Case presentation on malaria

introduction on malaria
case study on malaria

1. case presentation on malaria P resented by : PRIYANKA K 1st Pharm D (PB) Shree devi college of pharmacy Mangalore

2. content Definition Epidemology Life cycle Signs and symptoms Clinical presentation Risk factors Complication Diagnosis Treatment Malaria in pregnancy Prevention Case study.

3. MALARIA DEFINITION Malaria is an infectious disease caused by protozoan parasites of genus plasmodium that can be transmitted by the bite of the Anoheles mosquito or by a contaminated needle or transfusion. CAUSATIVE ORGANISM P. falciparum ( the most common and dangerous) P. viva P. ovale P. malaria P. knowlesi

4. EPIDEMIOLOGY The WHO estimates that in 2010 there were 219 million cases of malaria resulting in 660,000 deaths. Others have estimated the no. of cases at between 350 and 550 million for falciparum malaria and deaths in 2010 at 1.24 - 1.0 million deaths in 1990. The majority of cases occur in children under 15 years old. P. vivax and P. ovale causes relapsing malaria. P falciparum is found in the tropical region and causes the most severe and fatal disease. P. vivax is the most common cause of malaria and is found insubtroical and temperate areas of the world. P. ovale is the least common malarial species .

5. LIFE CYCLE

6. LIFE CYCLE The life cycle of malaria parasite consists of following phases: Sexual cycle : in female anopheles mosquito, definitive host Asexual cycle : in human, as intermediate host. Sporozoites are the sexual form of the parasite. When the infected female anopheles mosquito bites the human then the sporozoites enter the human along with the saliva of the mosquito. Within 30min they enter the parenchymal cells of the lier , where during next 10 - 14 days, they undergo pre- erythrocytic stages of development and multiplication.

7. Following mitotic replication of its nucleus, the parasite is termed as schizont . Atlast the parasites rupture the liver cell and merozites are released The merozoites from the liver cell then bind to or enter the RBC and further develops into trophozoites . The mulitplication here results to Erythrocytic schizont . Some merozoites of erythrocytic schizony develop into male and female gametocytes known as microgamates and macrogamates . They are sexual form and are found in peripheral blood.

8. Some of the sporozoites also, on entering into the liver cells, do not undergo asexual multiplication but enter into a resting phase called hypnozoite The sexual cycle of malaria parasites actually starts in the human host by the formation of gametocytes which are then transferred to mosquito for further develoment. In the midgut of the mosqito, one microgametocyte develops into 4 to 8 thread like filamentous structures named microgamates. From one microgamate only one microgamate is formed

9. The fertilization occurs, and the gamate is known as zygote . The zygote matures into an ookinete and it further develops into an oocyts. An oocyts mature and it increases in size and a large no of sporozoites develop inside it. The oocyts rupture and releases sporozoites in the body cavity of mosquito. The sporozoites are distributed to different organs of the mosquito and they have a special predilection for salivary glands. The mosquito is now capable of transmitting the infection to man.

10. INCUBATION PERIOD OF THE PARASITE SPECIES INCUBATION PERIOD (LIVER CYCLE) P. falciparum 7-14 days P. vivax 12-17 days (withrelapse upto 3 yrs) P. ovale 9-18 days (with relapse upto 20 yrs) P. malaria 13-40 days.

11. SIGNS AND SYMPTOMS

12. Clinical Presentation of Malaria Initial Presentation Nonspecific fever, chills, rigors, diaphoresis, malaise, vomiting Orthostatic hypotension Electrolyte abnormalities Erythrocytic Phase Prodrome : Headache, anorexia, malaise, fatigue, myalgias Nonspecific complaints such as abdominal pain, diarrhea, chest pain, and arthralgias Paroxysm : High fever, chills, and rigor Cold phase: Feeling of intense cold , vigorous shivering , lasts 15- 60 min, Severe pallor, cyanosis of the lips and nail bed, and cutis anserina (“goose flesh ”) Hot phase: intense heat ,Fever between 40.5◦C (104.9◦F) and 41◦C (105.8◦F), dry burning skin, throbbing headache , last 2-6 hours.

13. Sweating phase: Follows hot phase by 2–6 hours , profuse sweating, decline temperature, exhausted and weak sleep Fever resolves Marked fatigue and drowsiness, warm, dry skin, tachycardia, cough, severe headache, nausea, vomiting, abdominal pain, diarrhea, and delirium Lactic acidosis and hypoglycemia (with falciparum malaria) Anemia Splenomegaly P. falciparum Infections Hypoglycemia, acute renal failure, pulmonary edema, severe anemia, thrombocytopenia, high-output heart failure, cerebral congestion, seizures and coma, and adult respiratory syndrome

14. RISK FACTORS OF MALARIA Living or traveling in a region where malaria is present. Travelling to area where malaria is common: - without taking medicine to prevent malaria. - being outdoors, especially in rural areas. - not taking steps to protect yourself from mosquito bites. pregnant women. Children under 5yrs of age. Patients with HIV/AIDS.

