Ilana Belmaker

The effect of measles–mumps–rubella (MMR) immunization on the immune responses of previously immunized primary school children

Current policies for measles control call for administration of a second dose of vaccine to immunize those who failed to respond to the initial dose and to boost the responses of those with low levels of antibody. However, there has been concern expressed publicly that reimmunization may have adverse immunologic consequences. To determine the effects of reimmunization on immune responses, primary school children (N=38, mean age=6.14+/-0.35 years) with documented previous measles-mumps-rubella vaccine (MMR) immunization during infancy 4-5 years earlier were studied before and 1 month after receiving MMR as a part of routine reimmunization in Beer-Sheva, Israel. A substantial number of children were seronegative to measles (24%), mumps (34%) and rubella (44%). On reimmunization all seroconverted to mumps and rubella and all but one (92%) seroconverted to measles. The geometric mean titer of measles virus neutralizing antibody increased from 171 to 724 and the greatest increases occurred in those with the lowest pre-immunization titers. Moderate increases in levels of total IgM, IgG and IgE were detected in those with increases in antibody to measles virus. After reimmunization leukocyte counts decreased significantly from (5.8 x 10(6))+/-2.3 to (3.4 x 10(6))+/-0.7 ml(-1) (P=0.0001). The percentages of both CD4(+) and CD8(+) T cells decreased while the CD4:CD8 ratio remained unchanged. The percentage of CD56(+) natural killer (NK) cells increased from 5.2+/-2.7 to 7.2+/-2.8 (P=0.01). Functional assays showed improved lymphoproliferation in response to stimulation with phytohemagglutinin and tetanus toxoid and stable NK lytic activity. Therefore, reimmunization was accompanied by decreased leukocyte counts, but leukocyte function was unchanged or improved.

Elimination of hepatitis a infection outbreaks in day care and school settings in southern Israel after introduction of the national universal toddler hepatitis a immunization program.

Background: In 1999, Israel became the first country to begin universal toddler immunization against hepatitis A infection with a 2-dose schedule at 18 and 24 months. The effect of the Israeli program on outbreaks of Hepatitis A in day care and school settings was studied. Methods: The records of all hepatitis A illness outbreaks in day care and school settings reported to the Ministry of Health in Southern Israel during 1993 through 2005 were reviewed. The number of exposed contacts for whom postexposure prophylaxis was administered was retrieved from records of epidemiologic investigations. Rates of immunization coverage were extracted from records of Maternal and Child Health Clinics. Results: Three hundred nineteen cases of hepatitis A illness during the years 1993 through 2005 were associated with 113 outbreaks in day care and school settings of which 92% occurred before the institution of universal toddler immunization. Since 2000, no hepatitis A infection outbreaks have been reported in any day care and school settings in the region. An average of 732 children received immunoglobulin prophylaxis yearly because of exposure to an outbreak in an educational setting during the preimmunization period, 106 in 2000 and zero in the 5 years since 2001. The data showed marked herd immunity since school-aged children born before 1999 were not immunized, but elimination of outbreaks occurred equally in that age group. Immunization coverage was 86.4% for one dose of hepatitis A vaccine by age 3 years and 77.3% for 2 doses among the birth cohort of 2000. Conclusions: Universal hepatitis A immunization of toddlers was associated with disappearance of outbreaks in educational settings. This included cohorts of nonimmunized children representing marked herd immunity.

Major congenital malformations and residential proximity to a regional industrial park including a national toxic waste site: An ecological study

BackgroundPublic concern about exposure to emissions from the regional industrial park (IP), including 17 chemical plants and the national industrial toxic waste site, initiated this study of the possible association between major congenital malformations (MCM) and residence near the IP in Israels Southern District.MethodsThe study was conducted during the period 1995–2000 and included 63,850 deliveries. Data on deliveries and MCM detected at births were obtained from the regional medical center, and stratified by ethnicity and type of locality. As exposure indicator we used distance categories (proximal and distant) and predominant wind direction from the IP. Distance stratification was based on the geographical distribution of the localities and complaints about the odor related to IP emissions. Based on these complaints, localities up to 20 km from the IP were considered proximal to the IP.ResultsAverage rates of MCM were 5.0% and 4.1% for Bedouin and Jewish newborns, respectively. The rate of MCM for Bedouin from proximal localities was significantly greater compared with distant localities (5.6% vs. 4.8%; RR = 1.17 with 95% CI: 1.04–1.29). In the proximal Bedouin permanent localities, the MCM rate reached 8.2 %, which was significantly higher than in distant areas (RR = 1.63, 95% CI: 1.39–1.80). Significant risk increase of central nervous system MCM was found in these localities, compared to distant ones (RR = 2.27, 95% CI: 1.44–3.60). Among newborns from the traditional tribal settlements, proximity to the IP was associated with increased rates of the following MCM: 1) all combined, 2) those associated with chromosomal abnormalities, and 3) those defined as others unclassified MCM. Comparison of autosomal recessive disease rates by proximity to the IP in Bedouin newborns indicates that the observed increased risk of MCM is not explained by consanguineous marriages. The rates of MCM in the Jewish population were similar among exposed and unexposed inhabitants.ConclusionResidential proximity to the IP is associated with increased rates of MCM among Arab-Beduin but not in Jewish populations. These observations indicate the need for public health protection of a vulnerable society in transition, although the relative importance of chemical exposure and health care utilization requires further study.

