N Engl J Med. Pneumonia and Respiratory Failure from Swine-Origin Influenza A (H1N1) in Mexico

[Giuseppe]

NEJM -- Pneumonia and Respiratory Failure from Swine-Origin Influenza A (H1N1) in Mexico

Original Article

Published at www.nejm.org June 29, 2009 (10.1056/NEJMoa0904252)

Pneumonia and Respiratory Failure from Swine-Origin Influenza A (H1N1) in Mexico

Rogelio Perez-Padilla, M.D., Daniela de la Rosa-Zamboni, M.D., Samuel Ponce de Leon, M.D., Mauricio Hernandez, M.D., Francisco Qui?ones-Falconi, M.D., Edgar Bautista, M.D., Alejandra Ramirez-Venegas, M.D., Jorge Rojas-Serrano, M.D., Christopher E. Ormsby, M.Sc., Ariel Corrales, M.D., Anjarath Higuera, M.D., Edgar Mondragon, M.D., Jose Angel Cordova-Villalobos, M.D., for the INER Working Group on Influenza

Abstract

Background
In late March 2009, an outbreak of a respiratory illness later proved to be caused by novel swine-origin influenza A (H1N1) virus (S-OIV) was identified in Mexico. We describe the clinical and epidemiologic characteristics of persons hospitalized for pneumonia at the national tertiary hospital for respiratory illnesses in Mexico City who had laboratory-confirmed S-OIV infection, also known as swine flu.

Methods
We used retrospective medical chart reviews to collect data on the hospitalized patients. S-OIV infection was confirmed in specimens with the use of a real-time reverse-transcriptase?polymerase-chain-reaction assay.

Results
From March 24 through April 24, 2009, a total of 18 cases of pneumonia and confirmed S-OIV infection were identified among 98 patients hospitalized for acute respiratory illness at the National Institute of Respiratory Diseases in Mexico City. More than half of the 18 case patients were between 13 and 47 years of age, and only 8 had preexisting medical conditions. For 16 of the 18 patients, this was the first hospitalization for their illness; the other 2 patients were referred from other hospitals. All patients had fever, cough, dyspnea or respiratory distress, increased serum lactate dehydrogenase levels, and bilateral patchy pneumonia. Other common findings were an increased creatine kinase level (in 62% of patients) and lymphopenia (in 61%). Twelve patients required mechanical ventilation, and seven died. Within 7 days after contact with the initial case patients, a mild or moderate influenza-like illness developed in 22 health care workers; they were treated with oseltamivir, and none were hospitalized.

Conclusions
S-OIV infection can cause severe illness, the acute respiratory distress syndrome, and death in previously healthy persons who are young to middle-aged. None of the secondary infections among health care workers were severe.
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<cite cite="http://content.nejm.org/cgi/content/full/NEJMoa0904252">NEJM -- Pneumonia and Respiratory Failure from Swine-Origin Influenza A (H1N1) in Mexico</cite>

[gsgs]

Re: N Engl J Med. Pneumonia and Respiratory Failure from Swine-Origin Influenza A (H1N1) in Mexico

why did I miss this




case 2 here:

http://content.nejm.org/cgi/content/full/NEJMoa0904252v1/F2

was a 50 year old female with asthma from Mexico City,
symptoms March 23, hospitalized 5.April, discharged 12.May

http://content.nejm.org/content/vol0/issue2009/images/medium/NEJMoa0904252f2.gif

> All patients resided in the Mexico City greater metropolitan area.


> Patient 2, (the 50f) in whom severe respiratory failure developed, is the mother of Patient 9,
> who had milder disease and received early treatment with oseltamivir.

patient 9 (19f) had symptoms April 3, was hospitalized April 8, discharged April 10.
But they may have sampled her April 14 ?


so 2 could be 4115 , 9 could be 4487 - that would explain why the sequences
are almost identical.

But 4487 ("InDRE4487") was sent to Canada as was reported they had done
with Gutierrez' sample. (collected 13.April or earlier)

The only other "InDRE" is 4114.


