Study on Effects of FDA Warning Letters on Dietary Supplements

new class of antibioticsAccording to an article from the online The People’s Pharmacy, Joe Graedon, pharmacologist, 7.28.22, from 2007 through 2016, the Food and Drug Administration (FDA) identified ‘adulterated dietary supplements’ and sent 700 + warning letters to dietary supplement manufacturers after detecting undeclared and potentially harmful drugs in product. The article provides a summary of the problem and reveals that no action has been taken by some of the companies.  The article cites as a basis, a research letter published in JAMA, Cohen, P.A.  et al, 7.26.22, where researchers looked at 31 of the reviewed dietary supplement products subject to the warning letters and found some of those products are still being sold.  

More Information  

Read The People’s Pharmacy article

See JAMA abstract

Neurological Pain, Psychological Symptoms & Diagnostic Struggles Among TBD Patients

symptoms of tick-borne diseasesIn the journal, Healthcare, Sarah P. Maxwell, et al., lay out the limited information from public health reports on psychological and neurological symptoms of tick-borne diseases (TBD).  “… Out of the fifteen neuropsychiatric symptoms reported in the medical literature for common TBDs, headaches and fatigue and/or malaise are the only two symptoms fully recognized by public health officials. Of TBDs, Lyme disease is the least recognized by public health officials for presenting with neuropsychiatric symptoms; only headaches and fatigue are recognized as overlapping symptoms of Lyme disease. Comparisons from a patient symptoms survey indicate that self-reports of TBDs and the associated symptoms align with medical and case reports. Anxiety, depression, panic attacks, hallucinations, delusions, and pain – ranging from headaches to neck stiffness and arthritis – are common among patients who report a TBD diagnosis. Given the multitude of non-specific patient symptoms and the number and range of neuropsychiatric presentations that do not align with public health guidance, this study indicates the need for a revised approach to TBD diagnosis and for improved communication from official public health sources regarding the wide range of associated symptoms.”

The article provides tables of key symptoms with information on each, providing information reported by the Centers for Disease Control & Prevention (CDC), reported in scientific and medical literature, and reported in scientific literature but not recognized by the CDC. This enables readers to use the content to provide references for symptoms.

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium provided the original work is properly cited

More Information:

View a PDF of the article.

Learn more about Lyme & TBD symptoms. 

LDA NOTE: This article provides a wealth of information that can be used by patients and/or healthcare providers to document symptoms for diagnosis and/or treatment.

Rickettsia Tillamookensis from Ixodes Pacificus Found in Several California Counties

A study in Journal of Medical Entomology by Christopher D. Paddock, et al., took a deeper look into Rickettsia tillamookensis (Rickettsiales: Rickettsiaceae), a unique Rickettsia species that may possibly be pathogenic and occurs in I. pacificus (Acari: Ixodidae), the Western blacklegged tick. The R. tillamookensis agent was first mentioned in 1978 and has been recently recognized as a novel transitional group agent. Historically, incidence rates and distribution levels of R. tillamookensis have been widely unknown.

Rickettsia Tillamookensis
Western blacklegged tick (Ixodes pacificus), photo courtesy of Bob Lane, PhD.

By using a real-time PCR specifically designed to detect R. tillamookensis DNA, the researchers analyzed isolated DNA samples from 348 host-seeking I. pacificus nymphal ticks that were gathered from nine sites within five California counties as well as samples from 916 I. pacificus adult ticks from 24 sites located in 13 counties. The DNA of R. tillamookensis was identified in 10 nymphs (2.9%) and 17 adults (1.9%) that were sourced from 11 northern California counties. According to the study, site-specific infection rates fluctuated considerably, and infection frequencies were consistently low when grouped by stage, sex, habitat type, or geographical region.