Utilization of Antenatal Care Services by a Semi-Nomadic Bedouin Arab Population: Evaluation of the Impact of a Local Maternal and Child Health Clinic

Objective. The objective of this study was to evaluate changes in antenatal care (ANC) utilization among semi-nomadic Bedouin Arab women living in the Negev desert of Israel before and after the establishment of a local Maternal and Child Health (MCH) Clinic. Methods. Retrospective record review of ANC utilization by pregnant women in two successive pregnancies, one before and one after the establishment of a local MCH Clinic. The study population was comprised of all 85 women who registered their newborns for care at MCH Clinic A, regardless of whether or not they had registered at the clinic for ANC. Records of their care in previous pregnancies were obtained from other MCH Clinics previously utilized by the family. Results. There was a significant increase in the percent of women receiving ANC from 31.8% to 57.6% with the establishment of the local MCH Clinic (pu2009=u20090.004), increase in the percent of pregnant women who had at least one physician examination from 27% to 45% (pu2009=u20090.003), in the percent who had at least 3 nursing visits from 25% to 39% (pu2009=u20090.011) and in the compliance with screening tests. There was no significant change in birth week and birth weight between pregnancies before and after the establishment of Clinic A. Conclusions. The study demonstrated improvement in utilization of ANC in the study population. However, after the establishment of a local MCH clinic, over 40% of pregnant women still received no ANC. Non-geographic barriers to ANC are important and need to be addressed through community-based intervention programmes.

Reduction of vaccine-preventable communicable diseases in a Bedouin population: summary of a community-based intervention programme

BACKGROUNDnThe Bedouin Arab population of southern Israel is in transition from a semi-nomadic lifestyle to permanent settlement, with many characteristics of a third-world population. A major outbreak of measles in the winter of 1990-91, with an incidence of 415.6 per 100,000 and a case fatality rate of 2.2 % among the Bedouin, led to the establishment of a national committee, which recommended an intervention programme. We report on the effect of the programme implementation on the reduction of vaccine-preventable communicable diseases in a Bedouin Arab population.nnnMETHODSnWe compared immunisation coverage and incidence of reportable vaccine-preventable communicable diseases before and after implementation of the intervention programme.nnnFINDINGSnImplementation of the intervention programme was associated with a marked increase in immunisation coverage, from 53% for first measles immunisation among those born in 1988, and reaching 2 years of age in 1990 at the start of the outbreak, to 90% at age 2 years among those born in 2001. We noted a decrease in all vaccine-preventable communicable diseases, except for pertussis, during this period.nnnINTERPRETATIONnThe implementation of a targeted programme to improve immunisation coverage, and other concomitant changes in health-care delivery, was temporally associated with reduction of vaccine-preventable communicable diseases in a population of Bedouin Arabs in Israel who are living in semi-nomadic conditions. The success of the programme could be applicable to semi-nomadic populations living in other areas of the middle east.

Women's health custom made: building on the 40 days postpartum for Arab women.

The 40-day postpartum period is characterised in the Middle East and elsewhere by an observance of seclusion, congratulatory visiting, the reciprocal exchange of gifts and money, and a special diet. Based on primary data from in-depth interviews among the Negev Bedouin in Israel, health enhancing practices are reviewed. The data are a subset from a larger study carried out in this setting. Often postnatal checkups, family planning counselling, and immunization services may not be routinely available or used. It is argued that these health services could be provided at the end of the 40-day period for mother and child, as in a pilot study in Tunisia some years ago. Health service provision would thus build on the health enhancing practices of the 40-day period.The 40-day postpartum period is characterised in the Middle East and elsewhere by an observance of seclusion, congratulatory visiting, the reciprocal exchange of gifts and money, and a special diet. Based on primary data from in-depth interviews among the Negev Bedouin in Israel, health enhancing practices are reviewed. The data are a subset from a larger study carried out in this setting. Often postnatal checkups, family planning counselling, and immunization services may not be routinely available or used. It is argued that these health services could be provided at the end of the 40-day period for mother and child, as in a pilot study in Tunisia some years ago. Health service provision would thus build on the health enhancing practices of the 40-day period.

The effect of universal toddlers-only hepatitis A virus vaccination program on seropositivity rate in unvaccinated toddlers: evidence for reduced virus circulation in the community.

