Plasmodium Species and Babesia Chapter Notes | Microbiology - NEET PG PDF Download

Plasmodium

Plasmodium species responsible for malaria include the following:

• Species: Plasmodium vivax, Disease: Benign tertian, Periodicity (Hours): 48
• Species: Plasmodium falciparum, Disease: Malignant tertian, Periodicity (Hours): 48
• Species: Plasmodium ovale, Disease: Ovale tertian, Periodicity (Hours): 48
• Species: Plasmodium malariae, Disease: Quartan, Periodicity (Hours): 72
• Species: Plasmodium knowlesi, Disease: Quotidian, Periodicity (Hours): 24

Life Cycle

• Definitive host involves female Anopheles mosquitoes.
• Intermediate host is humans.
• Infective form to humans consists of sporozoites located in the mosquito's salivary gland.
• Infective form to humans via blood transfusion or vertical transmission is the trophozoite.
• Differences in life cycle when transmitted by blood transfusion or vertical mode include:
  • Absence of liver stage, with infective form being trophozoite leading to merozoite.
  • No production of hypnozoites.
  • Therefore, no relapse occurs.
  • Hence, primaquine is not required.
• Infective form to mosquito is the gametocyte.
• For mosquitoes to be infected, gametocytes must be mature, viable, and present in counts greater than 12 per cubic mm of blood.
• Asexual cycle in humans:
  • Following mosquito bite, sporozoites enter blood and are transported to liver.
  • Liver cycle (pre or exoerythrocytic cycle): Sporozoites change into trophozoites, then pre-erythrocytic schizont performs schizogony to yield pre-erythrocytic (PE) merozoites.
  • RBC cycle: PE merozoites enter RBCs, become early trophozoites (ring form), progress to late trophozoites, then erythrocytic schizont, which undergoes schizogony to form merozoites.
  • Merozoite release causes clinical symptoms to appear.
  • Merozoites can either invade more RBCs to continue the cycle or develop into gametocytes that can infect mosquitoes.
• Sexual cycle (Sporogony): Starts with gametocytes entering female Anopheles mosquito, transforming into gametes, then zygote, ookinete, oocyst, and finally sporozoites.

Recrudescence

• In P. falciparum malaria: Caused by survival of drug-resistant parasites, with fever returning after 2–3 weeks post-treatment.
• In P. malariae infection: Long-term recrudescences can occur up to 60 years, due to prolonged survival of erythrocytic stages at low, undetectable levels in blood.

Relapse

• Caused by hypnozoites (dormant stage) that can reactivate after 2-3 years of malaria infection.
• Occurs in P. vivax and P. ovale.
• Treatment for relapse involves primaquine.

Differences between the four malaria parasites

Pathogenesis of P. falciparum

• Sequestration refers to parasites being retained in blood vessels of deep organs like brain and kidney, causing vascular blockage.
  • Cytoadherence involves binding of RBC to endothelium via Pf EMP.
  • Rosetting occurs when unparasitized RBCs cluster with parasitized RBCs.
• Cytokines are released due to GPI (glucosylphosphatidyl Inositol).
• Antigenic diversity exists in Pf EMP.

Immunity

• Nature of Hemoglobin:
  • Sickle cell anemia trait provides protection from P. falciparum.
  • Thalassemia trait offers protection from P. falciparum.
  • Fetal Hb gives protection from P. falciparum.
• Nature of RBC:
  • P. falciparum infects RBCs of all ages.
  • P. malariae infects old RBCs.
  • P. ovale and P. vivax infect young RBCs.
• Nature of Enzyme: G6PD deficiency protects from P. falciparum.
• Ovalocytosis makes RBC rigid, protecting from P. falciparum.
• Duffy negative RBC protects from P. vivax.
• HLA-BW53 and haplotypes with DRW13.02 antigen and R111 gene contribute to immunity.
• Nutritional status has a paradoxical effect.
• Predisposing factors:
  • Density of the vector.
  • Number of human bites per day per mosquito.
  • Time of mosquito bite (more after dusk).
  • Optimum temperature (20–30 °C).
  • Optimum humidity (60%).
  • Rainfall (July to November).
  • Altitude below 2000 meters.
  • Mosquito longevity (as sporogony lasts for 7–30 days, thus, to transmit malaria, the mosquito must live > 7 days).

Epidemiology

Situation in World

• Most affected area is Sub-Saharan Africa (85%), followed by South East Asia Region (SEAR) (10%) and Mediterranean (4%).
• P. vivax is the predominant species.
• Age: Children are most affected.

Situation in India

• P. falciparum accounts for 51% and P. vivax for 49%, with few mixed infections reported.
  • 22% of people live in high transmission areas (≥ 1 case per 1000).
  • 67% in low transmission areas (0–1 case per 1000).
  • 11% in malaria-free areas.
• Odisha is most affected (24%), with 92% cases due to P. falciparum.
• P. malariae is less than 1% in India, mainly in Tumkur and Hassan districts of Karnataka.
• P. ovale is confined to tropical Africa, with only few cases from India (Odisha, Delhi, Assam, Gujarat, and Kolkata).
• Roll back malaria: Launched in 2000, aims to reduce malaria cases by 50% by end of 2010 and 75% by end of 2015.
• World malaria day: Observed every year on 25th April.

