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Tuesday, September 20, 2011

Babesia, re-visited

Those in the chronic Lyme community have a narrative for explaining the chronicity of Lyme disease or at least the persistence of Borrelia despite the onslaught of immune responses and antimicrobiobials, including such things as: genetic switching - up and down regulating of key surface proteins at key times, protection of the bacteria within a niche, polymorphic switching from spirochetes to cysts and then back again, biofims, and other proven effective stratagies for survival. Despite this evidence, we are still convincing the few.

With chronic Babesiosi we lack such a narrative. Patients are frequently treated for months or longer without clinical resolution. Patients have repeatedly shown me positive FISH(RNA)results for Babesia after extensive therapy, still sick with the disease. As one of my patients recently described in a YouTube video, two ID specialists at Johns Hopkins dismissed this evidence claiming that IgeneX is not a trustworthy lab and suggested the patient seek psychiatric care.

Although there is a great deal of overlap between the symptoms of Lyme and Babesia, certain symptoms are quite specific for babesiosis, inlcuding: recurrent flu like symptoms with low grade fevers, air hunger and night sweats.

Frequently the diagnosis of babesiosis is made on clinical grounds. There are over 100 known species of Babesia but only a few are though to cause human disease. In the US we look for B. microti and B. duncani. Another, yet unnamed species, MO1 has been shown to cause human disease in the US. Others are likely.

Babesia in humans is an infection of red blood cells. The protozoa invade and reproduces within red blood cells. When the cells rupture Babesia forms quickly attach to other red blood cells. Babesia has two hosts: mouse and tick, both of which are required for the parasite's normal life cycle. The tick is considered the definitive host because this is where sexual reproduction of the organism occurs. Humans are considered an unintended, bystander host, unlucky enough to have been bitten by the wrong tick. In humans Babesia is seen as any of three forms: sporozoites which microscopically have a spherical form, trophozoites which have a ring appearance and merozoites which may have the "Maltese cross" (tetrad) appearance.

Unfortunately, Babesia sp infect only a small percent of circulating red blood cells and direct evidence of its presence via microscopy is rarely evident.

Standard, and largely unchallenged dictum states that the microbe lives only within red blood cells, it does not hide in tissues, all of the forms are killed by the same antimicrobials/antiparasitics. The narrative to support the parasite's longevity seems lacking. Well, lets look at some recent medical literature: Clinical Infectious Diseases, 2008, Florescu, highlighted as important by the IDSA.

Two cases of Spenic Infarct are discussed. Both patients were critically ill, one succumbed. At autopsy Babesia-infected red blood cells were noted with the spleen, liver and lymph nodes. One then wonders, is the parasite seeking safe harbor within the microvasculature of these organs?

Of interest, the authors observed that the first patient who survived was co-infected with anaplasmosis "which may have contributed to the prolonged course of the illness." The implication is obvious to chronic TBD believers. The authors report that Babesia has been associated with retinal damage, ostensibly as a consequence of "microobstruction" of tiny blood vessels (by the parasites).

The authors report that multifocal coagulative necrosis has been shown to occur with B. duncani at least in Syrian hamsters. This means that Babesial infection within narrow blood vessels likely caused blood clotting associated with multi-organ damage.

In May 2011, The CDC reports a study of Babesia sp. EU1 (of reindeer) which found hemosiderin laden macrophages in multiple tissues, meaning that infected red blood cells were ingested by macrophages. Babesia DNA was found in: bone marrow, brain, heart, kidney, liver, lung, lymph nodes, small intestinal wall and spleen. Perhaps Babesia can sequester itself with organs.

In summary: Babesia can likely cause blood clotting with localized tissue damage. It may persist only within tiny blood vessels or it may be able to exist within tissues. There are many species of Babesia. They may exhibit different biological behavior. Little is known here.

The evolving science may help us uncover a better narrative by which we may describe patho-anatomic-physiological mechanisms supporting the notion of chronic Babesiosis.

In the meantime, our clinical experience and our supporting laboratory data cannot and should not be ignored.

Thursday, September 1, 2011

Fear

Every once in a while a patient surprises me and makes it all worthwhile. This is such a story. A 17 year-old female presented in my office in a wheelchair this past spring. She was holding her head, her neck flexed, her face invisible to me. Severe unrelenting daily headaches were unbearable and driving her mad.(in the British sense). She was disoriented - cognitive impairments were profound. For me the most frightening aspect of her presentation was profound weakness. When I asked her to get out of the wheel chair her thighs muscles appeared to contract in a floppy, asynchronous fashion. The analogy that came to my mind was a fish hopelessly flopping on the deck of my boat. I quickly asked her to sit back down. After examining her I thought she was suffering with a severe motor neuropathy.

She had a well documented diagnosis of Lyme disease. She had been treated by another physician in a nearby state with oral antibiotics for an entire year. Despite this, her condition had steadily deteriorated.

I knew that the only treatment that might be effective was IV antibiotics. I ordered a PICC and started Rocephin. I saw her back in two weeks, as is my practice. She was no better. At that point I decided she should be evaluated in a tertiary care center. I sent her to Georgetown. I have found Georgetown more Lyme friendly than hospitals in my own state.

My experience had been with adult side. She was 17, so she was admitted to the pediatric ward. A neurologist barely peaked at her. No EMG/NCV test was performed as I requested. The ID doctor stopped in for a moment I was told. The attending pediatrition diagnosed fibromyagia and a somatoform disorder - a psychiatric condition. The good doctor wanted to stop the IV antibiotics. The youg lady's father insisted otherwise (with some vehemence I suspect) and won the day.

After a few days she was sent to the National Rehabilitation Hospital. This was helpful and she got stronger. The doctors there also reluctantly agreed to continue the Rocephin. Two weeks later she was back in my office.

She looked better. A little better. I felt encouraged and continued the treatment. The brain fog lifted a bit. She asked me if she would be able to attend an important camp activity three months hence. I looked at her in the wheel chair and said: "we'll see."

And then something magical happened. She started getting better - fast. I used the regimen which has served me best. Rocephin layered with Zithromax and the Flagyl IV. I also prescribed Mepron for Babesia symptoms.

After two more months it looked like she might actually be able to go to the activity. A positive thing for her is that she forgot how sick she had been as she improved. Not only was she out of the chair, she was running and dancing.

All of her symptoms gradually began to peel away. She had missed a whole year of school and was now reading and catching up on her studies.

After 3 and 1/2 months, she was looking good. Essentially back to normal. She did no get to go to the camp activity, but she did go to her family beach vaccation, sans PICC line.

Doctors are afraid. They are afraid to prescribe IV antibiotics. To do so you need to be on staff at a local hospital. You have to face the scrutiny of the Infectious disease doctors, the neurologists, the hospital board and various attendant committies - And possibly - the State licensing board. It is safer to prescribe oral antibiotics, to keep plugging away with all the oral medicines in your arsenal. Harder. More. Something will work if you keep trying. It is safer.

Fear.

What else is there to do.