ICD Cold Shivers after a Hot Trip

1. ICDCold Shivers after a Hot Trip LeeChuy, Katherine Lee, Sidney Abert Lerma, Daniel Joseph Legaspi, Roberto Jose Li, Henry Winston Li, Kingbherly Lichauco, Rafael Lim, Imee Loren Lim, Jason Morven Lim, John Harold Lim, Mary Lim, Phoebe Ruth Lim, SyndelRaina Lipana, Kirk Andrew Liu, Johanna Llamas, Camilla Alay

2. Salient Features Negative findings • Pupils ERTL • JVP normal • No Thyromegaly • Heart and Lungs normal • No skin lesions • No pedal edema Positive findings • Temp: 40°C • PR: 110/min • RR: 22/min • BP: 120/60 • Pale palpebralconjuntiva • Slightly icteric sclera • Traube’s space obliterated

3. What are the probable reasons for this patient to have another episode of malaria? RELAPSE REINFECTION RECRUDESCENCE

4. Most patients re-infected with malaria are those that live in endemic areas, or those that travel repeatedly to these areas. Over time, these people may develop immunity to malaria by acquiring mechanisms which can kill the parasites or stop the replication of these parasites. However, what is important is the ability of their immune system to regulate its response to these infections, so as not to produce an overblown reaction to malaria. • This occurs as the first infection “primes” the immune system, while re-infection leads to an exaggerated, and very harmful response by the body.

5. RELAPSE • renewed manifestation arising from survival of exoerythrocytic forms (hypnozoites) either at relatively short intervals or after long period (8-24 weeks) • confined to P. Vivax and P. Ovale infections • primaquine resistance or incomplete response or inadequate primaquine treatment • Chloroquine resistant Plasmodium • Counterfeit/substandard chemoprophylactic drug

6. REINFECTION • fresh infection occurring in a patient who has suffered from Malaria and can occur at any time after 2 weeks of the 1st attack. • This may be due to persistent source of infection such as an asymptomatic carrier or persistent malaria in the neighborhood or household because of high endemicity and persistent breeding centers for mosquitoes. • Luty et al in a study of plasmodium falciparum infection in African children have shown that in Gabonese children with mild malaria, production of interferon - gamma by peripheral blood mononuclear cells in response to either Liver-stage or merozoite antigen peptides was associated with significantly delayed first re-infection or lower rates of re-infection. Hence re-infections among select few members of a family may be due to lack of gamma interferon response to the first attack of malaria.

7. RECRUDESCENCE • renewed manifestation of infection due to survival of erythrocytic forms • a repeated attack of malaria (short term relapse or delayed), due to the survival of malaria parasites in red blood cells. • Characteristic of P. malariae infections.

8. Pathogenesis of Malaria

10. Erythrocyte Changes in Malaria • Consumes and degrades proteins especially hemoglobin 2. Toxic heme is detoxified (polymerization) to biologically innert hemozoin 3. Cytoadherence Reference: Harrison’s principles of internal medicine 17th edition, 2008 By: Fauci et al

11. Cytoadherence

12. HOST RESPONSE

13. Complications of severe falciparum malaria • Morbidity and mortality of P. falciparum species is greatest among the malaria species because of its increased parasetemia and its ability to cytoadhere • Mortality rises once vital organ dysfunction occurs or proportion of erythrocytes infected increases to >3% • P. falciparum is also known for developing drug resistance to chloroquine, quinine and tetracycline

14. Complications • Cerebral malaria • Hypoglycemia • Lactic acidosis • Noncardiogenic pulmonary edema • Renal impairment • Hematologic abnormalities • Liver dysfunction

15. Cerebral malaria • Coma: characteristic & ominous feature of falciparum malaria; mortality rate of ~0.1%, but if there is vital-organ dysfunction, mortality rises steeply • Manifests as diffuse symmetric encephalopathy • Eyes may be divergent • Muscle tone increase or decrease • ~15% have retinal hemorrhages • Convulsions: generalized; occur up to 50% of children with cerebral malaria

16. Cerebral malaria • ~15% of children with cerebral malaria have been reported to suffer neurologic deficit when they regain consciousness: • Hemiplegia • Cerebral palsy • Cortical blindness • Deafness • Impaired cognition and learning

17. Hypoglycemia • Common complication of severe malaria • Associated with poor prognosis • Particularly problematic in children and pregnant women • Results from a failure of hepatic gluconeogenesis & an ↑ in the consumption of glucose both by host & the malaria parasites • Quinine & quinidine are powerful stimulants of pancreatic insulin secretion

18. Lactic acidosis • Commonly coexists with hypoglycemia • Caused by combination of: • Anaerobic glycolysis in tissues where sequestered parasites interfere with microcirculatory flow • Hypovolemia • Lactate production by the parasites • Failure of hepatic and renal lactate clearance • Coexisting renal impairment compounds acidosis • Acidotic breathing: sign of poor prognosis • Plasma concentrations of bicarbonate or lactate: best biochemical prognosticators in severe malaria

