Malaria

Malaria

1. MALARIA www.medrockets.com Fb:Medrockets

2. Global burden of malaria Most important parasitic disease of humans Disease burden: 300 – 500 Mil . Cases; 90% in Africa 103 countries in the world are malarious . 2 Bil . people exposed to the risk of infection annually. Eliminated from north America, Europe and Russia Residents of non-endemic areas may also have Travel malaria Airport malaria Mortality very high in this group www.medrockets.com Fb:Medrockets

3. Malaria transmission occurs in more than 100 countries. Majority of which, possess tropical or subtropical zones where anopheles mosquito habitats exist.   A child dies every 5 seconds from malaria in Africa New methods estimate the number of malaria cases to be 243 million clinical cases and 863 thousands deaths (2008 estimates) More than 85% of malaria cases and 90% of malaria deaths occur in Africa south of the Sahara Responsible for 1 in 4 childhood deaths in Africa Accounts for 10% of Africa’s disease burden It is the leading cause of Under-5 mortality in Africa [20%] It accounting for about 40% of public health expenditure in many African homes In Nigeria, N132 billion is lost annually from malaria. Global burden of malaria www.medrockets.com Fb:Medrockets

4. ETIOLOGY The parasite (Plasmodium) is introduced into the host through a bite by a female Anopheles mosquito Plasmodium is an obligate intracellular blood protozoa with 100 species but only 4 [+1] species implicated in malaria. They are Plasmodium falciparum, vivax, ovale & malariae . Plasmodium falciparum is the most common and causes the most lethal infection in the tropics and subtropics, as it destroys RBCs of all ages and multiply infects red cells to a high degree Plasmodium malariae destroys the aged RBCs, causing a mild infection.

5. Plasmodia ovale and vivax destroy young RBCs, resulting in a mild infection but relapse due to the presence of hypnozoites in the hepatic tissues. Plasmodium falciparum is responsible for 80-90% of malarial infection either alone or in combination. Plasmodium vivax is uncommon in Africa . Less common means of infection includes: -Congenital acquisition through the placenta. -Infected blood transfusion. -Perinatally due to mingling of blood during birth. ETIOLOGY

6. Endemicity and immunity to malaria Endemicity refers to the amount or severity of malaria in an area or community. Measured by parasitaemia or palpable spleen rates: Hypoendemicity - little transmission and the disease has little effect on the population. (<10%) Mesoendemicity - varying intensity of transmission; typically found in rural communities of the sub-tropics. (10-50%) Hyperendemicity - intense but seasonal transmission; immunity is insufficient to prevent the effects of malaria on all age groups. (51-75% ) D. Holoendemicity - intense transmission occurs throughout the year. As people are continuously exposed to MPs they gradually develop immunity to the disease . (>75% )

7. Endemicity and immunity to malaria Depending on the intensity of transmission, malaria can be stable or unstable, reflecting different epidemic scenarios . Stable malaria: Sustained incidence over several years. Seasonal fluctuations in transmission may occur but epidemics are unlikely. Unstable malaria: Marked variations in the incidence of malaria over time. Population does not develop immunity and people of all ages are susceptible to severe disease when transmission increases.

8. Predisposition Malaria and hemoglobinopathies Geographical distribution of sickle-cell gene closely follows that of endemic P. falciparum malaria Subjects with sickle cell trait (Hb AS) have less severe malaria than individuals with AA genotype Susceptibility to malaria is increased by: Splenectomy Pregnancy (especially primigravidae ) Malnutrition www.medrockets.com Fb:Medrockets

9. Pathogenesis P. falciparum causes most severe disease because it can infect RBCs of any age Immunity can be natural or acquired Natural: Duffy-negative blood group- P. vivax (lacks receptor) Genotype AS Thalassemia G6PD deficiency Pyruvate Kinase deficiency Functional spleen Acquired : Following attack of malaria www.medrockets.com Fb:Medrockets

10. LIFE CYCLE

11. PATHOLOGY It is due to Haemolysis of infected RBCs and adherence of infected RBCs to capillaries. Profound anaemia is seen in prolonged attack due to haemolysis of RBCs. More severe haemolysis due to P. falciparum infection, as it invades RBCs of all ages. Liberation of toxic haemozoin and antigenic substances upon rupture of schizonts, which may further damage the capillaries. Adherence of parasitized cells to capillaries of major organs-brain, kidney, lungs, gut, liver, could cause organ congestion and anoxia.

