Malaria B54.x

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 28.03.2023

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Synonym(s)

Swamp fever

History
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Laveran, 1880; Ross, 1897; Grassi, 1900

Definition
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Tropical infectious disease caused by Plasmodium spp. (protozoa) with typical periodicity of fever and intravascular haemolysis.

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Pathogen
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  • Plasmodium falciparum (Malaria tropica)
  • Plasmodium vivax (Malaria tertiana)
  • Plasmodium ovale (Malaria tertiana)
  • Plasmodium malariae (Malaria quartana).

Occurrence/Epidemiology
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  • Incidence (worldwide): 300-500 million diseases/year.
  • Mortality (worldwide): 1-5 million deaths per year.
Distribution of the malaria forms and their pathogens:
  • Malaria tropica (P. falciparum): in the tropics of both hemispheres, predominant in Africa (especially south of the Sahara), Haiti, New Guinea.
  • Malaria quartana (P. malariae): Tropical and subtropical areas worldwide.
  • Malaria tertiana (P. ovale): Mainly in the tropical areas of Africa (especially West Africa and sub-Saharan Africa), occasionally also in South East Asia.
  • Malaria tertiana (P. vivax): Worldwide, mainly in tropical and subtropical, but also temperate climates, predominant in Central America and Southeast Asia.

Etiopathogenesis
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Transmission through the bite of the female Anopheles mosquito, usually at dusk or at night. Peripartal transmission, transmission by blood transfusion or needle stick injuries are also described.

Manifestation
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Possible at any age.

Clinical features
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  • Incubation period: 7-25 days for P. falciparum (longer in isolated cases), 7-14 days for P. ovale and P. vivax (up to several months in isolated cases), 30 days for P. malariae.
  • Skin manifestations: erythema, hemorrhagic diathesis, rarely erythema nodosum-like or Raynaud's-like skin lesions. Frequent drug exanthema, especially due to quinine.
  • Classic relapsing course: Frequent flu-like early symptoms (headache and pain in the limbs, diarrhea, vomiting), then chills (cold stage), periodic fever attacks (hot stage, 39-41 °C) every 2-3 days (tertianate type in Plasmodium falciparum, vivax and ovale) or every 3-4 days (quartanate type in Plasmodium malariae), after a few hours drop in temperature with profuse sweating (wet stage).
  • In malaria tropica the course of fever is irregular, often there is febris continua.
  • Occasionally, fever-free courses or plasmodial infections with subfebrile temperatures are described.

Laboratory
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  • Direct pathogen detection (gold standard): In the blood smear (Giemsa stain: trophozoites, merozoites, schizonts) or in the "thick drop" to enrich the pathogens.
  • Also: anaemia, thrombocytopaenia, increase in LDH, renal values, total bilirubin and transaminases.

Diagnosis
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  • Diagnosis in principle for every patient with fever after staying in malaria endemic areas 6 days to 1 year before the onset of the disease, if necessary also when staying near international airports ("airport malaria").
  • Medical history: country of travel, type and compliance of a medical prophylaxis, general medical history and medication history.
  • Parasitological examination results: species differentiation, quantification of the number of parasites, laboratory tests and technical findings.

Complication(s)
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  • Recurrences: Due to dormant pathogens in the liver (hypnozoites), infections with P. ovale and P. vivax can lead to recurrences over several years. In malaria quartana, relapses are possible up to 40 years after initial infection due to persistent circulating plasmodia if insufficient therapy is given.
  • Infections with P. falciparum: In non-immune patients often progressive with severe organ manifestations (hypoglycaemia, coagulation disorders, liver and kidney failure, pulmonary oedema and cerebral complications); often comatose and lethal if left untreated.
  • Infection with P. malariae, P. ovale and P. vivax: Rare complications (especially in children!) are severe anemia and splenic rupture in infection with P. vivax and immune complex glomerulonephritis with consecutive nephrotic syndrome in infection with P. malariae.
  • Pregnancy: Often severe course and damage of the fruit due to massive multiplication of parasites in the placenta.

General therapy
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Therapy should be started as soon as possible in case of suspicion (emergency treatment, see table) or diagnosis.

