関谷紀貴, 藤由香, 田原寛之, 他: 宮崎県における髄膜炎菌感染症集団発生事例．病原微生物検出情報（IASR）2011;32：298-299.
CDC： Meningococcal Disease．Epidemiology and prevention of vaccine-preventable diseases (The Pink Book, 12th ed.) Atlanta：CDC, 2011;193-204.
American Academy of Pediatrics: Meningococcal Infectious. Red Book 2009．28th ed. Elk Grove Village：American Academy of Pediatrics, 2009;455-463.
F G Hayden, R Fritz, M C Lobo, W Alvord, W Strober, S E Straus
Local and systemic cytokine responses during experimental human influenza A virus infection. Relation to symptom formation and host defense.
J Clin Invest. 1998 Feb 1;101(3):643-9. doi: 10.1172/JCI1355.
Abstract/Text
To further understand the role of cytokine responses in symptom formation and host defenses in influenza infection, we determined the levels of IL-1beta, IL-2, IL-6, IL-8, IFN-alpha, TGF-beta, and TNF-alpha in nasal lavage fluid, plasma, and serum obtained serially from 19 volunteers experimentally infected with influenza A/Texas/36/91 (H1N1) and correlated these levels with various measures of infection and illness severity. We found that IL-6 and IFN-alpha levels in nasal lavage fluids peaked early (day 2) and correlated directly with viral titers, temperature, mucus production, and symptom scores. IL-6 elevations were also found in the circulation at this time point. In contrast, TNF-alpha responses peaked later (day 3 in plasma, day 4 in nasal fluids), when viral shedding and symptoms were subsiding. Similarly, IL-8 peaked late in the illness course (days 4-6) and correlated only with lower respiratory symptoms, which also occurred late. None of IL-1beta, IL-2, or TGF-beta levels increased significantly. These data implicate IL-6 and IFN-alpha as key factors both in symptom formation and host defense in influenza.
F G Hayden, J J Treanor, R S Fritz, M Lobo, R F Betts, M Miller, N Kinnersley, R G Mills, P Ward, S E Straus
Use of the oral neuraminidase inhibitor oseltamivir in experimental human influenza: randomized controlled trials for prevention and treatment.
JAMA. 1999 Oct 6;282(13):1240-6.
Abstract/Text
CONTEXT: Influenza virus neuraminidase is thought to be essential for virus replication in humans; however, to date, available neuraminidase inhibitors are limited to zanamivir, which is topically administered.
OBJECTIVE: To determine the safety, tolerability, and antiviral activity of oral neuraminidase inhibitor oseltamivir (GS4104/Ro64-0796) for prevention and the early treatment of influenza in experimentally infected humans.
DESIGN: Two randomized, double-blind, placebo-controlled trials conducted between June and July 1997.
SETTING: Individual hotel rooms; 2 large US university medical schools.
PARTICIPANTS: A total of 117 healthy adult volunteers (aged 18-40 years; median age, 21 years) who were susceptible (hemagglutination-inhibition antibody titer < or =1:8).
INTERVENTIONS: All subjects were inoculated intranasally with influenza A/Texas/36/91 (H1N1) virus. For the prophylaxis study, oral oseltamivir (100 mg once daily [n = 12], 100 mg twice daily [n = 12], or matching placebo [n = 13], starting 26 hours before virus inoculation) was administered. For the treatment study, the same drug was given (20 mg, 100 mg, or 200 mg twice daily, 200 mg once daily, or matching placebo [n = 16], in each group starting 28 hours after inoculation). All regimens were continued for 5 days.
MAIN OUTCOME MEASURES: Comparing placebo groups with pooled treatment groups, for prophylaxis, outcomes included frequency of infection and viral shedding; for treatment, viral shedding in titers.
