Archive for the ‘research’ Category

Bb Endemic in Ticks & Hosts Outer Banks of North Carolina

http://doi.org/10.1111/zph.12302

Abstract

The spirochaete Borrelia burgdorferi associated with Lyme disease was detected in questing ticks and rodents during a period of 18 years, 1991–2009, at five locations on the Outer Banks of North Carolina. The black-legged tick Ixodes scapularis was collected at varied intervals between 1991 and 2009 and examined for B. burgdorferi. The white-footed mouse Peromyscus leucopus, house mouse Mus musculus marsh rice rat Oryzomys palustris, marsh rabbit Sylvilagus palustris, eastern cottontail Sylvilagus floridanus and six-lined racerunner Cnemidophorus sexlineatus were live-trapped, and their tissues cultured to isolate spirochaetes.

Borrelia burgdorferi isolates were obtained from questing adult I. scapularis and engorged I. scapularis removed from P. leucopus, O. palustris and S. floridanus. The prevalence of B. burgdorferi infection was variable at different times and sites ranging from 7 to 14% of examined questing I. scapularis. Mitochondrial (16S) rRNA gene phylogenetic analysis from 65 adult I. scapularis identified 12 haplotypes in two major clades. Nine haplotypes were associated with northern/Midwestern I. scapularis populations and three with southern I. scapularis populations. Sixteen isolates obtained from tick hosts in 2005 were confirmed to be B. burgdorferi by amplifying and sequencing of 16S rRNA and 5S-23S intergenic spacer fragments. The sequences had 98–99% identity to B. burgdorferi sensu stricto strains B31, JD1 and M11p.

Taken together, these studies indicate that B. burgdorferi sensu stricto is endemic in questing I. scapularis and mammalian tick hosts on the Outer Banks of North Carolina.

Bb Infects Murine Bone and causes Trabecular Bone Loss

http://iai.asm.org/content/early/2016/12/08/IAI.00781-16

Abstract

Lyme disease is caused by members of the Borrelia burgdorferi sensu lato species complex. Arthritis is a well-known late-stage pathology of Lyme disease, but the effects of B. burgdorferi infection on bone at sites other than articular surfaces are largely unknown. In this study, we investigated whether B. burgdorferi infection affects bone health in mice.

In mice inoculated with B. burgdorferi or vehicle (mock infection), we
measured the presence of B. burgdorferi DNA in bones, bone mineral
density (BMD), bone formation rates, biomechanical properties, cellular
composition, and two- and three-dimensional features of bone
microarchitecture. B. burgdorferi DNA was detected in bone. In the
long bones, increasing B. burgdorferi DNA copy number correlated with
reduction in areal and trabecular volumetric BMD. Trabecular regions of
femora exhibited significant, copy number-correlated microarchitectural
disruption, but BMD, microarchitectural, or biomechanical properties of
cortical bone were not affected.

Bone loss in tibiae was not due to increased osteoclast numbers or
bone-resorbing surface area, but was associated with reduced osteoblast numbers, implying that bone loss in long bones was due to impaired bone building. Osteoid-producing and mineralization activities of existing osteoblasts were unaffected by infection. Therefore, deterioration of trabecular bone was not dependent on inhibition of osteoblast function, but was more likely caused by blockade of osteoblastogenesis, reduced osteoblast survival, and/or induction of osteoblast death.

Together, these data represent the first evidence that B. burgdorferi infection induces bone loss in mice, and suggest that this phenotype results from inhibition of bone building rather than increased bone resorption.

Standardized Symptom Measurement of Early Lyme Disease Over Time

http://acn.oxfordjournals.org/content/early/2016/11/23/arclin.acw098.abstract

Abstract

Objective Understanding the Lyme disease (LD) literature is challenging given the lack of consistent methodology and standardized measurement of symptoms and the impact on functioning. This prospective study incorporates well-validated measures to capture the symptom picture of individuals with early LD from time of diagnosis through 6-months post-treatment.

Method One hundred seven patients with confirmed early LD and 26 healthy controls were evaluated using standardized instruments for pain, fatigue, depressive symptoms, functional impact, and cognitive functioning.

Results Prior to antibiotic treatment, patients experience notable symptoms of fatigue and pain statistically higher than controls. After treatment, there are no group differences, suggesting that symptoms resolve and that there are no residual cognitive impairments at the level of group analysis. However, using subgroup analyses, some individuals experience persistent symptoms that lead to functional decline and these individuals can be identified immediately post-completion of standard antibiotic treatment using well-validated symptom measures.

Conclusions Overall, the findings suggest that ideally-treated early LD patients recover well and experience symptom resolution over time, though a small subgroup continue to suffer with symptoms that lead to functional decline. The authors discuss use of standardized instruments for identification of individuals who warrant further clinical follow-up.

