踢爆溫家寶家族斂財 紐時獲普立茲獎
〔編譯魏國金／綜合報導〕紐約時報去年揭發時任中國國務院總理溫家寶家族聚斂財富的報導，十五日榮獲美國新聞最高榮譽普立茲獎。紐時共獲得四項大獎，是本屆普立茲獎最大贏家，其中榮獲「釋義性新聞獎」（Explanatory 美國哥倫比亞大學十五日公布第九十七屆普立茲獎。紐時上海分社社長張大衛（David 紐時指出，另一與中國有關的得獎報導「蘋果經濟」，則是多面向地分析蘋果等科技公司的商業行為，特別是中國在全球科技供應鏈中的角色。 紐時還拿下「調查報導」、「特寫寫作」獎，其中「沃爾瑪深陷墨西哥賄賂門」的調查報導，最終導致零售巨擘沃爾瑪改變其商業行徑。紐時是獲得最多獎項的美國全球性報紙，華爾街日報則獲得評論類獎、華盛頓郵報拿下批評獎。 | ||
可參照下面幾篇文章: "溫嘉寶抗議紐約時報報導溫家隱藏龐大財產 " http://tw.myblog.yahoo.com/ccshsu-clement/article?mid=10052&prev=10056&next=10050&l=f&fid=63 "溫家寶一族隱藏的巨額財產!! (又加後續消息)" "原來如此!! 中國高幹子孫都是超巨富!! 不知如何得來的??" "中國領導要掃貪哪! 很難很難!! 當笑話聽聽就好。--看習近平如何!" |
2013年4月17日 星期三
踢爆溫家寶家族斂財 紐時獲普立茲獎
2013年4月16日 星期二
曹長青：談金恒煒再次「被打」
重讀曹長青先生這篇文章, 對金恆煒和曹長青兩位先生更加敬佩. 兩位先生都是大筆如椽、正氣浩然; 如曹長青說:
"...就是支持這種「雖千萬人吾往矣」的獨立精神，就是支持言論自由的理念。而只有這種價值理念被更多的台灣知識分子認同和追求，台灣才會有真正的希望！"
"...就是支持這種「雖千萬人吾往矣」的獨立精神，就是支持言論自由的理念。而只有這種價值理念被更多的台灣知識分子認同和追求，台灣才會有真正的希望！"
是的, 「言論自由」是民主社會最根本的「理念」, 曹長青也經常強調:
"跟隨理念不跟人"
"Follow Principles, Don't Follow a Person/Don't Idolize a Leader!"
不尊重「言論自由」的社會或社團中, 就會有「言論查禁」(Censorship)這種見不得人、見不得陽光的野蠻行為!
在台灣人、台美人的社團中, 真正尊重百分之百的「言論自由」(100% Freedom of Speech)理念的社團又有多少呢?
不尊重「言論自由」的社會或社團, 一定沒有公平正義, 就可能是個正在走向「一言堂」的「半奴隸」社會或社團!
Bill Huang, 4/13/2013, Sacramento
************************************************
|
2013年4月14日 星期日
H7N9 疫情續報 2013-4-14
北京淪陷// H7N9 上海首見家庭群聚感染
〔記者邱宜君／台北報導〕中國北京出現首例H7N9個案，是一名七歲女童，中央流行疫情指揮中心指揮官張峰義表示，這是中國疫情爆發以來第二名兒童病例，兩人都曾接觸禽鳥，已將北京列入疫區。
 |
| 中國北京十三日出現首例H7N9禽流感確診病例，是一名七歲女孩，記者在她就診的北京地壇醫院病房外拍攝。（路透） |
〔編譯魏國金、記者邱宜君／綜合報導〕H7N9禽流感疫情已跳脫華東地區，蔓延到千里之外的北京市，一名七歲女孩確診感染H7N9，是北京首起感染病例；此外，上海也出現首起「家庭群聚感染」，一對夫妻先後染病。目前中國確診病例達四十九例，其中十一人死亡。
7歲女童確診 北京緊張
北京市衛生局指出，七歲姚姓女孩於十一日上午九時出現發燒、喉嚨痛、咳嗽、頭痛等症狀，父母帶她就醫。院方以克流感救治，當晚情況惡化後轉至加護病房，十三日凌晨確診出H7N9病毒，目前她的呼吸改善、體溫下降，情況轉趨穩定。姚姓女童的父母從事活禽交易工作，經隔離觀察，迄今未出現感染症狀。
上海三月底出現疫情後，北京即禁止活禽交易與釋放鴿子。北京人口逾兩千萬人，昨天傳出第一起確診病例後，當地民眾十分緊張，不少網友透過微博呼籲朋友要多休息、少出門。當局則在姚家居住的北京東北區撲殺了五百餘隻鳥禽，並下令儲存克流感。
上海一對夫妻 先後發病
上海當局昨日公布五十六歲顧姓男子也確診染病，小他四歲的妻子早在四月四日便確診染病。顧男於四月一日出現發燒、全身無力症狀，之後接連就醫，經兩度採樣化驗，直到十一日才確診染患H7N9。這是第一起家庭群聚事件，顧男是一般職員，與他密切接觸的四人皆無異樣。
中央流行疫情指揮中心表示，依據目前中國提供的資料，無法排除這對夫婦為互相傳染。疾管局防疫中心主任莊人祥表示，防疫等級第三級包括「禽傳人」和「侷限性的人傳人」，親密接觸者之間的「侷限性人傳人」，尚未達到社區流行（有效人傳人），疫情等級仍維持為第三級，不需要提高防疫等級。如果進入到第四級社區流行，可高達四、五十人以上感染。
H5N1過去十多年來出現過非常多起家庭群聚，例如印尼一家八口參加喪禮後全部感染，但這都只是侷限性人傳人，H7N9現在也是這種情況。
台大醫院兒童感染科主任黃立民表示，顧氏夫婦發病間隔七到十天內，有可能是人傳人，不過家庭群聚事件仍屬於第三級。
台灣感染症醫學會發言人李秉穎認為，親子之間、醫護人員與病人之間的傳染，都是侷限性的，還稱不上有效人傳人的規模。
中國病例續增 49例11死
江蘇省衛生廳十三日通報兩起新增病例。七十七歲的顧姓老婦為南京市民，另一位七十二歲的馬姓老翁家住常熟市，兩人病危。
中國商業活動已經受到疫情波及，中國肯德基三月銷售額大跌十六％，母公司百勝集團坦承是受到禽流感的衝擊。
H7N9 恐已在中國禽類間蔓延
 |
| 北京出現七歲女童病患。（路透） |
〔記者洪素卿／台北報導〕中國緊急關閉多處活禽市場後，疫情似乎仍未降溫，昨日北京再傳一名H7N9禽流感病例。由於病童家長從事活禽販賣，病毒來源直指家禽，但原本侷限在長江三角地帶的H7N9禽流感病毒，如何來到千里之外的北京，也為這場疫情增加許多變數。
台大獸醫學院名譽教授賴秀穗指出，由於家禽感染後沒有病徵，這例新病例顯示這株對家禽屬低病原性的病毒，恐怕已經在中國禽類間持續蔓延開來。
候鳥北飛？ 搭車運載？ 跳過河北、山東令人費解
賴秀穗指出，要看疫情走勢，七天之內的變化是重要的觀察指標，而過去這一週感染人數倍數上升，同時區域擴大，顯示這場疫情「不能小看」。
前台灣省家畜衛生試驗所所長劉培柏則認為，一時之間很難釐清這病毒究竟是如何跳過山東、河北，一下子就到了千里之外的北京。他表示，如果以養雞的規模，山東在中國算是不小的據點，但山東沒有疫情，反倒是北京傳出病毒，的確讓人難以理解。
劉培柏指出，兩地距離實在太遠，不大可能是因為活禽交易，使得帶病毒雞隻直接進入北京。那麼會是因為候鳥北飛？或是交通運輸工具？或是有其他原因？從現有資訊難以斷定。
更令人難以理解的是，這次中國找到的病毒樣本數是來自活禽集散市場禽鳥樣本以及部分環境樣本，反倒養殖場迄今沒有驗出病毒？
農委會防檢局副局長黃國青表示，以我國的防檢機制，一旦在批發市場發現，一定是往上找養殖場。究竟問題發生在那些環節？還是得等到農委會前往中國的官員帶回多一些資訊才能判讀。
病毒基因變異？ 我將北京列疫區
〔記者邱宜君／台北報導〕中國北京出現首例H7N9個案，是一名七歲女童，中央流行疫情指揮中心指揮官張峰義表示，這是中國疫情爆發以來第二名兒童病例，兩人都曾接觸禽鳥，已將北京列入疫區。
疾管局：輕症人數將增 死亡率會降
疾管局防疫中心主任莊人祥分析，中國已於十一日放寬檢驗與給藥條件，未來輕症確診的人數應會越來越多，死亡率會下降。
第一例H7N9兒童病例是一位四歲上海男童，四月十日痊癒出院；這名七歲北京女童是在四月十一日出現發燒、喉嚨痛、咳嗽、頭痛等症狀，後因「肺部感染」住院，十三日確診感染H7N9病毒。兩位兒童都有禽鳥接觸史，上海男童家裡養四隻雞，北京女童雙親則皆從事活禽販賣工作，家長皆無不適症狀。
台大醫院小兒部感染科主治醫師呂俊毅表示，疾病是否能廣泛感染人類，關鍵在於病毒本身，而「小孩」就是人傳人疾病的重要媒介，孩童經由與同伴玩耍、與家人親密接觸，將疾病從學校帶入家裡，或從家裡帶進學校。
不過呂俊毅認為，疫情成謎之處在於「為什麼到處都是？」關閉活禽交易市場可能幫助有限，因為「中國太大」，小市場和家庭飼養的狀況，難以充分掌握。
指揮官張峰義指出，無法確定這位北京女童感染的病毒與其他四個疫區的病毒相同，還是病毒基因已產生變異或重組。但北京出現首例不應視為疫情「擴散」，只能說「越來越清楚」，因為之前「可能有人肺炎死了，也不知道那就是H7N9」。
農委會防檢局組長邱垂章也說，防疫最難的就是防範「沒有症狀的動物」，目前中國透過加強禽鳥監測與加強人類防疫工作來防堵。
張峰義擔心，候鳥四月是由南往北飛，但九月就會開始有由江蘇、浙江南飛到台灣的候鳥，極可能由此引發本土案例。從五月到九月之間，台灣政府必須做好包括監測病毒變化、市場管理、養殖場圍網等工作。
Date: 13 Apr 2013
Source: Xinhua Net
<http://news.xinhuanet.com/english/health/2013-04/14/c_132306889.htm>
China reports 2 more H7N9 cases
- ---------------
Two new cases of H7N9 bird flu infection were reported in Central
China's Henan Province on Sunday [14 Apr 2013], bringing the total
number of such cases in country to 51.
- --
Communicated by:
Ryan McGinnis
<digicana@gmail.com>
[Henan province borders with Anhui province to the east. As mentioned
in yesterday's post announcing the 1st case in Beijing outside of the
small block of Eastern Provinces where the virus has been circulating
