Babesiosis and Malaria Flashcards
1
Q
Babesiosis
A
- Protozoan sometimes mistaken for malaria (North American malaria)
- Babesia microti is most common
- Transmitted by nymph of Ixodes scapularis
- Transovarial transmission does not occur (as it does with RMSF)
- Sporozoites from Ixodid tick (typically the nymph stage) infect the red cell
- Tick will often transmit multiple diseases at one feeding (Babesia, Anaplasmosis, Lyme)
2
Q
Babesiosis Pathogenesis
A
- B. microti common in white-footed mice
- Can be transmitted to humans through blood transfusion
- Humans are dead end hosts; deer are multipliers
3
Q
Babesiosis Clinical Presentation
A
- Clinical presentation is anemia and fever
- Most severe in people lacking a spleen or immuno-compromised (AIDS)
- Severe hemolytic anemia, thrombocytopenia, DIC
4
Q
Babesiosis Diagnosis
A
•Blood smear (ring form, Maltese cross), PCR
5
Q
Babesiosis Treatment
A
•Atovaquone + Azithromycin
6
Q
Malaria
A
1•00,000,000 cases at any one time
- 1,000,000 deaths/yr in Africa
- Plasmodium is a sporozoan
- Four species of Plasmodium:
○ P. falciparum
○ P. vivax
○ P. malariae
○ P. ovale
- Almost all mortality from P. falciparum
- Drug resistance (especially with P. falciparum)
7
Q
Malaria Transmission
A
•Transmission from female Anopheles spp. mosquitos bite
-Not zoonotic, except P. knowlesi, a monkey malaria that also infects humans in Asia
- Sexual cycle in mosquito is completed in 2 weeks, sporozoites (infective stage, sexual reproduction) in the salivary glands, ready to infect a host
- Mosquito bites between dusk and dawn
- Two phases of replication in humans
- Hepatic phase
- Red blood cell phase
8
Q
Malaria: Pathogenesis Hepatic Phase
A
- Mosquito bites to human injects sporozoites that travel immediately to the liver and multiply as exoerythrocytic forms to become hepatic schizonts (multinucleated stage of the parasite undergoing asexual reproduction)
- The hepatic schizonts rupture in 1-2 weeks and release merozoites (a stage in the life cycle of the parasite resulting from asexual division; a daughter cell) into circulation, where they invade erythrocytes
- With P. falciparum and P. malariae, all the hepatic organisms are released as merozoites. In contrast, P. vivax and P. ovale have latent hepatic stages from and merozoites may be released months or years later
9
Q
Malaria: Pathogenesis Red Blood Cell Phase
A
- Merozoites released from the liver invade red cells by a receptor-mediated process
- P. vivax infects only reticulocytes (young and large erythrocytes) and requires two receptors on red cell, Duffy antigen and reticulocyte-specific receptor. Parasitemia limited to the number of reticulocytes in the circulation
- P. falciparum is more promiscuous because it infects all ages of red cells. It uses two proteins to bind on the red cell, Glycophorin A and other receptors when necessary
- Following attachment, the merozoite invades the erythrocyte where it successfully evades the immune response of the host. Hemoglobin provides the parasite nutrition. Completion of the red cell phase requires two days for P. falciparum, P. vivax, and P. ovale, and three days for P. malariae
- This phase is fairly well coordinated for all infected cells, so that they all rupture at about the same time, releasing the parasites and causing the high fever associated with malaria.
- This can degenerate so one doesn’t always see the fever every two days, especially with P. falciparum.
- Multiple infections from multiple bites are common with P. falciparum and in these cases, the fever will be less predictable.
10
Q
Malaria: Pathogenesis Sequestration
A
- The knobs of P. falciparum-infected red cells have antigenic variant proteins, called PfEMP1 encoded by var genes, that are highly regulated, mediate attachment to several host proteins.
- One PfEMP1 attaches to CD36 and another to ICAM1. One form is highly associated with placental malaria and the other with cerebral malaria.
- Because of the knobs, the parasites are sequestered in the microvasculature where schizogony occurs, which are not blood. If you see a blood smear with numerous trophozoite forms and no schizonts, then P. falciparum is the etiologic agent
- Because of the sequestration, parasites are protected from removal of infected RBCs in the spleen. It’s a pathogenic factor in cerebral malaria with P. falciparum.
11
Q
Genetic/Host Factors
A
•The Duffy receptor is required for P. vivax to invade red cells. People from West Africa are Duffy negative and resistant to P. vivax infection.
-Since there are few people living in West Africa who are susceptible, there is little endogenous transmission of P. vivax; P. ovale is the cause of relapsing malaria in this area and accounts for about 10% of malaria in West Africa.
•Plasmodium species prefer normal red cells and abnormal cells frequently inhibit infection or severe disease.
- The most notable is the hemoglobin S beta-globin mutation that causes sickle cell disease. Sickle trait reduces severe malaria (cerebral or severe anemia) by over 90%, accounting for its high prevalence in West Africa.
- Alpha thalassemia trait reduces severe anemia and hemoglobin C reduces cerebral malaria, but neither as much as hemoglobin S.
12
Q
Hemoglobinopathies that are probably protective from severe malaria:
A
- Hereditary Ovalocytosis - resistant to Plasmodium invasion (? altered cytoskeleton)
- Elliptocytosis - resistance to Plasmodium invasion, secondary to altered cytoskeleton
- Hemoglobin S - Parasites don’t develop in the erythrocytes and people heterozygous (or homozygous) for the sickle cell mutation are substantially protected from severe malaria.
- G6PD deficiency - ? deficiency of G6PD enzyme needed for parasite
- HLA- Certain Bw and D haplotypes found commonly in West Africa are protective, not against infection, but against severe malaria.
- Thalassemia: an inherited disorder characterized by abnormal formation of hemoglobin
13
Q
Malaria Immunity
A
- Combination of innate and acquired
- Never protects from re-infection
- However prior infection confers substantial protection from severe disease
- Adults in highly endemic areas seldom die from malaria (or even become that ill)
14
Q
Malaria: Clinical Illness
A
- Fever and chills (cold, hot, wet)
- The fever coincides with erythrocyte rupture and release of merozoites
- Periodicity (48 or 72 hours), (48 hrs; P. falciparum, P. vivax, P. ovale; 72 hrs, P. malariae)
- Headache
- GI symptoms are also common
- Severe malaria, almost always caused by P. falciparum
- Cerebral malaria primarily in children nonimmune individuals
15
Q
Malaria: Physical findings associated with poor prognosis
A
- Impaired consciousness - Coma
- Respiratory distress - pulmonary edema, tachypnea, labored deep breathing
- Repeated seizures
- Shock
- Abnormal bleeding; retinal hemorrhages
- Jaundice
- Dark urine (hemolysis)
