Cell adhesion proteins in the cerebrospinal fluid of neonates prenatally exposed to Zika virus: A case-control study.

To compare cell adhesion molecules levels in cerebrospinal fluid (CSF) between Zika virus (ZIKV)-exposed neonates with/without microcephaly (cases) and controls, 16 neonates (cases), 8 (50%) with and 8 (50%) without microcephaly, who underwent lumbar puncture (LP) during the ZIKV epidemic (2015-2016) were included. All mothers reported ZIKV clinical symptoms during gestation, all neonates presented with congenital infection findings, and other congenital infections were ruled out. Fourteen control neonates underwent LP in the same laboratory (2017-2018). Five cell adhesion proteins were measured in the CSF using mass spectrometry. Neurexin-1 (3.50 [2.00-4.00] vs. 7.5 [5.00-10.25], P = 0.001), neurexin-3 (0.00 [0.00-0.00] vs. 3.00 [1.50-4.00], P = 0.001) and neural cell adhesion molecule 2 (NCAM2) (0.00 [0.00-0.75] vs. 1.00 [1.00-2.00], P = 0.001) were significantly lower in microcephalic and non-microcephalic cases than in controls. When these two sub-groups of prenatally ZIKA-exposed children were compared to controls separately, the same results were found. When cases with and without microcephaly were compared, no difference was found. Neurexin-3 (18.8% vs. 78.6%, P = 0.001) and NCAM2 (25.0% vs. 85.7%, P = 0.001) were less frequently found among the cases. A positive correlation was found between cephalic perimeter and levels of these two proteins. Neurexin-2 and neurexin-2b presented no significant differences. Levels of three cell adhesion proteins were significantly lower in CSF of neonates exposed to ZIKV before birth than in controls, irrespective of presence of congenital microcephaly. Moreover, the smaller the cephalic perimeter, the lower CSF cell adhesion protein levels. These findings suggest that low CSF levels of neurexin-1, neurexin-3 and NCAM2 may reflect the effects of ZIKV on foetal brain development.

Zika-exposed microcephalic neonates exhibit higher degree of inflammatory imbalance in cerebrospinal fluid.

Not every neonate with congenital Zika virus (ZIKV) infection (CZI) is born with microcephaly. We compared inflammation mediators in CSF (cerebrospinal fluid obtained from lumbar puncture) between ZIKV-exposed neonates with/without microcephaly (cases) and controls. In Brazil, in the same laboratory, we identified 14 ZIKV-exposed neonates during the ZIKV epidemic (2015-2016), 7(50%) with and 7(50%) without microcephaly, without any other congenital infection, and 14 neonates (2017-2018) eligible to be controls and to match cases. 29 inflammation mediators were measured using Luminex immunoassay and multidimensional analyses were employed. Neonates with ZIKV-associated microcephaly presented substantially higher degree of inflammatory perturbation, associated with uncoupled inflammatory response and decreased correlations between concentrations of inflammatory biomarkers. The groups of microcephalic and non-microcephalic ZIKV-exposed neonates were distinguished from the control group (area under curve [AUC] = 1; P < 0.0001). Between controls and those non-microcephalic exposed to ZIKV, IL-1ß, IL-3, IL-4, IL-7 and EOTAXIN were the top CSF markers. By comparing the microcephalic cases with controls, the top discriminant scores were for IL-1ß, IL-3, EOTAXIN and IL-12p70. The degree of inflammatory imbalance may be associated with microcephaly in CZI and it may aid additional investigations in experimental pre-clinical models testing immune modulators in preventing extensive damage of the Central Nervous System.

Cerebrospinal fluid immunoglobulins are increased in neonates exposed to Zika virus during foetal life.

