Failure of rapid diagnostic tests in Plasmodium falciparum malaria cases among travelers to the UK and Ireland: Identification and characterisation of the parasites.

OBJECTIVES: Our objective was to systematically investigate false-negative histidine-rich protein 2 rapid diagnostic tests (HRP2-RDT) in imported Plasmodium falciparum malaria cases from travelers to the UK and the Republic of Ireland (RoI). METHODS: Five imported malaria cases in travellers returning to the UK and RoI from East Africa were reported to the PHE Malaria Reference Laboratory as negative according to histidine-rich protein (HRP2)-RDT. The cases were systematically investigated using microscopic, RDT, molecular, genomic, and in in vitro approaches. RESULTS: In each case, HRP2-RDT was negative, whereas microscopy confirmed the presence of P. falciparum. Further analysis revealed that the genes encoding HRP2 and HRP3 were deleted in three of the five cases. Whole-genome sequencing in one of these isolates confirmed deletions in P. falciparum chromosomes 8 and 13. Our study produced evidence that the fourth case, which had high parasitemia at clinical presentation, was a rare example of antigen saturation ('prozone-like effect'), leading to a false negative in the HRP2-RDT, while the fifth case was due to low parasitemia. CONCLUSIONS: False-negative HRP2-RDT results with P. falciparum are concerning. Our findings emphasise the necessity of supporting the interpretation of RDT results with microscopy, in conjunction with clinical observations, and sets out a systematic approach to identifying parasites carrying pfhrp2 and pfhrp3 deletions.

Reducing unnecessary inpatient laboratory testing in a teaching hospital.

After an inpatient phlebotomy-laboratory test request audit for 2 general inpatient wards identified 5 tests commonly ordered on a recurring basis, a multidisciplinary committee developed a proposal to minimize unnecessary phlebotomies and laboratory tests by reconfiguring the electronic order function to limit phlebotomy-laboratory test requests to occur singly or to recur within one 24-hour window. The proposal was implemented in June 2003. Comparison of fiscal year volume data from before (2002-2003) and after (2003-2004) implementation revealed 72,639 (12.0%) fewer inpatient tests, of which 41,765 (57.5%) were related directly to decreases in the 5 tests frequently ordered on a recurring basis. Because the electronic order function changes did not completely eliminate unnecessary testing, we concluded that the decrease in inpatient testing represented a minimum amount of unnecessary inpatient laboratory tests. We also observed 17,207 (21.4%) fewer inpatient phlebotomies, a decrease sustained in fiscal year 20042005. Labor savings allowed us to redirect phlebotomists to our understaffed outpatient phlebotomy service.