Co-infection Babesia

Babesiosis is an infectious disease caused by the Babesia parasite. It is a malaria-like parasite that infects red blood cells. Babesia can be transmitted through a tick bite. In addition Babesia can be transmitted via a contaminated blood transfusion. This appears to be an increasing problem because blood donors are rarely screened for parasites such as Babesia. Transmission from mother to unborn child is also documented.

The incubation period of a Babesia infection is 1 to 3 weeks but not more than 6 weeks. The incubation period of infection through a blood transfusion is up to 9 weeks. The parasite is transmitted by ticks that can also transmit Lyme disease.

Healthy people recover without pharmaceutical intervention but the infection can be fatal in patients with a compromised immune system, individuals without a spleen or people with concomitant Lyme disease.

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The parasite

Babesia are parasites and not bacteria. It is a one-celled organism with a nucleus surrounding its DNA as opposed to bacteria which have no true nucleus. In addition to bacteria, parasites are 10-100x larger. In other aspects  it is more bacteria-like and even responds to some anti-bacterial agents.

Babesia, like malaria parasites, infects red blood cells. They steal nutrients from these cells for their own propagation. Babesia infects anything that has red blood cells: mammals, birds and reptiles.

Multiple species

Up to now, more than 110 different Babesia species have been discovered but only 12 species of Babesia are known to cause human illness. The search for this organism has only started a few decades ago and the basis for knowledge is still quite thin. While research is catching up, more and more species that can infect people are being discovered. The most common Babesia species known to cause human illness are Babesia microti, Babesia divergins and Babesia ducani (WA-1). Divergens is a European strain and duncani and microti are both found in the United States.

To make things complicated: within the 12 species that can infect people, there are several genotypes. In other words, in order to avoid the human immune system, these different species make several copies of themselves during an infection that are slightly different.

Adaptability

Babesia parasites have existed for hundreds of millions of years. Studies on their genetic composition have shown that the ancestors of Babesia parasites already existed in the precursors of what we now know as ticks. They have co-evolved into the form by which we now know them. Long ago they infected dinosaurs and when mammals developed they infected mammals, including primates.

Babesia reacts with genetic adaptations to changes in their environment like the presence of antibiotics. Different types of Babesia actively exchange genetic material between each other and with different bacteria, which further promotes the emergence of new genotypes.

Despite the desire to give a simple description of Babesia, this is quite difficult. Babesia has a core identity, but the physical appearance is highly variable. The genetic structure is constantly subject to changes, resulting in different physical and behavioral forms. They can be totally unrecognizable from one host to another even if you can see them under the microscope.

The three most constant factors are:

  • They are parasitic organisms, meaning they need a host to survive
  • They are mainly spread by ticks
  • They infect red blood cells

Symptoms

Most people that get infected show few symptoms. When people are healthy, they and the Babesia are happy residents of the same body without interfering with each other.  These are the people who donate blood and cause Babesia to spread through blood transfusion. However, if the immune system is temporarily under stress, Babesia can cause problems.

Some people experience flu-like symptoms for a few weeks before symptoms resolve. In many cases, Babesia is completely eradicated after a couple of weeks but a small group of people become carriers of Babesia without having disease symptoms. Again, when the immune system is temporarily under stress, the infection can resuscitate.

The symptoms of people who can control the infection without the need for pharmaceutical intervention are limited to general pain, fatigue and chills. Patients that need to be hospitalized have a more serious course of the disease. Their fever is higher, their fatigue is worse and the chills are accompanied by sweating. Often the patients also suffer from overall malaise, abdominal pain and diarrhea.

As with malaria, repeated periods of symptoms are common. Different strains of Babesia can cause different symptoms and all can exacerbate a Lyme disease infection. Most Babesia infections are generally associated with fatigue, malaise and periodic fever accompanied by day sweats, night sweats, chills, flushing, air hunger, cough and mild spleen and / or liver enlargement, headache, muscle aches, anorexia, vomiting, nausea and intestinal problems. In some people, the disease takes weeks or months; in some cases full recovery may take years.

Severe infection

In those in whom the infection becomes severe, the fever may increase to 40C with severe chills and inflammation of the liver and spleen. Other symptoms include accumulation of fluid in the lungs, decreased blood pressure, hemolysis (ruptured red blood cells), jaundice, dark urine, excess protein in the urine, low numbers of neutrophils, low numbers of leukocytes, an increase in lymphocytes, abnormal amounts of platelets, anemia and bruising due to ruptured blood vessels.