Internal therapy
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  • Malaria tertiana and uncomplicated malaria quartana: Chloroquine (e.g. Resochin): Initial 10 mg Chloroquin-Base/kg bw p.o., 6 hours after the start of therapy 5 mg Chloroquin-Base/kg bw, 24 hours after the start of therapy 5 mg Chloroquin-Base/kg bw, 48 hours after the start of therapy 5 mg Chloroquin-Base/kg bw.
If the patient originates from Southeast Asia or the Pacific region, M. tertiana can be treated with mefloquine (e.g. Lariam) because of possible chloroquine resistance, in the same dosage as Malaria tropica (see below). The therapy can be carried out on an outpatient basis.
  • Malaria tertiana: Follow-up treatment with primaquine (e.g. Fansidar) 15 mg base/base (alternatively 0.25 mg base/kg bw) once/day for 14 days to kill any hypnozoites in the liver and thus prevent recurrences. In case of therapy failure, increase the dose to 0.33 mg base/kg bw once/day for 14 days.
  • Uncomplicated malaria tropica: If the pathogen originates from areas without chloroquine resistance: therapy with chloroquine, dosage as for malaria tertiana (see above). If the pathogen originates from areas with chloroquine resistance, therapy with mefloquine or atovaquon/proguanil or artemether/lumefantrine.
    • Treatment of malaria tropica with mefloquine (e.g. Lariam): Initial 750 mg mefloquine-base p.o., 6 hours after therapy start 500 mg mefloquine-base p.o., 12 hours after therapy start (only for body weight over 60 kg) 250 mg mefloquine-base p.o.
    • Treatment of malaria tropica with atovaquone/proguanil (e.g. combination preparation "Malarone"; contains 250 mg atovaquon and 100 mg proguanil/tbl: Adults and children > 40 kg KG: 4 film sheets as ED on 3 consecutive days.
    • Treatment of malaria tropica with artemether/lumefantrine (e.g. combination preparation "Riamet"; contains 20 mg artemether and 120 mg lumefantrine): Adults/children > 12 years and > 35 kg bw: 6 times 4 tablets spread over a total of 60 hours (ED with 4 tablets at the start of therapy and after 8, 24, 36, 48 and 60 hours).
  • Complicated malaria tropica:
    • Quinine (e.g. Chininum dihydrochloricum): Adults: 4-6 times/day 250 mg p.o. over 1 week. Children: 3 times/day 10 mg/kg KG quinine salt day for 7-10 days. Cave! Therapy because of strong side effects only stationary!

Progression/forecast
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With early therapy restitutio ad integrum, with therapy delay of more than one week danger to life, relapses possible after up to 20-40 years.

Prophylaxis
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  • Chemoprophylaxis (see table): The type of prophylaxis must be chosen individually depending on the destination, travel duration and travel style. Chloroquine can be used for prophylaxis in areas without chloroquine resistance (see table 1). In areas with resistance, an additive protective effect can be achieved by combination with proguanil. In areas with a very high risk of malaria, mefloquine currently offers the best protection. Other antimalarial drugs are only to be used for specific contraindications.
  • Exposure prophylaxis: Use of mosquito nets, rubbing of uncovered skin areas with mosquito repellents (e.g. repellents with the active ingredients diethyltoluamide (DEET) in a concentration of 30-50% (e.g. No-Bite) or Bayrepel (e.g. Autan) or Icaridin. Wear light-coloured clothing that covers the skin and should be sprayed with suitable products; stay in mosquito-proof rooms with air conditioning and fly screens in front of the windows. Use of insecticides in aerosols, vaporizers, smoking spirals ("mosquito coils") etc. and for impregnating mosquito nets.

Naturopathy
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In traditional Chinese medicine, the tea of the annual mugwort(Artemisia annua) is used effectively against malaria. The annual mugwort is used to extract artemisinin, the basis for the most effective antimalarial agent currently available. The discovery of the active ingredient artemisinin by Youyou Tu received the Nobel Prize in 2015. In addition to malaria, artemisinin is effective against a variety of carcinomas: breast, prostate, colon.

Tables
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Dosage of antimalarials for prophylaxis and emergency self-treatment

Drug

Side effects

Prophylaxis (1 week before to 4 weeks after leaving the malaria area)

Comments

Emergency medication (Stand By) (if no medical care is available within 24 hrs)

Chloroquine (Chlorochine, Resochine, Weimerquine)

Acute: stomach discomfort, eye flutter, dizziness.

1 week before to 4 weeks after stay in malaria area

Can be used in pregnant women and children

Adults: 600 mg (e.g. 4 tbl. Resochin) on 1st and 2nd day, 300 mg (e.g. 2 tbl. Resochin) on 3rd day

Adults: 300 mg/week (e.g. 2 tablets of Resochin); in persons > 75 kg bw: 450 mg/week (e.g. 3 tablets of Resochin)

Long-term: damage to the retina (if taken continuously for more than 5 years, maximum dose according to WHO: 100 g chloroquine base).

Children: 5 mg/kg bw/week

Children: 5 mg/kg bw

Artemether/Lumefantrine (Riamet)

Headache, dizziness, nausea, vomiting, abdominal pain, exanthema, pruritus, arthralgias, myalgias.

Not suitable

Not for use in pregnant women and children < 12 years of age

80 mg/480 mg (e.g., 4 tbl. Riamet) initially, after 8 hrs, another 80 mg/480 mg (4 tbl. Riamet), then 2 times/day each 80 mg/480 mg (4 tbl. Riamet) on days 2 and 3

Atovaquone/Proguanil (Malarone).

