CLINICAL CLUES • Abrupt onset of initial illness • Obvious sweats especially at night • Fatigue, air hunger, unexplained cough • Global, migraine-like headaches that may respond to the tripans • Tippy, off-balance without vertigo • B. duncani is associated also with anxiety and Gl distress • Hypercoagulation (responds to heparin) • Very severe Lyme symptoms and poor response of Lyme to otherwise appropriate treatment
VARIABLE CLINICAL PRESENTATION WEB • Clinical manifestations of Babesiosis can range from asymptomatic, to multi-organ failure. Severe illness is frequently seen in elderly, immunocompromised, and splenic patients • However, in patients chronically co-infected with multiple tick-borne diseases (TBDs), immunity is often suppressed and severe presentations are possible • When Babesia is present in a Lyme patient, the Lyme symptoms are more severe and the Lyme is more treatment resistant, so think of Babesia in Lyme patients that have a severe illness.
BABESIA TESTING DIFFICULTIES • Parasitemia is highest with initial infection, then diminishes rapidly unless immunosuppressed, or have a late chronic infection. • Nevertheless, it may be difficult to detect Babesia directly in the blood, even in early cases • Antibody levels are not always high enough to be detected-immunosuppression? Immune complexes? • Multiple Babesia species may be infecting patients and not every test is validated for all of them • Are at least 13 pathogenic species, and non-human parasites may infect those with severe immune deficiencies or asplenism
BABESIA- DIRECT TESTING METHODS-1 WEB • Standard giemsa-stained smears- done in hospitals- only useful within first week of infection • Limit of detection (LOD) no better than 0.5% RBC infection • FISH- Fluorescent in-situ hybridization assay (IGeneX) • Blood slides target specific rRNA sequences using fluorescent probes • Can detect organisms in biofilms • Genus-level test so has broad coverage • Far more sensitive than a standard smear: LOD of 0.001% • Despite genus-level detection, may miss atypical species
BABESIA- DIRECT TESTING METHODS-2 WEB • PCR • Results depend upon which DNA primer sets are used • Can be genus-specific or species specific • Sensitivity is poor • Culturing is the "gold standard" of infectious diseases • Culturing is a direct test- a positive result indicates the infection was present and active the day the blood was drawn • IGeneX cePCR- "Culture-enhanced PCR" • Is a genus-level test so it can detect microti, duncani and others • So sensitive that rare and unusual species have been detected
BABESIA- INDIRECT TESTING METHODS Multiplexed recombinant technology has replaced other serologic methods in TBD lab diagnosis • ImmunoBlot (IGeneX) • Antigen source: pure, lab-created, highly specific recombinant proteins • Antigen content: multiple protein antigens from multiple species are included in each ImmunoBlot • Allows for detection of a broad array of species • Will identify and name microti and duncani; others are simply reported as "genus positive" • Detects the full spectrum of disease: early, acute and late-stage • More sensitive and specific than "standard serologies"
MEDICATIONS IN USE • Clindamycin + quinine- • The originally recommended regimen • Very difficult to tolerate • Many treatment failures- no longer the first choice • Atovaquone + azithromycin • The currently recommended regimen • Must be taken with food to ensure optimal absorption • Better tolerated but many cases of resistance are appearing • May need to push the dose; especially with B duncani • Atovaquone-proguanil combination tablet (Malarone®) • Note poor blood atovaquone levels- risk for treatment failures and drug resistance- Not a good choice!!
BASIC STARTING REGIMEN WEB • Atovaquone 750 mg po bid with food + azithromycin 500 mg po or IV daily, + artemesinin compound • May need to increase dose of atovaquone to 1500mg bid • High blood levels may temporarily affect vision (everything looks yellow!!) • May substitute or add the combination tablet atovaquone-proguanil • NOTE: Starting dose is equivalent of 750 mg of the atovaquone component- (THREE tablets bid), but must monitor LFTs, RFTs and blood counts, and be aware of Gl and neuropsych side effects Adding trimethoprim-sulfamethoxazole or metronidazole may potentiate primary therapy
OTHER PHARMACEUTICALS BEING TRIED WEB • Artemether-lumefantrine combination (Coartem®) • Many prescribe several pulses- one week on, and one week off. • Potential side effects include muscle and joint pains, fever, loss of appetite, headache, sleep disorder, tinnitus, tremor, palpitation, vertigo, gastrointestinal disorders, itch and nasopharyngitis • May prolong the QT interval • Disulfiram • Published reports of efficacy in treating Lyme Borreliosis co-infected with Babesia • MUST become familiar with subtleties of prescribing for TBDs (suggested reference guide: Dan Kinderlehrer MD) • Severe side effects possible- autonomic dysregulation, neuropathy, headache, GI issues
OTHER PHARMACEUTICALS BEING TRIED WEB • Mefloquine (Lariam® • Boxed warning regarding the potential for neuropsychiatric side effects that may persist even after discontinuing administration of the medication. • "Neurologic side effects can occur at any time during drug use, and can last for months to years after the drug is stopped, or can be permanent." • Neurologic effects include dizziness, loss of balance, seizures, and tinnitus. • Psychiatric effects include nightmares, visual hallucinations, auditory hallucinations, anxiety, depression, unusual behavior, and suicidal ideations. • Not recommended IMO!
