vivax or benign tertian malaria Malaria is a mosquito-borne infectious disease affecting humans and other animals caused by parasitic protozoans (Plasmodium) P.vivax: vivax or benign tertian malaria Most predominant P.ovale: ovale or ovale tertian malaria Tropics P.malariae: malariae or quartan malaria Temperate zones P.falciparum: falciparum or subtertian or malignant malaria Tropics Geographical Distribution Presence of Malaria = Presence of Anopheline mosquito

Development of Plasmodium in infected human Infective♀ Anopheles injects sporozoites in its saliva at the site of bite I- Liver phase within 40 min in blood Liver merozoites P.vivax P.ovale hypnozoites Trophozoite Schizont Rupture II- Blood phase ♂ Blood merozoites P.v. 3rd d P.o. 3rd d ♀ P.m. 4th d Malaria pigment or haemozoin Ring Trophozoite Schizont Rupture P.f. irreg. gametocyte

Development in Anopheles Mosquito gut ♀ ♂ ♀ gametocytes Sporozoites in salivary gland Reduction division ♂ ♀ to form gametes Infective Stage Sporocyst Oocyst exflagellation Ookinete fusion Female Anopheles Malaria transmitter Alimentary canal of Anopheles mosquito Zygote

Pathology Malaria

Symptoms of malaria are due to the release of massive number of merozoites into the circulation. Infection results in the production of antibodies against merozoites and schizonts. The activated macrophages help in the destruction of infected erythrocytes and antibody-coated merozoites.. Malarial infection is associated with immunosuppression. Hemolysis of infected and uninfected R.B.Cs

In Falciparum malaria, ( adhesion phenomenon) occurs. Pathology In Falciparum malaria, ( adhesion phenomenon) occurs. Merozoites of P. vivax and P. ovale are able to invade only reticulocytes, P. malariae are limited to the old cells while, P. falciparum is able to invade all ages of R.B.Cs indifferently

Pathogenesis and Clinical Picture Incubation period followed by influenza-like symptoms. Malaria paroxysm (clinical attack): Coincides with: Haemozoin - Rupture of infected and uninfected RBCs. - Release of parasite metabolites. - Host immunologic response. Metabolites Includes: - Cold stage Lasts about 15 min. - Hot stage Lasts 2-6 hours - Sweating stage Lasts for hours

Pathogenesis and Clinical Picture Malarial paroxysmal attacks recur at the following intervals:- P. vivax and P. ovale attack occurs every 48 hours (tertian malaria). P. malariae attack occurs every 72 hours (quartan malaria). P. falciparum attack occurs from 24 -48 hours (malignant or irregular malaria).

Pathogenesis and Clinical Picture Patients also complain from headache, fatigue, dizziness, anorexia, arthralgia, abdominal pain, diarrhea and vomiting. There is anemia, splenomegaly and hepatomegaly. Between paroxysms, the patient may be tired but otherwise feel fairly good.

Pathogenesis and Clinical Picture Enlargement of liver and spleen. occurs due to enhanced phagocytosis of remnants of ruptured red cells and debris of schizont. Remnants

Anaemia: haemolytic anaemia Relapse (in P.vivax and P.ovale infection) due to presence of hypnozoites in the liver. Recrudescence (All species may recrudesce, especially P.malariae and P.falciparum infection) persistent low-grade parasitaemia due to incomplete treatment or failure of immune system to destroy the parasite . Anaemia: haemolytic anaemia Plasmodium parasite invades: - Reticulocytes only (in P.vivax and P.ovale). Restricted anaemia - Old RBCs only (in P.malariae). - RBCs at any age (in P.falciparum). Severe anaemia

MALARIA MALIGNANT P.falciparum

The most dangerous type, may be severe and fatal. Paroxysms are less well defined and fever may be continuous or irregular. In non-immune, the primary attack can be fatal whereas in endemic areas in immune adults it leads to parasitemia with no fever or illness. Recrudescences may occur up to 1 to 2 years, rarely longer.

