Malaria¶
Infectious Diseases · Part 5 – Infectious Diseases: Parasitic · Part 5 – Infectious Diseases: Parasitic · Chapter 231
Key Clinical Points¶
- Malaria is a protozoan disease transmitted by infected female Anopheles mosquitoes and is the most important parasitic disease of humans.
- Six Plasmodium species cause human infections: P. falciparum, P. vivax, P. ovale (curtisi/wallikeri), P. malariae, and P. knowlesi.
- P. falciparum predominates in Africa, New Guinea, and Hispaniola; P. vivax is more common in Central/South America and Asia.
- Severe falciparum malaria involves sequestration of infected RBCs in vital organs via PfEMP1-mediated cytoadherence.
- Cerebral malaria presents as diffuse symmetric encephalopathy with rare focal signs.
- Hypoglycemia is a common complication in severe malaria, especially in children and pregnant women.
- Malaria in early pregnancy causes fetal loss; falciparum malaria in primigravid women correlates with low birth weight.
- Most falciparum malaria deaths (~600,000/year) occur in young African children.
- Clinical diagnosis is unreliable; classic paroxysms are rare and suggest relapse with P. vivax/ovale.
- Distinct parasite morphologies (e.g., banana-shaped gametocytes for P. falciparum, Schüffner's dots for P. vivax) are critical for identification.
1. DEFINITION & OVERVIEW¶
Malaria is a protozoan disease transmitted by the bite of infected female Anopheles mosquitoes and is the most important of the parasitic diseases of humans.
Historical Context: • Elimination from temperate zones (US, Canada, Europe, Russia) >50 years ago • Prevalence rose in tropics 1970–2000 • Mortality reduction 2000–2015 due to control programs • Resurgence since 2015 with rising case numbers in sub-Saharan Africa • Elimination efforts hindered by drug/insecticide resistance
2. EPIDEMIOLOGY¶
Global Burden: • ~249 million cases and 608,000 deaths globally in 2022 • ~1,660 deaths daily
Species Distribution: • P. falciparum: Africa, New Guinea, Hispaniola • P. vivax: Central/South America, Asia • P. ovale: Africa (curtisi/wallikeri) • P. malariae: Sub-Saharan Africa and globally • P. knowlesi: Borneo, Southeast Asia
Endemicity Classification: • Hypoendemic: <1% parasitemia in children 2–9 years • Mesendemic: 1–75% • Holoendemic: >75%
Vector Biology: • Transmission proportional to vector density, human-bite rate², and mosquito survival • Sporogony requires >7-day mosquito survival (8–30 days depending on temperature)
3. ETIOLOGY & PATHOPHYSIOLOGY¶
Parasite Characteristics (Table 1): • P. falciparum: 5.5-day intrahepatic phase; 30,000 merozoites released; 48h erythrocytic cycle; infects younger cells; no relapses; morphology includes ring forms and banana-shaped gametocytes. • P. vivax: 8-day intrahepatic phase; 10,000 merozoites released; 48h erythrocytic cycle; infects reticulocytes/cells up to 2 weeks old; relapses possible; morphology includes large rings and Schüffner's dots. • P. ovale: 9-day intrahepatic phase; 15,000 merozoites released; 50h erythrocytic cycle; infects reticulocytes; relapses possible; morphology includes enlarged erythrocytes with tufted ends. • P. malariae: 15-day intrahepatic phase; 15,000 merozoites released; 72h erythrocytic cycle; infects older cells; no relapses; morphology includes band or rectangular forms. • P. knowlesi: 5.5-day intrahepatic phase; 20,000 merozoites released; 24h erythrocytic cycle; infects younger cells; no relapses; resembles P. falciparum/P. malariae.
