Parasitic Infections

Parasitic Infections

Malaria

Malaria is considered the world's most important parasitic disease, responsible for an estimated 300 to 500 million cases and annual deaths in excess of 1 million.1

The distribution of the four Plasmodium species of malaria varies worldwide, with Plasmodium falciparum, which has the highest mortality,
Malaria transmission in the United States has occurred from the blood of immigrants and rarely through blood transfusions.Malaria can also be transmitted congenitally and through contaminated needles.
The characteristic malarial paroxysms of chills and fever in patients usually coincide with the periodic release of merozoites and other pyrogens in the blood.
In P. falciparum infections, this periodicity may not always be apparent. However, intervals of 48 hours between paroxysms are reported for Plasmodium vivax, Plasmodium ovale, and P. falciparum (tertian periodicity), and 72 hours for Plasmodium malariae (quartan periodicity).
Unlike infections caused by P. falciparum and P. malariae,infections with P. vivax and P. ovale have a latent form of the exoerythrocytic phase that can persist in the host liver for months to years. This latent form can produce relapses of the erythrocytic infection
Most fatal cases of imported malaria in the United States are the result of travelers' failure to comply with appropriate chemosuppressive regimens, delays in seeking treatment, misdiagnosis by physicians or laboratories, and inappropriate antimalarial regimens.2,13 Prophylactic drug regimens for individuals traveling to endemic areas are problematic

Acute Malaria

Signs and Symptoms

Abdominal examination reveals a soft, tender spleen that is slightly enlarged.
↓Blood pressure (BP); pulse 120 beats/minute, respiration rate 32 breaths/minute, and temperature 40°C.
Laboratory findings include hemoglobin (Hgb) 11 g/dL (normal, 12–16); hematocrit (Hct) 34% (normal, 36%–47%);↓ white blood cell (WBC) count with 76% neutrophils (normal, 45%–65%), 23% lymphocytes (normal, 15%–35%), and 1% monocytes (normal, 1%–6%); platelets 83 × 103/mm3 (normal, 150–450); and bilirubin 1.0 mg/dL (normal, 0.1–1).
Urinalysis reveals trace amounts of albumin and the presence of urobilinogen.

Treatment

Quinidine and Quinine

Start on intravenous (IV) quinidine gluconate.4,9,11,18,27 For doses of IV quinidine, see Table 74-1. If >48 hours of parenteral therapy is required, the dosage of quinidine should be reduced by one-third to one-half.

Oral quinine and clindamycin or the combination of atovaquone and proguanil (Malarone) can be used until IV quinidine is available.

While receiving the IV quinidine, M.L.'s electrocardiogram, BP, and serum glucose should be monitored closely.4,7,9 Supportive care, including fluid, IV dextrose 5% to 10% and electrolyte management, dialysis, blood transfusion, and mechanically assisted ventilation, are important adjunctive therapies in seriously ill patients. The serum concentration of quinidine should be determined once daily during the continuous infusion.

Managing Chloroquine-Resistant Plasmodium falciparumCRPF

One of the recommended drug treatments for CRPF infection, which is added to quinine therapy, is doxycycline 100 mg twice daily for 7 days (doxycycline should overlap the quinine for 2 to 3 days before the latter is discontinued) or clindamycin 900 mg three times a day for 5 days.27 If the patient cannot tolerate oral doxycycline, IV doxycycline 100 mg Q 12 hr can be substituted. An alternative in a patient who can tolerate oral therapy and in whom it is not contraindicated (i.e., history of seizures, or endemic area where P. falciparum is not resistant to the agent) mefloquine 750 mg can be initiated, followed by 500 mg 12 hours later.

Managing Other Plasmodia Species

A patient infected with one of the other species of Plasmodia (P. vivax, P. ovale, or P. malariae) should receive oral chloroquine phosphate (Aralen). The initial dose is 1 g (600 mg base) followed by 500 mg (300 mg base) 6 hours later; subsequently, 500 mg (300 mg base) is administered daily for 2 days.27 For patients who cannot tolerate the oral doses of chloroquine, parenteral doses of quinidine can be administered (Question 2 lists doses).27 Patients with P. ovale and P. vivax also should be given primaquine to prevent relapses from the latent exoerythrocytic stages in the liver. The adult dosage of primaquine is 52.6 mg/day (30 mg base) for 14 days; this should follow the chloroquine regimen.

Chemoprophylaxis and Pregnancy

All travelers to endemic areas should receive chemoprophylaxis for malaria.

