Will the high rates of post‐treatment sexual stage parasitaemia seen in malaria‐endemic areas make the optiMAL antigen test unreliable in predicting malaria treatment outcome?
Year: 2001
Type: letter
Abstract: We read with interest the recent report by Moody et al (2000), evaluating the ability of the OptiMAL malaria antigen capture test to follow the course of Plasmodium falciparum asexual stage parasitaemia after treatment of uncomplicated malaria in London. Levels of plasmodium-specific lactate dehydrogenase (pLDH) declined in parallel with clearance of asexual parasitaemia, and the investigators suggested that this lack of antigen persistence after treatment may make this test useful in the prediction of treatment outcome in both developed and less-developed countries (Moody et al, 2000). However, this and related studies, suggesting potential utility in predicting treatment outcome (Piper et al, 1999; Srinivasan et al, 2000), have been performed in large urban referral centres, and no details of post-treatment sexual stage parasitaemia/gametocytaemia were reported. In these settings, early, highly effective treatment is uncommonly associated with post-treatment gametocytaemia (Price et al, 1999; Eisen & Saul, 2000). This contrasts with higher rates and higher levels of post-treatment gametocytaemia seen in primary health centres in malaria-endemic areas (even in those treated with effective drugs), where there is often a longer duration of illness before treatment (Robert et al, 1996; Price et al, 1999). The pLDH monoclonal antibodies of the OptiMAL test detect not only asexual parasites but also the non-disease causing sexual stage parasites/gametocytes (Oduola et al, 1997; Makler et al, 1998; Cooke et al, 1999), with reported OptiMAL pLDH sensitivity for gametocytes ranging from 80% (Moody et al, 2000) to 92% (Cooke et al, 1999). This suggests that in contrast to the referral centre findings reported to date, the high rates and levels of post-treatment gametocytaemia found in primary health centres in many malaria-endemic areas, may lead to gametocyte-associated persistence of pLDH despite clearance of asexual parasites, and may make it unreliable in predicting treatment outcome. One African outpatient clinic study that has assessed persistence of pLDH after treatment of uncomplicated malaria (Oduola et al, 1997) is not representative of current African practice, as most patients were treated with artemether which is currently rarely used in Africa and is known to result in very low gametocyte carriage in convalescence (Price et al, 1999). Among the minority in this study treated with sulphadoxine-pyrimethamine or halofantrine, two of the four patients with convalescent gametocytemia had elevations of pLDH persisting to d 7 (Oduola et al, 1997). This is analogous to our recent findings using another immunochromatographic test, ICT P.f/P.v (Tjitra et al, 1999). Like OptiMAL pLDH, the panmalarial monoclonal antibody of this test also appears to detect gametocytes of P. falciparum, with persistent panmalarial antigenaemia following successful treatment being closely associated with gametocytaemia (unpublished observations). As in the OptiMAL study (Moody et al, 2000) referral centre studies with the ICT P.f/P.v test have shown rapid clearance of the ICT P.f/P.v panmalarial antigen with clearance of asexual parasitaemia (Eisen & Saul, 2000). Early, highly effective treatment in these patients resulted in no post-treatment gametocytaemia. In contrast, our studies in Radamata Primary Health Centre in malaria-endemic eastern Indonesia have shown high rates (> 50%) of post-treatment gametocytaemia after chloroquine and sulphadoxine-pyrimethamine and persistent gametocyte-associated panmalarial antigenaemia despite clearance of asexual parasites. This resulted in the ICT P.f/P.v panmalarial antigen being unreliable in predicting treatment outcome in this malaria-endemic setting (unpublished observations). For this reason it would be useful if Moody et al (2000) could indicate whether the rapid clearance of pLDH in their London study was associated with low rates and levels of post-treatment gametocytaemia. We agree that the pLDH may prove to be useful in predicting treatment failure in settings where post-treatment gametocytaemia is rare, e.g. in non-immune travellers with short duration of illness and in patients treated with artemisinin derivatives (Price et al, 1999). However, in most malaria-endemic areas, chloroquine and sulphadoxine-pyrimethamine remain the most commonly used drugs, both of which are associated with high rates and levels of post-treatment gametocytaemia. We believe that before pLDH rapid-antigen tests can be advocated as potential predictive tools in malaria-endemic areas, studies evaluating the ability of OptiMAL pLDH clearance to predict treatment outcome in primary health centres in these areas are required, and we need to establish that gametocytes do not result in persistent positive tests for pLDH after treatment.
Source: British Journal of Haematology
Authors: Emiliana Tjitra, Nicholas M. Anstey
Language: English
Topic: Malaria Research and Control
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2141214547