Closer to the Cure? More on Lyme drug combos - latest study

Front Microbiol. 2016 May 23;7:743. doi: 10.3389/fmicb.2016.00743. eCollection 2016.

A Drug Combination Screen Identifies Drugs Active against Amoxicillin-Induced Round Bodies of In Vitro Borrelia burgdorferi Persisters from an FDA Drug Library.

Feng J1, Shi W1, Zhang S1, Sullivan D1, Auwaerter PG2, Zhang Y1.

Author information

• 1Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore MD, USA.
• 2Fisher Center for Environmental Infectious Diseases, School of Medicine, Johns Hopkins University, Baltimore MD, USA.

Abstract

Although currently recommended antibiotics for Lyme disease such as doxycycline or amoxicillin cure the majority of the patients, about 10-20% of patients treated for Lyme disease may experience lingering symptoms including fatigue, pain, or joint and muscle aches.

Under experimental stress conditions such as starvation or antibiotic exposure, Borrelia burgdorferi can develop round body forms, which are a type of persister bacteria that appear resistant in vitro to customary first-line antibiotics for Lyme disease.

To identify more effective drugs with activity against the round body form of B. burgdorferi, we established a round body persister model induced by exposure to amoxicillin (50 μg/ml) and then screened the Food and Drug Administration drug library consisting of 1581 drug compounds and also 22 drug combinations using the SYBR Green I/propidium iodide viability assay.

We identified 23 drug candidates that have higher activity against the round bodies of B. burgdorferi than either amoxicillin or doxycycline. Eleven individual drugs scored better than metronidazole and tinidazole which have been previously described to be active against round bodies.

In this amoxicillin-induced round body model, some drug candidates such as daptomycin and clofazimine also displayed enhanced activity which was similar to a previous screen against stationary phase B. burgdorferi persisters not exposure to amoxicillin.

Additional candidate drugs active against round bodies identified include artemisinin, ciprofloxacin, nifuroxime, fosfomycin, chlortetracycline, sulfacetamide, sulfamethoxypyridazine and sulfathiozole.

Two triple drug combinations had the highest activity against amoxicillin-induced round bodies and stationary phase B. burgdorferi persisters: artemisinin/cefoperazone/doxycycline and sulfachlorpyridazine/daptomycin/doxycycline.

These findings confirm and extend previous findings that certain drug combinations have superior activity against B. burgdorferi persisters in vitro, even when pre-treated with amoxicillin. These findings may have implications for improved treatment of Lyme disease. 

KEYWORDS: 

Borrelia burgdorferi; FDA drug library; drug combination drug screen; persisters; round bodies

PMID:

 

27242757

 

[PubMed] 

Link Here-  http://www.ncbi.nlm.nih.gov/pubmed/27242757

UPDATE: Body of missing student found

By The Cougar News Services May 30, 2016

The body of missing 22-year-old Jennifer Hollis was found early Monday morning. According to a Facebook page set up by her family, Hollis took her own life after a long struggle with Lyme disease.

"The problem is that Jennifer suffered an absolutely horrible illness called Lyme disease which bore a pain that is unbearable for those who are inflicted," Hollis' family said in a Facebook post. "Most people didn't realize this about Jennifer. She suffered in silence. She tried to mask her pain and suffering with her infectious smile, laughter and enduring love of life."

http://thedailycougar.com/2016/05/30/update-body-missing-student-found/

Borrelia bacteria hides inside parasitic worms, causing chronic brain diseases

Lyme discovery: Borrelia bacteria hides inside parasitic worms, causing chronic brain diseases

Posted by Press Release on May 23, 2016 

The examination of autopsied brain tissues from patients who died of serious neurological conditions has revealed that many tick-borne infections, such as Lyme disease, go undiagnosed and untreated. Board-certified pathologist, Alan B. MacDonald, MD, says his research shows "tick infections are not easily detected with routine tests, nor are they easily cured with short courses of antibiotics."

Borrelia burgdorferi/CDC

MacDonald presented his findings Thursday on Capitol Hill, in the Rayburn House Office Building, at a forum to explore the scientific, economic, and policy challenges posed by the epidemic of Lyme disease and associated tick-borne illnesses.

MacDonald found three Borrelia pathogens, including B. burgdorferi the causative agent of Lyme disease, thriving inside parasitic nematode worms, worm eggs or larvae in the brain tissue of nineteen deceased patients. These microscopic worms are endosymbionts, meaning the Borrelia bacteria dwell inside the worms. A tick bite delivers the nematode into the human body...