Pregnant women are at greater risk for malaria infection and its complications (especially severe hemolytic anemia and splenomegaly) and should be advised not to travel to areas endemic for malaria

Chloroquine and Primaquine Phosphate

Chloroquine phosphate is an effective chemoprophylactic agent against all species of Plasmodia except drug-resistant P. falciparum. The adult dosage of chloroquine phosphate is 500 mg (300 mg base) once weekly beginning 1 week before departure and continuing for 4 weeks after last exposure. The pediatric dosage of chloroquine is 5 mg/kg base (8.3 mg chloroquine phosphate) once weekly beginning 1 week before departure and continuing for 4 weeks after exposure. A suspension of chloroquine in chocolate syrup can be prepared for children (5 mg/mL). Chloroquine prophylaxis is safe during pregnancy, and the benefits outweigh the risk of malaria and the drug's possible side effects.9,11,13,27,29,31 Mefloquine and Malarone may be options for prophylaxis and treatment in pregnancy29,30,31,32,33,34; however, these are not recommended for this particular indication in the United States.27

By taking the chloroquine 1 week before travel, the patient can achieve adequate antimalarial chloroquine levels in the blood by the second week. Potential side effects also can be detected early. A weekly dose of 0.5 g of chloroquine phosphate produces average plasma concentrations of chloroquine between 0.47 and 0.78 mcmol/L Most strains of P. vivax and P. falciparum are susceptible to plasma levels between 0.046 and 0.093 mcmol/L, respectively.7,18,35 Mefloquine (Lariam) 250 mg (salt) once weekly beginning 1 week before departure and continuing for 4 weeks after leaving a malarious area is an alternative regimen to chloroquine.7,18,27,36 Mefloquine is not recommended during pregnancy or in children weighing ≤5 kg, however, because the safety of this agent has not been fully established in these populations.27 Recently, P. vivax was reported to be resistant to chloroquine in Indonesia and New Guinea, and despite the lack of data on mefloquine in pregnancy (T.R. is in the second trimester), T.R. may have to be given this agent.15,18,32,33,37,38 Chloroquine suppresses the asexual erythrocytic forms of the malaria parasite and has no action against the exoerythrocytic phase of P. vivax and P. ovale.7,18 However, primaquine phosphate prevents relapses of P. vivax and P. ovale by inhibiting the exoerythrocytic stage; it also has a significant gametocidal effect against all species.11,15,18 To prevent an attack after departure from an area where P. vivax and P. ovale are present, the clinician should also prescribe primaquine phosphate 52.6 mg/day (30 mg base) for 14 days to coincide with the last 2 weeks of the chloroquine regimen. Primaquine should not be administered to pregnant patients.27 The major toxicity of concern, aside from the teratogenic risk, is hemolytic anemia in patients with RBC glucose-6-phosphate dehydrogenase (G6PD) deficiency7,18,28,36,39

Prophylaxis for Chloroquine-Resistant Plasmodium falciparum

Prophylaxis for CRPF also can be achieved by taking mefloquine in the doses indicated above instead of using the

chloroquine regimen.27 An alternative to mefloquine is doxycycline 100 mg/day beginning 1 day before travel and continuing for the duration of the stay and for 4 weeks after leaving the malarial area

An alternative to the mefloquine chemoprophylaxis regimen in CRPF areas is the combination of atovaquone 250 mg and proguanil 100 mg (Malarone) administered once daily taken 1 to 2 days before departure and continued for 1 week after return.1,2,27 The pediatric dosage (Malarone Pediatric) contains 62.5 mg of atovaquone and 25 mg of proguanil.

Pyrimethamine has teratogenic effects and sulfonamides are contraindicated in early pregnancy; however, chloroquine, quinine, and quinidine have been suggested as safe treatments during pregnancy.2,4,27,29,32,33,39,43 Although not associated with abortions, low birthweight, neurologic retardation, or congenital malformations, mefloquine is associated with an increased risk of stillbirth.

Malaria Vaccine

At present, three types of vaccines against P. falciparum are under study: a merozoite vaccine that would induce immunity against the erythrocytic forms of plasmodia in the blood, a sporozoite vaccine that would protect against the exoerythrocytic or liver phase, and a gamete vaccine (“transmission blocking”) that would prevent transmission of malaria in endemic areas.49 When a vaccine for malaria is available, it is expected to provide an immune response for at least 1 year. The safety of these vaccines to the fetus and mother during pregnancy will require evaluation.

Multidrug-Resistant Plasmodium Falciparum Malaria

Chemoprophylaxis against malaria in this region of southeast Asia has become progressively difficult because of the appearance of P. falciparum strains resistant to chloroquine, pyrimethamine-sulfadoxine, quinine, and even mefloquine.