4115 (=Patient 2 ?)
2 had symptoms March 23 and sequences (on 14.April) very close to the origin of ******.





this is strange, why they don't assign the sequence-numbers to the patients
why they sometimes give no age,gender,collection date.
Also in the press-releases and newspaper articles.
Maybe it's to protect the privacy of the patients.
Maybe they just don't know about the seuences
or they _want_ to ignore it, they don't want us
to explore the origin of this virus.
They must have the data, must have done this exploration
already, but I can't find anything about it on the web.



the delay of this article is ~2 months, which is much better than usual
and it's freely available. But it's still 2 months lost, in which hospitals
and planners might have needed the data to decide how many ventilators
are needed how to protect the nurses etc.

...And researcher to decide how it had started, whether it might easily
happen again, how it transmits, which substrains are more virulent...


available viruses from Mexico,April 2009:

Mexico/InDRE4114/2009
Mexico/3955/2009 04-02-09 F 9
Mexico/4108/2009 04-02-09 M 4
Mexico/4115/2009 04-07-09 F 50
Mexico/4176/2009 04-13-09 M 12
Mexico/InDRE4487/2009 04-14-09
Mexico/4482/2009 04-14-09 F 29
Mexico/4486/2009 04-14-09 M 3
Mexico/4269/2009 04-15-09 M 3
Mexico/4502/2009 04-17-09 F 3
Mexico/4603/2009 04-19-09 F 59
Mexico/4604/2009 04-19-09 F 52
Mexico/4575/2009 04-20-09 F 49
Mexico/4593/2009 04-20-09 F 13
Mexico/4595/2009 04-20-09 F 8
Mexico/4627/2009 04-20-09 M 3
Mexico/4635/2009 04-20-09 F 30
Mexico/4646/2009 04-20-09 F 24
Mexico/47N /2009 04-25-09 M 5 Mexico City
Mexico/4516/2009 04-25-09 M 41

Monterrey/1/2009 05-07-09 M
Monterrey/2/2009 05-08-09 M Nuevo Leon


the 18 patients
--------------
number,gender,age,days before admission,died?,
day,month of symptom-onset, day,month of admission

1,m,13,5,y,19,3,23,3
2,f,50,13,n,23,3,5,4
3,m,43,7,y,24,3,31,3
4,f,9,6,y,25,3,31,3
5,f,4,5,n,27,3,1,4
6,m,45,6,y,31,3,6,4
7,m,38,7,n,1,4,8,4
8,m,52,5,y,2,4,7,4
9,f,19,5,n,3,4,8,4
10,m,.75,6,n,5,4,11,4
11,f,26,8,n,6,4,14,4
12,f,37,5,n,8,4,13,4
13,f,1,4,n,8,4,12,4
14,f,61,6,n,10,4,16,4
15,m,40,11,n,12,4,23,4
16,f,48,6,y,12,4,18,4
17,m,47,8,y,15,4,23,4
18,m,39,5,n,16,4,21,4

these 18 tested positive, but there are no sequences

[german-docter]

Re: N Engl J Med. Pneumonia and Respiratory Failure from Swine-Origin Influenza A (H1N1) in Mexico

Comment: This report of 18 cases of pneumonia and confirmed S-OIV infection in Mexico, recently published in the New England Journal of Medicine, shows some illustrative aspects. Those who died already were in an advanced state of sepsis and SIRS at the time of admission with respiratory failure, ARDS, hypoxemia, acidosis, DIC and renal failure as well. In both groups (those who resolved the disease and the fatal cases) the time between onset of illness and time of admission was 6 days (median). Nobody of them had been given antivirals until they were hospitalized, although 12 of 18 patients (67 percent) had been seeking medical advice at other institutions as outpatients before hospitalisation. That obviously might have contributed to the high cfr in the early days of novel influenza in Mexico.

