Atypical Pneumonia


Atypical Pneumonia
The atypical pneumonia (also known as atypical pneumonia) is a highly infectious disease from SARS-CoV virus of the coronavirus family. It is characterized by severe acute respiratory syndrome (SARS in English, for Severe acute respiratory syndrome).

It appeared for the first time in China in November 2002, and caused a global epidemic in May 2003.

The atypical pneumonia has appeared in Hong Kong at the hotel metropolis (9th floor), then Singapore and Hanoi in Vietnam. A global alert was launched by the WHO (World Health Organization) on March 12, 2003. The hotel is a major trade and what explains that the epidemic has spread throughout the world since the first bearers have traveled between Hong Kong and the rest of the home infected.

Given its transmission by air, the disease has quickly spread to a large number of people and in many countries. China, which seems to have been the original outbreak of the disease (see below), has been very hard hit by the epidemic. The Chinese authorities seem not to have taken early enough security measures very strict as the quarantining of probable cases and adequate public information. Thus, 7761 cases of atypical pneumonia were reported in China (Hong Kong, Taiwan and Macao). The cities of Singapore and Toronto were also affected, with respectively 206 and 252 cases.

In addition, a real psychosis moved to Beijing, Hong Kong and Singapore, where the population systemically wearing respiratory masks when travelling in public to avoid contagion.

The record of 1 November 2002 to 1 July 2003 (source: WHO), is:

* 8445 cases of illness identified;
* 916 deaths so far

On July 2, 2003 (source: WHO), the epidemic seems to have been almost completely contained. Taiwan is the last possible outbreak of a local chain of transmission of the disease. The epidemic has been limited in Canada, Singapore and in almost all of China, the three main countries affected by SARS. According to statistics of WHO, 8445 cases of atypical pneumonia identified in total, 812 would be dead, only 211 people are still suffering.

Economic Impacts
The atypical pneumonia has led to many cancellations of trips to Asia, which has put many airlines, European, but especially American, in an economic situation even more critical.

In addition, many contracts could not be reached, due to the cancellation of trips to Asia. Some industries, however, have benefited to some extent, Mexico, for example, to which temporarily turn passengers and American entrepreneurs.

Guests Asian salon watches in Basel (Switzerland) were forced to return without participating in the event.

Events 2003-2004
New cases have occurred in September 2003 in Singapore. It seems that the cause is a bad containment of the virus in the laboratory. The disease is contained in May 2004. During this period, 9 people seem to have contracted the disease.

Diagnostic Clinic, biological and radiological
The diagnosis of infection by the SARS-CoV based on clinical examination, radiological signs and the notion of travel in a country where the virus has been detected. The initial signs of infection are not specific and diagnosis remains a diagnosis of exclusion. The most common symptom of SARS is a fever over 38 ° C appearing quite suddenly after an incubation period of 2 to 10 days. However, this fever may be absent at the beginning of the disease in patients or carriers of a disease affecting other febrile reactions. The fever may be associated with chills, myalgia, malaise, headache. The initial symptoms resemble especially at a table of atypical pneumonia. A productive cough, a painful dysphagia, nausea and vomiting are more rare. Diarrhea was a common symptom in epidemiological reported an outbreak in Hong Kong but seems rare in other groups which have been described. The pulmonary auscultation may find inspiratoires rails at the base but there is usually no wheezing.

In biological terms, many hematological abnormalities have been reported during the course of the disease. A lymphopenia is present in 98% of patients with the lowest rates recorded during the second week of development and standardization during the third week. However, in 30% of cases, lymphopenia persisted in the fifth week of development. At the initial stage of the disease, the rate of CD4 and CD8 could be lowered. According to some studies, low CD4 and CD8 would be a factor of poor prognosis. A transitional leukopenia has been reported in 64% of patients during the first week of the disease. However, at 61% of patients, leukocytosis was found during the second and third week of evolution. A neutrophilia was observed in 82% of cases, probably related to treatment with corticosteroids. A self-related thrombocytopenia was found in 55% of patients. No serious bleeding was observed. The rest of the biological balance shows an increase of LDH, AST and ALT and creatine kinase. High levels of LDH and transaminases may be secondary to treatment with ribavirin. However, in some studies, high LDH is reported as a factor of poor prognosis. Finally, D-Dimères can be high and the TCA lying in a significant number of patients.