The scientists cultivated four novel isolates of R. tillamookensis in Vero E6 cells from adult ticks found in Alameda, Nevada, and Yolo counties. Past isolate strains that had been previously serotyped as ‘Tillamook-like’ and placed in long-term storage over four decades ago were restored and later, using molecular methods were confirmed to be isolates of R. tillamookensis.

Further investigation is needed to better understand the possible impact that R. tillamookensis may have on public health.

Read the study in Journal of Medical Entomology.

Read more about other Rickettsia species.

Scientists Develop a Diagnostic Test for Gene Expression-Based Diagnosis of Early-Stage Lyme Disease

Venice Servellita, et al., published results of a study in Communications Medicine designed to address the urgent need for new diagnostic tests with improved sensitivity and specificity for Lyme disease.

The study carried out transcriptome modeling via RNA sequencing (RNA-Seq), targeted RNA-Seq, and/or machine learning-based designation of 263 peripheral blood mononuclear cell samples collected from 218 study participants. The samples included 94 patients with early-stage Lyme disease, 48 uninfected control participants, and 57 patients with other diseases such as influenza, bacteremia, or tuberculosis.

The end result of the study involved identifying a 31-gene Lyme disease classifier (LDC) panel that can differentiate early-stage Lyme patients from the control group including 23 genes (74.2%) formerly purported to be associated with clinical studies of Lyme disease patients or in vitro cell culture and rodent studies of Borrelia burgdorferi infections. The LDC was assessed using an impartial test set of samples from 63 patients yielding an overall sensitivity of 90.0%, specificity of 100%, and accuracy of 95.2%. The LDC test was positive in 85.7% of seronegative patients and was observed to endure for ≥3 weeks in 9 out of the 12 patients (75%).

The researchers conclude that the study results emphasize the prospective clinical value of a gene expression classifier for diagnosing early-stage Lyme disease, especially for patients who would otherwise be found to have negative test results based on conventional serologic testing that is currently used.

Read the full study in Communications Medicine.

Read more about Lyme disease testing.

Transmission Study of Borrelia miyamotoi in Blacklegged Ticks

Deer tick on leaf
Blacklegged Deer Tick (Ixodes scapularis), female

A recent study published in Ticks and Tick-Borne Diseases compared the efficacy of transmission routes, both horizontal (between life stages of developing ticks) and transovarial (from infected female tick to larvae), of Borrelia miyamotoi from Ixodes scapularis (blacklegged ticks). Results show that although multiple transmission routes contribute to maintenance of B. miyamotoi in the ecosystem, transovarial transmission is likely the primary contributing factor to infected ticks in nature.

Authors suggest that risk assessment and tick control strategies should target adult female ticks.

Access to full text study article can be found here

Read more LDA articles on Borrelia miyamotoi here

Asian Longhorned Tick Now in 17 States

Farm Journal has published an article on the increasing presence of Haemaphysalis longicornis, the Asian longhorned tick (ALT), in the U.S. Since arriving in the country four years ago from Southeast Asia, ALT has now been detected in one-third of the nation’s states.

Asian Longhorned Tick, Haemaphysalis longicornis
Photo courtesy of J. Occi

This tick was first detected in the U.S. in 2017 on an Icelandic sheep in New Jersey and later verified by the Rutgers Center for Vector Biology. By September 2021, the CDC confirmed that ALT had been confirmed in Arkansas, Connecticut, Delaware, Georgia, Kentucky, Maryland, Missouri, New Jersey, New York, North Carolina, Ohio, Pennsylvania, Rhode Island, South Carolina, Tennessee, Virginia, and West Virginia.

Johns Hopkins University claims that there have been no pathogens detected so far in any ALT that has been found in the U.S., although in eastern Asia, the species carries a virus that causes human hemorrhagic fever.

There is concern for ALT’s possible impact on animals. It has been detected in small numbers on horses, pigs, sheep, goats, and chickens. In the article, Virginia Tech veterinary pathologist, Kevin Lahmers, warns of potential losses due to T. orientalis, a disease that it carries which causes symptoms in cattle that are similar to those caused by anaplasmosis. There is no effective treatment for T. orientalis besides supportive care and although it can cause severe illness and even death in up to 5% of infected hosts, most infected cattle develop little to no symptoms.

