Is Lariam Malaria's Revenge?

The antimalarial compound mefloquine (also known by its former brand name) Lariam is a mainstay of malaria prophylaxis. First developed in the 1970's by the US Military, to whom malaria has historically inflicted a countless amount of suffering, it has risen to such wide use that it is one of the drugs included on the WHO's Essential Medication List. 

The advantage of mefloquine, in an era of malaria-drug resistance, was that it could be used as a preventative prophylactic in many malarious regions of the world (with parts of, for example Vietnam and Laos excepted). 

All medications have side effects, however one of mefloquine's is becoming so notorious that it was used as a plot device on ABC's Revenge (Lariam is not a character's name, though it would be a good one). The side effect in questions are neuropsychiatric in nature and include hallucinations and bizarre behavior. Milder side effects such as vivid dreams occur in 25% of those taking the medication. In the show mefloquine was employed as a surreptitious means of causing a character to appear mentally ill. 

These side effects are very real and have even had ramifications in the military's trial of Staff Sergeant Robert Barnes, convicted of killing 17 unarmed Afghanis. Barnes had no rationale to offer for his behavior and he had been on mefloquine in the past.  

While I believe it not likely that a medication can induce someone to commit such an act. Psychiatric disturbances induced by the drug, in the presence of severe underlying neurologic or psychiatric disorders, may exacerbate homicidal or paranoid thoughts to extreme levels. 

In today's legal environment, it will not be surprising when mefloquine use is cited as a mitigating factor in a legal proceeding. Fortunately, there are, in most cases, alternatives that can be used and the military has moved away from using mefloquine as its first line antimalarial. Additionally, more general usage has fallen off steeply since the FDA issued a black box warning regarding these side effects, which in some cases are permanent. 

But, the importance of antimalarial prophylaxis can not be understated. Malaria is a killer and in 2011 the US reached a 40 year high of malaria importations when nearly 2,000 cases were reported. In 2012, approximately 1600 imported cases occurred with 6 deaths; ominously only 6% (!!) of individuals reported adherence to a recommended anti-malarial regimen. 

Though mefloquine has serious side effects, the role of other anti-malarials is very important and non-compliance is a sure way to contract this dread disease. 

Faith Healers & Infectious Diseases: Never Should the Twain Meet

I think that more than any other category of illness (with the possible exception of cancer) infectious diseases, because of their penchant to be explosive, mysterious, and sometimes deadly, attract faith healers to the scene. It's not surprising since the germ theory of disease has really been an accepted part of medical practice for only about 150 years. 

The germ theory supplanted fallacious ideas about the four humors, miasmas, and even the evil eye as well as evil spirits. So it is not surprising that faith healers and mystics had roles in prior plagues, epidemics, and pandemics. Even in the modern era, witch doctors were prominent in the West Africa Ebola outbreak.

The movie 6 Souls, which I recently watched, addresses this topic with respect to the 1918 influenza pandemic. 

A few facts about the 1918 Spanish Flu:

• Caused by an H1N1 virus
• Spread was likely fostered by WWI
• Killed at least 50 million people worldwide

In 6 Souls, a faith healer offers his "skills" to those who fear the pandemic while having his own children inoculated (an anachronism since the influenza vaccine was not available at that time). The townspeople figure out this hypocrisy and punish the faith healer accordingly.

It's important to remember that during the time of the 1918 pandemic the cause of influenza--so named because it was originally thought to be due to the influence of the stars--had not been established. There was no vaccine, no antivirals, and no antibiotics to treat the secondary bacterial infections that were the chief cause of death. I am sure that desperate individuals, like those in the film, unfortunately turned to faith healers who preyed upon the relative ignorance and desperation of the world at that time. 

To me the pathbreaking nature of the germ theory stems from its ability to provide a rational, natural, and causal explanation for illness, sweeping away any appeal to the mystical and cutting off faith healers at the root. Even today, let alone in 1918, there are pockets of the population where the germ theory has not penetrated fully into the populace as evidenced by those who forego vaccination and the practitioners of Christian Science who eschew antibiotics. 

Measles at Disneyland: Donald Duck Can Give You More than Bird Flu

When I try to quantify the contagiousness of diseases, I always use measles as an example of extreme contagiousness. On stage giving lectures, I tell the audience that if I had measles they would all be exposed. Fortunately many were lucky enough to be vaccinated as children and grow up in an era with high levels of immunization, conferring the protection of the herd (i.e. herd immunity). 

However, largely due to the efforts of the anti-vaccine movement, there are pockets of this nation in which immunization levels have fallen to levels that have fostered the return of this dread disease that causes pneumonia in 1 of 20 who contract it and kills at a rate of 1 per 1000. 

