​Kembara Xtra - Medicine - Malaria

​Kembara Xtra - Medicine - Malaria 
Anopheles mosquitoes can transmit potentially fatal Plasmodium species infections to people. Affected systems include the circulatory, hematologic, renal, pulmonary, cerebral, lymphatic, immune, and hepatic systems.

Plasmodium falciparum accounts for 79% of imported cases in the United States, followed by 11% Plasmodium vivax, 6% Plasmodium ovale, and 3% Plasmodium malariae. There are around 229 million cases worldwide each year, with 400,000 deaths (mostly children in sub-Saharan Africa).
7 deaths and 2,000 cases (more than 99% of which are imported) each year in the United States
Prevalence
 Age distribution: all ages Males predominate over females.


Pathophysiology and Etiology 

Plasmodia are spread from an infected Anopheles mosquito to a human during a blood meal by saliva.
Red blood cells (RBC) are invaded by circulating plasmodia, which then degrade RBC proteins and change the RBC membrane, resulting in hemolysis, increased splenic clearance, and anemia.
RBC lysis promotes cytokine and TNF release, which results in fever and other systemic symptoms.
RBC viscosity is changed by P. falciparum, leading to blockage and end-organ ischemia.
Genetics
Disease severity and susceptibility may be impacted by inherited disorders (such as the trait or disease of sickle cell anemia).

Travel to or migration from endemic areas are risk factors. Blood transfusions, congenital transmission, and autochthonous transmission occur in nonendemic areas seldom.


Prevention 
Use insect repellent, cover up any exposed skin, use mosquito nets coated with insecticides like permethrin, and stay indoors from dusk to dawn when the Anopheles mosquito is most active in its feeding activity.
Malaria chemotherapy in endemic regions
- Atovaquone/proguanil: Start taking everyday till a week after leaving the area, starting 1 to 2 days before arrival. Children 5 to 8 kg receive half a pediatric tablet, children 9 to 10 kg receive a full pediatric tablet, children >10 kg receive one pediatric tablet, children >20 kg receive two pediatric tablets, children >30 kg receive three pediatric tablets, and children >40 kg receive one adult tablet.
 Unsafe for use during pregnancy and in children under 5 kg
- Chloroquine: Start taking it a week before you arrive and continue doing so for 4 weeks after you leave the area. Adults: 500 mg (300 mg base) of salt weekly; children: 8.3 mg (5.0 mg base) of salt weekly up to 500 mg of salt.
Caution: can exacerbate psoriasis
Doxycycline should be taken daily for 4 weeks after leaving the area, starting 1 to 2 days prior to arrival. Adults: 100 mg once daily; kids over 8: 2 mg/kg to 100 mg QD
Pregnant women and children under the age of eight should not use this product.
- Hydroxychloroquine: Start taking it a week before you arrive and continue doing so for 4 weeks after you leave the area. Adults need 400 mg of salt (310 mg of base) per week; children need 6.5 mg of salt (5.0 mg of base) each week up to 400 mg of salt.
Mefloquine should be taken weekly until four weeks after leaving the area, starting at least two weeks prior to arrival. Adults should take 250 mg (1 tablet) every week; children under 9 kg should take 5 mg/kg every week; children between 9 and 19 kg should take 1/4 tablet; children between 30 and 45 kg should take 3/4 tablet; and children over 45 kg should take 1 tablet every week.
Primaquine should be taken daily for a week after leaving the area, starting 1 to 2 days prior. Adults should take 30 mg QD, while children should take 0.5 mg/kg/day up to adult dose.
Use only in regions where P. vivax is endemic.
Before using, rule out G6PD deficiency; if newborn hasn't had a G6PD deficiency test, avoid using in pregnant or nursing mothers.
- Tafenoquine: Start three days prior to arrival and continue taking it daily for one week after leaving the area for adults.
Before using, rule out G6PD deficiency; avoid using if you have a history of psychiatric illnesses; and avoid using on minors or on women who are pregnant or nursing.

Accompanying Conditions 
Bacterial coinfections can occasionally happen.
The sickle cell trait offers some level of defense.