OBJECTIVE: To compare immunoglobulin levels in cerebrospinal fluid (CSF) of neonates exposed to Zika virus (ZIKV) during foetal life (cases) with levels in CSF of control neonates. METHODS: We identified 16 neonates who underwent lumbar puncture (LP), during the ZIKV epidemic (December/2015 to March/2016) whose mothers reported ZIKV clinical symptoms during gestation (cases). Congenital microcephaly was defined as head circumference ≤31.9 cm (boys) and ≤31.5 cm (girls) for term neonates, or ≤2 standard deviations below the mean for premature (<37 weeks) neonates. Subsequently, we identified neonates who underwent LP in the same lab and fulfilled criteria to be controls: age ≤4 days, CSF white blood cell count ≤8/mm3, CSF protein ≤132 mg/dL, CSF red blood cell count ≤1,000/mm3, neither central nervous system illness, nor congenital infection, nor microcephaly. CSF immunoglobulin concentrations were measured by mass spectrometry. RESULTS: 13 controls were included. IgM, IgA, IgG, IgK, and IgL were significantly higher among cases (p < 0.001). Eight (50%) ZIKV exposed infants had congenital microcephaly. These showed the strongest immunoglobulin elevation of the IgM and IgA classes. CONCLUSION: Neonates exposed to ZIKV infection during gestation present with elevated distinct immunoglobulins in CSF, both in cases that developed microcephaly and in cases that did not.

Neuroschistosomiasis due to Schistosoma mansoni: a review of pathogenesis, clinical syndromes and diagnostic approaches.

Neuroschistosomiasis (NS) is the second most common form of presentation of infection by the trematode, Schistosoma mansoni. Granulomatous inflammatory reaction occurs as a result of schistosome eggs being transmitted to spinal cord or brain via the vascular system, or by inadvertent adult worm migration to these organs. The two main clinical syndromes are spinal cord neuroschistosomiasis (acute or subacute myelopathy) and localized cerebral or cerebellar neuroschistosomiasis (focal CNS impairment, seizures, increased intracranial pressure). Presumptive diagnosis of NS requires confirming the presence of S. mansoni infection by stool microscopy or rectal biopsy for trematode eggs, and serologic testing of blood and spinal fluid. The localized lesions are identified by signs and symptoms, and confirmed by imaging techniques (contrast myelography, CT and MRI). Algorithms are presented to allow a stepwise approach to diagnosis.

Neuroschistosomiasis due to Schistosoma mansoni: a review of pathogenesis, clinical syndromes and diagnostic approaches

Neuroesquistossomose (NS) é a segunda forma mais freqüente de apresentação da infecção causada pelo trematódeo Schistosoma mansoni. A inflamação do tipo granulomatosa ocorre como resultado da presença de ovos do S. mansoni que atingiram a medula espinhal ou o encéfalo via o sistema vascular ou pela migração inadvertida de vermes adultos para estes órgãos. Duas síndromes clínicas principais podem ser identificadas: a mielopatia esquistossomótica (aguda ou subaguda) e a neuroesquistossomose cerebral ou cerebelar localizada (comprometimento focal do Sistema Nervoso Central, convulsões, hipertensão intracraniana). O diagnóstico presumido da NS requer a confirmação da presença da infecção por exame microscópico de fezes ou pela biópsia retal em busca de ovos de trematódeo e testes sorológicos no sangue e no líquor. As lesões localizadas são identificadas por sinais e sintomas, e confirmadas por exames de imagem (mielografia contrastada, tomografia computadorizada e ressonância magnética). Algoritmos são apresentados para orientar uma avaliação diagnóstica seqüencial.

Etiology of bacterial meningitis among children aged 2-59 months in Salvador, Northeast Brazil, before and after routine use of Haemophilus influenzae type B vaccine.

