Malaria Presented by Dr Malaria Presented by Dr. Abdalla Abu Gabal Cnsultant of fevers Imbaba Fever Hospital

It is a parasitic disease affecting nearly 500 million persons globally with 1.5-3.5 deaths every year. It is one of most prevalent 10 diseases in the world. It occurs in tropical and subtropical countries laying between latitude 30S – 40N . About 80%-90% of cases occur in Africa.

Causative organism: It is caused by plasmodium species which are unicellular parasites , only 4 of them affect human, Plasmodium P.vivax P.ovale P. malariae P.falciparum

Anopheles Mosquito Live in hot humid atmosphere it bites at night only The female only uses human blood. make an acute angle when stand on the skin inject its saliva in the puncture site before sucking

Sexual cycle in mosquito. Life cycle Asexual cycle in man Sexual cycle in mosquito.

Asexual cycle Pre-erythrocytic schizogony Erythrocytic schizogony Gametogony Erythrocytic schizogony Exo-erythrocytic schizogony

Pre- erythrocytic schizogony -Occurs in the liver cells. -Multiply and mature to mature schizont -Containes 4-32 merozoites - In a time from 8-30 days - Hypnozoite, in vivax and probably in ovale,

Erythrocytic schizogony - starts with the penetration of the merozoites to the R.B.Cs. - In P.vivax & P.ovale, it attacks reticulocytes. - In P.malariae, it attacks young R.B.Cs. - In P. falciparum it attacks all types of R.B.Cs. -Divides and mature, ring form, trophozoite mature trophozoite and schizont, rupture and release the erythrocytic merozoites .

- Depends on digestion of hemoglobin with production of hemozoin or malaria pigment. - The release of this pigment is responsible for clinical symptoms and cytokine production [TNF alpha, IL1& IL6]. -The time of this cycle is 48 hours in P.vivax., P.ovale & P.falciparum. and 72 hours in P.malariae.

Gametogony - After several cycles in the R.B.Cs. some merozoites developed into male or female gametocytes [micro & macrogametocytes], - It appear in the peripheral blood and when sucked by anopheles mosquito, it complete the sexual cycle.

Exo-erythrocytic schizogony - Some merozoites released from R.B.Cs re-invade the liver cells, divide and produce exo-erythrocytic merozoites again . - Occur in all types except in P. falciparum - Responsible for the chronic form in the three types.

sexual cycle - Occurs in mosquito after ingestion of male & female gametocytes - On reaching the midgut, it fuses together forming the zygote. - Develops into ookinete then penetrate gut wall and form an oocyst. - Asexual divisions takes place giving rise to sporoblasts containing sporozoites that migrate to the salivary gland and appears in saliva. - A journey of about 59 days.

Pathophysiology: The plasmodium itself is non-toxin producer and live always far from the immune system except for short period of time The hazards are due to: hemozoin, that stimulate the cytokine production , its usage of glucose . rupture of parasitized R.B.Cs. and waste of hb. cyto-adherence and rosette formation in falciparum M immune reaction in chronic malaria may lead to nephritis.

Effects and coplications of Malaia Anemia: prominent specially in falciparum malaria Thrombocytopenia: Mainly due sequestration in the spleen Hypoglycaemia: Occurs in heavy parasitaemia specially in falciparum infection Hyponatraemia: Hypovolaemia and shock [Algidmalaria]: Cerebral Malaria: Is characteristic of falciparum malaria With heavy parasitaemia Acute renal failure: Pulmonary edema:

* Blood transfusion from an infected donor. Mode of transmission . * Biting with an infected female anopheles mosquito * Blood transfusion from an infected donor. * Through an infected syringe in between drug user addicts. * Congenital: very rare, it can occur all types of malaria but the etiology is not clear until now.

Clinical Picture I.P: 10-14 days in P.vivax, P.ovale, & P. falciparum and 18 days to 6 weeks in P. malariae infection. febrile paroxysms, anemia, splenomegaly and hepatomegaly are usually present.

Malarial febrile paroxysms have 3 stages. 1-The ,cold stage: * lasts from 30 minutes to one hour. *There is marked shivering . *Temperature rises rapidly , often to as high as 41 c. 2-The Hot stage: *Abruptly follows and lasts for 2-6 hours . * the patient feels intensely hot and uncomfortable . * delirium may be present. 3-The sweating stage : * It quickly follows with drenching sweat. *The patien feels fatigued and exhausted and often sleep. *Herpes labialis frequently occur in established malaria.

