Malaria An Overview of Life-cycle, Morphology and Clinical Picture

Malaria Species Five species of malaria infect humans: Plasmodium falciparum: malignant tertian malaria Plasmodium vivax: benign tertian malaria Plasmodium ovale : benign tertian malaria Plasmodium malariae: quartan malaria Plasmodium knowlesi (zoonotic)

Distribution of Plasmodium knowlesi Plasmodium knowlesi infections reported in humans and macaques and limits of natural distribution of mosquito vectors and of macaques. The numbers in parentheses represent numbers of P. knowlesi cases reported for each Southeast Asian country or region in Malaysia.

Distribution of malaria in KSA

LIFE CYCLE OF MALARIA sporozoites Stomach Wall Pre-erythrocytic Oocyst Stomach Wall Sporozoites Salivary Gland Zygote Gametocytes sporozoites Pre-erythrocytic (hepatic) cycle Hypnozoites Exo-erythrocytic (hepatic) cycle Erythrocytic Cycle

Plasmodium vivax, Plasmodium ovale Plasmodium falciparum:: Plasmodium vivax, Plasmodium ovale Plasmodium malariae\:

CLINICAL SIGNS & SYMPTOMS OF MALARIA Fever Chills Sweating

feeling of intense cold vigorous shivering lasts 15-60 minutes Malarial Paroxysm cold stage feeling of intense cold vigorous shivering lasts 15-60 minutes hot stage intense heat dry burning skin throbbing headache lasts 2-6 hours   sweating stage profuse sweating declining temperature exhausted and weak → sleep lasts 2-4 hours

CLINICAL PICTURE Chronic Disease Acute Disease Infection During Pregnancy Non-severe Acute Febrile disease Chronic Asymptomatic Infection Placental Malaria Cerebral Malaria Anemia Low Birth weight Developmental Disorders; Transfusions; Death Increased Infant Mortality Death

Components of the Malaria Life Cycle Sporogonic cycle Infective Period Mosquito bites uninfected person Mosquito Vector Parasites visible in blood Human Host Mosquito bites gametocytemic person Symptom onset Prepatent Period Recovery Incubation Period Clinical Illness

Definition Severe malaria is defined as symptomatic malaria in a patient with P. falciparum asexual parasitaemia with one or more of the following complications: Cerebral malaria (unrousable coma not attributable to other causes). Generalised convulsions (> 2 episodes within 24 hours) Severe normocytic anaemia (Ht<15% or Hb < 5 g/dl) Hypoglycaemia (glood glucose < 2.2 mmol/l or 40 mg/dl ) Metabolic acidosis with respiratory distress (arterial pH < 7.35 or bicarbonate < 15 mmol/l) Fluid and electrolyte disturbances Acute renal failure (urine <400 ml/24 h in adults; 12 ml/kg/24 h in children) Acute pulmonary oedema and adult respiratory distress syndrome Abnormal bleeding Jaundice Haemoglobinuria Circulatory collapse, shock, septicaema (algid malaria) Hyperparasitaemia (>10% in non-immune; >20% in semi-immune)

Definition Uncomplicated malaria is defined as: Symptomatic infection with malaria parasitemia without signs of severity and/or evidence of vital organ dysfunction.

Complications of malaria : Cerebral malaria

Complications of malaria : Pulmonary oedema

Complications of malaria : anaemia Child with severe malaria anaemia and no other malaria complication

Child with severe malaria anaemia in conjunction with acidosis and respiratory distress

Malarial haemoglobinuria Clinical Picture : Patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency may develop intravascular haemolysis and haemoglobinuria precipitated by primaquine and other oxidant drugs, even in the absence of malaria. Haemoglobinuria associated with malaria (“blackwater fever”) is uncommon and malarial haemoglobinuria usually presents in adults as severe disease with anaemia and renal failure.

