H5N1 makes a New Mile Stone - Human to Human transfer
- Thread starter The Flying Dutchman
- Start date
Semantics?
It didn't say it wasn't spreading from person to person.
It says it wasn't spreading easily.
I'm certainly no expert on this subject. I've followed it some but not as closely as many others. I remember last year they thought it had transferred from human to human. Was that disproved?
snip
Thai and international health officials were due to hold an emergency meeting on Monday to review a case in which there is a "very remote possibility" bird flu was passed from human to human, a senior WHO official said.
http://www.chinadaily.com.cn/english/doc/2004-09/27/content_378111.htm
It didn't say it wasn't spreading from person to person.
It says it wasn't spreading easily.
I'm certainly no expert on this subject. I've followed it some but not as closely as many others. I remember last year they thought it had transferred from human to human. Was that disproved?
snip
Thai and international health officials were due to hold an emergency meeting on Monday to review a case in which there is a "very remote possibility" bird flu was passed from human to human, a senior WHO official said.
http://www.chinadaily.com.cn/english/doc/2004-09/27/content_378111.htm
Maybe a new thread should be started on how to survive a flu pandemic.
All I can think of is :
Avoid crowds and public places. (Prepping makes that possible)
But it seems that many species can catch this bug.
Wash hands often. Face mask and goggles maybe, if only to
keep your hands from touching those areas.
All I can think of is :
Avoid crowds and public places. (Prepping makes that possible)
But it seems that many species can catch this bug.
Wash hands often. Face mask and goggles maybe, if only to
keep your hands from touching those areas.
JohnGaltfla
#NeverTrump
The final nail in the coffin of the American Republic.
closet squirrel
Veteran Member
I just got my 4 big bottles of Sambucol in the mail today! The numbers in Indonesia keep going up.
One plane ride away
One plane ride away
Grock
Veteran Member
Gayla said:
If anyone can show me any documented proof of human to human spread I'll listen.
I have Tamiflu for the family already.
But I'm not into the hype, and in fact, consider it t be damaging to the cause, as it clouds the importance of proper preparation with a phog of confusion.
I understand, Grock.
I'm not into hype either.
I know there have been repeated warnings about the way this thing mutates and they are fearful it will become the next global pandemic.
That alone is rather scary.
I don't have the answer about the human to human transmission. I'm hoping someone can tell me if the above article has been disproved or not.
I'm not into hype either.
I know there have been repeated warnings about the way this thing mutates and they are fearful it will become the next global pandemic.
That alone is rather scary.
I don't have the answer about the human to human transmission. I'm hoping someone can tell me if the above article has been disproved or not.
Blackhorse
Inactive
Shakey thank you, for the posts on this subject. Closet squirrel, where did you buy
your sambucol?
your sambucol?
There is a great deal of information out there for all to search through. There are numerous steps to take to help mitigate any flu exposure and subsequent effects of infection. Sambucol can be purchased at most health food stores and you can also find it on the net through various suppliers. Vitacost.com is just one site that carries it. Check out http://www.fluwikie.com and http://www.curevents.com/vb/forumdisplay.php?f=40 for even more information. An informed person makes for a more prepared person. Panic does not help.
Indiansummer
Inactive
Shakey, Thanks for your superior tracking. This is important information, and it needs to stay on the front page. I can add nothing more than this, for a bump!
MaureenO
Another Infidel
Grock said:
Grock, I'm by no stretch an alarmist, however, I know positively that by the time the news is officially announced re: human-to-human exposure it will be too late.
Skakey just made a timely series of posts that may well save some lives here if those ears are open.
Maureen
Grock
Veteran Member
MaureenO said:Grock, I'm by no stretch an alarmist, however, I know positively that by the time the news is officially announced re: human-to-human exposure it will be too late.
Skakey just made a timely series of posts that may well save some lives here if those ears are open.
Maureen
I know what you're saying, and I agree. As a .gov employee I have seen plenty of examples of foot dragging... But lets stay in the realm of fact.
And I have the same fears as the rest of you that this will evolve, mutate, etc.
The latest edition of National Geographic has an large article on the topic, that alone is significant.
My personal belief is that we all need to be ready. That includes Relenza/ Tamiflu, and even sambucol, though it is more controversial as an aid than Relenza/Tamiflu.
But lets try to maintain the steady and pragmatic approach. Panic is not useful in good planning.
LilRose8
Veteran Member
You know Claudia.... i really don't think it is a lack of interest here...but more of the, 'Yes I know this is really scary but what can I do about it' train of thought.Claudia said:
We have discussed preps for bird flu, meds for bird flu and quarantine issues.... but really, besides following the news, this is a waiting game. Either it will happen or it won't. Either people will get Tamiflu ( which may or may NOT be effective) or not. Either they will invest in some Sambucal before hand or they won't.
If you have some input that I am not aware of aside from being scared of this possible pandemic, I am interested in hearing it. But so far, All I have seen is the before mentioned info.
The Flying Dutchman
Inactive
-In respondse to some folks' questions - I never post news from ill-reputable sites. And if they *think* that H5N1 is not or has not passed from human to human. Then more power to them - I unfortunately will not live in the relm of make believe....
The New England Journal of Medicine says that *limited* human to human transfer has occured; and that was some weeks back...
Shakey
<B><font size=+1 color=red><center>New England Journal of Medicine</font>
<A href="http://content.nejm.org/cgi/content/full/353/13/1374">Volume 353:1374-1385 </A>
September 29, 2005 Number 1</center>
Avian Influenza A (H5N1) Infection in Humans</B>
The Writing Committee of the World Health Organization (WHO) Consultation on Human Influenza A/H5
An unprecedented epizootic avian influenza A (H5N1) virus that is highly pathogenic has crossed the species barrier in Asia to cause many human fatalities and poses an increasing pandemic threat. This summary describes the features of human infection with influenza A (H5N1) and reviews recommendations for prevention and clinical management presented in part at the recent World Health Organization (WHO) Meeting on Case Management and Research on Human Influenza A/H5, which was held in Hanoi, May 10 through 12, 2005.1 Because many critical questions remain, modifications of these recommendations are likely.
Incidence
The occurrence of human influenza A (H5N1) in Southeast Asia (Table 1) has paralleled large outbreaks of avian influenza A (H5N1), although the avian epidemics in 2004 and 2005 have only rarely led to disease in humans. The largest number of cases has occurred in Vietnam, particularly during the third, ongoing wave, and the first human death was recently reported in Indonesia. The frequencies of human infection have not been determined, and seroprevalence studies are urgently needed. The expanding geographic distribution of avian influenza A (H5N1) infections, with recent outbreaks in Kazakstan, Mongolia, and Russia, indicates that more human populations are at risk.2,3
Table 1. Cumulative Number of Virologically Confirmed Cases of Avian Influenza A (H5N1) in Humans Reported to the WHO since 2003.
<b>Transmission</b>
Human influenza is transmitted by inhalation of infectious droplets and droplet nuclei, by direct contact, and perhaps, by indirect (fomite) contact, with self-inoculation onto the upper respiratory tract or conjunctival mucosa.4,5 The relative efficiency of the different routes of transmission has not been defined. For human influenza A (H5N1) infections, evidence is consistent with bird-to-human, possibly environment-to-human,<b> and limited, nonsustained human-to-human transmission to date. </b>
<b>Animal to Human</b>
In 1997, exposure to live poultry within a week before the onset of illness was associated with disease in humans, whereas there was no significant risk related to eating or preparing poultry products or exposure to persons with influenza A (H5N1) disease.6 Exposure to ill poultry and butchering of birds were associated with seropositivity for influenza A (H5N1)7 (Table 2). Recently, most patients have had a history of direct contact with poultry (Table 3), although not those who were involved in mass culling of poultry. Plucking and preparing of diseased birds; handling fighting cocks; playing with poultry, particularly asymptomatic infected ducks; and consumption of duck's blood or possibly undercooked poultry have all been implicated. Transmission to felids has been observed by feeding raw infected chickens to tigers and leopards in zoos in Thailand17,18 and to domestic cats under experimental conditions.19 Transmission between felids has been found under such conditions. Some infections may be initiated by pharyngeal or gastrointestinal inoculation of virus.
Table 2. Serologic and Clinical Characteristics of Avian Influenza A (H5N1) Infection among Contacts of Patients or Infected Animals.
Table 3. Presentation and Outcomes among Patients with Confirmed Avian Influenza A (H5N1).
<b>Human to Human</B>
<b>Human-to-human transmission of influenza A (H5N1) has been suggested in several household clusters16 and in one case of apparent child-to-mother transmission</b> (Table 3).20 Intimate contact without the use of precautions was implicated, and so far no case of human-to-human transmission by small-particle aerosols has been identified. In 1997, human-to-human transmission did not apparently occur through social contact,8 and serologic studies of exposed health care workers indicated that transmission was inefficient9 (Table 2). Serologic surveys in Vietnam and Thailand have not found evidence of asymptomatic infections among contacts (Table 2). Recently, intensified surveillance of contacts of patients by reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assay has led to the detection of mild cases, more infections in older adults, and an increased number and duration of clusters in families in northern Vietnam,21 findings suggesting that the local virus strains may be adapting to humans. However, epidemiologic and virologic studies are needed to confirm these findings. To date, the risk of nosocomial transmission to health care workers has been low, even when appropriate isolation measures were not used10,11 (Table 2). However, one case of severe illness was reported in a nurse exposed to an infected patient in Vietnam.
<b>Environment to Human</b>
Given the survival of influenza A (H5N1) in the environment, several other modes of transmission are theoretically possible. Oral ingestion of contaminated water during swimming and direct intranasal or conjunctival inoculation during exposure to water are other potential modes, as is contamination of hands from infected fomites and subsequent self-inoculation. The widespread use of untreated poultry feces as fertilizer is another possible risk factor.
<b>Clinical Features</b>
The clinical spectrum of influenza A (H5N1) in humans is based on descriptions of hospitalized patients. The frequencies of milder illnesses, subclinical infections, and atypical presentations (e.g., encephalopathy and gastroenteritis) have not been determined, but case reports12,21,22 indicate that each occurs. Most patients have been previously healthy young children or adults (Table 3).
