Antibiotic Treatment in Complicated Appendicitis: Can It Be Optimized?

BACKGROUND: The management of complicated appendicitis is inconclusive. Guidelines have not been established for the use of personalized antibiotic treatment. OBJECTIVES: To investigate specific risk factors to consider during the initial first-choice antibiotic therapy in children with complicated appendicitis. METHODS: This study included all pediatric patients younger than 18 years of age who underwent a laparoscopic appendectomy during 2012-2022 at a single tertiary medical center. RESULTS: In total, 300 pediatric patients underwent laparoscopic appendectomy due to complicated appendicitis. The patients were treated with ceftriaxone + metronidazole (CM). For 57 (19%) patients, the empirical treatment was changed to tazobactam/piperacillin (TP) due to resistant bacteria or clinical deterioration. The presence of generalized peritonitis during surgery and C-reactive protein (CRP) levels above 20 mg/L at admission were identified as risk factors for changing the antibiotic regimen from CM to TP. CONCLUSIONS: Generalized peritonitis and CRP > 20 gr/L were highly correlated with changing the antibiotic regimen to TP. For such patients, initial treatment with TP may result in clinical improvement and shorter hospitalization.

Isolated Brain Cysts in Children Afflicted with Congenital Cytomegalovirus.

In our clinic, isolated brain cysts identified via early ultrasound are considered as central nervous system involvement in infants with children with congenital cytomegalovirus (cCMV). All infants were diagnosed with caudothalamic or subependymal cysts. When treated according to the cCMV protocol, these patients have an excellent prognosis and no neurological sequelae. Further data on the significance of different cysts in relation to cCMV is warranted.

Characteristics of pediatric recurrent acute mastoiditis: A case-control study.

BACKGROUND: Data on pediatric recurrent acute mastoiditis are lacking, despite its morbidity and clinical significance. Our aim was to describe the incidence, characteristics, and associated factors of recurrent mastoiditis in hospitalized children. METHODS: Using a case-control design, analyzing electronic data of hospitalized children with acute mastoiditis between June 2011 and December 2018, children with recurrent mastoiditis were compared to children with a single episode at the time of hospitalization. Recurrent episodes of mastoiditis were compared to the first episodes. Recurrent acute mastoiditis was defined as recurring mastoiditis ≥4-weeks after a completely resolved event. RESULTS: Of 347 children hospitalized with acute mastoiditis, 22 (6.3%) had recurrent mastoiditis; the median interval between episodes was 3 months (range: 1-36). The mean ± SD age was 2.3 ± 2.25 years. A comparison of first episodes in recurring cases to single episodes by univariate and multivariate analysis, showed no differences in the pre-admission management or in the isolated pathogens; however, a history of atopic dermatitis and percutaneous abscess drainage were more frequent in first episodes of recurring cases (27.3% vs. 1.2%, p < 0.001, and 27.3% vs. 10.0%, p = 0.026, respectively). The second episode of acute mastoiditis was characterized by a milder clinical course and shorter durations from symptoms to hospitalization, intravenous antibiotic therapy, and length of hospital stay. Linear regression showed that an increased interval from symptoms to hospitalization significantly increased length of hospital stay (regression coefficient of 0.215 [95% CI: 0.114-0.317], p < 0.001). CONCLUSIONS: Recurrent episodes of mastoiditis were clinically milder, with shorter length of hospital stay compared to first episodes, possibly because of early admission.

The Effect of the COVID-19 Pandemic on Pediatric Respiratory Hospitalizations.

BACKGROUND: During coronavirus disease 2019 (COVID-19) pandemic, less isolation of common winter viruses was reported in the southern hemisphere. OBJECTIVES: To evaluate annual trends in respiratory disease-related admissions in a large Israeli hospital during and before the pandemic. METHODS: A retrospective analysis of medical records from November 2020 to January 2021 (winter season) was conducted and compared to the same period in two previous years. Data included number of admissions, epidemiological and clinical presentation, and isolation of respiratory pathogens. RESULTS: There were 1488 respiratory hospitalizations (58% males): 632 in 2018-2019, 701 in 2019-2020, and 155 in 2020-2021. Daily admissions decreased significantly from a median value of 6 (interquartile range [IQR] 4-9) and 7 per day (IQR 6-10) for 2018-2019 and 2019-2020, respectively, to only 1 per day (IQR 1-3) in 2020-2021 (P-value < 0.001). The incidence of all respiratory viruses decreased significantly during the COVID-19 pandemic, with no hospitalizations due to influenza and only one with respiratory syncytial virus. There was also a significant decline in respiratory viral and bacterial co-infections during the pandemic (P-value < 0.001). CONCLUSIONS: There was a significant decline in pediatric respiratory admission rates during the COVID-19 pandemic. Possible etiologies include epidemiological factors such as mask wearing and social distancing, in addition to biological factors such as viral interference. A herd protection effect of adults and older children wearing masks may also have had an impact.