15. Complication of malaria Anaemia – It results from the obligatory destruction of rbc containing parasites at merogony . The shortened survival of rbc from which parasites have been extracted by the spleen, and accelerated destruction of non- parasitized rbc all compound by bone marrow dyserythropoeisis . In severe malaria anaemia develops rapidly because of the rapid haemolysis of rbc and decline in the haematocrit . Renal failure – There is renal vasoconstriction and hypoperfusion in severe falciparum malaria. The renal injury in severe malaria results from acute tubular necrosis. Fluid space and electrolyte changes – The general vasodilation and a falling haemtocrit there will be increase in the plasma renin activity, anti diuretic harmone concentration

16. Pulmonary oedema – in malaria results from a sudden increase in pulmonary capillary permeability ( due to of presence of sequestered rbc and host leucocytes in pulmonary capillary endothelial dysfunction). Coagulopathy and thrombocytopenia – In acute malaria coagulation cascade activity is increased with accelerated fibrinogen turnover, consumption of antithrombin III, reduced factor XIII and increased concentration of fibrin degradation products. Blackwater fever – massive intravascular haemolysis and the passage of ‘coco cola’ coloured urine. It may be associated with acute renal failure.

17. Liver dysfunction – jaundice Acidosis – major cause of death in severe falciparum malaria. Gastrointestinal dysfunction- abdominal pain, enlarged soft, dark or black, firable spleen. Hypoglycaemia Placental dysfunction

18. DIAGNOSIS Clinical diagnosis Malaria blood smear Fluorescent microscopy Antigen detection Serology Polymerase chain reaction

19. Malarial Blood Smear Remains the gold standard for diagnosis. Giemsa stain - distinguishes between secies and life cycle stages - parasitemia is quantifiable

20. Interpreting thick and thin films THICK FILMS THIN FILMS Lysed RBCs Larger volume 0.25 µl blood/ 100 fields blood elements more concentrated good screening test positive or negative parasite density more difficult to diagnosis species. fixed RBCs, single layer smaller volume 0.005 µl blood/ 100 fields good species differentiation requires more time to read low density infections can be missed.

21. ANTIGEN DETECTION Various test kits are available to detect antigens derived from malaria parasites. Such immunologic tests most often use a dipstick or cassette format, and provide results in 2-15mins. These “Rapid Diagnostic Test” (RTDs) offer a useful alternative to microscopy in situations where reliable microscopic diagnosis is not available. Malaria RDTs are currently used in some clinical settings and programs. The use of this RDT may decrease the amount of time that it takes to determine that a patient is infected with malaria

22. MOLECULAR DIAGNOSIS Parasite nucleic acids are detected using polymerase chain reaction Although this is technique may be slightly more sensitive than smear microscopy, it is of limited utility for the diagnosis of acutely ill patients in the standard healthcare setting. PCR is most useful for confirming the species of malarial parasite after the diagnosis has been established by either smear microscopy or RDT. SEROLOGY Serology detects antibioties against malaria parasites, using either indirect immunofluorescence or enzyme- linked immuno - sorbent assay (ELISA). Serology does not detect current infection but rather measures past exposure.

23. treatment

24. 4- AMINOQUINOLINES - Chloroquine spectrum of activity : rapid acting erythrocytic schizontic against all species of malaria MOA :- Accumulates in acidic vacuole of parasite it increases ph and inhibits heme polymerisation . by formation CQ- heme complex it damages plasmodial membrane complex inhibits formation of hemozoin . dosage uncomplicated vivax / ovale / malaria: 600mg- 300mg after 8hrs, continue for next 2days, total 25mgkg over 3days + primaquine 15mg(0.25mg/kg)daily for 14 days chloroquine sensitive falciparum :- dose as above + primaquine 45mg(0.75mg) single dose Adverse effects nausea, vomiting, anorexia, itching, epigastric pain, difficult in accommodation, headache are frequent and unpleasent .

25. toxic effects after prolonged use: skin eruptions, headache, blurring of vision, diplopia , confusion and convulsion. haemolysis and blood dyscrasis discolouration of nail beds, hairs and mucoucs membrane. ototoxicity irreversible myoppathy , cardiomyopathy , peripheral neuropathy, suicidal tendency occurs mental confusion, convulsion and coma. interactions and precautions of CQ With Mefloquine convulsion Will occur. Digoxin level increases used along with gold and phenylbutazone dermatitis will occur. haemolysis occurs in G6PD deficient patients.