<b>Incubation</B>
The incubation period of avian influenza A (H5N1) may be longer than for other known human influenzas. In 1997, most cases occurred within two to four days after exposure13; recent reports15,16 indicate similar intervals but with ranges of up to eight days (Table 3). The case-to-case intervals in household clusters have generally been 2 to 5 days, but the upper limit has been 8 to 17 days, possibly owing to unrecognized exposure to infected animals or environmental sources.
<b>Initial Symptoms</b>
Most patients have initial symptoms of high fever (typically a temperature of more than 38°C) and an influenza-like illness with lower respiratory tract symptoms1 (Table 3). Upper respiratory tract symptoms are present only sometimes. Unlike patients with infections caused by avian influenza A (H7) viruses,23 patients with avian influenza A (H5N1) rarely have conjunctivitis. Diarrhea, vomiting, abdominal pain, pleuritic pain, and bleeding from the nose and gums have also been reported early in the course of illness in some patients.14,15,16,24 Watery diarrhea without blood or inflammatory changes appears to be more common than in influenza due to human viruses25 and may precede respiratory manifestations by up to one week.12 One report described two patients who presented with an encephalopathic illness and diarrhea without apparent respiratory symptoms.22
<b>Clinical Course</b>
Lower respiratory tract manifestations develop early in the course of illness and are usually found at presentation (Table 3). In one series, dyspnea developed a median of 5 days after the onset of illness (range, 1 to 16).15 Respiratory distress, tachypnea, and inspiratory crackles are common. Sputum production is variable and sometimes bloody. Almost all patients have clinically apparent pneumonia; radiographic changes include diffuse, multifocal, or patchy infiltrates; interstitial infiltrates; and segmental or lobular consolidation with air bronchograms. Radiographic abnormalities were present a median of 7 days after the onset of fever in one study (range, 3 to 17).15 In Ho Chi Minh City, Vietnam, multifocal consolidation involving at least two zones was the most common abnormality among patients at the time of admission. Pleural effusions are uncommon. Limited microbiologic data indicate that this process is a primary viral pneumonia, usually without bacterial suprainfection at the time of hospitalization.
Progression to respiratory failure has been associated with diffuse, bilateral, ground-glass infiltrates and manifestations of the acute respiratory distress syndrome (ARDS). In Thailand,15 the median time from the onset of illness to ARDS was 6 days (range, 4 to 13). Multiorgan failure with signs of renal dysfunction and sometimes cardiac compromise, including cardiac dilatation and supraventricular tachyarrhythmias, has been common.14,15,16,24 Other complications have included ventilator-associated pneumonia, pulmonary hemorrhage, pneumothorax, pancytopenia, Reye's syndrome, and sepsis syndrome without documented bacteremia.
<b>Mortality</B>
The fatality rate among hospitalized patients has been high (Table 3), although the overall rate is probably much lower.21 In contrast to 1997, when most deaths occurred among patients older than 13 years of age, recent avian influenza A (H5N1) infections have caused high rates of death among infants and young children. The case fatality rate was 89 percent among those younger than 15 years of age in Thailand. Death has occurred an average of 9 or 10 days after the onset of illness (range, 6 to 30),15,16 and most patients have died of progressive respiratory failure.
<b>Laboratory Findings</b>
Common laboratory findings have been leukopenia, particularly lymphopenia; mild-to-moderate thrombocytopenia; and slightly or moderately elevated aminotransferase levels (Table 3). Marked hyperglycemia, perhaps related to corticosteroid use, and elevated creatinine levels also occur.16 In Thailand,15 an increased risk of death was associated with decreased leukocyte, platelet, and particularly, lymphocyte counts at the time of admission.
<b>Virologic Diagnosis</b>
Antemortem diagnosis of influenza A (H5N1) has been confirmed by viral isolation, the detection of H5-specific RNA, or both methods. Unlike human influenza A infection,26 avian influenza A (H5N1) infection may be associated with a higher frequency of virus detection and higher viral RNA levels in pharyngeal than in nasal samples. In Vietnam, the interval from the onset of illness to the detection of viral RNA in throat-swab samples ranged from 2 to 15 days (median, 5.5), and the viral loads in pharyngeal swabs 4 to 8 days after the onset of illness were at least 10 times as high among patients with influenza A (H5N1) as among those with influenza A (H3N2) or (H1N1). Earlier studies in Hong Kong also found low viral loads in nasopharyngeal samples.27 Commercial rapid antigen tests are less sensitive in detecting influenza A (H5N1) infections than are RT-PCR assays.15 In Thailand, the results of rapid antigen testing were positive in only 4 of 11 patients with culture-positive influenza A (H5N1) (36 percent) 4 to 18 days after the onset of illness.
<b>Management</B>
Most hospitalized patients with avian influenza A (H5N1) have required ventilatory support within 48 hours after admission,15,16 as well as intensive care for multiorgan failure and sometimes hypotension. In addition to empirical treatment with broad-spectrum antibiotics, antiviral agents, alone or with corticosteroids, have been used in most patients (Table 3), although their effects have not been rigorously assessed. The institution of these interventions late in the course of the disease has not been associated with an apparent decrease in the overall mortality rate, although early initiation of antiviral agents appears to be beneficial.1,15,16 Cultivable virus generally disappears within two or three days after the initiation of oseltamivir among survivors, but clinical progression despite early therapy with oseltamivir and a lack of reductions in pharyngeal viral load have been described in patients who have died.
<b>Pathogenesis
Characterization of Virus</b>
Studies of isolates of avian influenza A (H5N1) from patients in 1997 revealed that virulence factors included the highly cleavable hemagglutinin that can be activated by multiple cellular proteases, a specific substitution in the polymerase basic protein 2 (Glu627Lys) that enhances replication,28,29 and a substitution in nonstructural protein 1 (Asp92Glu) that confers increased resistance to inhibition by interferons and tumor necrosis factor (TNF-) in vitro and prolonged replication in swine,30 as well as greater elaboration of cytokines, particularly TNF-, in human macrophages exposed to the virus.31 Since 1997, studies of influenza A (H5N1)32,33,34 indicate that these viruses continue to evolve, with changes in antigenicity35,36and internal gene constellations; an expanded host range in avian species37,38and the ability to infect felids17,18; enhanced pathogenicity in experimentally infected mice and ferrets, in which they cause systemic infections39,40; and increased environmental stability.
Phylogenetic analyses indicate that the Z genotype has become dominant33 and that the virus has evolved into two distinct clades, one encompassing isolates from Cambodia, Laos, Malaysia, Thailand, and Vietnam and the other isolates from China, Indonesia, Japan, and South Korea.21 Recently, a separate cluster of isolates has appeared in northern Vietnam and Thailand, which includes variable changes near the receptor-binding site and one fewer arginine residue in the polybasic cleavage site of the hemagglutinin. However, the importance of these genetic and biologic changes with respect to human epidemiology or virulence is uncertain.
<b>Patterns of Viral Replication</B>
The virologic course of human influenza A (H5N1) is incompletely characterized, but studies of hospitalized patients indicate that viral replication is prolonged. In 1997, virus could be detected in nasopharyngeal isolates for a median of 6.5 days (range, 1 to 16), and in Thailand, the interval from the onset of illness to the first positive culture ranged from 3 to 16 days. Nasopharyngeal replication is less than in human influenza,27and studies of lower respiratory tract replication are needed. The majority of fecal samples tested have been positive for viral RNA (seven of nine), whereas urine samples were negative. The high frequency of diarrhea among affected patients and the detection of viral RNA in fecal samples, including infectious virus in one case,22 suggest that the virus replicates in the gastrointestinal tract. The findings in one autopsy confirmed this observation.41
Highly pathogenic influenza A (H5N1) viruses possess the polybasic amino acid sequence at the hemagglutinin-cleavage site that is associated with visceral dissemination in avian species. Invasive infection has been documented in mammals,28,29,39,40 and in humans, six of six serum specimens were positive for viral RNA four to nine days after the onset of illness. Infectious virus and RNA were detected in blood, cerebrospinal fluid, and feces in one patient.22 Whether feces or blood serves to transmit infection under some circumstances is unknown.
<b>Host Immune Responses</b>
The relatively low frequencies of influenza A (H5N1) illness in humans despite widespread exposure to infected poultry indicate that the species barrier to acquisition of this avian virus is substantial. Clusters of cases in family members may be caused by common exposures, although the genetic factors that may affect a host's susceptibility to disease warrant study.
The innate immune responses to influenza A (H5N1) may contribute to disease pathogenesis. In the 1997 outbreaks, elevated blood levels of interleukin-6, TNF-, interferon-, and soluble interleukin-2 receptor were observed in individual patients,42 and in the patients in 2003, elevated levels of the chemokines interferon-inducible protein 10, monocyte chemoattractant protein 1, and monokine induced by interferon- were found three to eight days after the onset of illness.27 Recently, plasma levels of inflammatory mediators (interleukin-6, interleukin-8, interleukin-1, and monocyte chemoattractant protein 1) were found to be higher among patients who died than among those who survived (Simmons C: personal communication), and the average levels of plasma interferon- were about three times as high among patients with avian influenza A who died as among healthy controls. Such responses may be responsible in part for the sepsis syndrome, ARDS, and multiorgan failure observed in many patients.
Among survivors, specific humoral immune responses to influenza A (H5N1) are detectable by microneutralization assay 10 to 14 days after the onset of illness. Corticosteroid use may delay or blunt these responses.
<b>Pathological Findings</b>
Limited postmortem analyses have documented severe pulmonary injury with histopathological changes of diffuse alveolar damage,27,41,42 consistent with findings in other reports of pneumonia due to human influenza virus.43 Changes include filling of the alveolar spaces with fibrinous exudates and red cells, hyaline-membrane formation, vascular congestion, infiltration of lymphocytes into the interstitial areas, and the proliferation of reactive fibroblasts. Infection of type II pneumocytes occurs.41,42 Antemortem biopsy of bone marrow specimens has shown reactive histiocytosis with hemophagocytosis in several patients, and lymphoid depletion and atypical lymphocytes have been noted in spleen and lymphoid tissues at autopsy.13,15,27,42 Centrilobular hepatic necrosis and acute tubular necrosis have been noted in several instances.
