Abstract:
Background: Rapid diagnostic test (RDT) is an important tool for parasite-based malaria diagnosis. High specificity
of RDTs to distinguish an active Plasmodium falciparum infection from residual antigens from a previous infection is
crucial in endemic areas where residents are repeatedly exposed to malaria. The efficiency of two RDTs based on
histidine-rich protein 2 (HRP2) and lactate dehydrogenase (LDH) antigens were studied and compared with two
microscopy techniques (Giemsa and acridine orange-stained blood smears) and real-time polymerase chain reaction
(PCR) for assessment of initial clearance and detection of recurrent P. falciparum infections after artemisinin-based
combination therapy (ACT) in a moderately high endemic area of rural Tanzania.
Methods: In this exploratory study 53 children < five years with uncomplicated P. falciparum malaria infection were
followed up on nine occasions, i.e., day 1, 2, 3, 7, 14, 21, 28, 35 and 42, after initiation of artemether-lumefantrine
treatment. At each visit capillary blood samples was collected for the HRP2 and LDH-based RDTs, Giemsa and
acridine orange-stained blood smears for microscopy and real-time PCR. Assessment of clearance times and
detection of recurrent P. falciparum infections were done for all diagnostic methods.
Results: The median clearance times were 28 (range seven to >42) and seven (two to 14) days for HRP2 and LDHbased
RDTs, two (one to seven) and two (one to 14) days for Giemsa and acridine orange-stained blood smear and
two (one to 28) days for real-time PCR. RDT specificity against Giemsa-stained blood smear microscopy was 21% for
HRP2 on day 14, reaching 87% on day 42, and ≥96% from day 14 to 42 for LDH. There was no significant
correlation between parasite density at enrolment and duration of HRP2 positivity (r = 0.13, p = 0.34). Recurrent
malaria infections occurred in ten (19%) children. The HRP2 and LDH-based RDTs did not detect eight and two of
the recurrent infections, respectively.
Conclusion: The LDH-based RDT was superior to HRP2-based for monitoring of treatment outcome and detection
of recurrent infections after ACT in this moderately high transmission setting. The results may have implications for
the choice of RDT devices in similar transmission settings for improved malaria case management.
Trial registration: Clinicaltrials.gov, NCT01843764
