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

Ayesha M Shaukat1, Elizabeth A Gilliams1, Leo J Kenefic1, Matthew B Laurens1, Fraction K Dzinjalamala2, Osward M Nyirenda2, Phillip C Thesing12, Christopher G Jacob1, Malcolm E Molyneux35, Terrie E Taylor24, Christopher V Plowe1 and Miriam K Laufer1*

Author Affiliations

1 Malaria Group, Howard Hughes Medical Institute/Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD, USA

2 Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi

3 Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, University of Malawi, Blantyre, Malawi

4 Department of Medicine, College of Osteopathic Medicine, Michigan State University, East Lansing, MI, USA

5 Liverpool School of Tropical Medicine, University of Liverpool, Liverpool, UK

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Malaria Journal 2012, 11:207  doi:10.1186/1475-2875-11-207

Published: 18 June 2012

Abstract

Background

Distinguishing 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.

Methods

Children 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.

Results

Fever 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.

Conclusions

The 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.

Keywords:
Malaria; Sulphadoxine-pyrimethamine; Drug efficacy; Genotyping; Recrudescent infections; New infections; Malawi; Anaemia