Friday, August 29, 2014

Nowhere is it written that dangerous pathogens must have high basic reproduction ratios

As discussed previously, there are lessons aplenty to learn from the ongoing Ebola outbreak in West Africa. One simple lesson is this: Even with a low basic reproduction ratio (symbolized mathematically as R0), a pathogen can still spread widely under the right conditions.

Current estimates of the basic reproduction number for this Ebola outbreak are roughly in the range of 1.3-2.5. That's pretty modest when compared with other notorious agents. Estimates of R0 for smallpox outbreaks, for example, were typically 4-10 and those for cholera epidemics can be in the range of 3-12. Measles outbreaks can have R0 values of up to 18.

R0 itself is sometimes thought of as a surrogate for "epidemic potential". Certainly, and by definition, pathogens with high R0 spread quickly, whereas pathogens with lower R0 don't. Does this mean that pathogens possessing relatively low values of R0 have lower potential to harm public health?

Certainly not. In fact, pandemic influenza viruses, for example, often fall in the range 1.5-2.0. Pathogens associated with lower values of R0 can spread widely if control efforts are not effective. In the case of pandemic influenza, control measures include vaccination and handwashing. In the current Ebola situation, due to a range of social, economic, and political factors, it has been difficult to implement widespread, effective control measures. The infection has thus spread and will likely continue do so in the region.

Does this have implications for other infections? It absolutely does. One could imagine some theoretical pathogen, for example, that is spread predominantly by hands (call it "pathogen X") and that is not killed by alcohol based hand rub (ABHR). Then, in circumstances where ABHRs are used in place of handwashing, one might imagine that pathogen X could, over time, become widely prevalent, even if it does not possess a high R0. Pathogen X might be similar to Clostridium difficile; one estimate of R0 for C. difficile is in the range 0.5-1.5.

For this reason, we should not think only in terms of R0 for classifying pathogens as dangerous or not. While high R0 pathogens spread quickly, leaving little time to react and take action, Ebola in West Africa this year demonstrates that a pathogen possessing a more modest R0 can result in a dangerous public health situation. 

There's a story, which is possibly apocryphal, that Enrico Fermi once remarked that nowhere is it written that the laws of physics must be linear. I think there's an analogue that should be kept in mind in infectious disease epidemiology: Nowhere is it written that dangerous pathogens must have high R0.

(image source: ECDC

Sunday, August 17, 2014

Outbreaks and do-overs

Distribution map showing districts and cities reporting suspect cases of EbolaThe current Ebola outbreak in Western Africa has been remarkable in terms of the number of cases and deaths; length and geographic extent of the outbreak; and its designation as a public health emergency of international concern. What could have been done differently to change the course of events? Thorough analyses of the outbreak and response will be done, and that will take time, but I think there are several things to consider.

More international assistance early in the outbreak. Early intervention is a mantra of modern medicine and public health, and indeed organizations like MSF and others brought impressive resources to bear early in the outbreak. Yet, transmission wasn't controlled and the epidemic grew. More resources are needed urgently. In hindsight, greater multilateral international aid earlier in the outbreak was needed, but how can nations know when NGO efforts need supplemental resources? Perhaps studying the early phases of this outbreak can suggest a way.

Better communication. The social disruption evident in this event is painfully clear and may have been intensified by the difficulty of communicating important public health messages. Anecdotes of healthcare workers being attacked and of disbelief that Ebola virus even exists are but two examples.

Balanced communications in the United States was mixed. On the one hand, many valid messages were circulated, including that Ebola poses little risk to the US general population. On the other hand, one expert told Congress that
We know how to stop Ebola with strict infection control practices, which are already in widespread use in American hospitals, and by stopping it at the source in Africa.
The second part of the statement is true enough: stopping an outbreak before it spreads is canonical in public health. However, the first part of the statement implies that strict infection control practice can prevent infection of healthcare workers and others in a hospital. That's a little problematic. If that were so, there wouldn't be problems with hospital-associated infection in the US.

By that calculus, for example, the 2011 outbreak of KPC-producing Klebsiella pneumoniae at the NIH shouldn't have occurred -- and yet the infection control practice in that event was meticulous from the initial presentation of the patient at the facility. What if an Ebola patient isn't recognized immediately when presenting at a US emergency department? And if a case is recognized, is infection control as it is actually carried out in practice likely to be effective? Such questions apply to any nosocomial pathogen, and I think it's important to ask: Given that KPC escaped a patient's room even with full precautions, why not Ebola?