ALT is a difficult species to manage for various reasons, one being that it reproduces by parthenogenesis which means it doesn’t require a mate. The article states that, so far, only female ALT have been observed in the U.S., nonetheless, the tick manages to reproduce at high rates.

Furthermore, ALT can be found in pastures in large numbers, as they are hyperendemic. After only walking through pasture grass for less than a minute, one person can find hundreds of attached ATL. According to Lahmers, “You can find a density of 10 per blade of grass … think about that number of ticks.”

Lahmers advises implementing tick control, pasture management, and maintaining a good plane of nutrition. A blood PCR test is available, as well as a spleen PCR for necropsied animals. The author encourages veterinarians and producers to contact their state department of agriculture if they suspect the disease in their area.

Read the article on the Farm Journal website.

More information from the LDA on Longhorned tick:

Anaplasma phagocytophilum Human Agent Variant Detected in Asian Longhorned Ticks

IPM Pest Alert – Asian Longhorned Tick

Asian Longhorned Tick Now in 15 States

Asian Longhorned Tick Continues to Multiply, Can transmit to Animals in the Lab

Experts Say New TBD Spread by Asian Longhorned Tick Threatens VA Cattle

Thousands of Asian Longhorned Ticks Infest and Kill 5 Cows in NC

James L. Occi, PhD: 4 New Published Articles on Ticks

Lyme Bacteria DNA Found in PA Haemaphysalis longicornis Tick

SFTS Virus Outbreak in China from Ticks

CDC Sounds Warning About Longicornis Tick

Longhorned Tick Now Confirmed: NJ, VA, WV, AR, NC, NY, PA, CT, NH, KY, MD, & TN

Longhorned Ticks Survived the NJ Winter: Invasive Species May Be Established

New Tick Species to the US Identified in NJ: Disease Threat Being Evaluated

New Study Finds Haemaphysalis longicornis Fails as Experimental Vector of Lyme Disease

More James Occi research on ALT.

COVID Brain Study: Neuroinflammatory Changes & Neurovascular Injury

A study conducted was just published in Brain, which describes the vascular pathology and inflammatory changes, as well as the cellular and humoral immune responses by immunohistochemistry observed in autopsied brains of patients that died suddenly after a short duration of COVID illness. Some patients exhibited minimal respiratory symptoms with illness, but all had evidence of lung involvement at time of autopsy. Confirmation of COVID was made post mortem. 

All patients studied were adults that had died from March to July 2020 during the first wave of COVID outbreak. Researchers found that all patients had multifocal vascular damage. This was determined through observation of leakage of serum proteins into the brain parenchyma which results in breakdown of the blood–brain barrier. Vascular injury was observed more common in the hindbrain. Widespread endothelial cell activation was also seen with adherence of platelet aggregates along vascular lumina. Observed on these cells and platelets were immune complexes showing activation of the classical complement pathway.

Astrogliosis is a defense mechanism to minimize and repair the initial damage after CNS injuries, this was found to be prominent in the perivascular regions of the brain. Also predominant in the hindbrain were microglial nodules which were associated with damage resulting in focal neuronal loss and destruction of nerve cells by phagocytes. 

Researchers suggest that cytotoxicity which is antibody-mediated against the endothelial cells is likely the event that causes vascular leakage (damage to blood-brain barrier), platelet aggregation, inflammation and injury in the brain leading to death. Authors recommend investigation of therapies targeted against immune complexes.

