Naohide Takayama

Herpes zoster in immunocompetent and immunocompromised Japanese children

Abstract Background: To confirm epidemiological features of herpes zoster among children with or without immunosuppression, herpes zoster patients who had presented to this hospital were retrospectively investigated.

HIGH INCIDENCE OF BREAKTHROUGH VARICELLA OBSERVED IN HEALTHY JAPANESE CHILDREN IMMUNIZED WITH LIVE ATTENUATED VARICELLA VACCINE (OKA STRAIN)

In order to know the rate of occurrence of varicella among vaccinees (breakthrough varicella: BV), questionnaire postcards were sent to 593 healthy children who had received varicella vaccine (Oka strain) from March 1987 to December 1989. The questionnaire survey was repeated once a year until January 1996. The annual attack rate from the 1st to 3rd questionnaire was approximately 12%; however, from the 5th to 8th one it was 1–4%. To February 1996, the cumulative attack rate was 157/459 (34.2%). This rate was comparable to that among vaccinees who had confirmed seroconversion; namely, 51/132 (38.6%). These rates are much higher than those reported by other authors. All BV cases were clinically mild; even subjects who had received the vaccine 7 years prior to the disease showed mild symptoms. The high incidence may be partly explained by the regional epidemiology of varicella. The decrease in annual incidence with time after vaccination may be due to the following reasons: some vaccinees remained free from BV owing to reinforcement of their immunity from subclinical infection of varicella‐zoster virus (VZV) and others from diminution of opportunity for exposure to VZV with increasing age. Varicella vaccine seems to be effective in modifying the symptoms of varicella, but not potent enough in protecting from VZV infection.

New method of differentiating wild-type varicella-zoster virus (VZV) strains from Oka varicella vaccine strain by VZV ORF 6-based PCR and restriction fragment length polymorphism analysis

A new method was developed to distinguish accurately wild-type varicella-zoster virus (VZV) strains from the Oka vaccine strain. Several DNA fragments covering open reading frame (ORF) 1-37 were amplified from wild-type VZV strains including the Oka parent strain and from the Oka vaccine strain. Restriction fragment length polymorphisms of these regions were compared, and nucleotide differences between the vaccine virus and other wild-type VZV strains were noted in ORFs 6, 10, and 35. In addition, variations of the R2 and R4 reiterated structures of the vaccine and its parent strains were examined. The Oka vaccine strain used in Japan was shown to be a mixture of viruses with different nucleotide sequences that had variations in at least three nucleotide positions in ORF 1-37 and had variable polymorphisms at R2 and R4 repeat regions (two and three patterns, respectively). The Oka parent strain on the other hand showed a single sequence and had only one reiterated structure at these regions. When VZV ORF 6 was amplified and its product was digested with AluI, the Oka vaccine strain could be precisely differentiated from its parent and from 56 other Japanese clinical isolates.

Reduced immune response to influenza A (H1N1) 2009 monovalent vaccine in HIV-infected Japanese subjects.

We evaluated the immunogenicity and safety of the influenza A (H1N1) 2009 monovalent vaccine in HIV-infected Japanese subjects. A total of 182 HIV-infected and 42 HIV-uninfected subjects were enrolled, and antibody (ab) titers were measured by hemagglutination-inhibition assay at baseline and 32.3±10.4 and 29.7±3.3 days after vaccination, respectively. In the HIV-infected cohort, ab titers ≥ 1:40 at baseline and post-vaccination were 12.6% and 49.5%, respectively. The seroconversion rate, defined as either an ab titer ≤ 1:10 before and ≥ 1:40 after or ≥ 1:10 before and ≥ 4-fold increase in ab titer, was only 38.5% in the HIV-infected cohort, whereas the rate was 85.7% in the HIV-uninfected cohort. Multivariate logistic regression analysis showed that the CD4 cell count was the only significant predictor of a positive vaccine response. There were no serious adverse events in any of the subjects receiving the vaccine. Additional study is warranted to identify a more effective method of vaccinating HIV-infected Japanese subjects.

Chronic pneumonitis of infancy

Abstract. Chronic pneumonitis of infancy (CPI) is a very rare lung disease in infants and young children. We report a 33-day-old infant with CPI, focusing on the radiologic aspects of the disease. Chest radiographs showed variable and non-specific appearances including ground-glass shadowing, consolidation, volume loss, and hyperinflation. Dense alveolar opacities progressed as CPI advanced. The radiologic features of our case reflected pathologic changes.

