Category Archives: pathology

New Ebola can spread by people without obvious signs of the disease

From CNN, July 29, 2014

Brantly’s family had been with him in Liberia, according to the Centers for Disease Control and Prevention, but left for the United States before he became symptomatic; as such it is highly unlikely that they caught the virus from him. Out of an abundance of caution they are on a 21-day fever watch, the CDC said.

Nancy Writebol from Charlotte, North Carolina, has also been infected. She is employed by Serving in Mission, or SIM, and had teamed up with the staff from Samaritan’s Purse to help fight the Ebola outbreak in Monrovia when she got sick. She, too, is undergoing treatment.

It is believed one of the local staff was infected with Ebola and came to work with the virus on Monday and Tuesday, Isaacs told CNN. “We think it was in the scrub-down area where the disease was passed to both Nancy and Kent,” he said. That staff member died on Thursday.

Dr. Brantly is a doctor with obvious experience in diagnosing Ebola cases. Yet, he was unable to detect infection in the co-worker who infected both him and Mrs. Writebol. Further, the co-worker was able to function for two days while still being able to infect at least two other people.

This suggests that we are indeed dealing with a “New Ebola” (as Pixie has put it at PFI Forum). This New Ebola apparently leaves people well enough, while they are infectious, to both travel and work without being detected. This makes this new Ebola pandemic-capable.

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pH1N1 and suppression of the immune system – another report

From NBCDFW, January 19, 2014 [hat-tip, Pixie]

“I have never seen a case of [Influenza] Type A followed by Type B right off,” said Dr. Honaker. “The immune system should kick in with Type A so you don’t get Type B, and this year we are seeing people in my office who have Type A and two or three weeks later they have type B.”

This is an anecdotal report from a physician in North Texas. An adequately powered study will need to be conducted before we can be sure that Dr. Honaker’s impression is true. However, given that there have been previous reports that pH1N1 is associated with immune system dysfunction, this issue deserves additional scrutiny.

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IgG2 deficiency and pandemic H1N1 – cause or consequence?

The immune system protects us from viruses and bacteria. People without a properly working immune system are more likely to die of both. Some people are born with defective immune systems (Severe Combined Immunodeficiency) while others acquire a malfunctioning immune system as a result of viral infection (HIV/AIDs).

A recent report in Clinical Infectious Diseases by Gordon et al., suggests that pandemic H1N1 is associated with deficiency of one part of our immune response, immunoglobulin G2 (IgG2):

Patients with severe H1N1 infection were significantly more likely to be deficient in IgG2 than were patients with moderate H1N1 infection (P =  .001 ); IgG2 deficiency was not necessarily noticeable if only total IgG levels were assessed. Furthermore, our findings suggest that, for the majority of such patients (11 of 15 patients; 73%), IgG2 deficiency persists after recovery from H1N1 infection, regardless of whether the illness was associated with possible risk factors, such as pregnancy. Low IgG2 levels are therefore less likely to be simply related to a severe inflammatory response, as is sometimes noted for acute-phase reactants, such as albumin, creatine kinase, and lactate dehydrogenase [8, 11].

These findings raise an important question – did patients with severe H1N1 symptoms have a preexisting deficiency in their immune system or did H1N1 itself cause the deficiency?

At this point, there is insufficient evidence to say. From the paper:

…it is uncertain whether we have simply identified a cohort of patients with H1N1 infection with underlying unrecognized IgG2 deficiency, or whether there is an interaction between the H1N1 virus and the host that leads to such deficiency.

Apparently healthy individuals can have low levels of IgG (2-20%). However, if this is the group of people who experience more severe symptoms with the new H1N1, then it may be worth identifying this subgroup and making sure that they and their physicians are warned about their elevated risk for severe symptoms with the new H1N1 virus.

If the H1N1 virus is causing IgG2 deficiency, this is not a temporary effect. From the paper:

… the fact that the IgG2 deficiency that we identified appears to persist in most cases long after disease resolution … suggests the possibility of potential long-term implications for these patients and that follow-up of moderate and severe cases of H1N1 infection may be warranted.

The possibility of another virus (other than HIV) that causes permanent damage to the immune system is disturbing. If this is the case, there will be deaths due to pandemic H1N1 long after the pandemic is declared over.

Reference

Gordon et al. (2010) Association between Severe Pandemic 2009 Influenza A (H1N1) Virus Infection and Immunoglobulin G2 Subclass Deficiency. Clinical Infectious Diseases.

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Streptococcus pneumoniae and pandemic H1N1 severity – the data from Argentina

The influenza virus can kill directly. But it can also lower your immune defenses and open you up to bacterial infection. A study that examines the role of bacterial co-infections in the severity of pandemic H1N1 has recently been published in PLoS One.

