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עמוד בית
Thu, 07.11.24

May 2006


Israel Vaccine Research Initiative
O. Hochwald, E. Bamberger and I. Srugo

The Israel Ministry of Health’s epidemiology department reported a record number of 1564 new pertussis cases in 2004. This brings the incidence rate to 23 per 100,000 population, indicating a marked increase in the prevalence of pertussis, from 1–3/100,000 in 1998, 9 in 2001, to 14 in 2003. The rate of atypical pertussis presentations in vaccinated patients, the decline in pertussis immunity post-vaccination, and the decreased awareness of potential infections in the adult population make the diagnosis of pertussis difficult and contribute to the rising incidence. In this article we review the current literature in order to increase awareness of the occurrence of pertussis in children as well as adults, discuss the laboratory diagnostic methods being used, and report the currently recommended means of treating the disease.

L. Moerman, A. Leventhal, P.E. Slater, E. Anis, R. Yishai and E. Marva

Background: Pertussis is the only vaccine-preventable disease that has re-emerged in Israel. The reported crude incidence of the disease increased 16-fold since 1998.

Objectives: To describe the epidemiology of pertussis and to explain the substantial increase in reported pertussis incidence in Israel in recent years.

Methods: Crude and specific pertussis incidence by age, patient immunization status, hospitalization rate and national immunization coverage rate were calculated from information provided by the public health offices of the Ministry of Health.

Results: The reported crude incidence of pertussis increased from 1–2/100,000 in 1994–98 to 23/100,000 in 2004. The trend was observed in all age groups, being most prominent in infants under age 1 year and in children aged 5–14. The incidence of pertussis was substantially higher in unvaccinated and partly vaccinated compared to fully vaccinated persons. Fifteen percent of notified cases were hospitalized, but in infants under age 1 year the hospitalization rate was 50%. National pertussis immunization coverage by age 2 years was stable during the last 10 years.

Conclusions: There are several possible explanations for the re-emergence of pertussis in Israel. The most plausible reason seems to be the waning of vaccine-induced immunity in face of infrequent natural exposure to the infectious agent and lack of a pertussis vaccine booster dose after age 1.
 

L.M. Shulman, Y. Manor, D. Sofer, T. Swartz and E. Mendelson

Background: Poliovirus rapidly evolves by nucleic acid substitutions and genetic recombination with other polioviruses and non-polio enteroviruses. Evolving oral poliovirus (Sabin strains) can rapidly revert to neurovirulence and undergo antigenic alterations.

Objectives: To evaluate the threat of vaccine-derived poliovirus (1–15% divergence from the respective Sabin strain) for a poliomyelitis-free population in a country with a long-standing routine vaccination program.

Methods: We characterized genetic and antigenic changes in OPV[1] strains isolated from sewage in Israel and evaluated intestinal immunity by measuring fecal excretion after OPV challenge of vaccinated children.

Results: Characterization of poliovirus from sewage revealed eight type 2 and three type 3 vaccine polioviruses that had replicated and started to evolve (vaccine that replicated and diverged by 0.5 to ≤ 1.0%) and nine highly diverged type 2 vaccine-derived polioviruses (1–15% divergence from the respective Sabin strain) with 8–14% divergence between the years 1998 and 2005. Six of the eleven VRPV[2] uniquely recombined with OPV and/or NPEV[3]. The nine VDPV[4] were epidemically related, genotypically neurovirulent, and had 10–15 amino acid substitutions in antigenic sites altering their antigenicity, but shared a single recombination. Type 2 OPV was excreted by 23% and 17% of infants challenged with OPV 3 months after partial immunization (two doses each of OPV and enhanced inactivated poliovirus) or full immunization (three doses of each) respectively, despite high humoral antibody titers.

Conclusions: Our findings, which show that OPV is excreted for a significant period by children with high humoral immunity, emphasize the long-term potential threat from VDPV in highly vaccinated populations. An adequate immunization program, combined with environmental surveillance, is necessary to prevent poliomyelitis and community transmission of poliovirus. 


 




[1] OPV = oral poliovirus

[2] VRPV = vaccine poliovirus that has replicated and started to evolve but is < 1 % but at least 0.5% diverged from the respective Sabin strain

[3] NPEV = non-polio enterovirus

[4] VDPV = vaccine-derived poliovirus 1–15% divergence from the respective Sabin strain


S. Rishpon

For children born after 1 January 2005, use of the Sabin oral polio vaccine in combination with the enhanced-potency Salk inactivated polio vaccine as part of the routine vaccination schedule was discontinued. The schedule now includes only IPV [1]. In September 2005, a fifth dose of pertussis vaccine was added for pupils in their second year of elementary school. This article describes the reasons for these changes, which have rendered Israel's routine vaccination program one of the most effective in the world.