Clinical impact of biofire gastrointestinal panel testing for hospitalised children with acute gastroenteritis.

AIM: To investigate the clinical impact of BioFire FilmArray Gastrointestinal Panel (FGP) testing in real-life diarrhoeal episodes of hospitalised paediatric patients. METHODS: Children hospitalised between October 2018 and September 2020 for whom stool specimens for FGP were submitted at the clinician's discretion were retrospectively observed. For each episode, demographics, clinical information and stool tests were collected. RESULTS: The clinical impact for each case was evaluated by changing the antibiotic prescription, following the result of the FGP testing. Out of 140 diarrhoeal episodes, 25 pathogens were found in 24 cases using conventional methods, whereas, FGP testing identified 75 pathogens in 56 cases (p < 0.05). The pathogens more frequently identified by FGP testing were Campylobacter, Shigella, Rotavirus, Giardia lamblia and Cryptosporidium. The clinical impact of FGP testing was observed in 17/140 (12%) diarrhoeal episodes, and higher rates in previously healthy (19%) and solid organ-transplanted children (15%). CONCLUSION: We found that using FGP testing for hospitalised children with diarrhoeal episodes could increase pathogen identification and impact clinical decisions, especially in healthy and transplant patients.

Health Care Resource Utilization and Economic Burden Associated With Congenital Cytomegalovirus Infection: A Longitudinal Analysis of Data From Clinical Practice at a Large Health Care Provider in Israel.

PURPOSE: Congenital cytomegalovirus infection (cCMVi) is the leading cause of nonhereditary sensorineural hearing loss and can cause other long-term neurodevelopmental disabilities; however, data on the economic burden of cCMVi during early childhood are scarce. The primary objective of the study was to describe longitudinal patterns of health care resource utilization (HCRU) and direct medical costs among infants with cCMVi compared to infants unexposed to cCMVi. METHODS: A retrospective cohort study was performed using data on infants born between 2013 and 2017, as captured in the database of Maccabi Healthcare Services, a 2.5 million-member health care organization in Israel. cCMVi cases were identified by physician diagnosis and/or dispensed valganciclovir within 90 days after birth. Infants born to mothers CMV-seronegative throughout pregnancy were selected for comparison (unexposed controls). Infants were retrospectively followed up through December 31, 2018, or 4 years of age (Y4). HCRU included physician visits, hospital admissions, audiology tests/procedures, imaging, and valganciclovir treatment. Direct medical costs, in US dollars per person per year (USD PPPY) were calculated from the health-system perspective. To compare costs of cCMVi cases and controls, direct medical costs were estimated using a generalized linear model with a log link function and γ distribution after adjustment for patient characteristics. FINDINGS: A total of 351 cCMVi cases and 11,733 control infants with continuous follow-up during their first year of life (Y1) were included in the study. In Y1, cases were more likely to have a hospital admission (8.5% cases vs 4.5% control; P < 0.001) and higher numbers of pediatrician visits (median, 18 vs 15), audiology visits and tests, and cranial ultrasounds (all, P < 0.05). Longitudinally, incremental costs associated with cases were highest in Y1 (1686.7 USD PPPY; cost ratio = 2.6; P < 0.001) and remained elevated through Y4. IMPLICATIONS: cCMVi was associated with substantial increases in HCRU and economic burden during early childhood, and particularly during the first year of life.

Epidemiology of cytomegalovirus infection in pregnancy in Israel: Real-world data from a large healthcare organization.

