HIV and ID Observations

Here’s a surprising report in Science:

Studying peripheral blood mononuclear cells (PBMCs) from CFS patients, we identified DNA from a human gammaretrovirus, xenotropic murine leukemia virus-related virus (XMRV), in 68 of 101 patients (67%) compared to 8 of 218 (3.7%) healthy controls … These findings raise the possibility that XMRV may be a contributing factor in the pathogenesis of CFS.

I confess, I had never even heard of “xenotropic murine leukemia virus-related virus” (wow that’s a mouthful) before this report, but apparently virologists have been aware of it for some time, due to a possible association with prostate cancer.

The story behind the Whittemore Peterson Institute reporting these findings is almost as interesting as the paper itself.  From their web site:

In September of 2004, a group of dedicated citizens and clinicians proposed the concept of a medical institute for the millions of patients in the US suffering from the disorders known as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), fibromyalgia and other closely related illnesses. They were concerned by the lack of available doctors to understand and serve the growing numbers of patients with these complex chronic illnesses.

According to the coverage of the story in the Times, the Institute got its start with a several million dollar donation from Annette and Harvey Whittemore, whose child has been suffering from CFS for over twenty years.  The Times piece goes on to quote Dr. William Reeves from CDC, who sounds quite skeptical about the findings.

“We and others are looking at our own specimens and trying to confirm it,” he said, adding, “If we validate it, great. My expectation is that we will not.”

My take on all this?  Despite our being down this road before on CFS — EBV, HHV-6, candida, enterovirus, parainfluenza, Lyme, to list a few putative causes — without much to show for it scientifically, I’m all for having multiple groups working on trying to find the cause of this awful disorder, even if it seems likely that there is more than one cause.

And judging from some of the pained, angry, and frustrated comments posted here, I’m clearly not alone.

As every card-carrying ID specialist knows, hardly anything is more common these days than patients with — and questions about — MRSA.

And one question I’ve been hearing increasingly these days is “Could I be getting my recurrent infection from Rufus?”

To which the answer is, unfortunately, yes.

(I had a dog named Rufus.  No offense intended to people out there actually named Rufus.)

Now along comes this article in the New York Times, which no doubt will stimulate the economy by prompting massive sales of hand-sanitizers, plus a flurry of trips to the vet to have Otto cultured.

(That’s Otto — our cat — in the picture, FYI.)

The article is self-explanatory — pets get MRSA, they can spread it to their owners and back — but did they have to put this caption under the picture of the dog?

INFECTION Don Graff of Belle Mead, N.J., with his English setter, Sunny. The dog contracted MRSA after a spider bite [emphasis added] but was given medication and has improved.

Spider bite!  If there’s one thing this medical writer should have figured out in her background research for the piece, it’s that MRSA infections are frequently mistaken for spider bites.

And I’d bet good money that Sunny (the English setter) never had one — for which I’m sure he’s quite relieved.

The alphabet soup that characterizes HIV therapeutics has always been one of its quirky challenges — for example, who could possibly know that 3TC, CBV, TZV, EPZ, and LAM all refer to drugs that are (or contain) lamivudine?

This drives our ID fellows nuts, and is certainly a strong deterrent to non-HIV specialists to learning the field.

(Maybe that’s why they pay us the big bucks… oh wait.)

And while we’ve grown comfortable with the abbreviations for the 3 oldest drug classes — NRTI, NNRTI, and PI — what are we to do with integrase inhibitors?  Some candidates:

• “II” — sounds funny when you say it (”eye-eye”), and could be confused with “eleven” depending on the font
• “INSTI” — for “integrase strand transfer inhibitor”; I’ve already seen this one around a lot, but have also seen it written “InSTI” (lower-case n), which is hard to type
• “INI” — for “INtegrase Inhibitor”; same upper vs lower-case issue as “INSTI”, and saying “INI” always has an anatomic (especially umbilical) connotation to it

Still not sure where we’ll end up with this one, but I suspect “INSTI” will rule the day.

Interested in researching the cause of AIDS?  Well go ahead and give NetBase Solutions’ healthBase a try, but don’t expect much in the way of filtering:

One of the most unfortunate examples is when you type in a search for “AIDS,” one of the listed causes of the disease is “Jew.” Really. The ridiculousness continues. When you click on Jew, you can see proper “Treatments” for Jews, “Drugs And Medications” for Jews and “Complications” for Jews. Apparently, “alcohol” and “coarse salt” are treatments to get rid of Jews, as is Dr. Pepper!

To be fair, the site seems to have cleaned up its act quite a bit since this report — here’s an example of a search I just did.  Most of the results are now much more plausible, but there’s still some wacky stuff there.  HIV is the number two cause of AIDS (number two?), and number five is “Abbott” — and I don’t they’re referring to the guy up there in the baseball uniform.

