Ellen M. Andersen

Devices for Rapid Diagnosis of Malaria: Evaluation of Prototype Assays That Detect Plasmodium falciparum Histidine-Rich Protein 2 and a Plasmodium vivax-Specific Antigen

ABSTRACT The ParaSight F test was developed as a pioneer industry effort in the large-scale, process-controlled production of a device for the rapid diagnosis of malaria. This device performed well in field settings but was limited to the detection of a single malaria species, Plasmodium falciparum. The ParaSight F+V assay advanced upon the ParaSight F test format by incorporating a monoclonal antibody directed against a proprietary Plasmodium vivax-specific antigen, in addition to the antibody directed against P. falciparum histidine-rich protein 2, which was used in the ParaSight F assay. The modified assay was developed to add the capability to detect P. falciparum and P. vivax in a single-test-strip format. The present study evaluated three distinct ParaSight F+V prototypes with samples from symptomatic patients in regions of Thailand and Peru where malaria is endemic. Over a 2-year enrollment period (1998 and 1999), a total of 4,894 patients consented to participation in the study. Compared with the results for duplicate microscopic examinations of Giemsa-stained blood smears as the reference diagnostic standard, each successive prototype showed substantial improvement in performance. The final ParaSight F+V prototype, evaluated in 1999, had an overall sensitivity for detection of asexual P. falciparum parasites of 98%. The sensitivity of the device was 100% for P. falciparum densities of >500 parasites/μl, with a sensitivity of 83% for parasite densities of ≤500/μl. The specificity for the exclusion of P. falciparum was 93%. For P. vivax, the overall sensitivity was 87% for the final 1999 prototype. The sensitivities calculated for different levels of P. vivax parasitemia were 99% for parasite densities of >5,000/μl, 92% for parasite densities of 1,001 to 5,000/μl, 94% for parasite densities of 501 to 1,000/μl, and 55% for parasite densities of 1 to 500/μl. The specificity for the exclusion of P. vivax was 87%. The areas under the receiver operating characteristic curves for the diagnostic performance of the assay for the detection of P. falciparum and P. vivax were 0.8907 and 0.8522, respectively. These findings indicate that assays for rapid diagnosis have the potential to enhance diagnostic capabilities in those instances in which skilled microscopy is not readily available.

Purnomo Projodipuro (April 11, 1934–May 10, 2013)

The many dozens of our Society members who were clinicians and scientists assigned to the US Naval Medical Research Unit #2 (NAMRU-2) in Jakarta, Indonesia, during its 40-year presence (1970–2010) in that nation, along with many Indonesian colleagues, are also alumni of the School of Purnomo. This diminutive, quiet, and unassuming scholar and gentleman so profoundly affected nearly all of us professionally and personally that his imprint is as meaningful and lasting as our collective alma maters. His strongest legacy as a mentor and exemplar is that separating those two dimensions—personal and professional—should be virtually impossible. Our work, he instructed us, is a matter of the heart and soul. He considered parasitology and its proper study and practice an imbedded aspect of his inner being. He gave the work a palpable spiritual energy and chided those individuals who approached it dispassionately or impersonally. We strive to convey here the energy and output that was Purnomo as a medical and zoological parasitologist and a supreme master teacher and explorer of these fields. Purnomo was born of Javanese parents at Pontianak on the southwestern coast of Borneo in what was, in 1934, part of The Netherlands East Indies. As a boy at Pontianak, he witnessed firsthand some of the most gruesome and cruel aspects of the Pacific War—only rarely speaking of the events and always with an abject and dark despair at such inhumanity. The family escaped by boat to Jakarta sometime in 1942. At age 11 years, he saw the birth of the Republic of Indonesia and ultimately, new opportunities and possibilities. Purnomo earned a BSc in biology from the National University followed immediately by a second BSc in public health from the University of Indonesia. Remaining in Jakarta, he worked in the Department of Parasitology, Faculty of Medicine, University of Indonesia through the 1950s under the famous Professor Lie Kian You, founder of that department and a role model who Purnomo deeply admired and emulated. Lie Kian You instilled in Purnomo the personal character of humanitarian scientific work as well as the mantra, “we forget what we see; we remember what we hear; we know what we do.” Purnomo’s prolific teaching over the decades drove students to doing and practicing under his watchful eyes. In 1972, Purnomo began work as a medical parasitologist at NAMRU-2 Jakarta Detachment. After 35 years of uninterrupted service to that laboratory, he retired in 2007. Purnomo’s many research accomplishments (he published over 150 papers in journals of parasitology and medicine) were formally acknowledged in 1994 by the Helminthological Society of Washington, which bestowed on him an honorary membership in a ceremony at the Uniformed Services University of the Health Sciences. Purnomo tirelessly and passionately instructed many hundreds of students in parasitology at no less than seven prominent medical schools *Address correspondence to J. Kevin Baird, Jalan Diponegoro No.69, Eijkman–Oxford Clinical Research Unit, Jakarta 10430, Indonesia. E-mail: jkevinbaird@yahoo.com