TAFENOOUINE Recent in-vitro and animal data as well as case reports suggest that this may be highly effective for treating Babesiosis • Mode of action not clear but probably involves oxidative damage to Babesia organelles • Cannot be used if patient is G6PD-deficient • Incomplete cure when used as a single agent • Synergy when artemesinin compounds were added • Watch for hyperkalemia
TREATMENT PROBLEMS ALL currently recognized regimens are based upon Malaria protocols • Surprise! Quinine drugs target organelles NOT present in Babesia! • In malaria parasites- in the digestive vacuole, with quinine, hemoglobin is degraded, forming free ferriprotoporphyrin IX which inhibits parasite growth and disrupts hemozoin formation. • However, Babesia species don't have a digestive vacuole, do not degrade hemoglobin, and do not produce hemozoin. • The fact that these do have some clinical utility implies additional mechanisms of action- OXIDATIVE STRESS?? • Atovaquone- relative resistance develops due to the emergence of mutations in the cytochrome b of Babesia parasites in humans and animal models * kn darren, resistance to azithromycin implies resistance to clindamycin (same Nevertheless, these agents clinically have had successes so if these are to be used, definitely maximize dose and utilize logical med combinations
COMBINATION THERAPY The goal of combination therapy is to prevent development of drug resistance and broaden coverage • (But all have documented treatment failures) • Atovaquone liquid + azithromycin + artemesinin • Atovaquone-proguanil + artemesinin • Artemether-lumefantrine • Mefloquine + artemesinin • Clindamycin + Quinine + artemesinin (difficult to tolerate) • TMP-SMX or metronidazole may be added to the above Herbals and botanicals- can also be added to the above
BABESIOSIS- PROMISING BOTANICALS Recent published studies have demonstrated excellent results in Babesia culture systems of several botanicals • Cryptolepis sanguinolenta • Artemisia annua (sweet wormwood) • Scutellaria baicalensis (Chinese skullcap) • Polygonum cuspidatum (Japanese knotweed) • Alchormea cordifolia • Other botanicals and high dose vitamin C have demonstrated inhibitory effects and may be usetul • If used, recommendation is to use a combination of at least two botanicals, alone or with prescription meds > Adding botanicals is definitely recommended "It is required to monitor for lab abnormalities and drug interactions!!
BABESIOSIS- CAUTIONS REGARDING SUPPLEMENTS! WEB Atovaquone- • Targets electron transport chain • Co Q-10 and NADH supplementation may inhibit efficacy, so most practitioners omit these during treatment Tafenoquine- • Kills Babesia by OXIDIZING its organelles, therefore some advise stopping all antioxidants while on this med • Same may be true for all the quinine-based compounds
B. ODOCOILEI WEB B. odocoilei- controversial. • Found in many ticks all across North America • Published case report- two cases found in Canadian patients • Multiple IFA-stained patient samples said to indicate odocoilei • But a series of 460 Babesia-positive patient samples had DNA sequencing- did not find ANY B. odocoilei • Confusion may relate to which primer sets are being used for PCR and sequencing, and/or nonspecificity of the IFA stain • Immunoblot data shows a significant percentage of Babesia species in human patients are not microti or duncani. Could these be divergens and or odocoilei?
More info on link above. Thank you Dr Burrascano
Posts: 3023 | From Florida | Registered: Nov 2016
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Phoiph
Frequent Contributor (1K+ posts)
Member # 41238
posted
I truly appreciate all Dr. Burrascano has done in his decades (40+ years) of Lyme research and practice, and his ongoing dedication and loyalty to his patients.
Looking at the summary above, I do find it very sad that after all these years, the focus is still heavily on these powerful killing drugs with a high failure rate and horrible side effects (I speak from personal experience).
If these methods are working, then why are there so many chronically ill Lyme patients?
My experience is that chasing the bugs with drugs is rarely a solution in chronic conditions where the immune system is already compromised, as it will generally not have the capacity to fight residual pathogens, and/or will be further compromised by the toxicity of the drugs. It becomes a vicious downward spiral for so many.
Dr. Burrascano mentions:
"...The fact that these do have some clinical utility implies additional mechanisms of action- OXIDATIVE STRESS??...", and
"... Kills Babesia by OXIDIZING its organelles, therefore some advise stopping all antioxidants while on this med..."
"...Mode of action not clear but probably involves oxidative damage to Babesia organelles..."
Yes! OXIDATIVE STRESS (ROS) is one of the many powerful ways that mild hyperbaric oxygen disarms pathogens, without the risks and toxicity (if used properly), and with the added advantage of re-booting the immune system to fight the fight.
Unfortunately, there has been a lot of misinformation out there that oxygen "feeds' Babesia.
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