Clinical and Bacteriological Profiles of Patients with Typhoid Fever Treated during 1975–1998 in the Tokyo Metropolitan Komagome Hospital

Patients with typhoid fever presenting to the Tokyo Metropolitan Komagome Hospital during the period 1975–1998 were retrospectively investigated. All cases were diagnosed by a positive culture for Salmonella typhi in either of their clinical specimens. Of the total number of 130 patients, 57% contracted the disease abroad; this population increased in later years as the total numbers of cases decreased. The period from disease onset to diagnosis averaged 14 days with 20% of the cases requiring over three weeks to establish a diagnosis. As for symptomatology relative bradycardia was seen in less than half of the cases, and rose spots or splenomegaly in less than one third. A positive blood culture was the most frequent test establishing the diagnosis followed by a positive stool culture. Intestinal bleeding was recognized in as many as 35 cases (27%) and even intestinal perforation occurred in two cases (1.5%). Chloramphenicol was most commonly employed during the early study period, however, during the late period it was replaced by fluoroquinolones. The clinical cure rate was 98% with regimens that include fluoroquinolones/quinolone; however it was 87% with the other antimicrobial regimens. Bacteriological relapse occurred in 25% of the non‐fluoroquinolone group while only in 2.0% in the fluoroquinolone/quinolone group. Four strains of Salmonella typhi that were multi‐resistant to chloramphenicol, ampicillin and cotrimoxazole were isolated in travelers from Asia. Early diagnosis by appropriate bacteriological examination regardless of classical symptomatology should be stressed and the use of fluoroquinolones is warranted in the treatment of typhoid fever.

Multidrug-resistant typhoid fever outbreak in travelers returning from Bangladesh.

To the Editor: Enteric fever (typhoid and paratyphoid fever) is a systemic infection caused by several Salmonella enterica serotypes including S. Typhi and S. Paratyphi A. The Indian subcontinent, which has the highest incidence of the disease worldwide, is also an epicenter of enteric fever caused by multidrug-resistant (MDR; resistant to chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole) and nalidixic acid–resistant (NAR) strains, i.e., strains with decreased susceptibility to ciprofloxacin (1–3). A total of 57% of S. Typhi strains isolated at a referral center in Dhaka, Bangladesh, in 2005 were MDR and NAR (4). More than 80% of 442 enteric fever cases reported in Japan during 2001–2004 were imported (5). Most Japanese persons, especially the younger generation, are not immune to enteric fever as are persons living in other industrialized countries. Although the proportion of enteric fever cases related to international travel has increased in industrialized countries, few outbreaks of enteric fever have been reported in travelers (6,7). We describe an outbreak of MDR and NAR typhoid fever in young Japanese travelers returning from Bangladesh. This outbreak highlights the need for standard treatments for MDR and NAR enteric fever. Ten Japanese junior and senior high school students living in the Tokyo metropolitan area took part in a 9-day study tour to Dhaka in March–April, 2004. They were escorted by 2 Japanese college students and a 28-year-old Japanese instructor. The 13 participants returned to Japan on April 4, 2004. The purpose of the study tour was to acquire knowledge about street children in Dhaka. The students stayed at a guesthouse and visited orphanages in the city. The itinerary included a visit to a local home, where the family served them a meal. They shared all their meals during the tour. Fever and diarrhea developed in 2 participants on April 3 and 5, and these symptoms were later shown to be caused by shigellosis. On April 19, the index patient became febrile. From that date until April 28, there were 6 confirmed and 2 probable typhoid fever cases reported in the 13 tour participants, resulting in an attack rate of 62%. The median age of the patients was 17 years (range 12–28 years); 5 patients were female. No other cases of typhoid fever were reported in that period in Japan. All 6 S. Typhi isolates were Vi-phage type E9. These isolates were also MDR and NAR, and the MIC for ciprofloxacin for the 6 isolates was 0.38 μg/mL. It was strongly suspected that a single-point exposure to S. Typhi occurred in the tour participants during their stay in Bangladesh and caused this exceptional outbreak. None of the participants had received a typhoid vaccination. The 8 patients were admitted to 5 hospitals in the Tokyo metropolitan area. Four different antimicrobial drug regimens were used on the basis of the age of the patients and the hospital in which each patient was hospitalized (Table). Four patients at 2 hospitals who received fluoroquinolone monotherapies were given other regimens on days 4–6 of treatment because of concern of treatment failure. The median fever clearance time was 6 days (range 3–12 days). No complications occurred during any of the treatment regimens. Although a relapse occurred 15 days after completion of treatment in the oldest patient, who had received cefotaxime and oral tosufloxacin, retreatment cured the infection without fecal carriage. Table Characteristics of 8 case-patients with typhoid fever, Bangladesh, 2004* The high attack rate may reflect the high sensitivity of adolescents to typhoid fever and the high level of bacterial contamination in food the participants had eaten during travel (2). Although the meal at the private home was suspected as the source of infection, we could not determine the exact cause of this outbreak. The optimum treatment for MDR and NAR enteric fever has not yet been established. A third-generation cephalosporin or high doses of fluoroquinolones (e.g., ciprofloxacin, 20 mg/kg/day or levofloxacin, 10 mg/kg/day) for 10–14 days are the drugs of choice (1,2). Azithromycin is also a promising agent (8). However, for any of the regimens, the mean fever clearance times are relatively long (≈7 days), and the relapse rates are high (1). Although all 6 isolates showed reduced susceptibility to ciprofloxacin, a long course (14 days) of fluoroquinolones was still effective in this outbreak. However, clinicians should be aware of treatment failure in MDR and NAR enteric fever (3). The combination therapy of cefotaxime and a fluoroquinolone used in 3 patients has not shown greater efficacy than monotherapies. In fact, 1 patient who received this combination therapy experienced a relapse.

