Kiyoshi Kikuchi

National Institute of Allergy and Infectious Diseases, Maryland, United States

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Publications (12)15.39 Total impact

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    ABSTRACT: Syndromic surveillance, including prescription surveillance, offers a rapid method for the early detection of agents of bioterrorism and emerging infectious diseases. However, it has the disadvantage of not considering definitive diagnoses. Here, we attempted to definitively diagnose pathogens using polymerase chain reaction (PCR) immediately after the prescription surveillance system detected an outbreak. Specimens were collected from 50 patients with respiratory infections. PCR was used to identify the pathogens, which included 14 types of common respiratory viruses and Mycoplasma pneumoniae. Infectious agents including M. pneumoniae, respiratory syncytial virus (RSV), rhinovirus, enterovirus, and parainfluenza virus were detected in 54% of patients. For the rapid RSV diagnosis kit, sensitivity was 80% and specificity was 85%. For the rapid adenovirus diagnosis kit, no positive results were obtained; therefore, sensitivity could not be calculated and specificity was 100%. Many patients were found to be treated for upper respiratory tract infections without the diagnosis of a specific pathogen. In Japan, an outbreak of M. pneumoniae infection began in 2011, and our results suggested that this outbreak may have included false-positive cases. By combining syndromic surveillance and PCR, we were able to rapidly and accurately identify causative pathogens during a recent respiratory infection outbreak.
    BioMed Research International 01/2013; 2013:746053. · 2.88 Impact Factor
  • Pediatrics International 03/2008; 50(1):132-4. · 0.88 Impact Factor
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    ABSTRACT: Mumps immunization is not included in routine immunization in Japan. We measured the cost-effectiveness of routine immunization. We surveyed outpatients prospectively from June 15, 2004, for 19 months in an area with a population of 100,000. Almost all of the 11 pediatric clinics and hospitals in this area cooperated. In 2006, we retrospectively surveyed all inpatients hospitalized for more than 24 hours and dying of mumps. We collected data from 189 doctors who rated outpatients and 112 families. The disease burden for outpatients including family nursing was estimated to be 47.1 billion yen nationwide. We estimated the total number of inpatients as 4,596. The disease burden of inpatients including the cost of family nursing was estimated to be 1.35 billion yen. Adding cases of sequelae and death, the total disease burden was estimated to be 52.5 billion yen. The incremental benefit cost ratio for routine immunization is higher than 1 even in the lower bounds of the 95% confidence interval. The incremental benefit cost ratio shows that the additional benefit due to routine immunization exceeds additional cost, emphasizing the benefits of routine mumps immunization.
    Kansenshogaku zasshi. The Journal of the Japanese Association for Infectious Diseases 10/2007; 81(5):555-61.
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    ABSTRACT: We report on an 11-year-old boy who developed rhabdomyolysis and acute renal failure following Salmonella enteritidis gastroenteritis. Rhabdomyolysis should be considered as a potentially fatal complication in patients with Salmonella gastroenteritis.
    European Journal of Pediatrics 10/2007; 166(9):973-4. · 1.91 Impact Factor
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    ABSTRACT: Syndromic surveillance, which monitors symptoms rather than diagnosis as in traditional surveillance, is a useful tool for early detection of pandemic flu, bioterrorism attack or other emerging and reemerging diseases. Since we don't know when such a disaster may occur, we have to perform this syndromic surveillance routinely, and thus the system should be automatic. Namely, information is drawn from electronic medical records (EMR), and is statistical analyzed, aberrations are detected and then results are reported by e-mail or HP. It is preferable that this system be fully automatic. Many systems of this type have been developed in the US, such as the Biosense system at the Center for Disease Control and Prevention, the Realtime Outbreak Detection System at Pittsburgh university or ESSENSE at the Department of Defense and Harvard University. However, they have not been well developed in Japan. So as to develop such a system, we made a prototype case and have been performing prospectively and evaluating the system. Namely, 3 clinics and 1 large hospital with 700 beds in a local city which has a population of 0.1 million cooperated in this project. We developed the system within a clinic or hospital and then integrated the aberration information from those medical institutions since November 2006. The system is described briefly as follows: Using backup data from EMR, we count the number of cases of a designated symptom excluding negative meaning; we apply Poisson regression using the number of the week, dummies for holidays or the day after a holiday, the day-of-the-week, and time trends to the data for all days up until the day before yesterday. If the actual number of cases yesterday exceed the estimated number of cases and its probability is less than a certain criterion, an aberration is detected; These procedures are performed in a medical institution; Then the number of cases with a certain type of symptoms and aberration information are sent to a server outside of the medical institution; The server provides an HP which shows the number of cases in a medical institution only for that medical institution and local outbreak information which is the sum of the aberration level in each medical institution; The latter information is also provided to the public health center or local government. The system seems to be working well without any trouble.
