To the authors’ knowledge, this is the first study to suggest a benefit of preventing recrudescent compared to new infections. As expected, fever was more common among children with malaria infection than among those without. However, this study demonstrated that recrudescent infections are associated with worsened haematological outcomes compared to a new malaria infection acquired after successful treatment. Also, recrudescent infections occur sooner after treatment, leading to an overall increase in the incidence of infections. Thus, although new and recrudescent infections are clinically indistinguishable, curing the initial infection, even if a new infection occurs, improves the overall health of the patient.
Impaired haematological recovery in children with recrudescent parasitaemia is an objective measure and essential to the overall health of the population. With persistent infection, even when it is microscopically undetectable, on-going inflammation and erythrocyte destruction interferes with the recovery of the red blood cells . Interestingly, in almost all cases, haemoglobin levels increased despite the failure to completely cure the infection.
In this study, age was not a risk factor for recurrent infection in general nor was it associated with the classification of new versus recrudescent infection. This may be due to the intensity of transmission at the study site leading to early acquisition of immunity or it may be attributed to the homogeneity in the age of the participants.
As expected, infections were polyclonal within individuals in this study. At baseline measurement, patients with higher MOI at the time of recurrence were more likely to be classified as having a recrudescent infection. This may be a true biological phenomenon or it may be due to chance. When a participant’s MOI at baseline or at the time of reinfection was high, new infections could have been misclassified as recrudescent infections because some alleles from a new parasite genotype may have matched between the original and recurrent infection by chance. Infection with multiple malaria parasite strains may have had a greater probability of containing one or more malaria strains that were resistant to treatment, leading to a recrudescent infection.
Any genotyping technique may misclassify infections. If a parasite genotype is present, but below the level of detection at the initial infection and then grows to detectable levels at the time of recurrent infection, it may be classified as a new infection even though it was present initially. Alleles were identified using capillary electrophoresis, a method that is highly sensitive and less likely than other genotyping methods to fail to detect minority populations . Another limitation was the inability to discern haplotypes. Consequently, polyclonal infections that shared the same collection of alleles between the initial and recurrent infections may have appeared to be recrudescent infections, even though the haplotype profiles for the parasites in the recurrent infection were different.
The most notable limitation of this study is that these SP efficacy results may not be applicable to the currently used artemisinin-based combination therapies. SP was a failing drug at the time of this study, which resulted in more recrudescent infections than would be expected in a current artemisinin combination therapy drug efficacy study. It is also possible that current, more effective drugs keep recrudescent infections at a lower density of parasitaemia, which may produce a different clinical presentation compared to patients treated with SP. In addition, in current protocols for assessment of anti-malarial drug efficacy, all episodes of recurrent parasitemia are treated with rescue therapy, regardless of symptoms. As a result, this experiment is unlikely to be repeated.
In high transmission settings, when new infections frequently interfere with assessment of a drug’s efficacy in clearing the initial infection, using molecular methods to distinguish new from recrudescence provides useful information. This study’s results indicate that treating clinical malaria with drugs that provide sterile cure is the most beneficial to the patient when compared to suppressive treatment that fails to eliminate all asexual parasites from the blood even while preventing subsequent infections.
The results of this study confirm the paramount importance of providing effective treatment of all malaria infections. If malaria infection occurs several weeks after the initial treatment, full parasitological cure followed by a new infection is better for patients than suppressive treatment with persistent sub-patent infection that reaches detectable levels again. Thus, anti-malarial drugs that provide prolonged prophylaxis but poor curative efficacy will have a long-term detrimental effect on the health of children who suffer from anaemia due to malaria. However, new infections are far from benign. They are just as likely as recurrent ones to cause febrile illnesses in children, prompting treatment-seeking behaviour and leading to further burden on the health care system.