study aimed to estimate the survival and causes of death according to age group and sex among PLHIV monitored at two referral centers in the Northeastern Brazil. This is a prospective, retrospective cohort with death records from 2007 to 2018, based on a database that registers causes of death using the International Classification of Disease (ICD-10), which were subsequently coded following the Coding Causes of Death in HIV (CoDe). A total of 2,359 PLHIV participated in the study, with 63.2% being men, with a follow-up period of 13.9 years. Annual mortality rate was 1.46 deaths per 100 PLHIV (95% CI: 1.33 - 1.60) with a frequency of 20.9%. Risk of death for men increased by 49% when compared to women, and the risk of death in PLHIV increased by 51% among those aged 50 years and over at the time of diagnosis. It was observed that 73.5% accounted for AIDS-related deaths, 6.9% for non-AIDS defining cancer, 6.3% for external causes, and 3.2% for cardiovascular diseases. Among the youngest, 97.2% presented an AIDS-related cause of death. Highest frequency of deaths from neoplasms was among women and from external causes among men. There is a need for health services to implement strategies ensuring greater adherence to treatment, especially among men and young people. Moreover, screening for chronic diseases and cancer is essential, including the establishment of easily accessible multidisciplinary care centers that can identify and address habits such as illicit drug use and alcoholism, which are associated with violent deaths.

Sleep in children from northeastern Brazil with congenital Zika syndrome: assessment using polysomnography.

STUDY OBJECTIVES: We performed this study to describe the characteristics of sleep in children with congenital Zika syndrome through polysomnographic assessment. METHODS: Polysomnography with neurological setup and capnography was performed. Respiratory events were scored according to American Academy of Sleep Medicine criteria. Children were classified based on neuroclinical examination as having corticospinal plus neuromuscular abnormalities or exclusively corticospinal abnormalities. Neuroradiological classification was based on imaging exams, with children classed as having supratentorial plus infratentorial abnormalities or exclusively supratentorial abnormalities. RESULTS: Of 65 children diagnosed with congenital Zika syndrome, sleep apnea was present in 23 children (35.4%), desaturation in 26 (40%), and snoring in 13 (20%). The most prevalent apnea type was central in 15 children (65.2%), followed by obstructive apnea in 5 (21.7%) and mixed type in 3 (13%). The average of the lowest saturation recorded was slightly below normal (89.1 ± 4.9%) and the mean partial pressure of end-tidal carbon dioxide value was normal. Periodic leg movements were present in 48 of 65 children. Lower ferritin levels were observed in 84.6% of children. Palatine and pharyngeal tonsils (adenoids) were small in most children and not associated with the presence of obstructive apnea. Ventriculomegaly and subcortical and nucleus calcification were the most frequent neuroimaging findings. Supratentorial and infratentorial anomalies were present in 26.7% (16 of 60) and exclusively supratentorial changes in 73.3% (44 of 60). In the neuroclinical classification, isolated corticospinal changes were more frequent and the mean peak in capnography was lower in this group. There was no difference regarding the presence of apnea for children in the neuroclinical and neuroradiological classification groups. CONCLUSIONS: Sleep disorders were frequent in children with congenital Zika syndrome, with central sleep apnea being the main finding. CITATION: Brandão Marquis V, de Oliveira Melo A, Pradella-Hallinan M, et al. Sleep in children from northeastern Brazil with congenital Zika syndrome: assessment using polysomnography. J Clin Sleep Med. 2023;19(10):1759-1767.

Temporal trend, high-risk spatial and spatiotemporal clustering of leprosy indicators in Brazil: A 20-year ecological and population-based study.

