Identifying and monitoring transmission of P. vivax parasites remains a challenge in most countries that have entered the malaria elimination phase.
The goal of this project is to identify and validate serological markers of recent P. vivax infections. Such markers would allow more rapid and accurate evaluation of the impact of control and elimination measures. An added clinical benefit is the potential ability to identify carriers of latent forms of P. vivax parasites that can linger in the liver and cause relapses.
Between 2015 and 2017, FIND coordinated the activities of several partners who profiled the immune responses of a large panel of P. vivax malaria patients from Papua New Guinea, Brazil and Thailand. This permitted the identification and validation of markers of recent infection, which enabled the development of serological tests for P. vivax malaria. FIND also led a consensus-based process to develop target product profiles for diagnostic tests that will use these new biomarkers, and will conduct a technology landscape assessment as well as a market analysis on the use of such tests.
Low-density infections have been shown to significantly contribute to the ongoing transmission of malaria, especially in areas approaching elimination. The development of a highly sensitive malaria test, able to detect the very low levels of parasites found in asymptomatic individuals, is a priority.
In collaboration with a wide network of partners, FIND is establishing and maintaining a large repository of frozen whole blood specimens from asymptomatic individuals infected with Plasmodium falciparum parasites, as well as specimens from uninfected individuals collected in the same areas.
While this unique repository is being built, additional reference material is already being made available. This includes whole blood samples spiked with low densities of cultured P. falciparum parasites—a unique resource for researchers and test developers.
In addition, FIND and partners are producing standardized histidine-rich protein 2 (HRP2) recombinant proteins. HRP2 is secreted by P. falciparum parasites and is therefore a good marker of malaria infection.
The goal of these efforts is to make a common source of standardized specimens and HRP2 recombinant proteins available to malaria researchers and test developers. The reference materials can be used to assess the performance of prototype high-sensitivity tests and to calibrate currently available HRP2-detecting tests. The reference materials have already been used to assess the new high-sensitivity rapid diagnostic test for malaria (see link below).
- First-Ever Rapid Test to Screen for Malaria Infections in Asymptomatic Individuals, launched on World Malaria Day 2017
Loop-mediated isothermal amplification (LAMP) is a simplified DNA amplification technique that combines the high sensitivity of molecular diagnostic tools with minimal laboratory infrastructure requirements.
A commercially available LAMP-based diagnostic kit for the detection of Plasmodium falciparum exists, but no such kit is currently available for the identification of P. vivax, which requires a specific treatment course for cure, complicating the use of existing LAMP-based solutions in countries endemic for this species of malaria parasite.
To address this limitation, FIND is working in partnership with Eiken Chemical Co., Ltd. on the development of a P. vivax-specific LAMP kit that could be integrated with existing LAMP kits.
Prototype kits have shown excellent laboratory performance with analytical sensitivity and specificity matching those of marketed kits. A field study is currently ongoing in Columbia to confirm these performances in an endemic clinical setting. Results will be available shortly.
Fever is the most common symptom of infectious disease. The increased use of malaria rapid diagnostic tests has shown that less than half of fever cases in malaria-endemic countries are caused by malaria infections.
Simple tests adapted for use at the point of care are needed to quickly identify the cause of fever, treat appropriately and avoid the unnecessary use of antimalarial medicines or antibiotics.
Chembio Diagnostics, Inc., has developed a multiplex point of care diagnostic test capable of detecting seven different pathogens that cause febrile illnesses – some of them with outbreak potential. The test can detect the four malaria species that infect humans (Plasmodium falciparum, P. vivax, P. malariae and P. ovale) and six viruses: dengue, Zika, chikungunya, Ebola, Marburg and Lassa.
FIND conducted a clinical trial in Nigeria and Peru to evaluate the performance of this test for detecting malaria parasites in endemic settings at the point of care.
Results have been shared with Chembio Diagnostics Systems, Inc. with the goal of seeking regulatory approval (including FDA approval) in various countries for the malaria component of the test, to make the test available in areas of need.
With the expansion of molecular methods for malaria detection and renewed emphasis on malaria elimination, in 2013 the World Health Organization (WHO) recommended establishing an international external quality assessment (EQA) scheme for nucleic acid amplification (NAA) assays.
An EQA scheme would ensure that the data resulting from NAA assays are reliable and comparable, and can support policy development.
With the support of FIND, WHO and the UK National External Quality Assessment Service (UK NEQAS) have launched the WHO Malaria NAA EQA scheme, targeting public health and research laboratories in malaria endemic and non-endemic settings.
Since January 2017, four rounds of distribution of lyophilized blood samples and dried blood spots derived from in vitro cultures and clinical samples have been completed. Participants include 57 laboratories from 32 different countries, with 19% of laboratories located in Africa, 25% in Asia and South-East Asia, and 21% in South and Central America, and the remainder (35%) in Europe and North America.
FIND is coordinating the activities of several partners around the world to support the development of new diagnostic tools to improve the detection and treatment of sub-microscopic malaria infections during pregnancy.
Malaria during pregnancy is an important public health issue in endemic countries. Although most cases of malaria in pregnant women are asymptomatic, these subclinical infections can contribute to adverse effects, such as maternal and neonatal anaemia, and low birth weight.
Subclinical infections – particularly in low-transmission settings – are difficult to diagnose during pregnancy because of the sequestration of malaria parasites in the placenta, and their subsequent circulation at sub-microscopic densities in peripheral blood.
Read more about our ongoing work in malaria and pregnancy here.