This study was motivated by the apparently high case fatality rate reported in Argentina. From the paper:

Based on a study in the community of La Gloria, Mexico, where the virus was first detected early in 2009, and worldwide surveillance data and mathematical modeling, the CFR was estimated to be 0.6%. The first case in Argentina was reported on May 17, 2009; by July 16, 2009, just two months later, the number of cases in Argentina totaled 3056, with 137 deaths, representing a computed CFR of 4.5%. Although we could not exclude the possibility that this elevated CFR reflected underreporting of milder infections, the alternative, a bona fide increase due to differences at the level of host or pathogen, might have global implications.

Although some patient risk factors have been associated with a worse outcome, these were not at higher levels in Argentina than other countries, so this could not account for the apparently higher case fatality rates.

To determine whether severe cases had been infected with different strains than mild cases, the complete genomes of 26 viral samples collected from patients with a wide range of symptoms and outcomes were sequenced. No obvious differences were observed.

This left the possibility of bacterial co-infections. 199 samples from people infected with H1N1 were examined for the presence of a wide variety of bacteria and viruses. Many co-infections were found. Pathogens identified included:

…S. pneumoniae (n = 62); H. influenzae (n = 104); human respiratory syncytial virus (RSV) A (n = 11) and B (n = 1); human rhinovirus (HRV) A (n = 1) and B (n = 4); human coronavirus (HCoV) −229 (n = 1) and -OC43 (n = 2); K. pneumoniae (n = 2); A. baumannii (n = 2); S. marcescens (n = 1); and S. aureus (n = 35) and MRSA (n = 6)…

However, only one bacteria was associated with severe cases – S. pneumonia. Further, the effect of this bacteria on outcome was primarily observed in people aged 6 to 55, normally a low risk age group for severe influenza, but one which is at much higher risk with pandemic H1N1 than seasonal flu. This result is not entirely unexpected. As the authors point out:

…recent postmortem analyses indicated lower respiratory tract infection in 22 out of 77 lethal 2009 H1N1pdm cases in the United States (29%); S. pneumoniae was implicated in 10 of these cases.

From a practical standpoint, what do these results mean? Some might be tempted to conclude that treatment with antibiotics would be more effective than treatment with antivirals. However, when the authors examined this, they found the opposite:

Data concerning antiviral and antibiotic therapy were available for 120 subjects. Risk of severe disease was diminished in subjects who received only oseltamivir. Of 96 subjects receiving oseltamivir alone, 10 (10.4%) had severe disease. In contrast, 13 of 14 patients (92.9%) who received antibiotics without antiviral medication had severe disease (p<0.0001).

This is consistent with many other reports suggesting that treatment with Tamiflu (oseltamivir) is especially effective in limiting severity and preventing death from pandemic H1N1. The authors don’t speculate about why Tamiflu alone is more effective than antibiotic treatment alone, even though a bacterial agent appears to be correlated with severe disease. Perhaps the damage done by the virus gives bacteria such unusual access to lung tissue that antibiotics are not as effective as under normal circumstances. In any case, the results from this study clearly support the continued prescription of Tamiflu to limit damage from both the virus directly, and, perhaps, indirect damage from opportunistic bacteria.

Vaccines against Streptococcus pneumoniae are available. Whether they would reduce severe or fatal cases of pandemic H1N1 has not been demonstrated. However, the current paper provides further rationale for recommending such vaccination and study of its possible effectiveness.

References

Palaciaos et al. (2009) Streptococcus pneumoniae Coinfection Is Correlated with the Severity of H1N1 Pandemic Influenza. PLoS One.

CDC (2009) Bacterial coinfections in lung tissue specimens from fatal cases of 2009 pandemic influenza A (H1N1) – United States, May-August 2009. MMWR Morb Mortal Wkly Rep 58: 1071–1074.

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Pandemic H1N1 greatly increases the death rate among pregnant women – The California study

Pregnant women died at much greater rates during previous pandemics than other people. The 2009 pandemic is no exception.

From The New England Journal of Medicine

Eight patients in this series died…None of the eight received antiviral agents within 48 hours after symptom onset…

[snip]

Over the 4-month study period, the cause-specific maternal mortality ratio for 2009 H1N1 influenza was estimated at 4.3 in California. The maternal mortality ratio for death from any cause was 19.3 in California in 2005 and 13.3 in the United States in 2006. More than two thirds of maternal deaths in the United States each year are directly related to obstetrical factors, and maternal deaths due to influenza have been rare. The high 2009 H1N1 influenza–specific maternal mortality suggests that this pandemic has the potential to notably increase overall maternal mortality in the United States in 2009.

