Medical News Blog Information

The US CDC starts more gears turning.

US CDC asked local healthcare providers to keep an eye out for "signs of H7N9 flu". 

Rather than watch for feathers, this will entail being on the lookout for cases with influenza-like illness (ILI) among those who have themselves, or are in contact with someone who, recently traveled China who are influenzavirus-negative by standard laboratory testing methods. Rapid prescription of Tamiflu is recommended (within 48h). 

All commercially available influenzavirus tests on these cases should be disregarded because their ability to detect the new H7N9 is untested so the risk of false negatives is high.

A mutation musing

A collaborative report (by Dutch and Chinese contributor) published yesterday from Eurosurveillance shows that 5/7 H7N9 strains from humans, birds and the environment have an amino acid change in the HA gene called Q226L (the normal" glutamine [Q] found at amino acid position 226 has "mutated" to a Leucine[L]). 

In the past, this change has been associated with binding of influenzavirus to a receptor molecule called alpha(2,6,)-linked sialic acid, which is found in the human upper respiratory tract. 

A virus that is happy to replicate in the upper airways, one of the first ports of call for inspired virus-laded droplets, is going to have a good ability to spread by the aerosol route. [I include the eyes in here - but they may considered anatomically separate and the true first point of contact with virus-laden aerosols as they are probably open more than the mouth. 

Other influenza viruses have been shown, by testing of eye swabs, to cause conjunctivitis at this site and common cold viruses can enter the airways through the tear duct. 

More info on Q226L can be found here and here

The 15-person strong "influenza A-team"...

...have arrived in China to examine, understand and advise on the avian influenza A(H7N9) virus situation in Shanghai and Beijing. 

The comment that "with perhaps rare exceptions, people are not getting sick from other people. Of the many hundreds of people who were in close contact with the H7N9 patients, all the care-givers, neighbors, family members, and so on, there are only a very few cases where these contacts have become ill as well." exemplifies the search for symptomatic illness. 

However there is still an opportunity to test the contacts using sensitive laboratory methods. 

These results will be very important for ruling out (or in) the potential for stealthy H7N9 spread among people without predetermined clinical signs and symptoms.

Despite a dodgy serology test...

..not my interpretation, tweet from WHO's Gregory Hartl, it seems that at least one son of this outbreak's first reported H7N9 case (Case #1, 87M) has been confirmed as also being H7N9 positive. 

What does this mean? 

It doesn't mean the sky is falling - contacts, by their very nature share things. In a family you often share (inhale, have land in your eyes etc) aerosolized (virus-laden) droplets as well as common surfaces contaminated by with those aerosols, when you have an acute virus infection. 

Coughing and sneezing do that. But you also share common tasks. There is so far no clear evidence of direct Dad to Son (or Son to Dad) transmission here (there is a timing issue that is intriguing)- the father and son may have simply shared the same airspace (I think its pretty safe to say this is transmitted through the air in some form) with an animal host during contact, handling, butchery, cleaning etc. 

Despite testing of animals to date finding very few have detectable H7N9 infections.

How to solve a problem like transmission?

Perhaps once Prof Ron Fouchier can get the virus into his ferret model he should be able to definitively answer whether avian influenza A(H7N9) can be transmitted via the airborne route and the real impact of the much discussed mutations found in H7N9 over recent weeks. He will also look at the virus by infecting rhesus macaques and African green monkeys.

Looking like Shanghai contributed 6 cases overnight.

However, dates are scant and patchy so I have not further updated the charts yet. I'm hoping for some clear data later in the day. 

New retrospective test results have appeared - these comprise serological data for two cases (seroconversion to influenzavirus can take 12-21d which may vary further in the elderly or those with immunocompromise) and culture isolations for two cases as well as two deaths. 

Why PCR did not pick up the H7N9 in the cases from which virus was isolated? Unclear and surprising.

Aaron Berkowitz
PGY-3, Neurology
Travel Grant: Neurology Education in Malawi

Queen Elizabeth Central Hospital in Blantyre, Malawi is the country�s largest hospital, with over 1000 inpatients. As there is no district hospital in the vicinity, the hospital provides all levels of care from primary through tertiary care. It also serves one of the primary sites of medical education for medical students, residents, and clinical officers in training.





       

On the left, the recently built emergency department at Queen Elizabeth Central Hospital. On the right, mountains seen in the distance behind the hospital.







The main hallway (above) is reminiscent of Brigham and Women�s �Pike,� a seemingly infinite corridor with various �exits� to the wards of the different specialties: medicine, surgery, pediatrics, obstetrics, hemodialysis, oncology, radiology.



One specialty, however, is not represented: neurology. In fact, there are no adult neurologists in the entire country of Malawi (there is one pediatric neurologist). The number of patients admitted for neurologic problems, however, is substantial, as would be expected at any tertiary referral hospital. In just under 2 weeks since arriving and working with only the internal medicine service (generally serving 150-200 inpatients), I have been asked to see 22 inpatients and 9 outpatients with primary neurologic symptoms/signs. In contrast to the usual elderly average age on a neurology service in the United States, the average age of patients I have seen so far has been 36. A few consults have been straightforward (e.g., stroke, neuropathy), but many have been mysterious constellations of symptoms and signs in young patients without clear explanation, and limited diagnostic testing to pursue a diagnosis and craft a treatment plan.