that now that all provinces have the laboratory capabilities to
identify H7N9 infection, it is not surprising the more cases will be
found. Also, given the mobility of the population combined with the
mobility of the avian population, many of which may be healthy
carriers of the virus, spread outside of the originally identified
areas was only a matter of time.
<http://www.mytripolog.com/wp-content/uploads/2012/06/Map-Of-China-Provinces-and-capital-cities.jpg>
More information on the findings of the investigations into these 2
cases would be greatly appreciated by ProMED. - Mod.MPP]
AVIAN INFLUENZA, HUMAN (41): CHINA H7N9 UPDATE
**********************************************
In this update:
[1] Global concerns - NEJM
[2] European implications - Eurosurveillance
[3] WHO update - 2013
[4] UK: travel advice - Public Health England
******
[1] Global concerns - NEJM
Date: Thu 11 Apr 2013
Source: The New England Journal of Medicine, Perspective [edited]
<http://www.nejm.org/doi/full/10.1056/NEJMp1304661?query=featured_home>
[Ref: Uyeki TM, Cox NJ: Global Concerns Regarding Novel Influenza A
(H7N9) Virus Infections. N Engl J Med 2013. DOI:
10.1056/NEJMp1304661]
- ----------------------------------------------------------------------
Severe disease in humans caused by a novel influenza A virus that is
distinct from circulating human influenza A viruses is a seminal
event. It might herald sporadic human infections from an animal source
- -- such as, highly pathogenic avian influenza (HPAI) A (H5N1) virus;
or it might signal the start of an influenza pandemic -- such as,
influenza A(H1N1)pdm09 virus. Therefore, the discovery of novel
influenza A (H7N9) virus infections in 3 critically ill patients is of
major public health significance. Chinese scientists are to be
congratulated for the apparent speed with which the H7N9 virus was
identified, and whole viral genome sequences were made publicly
available in relatively short order. Because this H7N9 virus has not
been detected in humans or animals previously, the situation raises
many urgent questions and global public health concerns.
The key question for pandemic risk assessment is whether there is
evidence of either limited or, more important, sustained
human-to-human transmission -- the latter being indicative of an
emerging pandemic. If human-to-human transmission occurs, transmission
dynamics, modes of transmission, basic reproductive number, and
incubation period must all be determined. It is possible that these
severely ill patients represent the tip of the iceberg and that there
are many more as-yet-undetected mild and asymptomatic infections.
Determining the spectrum of illness will help us understand the scope
of the problem and assess severity. Enhanced surveillance for H7N9
virus infection is therefore urgently needed among hospitalized
patients and outpatients of all ages with less severe respiratory
illness. Other useful information can be derived from monitoring close
contacts of patients with confirmed H7N9 cases to assess whether
family members or health care personnel who provided care for patients
with H7N9 virus infection have respiratory illness and
laboratory-confirmed H7N9 virus infection. Such investigations will
clarify whether H7N9 virus transmission in people appears efficient,
or whether limited, nonsustained human-to-human transmission is
occurring in persons with prolonged unprotected exposures, such as in
clusters of HPAI H5N1 cases in blood-related family members. So far,
the information provided by Chinese health officials provides
reassurance that sustained human-to-human transmission is not
occurring.
In addition to causing severe illness and deaths, the novel H7N9
viruses reported by Gao and colleagues have genetic characteristics
that are of concern for public health. The hemagglutinin (HA) sequence
data suggest that these H7N9 viruses are a low-pathogenic avian
influenza A virus and that infection of wild birds and domestic
poultry would therefore result in asymptomatic or mild avian disease,
potentially leading to a "silent" widespread epizootic in China and
neighboring countries. If H7N9 virus infection is primarily zoonotic,
as reports currently suggest, transmission is expected to occur
through exposure to clinically normal but infected poultry, in
contrast to HPAI H5N1 virus infection, which typically causes rapid
death in infected chickens.
