Kei Numazaki

Chlamydia trachomatis infection in early neonatal period

BackgroundThe clinical characteristics of Chlamydia trachomatis respiratory tract infections in Japanese neonates were investigated.MethodsClinical, laboratory and microbiological characteristics of five infants with pneumonia due to C. trachomatis in early neonatal period were analyzed.ResultsOnly C. trachomatis was identified in 4 infants. Both C. trachomatis and cytomegalovirus was identified in one. Wheezing, tachypnea and cyanosis were common in infants. Mothers of five infants had negative chlamydial EIAs at 20 weeks of gestation.ConclusionsWe identified five cases of C. trachomatis respiratory tract infections in early neonatal period with the possibility of intrauterine infection. Targeted screening, early diagnosis, and effective treatment of perinatal and neonatal chlamydial infections seems to be necessary

Emergence of antiretroviral therapy resistance-associated primary mutations among drug-naive HIV-1-infected individuals in rural western cameroon

Summary: The prevalence of antiretroviral therapy (ART) resistance-associated mutations among HIV-1 strains in western Cameroon was evaluated by genotypically analyzing strains isolated from drug-naive individuals. Proviral DNA was extracted from 54 blood samples and amplified by polymerase chain reaction of protease, reverse transcriptase, integrase, and envelope genes. At least 4 clones per sample were analyzed. Of 54 HIV-1 strains, 45 (83.3%) had a concordant subtype or circulating recombinant form (CRF) designation: 40 CRF02_AG, 2 subtype A1, 2 G, and 1 F2. The remaining 9 (16.7%) had a discordant subtype: 6 subtype A1/CRF02_AG, 2 D/CRF02, and 1 G/CRF02. Protease inhibitor-associated primary resistance mutations were found in 4 (7.4%) cases: M46L with full clones in 1 case, and M46I, M46L, and V82A as minor populations in 1 case each. Reverse transcriptase inhibitor-associated primary resistance mutations were found in 5 (9.8%) samples: Y188C in 2 cases, and L100I, M184V, and V75I in 1 case each, although all of these mutations were found as minor populations. This is one of the first reports of the emergence of primary ART resistance mutations among drug-naive, non-B subtype HIV-1-infected individuals in Cameroon. Follow-up studies should be conducted to assess whether these drug-resistant mutants found as minor populations might impact future ART.

Prevalence of serum antibodies to cytomegalovirus in pregnant women in Sapporo, Japan.

Human cytomegalovirus (CMV) is the most common cause of congenital and perinatal infections throughout the world. The prevalence of congenital CMV infection varies widely between different populations (0.2-3.0%). Less than 5% of infants with congenital CMV infection have typical cytomegalic inclusion disease, another 5% have atypical involvement, and the remainder (90%) are asymptomatic at the time of delivery.’ Even when asymptomatic at birth, 5--17% of infants with these asymptomatic congenital CMV infections will develop progressive sensorineural hearing loss or other neurodevelopmental difficulties within the first 4 years of life. We have studied the incidence of congenital CMV infection in Japan. Of 7995 Japanese neonates, 31(0.39%) were identified as having congenital CMV infections on the basis of viruria at birth. Three of 31 infants had clinically severe disease resulting in death during the neonatal period. Prospective studies of children born with asymptomatic congenital CMV infection have also revealed a wide but significant spectrum of neurologic complications. A decrease in the prevalence of serum antibodies against CMV has been seen in recent years as a consequence of improvements in the social and economic conditions in Japan in the last 20 years.* From January to December 1988, serum samples were collected from 173 Japanese pregnant women who visited a hospital in Sapporo, Japan, at 32-36 weeks of gestation. Serum samples were also obtained from 345 pregnant women who visited the same hospital at the same stage of gestation during January 1999 to June 2000. Informed consent was obtained from those participating. CMV PCS (pipetted control system) Medac IgG and IgM test kits, kindly supplied by Medac Diagnostika, Hamburg, Germany, were used to detect serum IgG and IgM antibodies against CMV. All serum samples, from both 1988 and 1999-2000, were tested at the same time. Testing and interpretation of the results were performed according to the manufacturer’s instructions. Two hundred and thirty-five of 345 (68.1%) Japanese pregnant women at 32-36 weeks of gestation had IgG and seven (2.0%) had IgM antibodies to CMV in the years 1999-2000 in Sapporo, Japan, by enzyme immunoassay. One hundred and forty-seven of 173 (85.0%) sera had IgG and one (0.6%) had IgM antibodies in 1988. One hundred and sixty-one of 354 sera (46.7%) from the years 1999-2000 showed optical density (OD) titers of IgG antibody of more than 1.000. On the other hand, only three (1.7%) of 173 sera from 1988 showed OD

Current problems of perinatal Chlamydia trachomatis infections.

Chlamydia trachomatis has been recognized as a pathogen of trachoma, nongonococcal urethritis, salpingitis, endocervicitis, pelvic inflammatory disease, inclusion conjunctivitis of neonates, follicular conjunctivitis of adults, infantile pneumonia and associated conditions. Chlamydial infections during pregnancy may also cause a variety of perinatal complications. Different antigenic strains of C. trachomatis from endocervical, nasopharyngeal and conjunctival origins have been associated with different clinical conditions. Control programs emphasizing early diagnosis, targeted screening, and effective treatment will lead to an eventual decline in the incidence of perinatal chlamydial infection. This review focuses on current problems of perinatal C. trachomatis infections in the aspects of microbiological and immunological pathogenesis.