The radiological imaging occupies an important place in the initial diagnosis of infection by SARS and then in monitoring the effectiveness of treatment. The most typical images include a peripheral location predominant opacities cellular unilateral focal progressing under treatment to an attack multifocal unilateral or bilateral. There is no excavation or adenopathy, or pleural effusion. The scanner is a chest examination, which allows usually clear signs of severe pneumonia.

Many atypical tables have been described: apyrétiques patients, patient with diarrhea but without signs lung… These atypical forms constitute a threat to patients, hospital staff and relatives. The WHO therefore precisely defined the criteria for probable case of SARS: a fever over 38 ° C combined with signs of respiratory basis (cough, dyspnea, respiratory gene etc.). Occurring in a person from a country or an area where active transmission of SARS has been described or at someone (or worked) in a laboratory handling (or manipulated) of SARS (whatever its geographical location).

Diagnosis of viral infection by SARS-CoV
Currently, the diagnosis of SARS can not be raised until it eliminated other causes of pneumonia through direct methods of research officers usually responsible for pneumonia. In retrospect, the serological diagnosis may help to reconsider some difficult cases. In 2004, various methods virological diagnosis of SARS had been validated by the WHO. Since then, pharmaceutical companies have developed other tests or have refined sensitivity and specificity of existing tests but in the absence of resurgent epidemic, these tests have not been validated for infection by the SARS-CoV. The diagnostic tools that are described here are those who had been validated by the OMS1.

The virological diagnosis based on the identification of SARS-CoV virus from nasal swabs, pharyngés, sputum, endo-tracheal aspirations, blood, faeces or urine by RT-PCR or viral culture. The virus excretion of SARS-CoV is fairly low at the beginning of the disease, it is up approximately 10 days after the onset of clinical signs. The virus is then found in respiratory secretions and feces. A study of the clinical utility of various diagnostic tests showed that RNA SARS-CoV was detected by RT-PCR in the naso-pharyngeal secretions in only 32% of patients in the initial phase and in 68% of cases 14 after the onset of clinical signs (Peiris, Lancet 2003). A quantitative analysis showed that viral load reached its maximum 10 days after the onset of clinical signs. The viral RNA is detected in stool in 98% of patients later during the illness (to the 14th day) and in urine after the 15th day. The tests RT-PCR remain fairly insensitive and it is strongly advised to increase examinations of samples naso-pharyngés to improve the predictive value of the test. A test of RT-PCR negative does not exclude the diagnosis of SARS samples may have been taken at a time when the viral load was too weak to be detected by laboratory tests available.

The presence of infectious virus can be highlighted by inoculating cell cultures (Vero cells) from stool samples, blood or respiratory secretions. Once the virus isolated, it must use other tests (immunofluorescence for example) to identify the SARS-CoV. The isolation of SARS-CoV in cell culture must be made at least in a laboratory security level BSL3. The results of cell culture negative do not exclude the diagnosis of SARS, for the same reasons as in the case of RT-PCR negative.

The serological diagnosis can help to reconsider cases of unidentified pneumonia. A ELISA test can detect reliably on a mixture of IgG and IgM in serum of patients infected to the 21st day after the onset of clinical signs. Several tests immunofluorescence requiring the use of cells infected with SARS-CoV set on blades can detect antibodies patients (IgG, IgM or both). These tests are positive around the 10th day after the onset of illness, quantitative results can be made using dilutions series of sera from patients. A neutralization test has been developed that evaluates and quantifies the ability to neutralize serum of patients. This test requires work in a laboratory BSL3 level of containment.

The treatment of infection by the SARS-CoV is symptomatic. An antibiotic can be administered as the causes of bacterial pneumonia have not been eliminated. An oxygen therapy should be considered depending on the desaturation. The corticosteroids should be considered depending on the risk of RespiratoireAigu Distress Syndrome (ARDS). The prescription of ribavirin, antiviral used during the 2003 epidemic, is questioned because of the many side effects and their potential severity.

The isolation of patients and protection of the nursing staff and relatives of patients are an integral part of treatment because it is a disease transmitted by direct contact.

In 2006, the CDC in Atlanta (USA) reviewed scientific studies dealing with experimental treatment against SARS. Despite 54 clinical studies on 54 drugs tested on humans, no evidence of the effectiveness of a drug could not be identified. Eight showed significant side effects. For ethical reasons, clinical trials have been made in a hurry, without reference group receiving a placebo, which makes it difficult to assess medicines. (Source: journal Public Library of Science - Medicine).