The gene sequences also indicate that these viruses may be better
adapted than other avian influenza viruses to infecting mammals. For
example, the presence of Q226L in the HA protein has been associated
with reduced binding to avian-like receptors bearing sialic acids
linked to galactose by alpha-2,3 linkages found in the human lower
respiratory tract, and potentially an enhanced ability to bind to
mammalian-like receptors bearing sialic acids linked to galactose by
alpha-2,6 linkages located in the human upper airway. Equally
troubling is that Q226L in HA has been shown to be associated with
transmission of HPAI H5N1 viruses by respiratory droplets in ferrets,
one of the animal models for assessing pathogenicity and
transmissibility of influenza viruses. These H7N9 viruses also possess
the E627K substitution in the PB2 protein, which has also been
associated with mammalian adaptation and respiratory-droplet
transmission of HPAI H5N1 virus in ferrets. This H7N9 virus is a novel
reassortant with HA and neuraminidase (NA) genes from an ancestral
avian H7N9 virus and the 6 other genes from an avian H9N2 virus. The
animal reservoir now appears to be birds, but many experts are asking
whether these viruses might also be able to infect pigs, another
common reservoir for zoonotic infections. The viral sequence data
indicate antiviral resistance to the adamantanes and susceptibility to
neuraminidase inhibitors, except for a 292K mutation in the NA protein
of the A/Shanghai/1/2012 virus. Because this mutation has been
associated with in vitro resistance to neuraminidase inhibitors in
another N9 NA subtype virus, additional analyses must be undertaken to
understand its significance. It is not known whether this mutation
arose de novo in the host or is associated with oseltamivir treatment.
Ongoing surveillance is crucial to assessing the emergence and
prevalence of H7N9 viruses resistant to available antivirals.
Since available diagnostic assays used in clinical care (such as,
rapid influenza diagnostic tests) may lack sensitivity to identify
H7N9 virus and since existing molecular assays will identify H7N9
virus as a nonsubtypeable influenza A virus, a critical public health
issue is the rapid development, validation, and deployment of
molecular diagnostic assays that can specifically detect H7N9 viral
RNA. Such assays have been developed in China and are in development
in many countries including the United States, and they will be
deployed as they were for the 2009 H1N1 pandemic. Having available
H7-specific assays will facilitate surveillance of H7N9 virus
infections and help address key questions such as the duration of
viral shedding, the infectious period, the optimal clinical specimens
for laboratory confirmation, and the spectrum of clinical illness.
The clinical features described in the 3 patients with H7N9 virus
infection, including fulminant pneumonia, respiratory failure, acute
respiratory distress syndrome (ARDS), septic shock, multiorgan
failure, rhabdomyolysis, and encephalopathy, are very troubling.
Clinical care of severely ill patients should be focused on
evidence-based supportive management of complications such as ARDS.
Adherence to recommended infection-control measures in clinical
settings to reduce the risk of nosocomial transmission cannot be
overemphasised.
All 3 patients with H7N9 virus infection reported by Gao and
colleagues received late treatment with oseltamivir starting on day 7
or 8 of illness while critically ill. Data related to human infections
with seasonal, pandemic, and HPAI H5N1 viruses indicate that the
earlier antiviral treatment is initiated, the greater the clinical
benefit. Therefore, oral oseltamivir or inhaled zanamivir should be
administered to patients with suspected or confirmed H7N9 virus
infection as soon as possible. Secondary invasive bacterial infections
associated with influenza can cause severe and fatal complications,
and appropriate empirical antibiotic treatment for community-acquired
bacterial infections may be indicated for initial management of severe
H7N9 pneumonia. Caution should be exercised regarding the use of
glucocorticoids, which are not indicated for routine treatment of
influenza. Clinical research, including randomized, controlled trials
and observational studies, is urgently needed on new antiviral agents,
including parenteral neuraminidase inhibitors and drugs with different
mechanisms of action, combination antiviral treatment, and
immunotherapy. To inform clinical management, rapid clinical data
collection, data sharing, analysis, and timely feedback are needed
worldwide.
Because H7N9 virus infections have not occurred in humans before, it
is expected that persons of all ages might be susceptible worldwide.
Serologic assays must be developed so that studies can be conducted to
determine whether some people have cross-reactive antibodies to these
viruses from prior influenza A virus infections. Existing H7-vaccine
viruses are not well matched to this novel H7N9 virus, and extensive
efforts are under way to develop potential H7N9 vaccines as quickly as
possible. These efforts have started worldwide using the H7N9 sequence
data obtained from these early cases, and sharing of H7N9 viruses will
further facilitate vaccine development. There are many challenges to
making H7N9 vaccines available. Previously studied H7 vaccines were
poorly immunogenic in humans, and clinical trials to assess the safety
and immunogenicity of H7N9 vaccine candidates will be needed. But even
if new vaccine manufacturing technologies, such as
tissue-cell-culture-derived vaccine antigens, are utilized, the
process from vaccine development to availability will probably take
many months.
The 2009 H1N1 pandemic taught us many lessons, including that a
pandemic virus can emerge from an animal reservoir in an unexpected
location and be spread rapidly through air travel. The focus on
critically ill adults early in the pandemic led to elevated public
concern about pandemic severity. Clear communication of key messages
to the public and the clinical community is critical in implementing
successful prevention and control activities. The detection of human
H7N9 virus infections is yet another reminder that we must continue to
prepare for the next influenza pandemic. The coming weeks will reveal
whether the epidemiology reflects only a widespread zoonosis, whether
an H7N9 pandemic is beginning, or something in between. The key is
intensified surveillance for H7N9 virus in humans and animals to help
answer important questions. We cannot rest our guard.
******
[2] European implications - Eurosurveillance
Date: Thu 11 Apr 2013
Source: Eurosurveillance Edition 2013, 18(15) [summ., edited]
<http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20452>
A novel reassortant avian influenza A(H7N9) virus in China -- what are
the implications for Europe
- ----------------------------------------------------------------------
[Authors: A Nicoll, N Danielsson (Date of submission: 10 Apr 2013)
European Centre for Disease Prevention and Control (ECDC), Stockholm,
Sweden]
What are the possible implications of the current situation for Europe
and European citizens and which actions should the EU take and which
ones have been taken already? The European Centre for Disease
Prevention and Control (ECDC) published its 1st risk assessment on 3
Apr 2013 and is providing updated assessments and short reports on the
epidemiology as new information emerges. Several guidance documents on
prevention of infections, infection control and case management
developed earlier for influenza A(H1N5) by ECDC, WHO and Member States
are, with some modifications, applicable to the current situation].
Visitors to China and other countries where avian influenzas have
caused severe human disease of late, should avoid visiting bird
markets and follow basic hygienic measures. Persons returning from
China who develop severe respiratory infection within 10 days should
be evaluated and tested for the new virus to rule out such infection
[17], though most likely another infection will be detected. Case
management and infection control guidelines for A(H5N1) apply in the
short term. This will include antiviral treatment given that the
Chinese CDC promptly established that the A(H7N9)viruses are
susceptible to neuraminidase inhibitors [4,5].
There is a standing procedure in place in Europe to send all
non-subtypeable influenza A viruses isolated from humans promptly to
the WHO Collaborating Center in London for further analysis.
Notwithstanding this, ECDC, the WHO Regional Office for Europe, the
WHO Influenza Collaborating Centre, the University of Bonn, and the
Community Network Reference Laboratories are working in together to
make testing for A(H7N9) possible in all National Influenza Centres in
Europe as soon as possible.
Some candidate H7 and H9 vaccines viruses already exist under WHO's
strain selection system for the eventuality of an emerging virus [19].
They may not be effective against the new influenza A(H7N9) virus and
once the regulatory laboratories have obtained the novel virus, WHO
and presumably EU authorities will now need to consider if they wish
to proceed with the very early stages of vaccine development as has
been done for the candidate H7 and H9 viruses.