 




[1] IPV = inactivated polio vaccine (Salk)


Focus
P. Saenger

The plight and fate of German Jewish pediatricians during the Nazi period in Europe has not received much attention, yet the narratives of the victims still resonate today and they deserve to be remembered. The stories of two women serve as examples of the fateful turns taken by the lives of many German Jewish pediatricians between 1933 and 1945. The two women, Dr. Luci Adelsberger and Dr. Lilli Jahn, illustrate both the ordeals endured, and disparate ways the Nazi policies ultimately spared or ended lives.

Original Articles
R. Rubinshtein, D.A. Halon, A. Kogan, R. Jaffe, B. Karkabi, T. Gaspar, M.Y. Flugelman, R. Shapira, A. Merdler and B.S. Lewis

Background: Emergency room triage of patients presenting with chest pain syndromes may be difficult. Under-diagnosis may be dangerous, while over0diagnosis may be costly.

Objectives: To report our initial experience with an emergency room cardiologist-based chest pain unit in Israel.

Methods: During a 5 week pilot study, we examined resource utilization and ER [1] diagnosis in 124 patients with chest pain of uncertain etiology or non-high risk acute coronary syndrome. First assessment was performed by the ER physicians and was followed by a second assessment by the CPU[2] team. Assessment was based on the following parameters: medical history and examination, serial electrocardiography, hematology, biochemistry and biomarkers for ACS[3], exercise stress testing and/or 64-slice multi-detector cardiac computed tomography angiography. Changes in decision between initial assessment and final CPU assessment with regard to hospitalization and utilization of resources were recorded.

Results: All patients had at least two cardiac troponin T measurements, 19 underwent EST[4], 9 echocardiography and 29 cardiac MDCT[5]. Fourteen patients were referred for early cardiac catheterization (same/next day). Specific working diagnosis was reached in 71/84 patients hospitalized, including unstable angina in 39 (31%) and non-ST elevation myocardial infarction in 12 (10%). Following CPU assessment, 40/124 patients (32%) were discharged, 49 (39%) were admitted to Internal Medicine and 35 (28%) to the Cardiology departments. CPU assessment and extended resources allowed discharge of 30/101 patients (30%) who were initially identified as candidates for hospitalization after ER assessment. Furthermore, 13/23 (56%) of patients who were candidates for discharge after initial ER assessment were eventually hospitalized. Use of non-invasive tests was significantly greater in patients discharged from the ER (85% vs. 38% patients hospitalized) (P < 0.0001). The mean ER stay tended to be longer (14.9 ± 8.6 hours vs. 12.9 ± 11, P = NS) for patients discharged. At 30 days follow-up, there were no adverse events (myocardial infarction or death) in any of the 40 patients discharged from the ER after CPU assessment. One patient returned to the ER because of chest pain and was discharged after re-assessment. 

Conclusions: Our initial experience showed that an ER cardiologist-based chest pain unit improved assessment of patients presenting to the ER with chest pain, and enhanced appropriate use of diagnostic tests prior to decision regarding admission/discharge from the ER.


 




[1] ER = emergency room

[2] CPU = chest pain unit

[3] ACS = acute coronary syndrome

[4] EST = exercise stress testing

[5] MDCT = multi-detector cardiac computed tomography angiography


H. Joffe, E. Bamberger, S. Nurkin, E. Kedem, Z. Kra-Oz, S. Pollack and I. Srugo

Background: The co-morbidity of human immunodeficiency virus and other sexually transmitted diseases in Israel has not been established. 

Objectives: To compare the prevalence of STDs [1]among HIV[2]-positive patients to HIV-negative patients visiting an STD clinic in northern Israel. 

Methods: Between December 2000 and December 2001, 176 HIV-positive individuals (53% males) were screened and compared to 200 HIV-seronegative individuals (76% males). Demographics, symptomatology and risk factors were obtained via questionnaire. First-void urine samples were tested for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae. Serum was tested for type-specific herpes simplex virus-2, hepatitis B and syphilis. 

Results: Relative to the seronegative STD patients, HIV-positive patients exhibited significantly greater risk-reducing sexual behaviors such as consistent condom use [29/86 (33.7%) vs. 16/187 (8.6%), P < 0.001], and abstinence in the previous 6 months [43/125 (34%) vs. 7/185 (3.8%), P < 0.001]. Nevertheless, STD prevalence was higher among HIV-positive than HIV-negative patients (79.5% vs. 37.5%, P < 0.001). HSV[3]-2, syphilis and HBV[4] were more common among HIV-positive than HIV-negative patients [120/175 (68.8%)] vs. 18/200 (9%), P < 0.001)], [43/161 (26.7%) vs. 0%, P < 0.001)], [13/171 (7.6%) vs. 3/200 (1.5%), P < 0.01)], respectively. In contrast, Chlamydia and gonorrhea were more commonly found in HIV-negative patients than HIV-positive patients [3/176 (1.7%) vs.13/200 (6.5%), P < 0.05] vs. [0% vs.5/200 (2.5%), P < 0.05], respectively. 

