Usefulness of Plasmodium falciparum-specific rapid diagnostic tests for assessment of parasite clearance and detection of recurrent infections after artemisinin-based combination therapy.
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 LDH-based 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.


CONCLUSIONS
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.


BACKGROUND
Clinicaltrials.gov, NCT01843764.
Malaria Research, Department of Medicine-Solna, Karolinska University Hospital/Karolinska Institutet, Stockholm, Sweden. berit.schmidt@ki.se.
Berit
B
Aydin-Schmidt
Marycelina
M
Mubi
Ulrika
U
Morris
Max
M
Petzold
Billy E
BE
Ngasala
Zul
Z
Premji
Anders
A
Björkman
Andreas
A
Mårtensson
D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000627:therapeutic use*; D002675:Child, Preschool; D003955:Diagnostic Tests, Routine / Q000379:methods*; D004338:Drug Combinations; D004983:Ethanolamines / Q000627:therapeutic use*; D005260:Female; D005449:Fluorenes / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D007118:Immunoassay / Q000379:methods; D007223:Infant; D016778:Malaria, Falciparum / Q000175:diagnosis*; D008297:Male; D008853:Microscopy / Q000379:methods; D018512:Parasitemia / Q000175:diagnosis*; D010963:Plasmodium falciparum / Q000302:isolation & purification*; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D012008:Recurrence; D013636:Tanzania
D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes