Measles-related hospitalizations and associated complications in Jerusalem, 2018-2019.

OBJECTIVES: The 2018 measles outbreak in Israel affected >2000 people in Jerusalem. The aim of the study was to describe clinical features and complications of hospitalized measles patients in Jerusalem, as related to age group and risk factors. METHODS: All individuals hospitalized with measles in the three main hospitals in Jerusalem during March 2018 to February 2019 were included. Demographic, clinical and laboratory data were analysed. RESULTS: Of 161 hospitalized individuals, 86 (53.4%) were <5 years old, 16 (10%) were ≥5 years but <20 years old, and 59 (36.6%) were ≥20 years old. Most, 114/135 (85%), were unvaccinated. Immunocompromised state was identified in 12/161 (7.5%) patients, 20/161 (12.4%) had other underlying co-morbidities, and four were pregnant. Hypoxaemia on admission was a common finding in all age groups. Hepatitis was more common among adults ≥20 years old (33/59, 59%). Measles-related complications were noted in 95/161 (59%) patients, and included pneumonia/pneumonitis (67/161, 41.6%), which was more common in young (<5 years) children, diarrhoea (18/161, 11.2%), otitis (18/161, 11.2%), and neurological complications (6/161, 3.7%)-the latter occurring more frequently in the 5- to 20-year age group. Two of the 12 immunocompromised patients died of measles-related complications. A high re-admission rate (19/161, 11.8%) within 3 months was documented among hospitalized measles patients. CONCLUSION: The burden of hospitalization, as well as the high rate of short- and long-term complications observed in hospitalized patients, underscore the importance of maintaining a high measles vaccine coverage, with enhanced targeting of unvaccinated population pockets.

A cluster of invasive meningococcal disease revealed by the characterization of a novel serogroup B meningococcal clone.

The incidence of invasive infections due to Neisseria meningitidis in Israel is about 1/100 000 population annually. Three cases of meningococcal meningitis were reported in employees at a single plant; the first case appeared in March 2013 and the second and third cases appeared in December, almost 9 months later. N. meningitidis serogroup B was isolated from cerebrospinal fluid samples. Multilocus sequence typing assigned the three meningococcal isolates to ST10418, a new sequence type and a member of the ST32 clonal complex. The clonality was confirmed by performance of pulsed-field gel electrophoresis. Post-exposure antibiotic prophylaxis was administered to close contacts of the first case. Upon the diagnosis of the additional two cases, post-exposure prophylaxis was administered to all the plant employees. This report demonstrates the importance of combining public health measures and advanced laboratory studies to confirm clonality and to prevent further disease spread in a closed setting.

Characteristics of a large mumps outbreak: Clinical severity, complications and association with vaccination status of mumps outbreak cases.

In recent years, large mumps outbreaks, involving mainly adolescents and young adults, have re-emerged in several countries. We investigated a large mumps outbreak, evaluated the association between mumps clinical severity (complications, hospitalization) and vaccination status (number of previous measles, mumps and rubella - MMR vaccine doses), and assessed vaccine effectiveness. The first mumps cases emerged in an ultra-orthodox boys' school in Jerusalem and were epidemiologically linked to the mumps outbreak in New York. Overall, 3130 mumps cases were notified in the Jerusalem district during September 2009-August 2011 (median age 13y, 64% males). Most cases were reported from community clinics. Patients with systemic symptoms and/or complications (419, 13.4%) were either hospitalized (n = 79) or treated in an emergency medical center (n = 340). The main complications included orchitis (3.8% males> age 12y) and meningoencephalitis (0.5%). The mumps virus genotype was G5. The distribution of previous MMR vaccine doses (n = 0,1,2) was: 24.8%, 28.3% and 46.9%, respectively. The number of previous vaccine doses was inversely associated with clinical severity. Adjusted values for MMR vaccine effectiveness against complications were estimated as 52.1% (95% CI -4 -78%) for one vaccine dose and 62.7% (95% CI 25.7-81.3%) for 2 doses. The outbreak was characterized by predominance of male students; the majority of whom had been previously vaccinated. The reported complication rate was relatively low. Vaccination status was associated with age and disease severity. The combination of limited mumps vaccine effectiveness and the specific school setting (dense learning and living conditions) probably contributed to the disease spread.

Who are the children at risk? Lessons learned from measles outbreaks.

We investigated a measles outbreak in the Jerusalem district in 2007-2008 (992 cases). Most cases (72·6%) were aged <15 years, 42·9% aged <5 years, and 12·8% were infants aged <1 year. The peak incidence rate was in infants aged 6-12 months (916·2/100 000). This represents a significant shift from former outbreaks in 2003-2004, where the peak incidence was in the 1-4 years age group. Of children aged <5 years the proportion aged 6-12 months tripled (7·7% vs. 25·6%). In a case-control study (74 cases, 148 controls) children who developed measles were less likely to be registered in a well-baby clinic and had lower overall immunization coverage. The differences in proportions for registration, DTaP3 and MMR1 coverage were 35·1%, 48·6% and 80·8%, respectively (all P<0·001). Rising birth order of cases and their siblings was associated with non-registration and non-compliance with MMR immunization. The vulnerability of young infants and the risk markers noted above should be taken into account in planning intervention programmes.

The changing panorama of bacterial enteric infections.

We studied the age-specific population-based incidence of bacterial enteric infections caused by Shigella, Salmonella and Campylobacter, in Jerusalem. During 1990-2008, 32,408 cases were reported (incidence rate 232.1/100,000 per annum). The patterns of Shigella (47.4% of cases), Salmonella (34.4%) and Campylobacter (18.2%) infections evolved noticeably. Campylobacter rates increased from 15.0 to 110.8/100,000 per annum. Salmonella rates increased from 74.2 to 199.6/100,000 in 1995 then decreased to 39.4/100,000. Shigella showed an endemic/epidemic pattern ranging between 19.7 and 252.8/100,000. Most patients (75%) were aged <15 years; children aged <5 years comprised 56.4% of cases, despite accounting for only 12.9% of the population. Campylobacter was the predominant organism in infants aged <1 year and Shigella in the 1-4 years group. The hospitalization rates were: Shigella, 1.8%; Campylobacter, 2.3%; Salmonella, 6.9%. Infants were 2.2 times more likely to be hospitalized than children aged 1-14 years (P=0.001). Household transmission occurred in 21.2% of Shigella cases compared with 5% in the other bacteria.

Mumps outbreak in Jerusalem affecting mainly male adolescents.

From mid-September 2009 to 7 December 2009, 173 cases of mumps have been reported in the Jerusalem District. Most cases (82.1%) were male adolescents (median age 14.5 years) who are students in religious boarding schools. The majority of them (74%) are appropriately vaccinated for their age; 67% had received two doses of mumps-containing vaccine. An epidemiologic connection has been reported with visitors from New York, some of whom had recently had mumps.

An outbreak of measles in an ultra-orthodox Jewish community in Jerusalem, Israel, 2007--an in-depth report.

Measles elimination in Europe is hindered by recurrent outbreaks, typically in non-immunised specific sub-populations. In 2003 and 2004, two measles outbreaks occurred in Jewish ultra-orthodox communities in Jerusalem, Israel. In 2007, another measles outbreak emerged in Jerusalem. Epidemiological investigation and control activities were initiated. Three measles cases (15 years old, 22 years old and an infant; all unvaccinated) were diagnosed in Jerusalem in August 2007. All three belonged to Jewish ultra-orthodox communities in London, United Kingdom, and had had contact with patients in London. The epidemiological investigation did not reveal any connection between these cases other than their place of origin. The disease spread rapidly in extremely ultra-orthodox sub-groups in Jerusalem. Until 8 January 2008, 491 cases were reported. Most patients (70%) were young children (0-14 years old), 96% unimmunized. Frequently, all the children in a large family were infected; two thirds of the cases belonged to family clusters of more than two patients per family (in part due to non-compliance with post-exposure prophylaxis recommendations). The high age-specific incidence among infants 0-1-year- (408.5/100,000) and 1-4-year-olds (264.1/100,000) is a cause for concern. The hospitalisation rate was 15% (71/491), mainly due to fever, patients (26.7%) presented with pneumonitis or pneumonia and two patients presented with encephalitis. There have not been any deaths to date. The outbreak was apparently caused by measles importation into unprotected groups. Despite a high national immunisation coverage (94-95%), programmes to increase and maintain immunisation coverage are essential, with special focus on specific sub-populations.

Invasive meningococcal disease in children in Jerusalem.

