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Background  Since several malaria parasite species are usually present in a particular area, co-infections with more than one species of  Plasmodium  are more likely to occur in humans infected in these areas. In many mixed infections, parasite densities of the cryptic species may be low and often not recognized in clinical practice.    Case presentation  Two children (3 and 6 years old) adopted recently from Central African Republic were admitted to hospital because of intermittent fever. Thin blood smears stained with Giemsa showed  Plasmodium falciparum  and  Plasmodium malariae  co-infection for both children at admission. They were both treated with atovaquone-proguanil combination for 3 days. At day 7, both thin blood smears examination remained negative but at day 28, thin blood smear was positive for  P. malariae  trophozoites and for  Plasmodium ovale  for the girl and her brother, respectively. Samples collected at day 1 and day 28 were submitted to real-time PCR showing the presence of the three parasite species ( P. falciparum ,  P malariae  and  P. ovale ) in admission blood samples from the two children and only  P. ovale  at day 28.    Conclusions  Twenty-eight days follow-up after treatment led to detection of a third parasite species in the blood of these two patients suggesting covert co-infection and a delayed appearance of one cryptic species following treatment. Concurrently infecting malaria species could be mutually suppressive, with  P. falciparum  tending to dominate other species. These observations provide more evidence that recommendations for treatment of imported malaria should take into account the risk of concurrent or cryptic infection with  Plasmodium  species. Clinicians and biologists should be aware of the underestimated frequency of mixed infections with cryptic species and of the importance of patient follow-up at day 28. Future guidelines should shed more light on the treatment of mixed infection and on the interest of using artemisinin-based combinations for  falciparum  and non- falciparum  species.

Cryptic Plasmodium ovale concurrent with mixed Plasmodium falciparum and Plasmodium malariae infection in two children from Central African Republic