RESULTS: In the prophylaxis study, 8 (67%) of 12 placebo and 8 (38%) of 21 oseltamivir recipients became infected (P = .16; efficacy, 61%); 6 (50%) placebo compared with 0 oseltamivir recipients shed virus (P<.001; efficacy, 100%), and 33% of placebo but no oseltamivir recipient had infection-related respiratory illness (P<.01). Among infected subjects in the treatment study (n = 69), the viral titer area under the curve of the combined oseltamivir groups (n = 56) was lower (median [interquartile range [IQR]], 80 [23-151] vs 273 [79-306] log10 tissue culture-infective doses50 per milliliter x hour; P = .02) than the placebo group (n = 13), and the median (IQR) duration of viral shedding with therapy was reduced from 107 (83-131) to 58 (35-59) hours (P = .003). Oseltamivir treatment also reduced symptom scores (median [IQR] score-hours, 225 [97-349] vs 400 [189-645]; P = .05), and nasal proinflammatory cytokine levels. Transient mild to moderate nausea after dosing was observed in 15 (17%) of 88 oseltamivir and 2 (7%) of 29 placebo recipients (95% confidence interval for difference, -11% to 68%), which was largely prevented by ingestion with food.
CONCLUSIONS: In these trials, prophylaxis and early treatment with oral oseltamivir were both associated with significant antiviral and clinical effects in experimental human influenza.
Achuyt Bhattarai, Julie Villanueva, Rakhee S Palekar, Ryan Fagan, Wendy Sessions, Jörn Winter, Lashondra Berman, James Lute, Rebecca Leap, Tiffany Marchbanks, Samir V Sodha, Mària Moll, Xiyan Xu, Alicia Fry, Anthony Fiore, Stephen Ostroff, David L Swerdlow, Pennsylvania Working Group
Viral shedding duration of pandemic influenza A H1N1 virus during an elementary school outbreak--Pennsylvania, May-June 2009.
Clin Infect Dis. 2011 Jan 1;52 Suppl 1:S102-8. doi: 10.1093/cid/ciq026.
Abstract/Text
We report shedding duration of 2009 pandemic influenza A (pH1N1) virus from a school-associated outbreak in Pennsylvania during May through June 2009. Outbreak-associated students or household contacts with influenza-like illness (ILI) onset within 7 days of interview were recruited. Nasopharyngeal specimens, collected every 48 hours until 2 consecutive nonpositive tests, underwent real-time reverse transcriptase polymerase chain reaction (rRT-PCR) and culture for pH1N1 virus. Culture-positive specimens underwent virus titrations. Twenty-six (median age, 8 years) rRT-PCR-positive persons, for pH1N1 virus, were included in analysis. Median shedding duration from fever onset by rRT-PCR was 6 days (range, 1-13) and 5 days (range, 1-7) by culture. Following fever resolution virus was isolated for a median of 2 days (range, 0-5). Highest and lowest virus titers detected, 2 and 5 days following fever onset, were 3.2 and 1.2 log(10) TCID(50)/mL respectively. Overall, shedding duration in children and adults were similar to seasonal influenza viruses.
C B Hall, R G Douglas
Nosocomial influenza infection as a cause of intercurrent fevers in infants.
Pediatrics. 1975 May;55(5):673-7.
Abstract/Text
All patients on an infants' ward manifesting intercurrent fevers were studied for viral and bacterial etiology during a community outbreak of influenza A. During a one-month period, of 29 infants admitted to the ward, 17 were hospitalized for seven or more days. Intercurrent fever complicated the course of 13 (76%) of these 17 infants. Nosocomially acquired influenza A infection was found in 13 infants. Two of these also contracted a dual infection with influenza B. The fever lasted an average of 2.7 days with a peak of 38.2 to 39.8 C. Initial white blood cell counts tended to by high and shifted to the left. These infants appeared to be at high risk for developing lower respiratory tract disease. Seven of the 12 had infiltrates on chest X-ray, and five subsequently developed a secondary bacterial pneumonia. These infants tended to be young, five were under 6 months, and all but one had underlying cardiorespiratory disease. They also appeared to have prolonge shedding of influenza virus from their nasal secretions. Six of seven shed the virus for 7 or 21 days.
A L Frank, L H Taber, C R Wells, J M Wells, W P Glezen, A Paredes
Patterns of shedding of myxoviruses and paramyxoviruses in children.