F.S. will have to take chemoprophylaxis against both P. vivax and multidrug-resistant P. falciparum. Mefloquine (Lariam) 250 mg once weekly starting 1 week before travel and continuing weekly for the duration of the stay and for 4 weeks after leaving Thailand is recommended.27 On return from his visit, primaquine phosphate should be added to F.S.'s regimen to prevent an attack of P. vivax, because mefloquine has no effect on the exoerythrocytic phase of P. vivax (see Question 3 for doses of primaquine).27 Another alternative drug for prophylaxis against P. falciparum malaria for F.S. would be doxycycline 100 mg taken once daily beginning 1 to 2 days before departure and continuing for 4 weeks after he returns from Thailand.

Side Effects of Antimalarials

The major side effects of chloroquine (e.g., nausea, abdominal pain, pruritus, vertigo, headache, and visual disturbances

Abdominal cramps associated with primaquine may be relieved by antacids or by taking the drug after meals.

Glucose-6-Phosphate Dehydrogenase Deficiency

Primaquine sensitivity, or G6PD deficiency, is an inherited error of metabolism transmitted by a gene of partial dominance located on the X chromosome. Patients with this enzyme deficiency are sensitive to the 8-aminoquinolines, sulfonamides, para-aminosalicylates, nitrofurantoin, sulfone, aspirin, quinine, quinidine, nalidixic acid, and methylene blue.

Hemolysis reportedly occurs on the third day of drug ingestion and usually is manifested as abdominal discomfort, anemia, and hemoglobinuria

