Abstract:

Malaria rapid diagnostic tests (MRDTs) are important for malaria disease management. However, the performance of the RDTs is affected when the targeted antigens in the parasite have a variation or are altogether absent. The most common parasite target antigen in RDTs, Plasmodium falciparum histidine-rich protein 2 (HRP2), has been reported to be absent in some P. falciparum parasites. 371 patient samples, from Akuapem North (58.5%), Atiwa East (21.3%), and from New Juaben (20.2%), were used in the study. PCR provided the highest number, 14.8% (55/371), of positive detections for falciparum infections. Microscopy detected parasites in 20/261 (7.7%) samples, and the minimum parasite density by microscopy was 430 parasites/µL. Out of the 371 samples, 27 (7.3%) were positive by RDT. The highest RDT positivity rate, 13.3% (10/75), was observed at New Juaben. False-negative RDT results were obtained in 43/55 (78.2%) of the negative branded RDT kits. Only two microscopies positive sample were RDT positive. Using 18SrDNA PCR, 55 (14.8%) samples were positive for P. falciparum. In Akuapem North, 79.2 % (19/24) of the PCR positive samples had P. falciparum parasites that lacked exon 2 of PFHRP2. An overall RDT positivity rate of 7.3% (27/371) and false-negative rate of 78.2% (43/55) were observed for the study sites. Plasmodium falciparum parasite populations with deletions of the PFHRP2 and PFHRP3 genes are present in Ghana. There is an urgent need to investigate the prevalence and geographic distribution of these parasites.

References:

[1] WHO. (2016b). World Malaria Report, 2016. Retrieved from http://www.who.int/malaria/publications/world-malariareport-2016/report/en/.

[2] WHO. (2018). World Malaria Report 2018. Retrieved from Geneva: https://www.who.int/malaria/publications/world-malaria-report-2018/en/.

[3] WHO. (2011). Report on the regional workshop on strengthening quality management systems for parasitological diagnosis of malaria. Retrieved from http://applications.emro.who.int/docs/IC_Meet_Rep_2012_EN_14512.pdf.

[4] Abba, K., Kirkham, A. J., Olliaro, P. L., Deeks, J. J., Donegan, S., Garner, P., & Takwoingi, Y. (2014). Rapid diagnostic tests for diagnosing uncomplicated non-falciparum or Plasmodium vivax malaria in endemic countries. Cochrane Database Syst Rev (12), Cd011431. doi:10.1002/14651858.cd011431.

[5] Kumar, N., Singh, J. P., Pande, V., Mishra, N., Srivastava, B., Kapoor, R., Anvikar, A. R. (2012). Genetic variation in histidine-rich proteins among Indian Plasmodium falciparum population: a possible cause of variable sensitivity of malaria rapid diagnostic tests. Malar J, 11, 298. doi:10.1186/1475-2875-11-298.

[6] Lee, N., Gatton, M. L., Pelecanos, A., Bubb, M., Gonzalez, I., Bell, D., McCarthy, J. S. (2012). Identification of optimal epitopes for Plasmodium falciparum rapid diagnostic tests that target histidine-rich proteins 2 and 3. J Clin Microbiol, 50(4), 1397-1405. doi:10.1128/jcm.06533-11.

[7] WHO. (2015b). WHO-FIND malaria RDT evaluation programme: product testing round 5. Retrieved from http://www.who.int/malaria/mpac/mpac-sept2014-round5- product- testing-presentation.pdf.

[8] Maltha, J., Guiraud, I., Lompo, P., Kabore, B., Gillet, P., Van Geet, C., Jacobs, J. (2014). Accuracy of PFHRP2 versus Pf-pLDH antigen detection by malaria rapid diagnostic tests in hospitalized children in a seasonal hyperendemic malaria transmission area in Burkina Faso. Malar J, 13, 20. doi:10.1186/1475-2875-13- 20.

[9]    Mouatcho, J. C., & Goldring, J. P. (2013). Malaria rapid diagnostic tests: challenges and prospects. (1473-5644 (Electronic)).

[10] WHO. (2017b). Malaria rapid diagnostic test performance: results of WHO product testing of malaria RDTs: round 7 (2015-2016). Retrieved from http://www.who.int/malaria/publications/atoz/978924151268/en/.

[11] http://www.easternregion.gov.gh/index.php/profile/.

[12] Gupta, H., Matambisso, G., Galatas, B., Cisteró, P., Nhamussua, L., Simone, W., Mayor, A. (2017). Molecular surveillance of PFHRP2 and PFHRP3 deletions in Plasmodium falciparum isolates from Mozambique. Malar J, 16. doi:10.1186/s12936-017-2061-z.

[13] WHO. (2017a). False-negative RDT results and implications of new reports of P. falciparum histidine-rich protein 2/3 gene deletions. Retrieved from https://www.who.int/docs/default-source/documents/publications/gmp/false-negative-rdt-results.pdf?sfvrsn=ec917b72_2.