    06/2007;
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    ABSTRACT: To detect nosocomial outbreaks early we construct syndromic surveillance for inpatients with fever, respiratory symptoms, diarrhea, vomiting, or rash and evaluate it statistically. In hospital using electronic medical records since August 1999, we studied the number of inpatients with a certain symptoms from 1999 to 2005. To prospectively detect outbreaks after January 1, 2005, we first estimated the baseline using data from August 1, 1999 to the day before any given day. We then predicted the number of patients on the day and judge whether an outbreak has occurred, evaluating this by checking it sensitivity and specificity to detect outbreaks other than those with previous patterns. From August 1999 to December 2005, 115,532 patients had fever, 126,443 respiratory symptoms, 87,923 diarrhea, 32,858 vomiting, and 11,212 In 2005, in prospective detection, 23,617 had fever, 23,698 respiratory symptoms, 14,671 diarrhea, 5,893 vomiting, and 2,486 rash. This hospital had a nosocomial Noro virus outbreak on January 27, 2005. Syndromic surveillance identified an outbreak of vomiting at a 0.1% criterion. Our system thus detects nosocomial outbreaks and is of practical use. The next step will be ward-by-ward examination, after which we will experiment with rapid information collection, analysis, reports of results, and investigation by infection control teams.
    Kansenshogaku zasshi. The Journal of the Japanese Association for Infectious Diseases 04/2007; 81(2):162-72.
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    ABSTRACT: Syndromic Surveillance is typically a system used for early detection of bioterrorism attacks, pandemic flu or other emerging diseases, which monitors symptoms of outpatients or is conducted in the Emergency Department. However, if we monitor symptoms of inpatients, we can apply Syndromic Surveillance to early detection of nosocomial infection. To test this possibility, we constructed and are performing a Syndromic Surveillance System for inpatients who have fever, respiratory symptoms, diarrhea, vomiting or rash. We will then evaluate its statistical properties and its usefulness.
    Intelligence and Security Informatics: Biosurveillance, Second NSF Workshop, BioSurveillance 2007, New Brunswick, NJ, USA, May 22, 2007, Proceedings.; 01/2007
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    ABSTRACT: Immunization for varicella is not currently included in routine immunizations in Japan. This study was conducted to assess test its cost-effectiveness when it becomes a routine. We surveyed and collected information for the year beginning 15th June 2004 in one area. Almost all 11 pediatric clinics or hospitals in the area cooperated in this survey. There was a questionnaire form for families and for doctors. Absent days from routine tasks, i.e., job, housekeeping or study, for family nursing and others were asked on family form. Medical costs and other costs were asked on doctor form. Neither form included the patient's name or name of the medical institution. Doctors explained this survey to patients' family on their first visiting day and asked to cooperate. If they refused the doctor form was also discarded. Since family form was written after recovery and mailed, cooperation in this survey was voluntary. Opportunity cost for family nursing is estimated as opportunity cost based on the 2002 Basic Surveillance of Wage Structure. The burden of sequel cases was estimated assuming six million yen per Quality-adjusted Life Years (QALY). Total number of patients was estimated to be 0.84 million, which includes unvaccinated people in a birth cohort. We adopted incremental benefit cost ratios form societal viewpoint as a measure. We collected 402 data from the doctor form and 265 from the family form. Total disease burden in all of Japan is estimated to be 52.2 billion yen, but opportunity cost accounted for 80%. The incremental benefit cost rations averaged more than 4 when vaccination cost is assumed to be five to twelve thousand yen. The lower limit of the confidence intervals is about 1.5. The disease burden of varicella was greater than measles in 2000, when there were measles 0.2 million patients. The incremental benefit cost ratio showed that there will almost surely be an additional benefit due to routine immunization is greater than the additional cost. Therefore, we found strong evidence for routine immunization for varicella.
    Kansenshogaku zasshi. The Journal of the Japanese Association for Infectious Diseases 06/2006; 80(3):212-9.
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    ABSTRACT: We report the case of a 2-year-old boy who developed a small bowel intussusception during treatment failure of his first episode of nephrotic syndrome. Despite the absence of typical symptoms other than abdominal pain, the intussusception was diagnosed by ultrasonography and computed tomography and successfully reduced by air enema. No pathological lead point was discovered, and no symptoms of Henoch-Schönlein purpura developed later. Intussusception should be considered in the differential diagnosis of abdominal pain in patients with nephrotic syndrome, especially in patients exhibiting prolonged edema. Ultrasonography or computed tomography should be performed, even in the absence of other typical symptoms suggestive of intussusception. We should also bear in mind that the intussusception associated with nephrotic syndrome might occur at regions other than the typical ileocolic region, such as within the small intestine.