It is worth noting that none of the 8 patients who died with confirmed H1N1 had been treated with Tamiflu within the recommended 48 hours of symptoms. Given that approximately 50% of the pregnant women had received Tamiflu within 48 hours of symptoms, it is highly likely that Tamiflu greatly reduced the death rate among pregnant women.

Again, the stories suggesting pandemic H1N1 are no worse than seasonal flu are at variance with the truth. 2009 will likely go down in American history as one of the years with the highest recorded number of deaths among pregnant women, despite the advanced medical care most women received. In countries where Tamiflu and advanced medical care is not readily available, very large numbers of deaths among pregnant women is likely.

Reference

Louie et al. (2009) Severe 2009 H1N1 Influenza in Pregnant and Postpartum Women in California. New England Journal of Medicine. December 23.

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Pandemic H1N1 10 times more lethal to children than seasonal flu – The Argentinian study

One of the great falsehoods promulgated about the current influenza pandemic is that the new H1N1 virus is no worse than seasonal flu. This statement is based on comparing seasonal death rates among the elderly, which assume excess deaths in the winter are due to influenza, without testing, with lab-confirmed deaths due to pandemic flu. Such comparisons are not legitimate because we don’t know for sure that all the elderly deaths are due to influenza, not everyone who has died of pandemic flu is recorded due to inadequate testing and the current pandemic is not over yet. However, the most important reason why these comparisons are not valid is due to the ages of the people who die in a normal flu season versus this pandemic. The vast majority who die of seasonal flu are elderly. The vast majority of those who have died of the new H1N1 have been middle-aged and younger.

A recently published study in the New England Journal of Medicine attempts to quantify the mortality rate of the new H1N1 virus with seasonal flu on children in Buenos Aires. Here is what they found:

Pandemic 2009 H1N1 influenza was associated with pediatric death rates that were 10 times the rates for seasonal influenza in previous years.

This is likely an underestimate of the true lethality of the new H1N1 virus relative to seasonal flu. Although Argentina was slow to close their schools, once the burden on emergency rooms became too great, they did engage in extensive social distancing measures including school and business closures. These actions likely reduced the number infected and, consequently, the number of children who would otherwise have died from pandemic flu. Such extraordinary steps were not taken during normal flu seasons.

The antivrial drug oseltamivir (Tamiflu) is rarely prescribed in Argentina for seasonal flu. However, as the deaths mounted in Argentina, this drug was prescribed with increasing frequency. There is reason to believe that people who received it promptly were more like to survive. From the study:

Of the 13 patients who died, 5 were hospitalized within 48 hours after the onset of symptoms; none received timely oseltamivir.

Without Tamiflu, the number of deaths among children in Argentina might have been much higher.

The American CDC was in close contact with Argentinian authorities during their outbreaks this summer. Further, they were likely well aware of the results of this study months ago. Yet, the Director of the CDC, Thomas Frieden, saw no reason to close American schools until a vaccine was ready. Further, the CDC was slow to encourage the use of Tamiflu to treat patients, despite clear evidence that children were dying due to lack of access.

The failure of the CDC to warn American parents that their children would be 10 times more likely to die of pandemic flu than seasonal flu is inexcusable. Many American children likely died because of CDC policies on school closure and Tamiflu prescription.

Reference

Libster et al. (2009) Pediatric Hospitalizations Associated with 2009 Pandemic Influenza A (H1N1) in Argentina. New England Journal of Medicine. December 23.

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Unreported H1N1 deaths with hemorrhagic lungs in Iowa

The CDC is looking for clusters of people with hemorrhagic pneumonia. Perhaps they should talk to the coroner in Polk County, Iowa.

From KCCI, November 20, 2009

Iowa has officially recorded 21 H1N1 deaths, including seven in Polk County alone. But the county’s medical examiner said he has performed autopsies on some residents who were never diagnosed with H1N1, but actually had it.

“In the autopsy, what we’re seeing is very heavy, wet hemorrhagic lungs, lungs with a lot of blood in them,” said Dr. Gregory Schmunk.

He said the official count of seven H1N1 deaths is inaccurate, but patient rights laws prohibit him from giving specific numbers.

It seems unlikely that Polk County, Iowa is the only place this is happening. Thus, we do not know how many people are dying of H1N1 in the US. We do not know how many have hemorrhagic pneumonia. And we do not know if this symptom and associated deaths are due to a more virulent strain of H1N1.

And from the CDC? Other than bland assurances that they haven’t seen anything which is cause for alarm, nothing.

And that’s the problem.

Clusters of hemorrhagic pneumonia are cause for alarm.

Unfortunately, our public health “firemen” are sleeping through the alarm while the US burns.

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