Drug Therapy of Parasitic Infection
Drug of Choice / Dosage / Adverse Effects
Amebiasis (Including Cyst Passers)
Asymptomatic
Iodoquinol / Adults: 650 mg PO TID × 20 days / Rash, acne, thyroid enlargement
or / Children: 30–40 mg/kg/days PO TID × 20 days
Diloxanide furoate / Adults: 500 mg PO TID × 10 days / Flatulence, abdominal pain
or / Children: 20 mg/kg/day PO TID × 10 days
Paromomycin / Adults: 25–35 mg/kg/day PO TID × 7 days / Nausea, vomiting
Children: Same as adults
Mild to Moderate Gastrointestinal Disease
Metronidazole or / Adults: 750 mg PO TID × 10 days
Children: 35–50 mg/kg/day PO TID × 10 days / Nausea, headache, metallic taste, disulfiram reaction with alcohol, paresthesia
Tinidazole / Adults: 2 g once daily × 3 days / Metallic or bitter taste, anorexia, nausea, vomiting, epigastric discomfort, weakness, seizures, peripheral neuropathy
followed by / Children: 50 mg/kg (max. 2 g) × 3 days
Iodoquinol / Adults: 650 mg PO TID × 20 days / Rash, acne, thyroid enlargement
Children: 30–40 mg/kg/day PO TID × 20 days
Severe Gastrointestinal Disease
Metronidazole or / Adults: 750 mg PO TID × 10 days Children: 35–50 mg/kg/day PO TID × 10 days / Nausea, headache, metallic taste, disulfiram reaction with alcohol, paresthesia
Tinidazole
followed by / Adults : 2 g once daily × 5 days / Metallic taste or bitter taste, nausea, vomiting, epigastric discomfort, anorexia and weakness
Children : 50 mg/kg/day (max. 2 g) × 5 days
Iodoquinol / Adults: 650 mg PO TID × 20 days / Rash, acne, thyroid enlargement
Children: 30–40 mg/kg/day PO TID × 20 days
Alternatives
Dehydroemetine followed by / Adults: 1–1.5 mg/kg/day IM × 5 days (max. 90 mg/day) / Arrhythmias, hypotension; ECG: P-R, Q-T, QRS prolongation, S-T depression
Children: Same as adults
Iodoquinol / Adults: 650 mg PO TID × 20 days / Rash, acne, thyroid enlargement
Children: 35–40 mg/kg/day PO TID × 20 days
Amebic Liver Abscess
Metronidazole or / Adults: 750 mg PO TID × 10 days / Nausea, headache, metallic taste, disulfiram reaction with alcohol, paresthesia
Children: 35–50 mg/kg/day PO TID × 10 days
Tinidazole / Adults : 2 g once daily × 5 days
followed by / Children : 50 mg/kg (max. 2 g) × 5 days
Iodoquinol or / Adults: 650 mg PO TID × 20 days / Rash, acne, thyroid enlargement
Children: 30–40 mg/kg/day PO TID × 20 days
Alternatives
Dehydroemetine followed by / Adults: 1–1.5 mg/kg/d IM × 5 days (max. 90 mg/day) / Arrhythmias, hypotension; ECG: P-R, Q-T, QRS prolongation, S-T depression
Children: Same as adult
Diloxanide furoate or / Adults: 500 mg PO TID × 10 days
Children: 20 mg/kg/day PO TID × 10 days
Paromomycin / Adults: 25–30 mg/kg/day PO TID × 7 days / Nausea, vomiting
Children: Same as adults
Ascariasis (Roundworm)
Albendazole
Adults/Pediatric: 400 mg once / Nausea and headache
or
Mebendazole / Adults and children: 100 mg BID PO × 3 days / Diarrhea, abdominal pain
Enterobiasis (Pinworm)
Mebendazole / Adults and children: 100 mg once; repeat in 2 wk / Diarrhea, abdominal pain
Pyrantel pamoate or / Adults and children: 11 mg/kg PO once (max. 1 g), repeat in 2 wk / Nausea, headache, dizziness, rash, fever
Albendazole / Adult/Pediatric: 400 mg once; Repeat in 2 wk / Abdominal pain, reversible alopecia, increased transaminases, rarely leukopenia
Filariasis
Diethylcarbamazine / Adults: Day 1, 50 mg PO; day 2, 50 mg TID; day 3, 100 mg TID; days 4–14, 6 mg/kg/day in 3 doses / Severe allergic/febrile reactions, gastrointestinal disturbance, rarely encephalopathy
Children: Day 1, 25–50 mg; day 2, 25–50 mg TID; day 3, 50–100 mg TID; days 4–14, 6 mg/kg/day in 3 doses
Flukes (Trematodes)a
Praziquantel / Adults and children: 75 mg/kg/day in 3 doses × 1 day (exceptions: C. sinensis and P. westermani, × 2 days) / Malaise, headache, dizziness, sedation, fever, eosinophilia
Giardiasis
Metronidazole or / Adults: 250 mg PO TID with meals × 5 days / Nausea, headache, metallic taste, disulfiram reaction with alcohol, paresthesia
Children: 15 mg/kg/day PO TID × 5 days
Quinacrineb / Adult: 100 mg PO TID × 5 days / Gastrointestinal yellow staining of skin and psychosis
Pediatric: 2 mg/kg TID × 5 days (max 300 mg/day)
Nitazoxanidec / Pediatric: 12–47 mo / Abdominal pain, diarrhea, vomiting and headache
100 mg (5 mL) Q 12 hr × 3 days 4–11 yr
200 mg (10 mL) Q 12 hr × 3 days
Hookworm
Mebendazole / Adults and children: 100 mg PO BID × 3 days / Diarrhea, abdominal pain
Lice
1% Permethrin (NIX) or / Topical administration / Occasional allergic reaction, mild stinging, erythema
Ivermectin
Adults and Children : 200 mcg/kg × 3, day 1, day 2 and day 10 / Fever, pruritus, sore lymph nodes, headache, joint pains, rarely hypotension
Leishmaniasis
Sodium stibogluconate or / Adult: 20 mg SB/kg IV or IM × 20–28 days Pediatric: Same as adult / Gastrointestinal, malaise, headache arthralgias, myalgias, anemia, neutropenia, thrombocytopenia; ECG abnormalities (ST- and T-wave changes)
Liposomal Amphotericin B
======/ Adult: 3 mg/kg/day (days 1–5) and 3 mg/kg/days 14 and 21 Pediatric: Same as adult
