Accuracy of Pf HRP2 versus Pf-pLDH antigen detection by malaria rapid diagnostic tests in hospitalized children in a seasonal hyperendemic malaria transmission area in Burkina Faso

Abstract

BackgroundIn most sub-Saharan African countries malaria rapid diagnostic tests (RDTs) are now used for the diagnosis of malaria. Most RDTs used detect Plasmodium falciparum histidine-rich protein-2 (PfHRP2), though P. falciparum-specific parasite lactate dehydrogenase (Pf-pLDH)-detecting RDTs may have advantages over PfHRP2-detecting RDTs. Only few data are available on the use of RDTs in severe illness and the present study compared Pf-pLDH to PfHRP2-detection.MethodsHospitalized children aged one month to 14 years presenting with fever or severe illness were included over one year. Venous blood samples were drawn for malaria diagnosis (microscopy and RDT), culture and complete blood count. Leftovers were stored at −80 °C and used for additional RDT analysis and PCR. An RDT targeting both PfHRP2 and Pf-pLDH was performed on all samples for direct comparison of diagnostic accuracy with microscopy as reference method. PCR was performed to explore false-positive RDT results.ResultsIn 376 of 694 (54.2%) included children, malaria was microscopically confirmed. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value were 100.0, 70.9, 69.4 and 100.0%, respectively for PfHRP2-detection and 98.7, 94.0, 91.6 and 99.1%, respectively for Pf-pLDH-detection. Specificity and PPV were significantly lower for PfHRP2-detection (p <0.001). For both detection antigens, specificity was lowest for children one to five years and in the rainy season. PPV for both antigens was highest in the rainy season, because of higher malaria prevalence. False positive PfHRP2 results were associated with prior anti-malarial treatment and positive PCR results (98/114 (86.0%) samples tested).ConclusionAmong children presenting with severe febrile illness in a seasonal hyperendemic malaria transmission area, the present study observed similar sensitivity but lower specificity and PPV of PfHRP2 compared to Pf-pLDH-detection. Further studies should assess the diagnostic accuracy and safety of an appropriate Pf-pLDH-detecting RDT in field settings and if satisfying, replacement of PfHRP2 by Pf-pLDH-detecting RDTs should be considered.

Comparison of rapid diagnostic test Plasmotec Malaria-3, microscopy, and quantitative real-time PCR for diagnoses of Plasmodium falciparum and Plasmodium vivax infections in Mimika Regency, Papua, Indonesia

“…Published WHO product evaluation on different malaria RDT products submitted for testing has shown that targeting P. falciparum HRP2 has the highest and most consistent detection rate [16]. However, this conflicts with other findings in which HRP2-based RDTs have shown a lower performance value than products using pLDH for detecting P. falciparum , as the pLDH capture system is not affected by a possible ‘prozone’ effect, parasite antigen polymorphisms or gene deletions [37-41]. In Myanmar, a study comparing a commonly used RDT utilizing HRP2 and pan pLDH compared with microscopy demonstrated P. vivax and P. malariae were detected to a far lesser extent (lower sensitivity, NPV, and NLR) than P. falciparum [42].…”

Genetic diversity of Plasmodium falciparum histidine-rich protein 2 in the China–Myanmar border area

“…One important factor is the variability within the parasite antigens detected by the RDTs, which includes presence or absence of the target epitopes and variations in the number of epitopes in a particular parasite isolate (Lee et al, 2006; Lee et al, 2012; Maltha et al, 2014; Talman et al, 2007). Genetic diversity may be particularly important for PfHRP2-based RDTs, since most of the RDTs are based on this antigen (Mouatcho and Goldring, 2013).…”

Assessment of labor and delivery in pregnant women on sulfadoxine-pyrimethamine regimen in Yaoundé gynaeco-obstetric and paediatric hospital: a comparative study of 313 cases

“…The sensitivity of this test varies from 71 to 100% according to literature. 18,20,26 Labor was managed by midwives and residents, using a partograph, as recommended by the World Health Organization.…”

“…Positive *RDTm n (%) Negative*RDTm n (%) P-value (15)(16)(17)(18)(19)(20) Table 1 shows the characteristics of women included into the study. The (15-20) age group, single (marital status), lack of financial resources, <4 antenatal visits, the nonuse of mosquito bed nets, the absence of iron prophylaxis and a previous history of malaria crisis during the current pregnancy were associated with malaria infection at the onset of labor.…”

“…Many studies have proven the accuracy of RDTm in the detection of malaria infection, prompting the management thereof with biological evidence. 9,[19][20][21] The presence of clinical signs is not an indicator of the severity of the disease and placental malaria, which is the most common form of malaria in pregnant women, is asymptomatic. 22 Placental malaria could be responsible for adverse outcomes during labor and delivery for both the mother and her fetus.…”