<b>Case Detection and Management</b>
The possibility of influenza A (H5N1) should be considered in all patients with severe acute respiratory illness in countries or territories with animal influenza A (H5N1), particularly in patients who have been exposed to poultry (Table 4). However, some outbreaks in poultry were recognized only after sentinel cases occurred in humans. Early recognition of cases is confounded by the nonspecificity of the initial clinical manifestations and high background rates of acute respiratory illnesses from other causes. In addition, the possibility of influenza A (H5N1) warrants consideration in patients presenting with serious unexplained illness (e.g., encephalopathy or diarrhea) in areas with known influenza A (H5N1) activity in humans or animals.
Table 4. Exposures That May Put a Person at Risk for Infection with Influenza A (H5N1).
The diagnostic yield of different types of samples and virologic assays is not well defined. In contrast to infections with human influenza virus, throat samples may have better yields than nasal samples. Rapid antigen assays may help provide support for a diagnosis of influenza A infection, but they have poor negative predictive value and lack specificity for influenza A (H5N1). The detection of viral RNA in respiratory samples appears to offer the greatest sensitivity for early identification, but the sensitivity depends heavily on the primers and assay method used. Laboratory confirmation of influenza A (H5N1) requires one or more of the following: a positive viral culture, a positive PCR assay for influenza A (H5N1) RNA, a positive immunofluorescence test for antigen with the use of monoclonal antibody against H5, and at least a fourfold rise in H5-specific antibody titer in paired serum samples.44
<b>Hospitalization</b>
Whenever feasible while the numbers of affected persons are small, patients with suspected or proven influenza A (H5N1) should be hospitalized in isolation for clinical monitoring, appropriate diagnostic testing, and antiviral therapy. If patients are discharged early, both the patients and their families require education on personal hygiene and infection-control measures (Table 5). Supportive care with provision of supplemental oxygen and ventilatory support is the foundation of management.1 Nebulizers and high–air flow oxygen masks have been implicated in the nosocomial spread of severe acute respiratory syndrome (SARS) and should be used only with strict airborne precautions.
Table 5. Strategies to Prevent Avian Influenza A (H5N1) in Humans in a Nonpandemic Setting.
<b>Antiviral Agents</b>
Patients with suspected influenza A (H5N1) should promptly receive a neuraminidase inhibitor pending the results of diagnostic laboratory testing. The optimal dose and duration of treatment with neuraminidase inhibitors are uncertain, and currently approved regimens likely represent the minimum required. These viruses are susceptible in vitro to oseltamivir and zanamivir.46,47 Oral osel-tamivir46 and topical zanamivir are active in animal models of influenza A (H5N1).48,49 Recent murine studies indicate that as compared with an influenza A (H5N1) strain from 1997, the strain isolated in 2004 requires higher oseltamivir doses and more prolonged administration (eight days) to induce similar antiviral effects and survival rates.50 Inhaled zanamivir has not been studied in cases of influenza A (H5N1) in humans.
Early treatment will provide the greatest clinical benefit,15 although the use of therapy is reasonable when there is a likelihood of ongoing viral replication. Placebo-controlled clinical studies of oral oseltamivir51,52 and inhaled zanamivir53 comparing currently approved doses with doses that are twice as high found that the two doses had similar tolerability but no consistent difference in clinical or antiviral benefits in adults with uncomplicated human influenza. Although approved doses of oseltamivir (75 mg twice daily for five days in adults and weight-adjusted twice-daily doses for five days in children older than one year of age — twice-daily doses of 30 mg for those weighing 15 kg or less, 45 mg for those weighing more than 15 to 23 kg, 60 mg for those weighing more than 23 to 40 kg, and 75 mg for those weighing more than 40 kg) are reasonable for treating early, mild cases of influenza A (H5N1), higher doses (150 mg twice daily in adults) and treatment for 7 to 10 days are considerations in treating severe infections, but prospective studies are needed.
High-level antiviral resistance to oseltamivir results from the substitution of a single amino acid in N1 neuraminidase (His274Tyr). Such variants have been detected in up to 16 percent of children with human influenza A (H1N1) who have received oseltamivir.54 Not surprisingly, this resistant variant has been detected recently in several patients with influenza A (H5N1) who were treated with oseltamivir.21 Although less infectious in cell culture and in animals than susceptible parental virus,55 oseltamivir-resistant H1N1 variants are transmissible in ferrets.56 Such variants retain full susceptibility to zanamivir and partial susceptibility to the investigational neuraminidase inhibitor peramivir in vitro.57,58
In contrast to isolates from the 1997 outbreak, recent human influenza A (H5N1) isolates are highly resistant to the M2 inhibitors amantadine and rimantadine, and consequently, these drugs do not have a therapeutic role. Agents of clinical investigational interest for treatment include zanamivir, peramivir, long-acting topical neuraminidase inhibitors, ribavirin,59,60 and possibly, interferon alfa.61
<b>Immunomodulators</b>
Corticosteroids have been used frequently in treating patients with influenza A (H5N1), with uncertain effects. Among five patients given corticosteroids in 1997, two treated later in their course for the fibroproliferative phase of ARDS survived. In a randomized trial in Vietnam, all four patients given dexamethasone died. Interferon alfa possesses both antiviral and immunomodulatory activities, but appropriately controlled trials of immunomodulatory interventions are needed before routine use is recommended.
<b>Prevention
Immunization</b>
No influenza A (H5) vaccines are currently commercially available for humans. Earlier H5 vaccines were poorly immunogenic and required two doses of high hemagglutinin antigen content62 or the addition of MF59 adjuvant63 to generate neutralizing antibody responses. A third injection of adjuvanted 1997 H5 vaccine variably induced cross-reacting antibodies to human isolates from 2004.64 Reverse genetics has been used for the rapid generation of nonvirulent vaccine viruses from recent influenza A (H5) isolates,65,66 and several candidate vaccines are under study. One such inactivated vaccine with the use of a human H5N1 isolate from 2004 has been reported to be immunogenic at high hemagglutinin doses.67 Studies with approved adjuvants like alum are urgently needed. Live attenuated, cold-adapted intranasal vaccines are also under development. These are protective against human influenza after a single dose in young children.68
<b>Hospital-Infection Control</b>
Influenza is a well-recognized nosocomial pathogen.4,5 Current recommendations are based on efforts to reduce transmission to health care workers and other patients in a nonpandemic situation and on the interventions used to contain SARS (Table 5).1 The efficiency of surgical masks, even multiple ones,69 is much less than that of N-95 masks, but they could be used if the latter are not available. Chemoprophylaxis with 75 mg of oseltamivir once daily for 7 to 10 days is warranted for persons who have had a possible unprotected exposure.70,71 The use of preexposure prophylaxis warrants consideration if evidence indicates that the influenza A (H5N1) strain is being transmitted from person to person with increased efficiency or if there is a likelihood of a high-risk exposure (e.g., an aerosol-generating procedure).
<b>Household and Close Contacts</B>
Household contacts of persons with confirmed cases of influenza A (H5N1) should receive postexposure prophylaxis as described above. Contacts of a patient with proven or suspected virus should monitor their temperature and symptoms (Table 5). Although the risk of secondary transmission has appeared low to date, self-quarantine for a period of one week after the last exposure to an infected person is appropriate. If evidence indicates that person-to-person transmission may be occurring, quarantine of exposed contacts should be enforced. For others who have had an unprotected exposure to an infected person or to an environmental source (e.g., exposure to poultry) implicated in the transmission of influenza A (H5N1), postexposure chemoprophylaxis as described above may be warranted.
<b>Conclusions</b>
Infected birds have been the primary source of influenza A (H5N1) infections in humans in Asia. Transmission between humans is very limited at present, but continued monitoring is required to identify any increase in viral adaptation to human hosts. Avian influenza A (H5N1) in humans differs in multiple ways from influenza due to human viruses, including the routes of transmission, clinical severity, pathogenesis, and perhaps, response to treatment. Case detection is confounded by the nonspecificity of initial manifestations of illness, so that detailed contact and travel histories and knowledge of viral activity in poultry are essential. Commercial rapid antigen tests are insensitive, and confirmatory diagnosis requires sophisticated laboratory support. Unlike human influenza, avian influenza A (H5N1) may have higher viral titers in the throat than in the nose, and hence, analysis of throat swabs or lower respiratory samples may offer more sensitive means of diagnosis. Recent human isolates are fully resistant to M2 inhibitors, and increased doses of oral oseltamivir may be warranted for the treatment of severe illness. Despite recent progress, knowledge of the epidemiology, natural history, and management of influenza A (H5N1) disease in humans is incomplete. There is an urgent need for more coordination in clinical and epidemiologic research among institutions in countries with cases of influenza A (H5N1) and internationally.
The views expressed in this article do not necessarily reflect those of the WHO or other meeting sponsors.
We are indebted to the National Institute of Allergy and Infectious Diseases and the Wellcome Trust for their collaborative support of the WHO meeting; to Drs. Klaus Stohr and Alice Croisier of the Global Influenza Program at the WHO, Geneva; and to Drs. Peter Horby and Monica Guardo and the staff of the WHO Country Offices, Vietnam, for organizing the WHO consultation and for support in the preparation of the manuscript; and to Diane Ramm for help in the preparation of the manuscript.
<b>Source Information</b>
The writing committee consisted of the following: John H. Beigel, M.D., National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.; Jeremy Farrar, D.Phil., Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam; Aye Maung Han, M.B., B.S., Department of Child Health, Institute of Medicine, Yangon, Myanmar; Frederick G. Hayden, M.D. (rapporteur), University of Virginia, Charlottesville; Randy Hyer, M.D., World Health Organization, Geneva; Menno D. de Jong, M.D., Ph.D., Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam; Sorasak Lochindarat, M.D., Queen Sirikit National Institute of Child Health, Bangkok, Thailand; Nguyen Thi Kim Tien, M.D., Ph.D., Pasteur Institute, Ho Chi Minh City, Vietnam; Nguyen Tran Hien, M.D., Ph.D., National Institute of Hygiene and Epidemiology, Hanoi; Tran Tinh Hien, M.D., Ph.D., Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam; Angus Nicoll, M.Sc., Health Protection Agency, London; Sok Touch, M.D., Ministry of Health, Phnom Penh, Cambodia; and Kwok-Yung Yuen, M.D., University of Hong Kong, Hong Kong SAR, China.
