Resolution of the pathways of poliovirus type 1 transmission during an outbreak.

An outbreak of poliomyelitis with 20 cases occurred in Israel, Gaza, and the West Bank from October 1987 to October 1988. The wild type 1 poliovirus associated with the outbreak was most closely related to viruses found in the Nile Delta. The epidemiologic links among patients involved in the outbreak and patients with community-acquired infections during the outbreak were inferred from the evolutionary relationships among isolates of the outbreak virus. Complete VP1 sequences (906 nucleotides) were determined for 12 clinical and 4 sewage isolates. A total of 58 nucleotide differences were found among the 16 isolates; 74% of all substitutions were synonymous third-position transitions. An evolutionary tree, representing both the pathways of VP1 sequence evolution and the inferred chains of virus transmission during the outbreak, was constructed under the assumption that each substitution had occurred only once. The combined epidemiologic and molecular data suggest that a single founder strain was introduced into Israel from the vicinity of Gaza in the fall of 1987. Poliovirus circulation was apparently localized to southern communities during the winter and spread north by the following summer into the Hadera subdistrict of Israel, where it radiated via multiple chains of transmission into other communities in northern Israel and the West Bank. The close sequence matches (>99%) between clinical and sewage isolates from the same communities confirm the utility of environmental sampling as a tool for monitoring wild poliovirus circulation.

Detection of poliovirus circulation by environmental surveillance in the absence of clinical cases in Israel and the Palestinian authority.

The global eradication of poliomyelitis, believed to be achievable around the year 2000, relies on strategies which include high routine immunization coverage and mass vaccination campaigns, along with continuous monitoring of wild-type virus circulation by using the laboratory-based acute flaccid paralysis (AFP) surveillance. Israel and the Palestinian Authority are located in a geographical region in which poliovirus is still endemic but have been free of poliomyelitis since 1988 as a result of intensive immunization programs and mass vaccination campaigns. To monitor the wild-type virus circulation, environmental surveillance of sewage samples collected monthly from 25 to 30 sites across the country was implemented in 1989 and AFP surveillance began in 1994. The sewage samples were processed in the laboratory with a double-selective tissue culture system, which enabled economical processing of large number of samples. Between 1989 and 1997, 2,294 samples were processed, and wild-type poliovirus was isolated from 17 of them in four clusters, termed "silent outbreaks," in September 1990 (type 3), between May and September 1991 (type 1), between October 1994 and June 1995 (type 1), and in December 1996 (type 1). Fifteen of the 17 positive samples were collected in the Gaza Strip, 1 was collected in the West Bank, and 1 was collected in the Israeli city of Ashdod, located close to the Gaza Strip. The AFP surveillance system failed to detect the circulating wild-type viruses. These findings further emphasize the important role that environmental surveillance can play in monitoring the eradication of polioviruses.

The immunomodulator AS101 restores T(H1) type of response suppressed by Babesia rodhaini in BALB/c mice.

The immunomodulator AS101 has been previously shown to confer protection upon BALB/c mice infected with the intraerythrocytic parasite Babesia rodhaini (B. rodhaini). The present study focuses on the effect of AS101 administration on the acute phase of babesial infection where T helper cell subset patterns-TH1/TH2-were assessed in heavily infected mice. Secretion of cytokines of the TH1 subset (IL-2, IFN-gamma, IL-12) and of the TH2 subset (IL-10, IL-4) as well as TGF-beta was measured following the administration of AS101 2 weeks before parasite infection. Our results demonstrate that the parasites suppress IL-2 protein and IL-12 mRNA and that AS101 upregulates their secretion: IL-2, 8 u/ml vs 34 u/ml, respectively; IFN-gamma protein, 2370 pg/ml vs 4777 pg/ml, respectively. Conversely, babesial infection results in the upregulation of IL-10 and IL-4 proteins and TGF-beta transcripts, whereas AS101 downregulates their production: IL-10, 1800 pg/ml vs 360 pg/ml, respectively; IL-4, 58.3 pg/ml vs 24.5 pg/ml, respectively. A possible escape mechanism induced by B. rodhaini is suggested, starting with IL-10 inhibition of macrophage activities leading to a suppression of the TH1 response and of IL-2 in particular. It is therefore possible that AS101 may protect infected mice by activating cellular-mediated immunity and concurrently balancing the TH subset responses. It is suggested that AS101 may be effective as an antiparasitic drug.

Identification of a new strain of fastidious enterovirus 70 as the causative agent of an outbreak of hemorrhagic conjunctivitis.