Pathogenesis of Severe Falciparum Malaria: • PfEMP1-mediated cytoadherence to endothelial receptors (ICAM-1, EPCR) • Sequestration in brain, lungs, kidneys → microvascular obstruction • Rosetting/agglutination of infected RBCs → exacerbates sequestration • Asymptomatic parasitemia common in endemic areas (~5000/mL) • Immunity: Developed through strain-specific IgM/IgG responses
Immune Targets (Figure 1)¶
• Liver Stage: CD4+ and CD8+ T cells kill intrahepatic parasites • Blood Entry: Antibodies to merozoites block invasion of RBCs • Toxins: Antibodies to malaria 'toxins' • Coadherence/Clearance: Antibodies to parasite antigens on infected RBCs block cytoadherence to endothelium and augment splenic clearance • Mosquito Stage: Antibodies block fertilization, development, and invasion
4. CLINICAL FEATURES¶
General Presentation: • Early phase: Malaise, headache, myalgia, abdominal pain • Severe cases: Hyperpyrexia (>40°C), tachycardia, delirium
Severe Falciparum Malaria (Table 2): • Cerebral Malaria: Unarousable coma; failure to respond to stimuli; duration >30 min after seizure; GCS ≤8 (or Blantyre <3 in children) • Acidemia/Acidosis: Arterial pH ≤7.3, bicarbonate ≤15 mmol/L; venous lactate ≥5 mmol/L • Severe Anemia: Hemoglobin <50 g/L (<5 g/dL) with parasite density >100,000/μL • Renal Failure: Creatinine >265 μmol/L (>3 mg/dL) or BUN >20 mmol/L • Pulmonary Edema/ARDS: Noncardiogenic; oxygen saturation <92% on room air; RR >30/min • Hypoxemia: Plasma oxygen content <60 mL/dL • Hypotension/Shock: Systolic BP <70 mmHg (children 1–5y) or <80 mmHg (adults); capillary refill ≥2 s • Bleeding/DIC: Significant hemorrhage in gums, nose, GI tract; evidence of DIC • Convulsions: >2 generalized seizures in 24 h • Hyperparasitemia: >5% in nonimmune patients (≥10% in any patient) • Jaundice: Bilirubin >34 μmol/L (>3 mg/dL) with parasite density >100,000/μL
Other Clinical Findings: • Hemoglobinuria: Macroscopic black, brown, or red urine • Extreme weakness: Prostration; inability to sit unaided • Ocular signs (Figure 3): Perimacular whitening and pale-centered retinal hemorrhages
5. DIFFERENTIAL DIAGNOSIS¶
• Viral illness: Fever without rash, no meningismus • Dengue: Less severe myalgia, no hemorrhagic manifestations • Typhoid: No abdominal tenderness, no rose spots • Leptospirosis: No jaundice in uncomplicated cases • Bacterial meningitis: No neck stiffness, no purulent CSF
6. INVESTIGATIONS & DIAGNOSIS¶
- Clinical Suspicion: • Fever in endemic area with travel history • History of recent antimalarial drug use • Presence of splenomegaly or jaundice
- Microscopy (Table 4): • Thick film: Used for parasite quantification; sensitive (0.001% parasitemia); identifies species • Thin film: Used for morphology and specific identification of stages (e.g., ring forms, trophozoites)
- Rapid Diagnostic Tests (RDTs): • HRP-2 (P. falciparum), pLDH (all species), aldolase • Advantage: Rapid; sensitivity similar to thick films (~0.001% parasitemia)
- Molecular Methods: • PCR for species confirmation and mixed infections
- Specialized Techniques: • Microtube concentration with acridine orange (high sensitivity, but no speciation)
7. MANAGEMENT & TREATMENT¶
- Uncomplicated Malaria (Table 5): • Chloroquine: For known chloroquine-sensitive strains; 10 mg/kg stat followed by 5 mg/kg at 12, 24, and 36 h OR 10 mg/kg at 24 h and 5 mg/kg at 48 h • Amodiaquine: 10–12 mg/kg qd for 3 days
- Radical Treatment (Prevention of Relapse): • Primaquine: For P. vivax or P. ovale; 0.5 mg/kg qd for 14 days (Southeast Asia/Oceania) or 0.25 mg/kg elsewhere • Tafenoquine: Single dose 300 mg (only if G6PD levels are normal)
- Severe Falciparum Malaria: • Artesunate: 4 mg/kg qd for 3 days • Combination options:
- Artesunate + Sulfadoxine (25 mg/kg) / Pyrimethamine (1.25 mg/kg)
- Artesunate + Amodiaquine (10 mg/kg qd for 3 days)
- Artemether-lumefantrined (1.5/9 mg/kg bid for 3 days with food)
- DHA-piperaquined (target dose: 4/24 mg/kg qd for 3 days in children <25 kg; 4/18 mg/kg qd for 3 days in persons ≥25 kg)
- Artesunate-pyronaridine (4/12 mg/kg qd for 3 days)
- Support: Exchange transfusion for severe anemia (Hb <50 g/L); Dialysis for AKI
- Prophylaxis (Table 8):
- Atovaquone-proguanil (Malarone): 1 adult tablet daily; 300 mg base once weekly (specific cases). Must be taken with food or a milky drink.
