Plasmodium ( 疟原虫 )

History  Malaria is an old infectious disease. The first documentation about it is at 1500BC.  Until the end of the 19th century, it was commonly thought that malaria was caused by breathing bad air ( mal-aria ) and was associated with swamps

 Important application of the knowledge about malaria: W. Gorgas successfully implemented control strategies for malaria and yellow fever during the construction of Panama Canal History

Global distribution

Plasmodium that infect human

Malaria current status

Morphology Plasmodium is the one-cell parasite, so the basic morphology is a nucleus (chromatin), cytoplasma and cell membrane Wright or Giemsa stain gives the Cytoplasm – bluish; Chromatin - red to red-purple while the malarial pigments are yellow-brown There are three stages and six main forms of plasmodium in RBC

Plasmodium in RBC Trophozoites ( 滋养体期 ) ： ring form and developing trophozoites Schizonts ( 裂殖体期 ) ： immature and mature -- merozoites Gametocyte ( 配子体期 ) ： Microgametocytes and macrogametocytes

Trophozoites Fig. 1: normal red cell; Figs. 2-5: ring stage parasites (young trophozoites)

Ring form trophozoites Ring like plasma with one nucleus at one side Thin blood film (Giemsa stained)

Mature trophozoites (amoeboid form) The plasmodium grow with pseudopods, more cytoplasma and malarial pigment presented in the plasma Red blood cell enlarged and became pale with Schüffner‘s dots( 薛氏小点 )

Schizonts Figs. ： increasingly mature schizonts

Macrogametocyte (female gametocyte) of P.v Giemsa staining compact nucleus, usually at edge of the parasite scattered pigment granules The gametocyte is completely filling its host cell

Giemsa staining large nucleus at the center of the cell scattered pigment granules Microgametocyte (male gametocyte) of P.v

Macrogametocyte of P. f The crescent-shaped gametocytes of P. falciparum are very distinctive, but tend to only appear late in the infection Compact nucleus, red, usually at the center of the cell Malarial pigments around the nucleus

Microgametocyte of P. f Sausage-shaped with two blunt end Large nucleus at the center Sometimes hard to distinguish from the female gametocytes

exo-erythrocytic stage— merozoites in liver cells

The vector – female Anopheles

Development in the vector Gametocytes zygote oocyst sporozoites

Life Cycle

Life cycle Infective stage ： sporozoites Transmission – female Anopheles mosquito – transfusion – transplacental – needle stick Pathogenic stages ： erythrocytic stage Diagnositic stages ： erythrocytic stage

Pathogenesis

Clinical features Incubation period （潜伏期） Time interval between the mosquito bite and the onset of the clinical symptoms Time for the sporozoite reaching liver and entering Duration of the development in the liver Time of development in the RBC to produce sufficient erythrocytic merozoites to cause clinical symptoms – P. falciparum 7 to 27 days – P. vivax 8 to 31 days – P. malarie 18 to 40 days – P. ovale 16 to 18 days

Clinical features Typical malaria paroxysm （发作） l Malarial paroxysm -symptom for erythrocytic phase – RBCs rupture releasing merozoites, malarial metabolites, endotoxin in blood – shaking chill （寒战） followed by fever （高热） (2-20 hrs) – profuse sweating when fever breaks （出汗退热） – repeated characteristic cycle for each species P. falciparum 36-48hrs P. vivax 48hrs P. malariae 72hrs P. ovale 48hrs

Recrudescence versus relapse Recrudescence （再燃） is the return of the symptom of malaria after apparent cure, which is due to a sudden increase in what was a persistent, low-level parasite population in the blood. – The periodic increase in numbers of parasites results from a residual population persisting at very low levels in the blood after inadequate or incomplete treatment of the initial infection. – The asymptomatic situation may last for as long as 53 years.

Recrudescence versus relapse Victims may suffer relapse （复发） after apparent recovery of malaria. This is caused by the long prepatent sporozoites (LPPs) or hypnozoites which remain dormant in the hepatocytes for an indefinite period. – P. vivax and P. ovale will develop hypnozoites in the liver responsible for relapse while patients infected with P. falciparum and P. malariae have no phenomenon of relapse All four types of plasmodium can maintain low level of parasitemia and account for the recrudescence of the disease

Clinical features liver & spleen damage of long-term complications from P. falciparum – Anemia – tropical splenomegaly syndrome – cerebral malaria - 50% of deaths coma and renal failure due to tubular necrosis

tropical splenomegaly syndrome

Cerebral malaria

Diagnosis Travel history to endemic area & presence of symptoms, e.g., fever and chills Thick smears - hard to read Thin smears - see RBC morphology and parasite characteristics serology - helps rule out fever of unknown origin DNA probes- too slow & costly esp. in field

Diagnosis Thick blood smear Thin blood smear

Indirect fluorescent antibody test （ IFA ）

Treatment Quinidine( 奎尼丁 ), chloroquine( 氯喹 ), primaquine( 伯氨喹 ), pyrimethamine( 乙胺嘧 啶 ), artemisinin( 青蒿素 ), sulfadoxine( 磺胺 ), mefloquine( 甲氟喹 ), tetracycline( 四环素 ), proguanil( 氯胍 ) affect parasite in different ways depending on stage when administered different species react differently emergence of drug-resistant malaria

Prevention and control Personal protection- netting, repellents, etc. mosquito control or eradication - not easy avoid sharing needles develop vaccines - not currently available select proper treatment for species and morphological forms

summary Relapse Recrudescence Typical malaria paroxysm How to reduce the morbidity and mortality of malaria?