Background The initial symptoms are vague. Consider malaria in sick people returning from endemic areas if they have any of the following symptoms: - Fever, malaise, myalgias, chills, headache, nausea, splenomegaly (chronic infection), hypotension, anemia, thrombocytopenia, jaundice, vomiting, and/or diarrhea - P. falciparum - Incubation period 7 to 14 days, symptoms typically appear within 1 month of infection (partially immune people may become 
P. vivax and P. ovale - Incubation period 9 to 18 d for primary infection; up to 12 months or longer for relapses - Case reports of asymptomatic persistence in untreated individuals - P. malariae - Incubation period 18 to 40 days - P. knowlesi - Incubation period 9 to 12 days - Severe disease and complications: vascular collapse, central nervous system impairment, renal failure, and acute respiratory distress syndrome
PHYSICAL EXAMINATION Frequently not specific General: fever, exhaustion, tachycardia, tachypnea, and jaundice
 Cardiopulmonary exam: hemodynamic instability and symptoms of vascular leak (effusion; pulmonary edema) Skin exam: pallor, rash Abdominal exam: organomegaly Neurologic: change in mental status and motor-sensory abnormalities (cerebral malaria) 


Differential diagnosis Infections (localized or disseminated): abscess, viral, gastroenteritis, typhoid/paratyphoid, other bacteremias, rickettsial illness, mycobacteria
Vascular collagen disease
Severe malaria infection may mimic hepatitis, pneumonia, meningitis, stroke, or sepsis. Neoplasms (lymphoma, leukemia, other blood dyscrasias, other tropical causes of splenomegaly)

Laboratory Findings: Thrombocytopenia, anemia, and leukopenia; elevated liver enzymes; rapid antigen testing; malaria microscopy; thick and thin blood smears; rapid antigen testing can detect the presence of malaria parasites within minutes; other tests include PCR for species confirmation; general laboratory findings (nonspecific): rings, trophozoites, and schizonts; and thrombocytopenia, anemia, and leukopenia.


Initial examinations (lab, imaging)
Complete biliary and differential
Basic chemical panel with bilirubin and thick and thin blood films for malaria (If negative, repeat every 12 to 24 hours for a minimum of three sets.)
Only respiratory illnesses (chest x-ray) and cerebral malaria (CT scan before lumbar puncture) require imaging.
Tests in the Future & Special Considerations
CDC testing for speciation, medication resistance, and diagnostic confirmation should be requested.
Interpretation of Tests
Rapid diagnostic test: makes a preliminary determination. Microscopy: confirms diagnosis, includes species of plasmodium and measures percentage of red cells infected. Smears should be taken to validate results, identify species, and calculate the percentage of contaminated red blood cells.