- Doxycycline: 100 mg qd (adult) or 2 mg/kg qd (pediatric ≥8 years)
- Mefloquine: 228 mg base once weekly; 30 mg base qd for P. vivax
- Primaquine: 30 mg base qd for 14 days post-exposure
8. PROGNOSIS & COMPLICATIONS¶
Acute Complications: • Cerebral malaria: Mortality 15–20%; long-term neurological sequelae (epilepsy, cognitive deficits) • ARDS: Seen in 5–10% of cases • AKI: Creatinine >3 mg/dL • Severe anemia: Hb <5 g/dL
Pregnancy Complications: • Maternal mortality risk increased 3–5x • Fetal loss in first trimester; low birth weight in second/third • Placental sequestration with VAR2CSA binding
Pediatric Complications: • Higher parasite density threshold for symptoms (~100,000/μL) • Increased risk of cerebral malaria and anemia • Febrile convulsions (5–10% of cases)
Risk Factors (Table 3): • Anemia: Very frequent in children (+++) • Hypoglycemia: Very frequent in pregnant women (+++) and children (+++) • Renal failure: Frequent in nonpregnant adults (+++) and pregnant women (+++) • Pulmonary edema: Frequent in nonpregnant adults (+++) and pregnant women (+++)
9. SPECIAL CONSIDERATIONS¶
Pregnancy: • Increased risk of maternal mortality (3–5x higher) • Fetal loss in first trimester, low birth weight in second/third • Placental sequestration with VAR2CSA binding
Children: • Higher parasite density thresholds for symptoms (~100,000/μL) • Increased risk of cerebral malaria and anemia • Febrile convulsions common (5–10% of cases)
10. KEY PEARLS & CLINICAL TRAPS¶
Diagnostic Pitfalls: • Reliance on clinical diagnosis (sensitivity <30%) • Atypical presentations in immunocompromised patients • Mixed infections with multiple species
Prognostic Indicators (Table 2): • Platelet count <50,000/μL predicts poor outcome • Creatinine >265 μmol/L (>3 mg/dL) indicates severe AKI • Bilirubin >34 μmol/L (>3 mg/dL) with parasite density >100,000/μL • Hyperparasitemia (>5% in nonimmune patients; ≥10% in any patient)
Drug Specifics (Table 6): • Quinine: Causes cinchonism; acts on trophozoite blood stage • Primaquine: Risk of severe hemolytic anemia in G6PD deficiency • Artemether/Artesunate: Rapidly eliminated; no action on liver stages
Reference Tables¶
TABLE 231-1 Characteristics of Plasmodium Species Infecting Humans CHARACTERISTIC Duration of intrahepatic phase (days)…¶
Harrison's 22e, p.1760
| CHARACTERISTIC | FINDING FOR INDICATED SPECIES | ||||
|---|---|---|---|---|---|
| P. FALCIPARUM | P. VIVAX | P. OVALEa | P. MALARIAE | P. KNOWLESI | |
| Duration of intrahepatic phase (days) | 5.5 | 8 | 9 | 15 | 5.5 |
| 30,000 | 10,000 | 15,000 | 15,000 | ||
| Approximate duration of erythrocytic cycle (h) |
48 | 48 | 50 | 72 | 24 |
| Younger cells (but can invade cells of all ages) |
Reticulocytes and cells up to 2 weeks old |
Reticulocytes | Older cells | ||
| Morphology | Usually only ring forms; banana-shaped gametocytes |
Irregularly shaped large rings and trophozoites; enlarged erythrocytes; Schüffner’s dots |
Infected erythrocytes, enlarged and oval with tufted ends; Schüffner’sb dots |
Band or rectangular forms of trophozoites common |
Resembles P. falciparum (early trophozoites) or P. malariae (later trophozoites, including band forms) |
| Black | Yellow-brown | Dark brown | Brown-black | ||
| Ability to cause relapses | No | Yes | Yes | No | No |
TABLE 231-3 Features Indicating a Poor Prognosis in Severe Falciparum Malaria Clinical Marked agitation…¶
Harrison's 22e, p.1764
| SIGNS | MANIFESTATIONS |
|---|---|
| Major | |
| Unarousable coma/ cerebral malaria |
Failure to localize or respond appropriately to noxious stimuli; coma persisting for >30 min after generalized convulsion; a Glasgow Coma Score <11, or in young children a Blantyre Coma Score of <3 |
