Plasmodium malariae infection in spite of previous anti-malarial medication

Abstract

Plasmodium malariae is regarded as usually being susceptible to all anti-malarials whether applied for prophylaxis or treatment. We report on three cases of P. malariae infection which occurred 12-14 weeks after anti-malarial chemoprophylaxis or treatment with mefloquine or atovaquone/proguanil. The most likely explanation for the failure of mefloquine and atovaquone/proguanil to prevent quartan malaria occurring some months later is the insufficient effect on the particularly long-lasting pre-erythrocytic development stages of P. malariae.

Why do Plasmodium malariae infections sometimes occur in spite of previous antimalarial medication?

“…(quartan fever shall grip you) and an old Frisian proverb said: "die Einbildung ist leichter zu vertreiben als das Dritttagsfieber" (illusion is easier to dispel than quartan fever) (cited by Mühlens 1942). The present case of a malaria recurrence due to P. malariae adds to other similar cases published elsewhere, in which quartan malaria occurred in spite of previous antimalarial medication after a delay between 17 days and 14 weeks (Hess et al 1993;Grobusch et al 2004;Müller-Stöver et al 2008). Recurrent malaria attacks even years after last exposure have been described in Plasmodium vivax, Plasmodium ovale, P. falciparum and P. malariae infections (Shute 1946;Trager and Most 1963;Giobbia et al 2005;Greenwood et al 2008, Focá et al 2009Szmitko et al 2009;Theunissen et al 2009;White 2009;Markus 2011a, b;Richter et al 2010;White 2011).…”

“…Similarly, re-exposure was also reported not to have occurred in other cases published previously in returnees to Germany (Hess et al 1993;Grobusch et al 2004;Müller-Stöver et al 2008). …”

“…Moreover, the previous P. falciparum infection 4 months earlier may have elicited partial crossimmunity as supported by the antibody titre against P. malariae which was lower than that against P. falciparum detected in the moment of her quartan malaria fever attack. Whereas this hypothesis might explain the present observation, it is not sufficient to explain other cases where patients had received antimalarials after the maximum time of pre-erythrocytic development had elapsed (Hess et al 1993, Müller-Stöver et al 2008. Most interestingly, in former times, when malaria was still endemic in Germany, the peak of P. malariae infections usually occurred in the wintertime indicating that the European type of quartan fever usually had a latency considerably exceeding 30 days (Martini 1951).…”

Polymorphisms in TLR4 and TLR2 genes, cytokine production and survival in rural Ghana

“…Specific P. falciparum DNA was detected in a multiplex real-time PCR format as described before, 22,23 with some modifications. The assay was designed for the detection of all four human Plasmodium species, including the amplification and detection of a nonrelated DNA internal control.…”

“…Plasmodium-specific primers and Plasmodium species-specific minor groove binding TaqMan probes (Applied Biosystems, Foster City, CA, USA) based on an SSU RNA gene target were used to amplify and detect Plasmodium speciesspecific products of B150 bp. 22,23 Amplification consisted of 15 min at 951C, followed by 50 cycles of 15 s at 951C, 30 s at 601C and 30 s at 721C. Negative and positive control samples were included in each amplification run.…”