Presence of multiple HIV type 1 subtypes among mothers and children in Japan.

We collected blood samples from 70 HIV-1-infected pregnant women and 76 babies born to HIV-1-infected women in Japan, from 1989 to 1999. To analyze the genetic diversity of HIV-1 among mothers and children, we sequenced the C2-V3 regions of HIV-1 gp120. Phylogenetic tree analysis of these regions revealed that multiple HIV-1 subtypes, A, B, D, E, and G, were circulating among mothers and children in Japan. Thus, the genetic heterogeneity of HIV-1 among mothers and children in Japan is steadily increasing, although the number of cases remains small. Perhaps the longest term survivor, an 11-year-old child with a vertical HIV-1 subtype G infection in Japan, is one of our subjects.

成人水痘入院症例の検討: 臨床像, 重症度, 感染経路および合併症

Varicella has been thought to be one of the representative infectious disease in childhood, but recently we are under the impression that adults contracting varicella are increasing in number. On the other hand, they say that varicella generally causes a serious illness in adult patients. So we investigated signs and symptoms of varicella, source of infection, occupations of adult patients, except those who were immunologically compromised, by means of medical records, to know the characteristics of varicella in adulthood. According to the varicella severity score proposed by Nagai et al., varicella in the hospitalized adult patient was found to be much severer than that in children. The most remarkable symptoms, were high fever and sore throat, and these were the main reason of hospitalization in most of our patients. Although severity scores were very high in admitted adult patients with varicella, their clinical courses were not serious, and most of them recovered with only supportive therapy. These patients rarely suffered from complications, like pneumonia. If adult patients with varicella hospitalized in the early stage and received supportive care, they could recover without any complications. In most cases of adult varicella the source of infection was unknown. In the case of married persons, however, many of them were infected through their child. When adults contract varicella, not only the patients themselves suffer from high fever and sore throat, but also they act as the source of infection, if they are medical care workers. Furthermore, in public, the contraction of varicella results a socioeconomic loss from suspension of business caused by the illness. Prophylaxis with varicella vaccine, therefore, should be considered, when there are people who have never contracted varicella, whether or not they are medical staff.

Herpes simplex mimicking herpes zoster in a child immunized with varicella vaccine.

A 5-year-old boy had zosteriform vesicular lesions 4 years after immunization with varicella vaccine. PCR analyses of DNA extracted from the crusts revealed herpes simplex virus type 1 infection. Virologic examinations should be performed before the vesicular lesion is attributed to the varicella-zoster virus vaccine strain.