TABLE 231-3 Features Indicating a Poor Prognosis in Severe Falciparum Malaria
| Clinical | |
|---|---|
| Marked agitation Hyperventilation (respiratory distress) Low core temperature (<36.5°C; <97.7°F) Bleeding Deep coma Repeated convulsions Anuria Shock |
|
| Laboratory | |
| Biochemistry Hypoglycemia (<2.2 mmol/L) Hyperlactatemia (≥5 mmol/L) Acidemia (arterial pH <7.25, base deficit >8 meq/L, or serum HCO <15 mmol/L) 3 Elevated serum creatinine (>265 μmol/L) Elevated total bilirubin (>50 μmol/L) Elevated liver enzymes (AST/ALT 3 times upper limit of normal) Elevated muscle enzymes (CPK ↑, myoglobin ↑) Elevated urate (>600 μmol/L) |
|
| Hematology Leukocytosis (>12,000/μL) Severe anemia (PCV <10%) Coagulopathy Low platelet count (<50,000/μL) Prolonged prothrombin time (>3 s) Prolonged partial thromboplastin time Decreased fibrinogen (<200 mg/dL) |
|
| Parasitology Hyperparasitemia Increased mortality at >100,000/μL High mortality at >500,000/μL >20% of parasites identified as pigment-containing trophozoites and schizonts >5% of neutrophils contain visible malaria pigment |
|
| Severe normochromic, normocytic anemia |
Hematocrit of <15% or hemoglobin level of <50 g/L (<5 g/dL) with parasite density of >10,000/μLa |
| Pulmonary edema/ adult respiratory distress syndrome |
Noncardiogenic pulmonary edema, often aggravated by overhydration; radiologically confirmed or oxygen saturation <92% on room air with a respiratory rate >30/ min, often with chest wall indrawing and crepitations on auscultation |
| Hypotension/shock | Systolic blood pressure of <70 mmHg in children 1–5 years or <80 mmHg in adults; with evidence of impaired perfusion or capillary refill >2 s |
| Convulsions | More than two generalized seizures in 24 h; signs of continued seizure activity, sometimes subtle (e.g., tonic- clonic eye movements without limb or face movement) |
| Other | |
| Extreme weakness | Prostration; inability to sit unaidedd |
| Jaundice | Serum bilirubin level of >50 mmol/L (>3 mg/dL) if combined with a parasite density of >100,000/μL or other evidence of vital-organ dysfunction |
TABLE 231-4 Relative Incidence of Severe Complications of Falciparum Malaria COMPLICATION Anemia Convulsions…¶
Harrison's 22e, p.1765
| COMPLICATION | NONPREGNANT ADULTS |
PREGNANT WOMEN |
CHILDREN |
|---|---|---|---|
| Anemia | + | ++ | +++ |
| + | + | ||
| Hypoglycemia | + | +++ | +++ |
| +++ | +++ | ||
| Renal failure | +++ | +++ | + |
| ++ | +++ |
TABLE 231-5 Standard Methods for the Diagnosis of Malaria a METHOD Thick blood film b¶
Harrison's 22e, p.1769
| METHOD | PROCEDURE | ADVANTAGES | DISADVANTAGES |
|---|---|---|---|
| Thick blood filmb | Blood should be uneven in thickness but thin enough that the hands of a watch can be read through part of the spot. Stain dried, unfixed blood spot with Giemsa, Field’s, or another Romanowsky stain. Count number of asexual parasites per 200 WBCs (or per 500 WBCs at low densities). Count and report gametocytes separately.c |
Sensitive (0.001% parasitemia); species specific; inexpensive |
Requires experience (artifacts may be misinterpreted as low-level parasitemia); underestimates true count |
| Stain fixed smear with Giemsa, Field’s, or another Romanowsky stain. Count number of RBCs containing asexual parasites per 1000 RBCs. In severe malaria, assess stage of parasite development and count neutrophils containing malaria pigment.e Count and report gametocytes separately.c |
Rapid; species specific; inexpensive; in severe malaria, provides prognostic informatione |
||
| PfHRP2 dipstick or card test |
A drop of blood is placed on the stick or card, which is then immersed in washing solutions. Monoclonal antibody capture of parasitic antigens reads out as a colored band. |