Complications of falciparum malaria 1- Knobs develop on surface of infected RBCs Knobs are parasite antigens expressed on the surface of infected red cells containing trophozoites and schizont stages. They adhere to receptors found on endothelium of blood capillaries of internal organs blood supply anoxia and necrosis. Parasite antigens Normal RBC Blood capillary Infected RBC

In the lung : blood flow in pulmonary circulation. In brain : In the lung : blood flow in pulmonary circulation. In liver : impaired glycogenolysis In the kidney : acute renal failure. cerebral malaria. Headache, drowsiness, convulsions & coma Pulmonary oedema, difficulty in breathing Hypoglycemia: This is common in severe malaria, particularly in pregnancy.

In Gastrointestinal tract:- ischaemia in capillary bed of intestinal wall. An acute hepatitis with enlarged tender liver and jaundice. (b) Dysentery, which is very similar to acute bacillary dysentery. (c) Cholera-like, profuse diarrhea watery diarrhea, vomiting, dehydration and muscular cramps. Algid malaria: It resembles acute adrenal insufficiently with low blood pressure, collapse and peripheral vascular failure.

Tropical splenomegaly syndrome (Hyperactive malaria splenomegaly) Massive persistent splenomegaly in individual living in endemic area. A non transient reduction in spleen size upon antimalarial treatment. Lymphocytic infiltration of the liver. Anemia. Increased serum polyclonal IgM and antimalarial antibodies and immune complexes.

Anaemia, haemoglobinuria, jaundice. Black water fever (Malarial haemoglobinuria): Occurs: when? - Repeated attacks of P.falciparum infection. - The trigger mechanism is irregular dosage of Quinine with exposure to cold or exercise. Pathogenesis intravascular hemolysis, hemoglobinuria, and renal failure that affects only none or semi-immune individuals Anaemia, haemoglobinuria, jaundice. This is autoimmune with development of antibodies to infected red blood cells.

Pathogenesis of Black Water Fever Blood Vessel of the infected patient Auto-antibodies Normal RBCs Infected RBCs Normal urine Jaundiced patient Haemoglobinuria

Parasitological examination Diagnosis Clinical diagnosis Characteristic fever, enlarged tender spleen, anemia (microcytic hypochromic) and leucopenia or pancytopenia. Parasitological examination Blood film (thin and thick) stained by Giemsa or Leishman stains

Diagnosis 1- Thin and thick blood films to demonstrate the parasite. Thin blood film One drop of blood spread on a slide Finger prick Thick blood film 4 drops of blood spread in a small circle on a slide Giemsa stained blood films

X X P. vivax P. ovale P. malariae P. falciparum Infected RBC Enlarged, rounded Enlarged, oval Normal size & shape Ring 1/3 RBC size Ring 1/3 RBC size Ring 1/3 RBC size Ring 1/6 RBC size Ring Multiple rings Malaria pigments (Haemozoin) X Trophozoite Band-shaped Ziemann’s dots Maurer’s clefts Schuffner’s dots Schizont X Not seen in peripheral blood Gametocyte ♀ ♂ ♀ ♂ ♀ ♂ ♀ ♂

Malaria pigments = Haemozoin It is the remnants of haemoglobin that was digested by Plasmodium parasite Schuffner’s dots Ziemann’s dots Maurer’s clefts Called: Stippling It is degeneration process occurring in Plasmodium infected RBCs

Diagnosis Provocative test (Ascoli test) By injection of 1/2 cc adrenaline solution 1/1000 subcutaneously to stimulate the parasite to appear in peripheral blood in chronic cases (with no parasites in blood). Also, cold shower may be useful.

Serological Diagnosis 2- Detection of circulating parasite antigen using monoclonal antibodies. C T 3- Detection of parasite DNA and RNA in patient’s blood using DNA and RNA probes.

Treatment Radical cure drugs: Drugs acting on pre-erythrocytic and tissue forms and prevent relapses e.g. primaquine   Suppressive drugs: Act on erythrocytic stages to terminate acute attack, but relapses may occur e.g. Quinine, atebrine, chloroquine, comaquin and mefloquine. Gametocidal drugs: Destroy gametocytes, prevent infection of mosquito e.g. primaquine, pyrimethamine and proguanil.

Control Treatment of cases. Mosquito control. Chemoprophylaxis. Vaccination: Many methods of vaccination against malaria are now investigated, aiming either to prevent any infection or to alleviate clinical picture or to stop transmission to mosquito. None has been approved as effective vaccine for humans.