Neisseria meningitidis is an important cause of childhood meningitis and septicaemia. Between 1999 and 2005, 133 invasive meningococcal disease (IMD) cases occurred in Jerusalem, 112 (84.2%) of them in children aged 0-14 years. The annual incidence rate in Jerusalem was higher than the national average (2.45+/-0.6 vs. 1.13+/-0.16/100 000 population, P=0.002). Most of the children (82.1%) were from low socio-economic Arab and Jewish ultra-orthodox communities; mortality was higher among Arab than Jewish children (1.3 vs. 0.22/100 000 person-years, P=0.004). A cluster of 10 children with severe meningococcal sepsis (three fatalities) emerged in the winter of 2003-2004. Compared to the other 102 cases in 1999-2005 both meningococcaemia (100% vs. 51%, P=0.003) and mortality (30% vs. 6.9%, P=0.014) rates were higher. Serogroup B comprised 77.6% of the bacterial isolates. Pulsed-field gel electrophoresis showed considerable variability among cluster isolates, but significant resemblance in Arab cases throughout 1999-2005. The increased susceptibility of specific sub-populations to IMD necessitates further evaluation.

Measles outbreaks affecting children in Jewish ultra-orthodox communities in Jerusalem.

In 2003 and 2004 two measles outbreaks occurred in Jewish ultra-orthodox communities in Jerusalem. The index case of the first outbreak (March 2003) was a 2-year-old unvaccinated child from Switzerland. Within 5 months, 107 cases (mean age 8.3+/-7.5 years) emerged in three crowded neighbourhoods. The first cases of the second outbreak (June 2004) were in three girls aged 4-5 years in one kindergarten in another community. By November 2004, 117 cases (mean age 7.3+/-6.5 years) occurred. The virus genotypes were D8 and D4 respectively. Altogether, 96 households accounted for the two outbreaks, with two or more patients per family in 79% of cases. Most cases (91.5%) were unvaccinated. Immunization coverage was lower in outbreak than in non-outbreak neighbourhoods (88.3% vs. 90.3%, P=0.001). Controlling the outbreaks necessitated a culture-sensitive approach, and targeted efforts increased MMR vaccine coverage (first dose) to 95.2%. Despite high national immunization coverage (94-95%), special attention to specific sub-populations is essential.

Tuberculosis outbreak among students in a boarding school.

Tuberculosis (TB) outbreaks present a public health challenge. Six cases of active TB emerged in a boarding school in Israel during 1 yr. An epidemiological outbreak investigation was performed, followed by implementation of control measures. The investigation included interviews, tuberculin skin test (TST) and chest radiographs of the students. Close contact (n = 155) was defined as being in the same class or dormitory with a patient. Remote contact (n = 246) was defined as being in the school. An epidemiological association was detected among five of the cases and a distinct pattern was found in molecular analysis. TST was performed in 398 (99.2%) students. Repeated (two-step) TST was applied to the close contacts. The degree of contact, country of origin and previous bacille Calmette-Guérin vaccination were significantly associated with TST reactions. Preventive directly observed therapy was completed by 157 (91.3%) students. During 5 yrs follow-up, no additional cases emerged. While investigating a tuberculosis outbreak, the definition of degree of contact is a significant predictor for detecting positive tuberculin test. Immigration from an endemic country, as well as previous bacille Calmette-Guérin vaccination have a major effect on tuberculin skin-test results. The directly observed therapy approach was found to be successful in preventing further morbidity.

Fever of unknown origin in Israel.

INTRODUCTION: Fever of unknown origin (FUO) is still a diagnostic challenge for the family physician and the internist. In the last decades a few reports have emphasized a changing pattern in the prevalence of the 3 main categories of FUO: infections, malignancies and collagen diseases. AIMS: a. to find out if the changing pattern among the main diagnoses in patients with FUO is comparable to previous reports. MATERIAL AND METHODS: Medical files of patients that were admitted in two 450 beds rural Israeli hospitals were checked by two physicians. All files of patients with either the diagnosis of FUO, or files of patients with fever that were hospitalized for a week or longer in internal medicine departments were reviewed. RESULTS: 101 files of patients fulfilling the criteria of FUO were found. Surprisingly 54.5% of them had infectious diseases, 7.9% had malignant disease and only 2% had collagen disease. CONCLUSIONS: a. Infectious diseases are still the leading cause of FUO among Israeli patients. b. The prevalence of infectious and malignant diseases is comparable to other studies, however the low rate of connective tissue diseases in our study is unusual. c. The rate of undiagnosed FUO was remarkably high (32.7%), although all these patients recovered during hospitalization and probably had self limited infectious (viral) disease.