OBJECTIVE: To describe the frequency of etiologic agents of bacterial meningitis (BM) among children aged 2-59 months in a sample of patients in Salvador, Northeast Brazil, with emphasis on the frequency of BM of unknown etiology (BMUE), just before, during and after the implementation of routine immunization of infants with Haemophilus influenzae type b (Hib) vaccination. METHOD: Demographic, clinical and cerebrospinal fluid (CSF) information was collected from the chart of every patient, aged 2-59 months, whose CSF exam was performed at the CSF Lab - José Silveira Foundation, between January 1989 and December 2001. Every CSF exam was completely performed according to standard methods. The etiologic diagnosis was based on either culture and/or latex-agglutination test. When the agent was only seen on Gram stained smear, the diagnosis was descriptive. BMUE was defined as: glucose < 40mg / dl, protein > 100 mg / dl, white blood cell count > 20 cells / mm(3), percentage of neutrophils > 80%. RESULTS: Of 1519 patients, 894 (58.9%) had normal exams and BM was diagnosed in 95 (6.2%). Etiologic agents were: Hib (44.2%), meningococcus (13.7%), Gram-negative bacilli (11.6%), Mycobacterium tuberculosis (6.3%), pneumococcus (4.2%), other agents (4.2%); BMUE was diagnosed in 15.8% of cases with BM. By analysing the frequency of BMUE and Hib among all exams performed yearly, the peaks were recorded in 1989 (5.3%) and 1990 (16.9%), respectively, decreasing to 0.7% and 0% in 2001. CONCLUSION: It is possible that the implementation of the conjugate Hib vaccine during the 1990's has been decreasing not only the occurrence of Hib meningitis but also of BMUE.

Etiology of bacterial meningitis among children aged 2-59 months in Salvador, Northeast Brazil, before and after routine use of Haemophilus influenzae type b vaccine

OBJETIVO: Descrever a freqüência dos agentes etiológicos de meningite bacteriana (MB) em amostra das crianças com idade entre 2 e 59 meses, em Salvador, Nordeste do Brasil, com ênfase na freqüência de MB de etiologia indeterminada (MBEI), antes, durante e após a implementação da imunização rotineira de lactentes com vacina para Haemophilus influenzae tipo b (Hib). MÉTODO: Variáveis demográficas, clínicas e liquóricas (LCR) foram coletadas da ficha de cada paciente com idade entre 2 e 59 meses, cujo exame de LCR foi realizado no Laboratório de LCR - Fundação José Silveira, entre janeiro de 1989 e dezembro de 2001. Cada exame de LCR foi realizado por completo conforme os métodos padronizados. O diagnóstico etiológico foi baseado ou em cultura e ou teste de aglutinação em látex. Quando o agente foi identificado apenas no GRAM, o diagnóstico foi descritivo. MBEI foi definida como glicose < 40mg / dl, proteína > 100 mg / dl, celularidade global > 20 células / mm3 e percentual de neutrófilos > 80%. RESULTADOS: Dos 1519 pacientes, 894 (58,9%) tiveram exames normais e MB foi diagnosticada em 95 (6,2%). Os agentes etiológicos foram: Hib (44,2%), meningococo (13,7%), bacilos Gram-negativos (11,6%), Mycobacterium tuberculosis (6,3%), pneumococo (4,2%), outros agentes (4,2%); MBEI foi diagnosticada em 15,8% dos casos de MB. Ao analisar a freqüência da MBEI e por Hib entre todos os exames realizados a cada ano, os picos foram registrados em 1989 (5,3%) e 1990 (16,9%), respectivamente, diminuindo para 0,7% e 0% em 2001. CONCLUSÃO: É possível que a implementação do uso da vacina conjugada para Hib durante a década de 1990 tenha decrescido não apenas a ocorrência da meningite por Hib mas também a MBEI.

Clinical and cerebrospinal fluid findings in patients less than 20 years old with a presumptive diagnosis of neuroschistosomiasis.