Read the rest of the story:

http://outbreaknewstoday.com/lyme-discovery-borrelia-bacteria-hides-inside-parasitic-worms-causing-chronic-brain-diseases-13216/

For the Love of Worms -- The Ivermectin Man

William Campbell For the Love of Worms

A fascination with wiggly creatures led William Campbell to a cure for one of mankind's worst diseases (River Blindness) —and earned him a Nobel Prize.

By Leslie Garisto Pfaff | April 15, 2016

Lyme disease guidelines are in the top 5% of all research articles

We are proud to announce that Altmetrics has affirmed the evidence treatment guidelines for Lyme disease are in the top 5% of all research articles. Altmetrics citation-based metrics consists of qualitative data that tracks research publications and their ability to reach and influence their audience. According to Altmetrics, their data encompassed more than 107,000 downloads.

After the guidelines by the Infectious Disease Society of America (IDSA) had been criticized for not addressing the severity of chronic manifestations, ILADS published guidelines in hopes of filling the gap. Due to the growing number of chronic conditions, controversy over treatment, and high level of public concern, ILADS composed their guidelines based on The Grading of Recommendations Assessment Development and Evaluation (GRADE). ILADS assessed and graded available research evidence and shifted their guidelines from evidence to recommendations, providing individuals with a transparent and systematic framework. GRADE took in account the harm and benefits of interventions, patient preferences, and values.

The extended antibiotics recommendation provided by the ILADS guidelines has already been adopted, and that notion is continuing to grow. According to a survey in 2011, 50% of New England physicians believe long-term use of antibiotics was "sometimes useful," while 25% thought it was "always useful." The ILADS guidelines have been incorporated in the ILADS physician training program, accepted by the National Guideline Clearing House, where it can be seen on their website and professional conferences, and it was published in the open accessed journal Expert Review of Anti-Infective Therapy.

To view and download ILADS guidelines, visit: Link to 2014 ILADS guidelines at Expert Review of Anti-infective Therapy

Four news articles about Lyme

Lyme Disease Patients Seek Help As Doctors Debate Treatment

Lyme Disease Info Bill Passes NYS Senate

Niagara (NY) Legislature approves pamphlets to warn of Lyme disease

Canada:

Alberta doc pushes for broader guidelines to pinpoint Lyme disease as tick fears rise

Efficacy and safety of pharmacological agents in the treatment of early Lyme disease

Efficacy and safety of pharmacological agents in the treatment of erythema migrans in early Lyme borreliosis-systematic review protocol

Thu May 19, 2016 5:14 am (PDT) . Posted by: 

"Rick Laferriere" ri_lymeinfo 

*Efficacy and safety of pharmacological agents in the treatment of 
erythema migrans in early Lyme borreliosis-systematic review protocol *
Torbahn G, Hofmann H, Allert R, Freitag MH, Dersch R, Fingerle V, Sommer 
H, Motschall E, Meerpohl JJ, Schmucker C.
/Systematic Reviews/. 2016 May 3; 5(1):73.

http://dx.doi.org/10.1186/s13643-016-0251-3

Abstract

*Background*
Erythema migrans represents an early cutaneous and most common 
manifestation of Lyme borreliosis. Recommendations regarding 
pharmacological agents, dose and duration of treatment are subject of 
intense debate. This review aims to explore differences in efficacy and 
safety between pharmacological treatments and control treatment.

*Methods*
To identify relevant studies, we will conduct a systematic literature 
search. We will include randomised controlled trials (RCTs) and 
non-RCTs. Eligible comparative studies need to (1) consider patients 
with a diagnosis of erythema migrans resulting from Lyme borreliosis and 
(2) compare different pharmacological agents against each other, against 
any other non-pharmacological treatment, placebo or no treatment.

Two review authors will independently assess included studies for risk 
of bias according to the methods of the Cochrane Handbook for Systematic 
Reviews of Interventions and related to specific study designs. We will 
address patient-relevant outcomes including clinical remission of 
cutaneous symptoms, any treatment-related adverse events, quality of 
life and progressive symptoms such as neuroborreliosis or Lyme carditis 
and flu-like symptoms. Provided that the identified trials are 
comparable in terms of clinical issues, combined estimates will be 
provided.

Estimations of treatment effects will be calculated based on a random 
effects model. Heterogeneity will be evaluated based on /I/^/2/ and 
chi-square test. In case of significant heterogeneity, a pooled estimate 
will not be provided, but heterogeneity will be investigated on the 
basis of methodological and clinical study aspects. We plan subgroup 
analysis to reveal potential differences in the effect estimates between 
patient populations and treatment specifications.