Robust and relatively inexpensive; rapid; sensitivity similar to or slightly lower than that of thick films (~0.001% parasitemia) |
Detects only Plasmodium falciparum; remains positive for weeks after high-density infectionsf; does not quantitate P. falciparum parasitemia; evasion of detection by certain strains due to polymorphisms/deletions in HRP2/3 genes |
| A drop of blood is placed on the stick or card, which is then immersed in washing solutions. Monoclonal antibody capture of parasitic antigens reads out as two colored bands. One band is genus specific (all malarias) or P. vivax specific, and the other band is specific for P. falciparum. |
Rapid; sensitivity similar to or slightly lower than that of thick films for P. falciparum (~0.001% parasitemia) |
||
| Microtube concentration methods with acridine orange staining |
Blood is collected in a specialized tube containing acridine orange, anticoagulant, and a float. After centrifugation, which concentrates the parasitized cells around the float, fluorescence microscopy is performed. |
Sensitivity similar or superior to that of thick films (~0.001% parasitemia); ideal for processing large numbers of samples rapidly |
Does not speciate or quantitate; requires fluorescence microscopy |
TABLE 231-6 Regimens for the Treatment of Malaria a¶
Harrison's 22e, p.1770
| TYPE OF DISEASE OR TREATMENT | REGIMEN(S) |
|---|---|
| Uncomplicated Malaria | |
| Known chloroquine-sensitive strains of Plasmodium vivax, P. malariae, P. ovale, P. falciparumb |
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) or Amodiaquine (10–12 mg of base/kg qd for 3 days) |
| Radical treatment for P. vivax or P. ovale infection (prevention of relapse) |
In addition to chloroquine or amodiaquine or ACT, primaquine (0.5 mg of base/kg qd in Southeast Asia and Oceania [total dose 7 mg/kg] and 0.25 mg/kg elsewhere [total dose 3.5 mg/kg]) should be given for 14 days to prevent relapse.c In mild G6PD deficiency, 0.75 mg of base/kg should be given once weekly for 8 weeks. Primaquine should not be given in severe G6PD deficiency. Single dose tafenoquine (adult dose 300 mg) is being introduced for radical cure in some areas alongside quantitative G6PD testing. Can be given only If G6PD levels are normal. |
| P. falciparum malaria | Artesunated,e (4 mg/kg qd for 3 days) plus sulfadoxine (25 mg/kg)/pyrimethamine (1.25 mg/kg) as a single dose |
| or | |
| Artesunated (4 mg/kg qd for 3 days) plus amodiaquine (10 mg of base/kg qd for 3 days)d,e | |
| or Artemether-lumefantrined (1.5/9 mg/kg bid for 3 days with food) |
|
| or | |
| Artesunated (4 mg/kg qd for 3 days) plus mefloquine (24–25 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)f |
|
| or | |
| DHA-piperaquined (target dose: 4/24 mg/kg qd for 3 days in children weighing <25 kg and 4/18 mg/kg qd for 3 days in persons weighing ≥25 kg) or Artesunate-pyronaridined (4/12 mg/kg qd for 3 days) |
|
| Second-line treatment/treatment of imported malaria (if other ACT not available) |
Artesunatee (2 mg/kg qd for 7 days) or quinine (10 mg of salt/kg tid for 7 days) plus 1 of the following 3: Tetracyclinef (4 mg/kg qid for 7 days) Doxycyclinef (3 mg/kg qd for 7 days) Clindamycin (10 mg/kg bid for 7 days) or Atovaquone-proguanil (20/8 mg/kg qd for 3 days with food) |
| Severe Falciparum Malariag,h,i |
TABLE 231-7 Properties of Antimalarial Drugs DRUG(S) a Quinine¶
Harrison's 22e, p.1771
| DRUG(S)a | PHARMACOKINETIC PROPERTIES | ANTIMALARIAL ACTIVITY | MINOR TOXICITY | MAJOR TOXICITY |
|---|---|---|---|---|
| Quinine | Good oral and IM absorption (quinine); Cl and V reduced, but d plasma protein binding (principally to α1 acid glycoprotein) increased (90%) in malaria; quinine t : 16 h in 1/2 malaria, 11 h in healthy persons |
