Standby Emergency Treatment of Malaria in Travelers

Experience to Date and New Developments

Patricia Schlagenhauf; Eskild Petersen

Disclosures

Expert Rev Anti Infect Ther. 2012;10(5):537-546. 

In This Article

Areas Where P. vivax Malaria Is the Dominant Species

Chemoprophylaxis options such as atovaquone/proguanil, mefloquine and doxycycline will not prevent the occurrence of late-onset P. vivax and Plasmodium ovale infections. P. vivax is the predominant malaria species in many parts of Asia and South America, and the logic of using conventional chemoprophylaxis options for these areas is debatable.

SBET against P. falciparum will treat clinical P. vivax, P. ovale, Plasmodium malariae and Plasmodium knowlesi infections, but data are still limited. Therefore, in areas with even a small possibility of P. falciparum infections, the treatment recommendations should be the drug of choice for P. falciparum. In areas with no P. falciparum at all or P. falciparum with no known resistance to chloroquine, chloroquine can be used (Haiti, Dominican Republic, central America north of Panama, Turkey and Iraq). There is concern regarding the spread of chloroquine-resistant P. vivax in Asia. A recent study of 500 adults and children with acute vivax malaria on the northwestern border of Thailand showed that dihydroartemisin/piperaquine led to faster fever and parasite clearance times and significantly lower risk of P. vivax recurrence than chloroquine. The results suggest that dihydroartemisin/piperaquine is an effective alternative treatment for acute P. vivax malaria.[23,24]

SBET will not eradicate persistant liver forms of P. vivax and P. ovale, which need treatment with primaquine. However, it is not feasible to include primaquine in SBET regimens as the treatment is prolonged (duration of 14 days), and possible adverse events such as methemoglobinemia, need monitoring. A G6PD test is mandatory before prescription of primaquine, and for these and other reasons, it is difficult to envisage that primaquine be included in SBET regimens administered by the traveler.

There are several available medications that could be used as a treatment in emergency situations. The choice of SBET will depend on the expected parasite type (as discussed above) and level of drug resistance, the traveler's medical history, age, the availability or lack of medical attention at the destination, the prophylactic agent used (if applicable) and finally the ease of administration and cost of the SBET. The range of options and dosages available are outlined in Table 2, and data on the level of use of SBET are shown in Table 3.

In the WHO guidelines,[103] the drug options indicated for SBET are in principle the same as the treatment options for uncomplicated malaria: artemether/lumefantrine, dihydroartemisinin/piperaquine, mefloquine, atovaquone/proguanil, quinine with doxycycline or clindamycin or chloroquine (in limited geographic areas).

The trend is toward recommending the new artemisinin-containing combination antimalarial treatments. Mefloquine is effective outside Myanmar, Cambodia and Thailand and is cheap but neuropsychiatric adverse events are seen 60 times more often after treatment doses compared with doses used in chemoprophylaxis. The risk of serious neuropsychiatric AE is approximately 1:215 of users of therapeutic mefloquine doses.[25,26] Quinine has a complicated dosage schedule (a total of 42 tablets for an adult treatment course) and is not generally considered feasible as an SBET option except in pregnancy.[27] Primaquine is used for treatment of hypnozoites of P. vivax and P. ovale and is only exceptionally considered as a candidate SBET. If primaquine is provided as an SBET, the user should be tested for G6PD before leaving. Primaquine will not be discussed further here.

Artemether/Lumefantrine (Riamet®)

Artemether/lumefantrine is a good option for SBET if the traveler is going to Africa, Asia or South America except the areas listed below where chloroquine is still the drug of choice. This combination is effective and well documented with few adverse events. It is a recommended SBET in the UK, USA and Switzerland.

Dihydroartemisinin/Piperaquine (Eurartesim®)

Eurartesim, another artemisinin combination, is newly approved by the European Medicines Agency for the treatment of symptomatic, uncomplicated malaria in adults, children and infants older than 6 months and/or above 5 kg. It has been found to be as effective as artemether/lumefantrine in several trials.[28–32] More data are needed on the QTc prolongation effect of this combination. This medication should be administered without food.

Atovaquone/Proguanil (Malarone®)

Malarone is approved for use in uncomplicated malaria and is listed in many national guidelines for this indication. However, atovaquone/proguanil acts more slowly with a longer parasite clearance time and a longer interval before fever clearance and resolution of symptoms. Thus, on the basis of their rapid action, artemisinin-containing combinations have the advantage over atovaquone/proguanil in this setting.

Mefloquine (Lariam®)

Mefloquine has been used for more than 25 years and, despite a few reports of resistance, is considered effective in tropical Africa. There is well-documented resistance in Myanmar, Thailand, Laos, Cambodia and the eastern part of Bangladesh bordering Myanmar. The use of mefloquine as an SBET is decreasing due to the experience that the risk of serious adverse events is significantly higher after a treatment dose (1:216).[25] It still has a niche for some travelers and has the advantage of low cost and a simple dosage schedule.

Chloroquine

Chloroquine has been used for more than 60 years and has a good safety profile that includes use in pregnancy and infants. However, resistance is now widespread and it can only be used for SBET in central America north of Panama, Haiti and the Domican Republic, Turkey and Iraq. This medication if becoming defunct as an SBET.

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