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zoom RSS 間違いだった百日ぜきの流行/検査による擬陽性 米国

<<   作成日時 : 2007/08/26 01:50   >>

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 百日ぜきの流行とされた米国での三つの例は、PCR法による擬陽性の結果だったとCDCが発表した。
 細菌培養での確認と、ELISA法の併用と臨床経過の把握が重要である。2005年には2001に比し3倍の患者発生報告があり、成人へのワクチン接種が推奨された。増加しているのは事実だろうとのことだが、検査による擬陽性が関与している可能性あり、詳しい調査が必要。
 日本での集団感染報告は本当はどうだったのだろうか?


成人の百日咳患者が、重症化しやすい乳幼児への感染源に/百日ぜき ワクチン
http://kurie.at.webry.info/200706/article_21.html
原因不明の長引くせき、大人も百日ぜき注意
http://kurie.at.webry.info/200706/article_39.html
百日ぜきの患者数増加/大人の割合増加 /百日ぜき ワクチン
http://kurie.at.webry.info/200708/article_5.html

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CDC: Whooping Cough Cases Misdiagnosed
http://www.latimes.com/news/nationworld/nation/wire/ats-ap_health14aug23,1,4653439.story?coll=sns-ap-tophealth&ctrack=6&cset=true
By MIKE STOBBE, AP Medical Writer
5:37 PM PDT, August 23, 2007

ATLANTA -- A reported boom in U.S. whooping cough cases is now being questioned after health officials discovered a regularly used lab test misdiagnosed cases in suspected outbreaks in New Hampshire, Massachusetts and Tennessee.

The false test results led thousands of people to take antibiotics unnecessarily and even caused a New Hampshire hospital to limit the number of patients admitted since hospital workers were thought to be infected.
The testing errors were reported Thursday by researchers with the Centers for Disease Control and Prevention.
Pertussis, or whooping cough, is a potentially fatal bacterial respiratory infection. Its name comes from the sound victims make as they try to recover their breath after a coughing fit.
画像Government health officials say cases have tripled in the United States since 2001, with nearly 26,000 cases reported in 2005. Nearly half of those cases were diagnosed with the testing method now called into question, and that has raised doubts about the true number of cases.
"Are we in fact seeing an increase?" asked Dr. Tom Clark, summarizing what some are wondering. Clark, a CDC epidemiologist, is co-author of the report on the misdiagnoses.
The most accurate diagnostic testing for whooping cough requires a week or more to grow the pertussis bacteria from a sample from a patient's nose or throat. Sometimes that's too long for health authorities to take action to prevent the disease from spreading.
Increasingly, doctors have depended on a faster, but less accurate test. Different labs do the tests differently, leading to uneven results, experts say.
Last October, the less accurate method was used to diagnose a 20-month-old child with whooping cough at Children's Hospital Boston. Three dozen specimens from hospital workers also tested positive as well. But those results were wrong, according to the more reliable bacteria culture test results, the CDC reported.
The same situation occurred in March 2006, when a lab worker at Dartmouth-Hitchcock Medical Center in Lebanon, N.H., was diagnosed with the illness. Nearly 1,000 hospital workers were tested, treated and furloughed to prevent infecting patients. Thousands were given antibiotics and vaccinations. The precautions affected staffing levels, and the hospital had to close off some beds. About 100 employees were diagnosed with pertussis using the speedy test, results later found to be wrong.
In April 2004, a 5-week-old infant in one Tennessee community, which CDC wouldn't identify, was diagnosed with whooping cough. Health officials began looking for the illness in other residents. Ultimately nearly 1,500 people were checked or offered antibiotics; 43 tested positive at first. But the more reliable test turned up negative results for all except the baby, the CDC said.
"It's been a roller coaster. Whoa, looks at this big outbreak! Whoa, it wasn't really pertussis!" said Dr. William Schaffner, chairman of Vanderbilt University's department of preventive medicine.
It's not clear why so many errors were detected in each incident, Clark said. Contamination of samples does not appear to be the explanation, he added.
The CDC is planning a study to improve and standardize the method of faster testing. In the meantime, people should still get recommended pertussis vaccinations, Clark said.
Clark said he believes there is a real increase in cases, and that many are going undiagnosed. Two states, Minnesota and Massachusetts, have beefed up their case-finding and testing and have both seen whooping cough increases, he said.