A 1994 outbreak of acute hemorrhagic conjunctivitis in Israel was caused by an enterovirus 70 strain that was distinct from previously reported strains. Characterization was by electron microscopy (eye washes), reverse transcription-PCR (RT-PCR; eyewash, specimens, eye swabs, and tears), and sequence analysis of RT-PCR-amplified fragments from the 5' noncoding region and VP1.

Human immunodeficiency virus (HIV) inactivation of banked bone by gamma irradiation.

OBJECTIVE: The increasing number of patients with acquired immunodeficiency syndrome (AIDS) and human immunodeficiency virus(HIV)-positive carriers, poses difficulties when musculo-skeletal tissues are considered for banking in readiness for future clinical application. This study was conducted to test the actual yield of gamma irradiation on HIV infectivity, within HIV-infected bones. METHODS: The effect of gamma irradiation on bones containing T-cells chronically infected with HIV type I (HIV-I) was studied, in respect to inactivation of the virus. RESULTS: After exposure of the cell-free virus or infected T-cells to 2.5 megarads of gamma irradiation, the authors were able to demonstrate complete inactivation of the virus. CONCLUSIONS: It would appear from this study that gamma irradiation at this dose is sufficient to achieve clinical sterilisation of bones and facilitate their use for reconstructive procedures by eliminating the risk of HIV transmission to the recipient. Furthermore, when preparing bones for banking, this would also seem to be the method of choice in preventing the transmission of various strains of bacteria, fungi and other viruses.

Immediate immunosuppression caused by acute HIV-1 infection: a fulminant multisystemic disease 2 days post infection.

A healthy 19-year-old woman had vaginal intercourse on a single occasion with an HIV-1 positive male from Gambia. Two days later she developed an acute HIV infection presenting as a fulminant multisystem disease that lasted for 35 hospital days and included: immediate immunosuppression with extreme CD4+ lymphocytopenia and combined with CD8+ lymphocytosis, neutropenia and hypogammaglobulinemia; intermittent spiking fever; pneumonitis; hepatitis; changing skin rashes; peripheral neuropathy with myopathy, and panencephalitis. P24 antigen was detected by Western blot on day 23 and seroconversion was detected by ELISA on day 25. Cultured lymphocytes from peripheral blood and cerebrospinal fluid grew HIV-1.

Rearrangement of the immunoglobulin heavy chain gene in juvenile chronic myeloid leukaemia.

Five patients with clinical and laboratory features typical for juvenile chronic myeloid leukaemia (JCML) are presented. Rearrangement of the j joining region of the immunoglobulin heavy chain (Jh) was demonstrated in three children out of five analysed. As no Vh to DhJh nor kappa light chain rearrangements were demonstrated, it is reasonable to speculate that the transforming event of the stem cell happened at the stage when Dh to Jh rearrangement took place. As the monocytic lineage is prominent in JCML, it is suggested that the transforming event happens in a unique stem cell with intermediate differentiation towards the myelomonocytic as well as the B-lymphatic lineage. This stem cell, which is present at a certain stage of embryogenesis, disappears later. Such an early 'hybrid' cell is sometimes involved in leukaemias of early infancy, and may be the transformed cell in some cases of infantile leukaemia.

HIV-2 infection in Israel: a new epidemic?

AIDS may be caused by two different retroviruses, HIV-1 and HIV-2. Hitherto only HIV-1 has been reported in Israel. We recently discovered HIV-2 as a solitary pathogen in the blood of two foreign workers from West Africa. In view of the relative ease of travel to Israel, it is essential to perform screening for both HIV viruses in all subjects with an enhanced risk, including visitors from countries with a high incidence of HIV-1 or HIV-2 infection and their contacts.

Lymphomatous T-cell leukemia in two Arab children. Is there a role for an environmental effect.

Two Arab children from the Gaza strip presented with fever, weakness, hepatosplenomegaly, lymphadenopathy and leukocytosis. The peripheral and bone marrow blasts had an immunophenotype compatable with T-cell acute lymphoblastic leukemia, and exhibited unusual markers (CD2+, CD3+, CD4-, CD8-). Cytogenetic studies revealed t(8;14)(q24;q11), possibly involving the alpha/delta locus of the T-cell receptor gene on chromosome 14 rather than the immunoglobulin heavy-chain locus usually involved in the t(8;14)(q24;q32), which is typical for Burkitt's leukemia/lymphoma. One of the children had a brother who died of T-cell acute lymphoblastic leukemia a few years later, however, his blasts showed deletion of chromosome 12. The possible role for environmental factors associated with low socioeconomic status, as well as of genetic factors in leukemogenesis are discussed.