12. OTHER GENETIC FACTORS . These factors influence the susceptibility to malaria by reducing the ability of MP to penetrate the RBCs, thus reduce the severity of acute malaria & prevalence of chronic malaria. - HbS -G-6-PD deficiency - HbF - HbE -Thalassemia -Duffy-negative genotype - Well-nourished children (Malnutrition does not increase the severity of malaria, as well-nourished children are more likely to suffer from severe malaria)

13. Innate or Acquired INATE- Red cell abnormalities –sickle cell trait, G6PD deficiency, Thalassaemia trait, ovalocytosis etc. Duffy antigen in W/Africans and vivax ACQUIRED-require repeated exposure. Neonates protected by maternal Ig G in the first 6 months. Antiparasite dx occurs at 10 yrs of age in area of stable transmission. Well-nourished children (Malnutrition does not increase the severity of malaria, as well-nourished children are more likely to suffer from severe malaria) PROTECTION AGAINST MALARIA

14. The clinical course of P. falciparum Following a bite by an infected mosquito, many people do not develop any signs of infection. If infection does progress, the outcome is one of three depending on host and parasite factors: Asymptomatic parasitaemia (“clinical immunity”) Acute, uncomplicated malaria Severe malaria www.medrockets.com Fb:Medrockets

15. MALARIA – Clinical syndromes Chronic Disease Chronic or Recurrent Asymptomatic Infection Placental Malaria & Anaemia Anaemia Infection During Pregnancy Developmental Disorders Transfusions Death Low Birth weight Increased Infant Mortality Acute Disease Non-severe Acute Febrile disease Cerebral Malaria Death

16. ACUTE UNCOMPLICATED MALARIA - Most cases in tropics and its clinical manifestation ( symptoms ) includes : 1. FEVER -commonest symptom in childhood, though variable, showing remarkable periodicity. -bouts of fever corresponds to the maturation & rupture of erythrocytic schizonts with subsequent discharge of merozoites into the bloodstream. - P.vivax , ovale .. 48hrs (tertian) - P.malariae .. 72hrs ( quartan ) - P. falciparum .. Irregular tertian (malignant tertian pattern )

17. Acute Uncomplicated contd - Obscured periodicity is seen in younger children, who are non- or semi- immune, as it corresponds to the level of parasitaemia . -Malaria febrile paroxysms are preceded by 3 defined stages, especially in older children viz the cold, hot & sweating stages. 2. HEADACHE ..very common symptom in older children. 3. VOMITTING ..bilious especially in the absence of diarrhoea . 4. PALLOR ..usually mild to moderate from haemolysis . 5. PAIN & OTHER ACHES ..commonly seen in children presenting with acute malaria. 6. DIARRHOEA .. P. falciparum in infants. 7. COUGH ..atypical in younger children. OTHER SYMPTOMS - General malaise, anorexia, www.medrockets.com Fb:Medrockets

18. Clinical signs - On examination ; Fever Pallor Jaundice is not a feature except in haemoglobinuria or if there is underlying pathology eg in sickle cell anaemia , sepsis, G-6-P-D deficiency Hepatomegaly Splenomegaly Hepatosplenomegaly Tender enlarged spleen (rare cases). www.medrockets.com Fb:Medrockets

19. It is a life threatening condition of P.falciparum malaria. It is diagnosed by the presence of asexual form of the P.falciparum in the peripheral blood smear of a Patient who presents with a potentially fatal complications of acute malaria, provided all diagnosis in other systems have been excluded. The essential pathology is by deep microvasculature parasite sequestration with obstruction of vascular flow resulting in hypoxic-ischaemic injury to the tissues, with greatest affectation to the brain. SEVERE MALARIA ( Acute complicated malaria)

20. Types & Diagnostic features of severe malaria. Prostration (generalized weakness) Hyperparasitaemia ( 5% of RBCs or 250,000 cu. ml) Cerebral malaria ..altered sensorium (  30minutes) Hyperpyrexia (rectal temp  40C) Severe anaemia (Hb5.0g/dl or PCV0.15 or Hb3.1mmol/L) Severe jaundice (Serum bilirubin  51  mol /L) Hypoglycaemia (RBS  2.2  mol /L) Renal failure ( Oligouria or anuria & Serum creatinine  265mol/L.) Shock (hypotension, rapidly thready pulse, pallor) Pulmonary oedema (clinical & radiological diagnosis) Clotting disturbance (bleeding episodes) Electrolyte & Acid-base balance (clinically, low serum levels, pH7.2)

21. SEVERE MALARIA [any of these] Clinical features: impaired consciousness or unrousable coma: prostration: generalised weakness so that the patient is unable walk or sit up without assistance. Child is unable to feed. multiple convulsions – more than two in 24 hours deep breathing, respiratory distress: acidotic breathing circulatory collapse or shock: systolic blood pressure <70mmHg in adults and <50mmHg in children jaundice haemoglobinuria: coke coloured urine abnormal spontaneous bleeding pulmonary oedema: clinical and radiological www.medrockets.com Fb:Medrockets