Address reprint requests to Dr. Hayden at the Department of Internal Medicine, P.O. Box 800473, University of Virginia Health Sciences Center, Charlottesville, VA 22908, or at fgh@virginia.edu.
Please see references.
The New England Journal of Medicine says that *limited* human to human transfer has occured; and that was some weeks back...
Shakey
<B><font size=+1 color=red><center>New England Journal of Medicine</font>
<A href="http://content.nejm.org/cgi/content/full/353/13/1374">Volume 353:1374-1385 </A>
September 29, 2005 Number 1</center>
Avian Influenza A (H5N1) Infection in Humans</B>
The Writing Committee of the World Health Organization (WHO) Consultation on Human Influenza A/H5
An unprecedented epizootic avian influenza A (H5N1) virus that is highly pathogenic has crossed the species barrier in Asia to cause many human fatalities and poses an increasing pandemic threat. This summary describes the features of human infection with influenza A (H5N1) and reviews recommendations for prevention and clinical management presented in part at the recent World Health Organization (WHO) Meeting on Case Management and Research on Human Influenza A/H5, which was held in Hanoi, May 10 through 12, 2005.1 Because many critical questions remain, modifications of these recommendations are likely.
Incidence
The occurrence of human influenza A (H5N1) in Southeast Asia (Table 1) has paralleled large outbreaks of avian influenza A (H5N1), although the avian epidemics in 2004 and 2005 have only rarely led to disease in humans. The largest number of cases has occurred in Vietnam, particularly during the third, ongoing wave, and the first human death was recently reported in Indonesia. The frequencies of human infection have not been determined, and seroprevalence studies are urgently needed. The expanding geographic distribution of avian influenza A (H5N1) infections, with recent outbreaks in Kazakstan, Mongolia, and Russia, indicates that more human populations are at risk.2,3
Table 1. Cumulative Number of Virologically Confirmed Cases of Avian Influenza A (H5N1) in Humans Reported to the WHO since 2003.
<b>Transmission</b>
Human influenza is transmitted by inhalation of infectious droplets and droplet nuclei, by direct contact, and perhaps, by indirect (fomite) contact, with self-inoculation onto the upper respiratory tract or conjunctival mucosa.4,5 The relative efficiency of the different routes of transmission has not been defined. For human influenza A (H5N1) infections, evidence is consistent with bird-to-human, possibly environment-to-human,<b> and limited, nonsustained human-to-human transmission to date. </b>
<b>Animal to Human</b>
In 1997, exposure to live poultry within a week before the onset of illness was associated with disease in humans, whereas there was no significant risk related to eating or preparing poultry products or exposure to persons with influenza A (H5N1) disease.6 Exposure to ill poultry and butchering of birds were associated with seropositivity for influenza A (H5N1)7 (Table 2). Recently, most patients have had a history of direct contact with poultry (Table 3), although not those who were involved in mass culling of poultry. Plucking and preparing of diseased birds; handling fighting cocks; playing with poultry, particularly asymptomatic infected ducks; and consumption of duck's blood or possibly undercooked poultry have all been implicated. Transmission to felids has been observed by feeding raw infected chickens to tigers and leopards in zoos in Thailand17,18 and to domestic cats under experimental conditions.19 Transmission between felids has been found under such conditions. Some infections may be initiated by pharyngeal or gastrointestinal inoculation of virus.
Table 2. Serologic and Clinical Characteristics of Avian Influenza A (H5N1) Infection among Contacts of Patients or Infected Animals.
Table 3. Presentation and Outcomes among Patients with Confirmed Avian Influenza A (H5N1).
<b>Human to Human</B>
<b>Human-to-human transmission of influenza A (H5N1) has been suggested in several household clusters16 and in one case of apparent child-to-mother transmission</b> (Table 3).20 Intimate contact without the use of precautions was implicated, and so far no case of human-to-human transmission by small-particle aerosols has been identified. In 1997, human-to-human transmission did not apparently occur through social contact,8 and serologic studies of exposed health care workers indicated that transmission was inefficient9 (Table 2). Serologic surveys in Vietnam and Thailand have not found evidence of asymptomatic infections among contacts (Table 2). Recently, intensified surveillance of contacts of patients by reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assay has led to the detection of mild cases, more infections in older adults, and an increased number and duration of clusters in families in northern Vietnam,21 findings suggesting that the local virus strains may be adapting to humans. However, epidemiologic and virologic studies are needed to confirm these findings. To date, the risk of nosocomial transmission to health care workers has been low, even when appropriate isolation measures were not used10,11 (Table 2). However, one case of severe illness was reported in a nurse exposed to an infected patient in Vietnam.
<b>Environment to Human</b>
Given the survival of influenza A (H5N1) in the environment, several other modes of transmission are theoretically possible. Oral ingestion of contaminated water during swimming and direct intranasal or conjunctival inoculation during exposure to water are other potential modes, as is contamination of hands from infected fomites and subsequent self-inoculation. The widespread use of untreated poultry feces as fertilizer is another possible risk factor.
<b>Clinical Features</b>
The clinical spectrum of influenza A (H5N1) in humans is based on descriptions of hospitalized patients. The frequencies of milder illnesses, subclinical infections, and atypical presentations (e.g., encephalopathy and gastroenteritis) have not been determined, but case reports12,21,22 indicate that each occurs. Most patients have been previously healthy young children or adults (Table 3).
<b>Incubation</B>
The incubation period of avian influenza A (H5N1) may be longer than for other known human influenzas. In 1997, most cases occurred within two to four days after exposure13; recent reports15,16 indicate similar intervals but with ranges of up to eight days (Table 3). The case-to-case intervals in household clusters have generally been 2 to 5 days, but the upper limit has been 8 to 17 days, possibly owing to unrecognized exposure to infected animals or environmental sources.
<b>Initial Symptoms</b>
Most patients have initial symptoms of high fever (typically a temperature of more than 38°C) and an influenza-like illness with lower respiratory tract symptoms1 (Table 3). Upper respiratory tract symptoms are present only sometimes. Unlike patients with infections caused by avian influenza A (H7) viruses,23 patients with avian influenza A (H5N1) rarely have conjunctivitis. Diarrhea, vomiting, abdominal pain, pleuritic pain, and bleeding from the nose and gums have also been reported early in the course of illness in some patients.14,15,16,24 Watery diarrhea without blood or inflammatory changes appears to be more common than in influenza due to human viruses25 and may precede respiratory manifestations by up to one week.12 One report described two patients who presented with an encephalopathic illness and diarrhea without apparent respiratory symptoms.22
<b>Clinical Course</b>
Lower respiratory tract manifestations develop early in the course of illness and are usually found at presentation (Table 3). In one series, dyspnea developed a median of 5 days after the onset of illness (range, 1 to 16).15 Respiratory distress, tachypnea, and inspiratory crackles are common. Sputum production is variable and sometimes bloody. Almost all patients have clinically apparent pneumonia; radiographic changes include diffuse, multifocal, or patchy infiltrates; interstitial infiltrates; and segmental or lobular consolidation with air bronchograms. Radiographic abnormalities were present a median of 7 days after the onset of fever in one study (range, 3 to 17).15 In Ho Chi Minh City, Vietnam, multifocal consolidation involving at least two zones was the most common abnormality among patients at the time of admission. Pleural effusions are uncommon. Limited microbiologic data indicate that this process is a primary viral pneumonia, usually without bacterial suprainfection at the time of hospitalization.
Progression to respiratory failure has been associated with diffuse, bilateral, ground-glass infiltrates and manifestations of the acute respiratory distress syndrome (ARDS). In Thailand,15 the median time from the onset of illness to ARDS was 6 days (range, 4 to 13). Multiorgan failure with signs of renal dysfunction and sometimes cardiac compromise, including cardiac dilatation and supraventricular tachyarrhythmias, has been common.14,15,16,24 Other complications have included ventilator-associated pneumonia, pulmonary hemorrhage, pneumothorax, pancytopenia, Reye's syndrome, and sepsis syndrome without documented bacteremia.
<b>Mortality</B>
The fatality rate among hospitalized patients has been high (Table 3), although the overall rate is probably much lower.21 In contrast to 1997, when most deaths occurred among patients older than 13 years of age, recent avian influenza A (H5N1) infections have caused high rates of death among infants and young children. The case fatality rate was 89 percent among those younger than 15 years of age in Thailand. Death has occurred an average of 9 or 10 days after the onset of illness (range, 6 to 30),15,16 and most patients have died of progressive respiratory failure.
<b>Laboratory Findings</b>
Common laboratory findings have been leukopenia, particularly lymphopenia; mild-to-moderate thrombocytopenia; and slightly or moderately elevated aminotransferase levels (Table 3). Marked hyperglycemia, perhaps related to corticosteroid use, and elevated creatinine levels also occur.16 In Thailand,15 an increased risk of death was associated with decreased leukocyte, platelet, and particularly, lymphocyte counts at the time of admission.
<b>Virologic Diagnosis</b>
Antemortem diagnosis of influenza A (H5N1) has been confirmed by viral isolation, the detection of H5-specific RNA, or both methods. Unlike human influenza A infection,26 avian influenza A (H5N1) infection may be associated with a higher frequency of virus detection and higher viral RNA levels in pharyngeal than in nasal samples. In Vietnam, the interval from the onset of illness to the detection of viral RNA in throat-swab samples ranged from 2 to 15 days (median, 5.5), and the viral loads in pharyngeal swabs 4 to 8 days after the onset of illness were at least 10 times as high among patients with influenza A (H5N1) as among those with influenza A (H3N2) or (H1N1). Earlier studies in Hong Kong also found low viral loads in nasopharyngeal samples.27 Commercial rapid antigen tests are less sensitive in detecting influenza A (H5N1) infections than are RT-PCR assays.15 In Thailand, the results of rapid antigen testing were positive in only 4 of 11 patients with culture-positive influenza A (H5N1) (36 percent) 4 to 18 days after the onset of illness.