Congenital cytomegalovirus infection (cCMVi) is the leading cause of nonhereditary sensorineural hearing loss among newborns. Women newly acquiring cytomegalovirus infection (CMVi) during pregnancy have the highest risk of vertical transmission. This study aimed to describe the epidemiology of CMVi in pregnancy in a large healthcare database. A retrospective cohort study was performed using the Maccabi Healthcare Services database (Israel). Women aged 18-44 years old on July 1, 2013 with no record of pregnancy in the prior 6 months were followed through December 31, 2017 for first pregnancy occurrence. Pregnancy outcomes (live birth, spontaneous/therapeutic abortions, stillbirth, and uncertain outcomes) were captured. CMV test results were obtained to assess serostatus at the start of pregnancy (SoP) and primary CMV infection (CMVi) during pregnancy. Associations of demographic and reproductive factors with pCMVi were investigated (multivariable logistic regression). The study included 84 699 pregnant women (median age = 31 years; interquartile range = 28-35). Live birth, fetal loss, and uncertain pregnancy outcomes accounted for 76.8%, 18.2%, and 5.0%, respectively. The seroprevalence of CMV at the start of pregnancy in this cohort was 63.4% (95% confidence interval [CI]: 63.1-63.7). Among seronegative women with available test results (n = 10 657), CMVi incidence was 14.5 per 1000 (95% CI = 12.2-16.7). In multivariate logistic regression models adjusting for maternal age, CMVi was significantly associated with having one or more prior live births (odds ratio [OR]: 3.8 [95% CI: 2.6-5.4]) and having a child less than 6 years of age (OR: 4.3 [95%CI: 3.0-6.1]). One in three pregnant women in Israel is at risk for primary CMVi. This study demonstrates that real-world electronic healthcare data can be leveraged to support clinical management and development of interventions for congenital CMV by identifying women at high risk for CMVi during pregnancy.

EBV, CMV, and BK viral infections in pediatric kidney transplantation: Frequency, risk factors, treatment, and outcomes.

BACKGROUND: Improved short- and long-term outcomes of kidney transplantation have been achieved over the past decades due to improved immunosuppression. This may have increased the risk for infections and, particularly, for the viral infections: cytomegalovirus (CMV), Epstein-Barr virus (EBV), and polyoma BK virus (BKV). METHODS: A retrospective review of viremic CMV, EBV, and BKV infections in pediatric renal transplant recipients treated and followed by a national referral center over a 10-year period. RESULTS: Sixty-seven patients (68% males) received 68 kidney grafts (62% from living donors) during the study period; the mean follow-up period was 5.2 ± 2.4 years. Twenty-seven viremic episodes were documented (CMV: 13, EBV: 6, BKV: 8) in 24 patients (35.2%). The median time (interquartile range) to viremia post-transplant was 11 (4-38) months. The viral infection rate was significantly higher in the years 2014-2015 than in previous years (61% vs. 29%, p = .017). Compared to patients who did not develop viremia, patients with viremias were younger at the time of transplantation, were more likely to receive thymoglobulin induction pre-transplant and to develop an acute rejection. Multiple logistic regression modeling identified transplant year and recipient's age as significant risk factors for viremia. Graft outcome and eGFR at the last follow-up was similar between patients who did and did not develop viremia. CONCLUSIONS: Viral infections continue to be a major cause of morbidity in pediatric kidney transplant recipients. However, with close monitoring and prompt intervention, patient and renal outcomes remain favorable.

Adenovirus can be a serious, life-threatening disease, even in previously healthy children.

AIM: Adenovirus infections are exceedingly common in childhood. However, little is known of the clinical characteristics of children admitted with severe infection to the paediatric intensive care unit (PICU). METHODS: Clinical data on children hospitalised with adenovirus infection between January 2005 and March 2020 were collected. We compared data between children hospitalised in the PICU and those who were not in a 1:2 ratio. RESULTS: During the study period, 69 children with adenovirus infection were admitted to the PICU, representing 5% of all hospitalised children with adenovirus. Thirty-four (49%) were previously healthy children. Mortality occurred in 5 patients, and all had an underlying illness. Cidofovir was used in 21 children, including 11 who were previously healthy. No side effects were attributed to the treatment. During 2005-2014, viral co-infection rates were 42% in the PICU group and 11% in the control group (p = 0.002). However, during 2015-2020, when the viral panel became widespread in our institution, the rates of co-infection were similar in the two groups (32% and 34%, p = 1.0). CONCLUSION: Our findings suggest that adenovirus may present as a serious, life-threatening disease even in previously healthy children.

Orbital Cellulitis in a Pediatric Population - Experience From a Tertiary Center.