22. SEVERE MALARIA[any of these] Laboratory findings hypoglycaemia: blood glucose <2.2mmol/L or <40mg/dl metabolic acidosis: plasma bicarbonate <15mmol/L severe anaemia: ( Hb < 5g/dl, packed cell volume < 15%,) haemoglobinuria hyperparasitaemia : Parasite density >250,000/UL of blood or >5% parasitised red blod cells hyperlactataemia : lactate >5mmol/L renal impairment: serum creatinine >265micromol/L www.medrockets.com Fb:Medrockets

23. CEREBRAL MALARIA It is a rapidly progressive encephalopathy due to sludging of the cerebral capillaries by RBCs parasitized by asexual forms of P. falciparum and leading to cerebral hypoxia, edema. It is the most serious complication of falciparum malaria in children & occurs usually in children aged 6 mths to 5 yrs It is more prevalent in well-nourished children. Pathognomonic feature is the presence of ring haemorrhages surrounding the capillaries & arterioles in a brain biopsy and excess haemozoin (malarial pigment). Slatey grey appearance of brain tissue.

24. CEREBRAL MALARIA contd The ‘ Mechanical theory ’ postulates a phenomenom of reduced deformability and cyto-adherence in parasitized RBCs & rosetting in unparasitised RBCs causing obstruction of the cerebral capillaries & arterioles. WHO diagnostic criteria are Asexual parasitaemia of P. falciparum on blood film Altered sensorium lasting > 30 minutes. There is either no response or non-purposeful response to painful stimuli. Exclusion of other causes of encephalopathy eg meningitis [normal CSF ], encephalitis, hypoglycemia

25. Acute falciparum malaria which may be complicated by ARF & rarely by AGN . Also known to cause Quartan malarial nephropathy as it is caused by P. malariae. This is rarely reported in recent times. BLACKWATER FEVER -Is a syndrome of intravascular haemolytic episode with subsequent haemoglobinuria associated with falciparum malarial infection. -it is most likely due to hypersensitivity to incompletely killed parasites & usually follows inadequately treated acute P. falciparum infection or suppression by quinine. MALARIAL NEPHROPATHY

26. ANAEMIA IN MALARIA Multifactorial causes . They include : - Haemolysis -Sequestration of RBCs in RES & deep tissues. - Dyserythropoiesis -Capillary haemorrhages - Haemodilution due to expansion of plasma volume. -Bone marrow suppression. - Hypersplenism from hyperreactive splenomegaly ALGID MALARIA -It is characterised by shock [circulatory collapse]. -Usually associated with gram negative sepsis

27. Poor Prognostic symptoms 1 Clinical Marked agitation Hyperventilation (respiratory distress) Hypothermia (<36.5C) Bleeding Deep coma Repeated convulsions Anuria Shock

28. Poor Prognostic symptoms 2 Laboratory Hypoglycemia (<2.2 mmol /L) Hyperlactatemia (>5 mmol /L) Acidosis (pH <7.3, serum HCO3 <15 mmol /L) Elevated serum creatinine (>265 mol /L) Elevated total bilirubin (>50 mol /L) Elevated liver enzymes (AST/ALT 3 times upper limit of normal, 5- nucleotidase) Elevated muscle enzymes ( CPK, myoglobin) Elevated urate (>600 mol /L)

29. Poor Prognostic symptoms 3 Haematology Leukocytosis (>12,000/L) Severe anemia (PCV <15%) Coagulopathy Decreased platelet count (<50,000/L) Prolonged prothrombin time (>3 s) Prolonged partial thromboplastin time Decreased fibrinogen (<200mg/ dL ) Parasitology Hyperparasitemia Increased mortality at >100,000/L High mortality at >500,000/L >20% of parasites identified as pigment-containing trophozoites and schizonts >5% of neutrophils with visible pigment

30. DIAGNOSIS In endemic regions, malaria should be considered a cause in of fever in a febrile child. Confirmation is by microscopic demonstration of the parasite in a thick & thin blood smear stained with Giemsa stain (gold standard in developing countries) Finding of only the Ring forms (asexual forms) of P. falciparum is diagnostic. The thick film reveals the presence and the count[load] of the parasite while the thin film identifies the plasmodial spp. www.medrockets.com Fb:Medrockets

31. Non-microscopic techniques are been developed and involves the detection of plasmodial Ag, anti-plasmodial Abs or the parasitic metabolic products. Examples include; paraSight, F-test, ICT malaria P.F test, optiMal assay, PCR, ELISA,. Other investigations, depend on presentation. DIAGNOSIS www.medrockets.com Fb:Medrockets

32. BLOOD FILM Thick smears Parasite density Thin smears Specie identification

33. DIFFERENTIAL DIAGNOSIS This is very broad; in fact any “fever” in the tropics is assumed to be malaria until proven otherwise. Viral ailments: Influenza, hepatitis & even common cold. Typhoid fever, Yellow fever, Tuberculosis, Pneumonia, Meningitis, Septicaemia. www.medrockets.com Fb:Medrockets