<b>Management</B>
Most hospitalized patients with avian influenza A (H5N1) have required ventilatory support within 48 hours after admission,15,16 as well as intensive care for multiorgan failure and sometimes hypotension. In addition to empirical treatment with broad-spectrum antibiotics, antiviral agents, alone or with corticosteroids, have been used in most patients (Table 3), although their effects have not been rigorously assessed. The institution of these interventions late in the course of the disease has not been associated with an apparent decrease in the overall mortality rate, although early initiation of antiviral agents appears to be beneficial.1,15,16 Cultivable virus generally disappears within two or three days after the initiation of oseltamivir among survivors, but clinical progression despite early therapy with oseltamivir and a lack of reductions in pharyngeal viral load have been described in patients who have died.
<b>Pathogenesis
Characterization of Virus</b>
Studies of isolates of avian influenza A (H5N1) from patients in 1997 revealed that virulence factors included the highly cleavable hemagglutinin that can be activated by multiple cellular proteases, a specific substitution in the polymerase basic protein 2 (Glu627Lys) that enhances replication,28,29 and a substitution in nonstructural protein 1 (Asp92Glu) that confers increased resistance to inhibition by interferons and tumor necrosis factor (TNF-) in vitro and prolonged replication in swine,30 as well as greater elaboration of cytokines, particularly TNF-, in human macrophages exposed to the virus.31 Since 1997, studies of influenza A (H5N1)32,33,34 indicate that these viruses continue to evolve, with changes in antigenicity35,36and internal gene constellations; an expanded host range in avian species37,38and the ability to infect felids17,18; enhanced pathogenicity in experimentally infected mice and ferrets, in which they cause systemic infections39,40; and increased environmental stability.
Phylogenetic analyses indicate that the Z genotype has become dominant33 and that the virus has evolved into two distinct clades, one encompassing isolates from Cambodia, Laos, Malaysia, Thailand, and Vietnam and the other isolates from China, Indonesia, Japan, and South Korea.21 Recently, a separate cluster of isolates has appeared in northern Vietnam and Thailand, which includes variable changes near the receptor-binding site and one fewer arginine residue in the polybasic cleavage site of the hemagglutinin. However, the importance of these genetic and biologic changes with respect to human epidemiology or virulence is uncertain.
<b>Patterns of Viral Replication</B>
The virologic course of human influenza A (H5N1) is incompletely characterized, but studies of hospitalized patients indicate that viral replication is prolonged. In 1997, virus could be detected in nasopharyngeal isolates for a median of 6.5 days (range, 1 to 16), and in Thailand, the interval from the onset of illness to the first positive culture ranged from 3 to 16 days. Nasopharyngeal replication is less than in human influenza,27and studies of lower respiratory tract replication are needed. The majority of fecal samples tested have been positive for viral RNA (seven of nine), whereas urine samples were negative. The high frequency of diarrhea among affected patients and the detection of viral RNA in fecal samples, including infectious virus in one case,22 suggest that the virus replicates in the gastrointestinal tract. The findings in one autopsy confirmed this observation.41
Highly pathogenic influenza A (H5N1) viruses possess the polybasic amino acid sequence at the hemagglutinin-cleavage site that is associated with visceral dissemination in avian species. Invasive infection has been documented in mammals,28,29,39,40 and in humans, six of six serum specimens were positive for viral RNA four to nine days after the onset of illness. Infectious virus and RNA were detected in blood, cerebrospinal fluid, and feces in one patient.22 Whether feces or blood serves to transmit infection under some circumstances is unknown.
<b>Host Immune Responses</b>
The relatively low frequencies of influenza A (H5N1) illness in humans despite widespread exposure to infected poultry indicate that the species barrier to acquisition of this avian virus is substantial. Clusters of cases in family members may be caused by common exposures, although the genetic factors that may affect a host's susceptibility to disease warrant study.
The innate immune responses to influenza A (H5N1) may contribute to disease pathogenesis. In the 1997 outbreaks, elevated blood levels of interleukin-6, TNF-, interferon-, and soluble interleukin-2 receptor were observed in individual patients,42 and in the patients in 2003, elevated levels of the chemokines interferon-inducible protein 10, monocyte chemoattractant protein 1, and monokine induced by interferon- were found three to eight days after the onset of illness.27 Recently, plasma levels of inflammatory mediators (interleukin-6, interleukin-8, interleukin-1, and monocyte chemoattractant protein 1) were found to be higher among patients who died than among those who survived (Simmons C: personal communication), and the average levels of plasma interferon- were about three times as high among patients with avian influenza A who died as among healthy controls. Such responses may be responsible in part for the sepsis syndrome, ARDS, and multiorgan failure observed in many patients.
Among survivors, specific humoral immune responses to influenza A (H5N1) are detectable by microneutralization assay 10 to 14 days after the onset of illness. Corticosteroid use may delay or blunt these responses.
<b>Pathological Findings</b>
Limited postmortem analyses have documented severe pulmonary injury with histopathological changes of diffuse alveolar damage,27,41,42 consistent with findings in other reports of pneumonia due to human influenza virus.43 Changes include filling of the alveolar spaces with fibrinous exudates and red cells, hyaline-membrane formation, vascular congestion, infiltration of lymphocytes into the interstitial areas, and the proliferation of reactive fibroblasts. Infection of type II pneumocytes occurs.41,42 Antemortem biopsy of bone marrow specimens has shown reactive histiocytosis with hemophagocytosis in several patients, and lymphoid depletion and atypical lymphocytes have been noted in spleen and lymphoid tissues at autopsy.13,15,27,42 Centrilobular hepatic necrosis and acute tubular necrosis have been noted in several instances.
<b>Case Detection and Management</b>
The possibility of influenza A (H5N1) should be considered in all patients with severe acute respiratory illness in countries or territories with animal influenza A (H5N1), particularly in patients who have been exposed to poultry (Table 4). However, some outbreaks in poultry were recognized only after sentinel cases occurred in humans. Early recognition of cases is confounded by the nonspecificity of the initial clinical manifestations and high background rates of acute respiratory illnesses from other causes. In addition, the possibility of influenza A (H5N1) warrants consideration in patients presenting with serious unexplained illness (e.g., encephalopathy or diarrhea) in areas with known influenza A (H5N1) activity in humans or animals.
Table 4. Exposures That May Put a Person at Risk for Infection with Influenza A (H5N1).
The diagnostic yield of different types of samples and virologic assays is not well defined. In contrast to infections with human influenza virus, throat samples may have better yields than nasal samples. Rapid antigen assays may help provide support for a diagnosis of influenza A infection, but they have poor negative predictive value and lack specificity for influenza A (H5N1). The detection of viral RNA in respiratory samples appears to offer the greatest sensitivity for early identification, but the sensitivity depends heavily on the primers and assay method used. Laboratory confirmation of influenza A (H5N1) requires one or more of the following: a positive viral culture, a positive PCR assay for influenza A (H5N1) RNA, a positive immunofluorescence test for antigen with the use of monoclonal antibody against H5, and at least a fourfold rise in H5-specific antibody titer in paired serum samples.44
<b>Hospitalization</b>
Whenever feasible while the numbers of affected persons are small, patients with suspected or proven influenza A (H5N1) should be hospitalized in isolation for clinical monitoring, appropriate diagnostic testing, and antiviral therapy. If patients are discharged early, both the patients and their families require education on personal hygiene and infection-control measures (Table 5). Supportive care with provision of supplemental oxygen and ventilatory support is the foundation of management.1 Nebulizers and high–air flow oxygen masks have been implicated in the nosocomial spread of severe acute respiratory syndrome (SARS) and should be used only with strict airborne precautions.
Table 5. Strategies to Prevent Avian Influenza A (H5N1) in Humans in a Nonpandemic Setting.
<b>Antiviral Agents</b>
Patients with suspected influenza A (H5N1) should promptly receive a neuraminidase inhibitor pending the results of diagnostic laboratory testing. The optimal dose and duration of treatment with neuraminidase inhibitors are uncertain, and currently approved regimens likely represent the minimum required. These viruses are susceptible in vitro to oseltamivir and zanamivir.46,47 Oral osel-tamivir46 and topical zanamivir are active in animal models of influenza A (H5N1).48,49 Recent murine studies indicate that as compared with an influenza A (H5N1) strain from 1997, the strain isolated in 2004 requires higher oseltamivir doses and more prolonged administration (eight days) to induce similar antiviral effects and survival rates.50 Inhaled zanamivir has not been studied in cases of influenza A (H5N1) in humans.
Early treatment will provide the greatest clinical benefit,15 although the use of therapy is reasonable when there is a likelihood of ongoing viral replication. Placebo-controlled clinical studies of oral oseltamivir51,52 and inhaled zanamivir53 comparing currently approved doses with doses that are twice as high found that the two doses had similar tolerability but no consistent difference in clinical or antiviral benefits in adults with uncomplicated human influenza. Although approved doses of oseltamivir (75 mg twice daily for five days in adults and weight-adjusted twice-daily doses for five days in children older than one year of age — twice-daily doses of 30 mg for those weighing 15 kg or less, 45 mg for those weighing more than 15 to 23 kg, 60 mg for those weighing more than 23 to 40 kg, and 75 mg for those weighing more than 40 kg) are reasonable for treating early, mild cases of influenza A (H5N1), higher doses (150 mg twice daily in adults) and treatment for 7 to 10 days are considerations in treating severe infections, but prospective studies are needed.
High-level antiviral resistance to oseltamivir results from the substitution of a single amino acid in N1 neuraminidase (His274Tyr). Such variants have been detected in up to 16 percent of children with human influenza A (H1N1) who have received oseltamivir.54 Not surprisingly, this resistant variant has been detected recently in several patients with influenza A (H5N1) who were treated with oseltamivir.21 Although less infectious in cell culture and in animals than susceptible parental virus,55 oseltamivir-resistant H1N1 variants are transmissible in ferrets.56 Such variants retain full susceptibility to zanamivir and partial susceptibility to the investigational neuraminidase inhibitor peramivir in vitro.57,58
In contrast to isolates from the 1997 outbreak, recent human influenza A (H5N1) isolates are highly resistant to the M2 inhibitors amantadine and rimantadine, and consequently, these drugs do not have a therapeutic role. Agents of clinical investigational interest for treatment include zanamivir, peramivir, long-acting topical neuraminidase inhibitors, ribavirin,59,60 and possibly, interferon alfa.61
<b>Immunomodulators</b>
Corticosteroids have been used frequently in treating patients with influenza A (H5N1), with uncertain effects. Among five patients given corticosteroids in 1997, two treated later in their course for the fibroproliferative phase of ARDS survived. In a randomized trial in Vietnam, all four patients given dexamethasone died. Interferon alfa possesses both antiviral and immunomodulatory activities, but appropriately controlled trials of immunomodulatory interventions are needed before routine use is recommended.