Overall, how concerned Europe should be cannot yet be determined. The
new virus is a reassortant virus based on an haemaglutinin antigen
A(H7) to which most humans will not have been exposed. Therefore, if
human-to-human transmission starts, and that is only an 'if',
population immunity cannot be presumed. It would have to be assessed
now by determining age-specific sero-reactivity of human sera to this
influenza A(H7N9) virus as a priority. Immunity, or lack of it, in the
human population are key data required for assessing pandemic risk. As
stated above, they needed to come from field investigations in China
as well as seroepidemiological studies in Europe based on protocols
developed precisely for such situations [20].
At this very moment it cannot be ruled out that there are some
human-to-human transmissions causing mild or asymptomatic infections
as happened in the Netherlands in 2003. It also remains unclear to
what extent the predominance of severe disease may represent a bias
because mainly people with severe disease are tested. Investigations
of patients' contacts including serological studies, will clarify this
point. Such investigations orchestrated by the Chinese CDC are
underway.
There will be many other calls for research and it will be important
and difficult to prioritise. Fortunately a framework exists for making
decisions on priorities. The Influenza Risk Assessment Tool (IRAT) has
been developed since 2011 for this purpose by the United States (US)
Centers for Disease Control and Prevention with some international
partners [21,22]. It looks at 10 parameters bundled into three
families: properties of the virus, attributes of the population,
ecology and epidemiology. It has already been deployed to inform US
decisions on the A(H3N2)v vaccines. It does not predict pandemic risk
or make decisions but it informs decisions. Though the IRAT is still
being evaluated as a tool it will certainly indicate what should be
some of the most important public health research priorities for
A(H7N9).
It is also important that the sequence and virological analyses are
considered in combination with the epidemiological findings. Despite
the virological markers described in the recent report from the WHO
Collaborating Centres [5] it should not be seen as inevitable on the
longer term that this reassortant A(H7N9) will develop efficient
human-to-human transmissibility or become established in Europe,
though both should be kept in mind as possibilities. Neither has
happened for the highly pathogenic influenza A(H5N1) virus in the
decade and a half since its emergence in China in 1996 [23]. Despite
multiple detections of the A(H5N1)virus in wild birds and some
outbreaks in domestic poultry flocks in Europe, the high levels of
biosafety in the EU have not permitted A(H5N1) viruses to become
established in European domestic poultry. It is fortunate that the
European Commission and the Member States have since 2007 established
surveillance for low pathogenicity avian influenza in domestic and
wild birds in Europe [14]. The recent events have underlined the
importance of this system.
[The full article and references are available at the source URL
above. - Sr.Tech.Ed.MJ]
******
[3] WHO update - 12 Apr 2013
Date: Fri 12 Apr 2013
Source: WHO Global Alert and Response (GAR), Disease Outbreak News
[edited]
<http://www.who.int/csr/don/2013_04_12/en/index.html>
Human infection with influenza A(H7N9) virus in China -- update
- ---------------------------------------------------------------
As of 12 Apr 2013 (17:30 CET), the National Health and Family Planning
Commission notified WHO of an additional 5 laboratory-confirmed cases
of human infection with influenza A(H7N9) virus. Of the latest
laboratory-confirmed cases, 3 are from Zhejiang and 2 from Shanghai.
The 1st patient is a 66-year-old man from Zhejiang who became ill on 8
Apr 2013; the 2nd patient is a 74-year-old man from Zhejiang who
became ill on 6 Apr 2013; the 3rd patient is a 54-year-old woman from
Zhejiang who became ill on 6 Apr 2013; the 4th patient is a
53-year-old man from Shanghai who became ill on 3 Apr 2013; and the
5th patient is an 86-year-old man from Shanghai who became ill on 3
Apr 2013.
In addition, a patient earlier reported from Shanghai has died. To
date, a total of 43 patients have been laboratory confirmed with
influenza A(H7N9) virus in China; including 11 deaths. More than 1000
close contacts of the confirmed cases are being closely monitored.
The Chinese government is actively investigating this event and has
heightened disease surveillance. Retrospective testing of recently
reported cases with severe respiratory infection may uncover
additional cases that were previously unrecognized. An
inter-government task force has been formally established, with the
National Health and Family Planning Commission leading the
coordination along with the Ministry of Agriculture and other key
ministries. The animal health sector has intensified investigations
into the possible sources and reservoirs of the virus.
WHO is in contact with national authorities and is following the event
closely. The WHO-coordinated international response is also focusing
on work with WHO Collaborating Centres for Reference and Research on
Influenza and other partners to ensure that information is available
and that materials are developed for diagnosis and treatment and
vaccine development. No vaccine is currently available for this
subtype of the influenza virus. Preliminary test results provided by
the WHO Collaborating Centre in China suggest that the virus is
susceptible to the neuraminidase inhibitors (oseltamivir and
zanamivir).
At this time there is no evidence of ongoing human-to-human
transmission. WHO does not advise special screening at points of entry
with regard to this event, nor does it recommend that any travel or
trade restrictions be applied.
******
[4] UK: travel advice - Public Health England
Date: Fri 12 Apr 2013
Source: Public Health England, Health Protection Report 7(15), Travel
Health [edited]
<http://www.hpa.org.uk/hpr/infections/travel.htm#nthnch7n9>
H7N9 avian influenza in China -- travel advice
- ----------------------------------------------
The National Travel Health Network and Centre (NaTHNaC) has published
updated information for travellers and health professionals on H7N9
avian influenza human infections in China.
As of 11 Apr 2013, 38 human cases [now 43], including 10 [now 11]
deaths, had been reported from 4 different provinces, with no evidence
of ongoing human-to-human transmission.
The risk of disease spread to Europe remains low, although individual
cases arriving from China cannot be ruled out. NaTHNaC recommends that
basic hygiene practices and food safety precautions are taken by all
travellers. In addition, travellers should avoid visiting live bird
markets and, in particular, should avoid any direct contact with bird
and animal faeces and untreated bird feathers. Travellers who become
ill with respiratory symptoms within 7 days of a trip to China should
seek medical advice from their GP or NHS 111.
2013年4月12日 星期五
Thomas Jefferson 美國最受尊敬的三位總統之一
10 facts about Thomas Jefferson for his 270th birthday
By NCC Staff | National Constitution Center – 3 hrs ago
Thomas Jefferson is celebrating the big 2-7-0 this week, and we have 10 interesting facts about the versatile Founding Father.
Jefferson is best known for his role in writing the Declaration of Independence, his foreign service, his two terms as president, and his omnipresent face on the modern nickel.
The well-rounded Jefferson was also a Renaissance man who was intellectually curious about many things.
Here are 10 interesting facts about Jefferson’s pursuit of knowledge:
1. Thomas Jefferson really, really liked books. The third president, after his retirement, sold his library of 6,500 volumes to the Library of Congress after it was ransacked by the British. Jefferson needed the cash to pay off debts, but he started buying more books. “I cannot live without books,” he told John Adams.
2. Jefferson the economist. Jefferson was deeply engaged in economic theory, which he learned to love during his time in France. He was a friend and translator to leading European theorists; he believed in the free market policies; and he opposed bank notes as currency.
3. Jefferson the architect. He designed the rotunda for the University of Virginia, his own home at Monticello, and the Virginia State Capitol in Richmond. Monticello has some good resources about what he called the “hobby of my old age,” though architecture actually a lifetime pursuit. Monticello and the University of Virginia are on the World Heritage List.
4. Jefferson the food lover. On his return from France, Jefferson brought his love of that nation’s cuisine back with him. James Hemings went to France as his slave, and the pair agreed that if Hemings learned how to make French cuisine, he would be freed on his return to America.
5. Jefferson the wine snob. Yes, Jefferson brought his love of French wine back to America, too. He had two vineyards at Monticello, which he apparently used to experiment with. Acknowledged as a great wine expert of early America, he sought to promote wine as an alternative to whiskey and cider.