We will consider risk of bias using sensitivity analyses to decide 
whether to rely on the pooled estimates. The quality of a body of 
evidence for individual outcomes will be assessed using the GRADE approach.

*Discussion*
Benefits and harms of pharmacological treatment in erythema migrans have 
not yet been adequately assessed. This systematic review will evaluate 
and summarise available evidence addressing benefits and harms of 
different pharmacological treatments. In addition, this summary of 
clinical evidence will inform decision-making between clinicians and 
patients and will play an important part in patient care.

http://dx.doi.org/10.1186/s13643-016-0251-3

*Free, full text (pdf file, 437 KB)*:
http://systematicreviewsjournal.biomedcentral.com/track/pdf/10.1186/s13643-016-0251-3?site=systematicreviewsjournal.biomedcentral.com
or http://tinyurl.com/hchng68

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The mission of LymeInfo is to keep you informed of issues that might be of interest to Lyme disease patients.   Postings are not meant to imply that we agree with the content of all items we distribute.

For Lyme information, see:
http://www.LymeInfo.net

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A prospective evaluation of chronic Babesia microti infection

Thu May 19, 2016 11:23 am (PDT) . Posted by: 

"Rick Laferriere"  

*A prospective evaluation of chronic /Babesia microti/ infection in 
seroreactive blood donors*
Bloch, E. M., Levin, A. E., Williamson, P. C., Cyrus, S., Shaz, B. H., 
Kessler, D., Gorlin, J., Bruhn, R., Lee, T.-H., Montalvo, L., Kamel, H. 
and Busch, M. P.
/Transfusion/, online first May 17, 2016.

http://doi.org/10.1111/trf.13617

Abstract

*BACKGROUND*
/Babesia microti/ is the foremost infectious risk to the US blood supply 
for which a Food and Drug Administration (FDA)-licensed test is 
unavailable for donation screening. Characterization of the antibody 
response to /B. microti/ and correlation with parasitemia is necessary 
to guide screening and donor management policies.

*STUDY DESIGN AND METHODS*
During an FDA licensure trial, blood donors were prospectively screened 
(July-November 2013) using a /B. microti-/specific antibody enzyme 
immunoassay (EIA, Immunetics) in highly endemic (New York [NY]; 
n = 13,688), moderately endemic (Minnesota [MN]; n = 4583), and 
nonendemic (New Mexico [NM]; n = 8451) regions. Blood donors with 
repeat-reactive (RR) results participated in a 12-month prospective 
cohort study using /B. microti/ EIA, immunofluorescent assay, polymerase 
chain reaction (PCR), blood smear, and clinical questionnaire.

*RESULTS*
Thirty-seven (61.67%; 24 NY, seven MN, six NM) of 60 eligible RR donors 
enrolled in the study; 20 of 37 (54%) completed the 12-month follow-up 
visit of which 15 (75%) were still seroreactive. Nine PCR-positive 
donors were identified during index screening; five participated in the 
follow-up study, three were PCR positive at 6 months, and two remained 
positive at final follow-up (378 and 404 days). Most RR donors displayed 
low-level seroreactivity that was either stable or waning during 
follow-up. The level and pattern of reactivity correlated poorly with 
PCR positivity.

*CONCLUSION*
The findings indicate prolonged seropositivity in blood donors. Although 
rare, asymptomatic, persistent PCR positivity supports the current 
policy of indefinite deferral for donors with a history of babesiosis or 
positive test results. Repeat testing by PCR and serology will be 
necessary if reinstatement is to be considered.

http://doi.org/10.1111/trf.13617

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The mission of LymeInfo is to keep you informed of issues that might be of interest to Lyme disease patients.   Postings are not meant to imply that we agree with the content of all items we distribute.

For Lyme information, see:
http://www.LymeInfo.net

Please tell others how to subscribe to this group:
mailto:LymeInfo-subscribe@yahoogroups.com

Reflections on Canada's Lyme conference

https://www.linkedin.com/pulse/canada-lets-lead-lyme-charge-lori-dennis-ma-rp?published=t

Lyme Bacteria Hides Inside Parasitic Worms, Causing Chronic Brain Diseases

OK, this sounds pretty gross, but better to know than to not know, right?

Lyme Bacteria Hides Inside Parasitic Worms, Causing Chronic Brain Diseases 
www.prnewswire.com

http://www.prnewswire.com/news-releases/lyme-bacteria-hides-inside-parasitic
-worms-causing-chronic-brain-diseases-300270742.html