New diagnostic tools for malaria-challenges and opportunities

Nearly half of the world’s population is at risk for malaria and over 600,000 die from the disease every year. Access to prompt and correct parasite based diagnosis in order to target treatment to those with a confirmed malaria infection and improved malaria surveillance are cornerstones in malaria control. The availability of modern diagnostic tools such as rapid diagnostic test (RDT), polymerase chain reaction (PCR) and loop mediated isothermal amplification (LAMP) represent new opportunities besides microscopy for improved sensitive and accurate parasite-based diagnosis. However, there are different demands on diagnostic tools for different health care settings and endemic contexts.

The performance of RDT was compared to blood smear microscopy and PCR among febrile patients in a low endemic/pre elimination area (Zanzibar). Although the sensitivity of RDT was found to be relatively low (76.5%) the health care workers were highly adherent to test results in prescribing antimalarial drugs. Parasite clearance and detection of recurrent infections was assessed by different diagnostic methods after malaria treatment in febrile children in a relatively high endemic area of mainland Tanzania. Median clearance time was two days for PCR and microscopy whereas the clearance times were seven and 28 days for the pLDH and HRP2 based RDTs, respectively. pLDH based RDT was a better tool than HRP2 based for treatment follow up and detection of recurrent infection. The usefulness of RDT as a source of parasite DNA was evaluated through different parasite DNA extraction methods. DNA extraction efficacy varied with test device and extraction method. There was no difference in PCR detection rates between RDT and filter paper samples collected from the field. This confirms the usefulness of RDTs stored under field conditions as a modern tool for molecular malaria surveillance and RDT quality control. A LAMP kit was compared to conventional PCR methods for detection of parasite DNA from dried blood spots collected among both fever patients and asymptomatic individuals in Zanzibar. The LAMP kit had a sensitivity of 98% for detection of Plasmodium(P) falciparum among fever patients and a sensitivity of > 92% and 77% for detection of P. falciparum and P. malariae among asymptomatic individuals. The high diagnostic accuracy of the LAMP kit for detection of low density parasitaemias from minute blood volumes preserved on filter papers supports its role for improved case detection in areas of low density malaria infections.

The results in this thesis provide important data on the usefulness of new diagnostic tools for improved case detection and surveillance of malaria in different endemic contexts.

List of scientific papers

I. Shakely D, Elfving K, Aydin-Schmidt B, Msellem MI, Morris U, Omar R, Weiping Xu, Petzold M, Greenhouse B, Baltzell KA, Ali AS, Björkman A, Mårtensson A. The usefulness of rapid diagnostic tests in the new context of low malaria transmission in Zanzibar. PLoS One. 2013 Sep;8(9).
https://doi.org/10.1371/journal.pone.0072912

II. Aydin-Schmidt B, Mubi M, Morris U, Petzold M, Ngasala BE, Premji Z, Björkman A, Mårtensson A. Usefulness of Plasmodium falciparum-specific rapid diagnostic tests for assessment of parasite clearance and detection of recurrent infections after artemisinin-based combination therapy. Malar J. 2013 Oct;12:349.
https://doi.org/10.1186/1475-2875-12-349

III. Morris U, Aydin-Schmidt B, Shakely D, Mårtensson A, Jörnhagen L, Ali AS, Msellem MI, Petzold M, Gil JP, Ferreira PE, Björkman A. Rapid diagnostic tests for molecular surveillance of Plasmodium falciparum malaria -assessment of DNA extraction methods and field applicability. Malar J. 2013 Mar;12:106.
https://doi.org/10.1186/1475-2875-12-106

IV. Aydin-Schmidt B, Xu W, González IJ, Polley SD, Bell D, Shakely D, Msellem MI, Björkman A, Mårtensson A. Loop Mediated Isothermal Amplification (LAMP) Accurately Detects Malaria DNA from Filter Paper Blood Samples of Low Density Parasitaemias. PLoS One. 2014 Aug;9(8).
https://doi.org/10.1371/journal.pone.0103905