6. Jefferson the agriculturalist. He believed in the United States as an agrarian society, in part, because it would make the nation independent from other nations. Jefferson practiced what he taught: He was one of the first American farmers to employ crop rotation and redesigned the plow to make it more efficient.
7. Jefferson the paleontologist. He was also obsessed with fossils and was involved in a great debate about the mammoth that became a political cause. Jefferson raised the profile of paleontology as president, and he has a mammoth named after him.
8. Jefferson the astronomer. Jefferson loved stargazing almost as much as he liked books. He made sure astronomy was taught at the University of Virginia, and he designed what may have been the first observatory in the United States.
9. Jefferson the writer. He was a prolific writer during his lifetime, with his authorship of the Declaration of Independence and the Virginia Statute for Religious Freedom included in his epitaph (instead of his two terms as president). The Thomas Jefferson Papers at the Library of Congress includes about 27,000 documents, including his extensive correspondence with key historical figures.
10. Jefferson the musician. He took violin lessons as a child and played the violin as he courted his future wife, Martha Skelton. Jefferson spent considerable time studying the violin as an instrument, but by 1778 he complained about music being played in the New World as being in a “state of deplorable barbarism.”
2013年4月11日 星期四
perspective on H7N9
Global
Concerns Regarding Novel Influenza A (H7N9) Virus Infections
Timothy M. Uyeki,
M.D., M.P.H., M.P.P., and Nancy J. Cox, Ph.D.
April 11, 2013DOI: 10.1056/NEJMp1304661
Severe disease in
humans caused by a novel influenza A virus that is distinct from circulating
human influenza A viruses is a seminal event. It might herald sporadic human
infections from an animal source — e.g., highly pathogenic avian influenza
(HPAI) A (H5N1) virus; or it might signal the start of an influenza pandemic —
e.g., influenza A(H1N1)pdm09 virus. Therefore, the discovery of novel influenza
A (H7N9) virus infections in three critically ill patients reported in the Journal
by Gao and colleagues is of major public health significance. Chinese
scientists are to be congratulated for the apparent speed with which the H7N9
virus was identified, and whole viral genome sequences were made publicly
available in relatively short order. Because this H7N9 virus has not been
detected in humans or animals previously, the situation raises many urgent
questions and global public health concerns.
The key question for
pandemic risk assessment is whether there is evidence of either limited or,
more important, sustained human-to-human transmission — the latter being
indicative of an emerging pandemic. If human-to-human transmission occurs,
transmission dynamics, modes of transmission, basic reproductive number, and
incubation period must all be determined. It is possible that these severely
ill patients represent the tip of the iceberg and that there are many more
as-yet-undetected mild and asymptomatic infections. Determining the spectrum of
illness will help us understand the scope of the problem and assess severity.
Enhanced surveillance for H7N9 virus infection is therefore urgently needed
among hospitalized patients and outpatients of all ages with less severe
respiratory illness. Other useful information can be derived from monitoring
close contacts of patients with confirmed H7N9 cases to assess whether family
members or health care personnel who provided care for patients with H7N9 virus
infection have respiratory illness and laboratory-confirmed H7N9 virus
infection. Such investigations will clarify whether H7N9 virus transmission in
people appears efficient, or whether limited, nonsustained human-to-human
transmission is occurring in persons with prolonged unprotected exposures, such
as in clusters of HPAI H5N1 cases in blood-related family members. So far, the
information provided by Chinese health officials provides reassurance that
sustained human-to-human transmission is not occurring.
In addition to causing
severe illness and deaths, the novel H7N9 viruses reported by Gao and
colleagues have genetic characteristics that are of concern for public health.
The hemagglutinin (HA) sequence data suggest that these H7N9 viruses are a
low-pathogenic avian influenza A virus and that infection of wild birds and
domestic poultry would therefore result in asymptomatic or mild avian disease,
potentially leading to a “silent” widespread epizootic in China and neighboring
countries. If H7N9 virus infection is primarily zoonotic, as reports currently
suggest, transmission is expected to occur through exposure to clinically
normal but infected poultry, in contrast to HPAI H5N1 virus infection, which
typically causes rapid death in infected chickens.
The gene sequences
also indicate that these viruses may be better adapted than other avian
influenza viruses to infecting mammals. For example, the presence of Q226L in
the HA protein has been associated with reduced binding to avian-like receptors
bearing sialic acids linked to galactose by α-2,3 linkages found in the human
lower respiratory tract,1 and
potentially an enhanced ability to bind to mammalian-like receptors bearing
sialic acids linked to galactose by α-2,6 linkages located in the human upper
airway.1
Equally troubling is that Q226L in HA has been shown to be associated with
transmission of HPAI H5N1 viruses by respiratory droplets in ferrets, one of
the animal models for assessing pathogenicity and transmissibility of influenza
viruses.2,3
These H7N9 viruses also possess the E627K substitution in the PB2 protein,
which has also been associated with mammalian adaptation and
respiratory-droplet transmission of HPAI H5N1 virus in ferrets.3
This H7N9 virus is a novel reassortant with HA and neuraminidase (NA) genes
from an ancestral avian H7N9 virus and the six other genes from an avian H9N2
virus. The animal reservoir now appears to be birds, but many experts are
asking whether these viruses might also be able to infect pigs, another common
reservoir for zoonotic infections. The viral sequence data indicate antiviral
resistance to the adamantanes and susceptibility to neuraminidase inhibitors,
except for a 292K mutation in the NA protein of the A/Shanghai/1/2012 virus.
Because this mutation has been associated with in vitro resistance to
neuraminidase inhibitors in another N9 NA subtype virus, additional analyses
must be undertaken to understand its significance. It is not known whether this
mutation arose de novo in the host or is associated with oseltamivir treatment.
Ongoing surveillance is crucial to assessing the emergence and prevalence of
H7N9 viruses resistant to available antivirals.
Since available
diagnostic assays used in clinical care (e.g., rapid influenza diagnostic
tests) may lack sensitivity to identify H7N9 virus and since existing molecular
assays will identify H7N9 virus as a nonsubtypeable influenza A virus, a
critical public health issue is the rapid development, validation, and
deployment of molecular diagnostic assays that can specifically detect H7N9
viral RNA. Such assays have been developed in China and are in development in
many countries including the United States, and they will be deployed as they
were for the 2009 H1N1 pandemic.4
Having available H7-specific assays will facilitate surveillance of H7N9 virus
infections and help address key questions such as the duration of viral
shedding, the infectious period, the optimal clinical specimens for laboratory
confirmation, and the spectrum of clinical illness.
The clinical features
described in the three patients with H7N9 virus infection, including fulminant
pneumonia, respiratory failure, acute respiratory distress syndrome (ARDS),
septic shock, multiorgan failure, rhabdomyolysis, and encephalopathy, are very
troubling. Clinical care of severely ill patients should be focused on
evidence-based supportive management of complications such as ARDS. Adherence
to recommended infection-control measures in clinical settings to reduce the
risk of nosocomial transmission cannot be overemphasized.
All three patients
with H7N9 virus infection reported by Gao and colleagues received late
treatment with oseltamivir starting on day 7 or 8 of illness while critically
ill. Data related to human infections with seasonal, pandemic, and HPAI H5N1
viruses indicate that the earlier antiviral treatment is initiated, the greater
the clinical benefit. Therefore, oral oseltamivir or inhaled zanamivir should
be administered to patients with suspected or confirmed H7N9 virus infection as
soon as possible. Secondary invasive bacterial infections associated with
influenza can cause severe and fatal complications, and appropriate empirical
antibiotic treatment for community-acquired bacterial infections may be
indicated for initial management of severe H7N9 pneumonia. Caution should be
exercised regarding the use of glucocorticoids, which are not indicated for
routine treatment of influenza. Clinical research, including randomized, controlled
trials and observational studies, is urgently needed on new antiviral agents,
including parenteral neuraminidase inhibitors and drugs with different
mechanisms of action, combination antiviral treatment, and immunotherapy. To
inform clinical management, rapid clinical data collection, data sharing,
analysis, and timely feedback are needed worldwide.5
Because H7N9 virus
infections have not occurred in humans before, it is expected that persons of
all ages might be susceptible worldwide. Serologic assays must be developed so
that studies can be conducted to determine whether some people have
cross-reactive antibodies to these viruses from prior influenza A virus infections.