Drug therapy. There are no approved treatments for, or vaccines against, Ebola virus infection. The development of new drugs is a scientifically, economically, and politically complex activity. The urgent need for new antibiotics, for example, has been discussed in connection with a large and growing need. The CDC recently reported that
Each year in the United States, at least 2 million people become infected with bacteria that are resistant to antibiotics and at least 23,000 people die each year as a direct result of these infections. Many more people die from other conditions that were complicated by an antibiotic-resistant infection. 
That's a massive burden of disease compared to the Ebola outbreak at present. Every case of any infection deserves effective management, but where is the incentive for drug development for Ebola and other exotic, low incidence infections? It is literally taking on act of Congress to help spur new antibiotic drug development in the US. Clearly drug therapies for Ebola would have been beneficial in this outbreak, and how to incentivize development seems an important question. In the absence of effective therapies and drug regimens, misinformation about bogus cures inevitably spreads and requires time and resources to counter.

Certainly these and related issues will be discussed and studied in depth in the coming months and years. Answers to the question of what could we do better next time must be found, because there will be future outbreaks of virulent emerging infections. How will we react?

(image source: CDC

Thursday, August 7, 2014

Hepatitis in the summer of '69

http://upload.wikimedia.org/wikipedia/commons/f/f5/Hepatitis_A_virus_02.jpgA remarkable epidemic took place in 1969 at the College of the Holy Cross in Worcester, Massachusetts. In the autumn of that year, the college was forced to cancel the football season after the first two games due to an outbreak of hepatitis. 

The first football game of that season was against Harvard and took place on September 27th; Holy Cross lost 13-0. The team appeared sluggish to fans, and one player missed the game due to fever. Michael Neagle described what happened next in a 2004 essay:
Players began dropping out during the week leading up to the team’s next game at Dartmouth [on October 4th]. What had been described as a “flu bug” by newspapers during the week was confirmed as hepatitis the day of the game. Eight players did not make the trip because of illness. Some got sick on the drive up. More were sidelined when they fell ill during the game . . .
Holy Cross lost 38-6. There were interesting facets to this outbreak, as told in a 1972 Associated Press story:
The outbreak was somewhat puzzling because faculty members, the freshman football team, and others on the Worcester, Mass., campus before formal opening of classes were not affected. Food services were studied and did not produce suspicious leads.
Neagle describes what was eventually pieced together:
. . . [the] season was doomed after just the second day of practice. On Aug. 29, a hot summer day in Worcester, on the practice fields where the Hart Center now stands, players drank water from a faucet that was later found to be contaminated with hepatitis. Though investigators almost immediately suspected the drinking fountain as the source of the illness, it took nearly a year to determine conclusively the sequence of events that led to the contamination.

On that fateful day, firefighters battled a blaze on nearby Cambridge Street. This caused a drop in the water pressure, allowing ground water to seep into the practice field’s irrigation system. That ground water had been contaminated by a group of children living near the practice facility who were already infected with hepatitis. Once the players drank from the contaminated faucet, they too became infected.
A 1972 study by Morse et al described the epidemiology of the event:
Of 97 persons exposed, 90 were infected, 32 experienced typical icteric [jaundice] disease, 22 were anicteric but symptomatic, and 36 asymptomatic players were recognized as having significantly elevated serum glutamic pyruvic transaminase values (> 100 units). Other athletes, using the same facilities but arriving six days after the established date of exposure, were unaffected. The decision to obtain blood samples from the entire team, as soon as the initial cases were recognized, resulted in the demonstration of an unexpectedly high attack rate of 93% . . .
An attack rate of 93% is remarkable, but potentially consistent with a high inoculum that could have been delivered by contaminated water. Friedman et al returned to the event in a 1985 study. Using a radioimmunoassay to test stored serum samples for IgM antibody to hepatitis A virus, they found that
Only individuals with icteric hepatitis were found to have IgM anti-HAV in serum; those with presumed anicteric illness were shown not to be infected with hepatitis A virus. The attack rate was thus only 34%, not 93% as originally reported, and the incidence of icteric illness in those infected was 100%, not 33%.
What made the other players sick thus remains a mystery, though one can speculate about potential pathogens in the environment that could have contaminated the practice field faucet given the negative pressure scenario. I'm always intrigued by disease events that seem so open-and-shut based on the technology of one era but less so when analyzed with the technology of another. This is one of those events.

(image source: Wikipedia)

Friday, August 1, 2014

Public health events and open source software

As a quick follow up to the last post on Ebola and the one before that on open source software and computing, a great example of the intersection of public health, computing, and free analytic software has recently been published. In his Ecologically Oriented blog, Jim Bouldin has written about some of the statistics of the West African Ebola outbreak from its inception. In the piece he posts R code for scraping and analyzing up-to-date WHO data on cases and deaths in Africa. The post illustrates how data can be acquired and analyzed using robust open source software and how results -- including the code used to generate them -- can be promulgated rapidly. Bravo!