OBJECTIVES: Leprosy still represents a public health concern in Brazil. The country is the only one in America not to reach the global goal of leprosy disease control. Hence, this study aimed to assess the temporal, spatial and space-time patterns of leprosy cases in Brazil of the 20-year time series 2001-2020. METHODS: An ecological and population-based analysis was carried out, applying temporal and spatial techniques, and using the detection coefficient of sociodemographic and clinical-epidemiological variables of leprosy new cases in the 5570 municipalities of Brazil. Temporal trends were assessed using a segmented linear regression model. For spatial analysis, global and local Moran indexes were applied, and space-time scan statistics was used to identify risk clusters. RESULTS: The mean detection coefficient was 19.36/100,000 inhabitants, with a higher occurrence among men (21.29/100,000 inhabitants) and in the 60-69 age group (36.31/100,000). A decreasing temporal trend was observed in the country (annual percentage change: -5.20% per year). The North and Midwest regions were the most affected, exhibiting municipalities with a high/high standard, and with the highest annual percentage increase of multibacillary (MB) cases. Leprosy has a heterogeneous distribution throughout Brazil, but with high-risk spatiotemporal clusters, mainly located in the North and Midwest regions. CONCLUSION: Although Brazil has shown a decreasing temporal trend during the past 20 years, the country is still classified as highly endemic for leprosy, showing an increase in the proportion of new MB cases over the years.

Previous BCG vaccination is associated with less severe clinical progression of COVID-19.

BACKGROUND: BCG vaccination, originally used to prevent tuberculosis, is known to "train" the immune system to improve defence against viral respiratory infections. We investigated whether a previous BCG vaccination is associated with less severe clinical progression of COVID-19 METHODS: A case-control study comparing the proportion with a BCG vaccine scar (indicating previous vaccination) in cases and controls presenting with COVID-19 to health units in Brazil. Cases were subjects with severe COVID-19 (O2 saturation < 90%, severe respiratory effort, severe pneumonia, severe acute respiratory syndrome, sepsis, and septic shock). Controls had COVID-19 not meeting the definition of "severe" above. Unconditional regression was used to estimate vaccine protection against clinical progression to severe disease, with strict control for age, comorbidity, sex, educational level, race/colour, and municipality. Internal matching and conditional regression were used for sensitivity analysis. RESULTS: BCG was associated with high protection against COVID-19 clinical progression, over 87% (95% CI 74-93%) in subjects aged 60 or less and 35% (95% CI - 44-71%) in older subjects. CONCLUSIONS: This protection may be relevant for public health in settings where COVID-19 vaccine coverage is still low and may have implications for research to identify vaccine candidates for COVID-19 that are broadly protective against mortality from future variants. Further research into the immunomodulatory effects of BCG may inform COVID-19 therapeutic research.

Risk of adverse outcomes in offspring with RT-PCR confirmed prenatal Zika virus exposure: An individual participant data meta-analysis of 13 cohorts in the Zika Brazilian Cohorts Consortium.

Background: Knowledge regarding the risks associated with Zika virus (ZIKV) infections in pregnancy has relied on individual studies with relatively small sample sizes and variable risk estimates of adverse outcomes, or on surveillance or routinely collected data. Using data from the Zika Brazilian Cohorts Consortium, this study aims, to estimate the risk of adverse outcomes among offspring of women with RT-PCR-confirmed ZIKV infection during pregnancy and to explore heterogeneity between studies. Methods: We performed an individual participant data meta-analysis of the offspring of 1548 pregnant women from 13 studies, using one and two-stage meta-analyses to estimate the absolute risks. Findings: Of the 1548 ZIKV-exposed pregnancies, the risk of miscarriage was 0.9%, while the risk of stillbirth was 0.3%. Among the pregnancies with liveborn children, the risk of prematurity was 10,5%, the risk of low birth weight was 7.7, and the risk of small for gestational age (SGA) was 16.2%. For other abnormalities, the absolute risks were: 2.6% for microcephaly at birth or first evaluation, 4.0% for microcephaly at any time during follow-up, 7.9% for neuroimaging abnormalities, 18.7% for functional neurological abnormalities, 4.0% for ophthalmic abnormalities, 6.4% for auditory abnormalities, 0.6% for arthrogryposis, and 1.5% for dysphagia. This risk was similar in all sites studied and in different socioeconomic conditions, indicating that there are not likely to be other factors modifying this association. Interpretation: This study based on prospectively collected data generates the most robust evidence to date on the risks of congenital ZIKV infections over the early life course. Overall, approximately one-third of liveborn children with prenatal ZIKV exposure presented with at least one abnormality compatible with congenital infection, while the risk to present with at least two abnormalities in combination was less than 1.0%.