 

Syphilis Re-emerging

These findings are important for MSIDS (multi systemic infectious disease disease syndrome  or Lyme with friends) patients because people with false positive testing results for Syphilis may have Lyme Disease.  https://www.sharecare.com/health/stds-sexually-transmitted-diseases/why-false-positive-test-syphilis

When writer of The Joy Luck Club, Amy Tan, asked her doctor to test her for Lyme he insisted she didn’t have LD because it was too rare and proceeded to test her for Syphilis. https://www.amytan.net/lyme-disease.html

http://www.nature.com/articles/nmicrobiol2016245

Origin of modern syphilis and emergence of a pandemic Treponema pallidum cluster
Natasha Arora, Verena J. Schuenemann[…]Homayoun C. Bagheri
Nature Microbiology 2, Article number: 16245 (2016)
doi:10.1038/nmicrobiol.2016.245
Published online:
05 December 2016

Abstract
The abrupt onslaught of the syphilis pandemic that started in the late fifteenth century established this devastating infectious disease as one of the most feared in human history1. Surprisingly, despite the availability of effective antibiotic treatment since the mid-twentieth century, this bacterial infection, which is caused by Treponema pallidum subsp. pallidum (TPA), has been re-emerging globally in the last few decades with an estimated 10.6 million cases in 2008 (ref. 2). Although resistance to penicillin has not yet been identified, an increasing number of strains fail to respond to the second-line antibiotic azithromycin3. Little is known about the genetic patterns in current infections or the evolutionary origins of the disease due to the low quantities of treponemal DNA in clinical samples and difficulties in cultivating the pathogen4. Here, we used DNA capture and whole-genome sequencing to successfully interrogate genome-wide variation from syphilis patient specimens, combined with laboratory samples of TPA and two other subspecies. Phylogenetic comparisons based on the sequenced genomes indicate that the TPA strains examined share a common ancestor after the fifteenth century, within the early modern era. Moreover, most contemporary strains are azithromycin-resistant and are members of a globally dominant cluster, named here as SS14-Ω. The cluster diversified from a common ancestor in the mid-twentieth century subsequent to the discovery of antibiotics. Its recent phylogenetic divergence and global presence point to the emergence of a pandemic strain cluster.

http://www.theatlantic.com/health/archive/2016/06/how-syphilis-came-roaring-back/488375/

“Perhaps most concerning, the past two years have seen a cluster of cases of syphilis of the eye, and a rise in cases of congenital syphilis—something even developing countries have been able to eliminate.

The disease is curable with antibiotics, but it’s a bit of a secret agent, transmissible through almost every sexual means and erupting as a tiny lesion about a month after exposure. At various stages of the infection, it might cause no symptoms or a puzzling array of them. If gone undiagnosed, it can cause everything from disfigurement to seizures.”

https://www.poz.com/article/secret-life-syphilis  By Daniel Wolfe

“TB, rare cancers and pneumonias — all of these were documented, if unusual, expressions of syphilis before the antibiotic era,” says Joan McKenna, a research physiologist whose 1986 article in the journal Medical Hypotheses first presented the AIDS-syphilis connection.
McKenna found an unlikely ally in Sandra Larsen, MD, then a syphilis expert at the CDC. “The clinical manifestations of syphilis, which have taken various forms over the century, have now been transformed to mimic the appearance of the opportunistic infections and cancers that may accompany HIV infection, as well as the clinical symptoms of AIDS itself,” Larsen wrote. McKenna began sending AIDS patients in for confirmatory syphilis tests, even when they’d first tested negative. “We had people showing up negative on the initial tests even when they had known infections and tertiary symptoms,” she says. “These syphilis cases were being missed.”
Others interested in the AIDS-syphilis link scrapped the theory in the late ’80s, when doctors treating HIVers with IV antibiotics found that they still sickened and died. But the idea that a new form of chronic syphilis may be mistaken for HIV-related infections, has been kept alive by Toronto researcher John Scythes and colleague Colman Jones. “Repeated studies show that syphilis infection and, particularly, reinfection, may not be detected with current tests,” Jones says. “So some of those we say are cured of syphilis may instead be being missed. The CDC estimated there were 325,000 cases of untreated syphilis at the end of the 1970s. Where did they go?”
New research into syphilis’ suburban cousin — Borrelia burgdorferi, the spirochete that causes Lyme disease — has bolstered the case for better tests. Recently researchers have successfully cultured B. burgdorferi from the blood of Lyme disease patients supposedly cured by antibiotics and found a cyst-like form of the Lyme spirochete, adopted in response to meds, which is often missed with standard microscopy. Might syphilis similarly adapt to avoid antibiotics and detection? “There is much we do not yet know,” says Willy Burgdorfer, PhD, the Lyme spirochete’s discoverer. “But T. pallidum does behave in ways very similar to B. burgdorferi.”

http://www.environmentalevolution.org/environmentalevolution.org/Fair_Use_files/312-Roundbodies.pdf (2009)

“Far from eradicating syphilis, antibiotics are driving the disease underground and increasing the difficulty of detection. Although the incidence of disease has more than tripled since 1955, the chancre and secondary rash no longer are commonly seen. Undoubtedly, some of these lesions are being suppressed and the disease masked by the indiscriminate use of antibiotics. The ominous prospect of a widespread resurgence of the disease in its tertiary forms looms ahead” (Pereyra and Voller, 1970)…..We urge that the possible direct causal involvement of spirochetes and their round bodies to symptoms of immune deficiency be carefully and vigorously investigated.”