The CDC's Morbidity and Mortality Weekly Report: http://www.cdc.gov/mmwr

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Outbreaks of Respiratory Illness Mistakenly Attributed to Pertussis --- New Hampshire, Massachusetts, and Tennessee, 2004--2006
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5633a1.htm

画像Pertussis, or whooping cough, is a highly infectious, nationally notifiable* respiratory disease associated with prolonged cough illness and paroxysms of coughing, inspiratory "whoop," or posttussive vomiting. Reported pertussis cases have tripled in the United States since 2001, with 25,616 probable or confirmed cases reported in 2005 (Figure 1). This increase has been attributed to increased circulation of Bordetella pertussis, waning vaccine-induced immunity among adults and adolescents, heightened awareness of pertussis among health-care providers, increased public health reporting, and increased use of polymerase chain reaction (PCR) testing for diagnosis (1). To minimize the spread of pertussis, control measures must be implemented early in the course of illness when the risk for transmission is highest. However, diagnosis of pertussis is complicated by nonspecific signs and symptoms, particularly in the early catarrhal stage of disease. In addition, the lack of rapid, sensitive, and specific laboratory tests makes early and accurate identification of pertussis challenging. This report describes two hospital outbreaks and one community outbreak of respiratory illness during 2004--2006 in New Hampshire, Massachusetts, and Tennessee that were attributed initially to pertussis. However, subsequent investigations revealed negative or equivocal laboratory results and epidemiologic and clinical features atypical of pertussis, suggesting that pertussis was not the cause of these outbreaks. The findings in this report underscore the need for thorough epidemiologic and laboratory investigation of suspected pertussis outbreaks when considering extensive control measures.

New Hampshire. In March 2006, a laboratory worker from a 396-bed hospital visited the occupational medicine clinic with a 3-week history of paroxysmal cough and posttussive vomiting. The laboratory worker tested positive with the hospital's single-target PCR assay for pertussis (IS481).† The worker subsequently was treated with azithromycin and furloughed for 5 days. Postexposure prophylaxis (PEP) with azithromycin was administered to all close contacts. Case investigation from mid-March to early April identified 15 additional health-care personnel (HCP) in the same laboratory with respiratory illness and either a positive or equivocal PCR test result for pertussis, leading hospital investigators to suspect an outbreak. Suspected pertussis in HCP was defined as either 1) cough of any duration and at least one classic pertussis symptom (i.e., paroxysms of coughing, whoop, or posttussive vomiting) or 2) a positive or equivocal PCR test result. In April, to control the spread of the outbreak, the hospital's infection-control and occupational-medicine staff members offered PEP and vaccination with the newly licensed tetanus toxoid, reduced diphtheria toxoid, acellular pertussis vaccine (Tdap) to all personnel in the hospital's clinical laboratories. Despite these interventions, from late April to early May, 18 additional ill HCP with suspected pertussis were identified through passive surveillance in other parts of the hospital, including patient-care areas. In May, the hospital began screening all HCP for signs and symptoms of upper respiratory tract infection and began PCR testing for pertussis on symptomatic HCP. By June, 134 suspected pertussis cases had been identified: 98 (73%) by positive or equivocal PCR results and 36 (27%) by clinical symptoms alone. A total of 192 nasopharyngeal swabs or aspirates from symptomatic HCP, including specimens from 27 (20%) of the 134 HCP with suspected pertussis, were submitted for isolation of B. pertussis by culture throughout the course of the outbreak; none yielded B. pertussis.

Review of surveillance data revealed no increased pertussis activity in the surrounding community. No pertussis cases were identified among vaccinated or unvaccinated infants, either in the hospital or surrounding community. Retrospective interviews of 120 (90%) HCP with suspected pertussis indicated that 25 (21%) of those interviewed never had cough, a hallmark symptom of pertussis. Among the 95 (79%) HCP with cough, 33 (35%) reported never having a classic pertussis symptom (i.e., paroxysms, whoop, or posttussive vomiting). Myalgia, not typically associated with pertussis, was reported by 32 (34%) of 93 HCP who were asked whether they had this symptom.

Additional laboratory evaluation included retesting of initial DNA extracts at CDC using a two-target PCR assay (IS481 and ptxS1). Among 111 extracts available for testing, one was positive for both targets and interpreted as B. pertussis, and 24 extracts were positive by single target alone (IS481) and interpreted as indeterminate. Sera from 39 HCP who had not been vaccinated during the outbreak with Tdap and who met the hospital's definition for suspected pertussis were collected and tested at Vanderbilt University Medical Center in Nashville, Tennessee, for antipertussis toxin immunoglobulin G (IgG) by enzyme-linked immunosorbent assay (ELISA); one sample had a positive IgG level, one was intermediate, and 37 were negative. Samples of aspirates and DNA extracts were tested at the hospital and CDC for a panel of viral pathogens, other Bordetella species, Chlamydia pneumoniae, and Mycoplasma pneumoniae. PCR testing yielded two specimens with results consistent with Bordetella holmesii.