Acute: nausea, vomiting, headache, abdominal pain, inappetence, diarrhea, cough.

1-2 days before to 7 days after stay in malaria area

Adults: 1000 mg/400 mg/day (4 tbl. Malarone) as single dose on 3 consecutive days

Adults (> 40 kg bw): 250 mg/100 mg/day (e.g. 1 tbl. Malarone)

Children > 10-20 kg bw: 1 tbl/day for 3 consecutive days; 21-30 kg bw: 1 time/day 2 tbl for 3 consecutive days; 31-40 kg bw: 1 time/day 3 tbl for 3 consecutive days; > 40 kg bw: 1 time/day 4 tbl for 3 consecutive days.

Atovaquone/Proguanil(Malarone Junior).

Acute: nausea, vomiting, headache, abdominal pain, inappetence, diarrhea, cough.

Children > 11-20 kg bw: 62.5 mg/25 mg/day; bw > 20-30 kg: 125 mg/50 mg/day; bw > 31-40 kg: 187.5 mg/75 mg/day

Approved for treatment of children for a maximum of 28 days

Not suitable; therapy with "adult tablet" Malarone, see above.

Doxycycline

Phototoxic reactions

1-2 days before to 4 weeks after stay in malaria areas

Not in pregnant women and children < 8 years

Not suitable

Adults: 100 mg/day (in areas with mefloquine resistance).

Children > 8 LJ: 2 mg/kg bw/day

Proguanil (Paludrine)

Acute: transient hair loss, eye discomfort, mouth ulceration.

Adults: 200 mg/day

Can be used in pregnant women and children

Not suitable

Children: 3 mg/kg bw/day

Mefloquine (Lariam)

Neuropsychiatric NW, caution in persons who must remain spatially oriented (e.g., pilots), do not use in agitation conduction disorders and do not use concomitantly with quinine

1-2 days before to 4 weeks after stay in malaria area.

No intake recommended for pregnant women

Adults: initial 750 mg, after 6-8 hrs. another 500 mg, after another 6-8 hrs. another 250 mg

Adults: 250 mg/week

Children 3 months of age and older (> 5 kg bw): Initial 15 mg/kg bw, 6-24 hrs later 10 mg/kg bw.

Children from 3 months of age (> 5 kg bw): 5 mg/kg bw/week

Other antimalarials in case of contraindication or as stand-by in exceptional situations

Sulfadoxine-pyrimethamine (Fansidar)

Not suitable

1500 mg + 75 mg (3 tbl. Fansidar) as single dose

Quinine (Quininum hydrochloricum)

Not suitable

250 mg 4-6 times/day for 7-10 days

Quinine + Fansidar

Quinine 4-6 times/day 250 mg for 3 days, followed by 1 time 3 tbl. Fansidar (single dose)

Quinine + Tetracycline

Quinine: 4-6 times/day 250 mg

Tetracycline: concomitantly 1 g/day in 4 ED over 7 days.

Note(s)
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  • Duty to report illness and death.
  • Current therapy recommendations can be found in the DTG and AWMF guidelines.

Literature
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  1. Buchard GD et al (1996) Current malaria prophylaxis. Dt Ärztebl 93: 1380-1385
  2. Dorsey G et al (2003) Prevention of increasing rates of treatment failure by combining sulfadoxine-pyrimethamine with artesunate or amodiaquine for the sequential treatment of malaria. J Infect Dis 188: 1231-1238
  3. Grassi B (1900) Studi di uno zoologo sulla malaria. Atti Reale Accad Lincei Mem 3: 299-511
  4. Laveran A (1880) Note on a new parasite trouve in the singing of the plusieurs malades atteints de fie palustre. Bull Acad Med 9: 1235-1236
  5. Loscher T et al (2003) Malaria diagnosis. Dtsch Med Weekly 128: 1290-1293
  6. Re VL 3rd et al (2003) Prevention of malaria in travelers. On Fam Physician 68: 509-514
  7. Ross R (1897) On some peculiar pigmented cells found in two mosquitoes fed on malarial blood. Br Med J ii: 1736-1788
  8. Ross R (1898) The role of the mosquito in the evolution of the malaria parasite. Lancet ii: 488-489
  9. Schoneberg I et al (2003) Malaria surveillance in Germany 2000/2001--results and experience with a new reporting system. Public Health 65: 263-269
  10. Schwartz E et al (2003) Delayed onset of malaria--implications for chemoprophylaxis in travelers. N Engl J Med 349: 1510-1516
  11. Whitty CJ et al (2002) Malaria. BMJ 325: 1221-1224

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Authors

Last updated on: 28.03.2023