26. Amodiaquine decrease cost and safety in CQ resistance P. falciparum in certain areas faster action and better tolerance then chloroquine Prophylactically not used because of hepatotoxicity & agranulocytosis in certain areas can be used in clinical attacks. Doasge : 25 - 35mg/kg for 3days (10mg/kg is given immediately following 5mg//kg after 6hrs then 5mg/kg for next 2 days) Mechanism, uses &ADR are similar to CQ

27. Piperaquine Chloroquine congener with similar mechanism. high efficacy, erythrocytic schizonticide with prolonged action & onset is slow. Activity: chloroquine sensitive & chloroquine resistant P.falciparum malaria MOA :- Similar to morphological changes in the intraerythrocytic parasite of chloroquine & quinine. act in cytosol of the parasite mechanism is unclear it can also inhibit heme polymerization forming toxic complex with heme & damage membrane.

28. Dosage - 25mg/kg - 1.25gm sinle or 2doses of 750& 500mg 12hr apart. chlidren - first dose 15mg/kg → 10mg/kg after 12h after meals with plenty of water since its irritant Adverse drug effect Dizziness, nausea, vomiting, diarrhoea , abdominal pain, sinus bradycardia & QT prolongation. Safe during pregnancy but should be avoided in first trimester. Neuropsychiatric reactions present. Drug interaction Halofantrine or Quinine or Chloroquine with this drug causes QT lengthening and cardiac arrest.

29. CINCHONA ALKALOID - Quinine Isolated from bark of chinchona tree . MOA It forms heme - quinine complex. Inhibits polymerization of heme to hemozoin . Damages parasite membrane and kills it . Dosage : 7 day course Loading dose : 20mg/kg IV over 4hrs diluted in 5% dextrose to prevent hypoglycemia. Maintenance dose : 10mg/kg over 4hr in adults or 2hr in children every 8hr. Then switch over to oral 10mg/kg 8hrly Adverse effects : affects hearing & vision cardio depressent , anti arrythmic and hypotensive action similar to quinidine . On rapid IV it causes hypoglycemia. Toxicity : 8-10g taken in single dose may be fatal.

30. Biguanide - Proguanil Slow acting erythrocytic schizontocide . Inhibits pre erythrocytic stage of P.falciparum gametocytes prevents its development. It gets converted to active form cycloguanil , which inhibits plasmodial DHFRASE. MOA : Inhibits DHFRase - thymidylate synthetase Dosage : >200mg daily in adults & children 4weeks after leaving endemic area. Causal prophylaxis : 400mg proguanil + Atovaquine 1g for 3 days in multidrug resistence . Adverse effects : mild abdominal symptoms. occasional stomatitis , haematuria , rashes and transient loss of hair.

31. 8- Aminoquinolines - Primaquine Radical cure : given with choloroquine . Only agent active against dormant hepatic forms of vivax & ovale . Gametocidal action against all four species of plasmodium. MOA : not clear, its converted & produces active oxygen interfere with plasmodial mitochondrial function. Resistance induced among P.vivax . Adverse effect : haemolysis and methaemoglobinaemia commonly seen in G6PD deficiency. Causes nausea, headache, epigastric pain and abdominal cramps on empty stomach.

32. Artemisinin compounds Derived from plant Artemisia annua . Its sesquiterpine lactone endoperoxide , poorly soluble in oil and water-used orally/ rectally. Other compound : Dihydroartemisinin (oral) Artemether (oral or IM) & Artesunate (oral/rectal/IV/IM) Arteether – (IM) produced in India in 1990. Arterolone – (oral) synthetic ompound are developed. MOA : Endoperoxide moiety produces carbon centered radicals by intramolecular rearrangement which modify & damages malarial proteins. High reacted free radicals inhibit plasmodial sarcoplasmic endoplasmic calcium ATPase . Resistance decrease response & combination of drugs with different mechanism & longer acting drugs given with these drugs in 3 days course will solve the problem.

33. Dosage 12mg of total oral dose for both children & adults in which 4mg/kg given on first day followed by 2mg/kg for 4days. Parenteral : Artesunate – 120mg IV/IM on first day followed by 60mg for next 4days by same route. Artemether ; 2mg/kg for 5days Arteether : for complicated malaria in adults IM 150mg daily. Adverse effect: nausea, vomiting, abdominal pain, itching and drug fever. Headache, tinnitus, dizziness, bleeding, dark urine, ST segment changes, QT prolongation, first degree AV block, transient reticulopenia and leucopenia are rare.