The SARS-CoV, the causal agent of SARS
The identification of the virus was fast enough (a few months to several years against the HIV virus in the years 1980), 11 laboratories have been mobilized by WHO. The virus that causes SARS belongs to the family Coronaviridae, type of coronavirus.

The coronavirus are enveloped RNA virus simple bit of positive polarity. In electron microscopy, viral particles present protuberances surface giving them a "crown" (corona, latin), which has served the name of these viruses. The classification coronavirus test results serological reactions and analyses of genomic sequences. The family Coronaviridae is divided into three groups: Group 1 (canine coronavirus, the virus from feline infectious peritonitis virus transmissible gastroenteritis pork and pig respiratory virus) and Group 2 (bovine coronavirus, murine hepatitis virus, virus silodacryonite of the rat and human coronavirus OC43) are viruses infecting mammals.
The group consists of 3 known exclusively avian virus (virus of the avian infectious bronchitis, coronavirus turkey). Until now, humans were coronavirus associated with benign diseases. They belong to both the group 1 (HCoV-229E) and group 2 (HCoV-OC43) and are responsible for respiratory diseases usually benign. The coronavirus associated with SARS appears to be the first virus of this family to systematically cause serious illness in humans. In April 2003, the completion of sequencing the genome of the coronavirus associated with SARS shows that the SARS-CoV does not belong to any known groups of coronavirus and that it presents very little sequence homologies with the two human coronavirus, HCoV-OC43 and HCoV-229E. He therefore used to define a fourth lineage of coronavirus, the group 4. The data from genome sequencing show that this virus is not a mutant of a known coronavirus, nor a recombinant between coronavirus known.

The viral particles: The viral envelope is formed by a lipid bilayer from the budding of virions through the cytoplasmic membrane of the host cell. The viral envelope is associated with a protein transmembrane surface shaped spicule, the protein S. This protein associated in trimères binds to sialic acids on the surface of cells in the respiratory tree and confers properties hémagglutinantes the virus. The spicules present on the surface of the viral particle can be made of another viral protein, the protein ET. This protein has a dimérique type esterase activity. During a coronavirus infection, developed antibodies against the protein S and against the protein HE are neutralizing antibodies. Finally, the surface of the viral particle is a small envelope protein, the protein E. The viral membrane is bisected by a transmembrane protein, the protein M, which attaches the nucléocapside the envelope of the viral particle. Within the viral particle is the nucléocapside composed of RNA genome associated with protein nucléocapside, NP.

Epidemiology of infection by SARS-CoV
The human coronavirus OC43 and 229E are responsible for winter epidemics occurring mainly in small communities (homes, schools, families…) during usually a couple of weeks. The human infection is through inhalation of infected droplets salives or through direct contact with nasal secretions.

The Severe Acute Respiratory Syndrome (SARS) is a new infectious disease first identified in February 2003, but this in November 2002 in Guangdong Province (China). As the infection spreads to Hong Kong, however region near the initial focus, suggesting a low contagiousness of the virus. The epidemics that followed were restricted to family groups living in areas of high population density, hotels (Hong Kong) or hospitals (Hanoi, Toronto). This limited extension is an argument in favour of the low transmissibility of the virus. Compared with influenza viruses can quickly infect millions of people around the world, the SARS virus does not appear to spread rapidly. So far, only one outbreak occurred in 2003, affecting at least 8000 people, a number of secondary cases have probably not been identified. The following year, in 2004, 9 cases have been reported only in China. That year, the index cases were systematically described in people working in laboratories studying the virus that causes SARS (student in virology researcher contract). The index case was the source of contamination of other affected people (parents, nurse etc.)..

The SARS virus appears to spread primarily by direct contact with droplets of respiratory secretions of infected persons. A transmission through fecal or air seems possible, but rare (In 2003, outbreaks of infection occurred in a district of Hong Kong seems to have developed from sewage-contaminated). The air diffusion of the SARS virus does not seem important but should not be ruled out. Indeed, the contamination of the nursing staff carrying out acts of high-risk (bronchoscopy, endotracheal intubation…) is an argument in favour of air contamination from a contaminated environment.

Origin animal? In late May 2003, the study of samples of wild animals sold as food in markets of Guangdong province (China) showed the presence of coronavirus of SARS in civets, suggesting that the SARS virus has crossed the species barrier. In 2005, two studies have found coronavirus close to the SARS coronavirus in bats in china. The phylogenetic analysis of these viruses have found a strong likelihood that SARS from bats and has spread to humans, either through chat and / or civets. Bats infected did not show visible signs of illness.

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