Presentation on theme: "ICD Cold Shivers after a Hot Trip LeeChuy, Katherine Lee, Sidney Abert Lerma, Daniel Joseph Legaspi, Roberto Jose Li, Henry Winston Li, Kingbherly Lichauco,"— Presentation transcript:
ICD Cold 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, Syndel Raina Lipana, Kirk Andrew Liu, Johanna Llamas, Camilla Alay
General Data and History of Presented Illness 3 mos. Was assigned in the mountains of Palawan (took chloroquine weekly) 2 wks Fever and chills accompanied by headaches Treated with sulfadoxine-pyrimethamine (Fansidar) 33 y/o, news correspondent ADMISSION
Physical Examination Temp 40°C; PR 110/min; RR 22/min; BP 120/60 mmHg General: Ill-looking but well-nourished, no skin lesions, no pedal edema Eyes: Pale palpebral conjunctivae, slightly icteric sclera, pupils equally reactive to light Neck: no thyromegaly Heart and lungs: normal, JVP normal GI: Traubes space obliterated
Pertinent Findings Positive Travel history to Palawan – Chloroquine prophylaxis Fever and chills accompanied by headaches – Treated with sulfadoxine- pyrimethamine (Fansidar) Febrile, tachycardic, tachypnic Pale palpebral conjunctivae slightly icteric sclera Splenomegaly Negative BP 120/60 mmHg no skin lesions no pedal edema pupils equally reactive to light no thyromegaly Heart, lungs, and GI: normal
Areas with Malaria Estimated relative risk of malaria for US travelers Drug Resistance Malaria Species Recommended Chemoprophylaxis Present in rural areas below 600m (1,969ft), on islands of Luzon, Palawan, and Mindanao. None in urban areas. LowChloroquineP. falciparum 70-80% P. vivax 20-30% Atovaquone/ proguanil, doxycycline, or mefloquine http://www.cdc.gov/malaria/travelers/country_table/p.html Doxycycline 100 mg daily for 2 – 3 days before going to an endemic area, continue while in the endemic area and continue for 4 more weeks after leaving the endemic area. http://www.doh.gov.ph/faq/show/450.html
high fever – malarial toxins direct systemic release of proinflammatory cytokines (TNF-a) – stimulate T cells to directly secrete or induce production of cytokines icteric sclerae – Increased hemolysis due to malaria elevated pulse rate – compensatory mechanism for the hemolytic anemia Science. 1994 Jun 24;264(5167):1878-83
enlargement of the spleen – engorgement and edema – reticulo-endothelial hyperplasia – increased hemolytic and phagocytic function of the organ due to dysmorphic red blood cells absence of skin lesions – thrombocytopenia during the paroxysms of fever no pedal edema – Synthetic function of the liver
What are the probable reasons for this patient to have another episode of malaria? RELAPSE REINFECTION RECRUDESCENCE
Most re-infected with malaria: – live in endemic areas – travel repeatedly to these areas develop immunity to malaria by acquiring mechanisms which can kill the parasites or stop the replication of these parasites Regulation of response so as not to produce an overblown reaction to malaria first infection primes the immune system, while re-infection leads to an exaggerated, and very harmful response by the body
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
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 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 – production of interferon - gamma by peripheral blood mononuclear cells in response to either Liver-stage or merozoite antigen peptides – delayed first re-infection or lower rates of re-infection – re-infections among select few members of a family may be due to lack of gamma interferon response to the first attack of malaria
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.