OBJECTIVE: To describe our experience in treating children afflicted with orbital cellulitis. METHODS: A retrospective analysis of hospital records of children afflicted with orbital cellulitis was conducted between 2005-2018. Clinical, laboratory and radiology characteristics as well as management, microbiological data, and outcomes were collected. RESULTS: Of the 94 patients, painful restriction of ocular motility was observed in 37.2% and proptosis in 34%, whereas, only 18% of the children presented with both classical signs. Children aged older than 9 years presented with markedly elevated inflammatory markers i.e., leukocytosis and C-reactive protein (CRP). Only a minority (12, 12.4%) required functional endoscopic sinus surgery. CONCLUSION: Our data support the general approach that orbital cellulitis should be initially managed conservatively with close monitoring; since, only a minority of patients require surgical intervention.

The association between maternal cytomegalovirus urinary excretion and congenital infection rate.

BACKGROUND: In utero Cytomegalovirus (CMV) vertical transmission occurs predominantly during primary maternal infection. There are no known non-invasive methods for diagnosis of fetal infection before delivery, however some risk factors have been suggested. We aimed to evaluate the association between maternal CMV urinary excretion and congenital CMV infection. METHODS: A retrospective cohort study of all women who were diagnosed with primary CMV infection during pregnancy in a single university affiliated tertiary medical center, between 2012 and 2016. We examined congenital CMV infection and disease rates among infants born to women with and without CMV urinary excretion. RESULTS: Overall, 126 women were included, 77 in the positive urinary excretion group, and 49 in the negative urinary excretion group. There was no difference in maternal symptoms between the groups. We found no difference in congenital CMV infection and disease rates between infants born to women with and without urinary excretion of CMV (congenital infection rate 37.1% vs. 24.4%, p = 0.209, congenital disease rate of 18.2% vs. 22.4%, p = 0.648). Women with positive urinary CMV excretion had lower IgG avidity values (36.7% vs 54.6%, p = 0.007), with no additional difference in serology pattern. Compared to asymptomatic women, those with CMV related symptoms did not have significantly higher rates of urinary excretion of CMV (70% vs. 60.5%, p = 0.38) or congenital infection rates (40.7% vs. 31.2%, p = 0.48). CONCLUSION: Among infants of women with primary CMV infection in pregnancy, we did not find an association between urinary excretion of CMV and congenital CMV infection.

Adenovirus Infection in Children with Down Syndrome.

BACKGROUND: Adenovirus infections are prevalent in children. They usually cause a mild self-limited disease. However, this infection can be associated with considerable morbidity and mortality in specific populations, especially among immunocompromised children. Children with Down syndrome are susceptible to a higher frequency and increased severity of viral infections. Little is known about the severity and clinical course of adenovirus infections in children with Down syndrome. OBJECTIVES: To characterize hospitalized children diagnosed with Down syndrome and presenting with adenovirus infection. METHODS: We performed a retrospective review of children admitted with adenovirus from January 2005 to August 2014 from a single tertiary pediatric medical center in Israel. Data were compared between patients with and without Down syndrome. RESULTS: Among the 486 hospitalized children with adenoviral infection, 11 (2.28%) were diagnosed with Down syndrome. We found that children with Down syndrome were more likely to experience a higher incidence of complications (18.2% vs. 2.4%, P = 0.008), a higher rate of admissions to the intensive care unit (36.4% vs. 2.4%, P < 0.001), and more prolonged hospitalizations (17 ± 15.9 days compared to 4.46 ± 3.16, P = 0.025). CONCLUSIONS: Children with Down syndrome who were hospitalized with adenovirus infection represent a high-risk group and warrant close monitoring. If a vaccine for adenovirus becomes available, children with Down syndrome should be considered as candidates.

Transient Cardiac Injury in Adolescents Receiving the BNT162b2 mRNA COVID-19 Vaccine.

BACKGROUND: Vaccines are paramount in the effort to end the coronavirus disease 2019 global epidemic. BNT162b2 is approved for the vaccination of adolescents over 16 years of age. Systemic adverse events were scarce though the pretested cohort of this age group was relatively small. The aim of the current study is to raise awareness for potential adverse reactions. METHODS: This is a case series of patients diagnosed with perimyocarditis following vaccination. Patients were compiled from 3 pediatric medical centers in Israel through a network of pediatricians and data regarding those cases was collected. In addition, incidence of perimyocarditis during the vaccination period was compared with previous years. RESULTS: All patients were males 16-18 years old, of Jewish descent, who presented with chest pain that began 1-3 days following vaccination (mean, 2.1 days). In 6 of the 7 patients, symptoms began following the 2nd dose and in 1 patient following the 1st dose. All cases were mild and none required cardiovascular or respiratory support. The incidence of perimyocarditis during the vaccination period was elevated in comparison to previous years. CONCLUSIONS: This case series describes a time association between coronavirus disease 2019 vaccine and perimyocarditis in adolescents. All cases were mild, although only long-term follow-up can reveal the true impact of this cardiac injury. While it seems that the incidence of perimyocarditis during the vaccination campaign period is increased, a more comprehensive data collection on a wider scale should be done. We hope this report will serve as a reminder to report events and allow for analysis of potential adverse reactions.

