A high-throughput sample processing kit for loop-mediated isothermal amplification (LAMP) is now available for malaria diagnosis.
LAMP is more sensitive than microscopy and current rapid diagnostic tests, and it is faster and easier to use than alternative molecular approaches. It requires only minimal laboratory infrastructure, and the results are simple to interpret.
In 2010, FIND and partners finalized the development of a field-stable LAMP kit for the detection of all species of human malaria parasites. However, the standard LAMP kit was designed for individual diagnosis, not for screening large numbers of people at one time. Now, a high-throughput version has been created which is better adapted for mass population screening in endemic areas.
FIND, the London Hospital of Tropical Diseases, 42 Technology and Porvair Sciences have developed a simple, automated, high-throughput sample processing kit. It can be easily transported in a carrying case, and it can process and evaluate up to 96 samples in less than two hours with minimal hands-on time required. The kit can use whole blood samples or dried blood spot samples.
Why is this important?
Preventing ongoing malaria transmission requires the ability to detect infections in people with asymptomatic malaria infections – i.e., people who do not appear to be sick but have very low, even sub-microscopic levels of malaria parasites in their blood.
Recent studies have shown that low-density malaria infections are the source of 20-50% of human-to-mosquito malaria infection in areas with low or very low transmission intensity. This means that people with no apparent malaria symptoms are actually important contributors to ongoing malaria transmission in their communities.
Having highly sensitive diagnostic tools to screen communities for low-density malaria infections is critically important to interrupt ongoing malaria transmission, and to reach the goals of reducing global malaria incidence and mortality rates by 90% by 2030.
The challenge is that microscopy and most available rapid diagnostic tests (RDTs) are not sufficiently sensitive to detect such low parasite levels, and most molecular diagnostic approaches are too complex for screening large numbers of people in low-resource, community settings.
Two prospective performance evaluations have been completed – one in Zanzibar and the other using samples from a specimen bank at the Hospital for Tropical Diseases in London with results published in the first quarter of 2017.
What do the studies say?
The study by Perera et al. conducted at the Hospital for Tropical Diseases in London compared the performance of the high-throughput sample processing system using LAMP to that of a commercial DNA purification kit based on PCR detection (reference standard), using a set of more than 700 samples collected at the hospital from returning travellers suspected of having malaria. The performance of the high-throughput system was found to match that of PCR, with sensitivity and specificity above 95% for both liquid whole blood samples and dried blood spots. This study suggests that the high-throughput LAMP system is a highly sensitive diagnostic test, with the potential to allow large scale population screening in malaria elimination campaigns.
The study by Aydin-Schmidt et al. in Zanzibar compared the high-throughput LAMP kit with standard PCR methods. In the Zanzibar context, which is very close to eliminating malaria, infections are few and the malaria parasite density in blood samples is extremely low and close to LAMP’s limit of detection (1-2 parasites per µL of blood). As a result, a significant number of infections were not detected by LAMP, with a sensitivity of only 41%. Specificity, on the other hand, was found to be close to perfect at 99.9% – in other words, almost no false positives. Additional studies are required to demonstrate the performance of this test in different transmission settings.
- Development and clinical performance of high throughput loop-mediated isothermal amplification for detection of malaria. Perera RS, Ding XC, Tully F, Oliver J, Bright N, Bell D, Chiodini PL, González IJ, Polley SD, PLoS ONE 12(2): e0171126. doi:10.1371/
journal.pone.0171126, 6 Feb 2017 – Download PDF
- Field evaluation of a high throughput loop mediated isothermal amplification test for the detection of asymptomatic Plasmodium infections in Zanzibar. Aydin-Schmidt B, Morris U, Ding XC, Jovel I, Msellem MI, Bergman D, Islam A, Ali AS, Polley S, González IJ, Mårtensson A, Björkman A. PLoS ONE 12(1): e0169037. doi:10.1371/journal.pone.0169037, 17 Jan 2017 – Download PDF
For more information on the high-throughput processing kit, please contact Porvair Sciences at firstname.lastname@example.org
For more information on the high-throughput equipment set, please contact 42 Technology at http://www.42technology.com/contact-us/