======/ Hypotension, chills, headache, anemia, thrombocytopenia, fever, and elevated serum creatinine
======
Malaria
All Plasmodia Except Chloroquine-Resistant
Parenteral therapy
Quinidine gluconate / Adults: Loading dose 10 mg/kg of salt (6.2 mg base) diluted in 250 mL normal saline and infused IV over 2 hr, followed by a continuous IV infusion of 0.02 mg/kg/min (0.012 mg base) for 72 hr; switch to oral quinine 650 mg Q 8 hr as soon as possible / ECG: Q-T and QRS prolongation; hypotension, syncope, arrhythmias; cinchonism
Pediatric: Same as adult
Oral therapy
Chloroquine Phosphate / Adult: 1 g (600 mg base), then 500 mg 6 hr later, then 500 mg at 24 and 48 hr later. / Gastrointestinal, headache, pruritus, malaise, and cinchonism
Pediatric: 10 mg base (max. 600 mg base) then 5 mg base/kg 6 hr later, then 5 mg/base at 24 and 48 hr
Chemoprophylaxis
Chloroquine phosphate / Adult: 500 mg (base) once weekly (beginning 1–2 wk before departure and continuing through stay and up to 4 wk after returning) / Dose-related: vertigo, nausea, dizziness, light-headedness, headache, visual disturbances, toxic psychosis and seizures
Pediatric: 5 mg/kg base once weekly up to adult dose (300 mg base)
Chloroquine Resistant Therapy (CRF)
Mefloquine or / Adult: 750 mg followed by 500 mg 12 hr later / Nausea, vomiting, abdominal pain, arthralgias, chills, dizziness, tinnitus and A-V block
Pediatric: 15 mg/kg followed 8–12 hr later by 10 mg/kg
Atovaquone/ proguanil / Adult: 2 tablets BID × 3 days / Rash, nausea, diarrhea, increased aminotransferases, cholestasis
Pediatric: 11– 20 kg: 1 adult tablet/d × 3 days 21–30 kg: 2 adult tablets/day × 3 days 31–40 kg: 3 adult tablets/day × 3 days >40 kg: 2 adult tablets BID × 3 days
Chemoprophylaxis-CRF
Mefloquine or / Adult: 250 mg once weekly beginning 1–2 wk before departure, continuing through stay and for 1–4 wk after return
Pediatric: <15 kg: 5 mg/kg once weekly 15–19 kg: 1/4 tablet once weekly 20–30 kg: 1/2 tablet once weekly 31–45 kg: 3/4 tablet once weekly >45 kg: 1 tablet once weekly
Doxycycline / Adult: 100 mg daily beginning 1–2 days before departure continuing during stay and 1 wk after return / Nausea, diarrhea and monilial rash
Quinine sulfate / Adults: 650 PO TID × 3 days / Cinchonism
plus / Children: 25 mg/kg/day PO TID × 3 days
Pyrimethamine-sulfadoxine (Fansidar) or / Adults: 3 tablets at once (withhold until febrile episode) / Gastrointestinal, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis
Children: 1/2–2 tablets (depends on age)c
Mefloquine / Adults: 1,250 mg once / Dose-related: vertigo, nausea, dizziness, light-headedness, headache, visual disturbances, toxic psychosis seizures
Children: 25 mg/kg once (>45 kg)
Prevention of Relapses (P. vivax and P. ovale)
Primaquine phosphate / Adults: 52.6 mg/day (30 mg base) × 14 days; this follows chloroquine or mefloquine regimen / Abdominal cramps, nausea, hemolytic anemia in G6PD
======
Scabies / ======/ ======
5% Permethrin (Elimite cream) / Topical administration / Rash, edema, erythema
Alternatives
Ivermectin / Adults: 200 mcg/kg PO; repeat in 2 wk / Nausea, diarrhea, dizziness vertigo and pruritus
Lindane (Kwell) / Apply topically once / Not recommended in pregnant women, infants, and patients with massively excoriated skin
Crotamiton 10% (Eurax) / Topically / Local skin irritation
Tapewormd
Praziquantel / Adults and children: 5–10 mg/kg PO × 1 dose / Malaise, headache, dizziness, sedation, eosinophilia, fever
Hydatid Cystse
Albendazole / Adults: 400 mg BID × 8–30 days, repeat if necessary / Diarrhea, abdominal pain, rarely hepatotoxicity, leukopenia
Children: 15 mg/kg/day × 28 days, repeat if necessary (surgical resection may precede drug therapy)
Trichomoniasis
Metronidazole / Adults: 2 g PO × 1 day or 250 mg PO TID × 7 days / Nausea, headache, metallic taste, disulfiram reaction with alcohol, paresthesia
Children: 15 mg/kg/day PO TID × 7 days
aSchistosoma haematobium, S. mansoni, S. japonicum, Clonorchis sinensis, Paragonimus westermani.
bQuinacrine is available in the United States: Panorama Compounding Pharmacy, Van Nuys, CA 91406.
cSame dose is recommended in children with Cryptosporidium parvum.
dDiphyllobothrium latum (fish), Taenia solium (pork), and Dipylidium caninum (dog), except for Hymenolepis nana where the dose is 25 mg/kg × 1dose.
eEchinococcus granulosus, E. multilocularis. For neurocysticercosis: 400 mg BID 8–30 days.
BID, twice daily; ECG, electrocardiograph; G6PD, glucose-6-phosphate dehydrogenase; IM, intramuscularly; PO, orally; TID, three times daily.

Amebiasis

Giardiasis

Enterobiasis

Cestodiasis

PediculosisPediculosis

Prevalence

Pediculosis (lice infections) can be caused by head lice (Pediculus humanus capitis) (Fig. 74-10), body lice (P. humanus), or crab lice (Phthirus pubis). Lice infections can be present in all socioeconomic groups, but are seen more often among the poor because of crowded living conditions and infrequent washing.