[14] Baiden, F., Webster, J., Tivura, M., Delimini, R., Berko, Y., Amenga-Etego, S., Chandramohan, D. (2012). Accuracy of rapid tests for malaria and treatment outcomes for malaria and non-malaria cases among under-five children in rural Ghana. PLoS One, 7(4), e34073. doi: 10.1371/journal.pone.0034073.

[15] Nkrumah, B., Acquah, S. E., Ibrahim, L., May, J., Brattig, N., Tannich, E., Huenger, F. (2011). Comparative evaluation of two rapid field tests for malaria diagnosis: Partec Rapid Malaria Test(R) and Binax Now(R) Malaria Rapid Diagnostic Test. BMC Infect Dis, 11, 143. doi:10.1186/1471-2334-11-143.

[16] Bisoffi, Z., Sirima, S. B., Menten, J., Pattaro, C., Angheben, A., Gobbi, F., Van den Ende, J. (2010). Accuracy of a rapid diagnostic test on the diagnosis of malaria infection and malaria-attributable fever during low and high transmission season in Burkina Faso. Malar J, 9, 192. doi:10.1186/1475-2875-9-192.

[17] Rakotonirina, H., Barnadas, C., Raherijafy, R., Andrianantenaina, H., Ratsimbasoa, A., Randrianasolo, L., Menard, D. (2008). Accuracy and reliability of malaria diagnostic techniques for guiding febrile outpatient treatment in malaria-endemic countries. Am J Trop Med Hyg, 78(2), 217-221.

[18] Amoah, L. E., Abankwa, J., & Oppong, A. (2016). Plasmodium falciparum histidine-rich protein-2 diversity and the implications for PFHRP 2: based malaria rapid diagnostic tests in Ghana. Malar J, 15, 101. doi:10.1186/s12936-016-1159-z.

[19] Berzosa, P., de Lucio, A., Romay-Barja, M., Herrador, Z., Gonzalez, V., Garcia, L.,Benito, A. (2018). Comparison of three diagnostic methods (microscopy, RDT, and PCR) for the detection of malaria parasites in representative samples from Equatorial Guinea. Malar J, 17(1), 333. doi:10.1186/s12936-018-2481-4.

[20] Gatti, S., Gramegna, M., Bisoffi, Z., Raglio, A., Gulletta, M., Klersy, C., Scaglia, M. (2007). A comparison of three diagnostic techniques for malaria: a rapid diagnostic test (NOW Malaria), PCR and microscopy. Ann Trop Med Parasitol, 101(3), 195-204. doi:10.1179/136485907x156997.

[21] Tham, J. M., Lee, S. H., Tan, T. M., Ting, R. C., & Kara, U. A. (1999). Detection and species determination of malaria parasites by PCR: comparison with microscopy and with Parasite-F and ICT malaria Pf tests in a clinical environment. J Clin Microbiol, 37(5), 1269-1273.

[22] Gardner, M. J., Hall, N., Fung, E., White, O., Berriman, M., Hyman, R. W., Barrell, B. (2002). Genome sequence of the human malaria parasite Plasmodium falciparum. Nature, 419(6906), 498-511. doi:10.1038/nature01097.

[23] Gamboa, D., Ho, M. F., Bendezu, J., Torres, K., Chiodini, P. L., Barnwell, J. W., Cheng, Q. (2010). A large proportion of P. falciparum isolates in the Amazon region of Peru lack PFHRP2 and PFHRP3: implications for malaria rapid diagnostic tests. PLoS One, 5(1), e8091. doi: 10.1371/journal.pone.0008091.

[24] Abdallah, J. F., Okoth, S. A., Fontecha, G. A., Torres, R. E., Banegas, E. I., Matute, M. L., Udhayakumar, V. (2015). Prevalence of PFHRP2 and PFHRP3 gene deletions in Puerto Lempira, Honduras. Malar J, 14, 19. doi:10.1186/s12936-014-0537-7.

[25] Akinyi, S., Hayden, T., Gamboa, D., Torres, K., Bendezu, J., Abdallah, J. F., Udhayakumar, V. (2013). Multiple genetic origins of histidine-rich protein 2 gene deletion in Plasmodium falciparum parasites from Peru. Sci Rep, 3, 2797. doi:10.1038/srep02797.

[26] Kyabayinze, D. J., Zongo, I., Cunningham, J., Gatton, M., Angutoko, P., Ategeka, J., Bell, D. (2016). HRP2 and pLDH-Based Rapid Diagnostic Tests, Expert Microscopy, and PCR for Detection of Malaria Infection during Pregnancy and at Delivery in Areas of Varied Transmission: A Prospective Cohort Study in Burkina Faso and Uganda. PLoS One, 11(7), e0156954. doi: 10.1371/journal.pone.0156954.