Look, I’m all for using the internet for medical information, and acknowledge I can barely function without it these days.  But this kind of advanced search engine takes lots and lots of human oversight, and for now the swarm of medical data out there in web-land can be as misleading as it is vast.

(Hat tip to Graeme M for the link.)

A few ID/HIV items to cover before summer “unofficially” ends (Sept 1?  Kids back at school?  Labor Day?):

• Will US Public Health officials recommend infant male circumcision to prevent HIV?  They might be considering such a move, but I suspect it will not be strongly promoted.  After all, none of the studies demonstrating its efficacy have been done in developed countries, and the pattern of the US epidemic — predominantly gay men and women of infected male partners — excludes the very group circumcision has been shown to protect:  circumcised heterosexual men.  Look for lots of CDC-ese in these guidelines, with terms such as “consider” and “might choose” and “be offered.”
• Getting lots of questions from my patients about the H1N1 vaccine.  Some decent interim answers here.  When available?  (Don’t know yet.)  Who will get it?  (The young, pregnant women, those at risk for severe flu)  Will there be enough?  (Maybe.)  Will the regular flu vaccine still be needed?  (Yes.)  Will this season’s flu vaccination programs/clinics/sites be civilized affairs with minimal panic, anger, waiting lines, frustration?  (I hope so, but the media will do their best to portray the situation otherwise.)
• Anyone see this movie on chronic Lyme?  Would love to hear your impressions.  I have not seen it — but this will definitely be a Netflix choice when it a appears on DVD.  (Note that I did not link to Netflix; I’m a big fan, but they are the most egregious purveyors of annoying pop-up ads in the universe right now.)
• How’s this for a new definition of contagious?  Be reassured:  my little teaser photo has been thoroughly autoclaved.

Enjoy the sunshine …

From the New York Times last week:

Health officials in Los Angeles said Friday that 22 actors in adult sex movies had contracted HIV since 2004, when a previous outbreak led to efforts to protect pornography industry employees.

(snip)

Occupational health officials have long argued that failing to require that performers wear condoms during intercourse and other acts is a violation of safe-workplace regulations.

But Deborah Gold, a senior safety engineer with the California occupational health department, said violations in the pornography industry were so widespread that the state had a difficult time cracking down.

My first response on reading this was amazement that the number was so small – and, remarkably, that number turned out to be even smaller (1 case) when further details emerged in the LA Times:

Los Angeles County public health officials backtracked Tuesday on their statements last week that at least 16 unpublicized cases of HIV in adult film performers had been reported to them since 2004.

Despite their release of data to The Times describing the cases as “adult film performers,” the county’s top health official acknowledged that the agency does not know whether any of those people were actively working as porn performers at the time of their positive test.

(snip)

The county lacks sufficient information to delve deeply into the cases and still has received no formal report on the most recent case.

“The system we have and the laws we have do not facilitate the kind of contact tracing and verification that we’d like to see,” [LA County Health Officer] Fielding said. “AIDS has been treated separately from other STDs.”

Bottom line here:  Aside from this well-researched cluster of cases reported in 2004 in the MMWR, we likely only have a vague idea how many cases of HIV are in, or linked, to this “industry” — which in addition to these semi-regulated companies undoubtedly has a huge underground as well.

And until we get rid of this bit of HIV exceptionalism cited above by Dr Fielding, appropriate contact tracing and partner notification are going to be very difficult indeed.

The gang from Canada is at it again, reviewing human rabies cases from bats and trying to make some sense of the data.

(For a summary of their outstanding prior paper in CID, read this.)

But before we get to their latest masterwork, here are some questions to ponder.  While doing so, keep in mind the practice of giving the rabies vaccine to a person with “bedroom exposure to a bat while sleeping, without evidence of direct physical contact”:

1. Are you more motivated by avoiding an “error of omission” (a mistake from not doing anything) than an “error of commission” (a mistake from doing something)?
2. Do you ever envision yourself being named in a lawsuit for failure to provide preventive therapy?
3. Do you sometimes imagine yourself cited in a newspaper as the doctor who said, “that isn’t necessary”, only then to have the patient in question be the one in a zillion who gets rabies?  (”We called Dr. Freepner, and he said not to do it.  Later, she was dead.”)
4. Do you feel you have a moral imperative to provide preventive therapy for a condition that will likely be fatal, no matter how unlikely it is that a patient will develop it?
5. Do you think cost, limited supply, and personnel issues should always be secondary considerations when making decisions about an individual?
6. When you read official guidelines that state that preventive vaccination “can be considered” in low but not zero risk circumstances, do you interpret that to mean it should be given?
7. Did you ever find yourself doing something clinically that you just knew made no sense, yet you did it anyway?

I suspect we all could answer “yes” to some, if not all, of the above questions.  These are not rational decisions, they are emotional ones.