<b>Prevention
Immunization</b>
No influenza A (H5) vaccines are currently commercially available for humans. Earlier H5 vaccines were poorly immunogenic and required two doses of high hemagglutinin antigen content62 or the addition of MF59 adjuvant63 to generate neutralizing antibody responses. A third injection of adjuvanted 1997 H5 vaccine variably induced cross-reacting antibodies to human isolates from 2004.64 Reverse genetics has been used for the rapid generation of nonvirulent vaccine viruses from recent influenza A (H5) isolates,65,66 and several candidate vaccines are under study. One such inactivated vaccine with the use of a human H5N1 isolate from 2004 has been reported to be immunogenic at high hemagglutinin doses.67 Studies with approved adjuvants like alum are urgently needed. Live attenuated, cold-adapted intranasal vaccines are also under development. These are protective against human influenza after a single dose in young children.68
<b>Hospital-Infection Control</b>
Influenza is a well-recognized nosocomial pathogen.4,5 Current recommendations are based on efforts to reduce transmission to health care workers and other patients in a nonpandemic situation and on the interventions used to contain SARS (Table 5).1 The efficiency of surgical masks, even multiple ones,69 is much less than that of N-95 masks, but they could be used if the latter are not available. Chemoprophylaxis with 75 mg of oseltamivir once daily for 7 to 10 days is warranted for persons who have had a possible unprotected exposure.70,71 The use of preexposure prophylaxis warrants consideration if evidence indicates that the influenza A (H5N1) strain is being transmitted from person to person with increased efficiency or if there is a likelihood of a high-risk exposure (e.g., an aerosol-generating procedure).
<b>Household and Close Contacts</B>
Household contacts of persons with confirmed cases of influenza A (H5N1) should receive postexposure prophylaxis as described above. Contacts of a patient with proven or suspected virus should monitor their temperature and symptoms (Table 5). Although the risk of secondary transmission has appeared low to date, self-quarantine for a period of one week after the last exposure to an infected person is appropriate. If evidence indicates that person-to-person transmission may be occurring, quarantine of exposed contacts should be enforced. For others who have had an unprotected exposure to an infected person or to an environmental source (e.g., exposure to poultry) implicated in the transmission of influenza A (H5N1), postexposure chemoprophylaxis as described above may be warranted.
<b>Conclusions</b>
Infected birds have been the primary source of influenza A (H5N1) infections in humans in Asia. Transmission between humans is very limited at present, but continued monitoring is required to identify any increase in viral adaptation to human hosts. Avian influenza A (H5N1) in humans differs in multiple ways from influenza due to human viruses, including the routes of transmission, clinical severity, pathogenesis, and perhaps, response to treatment. Case detection is confounded by the nonspecificity of initial manifestations of illness, so that detailed contact and travel histories and knowledge of viral activity in poultry are essential. Commercial rapid antigen tests are insensitive, and confirmatory diagnosis requires sophisticated laboratory support. Unlike human influenza, avian influenza A (H5N1) may have higher viral titers in the throat than in the nose, and hence, analysis of throat swabs or lower respiratory samples may offer more sensitive means of diagnosis. Recent human isolates are fully resistant to M2 inhibitors, and increased doses of oral oseltamivir may be warranted for the treatment of severe illness. Despite recent progress, knowledge of the epidemiology, natural history, and management of influenza A (H5N1) disease in humans is incomplete. There is an urgent need for more coordination in clinical and epidemiologic research among institutions in countries with cases of influenza A (H5N1) and internationally.
The views expressed in this article do not necessarily reflect those of the WHO or other meeting sponsors.
We are indebted to the National Institute of Allergy and Infectious Diseases and the Wellcome Trust for their collaborative support of the WHO meeting; to Drs. Klaus Stohr and Alice Croisier of the Global Influenza Program at the WHO, Geneva; and to Drs. Peter Horby and Monica Guardo and the staff of the WHO Country Offices, Vietnam, for organizing the WHO consultation and for support in the preparation of the manuscript; and to Diane Ramm for help in the preparation of the manuscript.
<b>Source Information</b>
The writing committee consisted of the following: John H. Beigel, M.D., National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.; Jeremy Farrar, D.Phil., Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam; Aye Maung Han, M.B., B.S., Department of Child Health, Institute of Medicine, Yangon, Myanmar; Frederick G. Hayden, M.D. (rapporteur), University of Virginia, Charlottesville; Randy Hyer, M.D., World Health Organization, Geneva; Menno D. de Jong, M.D., Ph.D., Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam; Sorasak Lochindarat, M.D., Queen Sirikit National Institute of Child Health, Bangkok, Thailand; Nguyen Thi Kim Tien, M.D., Ph.D., Pasteur Institute, Ho Chi Minh City, Vietnam; Nguyen Tran Hien, M.D., Ph.D., National Institute of Hygiene and Epidemiology, Hanoi; Tran Tinh Hien, M.D., Ph.D., Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam; Angus Nicoll, M.Sc., Health Protection Agency, London; Sok Touch, M.D., Ministry of Health, Phnom Penh, Cambodia; and Kwok-Yung Yuen, M.D., University of Hong Kong, Hong Kong SAR, China.
Address reprint requests to Dr. Hayden at the Department of Internal Medicine, P.O. Box 800473, University of Virginia Health Sciences Center, Charlottesville, VA 22908, or at fgh@virginia.edu.
Please see references.
lovescrochet
Inactive
I'd like to see a review of ways to avoid coming into contact with H5N1 when it becomes H2H on a thread, if anyone has any good ideas. Yes, we can take the meds, if we have them.
But what else?
I plan on taking my daughter out of public school whenever I hear the first report that it is transferring H2H - not from some unknown third-world newspaper, but what I call a truly credible source. I think my feeling is that it will probably show up in Europe before here, does everyone agree? I know that travel is so common nowadays that being able to watch it as it spreads from East to West might not be as true as it was in previous decades.
I also thought about how I should handle getting out into the public when it comes to America. Should we be using surgical face masks and rubber gloves when we go out in public? I would be willing to do my necessary shopping at weired, off hours to avoid John Q., but what about the germs left behind on surfaces whenever a sick person coughs? Is this flue going to be like most germs and stay viable for a certain period of time outside a human host? Or, like certain viruses, does it die as soon as it hits the air?
And should we plan on showering and washing our clothes just as soon as we come in from the outdoors? I guess so, if the virus can "hang around" on the outside. Hmmm, yes, I have alot of questions about how to survive such a pandemic.
Thanks for keeping me updated!
But what else?
I plan on taking my daughter out of public school whenever I hear the first report that it is transferring H2H - not from some unknown third-world newspaper, but what I call a truly credible source. I think my feeling is that it will probably show up in Europe before here, does everyone agree? I know that travel is so common nowadays that being able to watch it as it spreads from East to West might not be as true as it was in previous decades.
I also thought about how I should handle getting out into the public when it comes to America. Should we be using surgical face masks and rubber gloves when we go out in public? I would be willing to do my necessary shopping at weired, off hours to avoid John Q., but what about the germs left behind on surfaces whenever a sick person coughs? Is this flue going to be like most germs and stay viable for a certain period of time outside a human host? Or, like certain viruses, does it die as soon as it hits the air?
And should we plan on showering and washing our clothes just as soon as we come in from the outdoors? I guess so, if the virus can "hang around" on the outside. Hmmm, yes, I have alot of questions about how to survive such a pandemic.
Thanks for keeping me updated!
Fuzzychick
Membership Revoked
Shakey, Thank You!...time to do serious hard core work on this...again Thanx! Love Fuzzy
Trasael Adnepos
Inactive
Someone more qualified than me please comment on the medical opinions I am hearing that it is only a matter of time before human flu sufferers exposed to the avian strain will pass a combinant/mutant to many other humans, and the plague is on. Is this documented or speculation due other known combinant strains?
Thanks, and thanks for your efforts, Shakey.
Tras
Thanks, and thanks for your efforts, Shakey.
Tras
Fuzzychick
Membership Revoked
Trasael Adnepos said:
Have a background...what's yours my friend? An exchange of ideas is always better than one... two heads better than one....esp. here.
Thanks Shakey. This is an important topic IMHO.
I recently had a discussion with several friends who are Drs. and RNs working in local hospitals in the PNW. Since this area is a major hub to the East, I was curious what level of preparedness was being established to combat a possible outbreak. I had asked them what they were hearing about this, and what plans were being made to deal with it should it become a pandemic. All but one of them just stared at me blankly and said they didn't know anything about it.
The one who did comment simply said "Oh, the hospital has emergency procedures. We'll just look up the necessary procedures if it ever happens." 
After reading the reports coming from WHO, CDC and others, I had assumed (I know, I know--dumb to assume anything these days!) there would have been at least some general knowledge of this topic by the people in the health care field. And I had hoped there might have been some level of alertness as to the potential for a major crisis. Their ignorance and seeming nonchalance stunned me. I hold out little hope that an outbreak would be spotted quickly if the rest of the medical profession in this country are as clueless as those I've talked to appear to be.
If the medical profession in this country are as blissfully ignorant as those I've talked to locally, what chance do we have of catching this if and when it comes to our shores?
I recently had a discussion with several friends who are Drs. and RNs working in local hospitals in the PNW. Since this area is a major hub to the East, I was curious what level of preparedness was being established to combat a possible outbreak. I had asked them what they were hearing about this, and what plans were being made to deal with it should it become a pandemic. All but one of them just stared at me blankly and said they didn't know anything about it.