Cerebral Malaria: It complicates severe form of falciparum malaria specially in non immune persons. The mortality is about 20% in adults & 15% in children It is characterized by marked elevation in body temperature , rapid deterioration in consciousness , convulsions , coma and death. It accounts for about 80% of deaths due to falciparum infection.

Diagnosis: A history of travel and awareness of possible diagnosis is vital and should be considered in any febrile patient. Blood film: Thin and thick blood smears stained with Giemsa, wright or leishman stains should indicate the plasmodium species and the percentage of infected RBCs. Dipstick test: A monoclonal antibody for detection malaia antigen . It is easy, accurate and specific for type of malaia . IgM&IgG level : By indirect immunofluorescence , indirect haemagglutination & gel diffusion techniques.It is used mainly for epidemiological survey Antigen detection: By ELISA. PCR: Is very sensitive and specific and can detect as few as 50 parasites.

This micrograph illustrates the trophozoite form, or immature-ring form, of the malarial parasite within peripheral erythrocytes. RBCs infected with trophozoites do not produce sequestrins and, therefore, are able to pass through the spleen.

A mature schizont within an erythrocyte A mature schizont within an erythrocyte.These RBCs are sequestered in the spleen when malaria proteins, called sequestrins, on the RBC surface bind to endothelial cells within that organ. Sequestrins are only on the surfaces of erythrocytes that contain the schizont form of the parasite.

Other lab. tests: Blood picture: Anaemia is prominent Neutrophil leucocytosis is usual in severe infection Thrombocytopenia is common in falciparum & vivax Prothrombin and partial thromboplastin time are prolonged in about 20% of cerebral malaria.

Liver Function Tests: Total & unconjugated s.bilirubin are usually increased corresponding to haemolysis. Total & direct bilirubin are increased in cases of liver cell dysfunction. S. albumen concentration is usually reduced. Aminotransferases and 5-nucleotidase and specially LDH are moderately elevated.

Electrolyte Level: Hyponatraemia is the most common electrolyte disturbance . Mild hypocalcaemia & hypophosphataemia are described.

S. Ureaincreased above 80 mg/dl and creatinine above 2 mg/dl S. Ureaincreased above 80 mg/dl and creatinine above 2 mg/dl.In about one third of cerebral malaria S. Glucose level: Hypoglycemia specially in children, pregnant women and severely ill patients Blood Culture: For gram –ve bacilli [ E.coli. pseudomonas aeruginosa, ect.] specially in patients with leucocytosis , shock or persistent fever usually positive Urine analysis: Proteinuria, microscopic haematuria , haemoglobinuria and RBCs casts are common abnormalities. Urine is black in severe haemolysis .

Treatment Chloroquine-sensetive P.falciparum,P. vivax, P.ovale & P.malariae malaria: 1.Chloroquine: Adults: 600 mg of the base on the 1st and 2nd days; 300 mg on the 3rd day. Children: approximately 10 mg base/kg on the 1st and 2nd days; 5 mg/kg on the 3rd day. 2.Primaquine: Adults (except pregnant and lactating women and G6PD-deficient patients): 15 mg base/day on days 4-17 or 45 mg/week for 8 weeks. Children: 0.25 mg base/kg/day on days 4–17 or 0.75 mg/kg/week for 8 weeks

1-Coartem: Chloroquine-resistant P. falciparum malaria. Adult dose consists of 24 tablets within 3 days as follows : 1st day.: 4 tablets ………8 hours……….. 4 tab. 2nd day 4 tablets……….12 hours……….4 tab. 3rd day 4 tablets……….12 hours……….4 tab. Children: 5-14 kgm wt (< 3 years old)…………..1 tab. 15- 24 kgm wt. ( 3-9 years old)…………..2 tab 25- 40 kgm wt. ( 9-14 years old)………....3 tab. 40 kgm wt. ( >15 years old) ………....4 tab.

Chloroquine-resistant P. falciparum malaria. 2.Quinine Adults: 600 mg of the salt( 1 tab.) tid for 7 days and, if quinine resistance is known or suspected, followed by either Fansidar 3 tablets once or Doxycycline 100 mg twice dailyfor 7 days Children: approximately 10 mg of the salt/kg 3 times each day for 7 days .