Existing H7-vaccine viruses are not well matched to this novel H7N9 virus, and
extensive efforts are under way to develop potential H7N9 vaccines as quickly
as possible. These efforts have started worldwide using the H7N9 sequence data
obtained from these early cases, and sharing of H7N9 viruses will further
facilitate vaccine development. There are many challenges to making H7N9
vaccines available. Previously studied H7 vaccines were poorly immunogenic in
humans, and clinical trials to assess the safety and immunogenicity of H7N9
vaccine candidates will be needed. But even if new vaccine manufacturing
technologies, such as tissue-cell-culture–derived vaccine antigens, are
utilized, the process from vaccine development to availability will probably take
many months.
The 2009 H1N1 pandemic
taught us many lessons, including that a pandemic virus can emerge from an
animal reservoir in an unexpected location and be spread rapidly through air
travel. The focus on critically ill adults early in the pandemic led to
elevated public concern about pandemic severity. Clear communication of key
messages to the public and the clinical community is critical in implementing
successful prevention and control activities. The detection of human H7N9 virus
infections is yet another reminder that we must continue to prepare for the
next influenza pandemic. The coming weeks will reveal whether the epidemiology
reflects only a widespread zoonosis, whether an H7N9 pandemic is beginning, or
something in between. The key is intensified surveillance for H7N9 virus in
humans and animals to help answer important questions. We cannot rest our
guard.
慢性鼻竇炎的病原是nontuberculous mycobacteria ?!!!
Nontuberculous Mycobacteria in Household Plumbing as Possible Cause of Chronic Rhinosinusitis
Emerging Infectious Diseases. 2012;18(10)
Abstract and Introduction
Abstract
Symptoms of chronic rhinosinusitis (CRS) often persist despite treatment. Because nontuberculous mycobacteria (NTM) are resistant to commonly used antimicrobial drugs and are found in drinking water that patients may use for sinus irrigation, we investigated whether some CRS patients were infected with NTM in New York, New York, USA, during 2001–2011. Two approaches were chosen: 1) records of NTM-infected CRS patients were reviewed to identify common features of infection and Mycobacterium species; 2) samples from plumbing in households of 8 NTM-infected patients were cultured for NTM presence. In 3 households sampled, M. avium sharing rep-PCR and pulsed field gel electrophoresis fingerprints identified M. avium isolates clonally related to the patients' isolates. We conclude that patients with treatment-resistant CRS may be infected with NTM and should have cultures performed for NTM so appropriate therapy can be instituted. In addition, the results suggest that CRS patients can be infected by NTM in their household plumbing.
Introduction
A subset of patients with chronic rhinosinusitis (CRS) often experience persistent symptoms, despite undergoing many medical and surgical modes of treatment. Current theories regarding the cause of CRS include immunologic reactions to microorganisms.[1,2] Even though they receive various treatments, including antimicrobial drugs and sinus irrigation, many patients continue to be symptomatic.[2] One possible reason for the persistence of symptoms is the presence of microorganisms that are resistant to typically prescribed antimicrobial drugs, for example, nontuberculous mycobacteria (NTM).
Recovery of NTM from the sinus cavity has been documented in 19 patients, including those with cystic fibrosis,[3] HIV infection,[4–10] and diabetes.[11] NTM isolation from the sinus cavity has been rarely reported in immunocompetent, nondiabetic patients who do not have cystic fibrosis.[12–15] One case of infection with NTM is documented in a study by Spring and Miller.[14] The patient had a 21-year history of rhinosinusitis and exhibited left maxillary facial pain, nasal discharge, and congestion. Mycobacterium chelonae, Staphylococcus aureus, and Pseudomonas aeruginosa were recovered from sinus cultures. Successful treatment ultimately required a 3-year course of multiple intravenous antimicrobial drug combinations and subsequent sinus operations.[14] Recently, a new member of the M. abscessus-chelonae complex, M. franklinii, was isolated from patients in the northeastern United States who have chronic sinusitis.[16]
NTM are environmental opportunistic pathogens found in natural and human-engineered waters, including drinking water distribution systems[17] and household plumbing.[18–20] NTM species can be classified into 2 groups on the basis of growth rates; rapidly growing mycobacteria (e.g., M. chelonae and M. abscessus) form colonies in <7 days at 37°C, and slowly growing mycobacteria (e.g., M. avium and M. intracellulare) take >7 days at 37°C to form colonies. Because NTM are resistant to commonly used antimicrobial drugs[21] and are found in drinking water, they might be responsible for antimicrobial drug–resistant, chronic rhinosinusitis. We report the isolation, identification, and fingerprinting of NTM isolates from patients with CRS and from their household plumbing.
Methods
Patient Histories
We reviewed the charts of 33 adult outpatients in whom CRS was diagnosed in the medical practice of W.S. Tichenor, whose endoscopically directed sinus cultures yielded NTM. The 33 represent ≈1% of patient samples collected over a 10-year period. In all patients, CRS had been diagnosed on the basis of a combination of initial evaluation; appearance of the sinuses by endoscopic examination; results of computed tomographic scan; and endoscopically directed cultures for bacteria, fungi, and NTM. From all patients, bacterial isolates had been cultured at the time of endoscopy.
Initial symptoms, NTM identity, surgical history, HIV status, cystic fibrosis history and carrier status, diabetes and immune-deficiency status, current nasal irrigations, presence of polyps, treatment, repeat culture results, and symptom reduction were assessed (). Common patient conditions at the time of nasal endoscopy included headache, nasal blockage or congestion, thick postnasal drip, and decreased ability to taste or smell. Thirty (91%) of the 33 patients had previously undergone endoscopic sinus surgery; 10 (30%) had histories of primary immunodeficiency. Twelve (36%) of the 33 patients had evidence of polyps at the time of nasal endoscopy; however, no clear association was found between NTM species and the presence of polyps. Thirty-one (94%) of 33 patients were using some form of nasal irrigation at the time of endoscopy. Of those, 26 were known to have used tap water to irrigate the sinuses.
Table 1. Characteristics of patients whose sinuses yielded NTM in study of NTM in household plumbing, New York, New York, USA, 2001–2011*
| Total patients | 33 (100) |
| Age range, y | 25–74 |
| Prior functional endoscopic sinus surgery | 30 (91) |
| Nasal polyps | 12 (36) |
| Primary immunodeficiency | 10 (30) |
| HIV positive | 0† |
| Cystic fibrosis carrier state | 1 (20)‡ |
| Diabetes | 0 |
| Repeat culture NTM negative | 21 (64) |
| Repeat culture NTM positive | 2 (6) |
| Repeat culture not performed or lost | 10 (30) |
| Symptoms improved | 14 (42) |
| Symptoms unchanged | 6 (18) |
| Other persistent microorganism§ | 1 (3) |
| Refused treatment | 3 (9) |
| Currently treated | 9 (27) |
*Values are no. (%) patients except as indicated. NTM, nontuberculous mycobacteria.
†No patients were known to be HIV positive; 16 were tested.
‡No patients were known to have cystic fibrosis; 5 were tested.
§Methicillin-resistant Staphylococcus aureus.