On the left, the entry to the Department of Medicine; on the right, one bay of the women's ward at QECH

When hearing the students and house staff present patients, one is struck by the fact that the first identifying statement for the patient (i.e., age, sex) always includes the patient�s HIV status, and this is presented even before the chief complaint. No presentation of a physical examination is complete without mentioning whether there are Kaposi sarcoma lesions. The prevalence of HIV/AIDS in Malawi is around 12%, and I have been told that 80-85% of the hospital�s patients at any given time are HIV positive. Of the 31 patients I have seen so far, 11 have been HIV positive. HIV and resultant opportunistic infections can affect any part of the nervous system at any stage of the illness from seroconversion to advanced AIDS, leading to complex diagnostic quandaries, especially in the setting of one or more additional systemic illnesses that may or may not be HIV-related.

The medicine department asked for visiting neurologists to come to teach students and residents as there are no neurologists in the country. I have truly enjoyed working with the extraordinarily enthusiastic students and housestaff. Given limitations in diagnostic testing (e.g., no basic chemistries, no CT scans), clinicians here are extraordinary bedside diagnosticians. Teaching how to use the detailed neurologic examination for localization and differential diagnosis in neurology is therefore a natural extension of the exceptionally astute clinical skills already deeply ingrained in the students and residents.

I also had the opportunity to teach the clinical officers staffing the emergency department. Clinical officers are the country�s first line of medical care at district hospitals, clinics, and emergency rooms, with training essentially analogous to a physician assistant in the U.S.

While my primary role here has been to teach, I have surely learned much more than I have taught, not only about HIV-related (as well as malaria and tuberculosis-related) neurologic disease and clinicial decision-making in the setting of limited diagnostic testing, but also about how to attempt to convey the essentials of neurologic clinical reasoning in different ways for non-neurologist practitioners at different levels of training practicing in different contexts.

I am grateful to the Partners Global Health Travel Grant and Partners Neurology Residency for supporting this work.

The old question of how much do we trust PCR?

Over at FluTrackers, expert virology communicator (the virology blog), picornavirologist and teacher Prof Vincent Racaniello reiterates a point that hasn't been mentioned much with respect to the H7N9 emergence. 

"Conclusions about etiology are more difficult to determine if viral sequences are detected by PCR in the absence of clinical symptoms". In other words its important to consider the much greater sensitivity of PCR compared to old culture-based diagnostics, in the context of false positives (environmental or laboratory cross-contamination) and what a weak H7N9-positive might practically mean. 

A good seroconversion still can't be beat in these cases!

IMHO - experienced diagnostic labs should have long ago dealt with this issue. PCR has been in use as the "gold standard" for years. 

In a situation like the one ongoing, I assume that all H7N9 positives are being suitably confirmed using follow-up confirmatory testing using previously established protocols.

(waaaay) Down the track...

..it will also be interesting to see whether the H7N9 circulation had an unusual impact on "seasonal" respiratory viruses like parainfluenzaviruses (PIVs), enteroviruses (EVs) and rhinoviruses (HRV) which reportedly, like influenzavirus, can peak in Beijing and Shanghai around May (Ren et al., Clin Microbiol Infect 2009;p1146-; Wang et al. J Clin Virol 2010;p211-)

A new question...

...to mull over: Have viral co-infections and bacterial super-infections been sought, or excluded, in the H7N9 fatalities to date (some mention the 3 cases NEJM article)? 

What contribution do they make, along with existing co-morbidities, in the deaths of the 14 (as of 15.04) H7N9-positive cases?

Asymptomatic H7N9 case detected.

Multiple reports of the first asymptomatic case in a 4-year old male (4M) living across the street from the previously H7N9-POS, 7F. This may demystify a lot of H7N9 confusion as well as seriously increase the threat level for H7N9 spread...a stealth virus not only in poultry but humans is a new game. 

As I've suggested earlier, the widespread use of sensitive molecular detection methods, not just on the cases with the most severe clinical signs and symptoms, is absolutely essential to detect mild or asymptomatic cases of infection. The use of PCR in this way seems to have done just that. 

I'll keep a close eye on this story but I suspect it will result in a drastic change to the landscape of detection numbers and epidemiology. 

Symptoms alone tell only a small part of the story of any respiratory virus. This may strengthen the case for H7N9 having been in the community for much longer than the pneumonia cases officially commencing back in Feb, suggest.

Biggest single H7N9 notification day?

Today saw a remarkable 11 H7N9 confirmations added including 2 new deaths and a new province (Henan; population >94,000,000) added to the list. FluTrackershas all the details...although many cases do not have full details; the best quality data come from Shanghai, Beijing and Henan at the moment. 

Cases jump to 60 with 13 deaths but the Case Fatality Rate remains steady at 22%. 

No sustained human-to-human transmission has been identified yet.

Like Us

Blog Archive