CNS manifestations are rarely attributable to Schistosoma mansoni infection although systemic distribution of S. mansoni eggs is well recorded. We describe 73 patients aged less than 20 years who presented S. mansoni eggs in the stool or rectal biopsy and IFA and/or HAI positive CSF tests to S. mansoni, and who had neurological signs and symptoms. Paraparesis (54.8 per cent), urinary retention (53.4 per cent), and paraplegia (20.5 per cent) were the most commonly observed CNS manifestations. In the CSF, pleocytosis (range 7-560 WBC/mm3) associated with eosinophilia (85.7 per cent vs. 50.0 per cent, p = 0.02) and elevated protein concentration (96.8 per cent vs. 40.0 per cent, p = 0.00003) were observed. We conclude that in areas of the world where infection by S. mansoni is common, neuroschistosomiasis should be an important diagnostic consideration in children with neurological signs and symptoms.

Frequency of lymphocytic meningitis associated with mumps before and after a mass campaign for mumps vaccination in children from Salvador, Northeast Brazil.

OBJECTIVE: To describe the frequency of lymphocytic meningitis(LM) concomitant with mumps, before and after the mumps mass immunization campaign in 1997. METHOD: Demographic, clinical and cerebrospinal fluid(CSF) information was collected from the chart of all patients aged from 2 to 59 months, whose CSF exam was performed at the CSF Lab/FJS, between 1989 and 2001. LM was defined as pleocytosis composed by lymphomononuclear cells and negative exams for bacterial or mycologic infection. RESULTS: Of 1,519 patients, 894(58.9%) had normal exams. LM was present in 301(19.8%) patients, out of which 22(7.3%) had concomitant mumps. The frequency of LM ranged from 15.8% in 1989 to 19.7% in 2001 and of LM with concomitant Mumps ranged from 10.5% in 1989 to 4.7% in 1995, when the last cases were registered. CONCLUSION: It is probable that the mumps vaccine campaign has influenced the absence of LM with concomitant Mumps, from 1996 to 2001.

[Invasive pneumococcal strains isolated from children and adolescents in Salvador]. / Cepas invasivas de pneumococo isoladas de crianças e adolescentes em Salvador.

OBJECTIVES: To describe the antimicrobial resistance and serotype distribution of pneumococcal strains. METHODS: In a 57-month period, a laboratory-based surveillance of invasive pneumococcal strains from patients aged < 20 years was conducted. Pneumococcus was identified by means of tests for solubility in bile and optochin. Pneumococcal resistance to penicillin was screened by 1 micro g oxacillin disc and minimal inhibitory concentration was determined for the strains not susceptible to penicillin. Disc diffusion and broth microdilution methods were used for surveillance of resistance to other antimicrobials. Pneumococci were serotyped by means of the Neufeld-Quellung reactions. RESULTS: Of 70 patients, 57.1% were males. The mean age was 1.92 yrs (mean 3.19 +/- 3.66 yrs, range 1 month to 19.5 yrs); 52.9% and 81.4% were < 2 yrs and < 5 yrs, respectively. The strains were isolated from blood (91.4%), CSF (2.9%), pleural (2.9%), peritoneal (1.4%) and abscess (1.4%) fluids from patients with pneumonia (77.1%), fever without localizing signs (10.0%), meningitis (4.3%), others (8.6%). Resistance was detected to penicillin (20.0%), trimethoprim-sulfamethoxazole (65.7%), tetracycline (21.4%), ofloxacin (6.3%), erythromycin (5.7%), clindamycin (2.9%). All tested strains were susceptible to chloramphenicol and vancomycin. Among penicillin-resistant strains, high resistance was detected in one, the same that showed intermediate resistance to cefotaxime. The most frequent serotypes were: 14 (22.9%), 5 and 6A (10.0% each), 6B and 19F (8.6% each), 9V, 18C and 23F (5.7% each). Resistance to penicillin was detected in serotypes 14 (71.4%), 6B and 19F (14.3% each). CONCLUSIONS: Of 70 strains, 67.2% were classified as serotypes included in the heptavalent conjugate pneumococcal vaccine, as were all penicillin-resistant strains.

