The case of a thirty-eight year old Congolese woman, a resident in Germany for 12 years, who returned from a four-week stay in Kinshasa with fever, chills, headache and myalgia, is reported. It was her first trip to Africa since she had settled in Germany and she took chloroquine for chemoprophylaxis. Blood smear examination revealed P. falciparum at a parasite density of 0.1% and an antigen capture test (Mala Quick, R-Biopharm, Germany) confirmed P. falciparum mono-infection.
The patient received a directly observed standard treatment course of Malarone® for three days, four tablets daily (one tablet is equivalent to 250 mg of atovaquone and 100 mg of proguanil hydrochloride). Tablets were taken with food and were well tolerated. No vomiting or diarrhoea occurred during hospitalization. High performance liquid chromatography (Shimatzu, Japan) on Day 2 of treatment confirmed a drug concentration of atovaquone above the required therapeutic plasma concentration (17.2 μg/mL) which excludes impaired bioavailability. Symptoms resolved and parasites were cleared after three days. Sixteen days after discharge from hospital, the patient presented at our clinic with fatigue and headache but no fever. A blood smear demonstrated once again P. falciparum mono-infection at an asexual parasite density of 0.01%. Re-treatment with a 6-dose regime of co-artemether (20 mg artemether and 120 mg lumefantrine) was successful.
For further analysis, the pre-treatment and the resistant P. falciparum
isolates were investigated for point mutations of cytochrome b
codon 268 by nested PCR and enzymatic restriction digest as recently described [6
]. Analysis revealed wild-type alleles in both isolates. A 716 bp fragment of the cytochrome b gene containing the encoding region of the putative atovaquone-binding domain was amplified [7
]. Sequencing (ABI, Applied Biosystem, MWG Biotech Ebersberg, Germany) revealed the absence of all mutations previously described to be involved in atovaquone-resistance in vivo
and in vitro
], no further variants were found.