The most serious problems occur when intravascular coagulation occurs. This causes excessive blood clotting in the blood vessels. In response, the body switches on the system to clear these clots causing bleeding everywhere. As a result, different organs can shut down and eventually death can follow. If this happens in the brain this can interfere with blood flow to different parts of the brain and cause seizures and stroke.

Function of the spleen

In people with a spleen the amount of parasites in the blood is about 5%, but in people without a spleen this can increase to 85%. The spleen helps to clear the parasites from the blood. It produces antibodies that attack the parasites after which the parasites are then eaten by macrophages. In addition, it works as a sieve by filtering infected red blood cells from the blood. In patients severely affected, the spleen can rupture. In patients without a spleen a Babesia infection can be lethal.

Diagnosis

Due to poor understanding of Babesia infections, the large amount of species and genotypes, and the various physical forms of the parasite, diagnosis is difficult. Diagnostic tests are unreliable and insensitive to the wide range of species and genotypes. Good testing involves a panel approach (Giemsa stain, IFA for microti and ducani, Babesia FISH and/or PCR).

Blood smear

The main method of diagnosing Babesia infection is via microscopic analysis of the red blood cells to literally look at Babesia’s appearance and structure.

Problems with this form of diagnosis occur when Babesia is present in low concentrations. In many cases only 1 percent of the red blood cells are infected. There are case descriptions of people admitted to hospital with signs of infection while no parasites are found in the blood.  It sometimes takes several tests before a blood smear comes back positive.

Polymerase Chain Reaction (PCR)

PCR is perhaps the best way to test for Babesia, especially when combined with microscopy. PCR tests are increasingly sensitive to the different types of Babesia, but no specific PCR has been developed that is sensitive to all types that can infect people.

Indirect Fluorescence Assay (IFA)

IFA is eligible after microscopy and PCR. There are some problems with the test. The main problem is that the test measures antibodies in the blood and antibodies are not always present at the beginning of the infection. False negative and false positive results are common.

Indirect Enzyme-Linked Immunosorbent Assay (ELISA)

Worthless but is sometimes used despite the lack of value in the diagnosis of Babesia infection.

The best approach to diagnosis is to consider the clinical picture and laboratory results. Negative test results cannot rule out infection.

Treatment

In patients who become ill from Babesia infection, the treatment fails often. Babesiosis is much easier to treat when caught early. Both variations in genotype and increase in resistance cause treatment failure.

One of the main causes of resistance is the use of anti-Babesia drugs in the bio industry. Babesia infections are a common and serious problem within this industry. As a result, many farmers mix anti-parasitic agents through animal feed to prevent infection.

Atovaquone + Azithromycin

The standard treatment for patients is atovaquone, 750mg orally 2x per day plus azithromycin. The dose for azithromycin is 500-1000mg on day 1 and 250-500mg on the following days. Both medications are given for 7-10 days. Resistance is reported in the literature.

Clindamycin + Quinine

This treatment combination is mainly used in patients with serious infection. Clindamycin 600mg orally 3x daily (or intravenously) plus quinine 650mg orally 3x daily. The duration of treatment is also 7-10 days. This treatment is often associated with side effects such as tinnitus, vertigo and intestinal problems. Unfortunately, this combination also fails regularly in patients without spleen, with HIV, or patients on corticosteroids. Resistance is also reported for this combination.

Treatment failure

The literature is full with reports of patients treated ‘successfully’ in whom Babesia was not detectable in the blood after treatment but had a resurgence of the infection after completion of therapy. In people with a compromised immune system, treatment of at least 6 weeks is required. Based on blood results, this should be extended by 2 weeks until blood results return negative.

In an animal model with dogs, 7-day atovaquone treatment shows clearance of parasites but 33 days later the infection returns. The parasites were more tolerant and more resistant with repeated treatment. The same results are reported for treatment with atovaquone plus azithromycin. In humans the same is observed. With short treatments of 7 to 10 days, the infection may resuscitate which can even lead to death. Because 40-50% of the treated patients relapse, a prolonged duration of therapy might be desirable.

Other drugs

Antibiotics: ciprofloxacin, cotrimoxazol, dapsone, doxycycline and rifampin
Anti-malarials: artemether, lumefantrine, mefloquine and proguanil

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