To the Editor

E. Vannier and P. J. Krause presented excellent comments on “Babesiosis in China, an emerging threat” [1] which updated and replenished the review of “human babesiosis” [2] and reported human babesiosis cases in China [3–7]. Here, we would like to address a neglected and emerging issue that babesiosis has sometimes been misdiagnosed initially as malaria because of the similarities on morphology and symptoms between the two diseases. Especially, the intraerythrocytic ring form stages of Babesia microti can be misdiagnosed as ring forms of Plasmodium falciparum which are smaller than that of P. viviax, for the following three reasons. First, to date, little was known by medical doctors about the prevalence of Babesia spp. in malaria-epidemic areas, where misidentification as Plasmodium spp. is most probable. For instance, one molecular survey on febrile cases in malaria epidemic areas of southwestern China has shown that co-infections with B. microti and P. falciparum parasites exist along the China-Myanmar border in Yunnan province [7]. Secondly, misidentification of babesiosis as drug-resistant malaria, especially in syndemic areas, may occur due to some antimalarial drugs, such as chloroquine and mefloquine, having little effect on babesiosis [7, 8]. It was also reported that two patients, with a history of malaria, were tracked following treatment with artemether plus pyronaridine in the China-Myanmar border area [4]. Thirdly, infections with either Babesia spp. or Plasmodium spp. can cause severe diseases. The health burden imposed by both babesiosis and malaria could be substantial in these syndemic areas of China (Fig. 1), such as Yunnan province. Artemisinin-resistant P. falciparum malaria has been reported in Cambodia and the Thailand-Myanmar border [9]. Based on a small animal model, B. microti can be responsive to artemisinin derivatives [10]. However, in human babesiosis cases, there are still insufficient data to confirm that artemisinin derivatives are also effective to control infections of Babesia. Therefore, we strongly recommended that infection of Babesia should be excluded based on the results of laboratory-based molecular tests when the emergence of artemisinin-resistant is detected in the syndemic areas. It will help the standardization of babesiosis treatment using first choice drugs consisting of atovaquone and azithromycin and second choice drugs consisting of clindamycin and quinine [2]. Otherwise, the co-infections of human babesiosis and malaria would undoubtedly increase the pressure of artemisinin-resistance in malaria endemic areas because of the misuse of drugs.

Fig. 1
figure 1

Syndemic areas of human babesiosis and falciparum malaria in China (High transmission areas of malaria including Yunnan province and Hainan province which are the syndemic areas of falciparum and vivax malaria (based on data in 2010). Unstable transmission areas including Jiangsu, Anhui, Shandong, Henan and Hubei province which are endemic areas of vivax malaria (based on data in 2010). Transmission controlled areas of malaria, other areas of China and all endemic areas of malaria were classified according to the National malaria control program ((2006-2015); Reported human babesiosis cases and falciparum malaria cases (2010-2014) were demonstrated by histograms)

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To promote correct identification and effective control of babesiosis and malaria in syndemic areas, clinical doctors and public health workers should be aware of the following information: (i) how to apply the molecular technologies to clearly distinguish babesiosis from malaria in order to overcome the difficulties in microscopy diagnosis due to their similarities in morphology and clinical symptoms, and (ii) to consider human babesiosis rather than drug-resistant malaria when febrile cases in anti-malaria treatment fail.