The one who did comment simply said "Oh, the hospital has emergency procedures. We'll just look up the necessary procedures if it ever happens." After reading the reports coming from WHO, CDC and others, I had assumed (I know, I know--dumb to assume anything these days!) there would have been at least some general knowledge of this topic by the people in the health care field. And I had hoped there might have been some level of alertness as to the potential for a major crisis. Their ignorance and seeming nonchalance stunned me. I hold out little hope that an outbreak would be spotted quickly if the rest of the medical profession in this country are as clueless as those I've talked to appear to be.
If the medical profession in this country are as blissfully ignorant as those I've talked to locally, what chance do we have of catching this if and when it comes to our shores?
AMEN Maureen!MaureenO said:Grock, I'm by no stretch an alarmist, however, I know positively that by the time the news is officially announced re: human-to-human exposure it will be too late.
Skakey just made a timely series of posts that may well save some lives here if those ears are open.
Maureen
Bumping and thanking Shakey for the research as well.
Sassy
Sadie-
Excellent point- I believe the whole purpose of our discussions is to be armed with information and observation. For example, your point that the NW is a hub for Asia regarding airline travel. We know that our system is unprepared for a major outbreak. We have learned from the latest major events in this country that our thinking must be geared to not depend on the system (.gov or medical) to "take care of us". So, as individuals, we can make decisions ahead of time to prepare. Then we follow through. There are NO guarantees in this life, but we are called to do the best we can with what we have, and then I leave it to the Lord. My days have been numbered since the moment I was born, and I don't spend alot of time worrying about how and when it's going to happen. I have been blessed however, with a goodly dose of common sense, and it tells me to watch and prepare. I may not live, but my family and friends just might benefit from the work I do now. That's good enough for me. The information coming out must be sifted to determine the closest possible truth. It's what we have to work with, and it is wonderful to see folks jump in with facts and opinions that help the process of discerning the truth. Y'all are doing a great job- Shakey - Thanks for your hard work, it's truly valuable.
Excellent point- I believe the whole purpose of our discussions is to be armed with information and observation. For example, your point that the NW is a hub for Asia regarding airline travel. We know that our system is unprepared for a major outbreak. We have learned from the latest major events in this country that our thinking must be geared to not depend on the system (.gov or medical) to "take care of us". So, as individuals, we can make decisions ahead of time to prepare. Then we follow through. There are NO guarantees in this life, but we are called to do the best we can with what we have, and then I leave it to the Lord. My days have been numbered since the moment I was born, and I don't spend alot of time worrying about how and when it's going to happen. I have been blessed however, with a goodly dose of common sense, and it tells me to watch and prepare. I may not live, but my family and friends just might benefit from the work I do now. That's good enough for me. The information coming out must be sifted to determine the closest possible truth. It's what we have to work with, and it is wonderful to see folks jump in with facts and opinions that help the process of discerning the truth. Y'all are doing a great job- Shakey - Thanks for your hard work, it's truly valuable.
ARUBI
Inactive
FYI,
scroll down to Bird Flu Posts at
http://effectmeasure.blogspot.com/
The Editors of Effect Measure are senior public health scientists and practitioners. Their names would be immediately recognizable to many in the public health community. They prefer to keep their online and public lives separate to allow maximum freedom of expression.
Paul Revere was a member of the first local Board of Health in the United States (Boston, 1799). The Editors sign their posts "Revere" to recognize the public service of a professional forerunner better known for other things.
----------------------------------------------------------------------------------------
In July they started;
http://www.fluwikie.com/
Friday, July 15, 2005
Flu Wiki update
The Flu Wiki is now two and a half weeks old and is no longer an infant but a thriving adolescent. New organization and navigational aids have been added to the wiki sidebar. The Forum has been active (under Main on the sidebar you will find Recent Forum Topics) and much new material has been added (click under All Recent Changes under Main). The participation of the blogosphere has been magnificent. It looks like almost all US states have had links contributed so now it is easy to see what your state is doing (or not doing) and compare it to other states (if you find a gap, fill it). Several other countries and world regions have had material added, but there is much to do here. Readers in other countries are strongly encouraged to inquire of their governments and add their experience and plans to the appropriate National section under Geographic Services and Draft Plans.
There are some (we hope) informative science primers geared specifically to the flu problem and more to come. There is a Timeline and a set of "imagined scenarios" and a template to do your own local Table Top Exercise (under Anticipated Consequences and Solutions).
In short, a genuine community response is underway. It will continue to grow and become enriched with your help and interest. In a short time it has already become one of the main sources of information for people wishing to learn how they can help their community prepare for a potential pandemic. It is experiencing steady traffic.
But there is much more to do. Lend a hand. Help your neighbor and your self and those you've never seen and will never meet. Because in truth we're all in this together.
posted by Revere
scroll down to Bird Flu Posts at
http://effectmeasure.blogspot.com/
The Editors of Effect Measure are senior public health scientists and practitioners. Their names would be immediately recognizable to many in the public health community. They prefer to keep their online and public lives separate to allow maximum freedom of expression.
Paul Revere was a member of the first local Board of Health in the United States (Boston, 1799). The Editors sign their posts "Revere" to recognize the public service of a professional forerunner better known for other things.
----------------------------------------------------------------------------------------
In July they started;
http://www.fluwikie.com/
Friday, July 15, 2005
Flu Wiki update
The Flu Wiki is now two and a half weeks old and is no longer an infant but a thriving adolescent. New organization and navigational aids have been added to the wiki sidebar. The Forum has been active (under Main on the sidebar you will find Recent Forum Topics) and much new material has been added (click under All Recent Changes under Main). The participation of the blogosphere has been magnificent. It looks like almost all US states have had links contributed so now it is easy to see what your state is doing (or not doing) and compare it to other states (if you find a gap, fill it). Several other countries and world regions have had material added, but there is much to do here. Readers in other countries are strongly encouraged to inquire of their governments and add their experience and plans to the appropriate National section under Geographic Services and Draft Plans.
There are some (we hope) informative science primers geared specifically to the flu problem and more to come. There is a Timeline and a set of "imagined scenarios" and a template to do your own local Table Top Exercise (under Anticipated Consequences and Solutions).
In short, a genuine community response is underway. It will continue to grow and become enriched with your help and interest. In a short time it has already become one of the main sources of information for people wishing to learn how they can help their community prepare for a potential pandemic. It is experiencing steady traffic.
But there is much more to do. Lend a hand. Help your neighbor and your self and those you've never seen and will never meet. Because in truth we're all in this together.
posted by Revere
Fuzzychick
Membership Revoked
BTW Shakey...thank you! 
Supposedly approximately 60 people have died from this flu. Under normal circumstances, that wouldn't even make the news - anywhere, except locally. However, the fed.gov has spent months hyping this, attempting to instill fear into the populace. Not only that, these viruses are genetically manipulated (three sources have reported this). They have been working to get them to spread from person-to-person for a couple of years, without much luck. Chances are they will announce that it is here, the herd will stampede to get a deadly vaccine, and that will be the end of hundreds of thousands of people who mistakenly thought the vaccine was harmless (even though it is "experimental"). And the herd of useless eaters will have been reduced, while the vaccine makers will make big bucks from federal tax outlays. Goal accomplished.
ARUBI
Inactive
http://www.medpagetoday.com/InfectiousDisease/PublicHealth/tb/1835
International Team Issues Avian Flu Recommendations
By Katrina Woznicki, MedPage Today Staff Writer
Reviewed by Zalman S. Agus, MD; Emeritus Professor at the University of Pennsylvania School of Medicine.
September 28, 2005
MedPage Today Action Points
Advise patients that the H5N1 flu can be contracted from infected birds. Although as yet there have been no confirmed reports of human-to-human transmission, scientists are concerned that the virus may mutate and become highly transmissible from person to person.
Advise patients traveling to countries where avian flu has been detected in animals and people to get a trivalent human vaccine preferably two weeks before traveling to the region.
Review
CHARLOTTESVILLE, Va. Sept. 28-As the avian flu, the H5N1 virus, continues to spread in Asia and threaten Europe's borders, an international team of physicians has issued clinical guidelines on detecting and managing the disease and containing transmission.
Writing in The New England Journal of Medicine, the clinicians offered advice on dealing with the evolving threat and the possible trajectory of the understudied pathogen.
So far, all the reported human infections have been from exposure to infected animals, and there have been no confirmed reports of efficient human-to-human transmission. Nevertheless, experts fear that risk could eventually materialize, said team leader Frederick G. Hayden, M.D., a professor of internal medicine and pathology at the University of Virginia Health Sciences Center here.
The detailed recommendations include information on how to detect and treat the illness and how to differentiate the disease from known human influenzas. The authors also provided recommendations for reducing the risk of transmission in a non-pandemic setting.
Some of these recommendations were presented last May at the World Health Organization meeting in Hanoi, although the current summaries do not represent official WHO guidelines.
"Continued monitoring is required to identify any increase in viral adaptation to human hosts," Dr. Hayden and colleagues wrote in the review article. However, knowledge of the disease continues to change as the disease continues to expand, they noted, and more data are sorely needed. "Because many critical questions remain, modifications of these recommendations are likely," they emphasized.
First, the physicians noted that influenza A H5N1 in humans differs in multiple ways from influenza due to human viruses, including routes of transmission, clinical severity, pathogenesis, and perhaps, response to treatment.
For example, the incubation period of H5N1 appears to be longer. Patients with H5N1 also rarely exhibit conjunctivitis. Upper respiratory tract symptoms are present only occasionally, while lower respiratory symptoms are more common. Fever, diarrhea, vomiting, abdominal pain, and bleeding from the nose and gums have also been reported early in the course of the illness.
The research team advises that in countries where there have been animal or human cases of H5N1, physicians should consider the possibility of H5N1 infection in any patient with severe acute respiratory illness, especially among those exposed to poultry.
When symptoms appear and a diagnosis is needed, clinicians may have better luck with throat cultures than nasal swabs, they advised.
"H5N1 may have higher viral titers in the throat than in the nose, and hence, analysis of the throat swabs or lower respiratory samples may offer more sensitive means of diagnosis," the experts wrote.
When treating H5N1, Tamiflu (oseltamivir) appears to be the most effective drug. The researchers noted that placebo-controlled studies comparing standard doses of oral Tamiflu and inhaled Relenza (zanamivir) with double-doses showed no significant difference between the two.