One of these pockets happens to be California which is currently in the midst of its worst measles year in two decades. Making matters much worse for California is the report that approximately one dozen cases of measles have been reported to be linked to exposures at Disneyland. Of the original cases reported, half were unvaccinated despite being eligible for vaccination.

To measles, Disneyland is a viral-exchange center in which it will gain access to individuals from all over the world some of who may not be vaccinated because of their parents' (deadly) choices, some because they are too young, and some whose immune system precludes it. From Disneyland, the virus can be carried to other states and nations.

The anti-vaccine movement has now made Disneyland the happiest place on earth--not for the children of the world--but for a wretched virus.

Control of Tuberculosis: An Agent Carter & Captain America Size Task

The popular culture infectious diseases references continue.

On last night's premiere of ABC's new 1940s-era show, Marvel's Agent Carter a character who sneezes exclaims that she likely has tuberculosis. (For those of who might not know, in the Marvel universe, Agent Carter was an associate of Captain America.) 

In the 1940s tuberculosis was a serious fear in the US and pre-streptomycin (1944) there was no effective treatment available. Despite this, deaths had been declining due to improving socioeconomic and health conditions in the US. However, in 1945 the incidence rate was still was at an alarming 87 per 100,000. For comparison, it was 3 per 100,000 in 2013--a 96% reduction.

Though, as I've written before, there are vulnerabilities in our control of tuberculosis including drug resistance and the fact that the bulk of tuberculosis cases in the US occur in foreign-born individuals, who may present special challenges with respect to case identification, contact tracing, and treatment. 

With those caveats, a 96% reduction in tuberculosis cases in 70 years, in the absence of a vaccine program, was a Captain America seized feat.

Flu in 2015: Just the Facts

Right now the infectious disease in the headlines is one that deserves a lot of attention and is always at  the top of my list of infectious disease threats: influenza. 

Why?

We are in the beginnings of what will be a rough influenza season. About a week ago, we hit the epidemic threshold when 6.9% of all deaths reported were due to pneumonia and influenza, prompting the CDC to declare an epidemic. In Allegheny County (PA), where I live, there have been 2 deaths reported with close to 2000 cases reported. Pediatric deaths this season number 21 nationally. 

The season is particularly rough because of two factors:

1. The dominant strain is H3N2: Of the several strains of influenza that circulate, H3N2 seasons tend to be more severe likely due to the inherent virulence of the strain with severe cases occurring in the very young and the very old.

2. The vaccine mismatch: Each year viral strains predicted to be dominant are placed in the (now) 4-strain vaccine. This year the H3N2 included is a mismatch and not fully protected against what is the dominant strain. What happened was a new "drifted" variant of H3N2 emerged too late to be included in this year's vaccine.

It's important to note that when you read about numbers of cases confirmed at the county, state, or national level these numbers are only the tip of the iceberg as many physicians don't test formally for influenza because they make the diagnosis clinically and hospitals use tests of varying accuracy (false negatives occur with rapid tests). Chances are if you have symptoms such as fever, muscle aches, and cough you have influenza. Note, influenza doesn't cause gastrointestinal symptoms such as vomiting or diarrhea; it is a pet peeve of mine to see viral gastroenteritis labeled "flu".

What to do?

All is not lost though. There have been rough H3N2 dominated seasons with vaccine mismatch before. There are several things that should be helpful to minimize the impact.

1. Get a vaccination: Though the vaccine is mismatched there will likely be some protection afforded. You may still get the flu, but it could be less severe and less likely to require a visit to the hospital.

2. Low-tech social distancing: If you're sick with the flu, don't go to work; if you're children are sick, keep them out of school. Also, cough into the crook of your elbow not your hands (which you should wash a lot).

A children's nursery rhyme about influenza ("in flew Enza")

3. High risk groups should not try and wait it out. If you're pregnant, immunosuppressed, have underlying health conditions you should not try and wait for the virus to pass. You should see a healthcare provider who may prescribe an antiviral (see #3 below)

3. Doctors should prescribe antivirals: Doctors notoriously under prescribe antivirals for influenza. This is unfortunate as these medications can lessen the severity of influenza symptoms and their duration. There is some concern about shortages, but they are not widespread and people should be able to find drugs like Tamiflu but it may take some looking.

The traditional peak of the flu season is next month, in February, so expect for the season to worsen before it improves.

You can take solace in the fact that next year's vaccine will contain the mismatched strain missing from this year's strain. A larger point to understand about flu vaccines is that because of the genetics of the virus  coupled to our vaccine technology we have to change vaccines frequently and changes can't happen on the fly because of the long lead time to make the vaccine. The scenario occurring this season is something that we will always remain at risk of until a universal flu vaccine--one which doesn't have to be changed seasonally--is developed. That would be something more valuable than the Holy Grail.