Accuracy of Malaria Tests Evaluated for Febrile Children

It remains challenging to distinguish malaria from other fever causing infections, as a positive rapid diagnostic test does not always signify a true active malaria infection. Antigen persistence could increase the rate of false positive test results, leading to a wrong diagnosis in settings where other diagnostic tools are unavailable.

The phenomenon of false positive results after successful treatment can result in an overestimation of malaria positive cases and lead to misdiagnosis of the true cause of fever in children. Recent studies have reported a decreasing specificity and positive predictive value of specific rapid diagnostic tests (RDT) up to three to four weeks after successful malaria treatment.

Scientists at the Clinical Research Unit of Nanoro (Ouaga, Burkina Faso) and their colleagues conducted a prospective etiology study 2015 among febrile children less than five years of age in Burkina Faso. To assess bacterial and viral infection status blood, urine and stool samples were analyzed. The malaria Rapid Diagnostic Test (RDT) used was the SD Ag Bioline Pf that detects Plasmodium falciparum histidine-rich protein-2 (PfHRP2) and this test was performed by trained study nurses at the health facilities or the district hospital. Malaria diagnosis by microscopy was performed by expert laboratory technicians. Venous blood was collected into a pediatric blood culture bottle and incubated in a BACTEC 9050 instrument. Urine culture was done when a urine sample was positive for leucocytes and nitrite as indicated by a urine dipstick. Stool samples were specifically analyzed for group A rotavirus using one step rotavirus and adenovirus serotype 40/41 in a human feces test.

The investigators analyzed a total 683 blood samples with microscopy and RDT-PfHRP2. P. falciparum malaria was diagnosed in 49.8% (340/683) by microscopy compared to 69.5% (475/683) by RDT-PfHRP2. The RDT-PfHRP2 reported 29.7% (141/475) false positive results and 1.8% (6/340) false negative cases. The RDT-PfHRP2 had a high sensitivity (98.2%) and negative predictive value (97.1%), but a low specificity (58.9%) and positive predictive value (70.3%). Almost 50% of the alternative causes of fever were diagnosed by laboratory testing in the RDT false positive malaria group. The most common other causes of fever were bacterial bloodstream infection (16.3%), followed by rotavirus and adenovirus infections (6.4%) and urinary tract infection (4.3%).

The authors concluded that RDTs based on PfHRP2 have a good sensitivity and negative predictive value, but their use in malaria endemic areas may result in missing true causes of fever mainly in the malaria false positive group. They recommend the use of a second malaria RDT based on a different target, such as pLDH and/or using other simple diagnostic tests like urine and feces dipstick. The study was published on July 20, 2017, in the Malaria Journal.