icd cold shivers after a hot trip

ICDCold Shivers after a Hot Trip

LeeChuy, KatherineLee, Sidney Abert

Lerma, Daniel JosephLegaspi, Roberto Jose

Li, Henry WinstonLi, Kingbherly

Lichauco, RafaelLim, Imee Loren

Lim, Jason MorvenLim, John Harold

Lim, MaryLim, Phoebe RuthLim, Syndel Raina

Lipana, Kirk AndrewLiu, Johanna

Llamas, Camilla Alay

Salient FeaturesPositive findings• Temp: 40°C• PR: 110/min• RR: 22/min• BP: 120/60• Pale palpebral conjuntiva• Slightly icteric sclera• Traube’s space

obliterated

Negative findings• Pupils ERTL• JVP normal• No Thyromegaly• Heart and Lungs normal• No skin lesions• No pedal edema

What are the probable reasons for this patient to have another episode of

malaria?

RELAPSEREINFECTION

RECRUDESCENCE

• 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.

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.• 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.

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.

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

Reference: Harrison’s principles of internal medicine 17th edition, 2008 By: Fauci et al

Cytoadherence

HOST RESPONSE

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

Complications

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

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 patient’s 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• 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.

Treatment of Malaria

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)



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.



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



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)


Uncomplicated malariaSensitive 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)

• Atovaquone-proguanil (20/8 mg/kg qd for 3 days with food)


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)


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

Drug Usage Adult Dose Comments

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). It is not recommended for children weighing <5 kg, pregnant women, or women breast-feeding infants weighing <5 kg. Should be taken with food or a milky drink.

Chloroquine phosphate (Aralen and generic)

Prophylaxis only in areas with chloroquine-sensitive P. falciparumc

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. Patients taking hydroxychloroquine for rheumatologic conditions may not need to take an extra drug. May exacerbate psoriasis.

Doxycycline (many brand names and generic)

Prophylaxis in areas with chloroquine- or mefloquine-resistant P. falciparumc

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. Patients taking this for acne do not need to take an extra drug. Doxycycline also can prevent some additional infections (e.g., Rickettsiae and leptospirosis) and so it may be preferred by people planning to do lots of hiking, camping, and wading and swimming in fresh water. Doxycycline is contraindicated in children <8 years of age and in pregnant women. Women prone to getting vaginal yeast infections when taking antibiotics may prefer taking a different medicine. Risk of photosensitivity.


Global Health – Division of Parasitic Diseases. Centers for Disease Control and Prevention, updated Feb. 8, 2010.

Hydroxychloroquine sulfate (Plaquenil)

An alternative to chloroquine for primary prophylaxis only in areas with chloroquine-sensitive P. falciparumc


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. Hydroxychloroquine may exacerbate psoriasis.

Mefloquine (Lariam and generic)

Prophylaxis in areas with chloroquine-resistant P. falciparum


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 used in second and third trimester of pregnancy, also in first if there is no other option. Mefloquine is contraindicated in persons allergic to this drug or related compounds (e.g., quinine and quinidine) and in persons with active or recent depression, generalized anxiety disorder, psychosis, schizophrenia, other major psychiatric disorders, or seizures. Use with caution in persons with psychiatric disturbances or a history of depression. Mefloquine is not recommended for persons with cardiac conduction abnormalities.

Primaquine An 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. It is the most effective medicine for preventing P. vivax and so it is a good choice for travel to places with > 90% P. vivax. Primaquine is contraindicated in persons with G6PD1 deficiency. It is also contraindicated during pregnancy and in lactation unless the infant being breast-fed has a documented normal G6PD level. Use in consultation with malaria experts.


Global Health – Division of Parasitic Diseases. Centers for Disease Control and Prevention, updated Feb. 8, 2010.

icd cold shivers after a hot trip

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