Acts mainly on trophozoite blood stage; kills gametocytes of P. vivax, P. ovale, and P. malariae (but not P. falciparum); no action on liver stages |
Common: cinchonism (tinnitus, high-tone hearing loss, nausea, vomiting, dysphoria, postural hypotension); ECG QT interval prolongation (usually by <10%). Rare: diarrhea, visual disturbance, rashes. Note: very bitter taste |
Common: hypoglycemia. Rare: hypotension, blindness, deafness, cardiac arrhythmias, thrombocytopenia, hemolysis, hemolytic-uremic syndrome, vasculitis, cholestatic hepatitis, neuromuscular paralysis. |
| Good oral absorption, very rapid IM and SC absorption; complex pharmacokinetics; enormous Cl and V (unaffected by malaria); blood d concentration profile determined by distribution processes in malaria; t : 1–2 months. Active desethyl 1/2 metabolite about 25% of parent drug concentrations |
As for quinine, but acts slightly earlier in asexual cycle |
Common: nausea, dysphoria, pruritus in dark-skinned patients, postural hypotension, ECG QT prolongation. Rare: accommodation difficulties, keratopathy, hypoglycemia, rash. Note: bitter taste but usually well tolerated |
||
| Piperaquine | Adequate oral absorption, may be enhanced by fats; similar pharmacokinetics to chloroquine; t : 1/2 21–28 days |
As for chloroquine; resistance has emerged in Southeast Asia |
Occasional epigastric pain, diarrhea, ECG QT prolongation |
None identified |
| Good oral absorption; largely converted to active metabolite desethylamodiaquine; t : 4–5 days 1/2 |
As for chloroquine, but more active against chloroquine-resistant P. falciparum |
Nausea (tastes better than chloroquine), dysphoria, headache, bradycardia, ECG QT prolongation |
||
| Primaquine | Complete oral absorption; active metabolite produced mainly via CYP2D6; t : 5–7 h 1/2 |
Radical cure; eradicates hepatic forms of P. vivax and P. ovale; kills P. falciparum gametocytes; kills developing liver stages of all species |
Nausea, vomiting, diarrhea, abdominal pain, hemolysis, methemoglobinemia |
Serious hemolytic anemia in severe G6PD deficiency; hemoglobinuria |
| Adequate oral absorption; no parenteral preparation; t : 1/2 14–20 days (shorter in malaria) |
As for quinine; resistance has emerged in Southeast Asia |
Nausea, giddiness, dysphoria, fuzzy thinking, sleeplessness, nightmares, sense of dissociation |
||
| Lumefantrine | Highly variable absorption related to fat intake; t : 3–4 days 1/2 |
As for quinine | None identified | None identified |
| Good oral absorption; good absorption of IM artesunate but slow and variable absorption of IM artemether; artesunate and artemether biotransformed to active metabolite dihydroartemisinin; all drugs eliminated very rapidly; t : <1 h 1/2 |
Broader stage specificity and more rapid than other drugs; no action on liver stages; kills all but fully mature gametocytes of P. falciparum |
Reduction in reticulocyte count (but not anemia); neutropenia at high doses; in some cases, delayed anemia after treatment of severe malaria with hyperparasitemia |
||
| Pyrimethamine | Good oral absorption, variable IM absorption; t : 4 days 1/2 |
For blood stages, acts mainly on mature forms; causal prophylactic |
Well tolerated | Megaloblastic anemia, pancytopenia, pulmonary infiltration |
| Good oral absorption; biotransformed to active metabolite cycloguanil; t : 16 h; biotransformation reduced 1/2 by oral contraceptive use and in pregnancy |
Causal prophylactic; not used alone for treatment |
Well tolerated; mouth ulcers and rare alopecia |
||
| Atovaquoneb | Highly variable absorption related to fat intake; t : 30–70 h 1/2 |
Acts mainly on trophozoite blood stage | None identified | None identified |
| Excellent absorption; t : 8 h for 1/2 tetracycline, 18 h for doxycycline |