Common methods for parasitological diagnosis of malaria The two methods common in use : 1: Light microscopy 2: Rapid diagnostic tests (RDTs).

Microscopy is the gold standard for diagnosis of malaria Parasite density Species diagnosis Monitoring response to treatment

Wellcome Trust (Modified) ACTION OF ANTIMALARIAL DRUG IN THE DIFFERENT LIFE STAGES OF THE MALARIA PARASITE Sporontocides Primaquine Pyrimethamine Proguanil Tissue Schizontocides Primaquine Pyrimethamine Tetracycline Proguanil Gametocyide Primaquine Anti-relapse (P.vivax) primaquine Blood Schizontocides Chloroquine Sulfadoxine/Pyrimethamine Quinine Quinidine Artemisinins Wellcome Trust (Modified)

Practical

PRACTICAL ON BLOOD PARASITES

Common methods for parasitological diagnosis of malaria The two methods common in use : 1: Light microscopy 2: Rapid diagnostic tests (RDTs).

Laboratory diagnosis of malaria Rapid diagnostic tests detect malaria antigens

RDT procedure

Laboratory diagnosis of malaria Light microscopy:1: Preparing blood film

Laboratory diagnosis of malaria Light microscopy:1: Preparing blood film

Laboratory diagnosis of malaria Light microscopy: Thick and thin films

Plasmodium falciparum (trophozoite stage in thick smear) Laboratory diagnosis of malaria Plasmodium falciparum (trophozoite stage in thin smear) Plasmodium falciparum (trophozoite stage in thick smear) CCMOVBD

The Malaria Parasite 34 Morphology of Malaria Three developmental CCMOVBD Trophozoites Three developmental stages seen in blood films: Trophozoite Schizont CCMOVBD CCMOVBD Gametocyte 2. Schizont 3. Gametocyte

35 Morphology of Malaria CCMOVBD Plasmodium vivax Species of malaria is identified by its chracteristic microscopic appearance: CCMOVBD Plasmodium malariae Malaria Tutorials, Wellcome Trust Plasmodium ovale

Plasmodium falciparum (trophozoite stage in thin smear) 36 Morphology of Malaria Plasmodium falciparum (trophozoite stage in thin smear) CCMOVBD

Plasmodium falciparum (trophozoite stage in thick smear) 37 Morphology of Malaria Plasmodium falciparum (trophozoite stage in thick smear) CCMOVBD

Plasmodium falciparum 38 Morphology of Malaria Plasmodium falciparum (characteristic banana-shaped or crescent –shaped gametocyte stage in thin smear) CCMOVBD

Diagnosis: malaria or Plasmodium vivax A 25 year-old male from India, who came 3 months ago was admitted in KKUH with a history of severe anaemia and intermittent high grade fever for the last two months not responding to antibiotics. WHAT IS THE DIAGNOSIS? Diagnosis: malaria or Plasmodium vivax

Diagnosis: malaria or Plasmodium vivax A businessman who makes frequent trips to Thailand , presents with intermittent fever . WHAT IS THE DIAGNOSIS? Diagnosis: malaria or Plasmodium vivax

Diagnosis: malaria or Plasmodium falciparum A student in KSU who returned three weeks from vacation in Africa , he developed intermittent fever last week and lost consciousness a short time ago. WHAT IS THE DIAGNOSIS? Diagnosis: malaria or Plasmodium falciparum

Plasmodium flaciparum , gametocyte stage The patient was then treated with schizontocidal antimalarial drugs, a follow-up blood film is shown . ARE THERE ANY PARASITES? WHAT STAGE ? Plasmodium flaciparum , gametocyte stage

Bone marrow aspiration Bone marrow amastigotes

Leishmania , amastigote stage A 7 year old child presented with anemia , hepatospenomegaly and fever .Not responding to antimalarials and antibiotics . Bone marrow smear is shown ARE THERE ANY PARASITES? WHAT STAGE ? Leishmania , amastigote stage