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Using humanized mouse model for in vivo study of Plasmodium vivax

Using humanized mouse model for in vivo study of Plasmodium vivax

28th February, 2018, Dr. Wanlapa Roobsoong

To date, the unavailability of the in vitro continuous culture of P. vivax imposing major obstacle for the study of any stages of the life cycle of this parasite. The routine studies of P. vivax solely depend on the variable clinical isolates obtain directly from patients. Humanized mouse model engrafted with human hepatocytes has been successfully used to study the complete life cycle of P. falciparum. The use of humanized mouse model to study P. vivax would constitute a major breakthrough and revolutionized the way that this unique parasite can be studied in laboratory.

Both liver stage schizont and hypnozoite have been observed. Moreover reactivation of the hypnozoite has been observed. The in vivo study of P. vivax *using humanized mouse model engrafted with human hepatocyte is the research collaboration between MVRU and Dr. Sebastian from CIDR, and MVRU and Prof. Osamu Kaneko from Nagasaki university. There are 2 humanized mouse models that effectively used for in vivo study of *P. vivax at MVRU, FRG-NOD and PXB mice. Both models support liver stage development and liver-to-blood stage transition of P. vivax which revolutionized the way that this parasite can be studied in laboratory. By injecting P. vivax sporozoites through tail vein, they can invade and develop inside the engrafted human hepatocytes with both active and dormant forms (hypnozoite) have been observed. In addition, by injecting human young red blood cells to catch up free merozoites that released from the liver, tightly synchronized blood stage can be obtained. This has opened a wide opportunity to study in vivo drug and vaccine’s efficacy against liver stage and blood stage of P. vivax.

During malaria elimination era, multiple measures and stringent control strategies are needed in order to completely eliminate malaria. One of the big challenge to eradicate P. vivax is the hypnozoite (dormant form that stay in the liver) which can cause relapse at any time after clinical malaria episodes. The drug that target the hypnozoites would help to protect patients from relapse. Beside primaquine and tefenoquine, there is no new drugs available in the pipeline. The use of humanized mouse model to study P. vivax has constituted a major breakthrough and revolutionized the way to test drug and vaccine’s efficacy in laboratory.

 

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LAMP for Rapid Malaria Diagnosis

LAMP for Rapid Malaria Diagnosis

28th February, 2018,Assoc. Prof. Dr. Wang Nguitragool

At MVRU, we have been working on new ways to diagnose malaria. We were one of the first research groups to apply Loop Mediate Isothermal Amplification (LAMP) to detect malaria parasites. This technology works by amplifying the target DNA molecule at a single temperature, thus requiring simple instrumentation while maintaining very high detection sensitivity comparable to PCR. Our LAMP assays were created in response to the need of quick and easy diagnosis in the remote sites in Thailand. Thousands of blood samples have been tested to validate the assays. All types of human malaria parasites can now be detected and differentiated. These tools have helped us find low-density asymptomatic malaria carriers in our study areas.

Our LAMP assays are simple. It can be performed with minimal staff training and equipment. All human malaria parasites are readily detected by our assays. The assays have been field evaluated in many places in Thailand and Korea. LAMP assays have revolutionalised malaria detection by enabling rapid, accurate and sensitive parasite diagnosis.

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Epidemiology and Transmission of Residual Malaria in Thailand

Epidemiology and Transmission of Residual Malaria in Thailand

The world is trying to eradicate Malaria. Countries in Asia pacific aims to eliminate malaria from the region by 2030. A key challenge to achieve this aim is the remaining large number of asymptomatic carriers, local endemic residents who are infected by malaria parasites but do not suffer acute malaria symptoms. Unaware of their silent infection, most people do not seek anti-malarial treatment and become the source of parasites that can be transmitted to others including naïve travellers. Understanding the behavioral and demographic factors that underlie asymptomatic malaria infection will help policy makers identify individuals under high risks for proper intervention.

Over the past several years, we have been conducting malaria mass blood and vector surveys in several hot-spot areas along the Thai-Myanmar border. Our field sites run from villages of northern Tak province to rubber plantations in southern Ranong province. Both cross-sectional and cohort study designs are used to precisely track malaria infections in human and their evolution over time. Mosquito captures are used to understand the seasonal dynamics of mosquito population as well as to identify the major malaria vectors in the study areas. These studies are also conducted in association with questionnaires developed to extract help identify groups of people who are under highest risk of malaria infection and to determine the effectiveness of interventions currently used in the country such as bednets and indoor residual sprays.

We have found that the vast majority of all malaria infection in the endemic area is asymptomatic and that P. vivax has undoubtedly become the most common parasite in Thailand. Anopheles minimus and Anopheles maculatus are the main malaria vectors. The wealth of data that we have accumulated over the past decade have helped us determine the hot spots of malaria infections and identified people who are most likely the silent parasite carriers. Whereas ethnic differences exist across our study populations, the major risks factors identified are constant. Importantly, we found strong association between indoor residual spraying with a reduction of malaria infection. We thus fully support the continuation of this intervention in the national malaria program.

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In collaboration with:
Liwang Cui, Professor, University of South Florida
Guiyun Yan, Professor, University of California Irvene
Ivo Mueller, Professor, Walter + Eliza Hall
Ingrid Felger, Professor, Swiss THP
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Transmission Blocking Vaccines for Vivax Malaria

Transmission Blocking Vaccines for Vivax Malaria

The MVRU team and its partners have been a pioneer in discovering and testing new candidates for malaria transmission blocking vaccines (TBVs). These vaccines aim to interrupt transmission of malaria parasites from an infected individual to mosquitoes. Utilizing laboratory reared An. dirus, a Southeast Asian vector of malaria, and malaria infected blood from volunteers, we have been evaluating TBV candidates since 1998 and participated in a clinical Phase I study for the most advanced candidate Pvs25. Together with Mahidol Oxford Research Unit (MORU), we are in the process of initiating the first Controlled Human Malaria Infection study for Plasmodium vivax in a malaria endemic country.

Our works have contributed to down selection of key candidates for P. vivax malaria TBV. Using mosquito membrane feeding assays (MFA), we have shown that several candidates (Pvs25, Pvs28, Pvs45/58, Pvs230, AnAPN1) can significantly reduce malaria infection of mosquito. In some cases, man-to-mosquito transmission of the parasite can be blocked completely. Our works have provided key vaccine efficacy data essential for advancing vaccine candidates to clinical trials.

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