Adherence to antiretroviral therapy and factors associated with non-adherence: a cohort study at two referral services in Brazil.

This cohort study evaluated non-adherence to antiretrovirals at referral services in Pernambuco, Brazil, 2016/2017, through self-report. A generalized mixed-effects model for binary outcomewas used. We assessed 542 participants with an adherence rate of 85.50%. A greater chance of non-adherence was associated with:a low/moderate level of nicotine dependence (OR = 2.79, p = 0.00, IC = 1.44-5.41); ≥7 tablets/day (OR = 6.14, p = 0.00, IC = 3.42-11.02); LPV/r (OR = 1.49, p = 0.6, IC = 0.98-2.26), ddI (OR = 3.34, p = 0.03, IC = 1.12-9.97), ABC (OR = 4.02, p = 0.05, IC = 1.01-16.03), RAL (OR = 2.49, p = 0.01, IC = 1.32-4.70) and DTG (OR = 4.65, p = 0.01, IC = 1.42-15.16); 6-10 year seropositive diagnosis (OR = 2.17, p = 0.01, IC = 1.20-3.92) and symptoms of depression (OR = 1.55, p = 0.03, IC = 1.03-2.33). Protective factors for non-adherence weres: ≥50 years (OR = 0.67, p = 0.06, IC = 0.45-1.01), secondary/higher education (OR = 0.48, p = 0.00, IC = 0.34-0.70), embarrassment at health service (OR = 0.49, p = 0.04, IC = 0.24-0.97), good understanding of antiretrovirals (OR = 0.62, p = 0.03, IC = 0.40-0.96), adverse event (OR = 0.74, p = 0,06, IC = 0.54-1.01), use of TDF (OR = 0.62, p = 0.01, IC = 0.43-0.90), NVP (OR = 0.41, p = 0.05, IC = 0.71-1.00) and EFZ (OR = 0.48, p = 0.01, IC = 0.29-0.80) and good knowledge of HIV/AIDS/ART. (OR = 0.67, p = 0.07, IC = 0.43-1.04). Variables with stronger association were those linked to ART. Systematic use of self-report adherence is recommended for priority groups.

Cortical Auditory Evoked Potentials in Children with Prenatal Exposure to Zika Virus.

Prenatal exposure to ZIKV can cause neurologic and auditory damage. The electrophysiological responses obtained by Cortical Auditory Evoked Potentials (CAEP) may provide an objective method to investigate the function of cortical auditory pathways in children exposed to ZIKV. This case series analyzed the findings of CAEP in prenatal-period ZIKV-exposed children with and without microcephaly. The CAEP was performed in a total of 24 children. Five magnetic resonance imaging (MRI) images of the inner ear and brain of microcephalic children were analyzed and compared with CAEP measurements. Ventriculomegaly (80%), cortical/subcortical calcification (80%), and brain reduction (60%) were the most common alterations in the MRI. The P1-N1-P2 complex of the CAEP was observed in all children evaluated. The peak N2 was absent in two children. In the comparison of the CAEP measurements between the groups, children with microcephaly presented a higher amplitude of P2 (p = 0.017), which may reflect immaturity of the auditory pathways. Microcephalic and normocephalic children with prenatal exposure to ZIKV presented with the mandatory components of the CAEPs, regardless of changes in the CNS, suggesting that this population has, to some extent, the cortical ability to process sound stimuli preserved.

Characteristics of children of the Microcephaly Epidemic Research Group Pediatric Cohort who developed postnatal microcephaly.