Background: In July 1999, a national toddler-only hepatitis A virus (HAV) vaccination program was introduced in Israel. Passive and active surveillance showed a large reduction in disease rate, but an objective measurement was needed. We hypothesized that toddlers vaccination in a population living in an endemic area would reduce virus circulation, resulting in reduced HAV seropositivity rates in unvaccinated toddlers. Methods: The study was conducted among Bedouin children in southern Israel, for whom HAV vaccine coverage reached 85.5% and 74.9% for first and second HAV vaccine doses, respectively, in 2000. Toddlers received 2 doses of HAV vaccine at 18 and 24 months. Data on vaccine coverage was received from well-baby clinics. Sera were obtained from healthy unvaccinated 16- to 20-month-old toddlers. Anti-HAV immunoglobulin (Ig)G concentrations were tested by enzyme-linked immunosorbent assay. Results: A total of 629 sera were tested (209 obtained in 1991–2000 and 420 obtained in 2001–2002). Seropositivity rates of ≥100 mIU/mL ranged from 16.2% to 19.6% in 1991 through 2000 (children born before immunization program). These rates dropped to 2% in 2001–2002 and to 0% in 2003 through 2007. Furthermore, IgG concentrations were significantly lower (P < 0.001) in samples taken in 2000, only a few months after beginning of vaccination, than in those taken before initiation of the HAV immunization program (1991–1998), suggesting a marked reduction in circulating HAV resulting in natural boosting. Conclusions: Because HAV vaccines are licensed in children ≥12 months old, rates of anti-HAV seropositivity in unvaccinated toddlers can be an objective and sensitive tool to evaluate the effect of immunization program on virus circulation. This method is of special value in communities where no appropriate surveillance is in place.

Differential immune responses to primary measles-mumps-rubella vaccination in Israeli children.

ABSTRACT Measles remains an important cause of morbidity and mortality worldwide, primarily due to problems associated with delivery of the live attenuated vaccine to susceptible populations. In some developed countries, there is concern about the effects of immunization on the immune system. In this study, we analyzed the responses of 12-month-old Bedouin and Jewish children living in Israel to routine measles-mumps-rubella (MMR) vaccination. Seroconversion to measles was 99% in Bedouin and 79% in Jewish children (P < 0.01), and that to mumps and rubella was 92 to 100% in both groups. Measles neutralizing antibody titers were higher in Bedouin (333 ± 39 mIU/ml) than Jewish (122 ± 60 mIU/ml) children (P < 0.002). Immunoglobulin G levels were higher in Bedouin than Jewish children (P = 0.007) and increased after vaccination (P = 0.0009). Leukocyte (P < 0.02) and lymphocyte (P = 0.04) counts were higher and CD4 lymphocyte percentages were lower (P < 0.001) in Bedouin than Jewish children before and after vaccination. Leukocyte counts and natural killer cell numbers did not change after vaccination, but lytic activity increased in Bedouin children (P < 0.005). Spontaneous proliferation of cultured peripheral blood mononuclear cells increased with vaccination, but there were no changes in the proliferative responses to phytohemagglutinin or tetanus toxoid. In summary, no adverse effects of MMR vaccination on immune function were detected. However, there were differences in underlying immunologic parameters and in response to the measles component of the vaccine between Bedouin and Jewish children. It is not known whether genetic differences or environmental exposure accounts for these differences.

Eliciting local voices using natural group interviews

Abstract As part of a 5 year intervention study to improve maternal and child health care, natural group interviews were carried out amongst a minority group of Israeli citizens, Palestinian Arabs of Bedouin origin living in the Negev. This paper argues that the use of individual questionnaires, in this setting, is inappropriate in that it would ignore the views of other household members, likely to be crucial to the parents’ decisions about health care utilisation. The interviews utilised the natural groups of women gathering to visit mothers during the first 40 days post‐partum, and of men who gather in family or sub‐tribal guest sections. Their views on issues concerning difficulties of access owing to distance, social and linguistic barriers and cost are reported. These local views are placed in the wider context of health care provision to disadvantaged ethnic minorities in Israel and elsewhere.

Perinatal mortality and residential proximity to an industrial park.

The authors objective was to determine whether residential proximity to an industrial park (IP) is associated with increased perinatal mortality (PM). This semiecological study included 63,850 delivered births with 840 cases of PM (1995-2000). The authors categorized the study populations by ethnicity (ie, Bedouin and Jewish) and type of locality. Residential distance from the IP served as a surrogate indicator of exposure. Among Bedouin newborns, proximity to the IP was associated with increased PM rates (relative risk = 1.45; 95% confidence interval = 1.22-1.72). The excess in PM was not related to maternal or newborn physical characteristics that the authors observed. The risk of PM and its components in the Jewish localities was not associated with IP proximity. The association between residential proximity to the IP and excess in PM among only Bedouin newborns may be related to vulnerability caused by the nomadic nature of the society.