Patient Sample Collections
Endoscopically directed samples were taken directly from the sinuses, middle meatus, or ostiomeatal unit by using a flexible catheter with a self-contained Lukens trap as described.[22] Samples (0.5–3 mL) were sent to the microbiology laboratories (Mayo Medical Laboratories, Rochester, MN, USA; Specialty Laboratories, Valencia, CA, USA; Quest Laboratories, Peterboro, NJ, USA) in sterile 5-mL containers.
Household Collections
Members of households with occupants who had NTM-associated CRS volunteered to participate in studies of their households' water systems. Informed consent was obtained from each collaborating patient, and the study was reviewed by the Virginia Tech Institutional Research Board and granted exempt status. NTM isolates from the patients were obtained through laboratories that cultured NTM from endoscopy samples. Containers, swabs, and tubes were sent to each collaborating patient's household. Directions were provided for the collaborating patient or family member to collect hot and cold water samples (500 mL) and biofilms/sediment from water taps and showerheads. Biofilm samples were collected by swabbing the inside of taps and showerheads, and swab specimens were placed in tubes containing 2 mL of tap water (from Blacksburg, VA, USA), sterilized by autoclaving. If in-line or point-of-use water filters were submitted by the patients, a 4-cm2 area was swabbed, and the swab was placed in 2 mL of sterile tap water.
NTM Isolation, Identification, and Fingerprinting
Patient NTM isolates were identified by various methods, depending on the laboratory: DNA probe, high-performance liquid chromatography, gas-liquid chromatography, internal transcribed spacer region or 16S rDNA sequencing. NTM in water and swab (taps and filters) samples were enumerated and isolated as described.[19] Household NTM isolates and those from patients were identified by nested PCR of 16S rRNA gene[23] and PCR amplification and analysis of restriction endonuclease digestion fragments of the hsp-65 gene.[24] When the Mycobacterium species of the patient and household water system isolates were identical, isolates were fingerprinted by rep-PCR[25] and pulsed-field gel electrophoresis (PFGE) of AseI and XbaI restriction endonuclease digests of genomic DNA.[26] To interpret PFGE in categories of "indistinguishable," "closely related," and "different," we used previously described criteria for the evaluation of Mycobacterium avium complex isolates.[27] With a minimum of 10 interpretable bands, strains were interpreted as indistinguishable (no band differences), closely related (1–3 band differences), possibly related (4–6 band differences), and different (>7 band differences). These isolates underwent species confirmation by sequencing of the internal transcribed spacer 1. M. intracellulare and M. chimaera are indistinguishable without gene/region sequencing.[28]
Results
Review of the charts of the 33 CRS patients showed that 39 NTM isolates belonging to 10 Mycobacterium species were recovered from samples from the ostiomeatal unit or paranasal sinuses (). The patients' mycobacterial isolates were identified by Mayo Clinic, Quest, and Specialty Laboratories. Two different Mycobacterium species were isolated from 6 patient samples (). Most isolates (25 [64%] of 39) were rapidly growing mycobacteria, primarily M. abscessus or M. chelonae. One laboratory that received patient samples did not distinguish M. abscessus from M. chelonae. The predominant slowly growing Mycobacterium species was MAC (6 [15%] of 39). M. gordonae was isolated from 4 (12%) of the 33 patients. Although the organism is normally considered a saprophyte, M. gordonae infection has been reported in immunodeficient persons,[29–31] and thus its isolation should not be dismissed.
Table 2. NTM isolated from sinus cavity samples of 33 patients in study of NTM in household plumbing, New York, New York, USA, 2001–2011*
| Mycobacterium abscessus-chelonae | 19 (58) |
| M. chelonae | 4 (12) |
| M. abscessus | 2 (6) |
| M. avium | 4 (12) |
| M. avium complex | 2 (6) |
| M. immunogenum | 1 (3) |
| M. asiaticum | 1 (3) |
| M. mucogenicum | 1 (3) |
| M. mageritense | 1 (3) |
| M. gordonae | 4 (12) |
*NTM, nontuberculous mycobacteria.
Table 2. NTM isolated from sinus cavity samples of 33 patients in study of NTM in household plumbing, New York, New York, USA, 2001–2011*
| Mycobacterium abscessus-chelonae | 19 (58) |
| M. chelonae | 4 (12) |
| M. abscessus | 2 (6) |
| M. avium | 4 (12) |
| M. avium complex | 2 (6) |
| M. immunogenum | 1 (3) |
| M. asiaticum | 1 (3) |
| M. mucogenicum | 1 (3) |
| M. mageritense | 1 (3) |
| M. gordonae | 4 (12) |
*NTM, nontuberculous mycobacteria.
NTM Isolates from Households of Current CRS Patients
A total of 80 samples (i.e., 43 water, 31 biofilm, and 6 from filters) for NTM isolation were received from the 8 collaborating CRS patients. NTM were isolated from water, biofilm, or filter samples from at least 1 sample from 5 (63%) of the 8 households sampled and from 35 (40%) of the 80 samples (). The frequency of NTM recovery from water (44%), biofilm (42%), and filter (50%) samples was not significantly different (p = 0.6065, Kruskal-Wallace test). NTM colony counts varied widely in samples from the different households (). In 4 households, at least 1 of the samples yielded an NTM isolate that was of the same species and had the same rep-PCR fingerprint as that of the patient according to published criteria[25] (Figure 1). The band patterns illustrate the large number and wide range of rep-PCR bands and illustrate the discrimination provided by rep-PCR fingerprinting.[25] To confirm the relatedness between isolates from patient and household plumbing, PFGE was performed[26] for the same isolates (Figure 2). The PFGE band pattern of the isolate from patient 2 and the pattern from the patient's household (lanes 10 and 11) appear almost identical ("closely related"). The PFGE patterns for 2 isolates from the household of patient 5 were "indistinguishable" and are "closely related" (clonal) to the respective patient isolates and thereby clonal (Figure 2, panel A). Isolates from patient 8 and the patient's household plumbing (not shown) gave faint signals by PFGE with repeat testing and both restriction enzymes. However, the patterns appeared "indistinguishable"(profile not shown). The lack of clear band patterns for the isolates from patient 8 and his or her household plumbing is likely because of the shared characteristic of resistance to lysis in the agar plugs.[26] The absence of a match for patient 1 (not shown) might be because the person moved throughout the United States, and some places where the patient lived were not sampled. Samples of showerheads were collected from 6 of the 8 households, and although NTM isolates of the same species as that of the patient (i.e., M. avium) were recovered from 2 households, none of the showerhead isolates shared the same fingerprint with isolates from the patient. Notably, the samples from the household plumbing of the patients with M. gordonae and M. immunogenum isolates did not yield any NTM.
Table 3. Recovery of NTM from households in study of NTM in household plumbing, New York, New York, USA, 2001–2011*
| 1 | M. abscessus | 9 | 5 (55) | None | NA | NA |
| 2 | M. avium | 9 | 4 (44) | Yes | Yes | Yes |
| 3 | M. immunogenum | 10 | 0 | NA | NA | NA |
| 4 | M. gordonae | 5 | 2 (40) | Yes | No | – |
| 5 | M. avium | 10 | 9 (90) | Yes | Yes | Yes |
| 6 | MAC-X† | 21 | 7 (33) | Yes | Yes | No |
| 7 | M. gordonae | 10 | 0 | NA | NA | – |
| 8 | M. avium | 14 | 8 (57) | Yes | Yes | Yes |
*NTM, nontuberculous mycobacteria; NA, not applicable; MAC-X, Mycobacterium avium complex "X" cluster; PFGE, pulsed-field gel electrophoresis.