Read the full text article here

Read more on COVID 19 here

Dapsone Combination Therapy for Treatment of Chronic Lyme Disease

Richard Horowitz, MD
          Richard Horowitz, MD

A new study by Richard Horowitz, MD and Phyllis Freeman, MD has been published in Antibiotics that evaluates the efficacy of using short-term high dose pulsed dapsone combination therapy (HDDCT) in the treatment of Chronic Lyme disease/Post Treatment Lyme Disease Syndrome(PTLDS).

This new study builds upon past studies conducted by Dr. Horowitz et al. and included 25 patients that had history of Lyme and associated co-infections. These patients, most who had ongoing symptoms after several courses of double dose dapsone combination therapy, were trialed with one or more courses of HDDCT (200 mg dapsone × 3–4 days and/or 200 mg BID × 4 days), depending on their persistence of symptoms.

Study results showed that the majority of patients reported sustained improvement in “eight major Lyme symptoms, including:  fatigue, pain, headaches, neuropathy, insomnia, cognition, and sweating.”  Dapsone dosage, not just the treatment length, showed a positive effect on patient outcomes. The study shows the risk/benefit ratio of using four days of higher dose dapsone combination therapy is evidenced by 84% of patients noting improvement of their tick-borne disease symptoms. Thirty-two percent of patients had resolution of all active Lyme symptoms for 3-months or longer post HDDCT even if there was evidence of prior active co-infections. Forty-three percent of patients with an EM rash and history of PTLDS remained in remission,  and 57% of patients reported mild-moderate improvement in their underlying symptoms from their baseline.

Authors note that these findings should be confirmed in randomized, controlled clinical trials as cases of Lyme disease continue to escalate and curative treatments have not yet been attained for Chronic Lyme/PTLDS.  

Read the full text article here

Read additional LDA articles on Dapsone studies by Dr. Horowitz et al. here


Adverse Childhood Events, PTSD, Infectious Encephalopathies and Immune-Mediated Disease

Robert C. Bransfield, MD
Robert C. Bransfield, MD

Robert C. Bransfield, MD, published a study examining how adverse childhood events (ACE), post-traumatic stress disorder (PTSD), and infectious encephalopathies are linked to immune-mediated disease in the journal, Healthcare. Bransfield reviewed supporting data and found that each of these issues correlates with intrusive symptoms and pathology of the temporal lobe.

The study demonstrates that ACE and PTSD can result in a decreased mental ability to distinguish external danger vs. safety. As well, infectious encephalopathies are associated with a breakdown in adaptive immunity and decreased immune capacity to determine internal danger vs. safety. Each of the three circumstances correlates with a diminished ability to differentiate danger vs. safety and adapt accordingly.

Bransfield identified reciprocal exchanges between ACE, PTSD, and infectious encephalopathies with subsequent enduring immune activation causing immune dysregulation, chronic hyperarousal, activation of the stress response, and impairments of the fear recognition and response neural circuits, hypothalamic–pituitary–adrenal axis, amygdala, and hippocampus.

These pathophysiological developments can result in a wide range of chronic neuropsychiatric and somatic symptoms/diseases. Bransfield concludes that having a better understanding of the psychodynamic, neurological, neuroimmune, inflammatory, and autoimmune components of this synergistic process can create opportunities for increased treatment efficacy.

Read the study in Healthcare.

Read more by Robert C. Bransfield, MD.

Relapsing Babesiosis Case Treated Successfully with Tafenoquine

A study published in Clinical Infectious Diseases, by Ralph Rogers, et al.,Relapsing Babesiosis examined antimicrobial resistance in an immunocompromised patient with relapsing babesiosis who was effectively treated with tafenoquine.   

The researchers describe a point mutation in the Babesia microti 23S rRNA gene which enabled them to predict the microbe’s resistance to azithromycin and clindamycin while an amino acid fluctuation in the parasite cytochrome b made it possible to project the microbe’s resistance to atovaquone. After the administration of tafenoquine, the patient’s symptoms and parasitic infection were resolved.

Find the study in Clinical Infectious Diseases.

Read more about tafenoquine treatment for babesiosis.