Chloroquine-resistant P. falciparum malaria. 3-Mefloquine: (Lariam 250 mg tablet) Adults: 15-25 mg of the base/kg (maximum 1500 mg) given as 2 doses 6-8 h apart Children: 25 mg of the base/kg given as 2 doses 6-8 h apart

Chloroquine-resistant P. falciparum malaria. 4-Malarone:. Adults: 4 adult tablets [ Atovaquone 250 mg , proguanil Hcl 100 mg tab.] in a single dose for three successive days after meal or with a cup of milk.

Chloroquine-resistant P. falciparum malaria. 4-Malarone:. Children: It is given according to the body wt. as shown in the table using the pediatric tablets [62.5 Atovaquone & 25 mg proguanil Hcl per tablet]: Wt. in kg Dose 5-8 kg 2 ped. tab. 9-10 kg 3 ped. tab. 11-20 kg 1 adult tab. 21-30 kg 2 adult tab. 31-40 kg 3 adult tab. > 40 kg 4 adult tab.

Chloroquine-resistant P. falciparum malaria. 5.Fansidar: Sulfadoxine (500 mg per tablet) pluspyrimethamine (25 mg); Adults: 3 tablets as a single dose Children: <1 year 1/4 tablet. 1-5 years 1/2 tablet. 6-9 years 1 tablet. 10-15 years 2 tablets

Chloroquine-resistant P. falciparum malaria. Primaquine: Must be given after treatment of falceparum malaria as follows: Adults (except pregnant and lactating women and G6PD-deficient patients): 15 mg base(1 tab.)/day and children, 0.25 mg base/kg/day for 3-5 days.

Treatment of cerebral malaria: * Patient should be treated in the ICU . * Convulsions can be controlled with IV diazepam. * Hyperthermia is treated by slow evaporative method . * Hypoglycemia with dextrose 10% infusion. * Drug therapy: Quinine dihydrochloride ,given IV in isotonic solution e.g. 5% dextose by drip over 2-4 hours. A loading dose 20 mg/kg is given first followed with a maintenance dose of 10 mg every 8 hours until the patient regains consciousness and complete orally to complete one week followed by 3 tablets of Fansidar.

Treatment of cerebral malaria: Artemisinin : can be used instead of quinine in the form of Artemether [Artenam] in adose of 3.2 mg/kg as a loading dose in the 1st day then 1.6 mg/kg daily until oral therapy is possible. It is given IM in the anterior aspect of the thigh.

Chemoprophylaxis For chloroquine-sensitive malaria : chloroquine phosphate: (Alexoquine 250 mg tab.) Adult dose: 2 tab orally, once/ week Pediatric dose: 5 mg/kg base (8.3 mg/ kg salt) orally, once/ week, up to maximum adult dose of 300 mg base ( 2 tab.). Begin 1-2 weeks before travel to malarious areas until 4 weeks after return

Chemoprophylaxis For chloroquine-resistent malaria : Mefloquine (Lariam 250 mg tab.): Started 1-2 weeks before travel to malarious areas. continued once a week, on the same day, during travel and for 4 weeks after return Adult dose: 1 tab. (250 mg) orally, once/ week Pediatric dose: ≤9 kg: 4.6 mg/kg base (5 mg/kg salt) once/week 10-19 kg: 1/4 tablet once/week 20-30 kg: 1/2 tablet once/week 31-45 kg: 3/4 tablet once/week ≥46 kg: 1 tablet once/ week In pregnancy : the drug of choice.

Chemoprophylaxis For chloroquine-resistent malaria : Atovaquone / proguanil (Malarone): Prophylaxis in areas with chloroquineresistant or mefloquine-resistant P. falciparum. Adult tablets 1 adult tablet (250 mg atovaquone and 100 mg proguanil hydrochloride) orally, daily 2 days before travel until one week after return Pediatric tablets (62.5 mg atovaquone and 25 mg proguanil hydrochloride). 5-8 kg: 1/2 pediatric tablet daily >8-10 kg: 3/4 pediatric tablet daily >10-20 kg: 1 pediatric tablet daily >20-30 kg: 2 pediatric tablets daily >30-40 kg: 3 pediatric tablets daily >40 kg: 1 adult tablet daily 41 kg or more: 1 adult tablet daily

Chemoprophylaxis For chloroquine-resistent malaria :. Doxycycline Prophylaxis in areas with chloroquine-resistant or mefloquine-resistant P. falciparum.( south east of Asia) Adult dose: 100 mg orally, daily Pediatric dose: ≥8 years of age: 2 mg/ kg up to adult dose of 100 mg/day. Taken 1-2 days before travel to malarious areas daily at the same time each day and for 4 weeks after return. Contraindicated in children <8 years of age and pregnant women..