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| COMMENTARY |
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| Year : 2022 | Volume
: 66
| Issue : 4 | Page : 522-523 |
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Malaria hemozoin: A target for point-of-care diagnosis
Shrikant Nema
Senior Research Fellow, ICMR-National Institute of Research in Tribal Health, Jabalpur, Madhya Pradesh; Scientist B, ICMR-National Institute of Malaria Research, New Delhi, India
| Date of Submission | 06-Aug-2021 |
| Date of Decision | 19-Oct-2022 |
| Date of Acceptance | 22-Oct-2022 |
| Date of Web Publication | 31-Dec-2022 |
Correspondence Address:
Shrikant Nema
ICMR-National Institute of Malaria Research, New Delhi - 110 077
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/ijph.ijph_1646_21
 Abstract | | |
The challenges in malaria diagnosis continue to threaten the malaria elimination goal in India and other malaria-endemic countries. A rapid diagnostic test (RDT) kit is widely used in resource-constrained areas where microscopy and molecular methods are not easily deployable. Considering the problems associated with the currently available RDT kit, such as histidine-rich protein 2 gene deletion and prolonged stability of the protein in the blood, it suggests that new potential biomarkers are urgently needed. Hemozoin (Hz) is an important biomarker for malaria diagnosis, which is the by-product of a detoxification mechanism in the malaria parasite. This article highlights the importance of “Hz” for point-of-care malaria diagnosis when India and other countries are moving toward the goal of malaria elimination.
Keywords: Hemozoin, histidine-rich protein 2 deletion, malaria diagnosis, malaria elimination
How to cite this article:
Nema S. Malaria hemozoin: A target for point-of-care diagnosis. Indian J Public Health 2022;66:522-3 |
Malaria remains a significant public health threat in tropical and subtropical regions of the world. According to the World Health Organization (WHO), there were an estimated 241 million malaria cases with 627,000 deaths occurring worldwide in 2020.[1] The diagnosis of malaria is majorly done by either microscopy or by rapid diagnostic test (RDT) kit in the peripheral areas of resource-limited areas of India and other malaria-endemic countries. The problems in malaria diagnosis are associated with the detection of mixed infections, afebrile cases, histidine-rich protein 2 (HRP2) deletion in the malaria parasite, and low-density parasite detection. Currently available RDTs use HRP2 as a biomarker to detect Plasmodium falciparum. The WHO has reported Pfhrp2 deletion in parasites from 32 countries, leading to false negative results by RDT, and prolonging the stability of HRP2 protein in the blood may give false positive results after parasite clearance.[1] When merozoites enter red blood cells in the bloodstream and reach the digestive vacuole, the hemoglobin degradation process occurs mostly inside the digestive vacuole of the parasite. The survival mechanism of the malaria parasite in the digestive vacuole by producing hemozoin (Hz) has been seen from a wider range of perspectives such as for diagnostic purposes and antimalarial drug targets. The process of hemoglobin degradation in the digestive vacuole has been of paramount interest as a target of antimalarial drugs.[2] However, the associated detoxification of toxic heme into Hz may stand out as an attractive target for new diagnostic biomarkers. Hz has been a target of interest in many ways. The importance of Hz has been underestimated previously due to an improper understanding of its physical structure and annotations. Nevertheless, research activity has increased considerably in the past two decades, with Hz appearing to be relevant in three key areas: (i) as an antimalarial drug target, (ii) in diagnostic applications, and (iii) it appears to be biologically active, especially as an immune modulator. All Plasmodium species produce different morphologies of Hz that could easily classify all Plasmodium species of malaria parasites that infect the human host.