Intracranial calcification with congenital rubella syndrome in a mother with serologic immunity.

We report a case of an infant with congenital rubella. The mother had received rubella vaccine at the age of 13 years. Rubella serology was performed on day 34 of pregnancy and the result was interpreted as being a positive titer. The patient was a girl born by cesarean section owing to intrauterine growth retardation and fetal distress after 37 weeks gestation. A computed tomographic scan at 4 days of age showed several cortical low-density areas and calcifications of the periventricular area and basal ganglia. Magnetic resonance imaging (MRI) performed at 4 weeks of age showed almost similar findings. The infant had serum IgG and IgM antibodies against rubella. Rubella virus ribonucleic acid (RNA) was detected from the serum, urine, and cerebrospinal fluid of the infant. At 2 months of age, the patient showed severe bilateral hearing loss. At 12 months of age, she had mild mental retardation and developmental delay. (J Child Neurol 2003;18:296—297).

Human cytomegalovirus infection during pregnancy and detection of specific T cells by intracellular cytokine staining

OBJECTIVEnThe flow cytometric assay was evaluated as a tool for real-time monitoring of human cytomegalovirus (HCMV)-specific cellular immunity in pregnant women.nnnMETHODSnWe screened for HCMV infection in pregnant women in Sapporo, Japan, during the year 2000, by serologic assays, virus isolation from urine, and PCR to detect DNA in cervical swabs. The frequencies of HCMV-specific CD4+ T cells in pregnant women with serum anti-HCMV IgG antibody were detected by intracellular cytokine (ICC), interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) staining.nnnRESULTSnThe levels of intracellular cytokines in pregnant women with serum anti-HCMV IgG antibody were significantly higher than those in women without anti-HCMV IgG antibody (P = 0.011 for IFN-gamma and P = 0.023 for TNF-alpha) but lower than those in non-pregnant women with serum anti-HCMV IgG antibody. Frequencies of HCMV-specific CD4+ T cells were higher in infants with symptomatic congenital infection than in infants with asymptomatic perinatal infection.nnnCONCLUSIONSnThis ICC assay may reflect immunologic activity against HCMV infection in pregnant women with immunosuppressive conditions.

Immunological evaluation and clinical aspects of children with congenital cytomegalovirus infection

ABSTRACTu2002 To determine the ability of immunological response to human cytomegalovirus (CMV), the flow cytometric assay was evaluated as a tool for real‐time monitoring of specific cellular immunity in children with congenital CMV infection. Longitudinal cohort study of 2 children with asymptomatic and 2 with symptomatic congenital CMV infection evaluated at birth and followed up with serial age‐appropriate neurodevelopmental testing. Frequencies of CMV‐specific CD4+ T cell in these children were detected by intracellular cytokines (ICC), interferon (IFN)‐γ and tumor necrosis factor (TNF)‐α, staining.

A case of meningoencephalitis associated with G1P[8] rotavirus infection in a Japanese child

We report the case of a 2-y, 11-month-old boy with G1P[8] rotavirus infection accompanied by acute meningoencephalitis. Substitutions in both the VP4 and VP7 genes were found in the identified strain. A commonly circulating G1P[8] rotavirus with such mutations might be associated with the pathogenesis of CNS complications, including meningoencephalitis.

Glycyrrhizin therapy for viral infections

Glycyrrhizin (GL) was reported as the most active in inhibiting replication of the severe acute respiratory syndrome (SARS)-associated coronavirus. Therapeutic effect of GL for liver dysfunction associated with cytomegalovirus (CMV) infection in immunocompetent individuals was evaluated. Liver dysfunction in 4 cases improved and CMV disappeared from urinary samples after administration of GL intravenously by the age of 12 months. GL treatment also should be applied for the patients with SARS. Key words : Glycyrrhizin, SARS, cytomegalovirus nAfrican Journal of Biotechnology Vol.2(10) 2003: 392-393

HIV-2 amino acid substitutions in Gag and Env proteins occurring simultaneously with viral load upsurge in a drug-naïve patient

It has been reported that the peptides of human immunodeficiency virus type 2 (HIV-2) most frequently recognized by cytotoxic T lymphocytes are firstly in Gag and secondly in Env proteins. In the present case study, we attempted to observe amino acid substitutions in Gag and Env proteins and related parameters possibly associated with an increase in HIV-2 load. A sudden, eightfold, increase in HIV-2 load occurred in a drug-naïve patient with human leukocyte antigen-B*5801 during the last phase of a longitudinal observation period from months 29 to 40. The genetic diversity of Gag and Env increased gradually prior to the HIV-2 load increase. The proportions of synonymous substitutions in both Gag and Env were greater than the proportions of nonsynonymous substitutions at every sampling point for 40 months, and the net charge of the V3-loop increased from months 29 to 40. Three amino acid substitutions (V2861 in Gag, K303T and N337 K/R in Env) were observed from months 29 to 40. Only one amino acid substitution (V286I) was observed with an increase in HIV-2 load in the Gag region where the clustering of epitopes was reported. These results suggest that the sites encompassing these three substituted positions are candidates for HIV-2 epitopes, although further careful examinations will be required.