    Pediatric Nephrology 01/2006; 20(12):1818-20. · 2.94 Impact Factor
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    ABSTRACT: Persistent hyperinsulinaemic hypoglycaemia of infancy (PHHI) is a disorder of glucose metabolism that is characterized by dysregulated secretion of insulin from pancreatic beta-cells. This disease has been reported to be associated with mutations of the sulfonylurea receptor SUR1 (ABCC8) or the inward-rectifying potassium channel Kir6.2 (KCNJ11), which are two subunits of the pancreatic beta-cell ATP-sensitive potassium channel. In 14 Japanese PHHI patients, all exons of SUR1 and Kir6.2 genes were analysed by polymerase chain reaction (PCR) and direct sequencing. Four patients responded to diazoxide, and nine patients underwent a subtotal pancreatectomy. Histologically, seven patients were diagnosed to have a focal form and two a diffuse form of the disease. We found nine novel mutations in the SUR1 gene and two in the Kir6.2 gene. In the SUR1 gene mutations, three were nonsense mutations (Y512X, Y1354X and G1469X), one was a one-base deletion in exon 7, and two were missense mutations in the nucleotide-binding domain 2 (K1385Q, R1487K). The other three mutations occurred in introns 14, 29 and 36, which might cause aberrant splicing of RNA. Two siblings in one family were heterozygotes for a missense mutation, K1385Q, which was maternally inherited. In Kir6.2 gene screening, one patient was found to be a compound heterozygote of a missense mutation (R34H) and a one-base deletion (C344fs/ter). The novel mutations reported here could be pathological candidates for PHHI in Japan. They also reveal that SUR1 and Kir6.2 mutations in the Japanese population exhibit heterogeneity and that they occurred at a frequency similar to other genetic populations.
    Clinical Endocrinology 05/2005; 62(4):458-65. · 3.40 Impact Factor
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    ABSTRACT: The majority of cases of combined anterior pituitary hormone deficiency (CPHD) reported in Japanese patients have PIT1 abnormality. This study describes for the first time a homozygous mutation of the PROP1 gene in two Japanese siblings with CPHD born to consanguineous parents. Two siblings were growth retarded at 3 years of age and developed hypothyroidism. Pituitary function tests showed combined deficiency of GH, TSH, PRL and gonadotrophins. The size of their pituitary glands decreased with age, as demonstrated by magnetic resonance imaging (MRI). The PROP1 gene was analysed by polymerase chain reaction (PCR) followed by direct sequencing. Both children were homozygous for a novel single base deletion at codon 53 (157delA), while their parents were heterozygous. This mutation, if translated, predicts the production of a protein lacking the paired-like homeodomain required for DNA binding, suggesting that the mutation was the direct cause of CPHD in these patients. 157delA is the first reported Japanese PROP1 gene mutation. In Japan, PROP1 abnormality appears to be a less frequent cause of CPHD than does PIT1 abnormality, whereas PROP1 abnormality predominates in CPHD patients of Caucasian and European origin.
    Clinical Endocrinology 12/2004; 61(5):635-40. · 3.40 Impact Factor
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    ABSTRACT: We conducted syndromic surveillance during the G8 summit meeting held in Toyako, Hokkaido, July 7–9, 2008, as a counter-measure to bioterrorism attacks or other health emergencies. Surveillance actually started on June 23, 2 weeks prior to the G8 summit, and ended on July 23, 2 weeks after the closing of the meeting. Part of the syndromic surveillance for prescription drugs was fully automated, while the remainder was done manually through the Internet. Similarly, data on ambulance utilization was collected and included in the syndromic surveillance system. We also purchased data on OTC sales from two private research firms in Japan. In an effort to share the surveillance information and discuss whether further investigation was needed, virtual conferences were held and Hokkaido local government, local health departments and laboratory, National Institute of Infectious Diseases, and Ministry of Health, Labor and Welfare personnel were among the attendees. Information was collected automatically from 23 pharmacies on prescription drugs and manually entered for 71 pharmaceutical companies on drug sales. One fire department that covered the Toyako area and was in charge of highlevel officers participated in the fully automated surveillance system, and seven other departments in the surrounding area conducted the manually-entered surveillance. OTC sales information was reported for 79 drugs with a delay of 1 day, and thus had to be processed manually. Health conditions were reported by 472 households that agreed to participate in the web-based survey; this data was analyzed automatically. Fortunately, we did not observe any suspected outbreaks during G8. However, local health departments investigated seven cases based on abberrances in ambulance utilization detected by the syndromic surveillance. Undoubtedly, a fully automated surveillance system is the best method for detecting an early signs of outbreak. Nevertheless, we had to use a semi-automated surveillance system during the G8 summit due to a limitation on our data collection. Our attempt at syndromic surveillance showed that it was useful and suggested that a routine and fully automated surveillance system, without manual data entry, would be needed for closer monitoring to catch signs of any suspected outbreak in the community. A routinized and fully automatic system without manual input is the next step for syndromic surveillance in Japan.