. 2024 Apr 30;12(5):909. doi: 10.3390/microorganisms12050909.
5. Conclusions
Lyme disease and its associated co-infections, including Babesia and Bartonella, are increasingly being reported in the medical literature as potential overlapping factors leading to chronic resistant symptomatology [14,38,39,63,73,234,235], where combination antibiotics effectively relieve tick-borne infection (TBI) symptoms, with good patient tolerance [236]. Our three patients with Borrelia, Bartonella, and/or Babesia, described in these case reports, all had excellent outcomes with short-term combination antibiotics, using pulsed persister drug regimens with biofilm agents. Bartonella specifically required one or more 6-day pulses of HDDCT in order for patients to achieve long-term remission, although the number of pulses of HDDCT needed to cure Bartonella will require further investigation. Multiple overlapping sources of inflammation on the 16-point MSIDS model (infections, toxins, leaky gut and/or food sensitivities with mast cell activation, microbiome abnormalities, nutritional deficiencies, and/or insomnia) with downstream effects of inflammation (mitochondrial dysfunction, POTS/dysautonomia, autoimmunity, hormonal dysregulation, pain syndromes, liver and neurological dysfunction, and/or neuropsychiatric manifestations) were also found to be playing a significant role in driving underlying chronic symptomatology [30,36,37]. Infection, immune dysfunction, and inflammation, i.e., the three ‘I’s’, and all 16 factors on the MSIDS model, have now been reported in the medical literature as being potential factors that increase the symptoms of CLD/PTLDS as well the symptoms of long COVID [40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59]. A paradigm shift from a one-cause/one-disease model to a multifactorial model in chronic disease is warranted based on the increasing numbers of individuals affected by both illnesses.
The role of co-infections in CLD/PTLDS is the topic of an ongoing debate, especially Bartonella, since its transmission via ticks has only been proven in one European study of Ixodes ricinus ticks to date [237], although the 2018 HHS Tick-borne Disease Working Group report to Congress highlighted the importance of Bartonella species complicating tick-borne infections in humans [190]. All three of our Lyme disease patients had overlapping co-infections complicating their clinical course, especially Bartonella, with associated neuropsychiatric symptoms. These included moderate to severe cognitive difficulties, neuropathy, double vision and/or visual loss, dizziness, tremors, twitching, tinnitus, anxiety, depression, OCD, psychosis, and paranoid ideation, although headaches, fatigue, and/or malaise are the only two tick-borne disease symptoms fully recognized by public health officials [238]. Among 148 patients who were recently surveyed as having Lyme disease or another TBD, bartonellosis, Lyme disease, and babesiosis were the three most-reported TBDs, where the authors noted a disconnect between the scholarly literature regarding the psychiatric manifestations of LD and the lack of inclusion of psychiatric symptoms by the CDC [236]. This has particular importance from a public health perspective, considering that Lyme disease has been associated with suicidal ideation [239], where individuals with Lyme borreliosis have higher rates of any mental or affective disorders, suicide attempts, and death by suicide compared to those without Lyme borreliosis [240]. Similarly, bartonellosis has recently been reported to have a high association with neuropsychiatric symptoms, especially in those presenting with Bartonella striae [163,164,241], which were present in two out of three of our patients. The treatment of Lyme disease and its associated co-infections, including Bartonella, using pulsed dapsone combination therapy relieved these resistant neuropsychiatric symptoms that had not been previously controlled with psychiatric medications. Overlapping psychosocial stressors also needed to be addressed in helping to heal from these TBDs, whether from abuse and trauma or the COVID-19 pandemic. The mental health consequences of the COVID-19 pandemic has now been associated with severe mental health issues in the global population, including relatively high rates of anxiety, depression, PTSD, and psychological distress in the population [242], where Lyme disease may be a mitigating factor that increases symptoms [24]. Climate change is increasing the rates of Lyme disease and other vector-borne diseases, including viral infections [243], and Bartonella [244], whether from tick bites or other arthropod vectors, including fleas, spiders, mites, red ants, keds, or lice, requires a One Health approach to mitigate the rise in vector-borne chronic illnesses, improve physical and mental health, and lower rising health care costs [245,246,247].
Future studies need to be conducted on persister drugs like dapsone, using pulsed antibiotics with biofilm agents, and to further elucidate the role of associated co-infections like Bartonella with MSIDS variables in those suffering from CLD/PTLDS. Our report represents one of the first successful treatments of a pediatric patient with CLD using a persister drug regimen, i.e., dapsone combination therapy. Future studies should be conducted in both the adult and pediatric populations since pediatric Lyme borreliosis (LB) represents a substantial proportion of affected individuals across countries in Europe and North America [248]. The four prior National Institutes of Health (NIH) randomized trials on treatments for CLD, conducted over 15 years ago, did not evaluate pulsing, combination persister drug regimens, and/or MSIDS variables in the treatment of those suffering from chronic Lyme symptoms, although two of the four U.S. treatment trials demonstrated the efficacy of IV ceftriaxone on primary and/or secondary outcome measures [249]. A multicenter, placebo-controlled, randomized trial using dapsone combination therapy to evaluate the role of co-infections including Babesia and Bartonella and screen for overlapping MSIDS variables is the next logical step to help end the decades-long scientific debate over the etiology and treatment of CLD/PTLDS. Based on the number of increasing cases of TBDs and vector-borne infections due to climate change [250], resulting in increased health inequities and associated patient suffering, disability, and rising healthcare costs [251], we urge Lyme groups and healthcare authorities to come together now to help solve this urgent global healthcare crisis [252].
roughly 7 million dollars