Epidemiology of hepatitis B virus infection among family members of chronic carriers in Israel.

BACKGROUND: Hepatitis B is a major problem worldwide. Israel has intermediate endemicity for hepatitis B virus, and an annual carrier rate of 1-3%. OBJECTIVE: To evaluate both the prevalence of HBV infection among family members of HBV carriers and the competence of family practitioners in performing a comprehensive assessment. METHODS: A total of 152 HB surface antigen-positive blood donors were discovered in our subdistrict during the years 1993-97. Their family physicians were questioned regarding the patients' family members. Specific information on 85 spouses and 200 children was also obtained. RESULTS: Among the 85 married carriers, 5 of the spouses (5.9%) were found to be HBsAg positive. None of the 200 children was HBsAg positive. We found that in a third (n = 52) of the patients, the sexual partner had never been tested by a primary care physician. Patients were not routinely tested for HB e antigen or anti-HBe antibodies. Neither the parents nor the siblings had undergone any serological evaluation. However, most family members of the carriers had received an HBV vaccine from their family physicians. CONCLUSIONS: Our findings show that horizontal transmission of HBV among spouses of HBV carriers still exists. We did not find any vertical transmission, probably due to male predominance and previous vaccination. Family physicians should be trained to perform an extensive serological evaluation of family members of patients with chronic HBV infection, including parents and siblings, and should vaccinate seronegative family members.

Control of a community-wide outbreak of hepatitis A by mass vaccination with inactivated hepatitis A vaccine.

The epidemiology and control of hepatitis A virus was investigated during an outbreak of hepatitis A in a village in Israel. Postexposure administration of immune globulin to contacts was ineffective in controlling the outbreak. However, within 2 weeks of starting a mass immunization campaign with hepatitis A vaccine, the incidence of hepatitis A declined dramatically; the last case occurred 6 weeks after the immunization program began. The study demonstrated that while postexposure administration of immune globulin may diminish but not entirely arrest transmission of hepatitis A virus, active hepatitis A vaccination is a safe and effective intervention that can be used safely in hepatitis A virus antibody-positive children.

Cystic fibrosis mutations in Israeli Arab patients.

Mutation analysis was performed on 42 unrelated Israeli Arab CF patients. The previously known mutations in this population, DF508, N1303K, G542X, 4010delTATT, and S549R(T>G), were identified in 57 CF alleles, leaving 28 CF alleles with unknown mutations. Screening of the coding sequence of the CFTR gene by a single strand conformation analysis (SSCA) and direct sequencing revealed three point mutations and two intragenic deletions, including 2183AA>G, R75X, S549R (A>C), 3120+1Kbdel8.6Kb and del(exon2). In the present sample of Israeli Arab patients, 12 mutations account for 92% of the CF alleles. The mutations DF508, N1303K, W1282X and 3120+1Kbdel8.6Kb were found in all Arab ethnic subgroups. The mutations G85E, R75X, 2183AA>G, and del(exon2) were confined to Muslim Arabs, and the mutations 4010delTATT, S549R(A>C) and G542X were confined to Christian Arabs. Hum Mutat 14:543, 1999.

Severe jaundice in a gunshot casualty due to the coexistence of Dubin-Johnson and glucose-6-phosphate dehydrogenase deficiency.

We report an unusual case of a 21-year-old man who was shot in his abdomen in the course of a robbery. He was previously diagnosed as glucose-6-phosphate dehydrogenase deficient. Mild icterus was noticed on admission to the emergency room. Exploratory laparotomy revealed a perforated ileal loop that was resected, and because the liver color was greenish black, a liver biopsy was performed during the operation. After operation the patient went through a severe icteric state that resolved spontaneously within a few days. Urinary coproporphyrin levels, along with compatible liver biopsy, confirmed the diagnosis of Dubin-Johnson disease. Severe hyperbilirubinemia after an abdominal injury is uncommon and is usually due to either a biliary duct injury or iatrogenic injury. This case presents an unusual cause of severe postoperative jaundice due to the rare coexistence of two inherited disorders.

Evaluation of screening for hepatitis B surface antigen during pregnancy in a population with a high prevalence of hepatitis B surface antigen-positive/hepatitis B e antigen-negative carriers.