management in the lead
Oral treatment for uncomplicated, chloroquine-resistant P. falciparum, P. vivax, or unknown species:
- 20 mg of artemether and 120 mg of lumefantrine are combined in one tablet (tab) under the brand name Coartem. 3 days worth of 6 dosages. First dose on day 1, followed by second dose eight hours later. BID on days 2 and 3.
1 tablet per dose for individuals 5 to 15 kg; 2 tablets per dose for those 15 to 25 kg; 3 tablets per dose for those 25 to 35 kg; and 4 tablets per dose for those over 35 kg.
Call 1-855-COARTEM to find a drugstore that has supplies.
Pregnant women in the first trimester and newborns under 5 kg are not advised to use this product.
- Atovaquone-proguanil (Malarone): 250 mg atovaquone and 100 mg proguanil per adult tablet. A pediatric pill containing 25 mg of proguanil and 62.5 mg of atovaquone. 4 adult pills every three hours for adults. Children 5 to 8 kg should take two pediatric tablets every day for three days. Children 8 to 10 kg should take three pediatric tablets every day for three days. Children 10 to 20 kg should take one adult tablet every day for three days. Children 30 to 40 kg should take three adult tablets every day. Children over 40 kg should take four adult tablets every day.
 Warning: Quinine sulfate and doxycycline, or clindamycin for individuals who cannot take doxycycline, are not advised for use in pregnant women and newborns under 5 kg: Adults should take 650 mg of quinine sulfate (salt) TID for 3 days (up to 7 days for illnesses originating in Southeast Asia). 100 mg BID of doxycycline for seven days. Clindamycin 20 mg (base)/kg/day divided TID for 7 days; for pediatric patients, quinine sulfate 10 mg (salt)/kg TID for 3 days (extended to 7 days for infections from Southeast Asia) and doxycycline 2.2 mg/kg BID for 7 days if the patient is under the age of 8, or clindamycin dosed as above if the patient is above the age of 8.
Doxycycline is not suggested for use in children under the age of eight and pregnant women.
- Mefloquine: the maximum daily dose is 1,250 mg for adults, followed by 750 mg, 500 mg, and 15 mg/kg for children.
Oral therapy for uncomplicated chloroquine-sensitive P. vivax, P. ovale, P. malariae, and chloroquine-sensitive P. falciparum (rare) infections is not advised due to drug resistance in infections from SE Asia or in patients with neuropsychiatric histories. Other treatment options, in addition to the above-mentioned regimens, include:
Children should receive 16.7 mg/kg (10 mg base/kg) on day 1 (maximum 1,000 mg [600-mg base]) and then 8.3 mg/kg (5 mg/kg base) at 6, 24, and 48 hours after the first dose of chloroquine for adults and 500 mg (300 mg base) at 6, 24, and 48 hours after the first dose.
Caution: can exacerbate psoriasis
Adults should take 800 mg of hydroxychloroquine sulfate (620 mg base), followed by 400 mg of salt (310 mg base) at 6, 24, and 48 hours after the initial dose; children should take 13 mg of salt (10 mg base/kg), followed by 6.5 mg of salt (5 mg base/kg) at 6, 24, and 48 hours.
Caution: can exacerbate psoriasis
– Add primaquine or tafenoquine to P. vivax or P. ovale to treat latent parasites. Chloroquine or hydroxychloroquine must be taken along with tafenoquine:
Primaquine dosage for adults is 30 mg base (52.6 mg salt) QD for two weeks; for children, the dosage is 0.6 mg base/kg/day for two weeks.
 Caution: Do not use in pregnant women; exclude G6PD before initial usage.
 Tafenoquine: kids under the age of 16; a single 300 mg dosage
 Caution: Before using, rule out G6PD deficiency; avoid using when nursing or pregnant.
Parenteral treatment is necessary for those with severe malaria who meet at least one of the following criteria:
 Parasitemia 5% or less, low level of awareness (LOC), convulsions frequently, respiratory distress, shock, renal failure, severe anemia (Hb 7), acidosis, disseminated intravascular coagulation, and jaundice.
- Each dose of intravenous artesunate (IVAS) is 2.4 mg/kg. dosing every 12 and 24 hours. For simple chloroquine-resistant P. falciparum infections, reevaluate the parasite density and continue the once-daily dose until the parasite density is less than 1%. Then, administer the entire oral regimen as previously mentioned. Commercial IVAS is offered.


Consultation on infectious diseases or tropical medicine. 

Further Therapies 
Nothing pertaining to children
Children are vulnerable to serious illness and are at risk for hypoglycemia. For maintenance, use glucose-containing IV fluids.
If visiting an endemic area, all children and newborns should take chemoprophylaxis.
Can have symptoms of acute gastroenteritis.

Considerations During Pregnancy Artesunate, chloroquine, mefloquine, quinine, and clindamycin are all safe when taken at the recommended doses. Coartem is also safe during the second and third trimesters, with some evidence of safety during the first trimester. Malarone has limited safety data.

Surgical Techniques 

Splenectomy with splenic rupture occurs infrequently.


Admission 
Outpatient care for all other cases; inpatient care for those with P. falciparum malaria or symptoms of severe disease, regardless of species.
Within 24 hours, every follow-up was treated as an outpatient.
 Keep an eye out for hypoglycemia, renal insufficiency, and fluid retention.
Add glucose to IV maintenance fluids. Clinical improvement and evidence of declining parasite numbers.

Information for patients: http://www.cdc.gov/travel Malaria chemoprophylaxis before travel

A malaria infection, especially one caused by P. falciparum, can be fatal. The prognosis is excellent in cases of early diagnosis and effective treatment.

Cerebral malaria, acute renal failure, respiratory distress syndrome, disseminated intravascular coagulation, hemolysis, and anemia are complications that can develop if not treated quickly.
Seizures, anuria, psychosis, coma, dysentery, and hyperpyrexia are further consequences.
P. malariae: Patients with a persistent infection may experience nephrotic syndrome