Currently, the WHO and other organizations including the European Union and the Centers for Disease Control and Prevention in this country are stockpiling doses of Tamiflu to prepare for a potential global pandemic many experts hope will remain only theoretical.
There is also no specific vaccine to prevent H5N1, although scientists at the National Institute of Allergy and Infectious Diseases recently tested a prototype vaccine that showed promise in clinical trials.
The authors also advise on how to help prevent the spread of avian influenza in a non-pandemic setting. For example, travelers going to countries where H5N1 was detected should be immunized with the available trivalent human vaccine two weeks before traveling.
Household members who may have come in contact with an infected family member or infected animals should wash their hands diligently and avoid face-to-face contact with infected patients. If they have come into close contact with an infected individual, they are advised to monitor their own temperature twice a day and check for symptoms one week after their last exposure.
Health care workers who start to show symptoms "should be treated immediately with oseltamivir on the assumption of influenza infection," the authors wrote. Patients who are infected should be treated with heavy-duty isolation precautions -- a combination of standard, contact, droplet, and airborne protection. In environments where single rooms aren't available for patients, beds should be placed a minimum of one meter apart between infected patients.
Since 2003, the virus has affected 11 countries and killed 62 people with the greatest number of deaths occurring in Vietnam. But the number of cases continues to climb.
Earlier this summer, H5N1 was detected in domestic and wild fowl in Russia sparking the European Union to take action. Health officials fear that like other known human influenza viruses, the longer H5N1 persists in the environment, the greater the risk it could mutate into a pathogen highly contagious among humans.
Although health authorities are closely monitoring the spread of H5N1, the authors said their work is cut out for them.
"There is an urgent need for more coordination in clinical and epidemiologic research among institutions in countries with cases of influenza A (H5N1) and internationally," they concluded. "The expanding distribution of avian influenza A (H5N1) infections, with recent outbreaks in Kazakstan, Mongolia, and Russia, indicates that more human populations are at risk."
International Team Issues Avian Flu Recommendations
By Katrina Woznicki, MedPage Today Staff Writer
Reviewed by Zalman S. Agus, MD; Emeritus Professor at the University of Pennsylvania School of Medicine.
September 28, 2005
MedPage Today Action Points
Advise patients that the H5N1 flu can be contracted from infected birds. Although as yet there have been no confirmed reports of human-to-human transmission, scientists are concerned that the virus may mutate and become highly transmissible from person to person.
Advise patients traveling to countries where avian flu has been detected in animals and people to get a trivalent human vaccine preferably two weeks before traveling to the region.
Review
CHARLOTTESVILLE, Va. Sept. 28-As the avian flu, the H5N1 virus, continues to spread in Asia and threaten Europe's borders, an international team of physicians has issued clinical guidelines on detecting and managing the disease and containing transmission.
Writing in The New England Journal of Medicine, the clinicians offered advice on dealing with the evolving threat and the possible trajectory of the understudied pathogen.
So far, all the reported human infections have been from exposure to infected animals, and there have been no confirmed reports of efficient human-to-human transmission. Nevertheless, experts fear that risk could eventually materialize, said team leader Frederick G. Hayden, M.D., a professor of internal medicine and pathology at the University of Virginia Health Sciences Center here.
The detailed recommendations include information on how to detect and treat the illness and how to differentiate the disease from known human influenzas. The authors also provided recommendations for reducing the risk of transmission in a non-pandemic setting.
Some of these recommendations were presented last May at the World Health Organization meeting in Hanoi, although the current summaries do not represent official WHO guidelines.
"Continued monitoring is required to identify any increase in viral adaptation to human hosts," Dr. Hayden and colleagues wrote in the review article. However, knowledge of the disease continues to change as the disease continues to expand, they noted, and more data are sorely needed. "Because many critical questions remain, modifications of these recommendations are likely," they emphasized.
First, the physicians noted that influenza A H5N1 in humans differs in multiple ways from influenza due to human viruses, including routes of transmission, clinical severity, pathogenesis, and perhaps, response to treatment.
For example, the incubation period of H5N1 appears to be longer. Patients with H5N1 also rarely exhibit conjunctivitis. Upper respiratory tract symptoms are present only occasionally, while lower respiratory symptoms are more common. Fever, diarrhea, vomiting, abdominal pain, and bleeding from the nose and gums have also been reported early in the course of the illness.
The research team advises that in countries where there have been animal or human cases of H5N1, physicians should consider the possibility of H5N1 infection in any patient with severe acute respiratory illness, especially among those exposed to poultry.
When symptoms appear and a diagnosis is needed, clinicians may have better luck with throat cultures than nasal swabs, they advised.
"H5N1 may have higher viral titers in the throat than in the nose, and hence, analysis of the throat swabs or lower respiratory samples may offer more sensitive means of diagnosis," the experts wrote.
When treating H5N1, Tamiflu (oseltamivir) appears to be the most effective drug. The researchers noted that placebo-controlled studies comparing standard doses of oral Tamiflu and inhaled Relenza (zanamivir) with double-doses showed no significant difference between the two.
Currently, the WHO and other organizations including the European Union and the Centers for Disease Control and Prevention in this country are stockpiling doses of Tamiflu to prepare for a potential global pandemic many experts hope will remain only theoretical.
There is also no specific vaccine to prevent H5N1, although scientists at the National Institute of Allergy and Infectious Diseases recently tested a prototype vaccine that showed promise in clinical trials.
The authors also advise on how to help prevent the spread of avian influenza in a non-pandemic setting. For example, travelers going to countries where H5N1 was detected should be immunized with the available trivalent human vaccine two weeks before traveling.
Household members who may have come in contact with an infected family member or infected animals should wash their hands diligently and avoid face-to-face contact with infected patients. If they have come into close contact with an infected individual, they are advised to monitor their own temperature twice a day and check for symptoms one week after their last exposure.
Health care workers who start to show symptoms "should be treated immediately with oseltamivir on the assumption of influenza infection," the authors wrote. Patients who are infected should be treated with heavy-duty isolation precautions -- a combination of standard, contact, droplet, and airborne protection. In environments where single rooms aren't available for patients, beds should be placed a minimum of one meter apart between infected patients.
Since 2003, the virus has affected 11 countries and killed 62 people with the greatest number of deaths occurring in Vietnam. But the number of cases continues to climb.
Earlier this summer, H5N1 was detected in domestic and wild fowl in Russia sparking the European Union to take action. Health officials fear that like other known human influenza viruses, the longer H5N1 persists in the environment, the greater the risk it could mutate into a pathogen highly contagious among humans.
Although health authorities are closely monitoring the spread of H5N1, the authors said their work is cut out for them.
"There is an urgent need for more coordination in clinical and epidemiologic research among institutions in countries with cases of influenza A (H5N1) and internationally," they concluded. "The expanding distribution of avian influenza A (H5N1) infections, with recent outbreaks in Kazakstan, Mongolia, and Russia, indicates that more human populations are at risk."
MaureenO
Another Infidel
Grock said:
Panic is certainly an enemy, however I stand by my assertion that by the time MSM release the documentaiton, it will be too late to stop the tide of death.
THAT is my point. Do NOT wait t see the New York Times headline to prepare for this mutation. MSM are already pussyfooting around the issue which should be a blazing beacon for anyone with eyes and ears.
Maureen
Fuzzychick
Membership Revoked
Amen Maureen...
Do Not Assume that drugs or vaccine will available and or effective.
Learn and practice disease prevention and disinfection protocols.
This is what germ warriors do when they travel to outbreak locales.
Check CDC website. Get your supplies NOW.
Do Not Expect the whole truth from the media.
Nations dealing with this have no interest in publicizing it:
- Citizens banned from international travel
- Borders closed
- exports banned
- recreational travel decimated
There is speculation that many more people
in China have died than what is publicized...
Tommy Thompson warned us of this when he left office.
Learn and practice disease prevention and disinfection protocols.
This is what germ warriors do when they travel to outbreak locales.
Check CDC website. Get your supplies NOW.
Do Not Expect the whole truth from the media.
Nations dealing with this have no interest in publicizing it:
- Citizens banned from international travel
- Borders closed
- exports banned
- recreational travel decimated
There is speculation that many more people
in China have died than what is publicized...
Tommy Thompson warned us of this when he left office.
Fuzzychick
Membership Revoked
BUMP.
Fuzzychick
Membership Revoked
suzy said:
Suzy, you're probably right...
Maybe a new thread should be started on how to survive a flu pandemic..quote
I started one a few days back and it feel to the side...no one seemed to be interested it was..posted as how to prep for bird flu and everyone suggested just going to current events. This site is all about the flu pandemic...
here is the site..
http://www.curevents.com/vb/index.php?
I started one a few days back and it feel to the side...no one seemed to be interested it was..posted as how to prep for bird flu and everyone suggested just going to current events. This site is all about the flu pandemic...
here is the site..
http://www.curevents.com/vb/index.php?
closet squirrel
Veteran Member
bumb
Trek
Inactive
I hope you are right rescath.
Even so... This thread is, imho, very important. Worthy of being pinned at the top throughout flu season at least.
Maybe I feel that way because my daughter has been sick with suspected bacterial pneumonia for almost a month and we are having a hell of a time trying to kick the illness. Doc's can't find the bacteria causing the disease, but she has shown some response to antibiotics so they assume it's not viral. All I know is that the docs know little, and it is harder than I imagined to boost a normally healthy immune system to fight whatever is causing her pneumonia.
If it were the avian flu... I have no idea what else we could do to fight the disease. This thread needs to be watched so everyone is well warned.
Even so... This thread is, imho, very important. Worthy of being pinned at the top throughout flu season at least.
Maybe I feel that way because my daughter has been sick with suspected bacterial pneumonia for almost a month and we are having a hell of a time trying to kick the illness. Doc's can't find the bacteria causing the disease, but she has shown some response to antibiotics so they assume it's not viral. All I know is that the docs know little, and it is harder than I imagined to boost a normally healthy immune system to fight whatever is causing her pneumonia.
If it were the avian flu... I have no idea what else we could do to fight the disease. This thread needs to be watched so everyone is well warned.