Detection of histidine rich protein 2 and panmalarial ICT Malaria Pf/Pv test antigens after chloroquine treatment of uncomplicated falciparum malaria does not reliably predict treatment outcome in eastern Indonesia.

Abstract

Abstract. In regions with drug-resistant malaria, the ability to rapidly detect or predict treatment failure (TF) soon after a course of standard therapy for Plasmodium falciparum malaria would facilitate the prompt institution of secondline therapy. We thus evaluated longitudinally the ability of the ICT Malaria Pf/Pv immunochromatographic test to predict treatment outcome. Sixty-six Sumbanese Indonesians with uncomplicated falciparum malaria were treated with chloroquine and followed for 28 days by use of 1997 World Health Organization criteria for assessment of therapeutic efficacy of antimalarial drugs. The ICT Pf/Pv testing could be compared with microscopy in approximately half of the patients on each day of follow-up. Although strongly positive histidine rich protein 2 (HRP2) line intensities (equal to or greater than the control band) in convalescence were highly predictive of TF, any degree of positivity for the HRP2 and panmalarial antigens in convalescence was only moderately predictive of TF. Positive predictive values of the HRP2 and panmalarial antigens for TF were 76.9% and 87.0%, respectively, on Day 3, 82.4% and 87.5% on Day 7, and 78.9% and 78.9% on Day 14. Negative HRP2 and panmalarial antigen results in convalescence were even less predictive of an adequate clinical response, and false-negative HRP2 and panmalarial antigen test results were found in one-sixth (6 of 37) of recrudescent infections diagnosed by microscopy among patients with late treatment failure. To reliably predict treatment outcome with rapid antigen tests, further development appears necessary to improve sensitivity for viable asexual parasites while avoiding detection of both gametocytes and persistent antigen in convalescence.

COMPARISON OF HRP2- AND pLDH-BASED RAPID DIAGNOSTIC TESTS FOR MALARIA WITH LONGITUDINAL FOLLOW-UP IN KAMPALA, UGANDA

“…The higher specificity and positive predictive value of the pLDH assay was due to the fact that pLDH antigenemia closely mirrors parasitemia, while HRP2 commonly persists in the bloodstream weeks after successful treatment of malaria. 10,12 Subpatent parasitemia, as detected by PCR, pre-patent infections, and gametocytemia, did not appear to contribute importantly to false-positive results for either RDT. In summary, both studied RDTs accurately identified clinically relevant malaria infections but they differed importantly in sensitivity and specificity.…”

“…A potential problem for HRP2-based assays is persistence of detectable circulating antigen for up to several weeks after parasites have been eradicated. [10][11][12] Persistent HRP2 antigenemia has not correlated with treatment failure, suggesting that this finding is not representative of persistent infection. 10,12 Persistent antigenemia thus may limit the usefulness of HRP2-based assays in areas of intense malaria transmission, where positive tests may commonly be due to prior infections that are no longer clinically relevant.…”

“…[10][11][12] Persistent HRP2 antigenemia has not correlated with treatment failure, suggesting that this finding is not representative of persistent infection. 10,12 Persistent antigenemia thus may limit the usefulness of HRP2-based assays in areas of intense malaria transmission, where positive tests may commonly be due to prior infections that are no longer clinically relevant. pLDHbased RDTs appear to be slightly less sensitive than those detecting HRP2, but the antigen is rapidly cleared from the bloodstream, becoming undetectable at about the same time blood smears become negative after antimalarial therapy.…”

Accuracy of Two Malaria Rapid Diagnostic Tests (RDTS) for Initial Diagnosis and Treatment Monitoring in a High Transmission Setting in Uganda

“…8,9 However, HRP2 antigen remains in the bloodstream for several weeks after parasite clearance, thus contributing to false-positive results and limiting specificity. [10][11][12][13][14] The pLDH-based assays may be more useful for monitoring patients' recovery after treatment and avoiding unnecessary retreatment of malaria because they turn negative soon after parasite clearance from the blood. 15 Additional information on RDT performance in high transmission areas will be helpful in guiding policy and practice.…”

Biomarkers of Vector Bites: Arthropod Immunogenic Salivary Proteins in Vector-Borne Diseases Control

“…Regarding malaria, the use of rapid diagnostic test may be an input for a simple and rapid detection of the parasite. But this method has shown some deficiencies that could alter its relevancy for diagnosing the disease (Tjitra et al 2001). ABDs involve dynamic interactions between the vector, pathogen, and human host.…”