Conclusion: Despite the low risk sexual behavior of Israeli HIV patients, they had a high prevalence of chronic STDs (e.g., HSV-2, HBV and syphilis). The lower prevalence of Chlamydia and gonorrhea among HIV-immunosuppressed patients may be attributed to routine antibiotic prophylaxis against opportunistic infections. Nevertheless, as advocated by international health organizations, it appears prudent to recommend the routine screening of these asymptomatic HIV-positive patients for STD pathogens. 


 




[1] STD = sexually transmitted diseases

[2] HIV = human immunodeficiency virus

[3] HSV = herpes simplex virus

[4] HBV = hepatitis B virus


D. Ergas, A. Keysari, V. Edelstein and M.Z. Sthoeger

Background: Q fever is endemic in Israel, yet a large series describing the clinical spectrum of inpatients with acute Q fever in Israel is lacking. 

Objectives: To report on the clinical characteristics and outcome of hospitalized patients with acute Q fever in Israel. 

Methods: We conducted a retrospective study of 100 patients hospitalized in six medical centers, in whom acute Q fever was diagnosed by the presence of immunoglobulin G and M antibodies to phase II Coxiella burnetti antigens. 

Results: The mean age of the patients was 42.7 ± 17.3 years with a male to female ratio of 1.6:1. Acute Q fever occurred throughout the year but was more common during the warm season. The most common clinical presentation was acute febrile disease (98%, mean length of fever 15.5 ± 8.6 days), followed by hepatitis (67%) and pneumonia (32%). The prominent laboratory findings included: accelerated erythrocyte sedimentation rate, normal or low white blood count with many band forms, thrombocytopenia, and abnormal urinalysis. Although the diagnosis of acute Q fever was not known during the hospitalization in the majority of patients, about 80% of our patients received appropriate antibiotic therapy and all patients recovered. 

Conclusions: Patients with acute Q fever present with a typical clinical picture that enables clinical diagnosis and empiric therapy in most cases. The prognosis of hospitalized patients with acute Q fever is excellent.

F. Sperber, Y. Weinstein, D. Sarid, R. Ben Yosef, A. Shalmon and N. Yaal-Hahoshen

Background: The current methods for pre‑ and post‑chemotherapy examination of the extent of disease in the breast and lymph nodes do not provide sufficiently accurate information and, not infrequently, the surgeon has to re‑operate.

Objectives: To correlate the findings between three methods of examination (physical examination, ultrasonography, mammography), all performed by the same oncologic and radiologic team, in patients with locally advanced breast cancer or a tumor/breast tissue ratio that precludes breast-conserving surgery.

Methods: Forty patients (median age 48 years, range 24–73) with locally advanced breast cancer or with a tumor/breast ratio that precluded breast‑conserving surgery were evaluated by the same medical team and received neoadjuvant chemotherapy. Surgery was performed in all, and the pathologic specimen was correlated with the results of the other examinations.

Results: In the pre‑chemotherapy evaluation, the imaging findings of the breast correlated with the physical findings in 78% of the patients and with the axilla examination in 66.7%. In the post‑chemotherapy analysis, imaging agreed with the physical findings of the breast in 62.2% and in 76.3% of the axilla. Sonography best detected occult breast disease and axillary lymph nodes but correlated with pathology in only 58% of the patients in diagnosing breast tumor and in 65.8% in diagnosing axillary lymph nodes. Mammography correlated with breast and lymph node pathology in half the patients.

Conclusions: None of the classical methods of post‑neoadjuvant chemotherapy evaluations could adequately delineate the actual extent of the disease in the breast and axillary lymph nodes. More exacting techniques of imaging combined with the classical methods are required.

 
 

Reviews
R. Kannai and I.R. Chertok

The Ashkenazi-Jewish population is at increased risk for several recessively inherited disorders. While some of the disorders have severe or fatal symptom manifestations, others, such as non-neuronopathic Gaucher disease, do not usually pose a serious, life-threatening illness. Many healthcare centers in Israel offer prenatal panel screening. Controversy exists over the inclusion of Gaucher disease in the panel screening, especially since Gaucher disease screening lacks prognostic reliability. Most screening participants do not discriminate between the specific tests in the panel and are unable to discern between severe, life-threatening diseases and those that are less severe and even treatable. By including screening for Gaucher in the panel screening program, there is risk of a "panel effect," leading to termination of a pregnancy positive for Gaucher disease, without sufficient knowledge and understanding of the disease. Increasing medical and public awareness and knowledge of the disease, its prognosis and treatment options may reduce the rate of under-informed abortions associated with prenatal screening of Gaucher disease.

Imaging
T. Arazi-Kleinman, D. Shepshelovich and Y. Shoenfeld
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