Substantial resources were invested to control this outbreak. During March--May 2006, approximately 1,700 visits by HCP to the occupational medicine clinic for respiratory illness were reported. Among 6,289 hospital HCP, 978 (16%) ill HCP were tested by PCR, treated, and furloughed pending negative PCR results. An additional 1,311 contacts of HCP with suspected pertussis received PEP. Other control measures included a 1-week Tdap vaccination campaign in May, during which 4,524 (72%) HCP were vaccinated.

Massachusetts. A child aged 20 months was admitted to a 347-bed pediatric hospital on September 21, 2006, with respiratory symptoms; the child had not received all age-appropriate doses of diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccine. Initial tests on September 24 were positive for respiratory syncytial virus. Subsequent testing for pertussis by two-target PCR assays (IS481 and ptxS1) at the Massachusetts State Laboratory Institute (MSLI) were positive for both targets on October 2, 2006. In October, the hospital initiated enhanced screening of symptomatic HCP with suspected pertussis and other HCP who had been in contact with the child.

A total of 507 HCP with upper respiratory symptoms were identified during the course of the investigation. Nasopharyngeal specimens from symptomatic HCP were tested by culture, PCR, or both during October 1--November 14. By December 2006, 36 specimens from HCP had tested positive for pertussis by PCR (33 at MSLI and three at a commercial laboratory). Twenty-eight of the 36 (78%) HCP had reported cough of fewer than 2 weeks and 33 (92%) had reported no classic pertussis symptoms. Of the 33 PCR-positive specimens tested for two targets at MSLI, 29 (88%) were positive by a single target (IS481) and four (12%) were positive by both targets (IS481 and ptxS1). Of the 32 PCR-positive specimens submitted for culture, none yielded B. pertussis. Sera were collected from 23 HCP who had positive PCR test results and were not vaccinated during the outbreak; all were negative for antipertussis toxin IgG by ELISA at MSLI.

Because a number of HCP had atypical symptoms and no culture or serologic confirmation of pertussis, repeat PCR testing was conducted at CDC and the Provincial Laboratory for Public Health in Alberta, Canada. Twenty-five initial DNA extracts with positive PCR test results were retested at CDC using two-target PCR assays (IS481 and ptxS1). One sample was positive by both targets (IS481 and ptxS1) and interpreted as positive for B. pertussis, and 24 were positive by a single target only (IS481) and interpreted as indeterminate. Six of the 25 initial DNA extracts also were retested by the Canadian laboratory; two extracts were positive by IS481 and ptxS1 (interpreted as positive for B. pertussis), three were positive by IS481 only (interpreted as possibly B. pertussis), and one result was uninterpretable. Overall, only one of six specimens tested by MSLI, CDC, and the Canadian laboratory was interpreted as positive for B. pertussis by all three laboratories. Six DNA extracts were tested for M. pneumoniae by PCR, and none were positive.

Tennessee. In April 2004, pertussis in an infant aged 5 weeks was confirmed by isolation of B. pertussis from a nasopharyngeal specimen. Before diagnosis, the infant had been taken to the local health department and two other medical facilities. Aggressive contact tracing and testing of symptomatic contacts was undertaken by the local health department. For this investigation, a laboratory-confirmed case was defined as a PCR-positive case in a symptomatic contact, using a single-target repeating sequence found in B. pertussis (RSBP1). A clinical case was defined as either cough illness of at least 2 weeks' duration or cough of any duration with paroxysms of coughing, whoop, or posttussive vomiting and an epidemiologic link to a laboratory-confirmed case. Antimicrobial treatment was offered to all patients, and PEP was offered to all asymptomatic close contacts. Further contact tracing and control measures were implemented for all patients with laboratory-confirmed or clinical diagnoses of pertussis.

During a 2-month period, 1,459 persons in the community who visited health-care providers with pertussis symptoms were evaluated for pertussis and offered treatment or PEP with erythromycin or azithromycin. A total of 317 symptomatic persons were tested by PCR; 43 (14%) were positive. Of these, only two (5%) had cough of at least 2 weeks' duration. Among 284 samples submitted for culture, only the specimen from the infant yielded B. pertussis. Because of the lack of culture confirmation, serologic testing for antipertussis toxin IgG by ELISA was performed at Vanderbilt University Medical Center on 21 patients and contacts. Four of 11 patients who were positive by PCR also had serologic evidence of recent pertussis infection. Testing for alternate pathogens was not performed.

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