34. Aim Of Treating Malaria To fight an established infection, and this includes Elimination of the parasites. Supportive measures to overcome morbidity associated with infection Monitoring to ensure early diagnosis and treatment of complication that can lead to death within hours.   TREATMENT

35. Clinical Case Management & Basic Supportive Care Rehydration Monitor Blood Sugar Anticonvulsants –to control seizures – rectal diazepam. Dialysis in renal shut down. Blood transfusion for anaemia- PCV < 20%. Antibacterial for bacterial infections - aspiration pneumonia and sepsis  Exchange blood transfusion www.medrockets.com Fb:Medrockets

36. WHO has recommended the use of Artemisinin Combination Therapy for the treatment of uncomplicated malaria. The recommended ACTs include: Artemether-lumefantrine (Nigeria) 1.5/9 mg/kg twice daily for three days   Artesunate+Amodiaquine Artesunate 4 mg/kg once dly for 3 days + Amodiaquine 10mg base/kg on days 1, 2, & 3   Artesunate+Mefloquine Artesunate 4 mg/kg once daily for 3 days + mefloquine 25 mg base/kg ( mefloquine 8.3mg/kg daily for 3 days)   Dihydroartemisinin-piperaquine This a new ACT that has been shown to be safe and equally effective   UNCOMPLICATED MALARIA

37. Specific Antimalarial Treatment for Severe Malaria The recommended treatment for severe malaria is Artesunate Injection Give 2.4 mg/kg IV bolus, repeat 1.2 mg/kg after 12 hours and then 1.2 mg/kg daily until patient can tolerate oral medication (or for a minimum of 48 hours). Thereafter given follow-on treatment using a full 3-day course of ACT  www.medrockets.com Fb:Medrockets

38. Possible alternatives if not available include Intravenous quinine Give 20 mg/kg of Quinine dihydrochloride salt as loading dose diluted in 10 ml/kg of 4.3% dextrose in 0.18% saline or 5% dextrose over a period of 4 hours. Then 12 hours after the start of the loading dose, give 10 mg salt /kg infusion over 2 hours every 12 hours until when patient is able to take orally. Change oral ACT once patient can tolerate oral medication OR Intramuscular Artemether :- 3.2 mg/kg IM on the first day and then 1.6 mg/kg daily for a maximum of 3 days until the patient can take oral treatment, then give a full 3-day course of ACT.   Specific Antimalarial Treatment for Severe Malaria

39. Advantages of ACT : High efficacy and rapid clearance of parasites Artemisinin reduces gametocyte carriage thus reduces malaria transmission Artemisinin derivatives – most rapidly schizonticidal antimalarial drugs known to date Used for >2 centuries in china and still effective ( artemisinin derivatives do not remain in the blood stream for long) Relatively good safety profile despite initial anxiety following pre-clinical findings Reduction in malaria transmission

40. Prevention & Control Good personal hygiene Environmental hygiene Good Nutrition and immunity Early diagnosis and treatment Presumptive treatment of severe cases. Make every effort to establish diagnosis in the laboratory before treatment. However, this should not delay treatment in cases of suspected severe malaria. Ensure compliance Protection against mosquito bites Chemoprophylaxis- indications Sickle cell anaemia Patients on immunosuppressive therapies or disease states Non-immune or semi-immune children Pregnant women www.medrockets.com Fb:Medrockets

41. MALARIA CONTROL- WHAT IS RBM This is a global movement mobilizing support for local initiative. It is a coordinated approach to strengthen public and private health care. It involves multiple strategies targeted to meet local malaria control needs. It was established 31st July 1998 Six Principles of RBM Early detection Rapid diagnosis and Effective Treatment Multiple prevention Focused research Well coordinated actions Dynamic movement www.medrockets.com Fb:Medrockets

42. Reduce Contact Between Humans And Mosquitoes www.medrockets.com Fb:Medrockets

43. Who Should Receive Malaria Chemoprophylaxis? Travelers to endemic countries Non-immune Returning immigrants to endemic areas (lost their immunity) Residents of endemic countries Targeted segments <5year olds Pregnant women Imunocompromised patients e.g. SCA, HIV/AIDS, Post splenectomy , Cancer, Post organ transplant www.medrockets.com Fb:Medrockets

44. Drugs For Chemoprophylaxis Pyrimethamine – No longer effective Proguanil – 200mg daily Doxycycline – Travelers 250mg daily. Not in children or pregnant women Malarone ( Atovaquone / proguanil ) – very effective, good safety margin but expensive ($32 – 35 USD/dose) Mefloquine – 250mg weekly (T 1/2 too long, neuro -psychiatric AE) Chloroquine / Amodiaquine Not recommended as it is used in Rx Resistance emerged Bone marrow suppression with amodiaquine www.medrockets.com Fb:Medrockets