Merozoites in the bloodstream invade RBC.When these reach a density of 50/uL in the blood, symptomatic stage begins. Merozoites from the blood, attach to erythrocytes to become trophozoites Trophozoites consuming all hemoglobin inside the RBC (schizont) Schizogony inside the RBC then rupture of daughter merozoites Processes Essential for the Pathogenesis of Malaria
Erythrocyte Changes in Malaria 1.Consumes and degrades proteins especially hemoglobin 2. Toxic heme is detoxified (polymerization) to biologically innert hemozoin 3. Cytoadherence Fauci et.al. Harrisons principles of Internal Medicine 17 th edition, 2008
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
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
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
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
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
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)
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 patients survival, particularly in acute hypercatabolic renal failure
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
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
First of all… The diagnosis of malaria has to be confirmed – Microscopy (blood smear) – Rapid Detection Test (PfHRP, LD antigen) 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 Fauci et.al. Harrisons principles of Internal Medicine 17th edition, 2008 Guidelines for the treatment of malaria – 2nd edition
Uncomplicated malaria Known chloroquine-sensitive strains of Plasmodium vivax, P. malariae, P. ovale, P. falciparum 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) Fauci et.al. Harrisons principles of Internal Medicine 17th edition, 2008 Guidelines for the treatment of malaria – 2nd edition
Uncomplicated malaria Radical treatment for P. vivax or P. ovale infection 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. Fauci et.al. Harrisons principles of Internal Medicine 17th edition, 2008 Guidelines for the treatment of malaria – 2nd edition
Uncomplicated malaria 1 st line Treatment for 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 Artesunate (4 mg/kg qd for 3 days) plus amodiaquine (10 mg of base/kg qd for 3 days) Fauci et.al. Harrisons principles of Internal Medicine 17th edition, 2008 Guidelines for the treatment of malaria – 2nd edition
Uncomplicated malaria 1 st line Treatment for Multidrug-resistant P. falciparum malaria Either artemether-lumefantrine (1.5/9 mg/kg bid for 3 days with food) artesunate (4 mg/kg qd for 3 days) plus Mefloquine (25 mg of base/kgeither 8 mg/kg qd for 3 days or 15 mg/kg on day 2 and then 10 mg/kg on day 3) Fauci et.al. Harrisons principles of Internal Medicine 17th edition, 2008 Guidelines for the treatment of malaria – 2nd edition
Uncomplicated malaria 2 nd line Treatment for 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: 1.Tetracycline (4 mg/kg qid for 7 days) 2.Doxycycline (3 mg/kg qd for 7 days) 3.Clindamycin (10 mg/kg bid for 7 days)
Severe Falcifarum malaria If patient is unable to tolerate oral therapy – 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) Once oral therapy is tolerable a full course of ACT is recommended Fauci et.al. Harrisons principles of Internal Medicine 17th edition, 2008 Guidelines for the treatment of malaria – 2nd edition
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
Table 203-8 Drugs Used in the Prophylaxis of Malaria DrugUsageAdult DoseComments Atovaquone/ proguanil (Malarone) Prophylaxis in areas with chloroquine- or mefloquine- resistant Plasmodium falciparum 1 adult tablet PO Good for last-minute travelers; begin 1–2 days before travel to malarious areas. Take daily at the same time each day while in the malarious area and for 7 days after leaving such areas. Side effects are uncommon. Contraindicated in persons with severe renal impairment (creatinine clearance rate <30 mL/min). Chloroquine phosphate (Aralen and generic) Prophylaxis only in areas with chloroquine- sensitive P. falciparum c 300 mg of base (500 mg of salt) PO once weekly Begin 1–2 weeks before travel to malarious areas. Take weekly on the same day of the week while in the malarious areas and for 4 weeks after leaving such areas. Can be given in all trimesters of pregnancy. Harrisons Internal Medicine, 17 th ed. Global Health – Division of Parasitic Diseases. Centers for Disease Control and Prevention, updated Feb. 8, 2010.
Doxycycline (many brand names and generic) Prophylaxis in areas with chloroquine- or mefloquine-resistant P. falciparum c 100 mg PO qd Good for last-minute travelers; begin 1–2 days before travel to malarious areas. Least expensive among anti-malarial agents. Take daily at the same time each day while in the malarious areas and for 4 weeks after leaving such areas. Hydroxychloro quine sulfate (Plaquenil) An alternative to chloroquine for primary prophylaxis only in areas with chloroquine-sensitive P. falciparum c 310 mg of base (400 mg of salt) PO once weekly Begin 1–2 weeks before travel to malarious areas. Take weekly on the same day of the week while in the malarious areas and for 4 weeks after leaving such areas. Harrisons Internal Medicine, 17 th ed. Global Health – Division of Parasitic Diseases. Centers for Disease Control and Prevention, updated Feb. 8, 2010.
Mefloquine (Lariam and generic) Prophylaxis in areas with chloroquine- resistant P. falciparum 228 mg of base (250 mg of salt) PO once weekly Begin 1–2 weeks before travel to malarious areas. Take weekly on the same day of the week while in the malarious areas and for 4 weeks after leaving such areas. PrimaquineAn option for prophylaxis in special circumstances; used for presumptive antirelapse therapy (terminal prophylaxis) to decrease risk of relapses of P. vivax and P. ovale. 30 mg of base (52.6 mg of salt) PO qd for 14 days after departure from the malarious area Good for last-minute travelers; begin 1–2 days before travel to malarious areas. Take daily at the same time each day while in the malarious areas and for 7 days after leaving such areas. This therapy is indicated for persons who have had prolonged exposure to P. vivax and/or P. ovale.
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