Hence this latest paper is such a joy to read.  It provides yet more evidence that a policy of giving the rabies vaccine to patients with a “bedroom bat exposure” but no contact is, to be blunt, pretty ridiculous.  Some of the key numbers:

• Based on a telephone survey done in Quebec, fewer than 5% of people with such bat exposure get vaccinated.
• The estimated incidence of rabies due to this exposure is 1 case per 2.7 billion person-years.
• The number needed to treat to prevent a single case of human rabies from bedroom exposure (but no contact) is around 2.7 million.
• If all potential exposures were investigated and evaluated fully — after all, this is recommended in the guidelines, right? — this would require 49 physicians, 491 nurses, and 259 veterinarians working full-time for a full-year.  And this estimate does not even include administration of the rabies vaccine!

In short, what we are doing is absurd — we are giving preventive therapy to a small proportion of the potentially exposed only because they show up, and because we can.  It has very little to do with preventing actual cases of rabies, but it sure makes us and our patients feel better.

But if it’s indicated for those who show up, what about the 95% who don’t?  Solid quote:

Failure to intensely pursue a greater proportion of eligible persons then becomes paradoxical public policy: a recommendation that is known to be sustainable only if ignored by most eligible persons is of doubtful usefulness and questionable ethics.

So what are we to do?  The authors conclude that the recommendations for rabies vaccine for bedroom or other occult exposures “be reconsidered.”  I read that to mean, “be scrapped.”

And someone please point me in the direction of why some irrational physician behavior is so hard to shake.

As every house officer, hospitalist, intensivist, and ID doc knows, ceftriaxone and calcium have been contraindicated since 2007 due to fears of a potentially fatal precipitation of the two that led to the death of 5 neonates.

Pediatricians are fond of saying “kids are not small adults” (I should know), and if that’s true, it’s even more so that “neonates are not really really tiny adults.”

So it’s not surprising that follow-up in vitro studies have shown that this is unlikely to be a problem when the drugs are administered sequentially.  It’s also not surrising since no case of this fatal ceftriaxone/calcium precipitation had ever occurred in adults, even though ceftriaxone has been one of the most commonly-given antibiotics on the planet for decades.

But now we can give them to the same patient again, so long as the person is older than 28 days, and ceftriaxone and calcium are administered sequentially.

Hooray.

A couple of interesting ID guidelines out this week.  For those of you too busy with basketball, here are the relevant links:

• Guidance for Control of Infections with Carbapenem-Resistant or Carbapenemase-Producing Enterobacteriaceae in Acute Care Facilities. Identified in 24 states and now found “routinely” in New York and New Jersey, these carbapenem-resistant Enterobacteriaceae (”CPE” is much easier to write and say) are resistant to virtually every available antibiotic.  Although these guidelines say that micro labs must do the so-called modified Hodge test (MHT) on enteric gram negatives that have elevated MICs to carbapenems — but still are within the susceptible range — it’s been shown that ertapenem resistance provides a surrogate marker for this carbapenemase production.  Nice recent review of the (scary) topic here; quick summary of the guidelines here.
• Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents.  This massive tome (only 207 pages, 1,391 references) was originally released in an on-line version this past summer at aidsinfo.nih.gov, and I commented on it then in AIDS Clinical Care.  It is an absolutely critical resource, so valuable that I’ve referred to it numerous times since then.  But to spare you the task of reading through the whole thing again for revisions, I have gone right to the source — one of the people closely involved in putting the guidelines together — and asked him, so what’s changed since the summer?  Here’s his answer:  “The current published document notes that in HIV-infected adults who need treatment for HBV infection, treatment for both HIV and HBV infections should be initiated regardless of CD4 cell count.  For persons who wish to defer HIV therapy, only anti-HBV agents without any HIV-activity should be used.  Oh yeah, and some typos were corrected.”

Happy reading.

Ciprofloxacin-resistant Neisseria meningitidis has now been documented in the United States. Here’s a nice summary in Journal Watch, with two different perspectives.

I suppose we shouldn’t be surprised, but it did take a while.  (At least compared to that other famous neisseria-bug, Neisseria gonorrhoeae.)

Oh well.

Why is this important?  As every practicing ID doc/primary care provider/public health official knows, nothing strikes fear into a community quite like a case of invasive meningococcal disease.  Since household contacts of these cases have a many-fold increased risk of developing the disease, preventive therapy is recommended for any close contact — with “close” being defined nicely by one infection-control practitioner I know as “coughing distance.”

But we all know that prophylaxis extends way beyond this — not surprisingly, many more people request and get preventive therapy than actually need it, and in part this is because it’s so easy to do:  a single dose of ciprofloxacin.

Now this needs to be reconsidered.  Although it’s up to each local department of health to determine the recommended preventive therapy, I suspect it won’t be long before we’re all back to rifampin (four doses over two days, drug interactions) or a shot of ceftriaxone (ouch).