Clinical Features of Malaria

• Fever.
• Sweating.
• Anemia.
• Splenomegaly (enlarged spleen).
• Irritability.
• Coma.
• Retinal Hemorrhages.
• Algid Malaria (a shock-like syndrome).
• Respiratory distress syndrome.

Complications

• Cerebral malaria.
• Black water fever.
• Tropical splenomegaly syndrome.
• Malarial hyperpyrexia.
• Gastrointestinal disorders.
• Algid malaria.
• Nephrotic syndrome: Associated with P. malariae infection.
• Promotes Burkitt’s Lymphoma.

Plasmodium Knowlesi

• It is a malaria parasite primarily of monkeys but can infect humans, recently reported from Asia.
• Not reported from India yet, although the vector Anopheles leucosphyrus is present in southwest coastal region.
• Large focus of P. knowlesi in humans: Recently identified in Malaysia, Singapore, and Thailand.
• Blood smear examination: Early trophozoite resembles P. falciparum, and late trophozoite resembles P. malariae.
• Produces acute illness and relatively high parasitaemia compared to P. malariae.
• Paroxysms of fever occur daily (quotidian malaria) due to short RBC cycle.

Laboratory Diagnosis

Microscopic Tests

• Examination of peripheral blood smears (thin and thick blood films): Considered the gold standard method.
  • Thick smear: More sensitive (40 times), used for quantification and detection of malaria pigment.
  • Thin smears: Used for species identification.
  • Feathery tail end of the smear should be examined.
  • At least 200–300 oil immersion fields should be examined before declaring negative.
• Stains used:
  • JSB (Jaswant Singh and Bhattacharya) stain – Used in malaria control programme in India.
  • Leishman’s, Giemsa, and Field’s, Wright’s.
• Fluorescence microscopy (Kawamoto technique) - by Acridine orange stain.
• Quantitative Buffy coat examination (QBC): Rapid method for parasite detection.
  • Blood is collected in a capillary tube coated with acridine orange, then centrifuged, and buffy coat region (junction of RBC & WBC) examined under UV.

Non-microscopic Tests

• Antigen detection tests: Rapid diagnostic tests (RDTs) or Immunochromatographic tests (ICTs).
  • Rapid and simple but less sensitive, costly, and may give false positives in RA factor positive cases.
  • pLDH and Aldolase: Common to all Plasmodium species.
  • HRP-2 Ag detection: Specific for P. falciparum.
• Antibody detection methods:
  • Used for epidemiological surveys in malaria.
  • Screening of blood banks: To identify infected donors.
• Culture of malarial parasites: Tragger and Jensen method using RPMI 1640 medium is used for research purposes.
• Molecular methods - PCR using PBRK1 primer.
  • It is 100 times more sensitive than thick blood smear.
  • Speciation can be performed.
  • Drug resistance genes can be detected.

Comparison of Peripheral Smear, QBC and Rapid Diagnostic Tests

Treatment

Uncomplicated Benign Malaria in India

• Chloroquine remains the drug of choice for uncomplicated benign malaria in India, administered as 25 mg/kg divided over three days.
• Relapse rate of vivax malaria is around 30% in India. Primaquine is administered as 0.25 mg/kg daily for 14 days to prevent relapse.

Complicated or Falciparum Malaria in India
Treatment of falciparum malaria in India depends on whether the area is resistant or sensitive to chloroquine.

• Artemisinin combination therapy (ACT) is recommended in chloroquine resistant areas, whereas chloroquine can be used in sensitive areas.
• Artemisinin combination therapy (ACT) includes a combination of artemisinin derivative (Artemisinin or artemether or arte-ether) and long-acting antimalarial drugs like sulfadoxine-pyrimethamine, mefloquine, or lumefantrine.
• For treatment failure of P. falciparum cases: Quinine combined with doxycycline or tetracycline is recommended.
• Chloroquine resistant areas where Artemisinin combination therapy (ACT) is recommended: Odisha, Jharkhand, Madhya Pradesh, Chhattisgarh, and Andhra Pradesh.
• In pregnancy: Quinine is recommended in first trimester, whereas Artemisinin combination therapy (ACT) is given in second and third trimester.
• Treatment of unconfirmed cases or mixed infection with P. falciparum should be treated as falciparum malaria, plus primaquine is given for radical cure.

Babesia

• Intraerythrocytic protozoa.
• Causes malaria-like illness in animals and zoonotic opportunistic infections in humans.
• Not found in India.
• Vector: Tick borne.
• Treatment: Clindamycin with oral quinine and atovaquone and azithromycin.
• Differences from Plasmodium:
  • Hemozoin absent.
  • Gametocyte not distinguished from asexual forms.
  • Maltese cross form seen: Ring forms arranged in tetrad.

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