Clinical manifestations of new versus recrudescent malaria infections following anti-malarial drug treatment

Ayesha M Shaukat,Fraction K Dzinjalamala,Christopher V Plowe,Malcolm E Molyneux,Phillip C Thesing,Elizabeth A Gilliams,Osward M Nyirenda,Terrie E Taylor,Leo J Kenefic,Miriam K Laufer,Matthew B Laurens,Christopher G Jacob

doi:10.1186/1475-2875-11-207

Abstract

BackgroundDistinguishing new from recrudescent infections in post-treatment episodes of malaria is standard in anti-malarial drug efficacy trials. New infections are not considered malaria treatment failures and as a result, the prevention of subsequent episodes of malaria infection is not reported as a study outcome. However, in moderate and high transmission settings, new infections are common and the ability of a short-acting medication to cure an initial infection may be outweighed by its inability to prevent the next imminent infection. The clinical benefit of preventing new infections has never been compared to that of curing the initial infection.MethodsChildren enrolled in a sulphadoxine-pyrimethamine efficacy study in Blantyre, Malawi from 1998–2004 were prospectively evaluated. Six neutral microsatellites were used to classify new and recrudescent infections in children aged less than 10 years with recurrent malaria infections. Children from the study who did not experience recurrent parasitaemia comprised the baseline group. The odds of fever and anaemia, the rate of haemoglobin recovery and time to recurrence were compared among the groups.ResultsFever and anemia were more common among children with parasitaemia compared to those who remained infection-free throughout the study period. When comparing recrudescent vs. new infections, the incidence of fever was not statistically different. However, children with recrudescent infections had a less robust haematological recovery and also experienced recurrence sooner than those whose infection was classified as new.ConclusionsThe results of this study confirm the paramount importance of providing curative treatment for all malaria infections. Although new and recrudescent infections caused febrile illnesses at a similar rate, recurrence due to recrudescent infection did have a worsened haemological outcome than recurrence due to new infections. Local decision-makers should take into account the results of genotyping to distinguish new from recrudescent infections when determining treatment policy on a population level. It is appropriate to weigh recrudescent malaria more heavily than new infection in assessing treatment efficacy.

Highlights

Distinguishing new from recrudescent infections in post-treatment episodes of malaria is standard in anti-malarial drug efficacy trials
Episodes of recurrent parasitaemia following treatment may be due to recrudescence of the initial infection, reflecting failure of the drug to clear the infection; or, they may be due to new infections that occurred during the follow-up period
The infections were classified as 119 recrudescent infections, 84 new infections and 19 with uninterpretable results

Summary

Introduction

Distinguishing new from recrudescent infections in post-treatment episodes of malaria is standard in anti-malarial drug efficacy trials. In moderate and high transmission settings, new infections are common and the ability of a short-acting medication to cure an initial infection may be outweighed by its inability to prevent the imminent infection. Anti-malarial drug efficacy studies serve several purposes They are used to assess drug efficacy and safety for licensing, for comparison of efficacy across different settings, and sometimes for validation of markers of drug resistance. New infections are not considered a failure of the curative efficacy of the drug This practice of polymerase chain reaction (PCR) correction of efficacy, leads to the discounting of the post-treatment prophylactic efficacy that can be an important secondary benefit of drug treatment, especially with longer-acting anti-malarial drugs. A drug that appears to cure the initial infection but offers no protection against the infection may appear to have the greatest clinical success rate, but in higher transmission settings, new infections are common and the ability of a short-acting medication to cure an initial infection may be outweighed by its inability to prevent the imminent infection

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Conclusion