http://www.academia.edu/5302525/Syphilis_in_the_AIDS_Era_Diagnostic_Dilemma_and_Therapeutic_Challenge_co-authored_with_John_Scythes_

This review argues that syphilis has been underdiagnosed and under treated… we suggest that latent syphilis is a chronic active immunological condition that drives the AIDS process and that non-treponemal tests have failed to associate syphilis with immune suppression since this screening concept was developed in 1906. In light of the overwhelming association between a past history of syphilis and HIV seroconversion, more sensitive tools, including recombinant antigen-based immunological tests and direct detection (PCR) technology, are needed to adequately assess the role of latent syphilis in persons with HIV/AIDS. Repeating older syphilis reinoculation studies may help establish a successful animal model for AIDS, and resolve many paradoxes in HIV science.

https://www.cdc.gov/std/syphilis/stdfact-syphilis-detailed.htm  (Syphilis fact sheet with symptoms)

https://www.cdc.gov/std/stats15/tables/1.htm  In the US in 2015, there were nearly 75,000 cases of Syphilis.

https://www.statnews.com/2016/03/01/syphilis-las-vegas/  Syphilis has more than doubled in Las Vegas since 2012.

http://wreg.com/2016/09/21/cases-of-syphilis-on-the-rise-in-mississippi/  Health Department in Mississippi says Syphilis cases are up 60% this year.

Cases of syphilis on the rise in Mississippi

 

Blood Screening for Babesia

http://doi.org/10.1056/NEJMoa1600897

Screening for Babesia microti in the U.S. Blood Supply
Erin D. Moritz, Ph.D., Colleen S. Winton, S.B.B. (A.S.C.P.), Laura Tonnetti, Ph.D., Rebecca L. Townsend, B.A., Victor P. Berardi, Mary-Ellen Hewins, B.S., Karen E. Weeks, B.S., Roger Y. Dodd, Ph.D., and Susan L. Stramer, Ph.D.
New England Journal of Medicine 2016; 375:2236-2245. Online first, December 8, 2016.

Abstract

Background
Babesia microti, a tickborne intraerythrocytic parasite that can be transmitted by means of blood transfusion, is responsible for the majority of cases of transfusion-transmitted babesiosis in the United States. However, no licensed test exists for screening for B. microti in donated blood. We assessed data from a large-scale, investigational product-release screening and donor follow-up program.

Methods
From June 2012 through September 2014, we performed arrayed fluorescence immunoassays (AFIAs) for B. microti antibodies and real-time polymerase-chain-reaction (PCR) assays for B. microti DNA on blood-donation samples obtained in Connecticut, Massachusetts, Minnesota, and Wisconsin. We determined parasite loads with the use of quantitative PCR testing and assessed infectivity by means of the inoculation of hamsters and the subsequent examination for parasitemia. Donors with test-reactive samples were followed. Using data on cases of transfusion-transmitted babesiosis, we compared the proportions of screened versus unscreened donations that were infectious.

Results
Of 89,153 blood-donation samples tested, 335 (0.38%) were confirmed to be positive, of which 67 (20%) were PCR-positive; 9 samples were antibody-negative (i.e., 1 antibody-negative sample per 9906 screened samples), representing 13% of all PCR-positive samples. PCR-positive samples were identified all through the year; antibody-negative infections occurred from June through September. Approximately one third of the red-cell samples from PCR-positive or high-titer AFIA-positive donations infected hamsters. Follow-up showed DNA clearance in 86% of the donors but antibody seroreversion in 8% after 1 year. In Connecticut and Massachusetts, no reported cases of transfusion-transmitted babesiosis were associated with screened donations (i.e., 0 cases per 75,331 screened donations), as compared with 14 cases per 253,031 unscreened donations (i.e., 1 case per 18,074 unscreened donations) (odds ratio, 8.6; 95% confidence interval, 0.51 to 144; P=0.05). Overall, 29 cases of transfusion-transmitted babesiosis were linked to blood from infected donors, including blood obtained from 10 donors whose samples tested positive on the PCR assay 2 to 7 months after the implicated donation.

Conclusions
Blood-donation screening for antibodies to and DNA from B. microti was associated with a decrease in the risk of transfusion-transmitted babesiosis. (Funded by the American Red Cross and Imugen; ClinicalTrials.gov number, NCT01528449 http://clinicaltrials.gov/show/NCT01528449.)

***For more on Babesia:   https://madisonarealymesupportgroup.com/2011/09/25/the-babesia-checklist-copyrighted-2011-james-schaller-md-mar-version-20/

https://madisonarealymesupportgroup.com/2016/01/16/babesia-treatment/

https://madisonarealymesupportgroup.com/2016/11/19/seroprevalence-of-babesia-in-individuals-with-ld/

https://madisonarealymesupportgroup.com/2016/12/05/babesia-cure-update/