The number of studies published on postnatal microcephaly in children with Congenital Zika Syndrome is small, clinical presentations vary and aspects of the evolution of these children remain unclarified. The present case series examined clinical characteristics and assessed the growth velocity of the head circumference, weight and height Z-scores in 23 children who developed postnatal microcephaly during follow-up in the Microcephaly Epidemic Research Group Pediatric Cohort. To estimate the change in the head circumference, weight and height Z-scores over time and compare the mean difference between sexes, we used multilevel mixed-effects linear regressions with child-specific random effects. Among these children, 60.9% (n = 14/23) presented with craniofacial disproportion, 60.9% (n = 14/23) with strabismus, 47.8% (n = 11/23) with early onset seizures, 47.8% (n = 11/23) with dysphagia and 43.5% (n = 10/23) with arthrogryposis. Of the 82.7% (n = 19/23) children who underwent neuroimaging, 78.9% (n = 15/19) presented with alterations in the central nervous system. Monthly growth velocity, expressed in Z-scores, of the head circumference was - 0.098 (95% CI % - 0.117 to - 0.080), of weight was: - 0.010 (95%-CI - 0.033 to 0.014) and of height was: - 0.023 (95%-CI - 0.046 to 0.0001). Postnatal microcephaly occurred mainly in children who had already presented with signs of severe brain damage at birth; there was variability in weight and height development, with no set pattern.

Zika-Related Microcephaly and Its Repercussions for the Urinary Tract: Clinical, Urodynamic, Scintigraphic and Radiological Aspects.

AIMS: Describing the urodynamic parameters of children aged 3 to 5 years with microcephaly related to congenital Zika syndrome and verifying the association with clinical, imaging and neurological characteristics. METHODS: From October 2018 to March 2020, children with Zika-related microcephaly underwent urological, ultrasonographic and urodynamic evaluation. In selected cases, complementary exams such as urethrocystography and scintigraphy were performed. The children also underwent a complete neurological evaluation. To compare frequency between groups, we used Pearson's chi-squared test or Fisher's exact test. RESULTS: This study evaluated 40 children, of whom 85% were 4 years old, and all had abnormalities on the urodynamic study, with low bladder capacity (92.5%) and detrusor overactivity (77.5%) as the most frequent findings. Only three children had ultrasound abnormalities, but no child had cystographic or scintigraphic abnormalities, and the postvoid residual volume was normal in 80% of cases. In spite of a frequency of 67.5% of intestinal constipation, there was no record of febrile urinary tract infection after the first year of life. All children presented severe microcephaly and at least one neurological abnormality in addition to microcephaly. The homogeneity of the children in relation to microcephaly severity and neurological abnormalities limited the study of the association with the urodynamic parameters. CONCLUSIONS: Urodynamic abnormalities in children aged 3 to 5 years with Zika-related microcephaly do not seem to characterize a neurogenic bladder with immediate risks for the upper urinary tract. The satisfactory bladder emptying suggests that the voiding pattern is reflex.

Risk of SARS-CoV-2 infection among front-line healthcare workers in Northeast Brazil: a respondent-driven sampling approach.