19. Noncardiogenic pulmonary edema • Mortality rate: >80% • Aggravated by overly vigorous administration of IV fluid • Can also develop in otherwise- uncomplicated vivax malaria (recovery is usual)

20. Renal impairment • Rare among children • May be related to RBC sequestration interfering with renal microcirculatory flow & metabolism • Manifests as acute tubular necrosis • Early dialysis or hemofiltration enhances the likelihood of a patient’s survival, particularly in acute hypercatabolic renal failure

21. Hematologic Abnormalities • Anemia • results from accelerated RBC destruction & removal by the spleen in conjunction with ineffective erythropoiesis • both infected & uninfected RBCs show reduced deformability • ↑ splenic clearance of RBCs • Slight coagulation abnormalities & mild thrombocytopenia

22. Liver Dysfunction • Severe jaundice – more common among adults than children • Results from hemolysis, hepatocyte injury, and cholestasis • Hepatic dysfunction contributes to hypoglycemia, lactic acidosis, and impaired drug metabolism

23. Treatment of Malaria First of all… • The diagnosis of malaria has to be confirmed • The infecting species has to be identified Upon confirmation • Treatment should be based on the ff factors; • Plasmodium species • Uncomplicated or Complicated (Severe) • Drug susceptibility Harrison’s Internal Medicine, 17th ed.

24. Uncomplicated malaria Known chloroquine-sensitive strains of Plasmodium vivax, P. malariae, P. ovale, P. falciparuma • Chloroquine (10 mg of base/kg stat followed by 5 mg/kg at 12, 24, and 36 h or by 10 mg/kg at 24 h and 5 mg/kg at 48 h) • Amodiaquine (10–12 mg of base/kg qd for 3 days) Harrison’s Internal Medicine, 17th ed.

25. Uncomplicated malaria Radical treatment for P. vivax or P. ovale infection  • In addition to chloroquine or amodiaquine as detailed above, primaquine (0.25 mg of base/kg qd; 0.375–0.5 mg of base/kg qd in Southeast Asia and Oceania) should be given for 14 days to prevent relapse. In mild G6PD deficiency, 0.75 mg of base/kg should be given once weekly for 6 weeks. Primaquine should not be given in severe G6PD deficiency. Harrison’s Internal Medicine, 17th ed.

26. Uncomplicated malaria Sensitive P. falciparum malaria • Artesunate (4 mg/kg qd for 3 days) plus sulfadoxine (25 mg/kg)/pyrimethamine (1.25 mg/kg) as a single dose or • Artesunate (4 mg/kg qd for 3 days) plus amodiaquine (10 mg of base/kg qd for 3 days)d Harrison’s Internal Medicine, 17th ed.

27. Uncomplicated malaria Multidrug-resistant P. falciparum malaria  • Either artemether-lumefantrine (1.5/9 mg/kg bid for 3 days with food) or artesunate (4 mg/kg qd for 3 days) • plus Mefloquine (25 mg of base/kg—either 8 mg/kg qd for 3 days or 15 mg/kg on day 2 and then 10 mg/kg on day 3) Harrison’s Internal Medicine, 17th ed.

28. Uncomplicated malaria Sensitive P. falciparum malaria • Either artesunate (2 mg/kg qd for 7 days) or quinine (10 mg of salt/kg tid for 7 days)plus 1 of the following 3: • Tetracycline (4 mg/kg qid for 7 days) • Doxycycline (3 mg/kg qd for 7 days) • Clindamycin (10 mg/kg bid for 7 days) • Atovaquone-proguanil (20/8 mg/kg qd for 3 days with food) Harrison’s Internal Medicine, 17th ed.

29. Severe Falcifarum malaria • Artemisin derivates • Artesunate (2.4mg/kg stat IV followed by 2.4mg/kg at 12 and 24 h then daily if necessary) • Artemether (3.2mg/kg stat IM followed by 1.6mg/kg qd) • Quinidine (20mg of salt/kg infused over 4 h, followed by 10mg of salt/kg infused over 2-8 h q8h) • Quinine (10mg of base/kg infused over 1-2 h, followed by 1.2mg of base/kg/h with electrocardiac monitoring) Harrison’s Internal Medicine, 17th ed.

30. Personal Protection Against Malaria • avoidance of exposure to mosquitoes at their peak feeding times (usually dusk and dawn) and throughout the night • use of insect repellents containing DEET (10–35%) or picaridin (7%; if DEET is unacceptable),suitable clothing, and insecticide-impregnated bed nets or other materials • Widespread use of bed nets treated with residual pyrethroids reduces the incidence of malaria in areas where vectors bite indoors at night

31. Harrison’s Internal Medicine, 17th ed. Global Health – Division of Parasitic Diseases. Centers for Disease Control and Prevention, updated Feb. 8, 2010.

32. Harrison’s Internal Medicine, 17th ed. Global Health – Division of Parasitic Diseases. Centers for Disease Control and Prevention, updated Feb. 8, 2010.