Frequency of lymphocytic meningitis associated with mumps before and after a mass campaign for mumps vaccination in children from Salvador, Northeast Brazil

OBJECTIVE: To describe the frequency of lymphocytic meningitis(LM) concomitant with mumps, before and after the mumps mass immunization campaign in 1997. METHOD: Demographic, clinical and cerebrospinal fluid(CSF) information was collected from the chart of all patients aged from 2 to 59 months, whose CSF exam was performed at the CSF Lab/FJS, between 1989 and 2001. LM was defined as pleocytosis composed by lymphomononuclear cells and negative exams for bacterial or mycologic infection. RESULTS: Of 1,519 patients, 894(58.9 percent) had normal exams. LM was present in 301(19.8 percent) patients, out of which 22(7.3 percent) had concomitant mumps. The frequency of LM ranged from 15.8 percent in 1989 to 19.7 percent in 2001 and of LM with concomitant Mumps ranged from 10.5 percent in 1989 to 4.7 percent in 1995, when the last cases were registered. CONCLUSION: It is probable that the mumps vaccine campaign has influenced the absence of LM with concomitant Mumps, from 1996 to 2001

Cepas invasivas de pneumococo isoladas de crianças e adolescentes en Salvador / Invasive pneumococcal strains isolated from children and adolescents in Salvador

Objetivos: descrever resistencia antimicrobiana e sorotipos de cepas de pneumococo. Metodos: durante 57 meses, foi conduzida uma vigilancia de cepas invasivas de pneumococo de pacientes com idade maior de 20 anos. O pneumococo foi identificado pelos testes de solubilidade da bile e optoquina. A resistência a penicilina foi avaliada com o disco de oxacilina (I╡g) e, para as cepas não suscetiveis, foi determinada a concentração inibitariamonima. Provas de difusão de disco e de microdiluiτπo em placa foram utilizadas para avaliação da resistência a outros antimicrobianos...

Normal cerebrospinal fluid values in full-term gestation and premature neonates

Results of cerebrospinal fluid (CSF) examinations from 77 high-risk neonates were reviewed. The mean CSF white cells (WBC) count was 4.5 cell/mm3, being two standard deviations above the mean 11.7 cells/mm3 in the full-term gestation neonate group; in the premature neonate one, the mean CSF WBC count was 5.1 cells/mm3, being two standard deviations above the mean 16.7 cell/mm3. PMNs (polymorphonuclear leukocytes) were present in less than 40 per cent of those children, being the mean PMN percentage 4.2 per cent and 0.6 per cent, the mean ANC (absolute neutrophil count) was 0.3/mm3 and 0.06/mm3, in full-term gestation neonate group and premature neonate one, respectively. The mean CSF protein concentration is significantly greater in those premature neonates (101.2 mg/dl) compared with that in term neonates (77.6 mg/dl). The average glucose was just the same in both groups (67 mg/dl). All of these values were from patients who underwent nontraumatic cisternal puncture, with no red blood cells (RBC/mm3=0). Traumatic puncture, even up to 500 RBC/mm3, interfered on CSF parameters.

Etiologia de meningites bacterianas da populaçäo de Salvador - Bahia / Etiology of bacterial meningitis among some children in Salvador - Bahia

As meningites bacterianas constituem patologia importante na faixa etária pediátrica. Com o objetivo de conhecer a distribuiçao da etiologia desta patologia em uma amostra da populaçao de Salvador, Bahia, foram analisados, retrospectivamente, 7000 exames de líquor, realizados entre setembro de 1988 a agosto de 1995, no laboratório de liquorologia da Fundaçao José Silveira. Foram selecionados 892 (12,7 por cento) exames realizados em pacientes menores de 16 anos e com suspeita de meningite, entre os 139 casos de meningite bacteriana, H. influenzae tipo b foi o agente mais frequente (26,0 por cento), ocorrendo em 100 por cento das vezes em menores de 5 anos. Observou-se tendência na queda do número de casos de meningite por H. influenzae tipo b a partir de 1992. Questiona-se se este fato decorre do uso da vacina anti H. influenzae tipo b nesta amostra da populaçao.