OBJECTIVES: We assessed the prevalence of SARS-CoV-2 infection, personal protective equipment (PPE) shortages and occurrence of biological accidents among front-line healthcare workers (HCW). DESIGN, SETTING AND PARTICIPANTS: Using respondent-driven sampling, the study recruited distinct categories of HCW attending suspected or confirmed patients with COVID-19 from May 2020 to February 2021, in the Recife metropolitan area, Northeast Brazil. OUTCOME MEASURES: The criterion to assess SARS-CoV-2 infection among HCW was a positive self-reported PCR test. RESULTS: We analysed 1525 HCW: 527 physicians, 471 registered nurses, 263 nursing assistants and 264 physical therapists. Women predominated in all categories (81.1%; 95% CI: 77.8% to 84.1%). Nurses were older with more comorbidities (hypertension and overweight/obesity) than the other staff. The overall prevalence of SARS-CoV-2 infection was 61.8% (95% CI: 55.7% to 67.5%) after adjustment for the cluster random effect, weighted by network, and the reference population size. Risk factors for a positive RT-PCR test were being a nursing assistant (OR adjusted: 2.56; 95% CI: 1.42 to 4.61), not always using all recommended PPE while assisting patients with COVID-19 (OR adj: 2.15; 95% CI: 1.02 to 4.53) and reporting a splash of biological fluid/respiratory secretion in the eyes (OR adj: 3.37; 95% CI: 1.10 to 10.34). CONCLUSIONS: This study shows the high frequency of SARS-CoV2 infection among HCW presumably due to workplace exposures. In our setting, nursing assistant comprised the most vulnerable category. Our findings highlight the need for improving healthcare facility environments, specific training and supervision to cope with public health emergencies.

Co-circulation of Chikungunya Virus during the 2015-2017 Zika Virus Outbreak in Pernambuco, Brazil: An Analysis of the Microcephaly Epidemic Research Group Pregnancy Cohort.

Co-circulation of arthropod-borne viruses, particularly those with shared mosquito vectors like Zika (ZIKV) and Chikungunya (CHIKV), is increasingly reported. An accurate differential diagnosis between ZIKV and CHIKV is of high clinical importance, especially in the context of pregnancy, but remains challenging due to limitations in the availability of specialized laboratory testing facilities. Using data collected from the prospective pregnancy cohort study of the Microcephaly Epidemic Research Group, which followed up pregnant persons with rash during the peak and decline of the 2015-2017 ZIKV epidemic in Recife, Pernambuco, Brazil, this study aims to describe the geographic and temporal distribution of ZIKV and CHIKV infections and to investigate the extent to which ZIKV and CHIKV infections may be clinically differentiable. Between December 2015 and June 2017, we observed evidence of co-circulation with laboratory confirmation of 213 ZIKV mono-infections, 55 CHIKV mono-infections, and 58 sequential ZIKV/CHIKV infections (i.e., cases with evidence of acute ZIKV infection with concomitant serological evidence of recent CHIKV infection). In logistic regressions with adjustment for maternal age, ZIKV mono-infected cases had lower odds than CHIKV mono-infected cases of presenting with arthralgia (aOR, 99% CI: 0.33, 0.15-0.74), arthritis (0.35, 0.14-0.85), fatigue (0.40, 0.17-0.96), and headache (0.44, 0.19-1.90). However, sequential ZIKV/CHIKV infections complicated discrimination, as they did not significantly differ in clinical presentation from CHIKV mono-infections. These findings suggest clinical symptoms alone may be insufficient for differentiating between ZIKV and CHIKV infections during pregnancy and therefore laboratory diagnostics continue to be a valuable tool for tailoring care in the event of arboviral co-circulation.

A new insight into the definition of microcephaly in Zika congenital syndrome era.

This study aimed to compare the anthropometric measurements and body proportionalities of neonates born before the Zika virus epidemic with those born during this period. We compared 958 neonates born during the pre-Zika epidemic with 264 neonates born during the epidemic period. The newborns had their head circumference, weight, and length classified according to the Fenton & Kim growth chart. We considered disproportionate those individuals that presented microcephaly and adequate weight or length for sex and gestational age, and those whose head circumferences were lower than the ratio ((length / 2) + 9.5) - 2.5cm. We estimated the frequencies of Zika positivity and brain imaging findings among neonates with microcephaly born during the epidemic period, concerning the anthropometric and body proportionality parameters. Low weight and proportionate microcephaly were similar among newborns from both periods. However, the frequencies of newborns with microcephaly with a very low length and disproportionate microcephaly were higher among the neonates of the epidemic period with brain abnormalities and positive for Zika virus. We conclude that, at birth, the disproportion between head circumference and length can be an indicator of the severity of microcephaly caused by congenital Zika.