†MAC-X is a mycobacterium that tests positive by DNA probe analysis for M. avium complex but is negative with specific M. avium and M. intracellulare probes and PCR analysis.
Table 4. Numbers of NTM in household samples in study of NTM in household plumbing, New York, New York, USA, 2001–2011*
| 1 | 4 | 5,632 ± 3,372 | 2 | 36,000 ± 49,500 |
| 2 | 5 | 49 ± 18 |  | 6 ± 2 |
| 3 | 0 | | 0 | |
| 4 | 1 | | 0 | |
| 5 | 13 | 420 ± 1,000 | 8 | 23,310 ± 41,700 |
| 6 | 3 | 17,052 ± 11,200 | 11 | 21,100 ± 27,700 |
| 7 | 0 | | 0 | |
| 8 | 7 | 27 ± 26 | 8 | 513 ± 632 |
| Total | 33 | 2,487 | 31 | 13,835 |
*NTM, nontuberculous mycobacteria.
Figure 1.
rep-PCR fingerprint patterns of patient and household isolates, New York, New York, USA, 2001–2011. Lane 1, 100-bp ladder; lane 2, patient no. 5 Mycobacterium avium isolate AG-P-1; lane 3, patient no. 5 household fi lter M. avium isolate AG-F-2–0–2; lane 4, patient no. 5 household fi lter M. avium isolate AG-F-2-I-1; lane 5, patient no. 6 M. avium complex 'X' cluster isolate GG-P- 1; lane 6, patient no. 6 household swab M. chimaera isolate GGSw- 9–1; lane 7, patient no. 8 M. avium isolate GW-P-1; lane 8, patient no. 8 household water M. avium isolate GW-W-1–1; lane 9, patient no. 8 household swab M avium isolate GW-Sw-7–2; lane 10, patient no. 2 M. avium isolate BB-P-1; lane 11, patient no. 2 household water M. avium isolate BB-W-4–5; lane 12, 100-bp ladder.
Figure 2.
Pulsed-fi eld gel electrophoresis (PFGE) of Ase I digest patterns of patient and household isolates, New York, New York, USA, 2001–2011. A) Patient and household isolates. Lane 1, λ ladder; lane 2, patient no. 5 Mycobacterium avium isolate AG-P-1; lane 3, patient no. 5 household fi lter M. avium isolate AG-F-2–0–2; lane 4, patient no. 5 household fi lter M. avium isolate AG-F-2-I-1 (environmental isolates in lanes 3 and 4 are indistinguishable; patient isolate in lane 2 considered clonal with 2 environmental isolates [6 bands difference]); with digestion with XbaI, the 3 were considered closely related.); lane 5, patient no. 6 M. avium complex 'X' cluster isolate GG-P-1; lane 6, patient no. 6 household swab M. chimaera isolate GG-Sw-9–1 (despite overall similarity, isolates in lanes 5 and 6 belong to different species and differ by 10 bands and are therefore unrelated). B) Additional patient and isolate from the person's household. Lane 1, patient no. 2 M. avium isolate BB-P-1; lane 2, patient no. 2 household water M. avium isolate BB-W-4–5; lane 3, λ ladder.
Discussion
Our study confirms the possibility of the involvement of NTM in sinuses of patients with CRS.[3,11,16] CRS patients who have not responded to medical treatment should undergo endoscopically directed sinus cultures for microorganisms, including fungi and NTM and other bacteria. Endoscopically directed sinus cultures have been shown to accurately replicate sinus puncture culture techniques.[22] The American Thoracic Society and the Infectious Diseases Society of America discourage the use of swabs for sampling because swabs may decrease the likelihood of recovering NTM.[21] Using a suction device to remove larger volumes of mucus helps increase the chances of obtaining representative sinus microflora.[22] Spurious recovery of NTM, because of endoscope contamination, is possible[32] as is the possibility that glutaraldehyde may not adequately kill NTM.[33] However, in the current study, endoscope contamination is an unlikely source of NTM because water samples from the physician's office did not reveal NTM. In addition, the patient and household samples were processed in different laboratories.
Besides establishing NTM as a potential agent of CRS, our results strongly suggest that in 3 of the 8 CRS patients studied here, the household plumbing was the source of infection, on the basis of identity of rep-PCR fingerprints of patient and household isolates and their clonal relatedness as determined by PFGE. Clonal variation in Mycobacterium species isolates is characteristic of isolates recovered from household plumbing, but because single Mycobacterium species isolates are typically recovered from patient samples, DNA fingerprint matches are not always obtained.[19,20] A study of persons with NTM pulmonary disease found that in 7 (41%) of 17 households, patient and household plumbing isolates were identical as shown by rep-PCR fingerprints.[20] Because NTM are found in household tap water,[19,20,34] CRS patients should avoid sinus irrigation with unsterilized tap water.
A major question concerning isolation of NTM from the sinus cavities of patients with CRS is whether NTM were involved in pathogenesis. No guidance exists for the diagnosis and treatment of NTM sinus infection. For pulmonary NTM disease, it is recommended that multiple cultures be obtained over time[21] to rule out transient colonization and avoid sampling deficiencies. Our experience suggests that multiple cultures may be necessary to find NTM because endoscopy samples from many patients will be found NTM positive only by 1 of 2–5 endoscopies. For example, 1 patient had cultures that yielded M. mageritense, but cultures obtained 1 week later were negative, even in the absence of antibacterial drug treatment. In addition, smears from 2 patients showed acid-fast bacilli, but cultures failed to yield any Mycobacterium species isolate; yet upon subsequent endoscopy, NTM were cultured. Several possible reasons could account for this low yield. First, hydrophobic NTM cells are likely adhering to the walls of the sinus cavity, and thereby a low number are in fluid removed during endoscopy. Second, the small volume of mucus removed at the time of culture also might reduce the likelihood of recovering NTM.[22] Third, topical anesthetics, typically lidocaine, are used for anesthesia for endoscopy and might inhibit the growth of many microorganisms, including NTM.[35] Although NTM could merely be colonizing the sinuses, several factors suggest otherwise. The samples that we collected were primarily mucus, and previously published reports on NTM in sinus samples from immunocompromised CRS patients were primarily based on biopsy specimens.[3,6,15] In addition, our patients typically have persistent symptoms despite treatment with multiple different antimicrobial drug regimens over several months. Because the results of NTM culture and sensitivity testing take several months to obtain, patients are typically treated for other possible infecting microorganisms until the results of the NTM cultures are reported. Resolution typically occurred only after an extended course of multiple antimycobacterial agents given simultaneously. Unfortunately, the combination of insufficient experience and the absence of an established treatment protocol for CRS caused by NTM[21] prevent any meaningful review of treatment regimens for CRS caused by NTM. Such patients are treated with 2 oral antimycobacterial drugs and urged to irrigate sinuses with sterile or boiled water or saline, followed by irrigation with a topical antimycobacterial agent for 3–18 months, depending on clinical response and, in some cases, on subsequent positive cultures for NTM
The role of NTM in infectious disease processes is only starting to be recognized. This work documents that a proportion of patients with CRS could be infected with NTM and that sinus samples should be cultured for NTM. In addition, CRS patients should avoid sinus irrigation with tap water because tap water may contain NTM, and it may not be possible to remove it. Sterile saline should be used instead.
Dr Tichenor is clinical associate professor of medicine at New York Medical College and maintains a private practice in New York, New York, focusing on treatment of patients with resistant chronic sinusitis. His research interests include NTM infections and primary immune deficiencies as they relate to treatment of chronic sinusitis.
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Acknowledgments
We acknowledge the efforts of Myra D. Williams, who processed samples and identified, enumerated, and fingerprinted NTM; and Elena Iakiaeva for performance of the multiplex PCR and for interspacer 1 DNA sequencing.
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