BACKGROUND: Universal hepatitis B vaccination in infancy was implemented in Israel in 1992. The program consists of active vaccination at birth and at 1 and 6 months of age, without hepatitis B surface antigen (HBsAg) screening during pregnancy. Infants of HBsAg carrier mothers do not receive specific hepatitis B immunoglobulin in addition to vaccine at birth. The recently arrived Jewish immigrants from Ethiopia are the group with the highest rate of HBsAg carriage (approximately 10%) in Israel. AIM: The objective of this study was to evaluate whether the present policy is effective against perinatal HBV transmission from mothers of Ethiopian origin to their infants. METHODS: The study group included 411 Israeli born children, offspring of mothers of Ethiopian origin. All infants were fully vaccinated starting at birth. Sera were collected from the children at the age of 9 to 36 months and from their mothers. Tests for HBsAg, antibodies to HBsAg (anti-HBs) and antibodies to hepatitis B core antigen (anti-HBc) were performed. RESULTS: Eighty-nine percent of the children had detectable anti-HBs, including 82.2% with protective anti-HBs concentrations (> or =10 mIU/ ml). Although 24 mothers (6.2%) were HBsAg carriers, none of the children was HBsAg-positive. Seven of 394 infants (1.7%) tested positive for anti-HBc. This test became negative in 5 of 6 who were followed for 12 months. The percentage of infants with protective anti-HBs concentrations decreased significantly from 91.4% at 9 to 12 months to 70.1% at 31 to 36 months of age. The mother's infection status was not associated with the infant's response to vaccine. Calculation based on the above data suggests that screening for HBsAg in pregnancy in that group is not cost-effective. CONCLUSIONS: Our results suggest that the Israeli vaccination program against HBV infection is effective, even in a high risk population, and additional measures are not cost-effective.

Hepatitis C virus seroconversion and genotype prevalence in patients and staff on chronic hemodialysis.

The prevalence of hepatitis C virus (HCV)-RNA positivity among hemodialysis patients varies between 10 and 70%. Few previous surveys revealed high frequency of seroconversion of HCV-RNA-negative patients over the years of hemodialysis. Only few studies reported HCV genotype variability. We evaluated all 65 patients on chronic hemodialysis in our dialysis unit. All sera positive to anti-HCV on ELISA were retested by reverse transcriptase polymerase chain reaction to HCV-RNA. Sixteen patients were found anti-HCV positive on ELISA, and 8 of them were also PCR positive. Three of these eight patients seroconverted during the year 1995. Four patients had both 1a and 1b genotypes of HCV, coexistence of genotypes 1b and 4a in one patient and genotypes 1a, 1b and 2a in the remaining three patients. Mean serum aminotransferase, duration of dialysis, and number of blood units transfused were significantly higher in the HCV-PCR-positive patients compared with the HCV-PCR-negative patients. Because strict isolation methods were initiated at the end of 1995, not one new case of HCV among dialysis patients was found in 1998, although new hemodialysis patients were diagnosed as having HCV. In conclusion, genotypes 1a and 1b, as is true for the general population in Israel, were also the predominant genotypes among hemodialysis patients; the coexistence of more than one genotype is common among hemodialysis patients; seroconversion is common among these patients and strict isolation methods are efficient and should be recommended.

[Low prevalence of hepatitis G infection in dialysis patients in Israel].

Prevalence of hepatitis G virus (HGV) infection in the general western population ranges from 0.2-1.5%. In high-risk groups, such as patients with chronic liver disease, hematologic disorders and drug addicts, prevalence is as high as 10%-15%. Dialysis patients have increased rates of HGV infection (6%-50%). We evaluated prevalence of HGV infection among dialysis patients, and the association between HGV infection and hepatitis C virus (HCV) infection. Serum samples were screened for HGV infection by RT-PCR. Screening for HCV infection was performed by an EIA test and confirmed by RIBA and RT-PCR for HCV. Sera were also tested for HBV markers. The study group included all 78 hemodialysis patients and 7 of the 12 peritoneal dialysis patients in our unit during September to November 1997. 4 (5.2%) were HGV-positive but none were peritoneal dialysis patients. 1 of the 12 HCV-positives was also infected with HGV. HGV infection was not associated with duration of dialysis, number of blood transfusions or levels of transaminases. Prevalence of HGV infection among our hemodialysis patients was low (5.2%), but higher than reported for the general population. Prevalence of HGV/HCV infection in hemodialysis patients was low and unrelated to duration of dialysis, number of blood transfusions and levels of transaminases.