Weak antimalarial activity; should not be used alone for treatment |
Gastrointestinal intolerance, deposition in growing bones and teeth (tetracycline), photosensitivity, moniliasis, benign intracranial hypertension |
||
| Pyronaridine | Rapid variable absorption, large V; d t : 12–14 days 1/2 |
Acts mainly on trophozoite blood stage; kills gametocytes of P. vivax, P. ovale, and P. malariae (but not P. falciparum); no action on liver stages |
Gastrointestinal intolerance, anemia, transient elevation of aminotransferases, hypoglycemia, headache |
None identified |
| t : 3 h 1/2 |
Broad stage specificity; no action on liver stages; kills all but fully mature gametocytes of P. falciparum |
Gastrointestinal intolerance, transient elevation of aminotransferases |
TABLE 231-8 Drugs Used in the Prophylaxis of Malaria a DRUG Atovaquone- proguanil (Malarone)¶
Harrison's 22e, p.1774
| DRUG | USAGE | ADULT DOSE | PEDIATRIC DOSE | COMMENTS |
|---|---|---|---|---|
| Atovaquone- proguanil (Malarone) |
Prophylaxis in areas with chloroquine- or mefloquine-resistant Plasmodium falciparum |
1 adult tablet POb | 5–8 kg: ½ pediatric tabletc daily ≥8–10 kg: ¾ pediatric tablet daily ≥10–20 kg: 1 pediatric tablet daily ≥20–30 kg: 2 pediatric tablets daily ≥30–40 kg: 3 pediatric tablets daily ≥40 kg: 1 adult tablet daily |
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. Atovaquone-proguanil is contraindicated in persons with severe renal impairment (creatinine clearance rate, <30 mL/min). In the absence of data, it is not recommended for children weighing <5 kg, pregnant women, or women breast-feeding infants weighing <5 kg. Atovaquone-proguanil should be taken with food or a milky drink. |
| Prophylaxis only in the very few areas with chloroquine-sensitive P. falciparumc or areas with P. vivax only |
300 mg of base (500 mg of salt) PO once weekly |
5 mg of base/kg (8.3 mg of salt/ kg) PO once weekly, up to maximum adult dose of 300 mg of base |
||
| Doxycycline (many brand names and generic) |
Prophylaxis in areas with chloroquine- or mefloquine-resistant P. falciparumd |
100 mg PO qd (except in pregnant women; see Comments) |
≥8 years of age: 2 mg/kg PO qd, up to adult dose |
Begin 1–2 days before travel to malarious areas. Take daily at the same time each day while in the malarious areas and for 4 weeks after leaving such areas. Doxycycline is contraindicated in children aged <8 years and in pregnant women. |
| An alternative to chloroquine for primary prophylaxis only in the very few areas with chloroquine-sensitive P. falciparumd or areas with P. vivax only |
310 mg of base (400 mg of salt) PO once weekly |
5 mg of base/kg (6.5 mg of salt/ kg) PO once weekly, up to maximum adult dose of 310 mg of base |
||
| Mefloquine (Lariam and generic) |
Prophylaxis in areas with chloroquine-resistant P. falciparumd |
228 mg of base (250 mg of salt) PO once weekly |
≤9 kg: 4.6 mg of base/kg (5 mg of salt/kg) PO once weekly >9–19 kg: ¼ tablete once weekly >19–30 kg: ½ tablet once weekly >30–45 kg: ¾ tablet once weekly >45 kg: 1 tablet 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. 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. |
| For prevention of malaria in areas with mainly P. vivax |
30 mg of base (52.6 mg of salt) PO qd |
0.5 mg of base/kg (0.8 mg of salt/kg) PO qd, up to adult dose; should be taken with food |
||
| Primaquine | 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 |
0.5 mg of base/kg (0.8 mg of salt/kg), up to adult dose, PO qd for 14 days after departure from the malarious area |
This therapy is indicated for persons who have had prolonged exposure to P. vivax and/or P. ovale. It is contraindicated in persons with G6PD deficiency as well as during pregnancy. |