The COVID-19 pandemic dramatically reduced admissions of children with and without chronic conditions to general paediatric wards.

AIM: We examined the impact of the COVID-19 pandemic on how many children were admitted to Israel's largest tertiary paediatric hospital and why they were admitted. METHODS: Israel declared COVID-19 a national emergency on 19 March 2020. This study examined daily hospital admissions to our three general paediatric wards during the COVID-19 lockdown period from 20 March to 18 April 2020. These 258 admissions were compared with the 4217 admissions from the period immediately before this, 1 February to 19 March 2020, plus 1 February to 18 April in 2018 and 2019. We also compared why patients were admitted during the study period, and any pre-existing conditions, with 638 children hospitalised during the same period in 2019. RESULTS: The mean number of daily hospitalisations during the COVID-19 lockdown period was 8.6, which was 59% lower than the 20.9 recorded during the other three periods before COVID-19. There was a significant decrease in the number of patients admitted with infectious (74%) and non-infectious (44%) aetiologies from 2019 to 2020, and these occurred among patients with (58%), and without (55%), pre-existing medical conditions. CONCLUSION: The Israeli COVID-19 lockdown had a dramatic effect on admissions to the paediatric wards of a tertiary hospital.

Pediatrician, watch out for corona-phobia.

The current outbreak of COVID-19 raging globally is taking a heavy toll on the adult population, with a rapidly growing number of newly infected and critically ill patients. However, to date, mortality rate among children is low as they mostly suffer from a mild disease. Yet, other more routinely encountered childhood diseases do not stand still and continue to be the main share of pediatricians' everyday challenges. Here we describe a case series of routinely seen pediatric diseases with delayed diagnosis due to different aspects of what we call "Corona-phobia". These cases were easily collected within a 1-week period which implies that this is a more widespread phenomenon.In conclusion, this raises the possibility that measures taken to mitigate this pandemic may be more damaging to children overall than the virus itself. We believe that pediatricians as well as policy makers should take this important aspect into consideration. What is Known: • COVID-19 manifests as a mild disease in most children; however, children are an important reservoir and may become spreaders of the disease. • Social distancing and isolation are important tools in mitigating COVID-19 transmission. What is New: • This case series describes 7 cases with delayed diagnosis of every-day pediatric diseases that were not caused by COVID-19 but were highly influenced by different aspects of "Corona-phobia". • Our objective is to highlight the possibility that measures taken to mitigate this pandemic may lead to a substantial delay in the diagnosis of other non-COVID-19 related diseases.

A Drop in Number of Hospitalizations Among Children with Bacterial Infections During the COVID-19 Pandemic.

A significant drop was found in the number of hospitalizations due to bacterial infections among children during the first peak period of COVID-19 in Israel. There was a 77% decrease in serious bacterial infections, and ≥50% decrease in most types of bacterial infections, especially osteoarticular and skin infections, followed by pneumonia and ENT infections.

Hyponatremia in childhood urinary tract infection.

Acute urinary tract infection (UTI) is the most common bacterial infection in childhood. Although hyponatremia was described in ~ 2/3 of these children, its clinical significance is still unclear. Herein, we evaluated the prevalence and clinical implications of hyponatremia in children hospitalized with a UTI. Medical records of previously healthy children hospitalized between January 2011 and December 2016 with UTI were retrospectively reviewed. Patients (median age 5.5 months) were divided into two groups according to their sodium levels: normonatremia (Na ≥ 135 mEq/L) and hyponatremia (Na < 135 mEq/L). Hyponatremia diagnosed on admission was found in 114/219 children (49%). Hyponatremic patients experienced a more severe disease manifested by a longer hospital stay (3.8 vs 3.4 days, p = 0.003), a higher prevalence of abnormal findings on renal ultrasound (10 vs 2, p = 0.01), higher C-reactive protein (CRP) levels (8.6 vs 3.4 mg/dl, p = <0.001), and a negative correlation between sodium levels and CRP (r = - 0.38, p < 0.001).Conclusion:Hyponatremia occurs frequently in children hospitalized with UTI and is associated with elevated inflammatory markers and a more severe disease course. What is Known: • Hyponatremia, one of the most common electrolyte abnormalities, occurs in approximately 1/3 of hospitalized children and in 2/3 of children with pyelonephritis. • In certain cases of various medical conditions, hyponatremia has been shown to correlate with disease severity. What is New: • Hyponatremia in hospitalized children with UTI correlates with elevated inflammatory markers and a more severe disease course.