[3] Several molecular methods have a limit of detection (LoD) of 22–1000 parasites/ml. Moreover, this requires a complex laboratory setup and an expert technician. These parameters do not render these methods suitable for deployment in resource-poor settings, where most malaria cases occur. Furthermore, malaria microscopy is widely preferred as it has a hundredfold higher LoD compared to a standard polymerase chain reaction (PCR) (50–100 parasites/μl).[4] For that reason, the detection of Hz in the blood could be useful for malaria diagnosis services, with the advantage of a rapid clearance time of Hz as compared to HRP2 protein in the blood. Hz particles consist of electromagnetic properties such as paramagnetism, optical dichroism, and optical nonlinearity that have been exploited to detect, separate, disrupt, or kill the malaria parasite, i.e., it is an optically birefringent crystalline pigment that reduces the amount of transmitted polarized laser light while passing through a sample.[2] Consequently, a group of researchers used magnets to detect the Hz in a magnetic field by blocking an amount of polarized light that is proportional to the concentration of Hz in the sample.[5] Recently, Hz-based malaria diagnosis, launched by Hemex Health, has shown high sensitivity and specificity compared to light microscopy, PCR, and RDT.[6] In addition, the photoacoustic property of Hz could be exploited for a diagnostic purpose that can assess the intraerythrocytic stages of the malaria parasite using a photoacoustic spectroscopy technique.[2] Furthermore, P. falciparum malaria infections during pregnancy lead to the accumulation of Hz in the placenta. However, Plasmodium vivax-infected erythrocytes do not accumulate in the placenta like P. falciparum.[7] Therefore, Hz can be used as an indicator of malaria infection in the placenta and may provide a more accurate estimate of the frequency of malaria infection during pregnancy. Researchers around the globe are striving to explore new potential biomarkers for malaria diagnosis. Biomarkers associated with the erythrocytic stage are of immense importance, such as heme detoxification protein[8] and its by-product Hz. Several private and government organizations are constantly making a sincere effort to achieve the targeted elimination goal by 2030.[9] Moreover, this is the right time to extend additional support to strengthen diagnostic research in this challenging malaria-elimination era.[10] Hz has been known for years, but its use for the quick and accurate diagnosis will undoubtedly strengthen the malaria elimination program.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | |  |
| 1. | |
| 2. | Coronado LM, Nadovich CT, Spadafora C. Malarial hemozoin: From target to tool. Biochim Biophys Acta 2014;1840:2032-41.  |
| 3. | Noland GS, Briones N, Sullivan DJ Jr. The shape and size of hemozoin crystals distinguishes diverse Plasmodium species. Mol Biochem Parasitol 2003;130:91-9. |
| 4. | World Health Organization, Diseases UBSP for R and T in T. Microscopy for the detection, identification and quantification of malaria parasites on stained thick and thin blood films in research settings (version 1.0): procedure: methods manual. World Health Organization, 2015 https://apps.who.int/iris/handle/10665/163782 [Last accessed on 2022 Oct 19]. |
| 5. | Grimberg BT, Grimberg KO. Hemozoin detection may provide an inexpensive, sensitive, 1-minute malaria test that could revolutionize malaria screening. Expert Rev Anti Infect Ther 2016;14:879-83. |
| 6. | Kumar R, Verma AK, Shrivas S, Thota P, Singh MP, Rajasubramaniam S, et al. First successful field evaluation of new, one-minute haemozoin-based malaria diagnostic device. EClinicalMedicine 2020;22:100347. |
| 7. | McGready R, Brockman A, Cho T, Levesque MA, Tkachuk AN, Meshnick SR, et al. Haemozoin as a marker of placental parasitization. Trans R Soc Trop Med Hyg 2002;96:644-6. |
| 8. | Nema S, Krishna S, Tiwari A, Bharti PK. Limited genetic diversity and expression profile of Plasmodium falciparum haem detoxification protein: a possible diagnostic target. Trans R Soc Trop Med Hyg 2022:trac055. doi: 10.1093/trstmh/trac055 |
| 9. | Nema S, Ghanghoria P, Bharti PK. Malar.ia elimination in India: Bridging the gap between control and elimination. Indian Pediatr 2020;57:613-7. |
| 10. | Nema S, Verma AK, Bharti PK. Strengthening diagnosis is Key to eliminating malaria in India. Lancet Infect Dis 2019;19:1277-8. |
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