08 October 2009

Differentiating Babesia from Malaria



Differentiating Babesia from Malaria
By:Devak Desai

Case Presentation
* Middle aged hypertensive and asplenic man presented with a pruritic rash on his right buttock accompanied by flu-like symptoms.
* 1010, arthralgias, myalgias, some nausea, and general malaise, and decreased appetite.
* Reports walking through a wooded area on Martha’s Vineyard, an island off the coast of Mass.
* PE shows a well nourished man with no significant findings other than an erythmatous oropharynx without exudate.

Laboratory Data
* Normal WBC differential
* Blood smear: numerous intraerythrocytes involving 2.7% of RBCs
* Direct Combs test was negative
* Positive serologic test for Lyme Disease

Peripheral Blood Smear
* Numerous erythrocytes are infected with the predominantly ring or pear-shaped form of Babesia microti.
* Pleomorphic rings with 1-3 chromotin dots per parasite.
* 3 dots is unique for Babesia.

Host Infection Cycle
* Infection begins when sporozoites are released from the deer tick’s salivary gland during a blood meal.
* Sporozoites replicate directly in RBCs.
* Attachment and adsorption seems mediated through the C3b receptor.
* During invagination a clear vacuole appears.
* Babesia divided by asynchronous budding.
* The replicating structures are now called trophozoites.
* This is an asynchronous process with varying degrees of hemolysis.

Life cycle of Babesia spp. in the tick and vertebrate hosts
High Power
* Ring shaped trophozites
* The intraerythrocytic trophozoites multiply by binary fission or schizogony, forming two to four separate merozoites.
* White eccentric “food vacuole” in a ring form.
* Very transient stage in Malaria. Very rarely seen.

the famous Maltese Cross
* Presence of 4 daughter merozoites in a tetrad is pathomnemonic.
* However, rarely seen.
* Never seen in malaria.

Multiply infected RBCs
* RBCs can be infected with multiple organisms at the same time. Up to 12 parasites may infect a single RBC.
* Plasmodium has up to 3 parasites/RBC.
* Unremarkable RBCs.

Other Sightings
* Parasite with a peripheral nuclear band
* Basket cell
* Syncytium of extracellular parasites
* Far more common in Babesia infections

Malaria Review
Epidemiology
* There are >100 specicies of this intracellular parasite.
* Babesia microti is the predominant human pathogen, endemic to the NE and Midwest.
* 10-20% of adults are seropositive in endemic areas
* Natural parasite reservoir is rodents
* Carried by the hard-bodied Ixodes Deer tick.
* Also carries agents for Lyme Disease, and Ehrlichoisis.
* Can also be transferred transplacentally and through blood transfusion.

Clinical presentation
* Ranges from asymptomatic infection to fatal illness (rare)
* No direct correlation between parasitemia and severity.
* More severe infection tends to occur in immunnocompromised, elderly, and the very young.
* The extreme end of the spectrum is often described as a malaria-like infection; symptoms may include malaise, chills, mylagia, anemia, fatigue, and fever (as high as 1040).
* Some cases also described emesis, night sweats, weight loss, and hematuria.

Special Case – Splenectomy
* Most important risk factor for infection, esp. severe.
* Illness appears suddenly, with hemoglobinuria as the presenting symptom followed by jaundice due to severe hemolysis.
* Parasitemia can reach 80% of RBCs
* Can be a medical emergency.
* In the most severe cases, patients develop a shock-like picture, with renal failure and pulmonary edema.
* Chronic disease with many relapses over months to years may occur if not treated.

Co-Infection
* It is estimated from serologic surveys that as many as 13% of Lyme disease patients in babesia-endemic areas are coinfected with B. microti
* The initial symptoms of both babesiosis and Lyme disease overlap significantly.
* Like babesiosis, Lyme disease also presents with nonspecific symptoms of fever,fatigue, and other flu-like symptoms.
* Patients coinfected with B. microti and B. burgdorferi experience more severe symptoms, but does not increase the duration of Babesia parisitemia.
* Doxycycline will not kill Babesia.

Diagnosis
* Diagnosis is based on clinical suspicion and history of exposure.
* Thick and thin smears remain most clinically used
* However, it is necessary to examine 200 to 300 oil immersion fields before declaring a specimen negative.
* Various PCR detection assays are available for detection of B microtic and other species.
* More sensitive but also more time consuming and expensive.
* Indirect fluorescent antibody test can also be used as a confirmatory test.
* Can have false negatives (HIV) or false pos (autoimmune)

Treatment
* Current treatment is Quinine plus Clindamycin
* Better alternative treatment is Atovaquone plus Azithromycin
* This combo is almost as effective with fewer side effects.
* 72% receiving quinine and clindamycin had side effects attributed to the drugs—diarrhea, tinnitus, or vertigo
* 15% receiving atovaquone plus azithromycin experienced side effects (usually diarrhea or rash).
* For severe cases (asplenic) with high levels of parasitemia, RBC exchange transfusions may also be necessary.

Summary
* History: check for recent travel
* Symptoms: Babesia is milder and tends not to be cyclic.
* Smear: Babesia has no schizonts, gametocyes, or ameboid trophozoites.
* Lab tests: PCR or indirect antibody test.

Conclusion
* Major deterrents to the diagnosis of babesiosis include the low index of suspicion by physicians (except in endemic areas), non-specific flu-like signs, and the use of automated cell readers that cannot detect merozoites in erythrocytes
* Disease is increasing in prevalence due to more people living in rural tick infested areas and as the number of immunocompromised in increasing.
* Also environmental such as the exponential rise in deer populations.
* Blood transfusion risk becoming an increasing problem.
References

Differentiating Babesia from Malaria.ppt

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