Valaciclovir to prevent vertical transmission of cytomegalovirus after maternal primary infection during pregnancy: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Cytomegalovirus is a common congenital infection, with high morbidity after an early primary maternal infection. No effective means exist to prevent viral transmission to the fetus. We aimed to investigate whether valaciclovir can prevent vertical transmission of cytomegalovirus to the fetus in pregnant women with a primary infection acquired early in pregnancy. METHODS: This prospective, randomised, double-blind, placebo-controlled trial was done at the Infectious Feto-Maternal Clinic of Rabin Medical Center (Petach Tikvah, Israel). Pregnant women aged 18 years or older, with serological evidence of a primary cytomegalovirus infection acquired either periconceptionally or during the first trimester of pregnancy, were randomly assigned to oral valaciclovir (8 g per day, twice daily) or placebo from enrolment until amniocentesis at 21 or 22 gestational weeks. Randomisation was done separately for participants infected periconceptionally or during the first trimester and was done in blocks of four. Patients and researchers were masked to participant allocation throughout the entire study period. The primary endpoint was the rate of vertical transmission of cytomegalovirus. Statistical analyses were done according to per-protocol principles. The study was registered at ClinicalTrials.gov, NCT02351102. FINDINGS: Between Nov 15, 2015, and Oct 8, 2018, we enrolled and randomly assigned 100 patients to receive valaciclovir or placebo. Ten patients were excluded, five from each study group; therefore, the final analysis included 45 patients (all singletons) in the valaciclovir group and 45 patients (43 singletons and two sets of twins) in the placebo group. In the valaciclovir group, including both first trimester and periconceptional infections, five (11%) of 45 amniocenteses were positive for cytomegalovirus, compared with 14 (30%) of 47 amniocenteses in the placebo group (p=0·027; odds ratio 0·29, 95% CI 0·09-0·90 for vertical cytomegalovirus transmission). Among participants with a primary cytomegalovirus infection during the first trimester, a positive amniocentesis for cytomegalovirus was significantly less likely in the valaciclovir group (two [11%] of 19 amniocenteses) compared with the placebo group (11 [48%] of 23 amniocenteses; p=0·020. No clinically significant adverse events were reported. INTERPRETATION: Valaciclovir is effective in reducing the rate of fetal cytomegalovirus infection after maternal primary infection acquired early in pregnancy. Early treatment of pregnant women with primary infection might prevent termination of pregnancies or delivery of infants with congenital cytomegalovirus. FUNDING: None.

Characterization of Congenital Toxoplasmosis in Israel: A 17-year Nationwide Study Experience.

BACKGROUND: Congenital toxoplasmosis (CT) can cause significant neurologic manifestations and other untoward sequelae. Neither the current epidemiology nor the disease severity of CT in Israel is known. METHODS: Records of CT were collected from the National Toxoplasmosis Reference Laboratory and from 15 medical centers across Israel between 2001 and 2017. Eligible case-patients were fetuses or infants <12 months of age at the time of diagnosis. RESULTS: Of the 43 CT cases identified, 24 (55%) were in Jews and the remaining 19 cases were in patients of Arab (non-Bedouin) origin. The overall annual estimated rate of symptomatic CT was calculated as 0.55 per 100,000 live births. One or more severe clinical manifestations were reported in 12 (46%) of the 28 live-born infants and included cerebral calcifications (7 cases), chorioretinitis (4 cases), hydrocephalus (2 cases) and 1 case of death. Sensitivities of blood polymerase chain reaction (PCR), cerebrospinal fluid PCR and IgM antibody tests were 50% each. However, analyzing PCR samples from both sites, together with IgM testing, increased the sensitivity to 93%. CONCLUSIONS: The relative rate of severe manifestations was higher than in previous European reports. It is possible that the greater disease severity observed in Israel is in part due to the lack of systematic antenatal treatment and screening. Arab (non-Bedouin) infants are at higher risk for contracting CT. Performing serologic and PCR tests simultaneously is essential to improve CT diagnosis. This study demonstrates a need for an educational program to target high-risk populations.