J Infect Dis. 1981 Nov;144(5):433-41.
Abstract/Text
In the Houston Family Study, young children were cultured for virus weekly or biweekly and during acute respiratory illnesses. The interval between the onset of illness and positive culture was examined for 179 infections during 1975-1979. In week 1 after onset, 73%, 73%, and 66% of cultures were positive for influenza A virus, respiratory syncytial virus (RSV), and parainfluenza virus type 3, respectively. Pooled data from influenza B virus infections in 1977 and 1980 showed that 73% of cultures were positive in week 1. Influenza A virus in week 2 or RSV in weeks 2 and 3 was isolated from very few children. However, 37% of cultures were positive for influenza B virus during week 2, and 17% of cultures were still positive for parainfluenza virus type 3 during week 3. Shedding of parainfluenza virus type 3 on days 29-38 was also observed. Parainfluenza virus type 3, RSV, and influenza A virus were isolated up to six days before the onset of illness.
American Academy of Pediatrics: Influenza. Red Book 2009．28th ed. Elk Grove Village：American Academy of Pediatrics, 2009; 400-412.
[www.mhlw.go.jp/bunya/kodomo/pdf/hoiku02.pdf 厚生労働省：保育所における感染症対策ガイドライン．平成21年8月].
American Academy of Pediatrics: Pertussis. Red Book 2009．28th ed. Elk Grove Village：American Academy of Pediatrics, 2009: 504-519.
Philip M Polgreen, Lucas C Bohnett, Joseph E Cavanaugh, Stefan B Gingerich, Lucy E Desjardin, Meghan L Harris, M Patricia Quinlisk, Michael A Pentella
The duration of mumps virus shedding after the onset of symptoms.
Clin Infect Dis. 2008 May 1;46(9):1447-9. doi: 10.1086/587104.
Abstract/Text
To determine how long people shed virus after the onset of mumps, we used logistic regression modeling to analyze data from the 2006 outbreak of mumps in Iowa. Our model establishes that the probability of mumps virus shedding decreases rapidly after the onset of symptoms. However, we estimate that 8%-15% of patients will still be shedding the virus 5 days after the onset of symptoms and, thus, may still be contagious during this period.
Takao Okafuji, Naoko Yoshida, Motoko Fujino, Yoshie Motegi, Toshiaki Ihara, Yoshinori Ota, Tsugunori Notomi, Tetsuo Nakayama
Rapid diagnostic method for detection of mumps virus genome by loop-mediated isothermal amplification.
J Clin Microbiol. 2005 Apr;43(4):1625-31. doi: 10.1128/JCM.43.4.1625-1631.2005.
Abstract/Text
Most mumps patients are clinically diagnosed without any virological examinations, but some diagnosed cases of mumps may be caused by other pathogens or secondary vaccine failure (SVF). To clarify these issues, a sensitive, specific, and rapid diagnostic method is required. We obtained 60 salivary swabs from 34 patients with natural infection during the course of the illness, 10 samples from patients with vaccine-associated parotitis, and 5 samples from patients with SVF. Total RNA was extracted and subjected to reverse transcription-PCR (RT-PCR) and loop-mediated isothermal amplification (LAMP) for genome amplification. We detected mumps virus RNA corresponding to 0.1 PFU by LAMP within 60 min after RNA extraction, with the same sensitivity as RT-nested PCR. Mumps virus was isolated in 30 of 33 samples within day 2, and mumps virus genome was amplified by LAMP in 32 of them. The quantity of virus titer was calculated by monitoring the time to reach the threshold of turbidity. The viral load decreased after day 3 and was lower in patients serologically diagnosed as having SVF with milder illness. Accuracy of LAMP for the detection of mumps virus genome was confirmed; furthermore, it is of benefit for calculating the viral load, which reflects disease pathogenesis.
American Academy of Pediatrics : Mumps. Red Book 2009．28th ed. Elk Grove Village：American Academy of Pediatrics, 2009; 468-472.
平山宗宏：集団かぜによる学級閉鎖の基準．CLINICIAN，1986；33：737-738.