Identification of feline- and canine-like rotaviruses isolated from humans by restriction fragment length polymorphism assay.

Restriction fragment length polymorphism assay of reverse-transcribed and polymerase chain reaction-amplified rotavirus gene segment 9 was developed to differentiate human serotype 3 rotaviruses from animal serotype 3 rotaviruses. On the basis of similarities or differences in HinfI and DdeI restriction profiles, unusual group A serotype 3 human rotaviruses that belonged to subgroup I were shown to be of feline and canine origin. By this approach, the new human rotavirus isolates 5193, AU-387, AU-720, AU-785 and AU-1115 were shown to resemble certain feline-like human rotaviruses. Similar results were previously obtained by Nakagomi et al. (O. Nakagomi, A. Hoshima, Y. Aboudy, I. Shif, M. Mochizuki, T. Nakagomi, and T. Gotlieb-Stematsky. J. Clin. Microbiol. 28:1198-1203, 1990) by using RNA-RNA cross hybridization with established feline rotaviruses. The restriction fragment length polymorphism assay can provide fast and valuable information on the interspecies transmission of rotaviruses in nature.

Molecular epidemiology of type 1 polioviruses isolated in Israel and defined by restriction fragment length polymorphism assay.

The genomic variability of 27 type 1 polioviruses (PV-1) isolated in Israel during 1980-1991 was examined by restriction fragment length polymorphism (RFLP) analysis of a reverse-transcribed genomic fragment amplified by polymerase chain reaction. By using the restriction enzymes HaeIII, DdeI, and HpaII, strain-specific restriction profiles were generated for the PV-1/Mahoney and PV-1/Sabin strains and 27 wild-type isolates. The profile observed for PV-1 isolated during an outbreak in 1988 was also observed for PV-1 isolated from different places in Israel in 1982 and 1983, 1987, and 1991. This profile, characterized by the lack of the DdeI site, was different from the DdeI profile of PV-1 isolated in 1984 or in 1986 from sporadic cases of poliomyelitis. The diversity of circulating PV-1 in Israel was also confirmed by nucleotide sequence analysis. The epidemiologic information provided by the RFLP and sequence data establishes a clear epidemiologic link between epidemic and sporadic virus strains and demonstrates the power of this molecular approach to epidemiology.

Inhibition of the reverse transcriptase activity and replication of human immunodeficiency virus type 1 by AS 101 in vitro.

In a search for compounds active against human immunodeficiency virus type 1 (HIV-1), it was found that the novel low-molecular weight immunoenhancer ammonium trichloro(dioxyethylene-O,O'-) tellurate (AS101) suppresses production of HIV-1 in vitro. Treatment of HIV-1-infected peripheral blood mononuclear cells (PBMC) with increasing concentrations of AS101 resulted in substantial inhibition of virus production as measured by both reverse transcriptase (RT) activity and antigen presence in supernatants of treated cells. AS101 had no effect on PBMC viability, growth, or morphology up to a concentration of 15 microM for 14 days. To elucidate a possible mechanism for the inhibition of AS101, we have analyzed the effect of the drug on the catalytic functions associated with HIV RT, namely the RDDP, DDDP, and RNase H activities. RDDP and DDDP activities were impaired by the drug with calculated IC50 value of about 4 microM. On the other hand, the RNase H activity was less sensitive to AS101, with an apparent IC50 value of about 30 microM. The anti-HIV-1 activity of AS101 as reflected by inhibition of the different catalytic functions associated with viral RT, in the absence of drug-related toxicity to lymphocytes, together with its immunomodulating activity strongly argues in favor of its evaluation, as a therapeutic agent for patients with HIV infection.

Prevalence of HIV antibodies in transsexual and female prostitutes.

Human immunodeficiency virus (HIV) prevalence was studied in an unselected group of 216 female and transsexual prostitutes. Subjects were asked about age, biological sex, marital status, children, length of occupation, sexual practices, and drug abuse history. Blood was drawn on site. All 128 females who did not admit to drug abuse were seronegative; 2 of the 52 females (3.8%) who admitted to intravenous drug abuse were seropositive. In contrast, 11.1% of the 36 male transsexuals (including 3 out of 32 non-drug abusers) were seropositive. The results support the notion that vaginal transmission of HIV is less effective than anal transmission.

'Silent' HIV infection among wives of seropositive HIV carriers in the Ethiopian community in Israel.