Quote:

http://content.nejm.org/cgi/reprint/NEJMoa0904252v1.pdf

Pneumonia and Respiratory Failure from Swine-Origin Influenza A (H1N1) in Mexico
Rogelio Perez-Padilla et al.
published on June 29, 2009, at NEJM.org. N Engl J Med 2009;361.
(?)
The time between onset of symptoms and admission to the hospital ranged from 4 to 25 days (median, 6) (Fig. 2). All patients had fever, with temperatures higher than 38?C, cough, and dyspnea or respiratory distress. Four of the five children (all under 14 years of age) had diarrhea, and only two patients (11%) reported wheezing. The median Acute Physiology and Chronic Health Evaluation II score was 14 (range, 4 to 32), and the median Sequential Organ Failure Assessment score was 6 (range, 1 to 13); both were higher, indicating more severe abnormalities among the patients who died than among those who lived (Table 2). Twelve patients sought medical care at other institutions as outpatients before hospitalization at INER and were treated with one or more antibiotics: ceftriaxone (five patients), amikacin (three), azithromycin (one), amoxicillin?clavulanate (two) or other macrolides (three), or another agent (two). (?)

Treatment
None of the patients had received oseltamivir before admission; 14 received it in the hospital, at a dose of 75 mg twice a day for a minimum of 5 days; 11 began receiving it at admission (a mean of 8 days after the onset of symptoms) and 3 between 2 and 10 days after admission. (?)

Some of these pathogenetic mechanisms have been discussed in the following thread in conjunction with the fatal Argentina-cases.

I give a warning that IMO any politically influenced strategy of restrictions in early antiviral treatment in supposed ?mild? cases (or prophylaxis) as is done in the UK now, might increase the number of fatal cases in novel Influenza.
Antivirals save lifes !

http://www.flutrackers.com/forum/showthread.php?t=112758&page=2

Quote:
Re: Argentina: unusual serious cases in young people
________________________________________
Quote:
Originally Posted by FrenchieGirl
It looks like the policy is changing towards more aggressive treatment, viz:

Lungs to be "burned" in hours
There is a seriousness of patients' unusual '

"We're seeing the placement of young patients, between 15 and 50 years with pneumonia, some rapidly evolving towards a gravity which for many is unusual, in which the lung is' fire 'in a matter of hours," said Dr. Jorge San Juan, head of the Department of Intensive Care Hospital Mu?iz.

This has led to patients with these characteristics begin to be treated in an increasingly aggressive. THE NATION As reported yesterday, doctors from the Ministry of Health received the directive to take, from now on, all cases of influenza and potential influenza A (H1N1), with the recommendation to perform chest radiographs for patients with symptoms of fever and fatigue and internal quickly to all suffering from pneumonia.

"Today, it is known that the virus is circulating mass, the attitude we have with patients depends on clinical assessment made by the doctor not to become a serious case. It is not necessary to diagnose laboratory [confirming the new virus infection] to begin treatment, "said Dr. Vilma Savy, Chief of the Respiratory Virus Malbr?n institute.

(...)

Changes in strategies for care of patients arriving with flu tables advanced aiming to be more aggressive: treat, then see what happens; leapfrogging. "This form of serious patient care will change the trend and prevent more deaths and pneumonia, said Dr. John, coordinator of the Emergency Committee of the Ministry of Health Epidemiological Aires.

For severe pneumonia, said San Juan, today patients do not receive empirical antibiotics and antiviral drugs but also does not delay the use of mechanical ventilation. "While generally expect 24 hours to see how it evolves, we do not, and if decompensation quickly reach intubation," said San Juan.

The province of Buenos Aires will, from next week, with rapid diagnostic tests that will discriminate in just 15 minutes by means of swabs, if the person is a carrier of influenza A. Anyway, the final confirmation will institute Malbr?n. The new test will begin before the treatment, health authorities reported ranches.

Comment of mine:
IMO in all reports of this thread, openly or between the lines you can read the following important facts regarding the severe course of the Argentina-cases:
They missed to take swabs in these cases (Had there been ILI or atypical ILI ?) in order to check on novel Influenza A at the time of admittance or at the beginning of the illness.