34. Malaria in pregnancy Malaria is more common in pregnancy compared to the general population. Immuno suppression and loss of acquired immunity to malaria could be the causes. Malaria in pregnancy being more severe, also turns out to be more fatal, the mortality being double (13%) in pregnant compared to the non- pregnant population(6.5%). Some anti malarials are contra indicated in pregnancy and some may cause severe adverse effects. Therefore the treatment may become difficult, particularly in cases of severe P.falciparum malaria.

35. In pregnant women the morbidity due to malaria includes anaemia , fever, hypoglycemia, cerebral malaria, pulmonary edema, puerperal sepsis and mortality can occur from severe malaria and haemorrhage . The problem in the new born include low birth weight, prematurity, IUGR, malaria illness and mortality. Drugs used in pregnancy: Proguanil with folic acid 5mg/day. Chloroquine in usual doses. Quinine in low dose- chloroquine resistant malaria High dose induce labour . Pryrimethamine + dapsone – 2 nd & 3 rd trimester with folinic acid. Chloroquine , quinine 7 proguanil safe but pyrimethamine with folic acid can be used.

36. Case study

37. DEMOGRAPHICS Patient name : Mr. XYZ Age : 26yrs Sex : Male IP No. : F34327 Deparment : General medicine Date of admission: 22/09/2019 Date of discharge: 27/09/2019

38. SUBJECTIVE DATA Chief complaints : C/o fever, vomiting, back pain, fatigue, headache × 3days History of present illness H/o backpain , headache. Past medical history : N/K/C/o DM, HTN, BA.

39. Past medication history: not significant Social history : not smoker and alcoholic Personal history Diet – mixed Sleep – adequate B and B – loose stool Appetite - normal no substance abuse

40. OBJECTIVE DATA General physical examination: Patient is conscious, cooperative, well oriented moderately built and nourished No pallor, icterus, clubbing,cyanosis, lymphadenopathy, edema Vital signs: BP- 120/80 mm/Hg RR – 20bpm TEMPERATURE – 104F PR- 80bpm Systemic examination CVS - S1 S2+ CNS – NFND RS – NVBS P/A - Soft

41. LABORATORY INVESTIGATIONS PARAMETER TEST VALUE NORMAL VALUE Hemoglobin 12.6 14 – 18 gm/dl RBC 4.4 4.2 – 5.6 million/cubic mm Platelet count 110 140- 450 cubic mm ESR 25 15 – 20 mm/hr Bilirubin (total) 1.8 0.2 – 1.4 mg/dl Bilirubin ( direct) 1.5 0.0 – 0.4 mg/dl Bilirubin (indirect) 0.3 0.2 – 1.0 mg/dl

42. OTHER TEST’S Dengue test – negative Polymerase chain reaction – positive MP QBC – Positive (P. vivax )

43. ASSESSMENT FINAL DIAGNOSIS BY SUBJECTIVE DATA AND OBJECTIVE DATA MALARIA

44. GOALS OF THE TREATMENT Releive the signs and symptoms of a disease. Decrease morbidity and mortality associated with the infection. To prevent the clinical attack of malaria ( prophylatic ). To treat the clinical attack of malaria ( clinical curative). To completely eradicate the parasite from the patients body ( radical curative). To cut down human to mosquito transmission ( gametocidal ).

45. MEDICATION Brand name Generic name Dose Freq ROA 22/09 23/09 24/09 25/09 26/09 27/09 Cap. DOXYCYCLINE DOXYCYCLINE 100mg BD Oral Tab. DOLO PARACETAMOL 650mg TDS Oral Tab. LARIAGO CHLOROQUINE PHOSPHATE 600mg OD Oral Inj. EMESET ONDRANSETRON 4mg STAT I V

46. DRUG INTERACTION CHLOROQUINE < - > ONDANSETRON The metabolism of ondansetron can be decreased when combined with chloroquine . DOXYCYLCINE <-> CHLOROQUINE Doxycyline may decrease the excretion rate of chloroquine which could result in a higher serum level.

47. DISCHARGE MEDICATION Tab. LARIAGO (600mg) OD for 14days Tab. DOLO (650mg) STAT Cap. DOXYCYCLINE (100mg) BD for 7days Review after 14days.

48. PATIENT COUNSELLING ABOUT THE DISEASE AND LIFESTYLE Research your destination to learn about any malaria risk. Consult a health practitioner to determine if you need antimalarial medication for your trip and take as presecribed . Prevent mosquito bite: use a repellent containing 20 – 30% DEET or 20% Picaridin . Wear neutral coloured clothing. Avoid scented soaps. Sleep under a permethrin – treated bed net.

49. THANK YOU