We have previously described the phenomenon of 'silent HIV carriers', i.e. individuals with HIV specific immunity and a positive PCR for HIV-1, yet HIV seronegative. In the present study, we have looked for such 'silent' carriers among wives of individuals infected with HIV in Africa (Ethiopia). In addition to determining HIV serology, peripheral blood mononuclear cells (PBMC) were tested by PCR for HIV-1 and for their ability to generate specific antibodies to HIV upon polyclonal B-cell activation (P-BAT). Out of 16 wives so tested, three were HIV seropositive and among the 13 seronegatives, eight were P-BAT positive and five were both P-BAT and PCR positive. These findings suggest that (1) 'silent' HIV carriers may indeed be present in African populations; (2) interpretation of the 'silent' carrier phenomenon is not clear and will depend on clinical follow-up and the ability to culture virus from such carriers; and (3) results of HIV serology in this population and probably in other African populations should be viewed with caution.

Detection of CMV-DNA in cells from peritoneal fluid of IPD/CAPD patients by polymerase chain reaction.

Documented viral peritonitis in peritoneal dialysis patients is rare, although up to 20% of all cases are culture negative (non-fungal, non-bacterial). CMV-infected peritoneal cells may serve as a reservoir for reinfection and/or reactivation of CMV after renal transplantation. CMV-Polymerase Chain Reaction (CMV-PCR) amplification analysis identified CMV-DNA in cells from the peritoneal dialysate of 8 patients (3 culture negative peritonitis from a total of 5 examined) and 5 asymptomatics) out of 17 potential kidney transplant recipients (6 on IPD 16.6 +/- 6 months, range 10-29 months; 11 on CAPD 28.1 +/- 25 months, range 2-81 months). Serum titers (10/17 patients analyzed) of anti-CMV IgG antibodies ranged from < 1:20 to 1:320 (no correlation with CMV-DNA) while anti-CMV IgM antibodies were undetectable. Detection of CMV specific sequences in peritoneal cells in peritoneal dialysis patients by the PCR assay is sensitive (amplification of a 133 bp immediate early CMV gene sequence allows detection of 10 CMV infected cells in a background of 10(5) uninfected peritoneal cells), rapid (1 day visual, 3 days with confirmation by Southern hybridization), specific (no amplification of human embryo and kidney cell DNA, or HSV, EBV, or VZV infected cells) and is non-invasive in IPD/CAPD patients since no additional invasive technique is required.

EBV genome and immunoglobulin gene rearrangement in the differential diagnosis of nasopharyngeal carcinoma and lymphoma.

Head and neck tumors include nasopharyngeal carcinoma (NPC) and lymphoma. The differential diagnosis of these tumors is based on histology, immunocytochemical staining, and EBV serology. In rare cases it might be difficult to distinguish between NPC and lymphoma in HE section or biopsies. DNA hybridization with cloned EBV and human immunoglobulin gene fragments allows the detection of EBV-related sequences and immunoglobulin gene rearrangements. The presence of EBV genome supports the diagnosis of NPC or EBV related BL, while rearrangement of immunoglobulin genes points to B-cell lymphoma. The diagnosis in 11 patients suspected of head and neck tumors was carried out by hybridization of DNA extracted from the tumors and assayed with cloned EBV and IgHCJ DNA probes. One patient proved to have EBV-associated BL based on positive hybridization with EBV probes and immunoglobulin rearrangement, presenting a unique hybridization with cloned EBV DNA BamHI W fragment, with bands of 3.2 and 3.9 kb. BL was confirmed in this patient by demonstration of c-myc rearrangement. A second patient was negative in hybridization with EBV, and positive for immunoglobulin rearrangement, and therefore was diagnosed as having B-cell lymphoma. In seven patients NPC was confirmed by hybridization with EBV-DNA probes. In two patients, both NPC and B-cell lymphomas were excluded.

Kaposi's sarcoma in immunosuppression. Possibly the result of a dual viral infection.

Kaposi's sarcoma of the gingiva and skin developed in an HIV-negative renal transplant patient while he was receiving cyclosporine therapy. The Kaposi's sarcoma developed shortly after the patient had an acute infection with cytomegalovirus (CMV). Electron microscopy of the tumor's established cell line showed two types of virus-like particles. CMV DNA was identifiable in the cell line whereas infectious CMV could be isolated only after repeated passages (only after 3 months of culture). The other virus could not be identified, but did not appear to be either HIV or papilloma virus. The patient's tumor regressed after the discontinuation of cyclosporine therapy and the recovery from the acute CMV infection.