LYMEPOLICYWONK: Embers Monkey Trials Part 5. Of Mice and Men and Monkeys.
The guidelines of the Infectious Diseases Society of America (IDSA) deny the existence of persistent infection. “There is no convincing evidence in North America for the persistence of B. burgdorferi in the skin of humans after treatment with antibiotic regimens known to be active against B. burgdorferi in vitro.” The Embers monkey research demonstrates persistence and is consistent with other animal model research. But, humans differ from animals in fundamental ways. So why not go further and demonstrate persistence in humans? The fact is that some experiments cannot be ethically conducted on humans. Hence, animal studies may be the only way research that can demonstrate a point. Such is the case with the Embers monkey trials. Embers demonstrated persistent bacteria notwithstanding 90 days of antibiotic treatment by using invasive tissue sampling that could not be conducted on humans.
Persistent infection notwithstanding antibiotics has also been demonstrated in mice, in ponies, in dogs and other animal models. While each animal is not the same as a human, the fact that persistence has been shown consistently over different animal models is compelling. And, as we’ve discussed, it is impossible to obtain this type of evidence from human because persistence is only found in the animal model by using invasive tissue sampling that cannot be performed on humans. Recall, that 100% of monkeys with persistence infection after treatment with antibiotics tested negative on the C6 commercial blood test. Hence, animal studies will be our highest level of evidence on the issue of persistence until better biomarkers for the disease are developed.
One of the ways that Embers demonstrated persistence was through the use of xenodiagnoses—where uninfected ticks were placed on infected monkeys and then examined for bacteria after feeding to repletion. Embers was able to demonstrate persistence in this manner. However, the study then raised the question whether these harvested bacteria were pathogenic—meaning do they cause disease. Embers suggested that this could be demonstrated by allowing the ticks that had fed on infected monkeys to feed on uninfected monkeys and then determining first, whether the ticks transmit the bacteria to the uninfected monkeys and, second, whether these monkeys developed the type of pathology that the monkeys in this study developed (heart impairment, etc.) This is the next question that Embers wants to pursue.
However, the first question—whether ticks infected through xenodiagnoses can infect other animals—has been answered in the mouse model by Barthold and colleagues. The Barthold study found that the ticks were able to transmit the bacteria to uninfected mice. As for whether the transmitted bacteria are pathogenic (that is, cause disease), these studies remain to be done.
One of the downsides to animal model studies is that we cannot ask the animal how it is feeling. The ability of humans to verbally report symptoms is an important piece of clinical information that animals cannot supply and, for now need to be the guiding principal in determining treatment.
This article is part of a series of reviewing the Embers findings for treatment of chronic and early disseminated Lyme disease as well as the effectiveness of the C6 antibody test. You can find these other posts here:
Embers ME, Barthold SW, Borda JT, Bowers L, Doyle L, Hodzic E, et al. Persistence of Borrelia burgdorferi in Rhesus Macaques following Antibiotic Treatment of Disseminated Infection. PLoS ONE. 2012;7(1):e29914.
Wormser GP, Dattwyler RJ, Shapiro ED, Halperin JJ, Steere AC, Klempner MS, et al. The clinical assessment, treatment, and prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006 Nov 1;43(9):1089-134
Barthold SW, Hodzic E, Imai DM, Feng S, Yang X, Luft BJ. Ineffectiveness of tigecycline against persistent Borrelia burgdorferi. Antimicrobial agents and chemotherapy. Feb;54(2):643-51.