They did not use antiviral treatment, at least not in the early stage of the disease. I guess, they even did not think of Influenza-pneumonia at that time.
They possibly even started antibiotics too late. Time delay between clinical onset of pneumonia and the first dose of antibiotics is a very important factor regarding the case fatality rate (of pneumonia).

They did no x-ray of they did it late. (At the time you can see signs of pneumonia on the chest x-ray the disease already is in an advanced stage. You certainly may hear rales on auscultation prior to x-ray results !)

At the time, a patient needs to be intubated with a tracheal tube and set on ventilator, damage to lung tissue already is on an advanced stage. Then the quite common problems of intensive care medicine (Sepsis, SIRS, kidney failure on so on) no longer are preventable. If you miss your chance in diagnosis and treatment at an early stage of the disease, then there will be a point of no return, no matter what you'll do on your ICU (ventilators, ECMO etc.). And rapid tests for Influenza A are false negative in 30 to 40 %.

No ideas --> no tests --> no diagnosis --> no antivirals --> no antibiotics (or at least: any of these too late).

To me, Argentina is more or less a "deja vu" of Mexico in the first days of its novel influenza A-Epidemic.

[gsgs]

Re: N Engl J Med. Pneumonia and Respiratory Failure from Swine-Origin Influenza A (H1N1) in Mexico

apparantly these 18 cases are somehow independent
of the 24 cases reported here:

http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5817a5.htm

since the age-counts and onset dates don't match.



confirmed S-OIV (cases,deaths):
Federal District (15,6),
Mexico State (7,0),
Veracruz (1,0),
Oaxaca (1,1)

Among the 16 patients with complete clinical records, 15 reported fever,
13 reported cough, 10 reported tachypnea, and nine reported dyspnea.
In addition, seven of 16 patients reported either vomiting or diarrhea.
Of these seven patients, two reported vomiting only, two reported
diarrhea only, and three reported both.

[german-docter]

Re: N Engl J Med. Pneumonia and Respiratory Failure from Swine-Origin Influenza A (H1N1) in Mexico

apparantly these 18 cases are somehow independent
of the 24 cases reported here:

http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5817a5.htm

since the age-counts and onset dates don't match. (...)
.

gsgs,
yes, the NEJM-paper especially focuses on the pneumonia-aspect, while the CDC-report is more ore less on all aspects of novel influenza in Mexico. So, only some of the patients might be in both reports ?

http://content.nejm.org/cgi/reprint/NEJMoa0904252v1.pdf

NEJM:
Pneumonia and Respiratory Failure (?)

From March 24 through April 24, 2009, a total of 18 cases of pneumonia and confirmed S-OIV infection were identified among 98 patients hospitalized for acute respiratory illness at the National Institute of Respiratory Diseases in Mexico City.

http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5817a5.htm

CDC (MMWR)
Outbreak of Swine-Origin Influenza A (H1N1) Virus Infection --- Mexico (?)

Of the 24 patients for whom demographic and clinical information is available, 20 (83%) were hospitalized, three were examined in outpatient settings, and one had illness that was not medically attended. Patients ranged in age from <1 to 59 years, with 79% aged 5 to 59 years (Table 2); 15 (62%) patients were female. Patients with confirmed S-OIV infection were identified in four states: Federal District (15 cases), Mexico State (seven), Veracruz (one), Oaxaca (one). Of the seven deaths, six occurred in Federal District, and one occurred in Oaxaca. (?) Twelve of 15 patients with radiography records available had confirmed pneumonia.
TABLE 2. Number of patients and deaths (?) Total: 24 deaths: 7 (...)

[gsgs]

Re: N Engl J Med. Pneumonia and Respiratory Failure from Swine-Origin Influenza A (H1N1) in Mexico

hard to match the onset dates, sampling dates and
genbank numbers to the people.


To make one combined list with age,gender,onset date,sampling date,
release date,outcome,location,genbank-number
(if available)

and give me the email adress of Mrs.4115, please