ANALYSIS
Scientific and Medical Impacts of Genomic Tools
Genomic and genetic analysis tools have promising scientific and medical applications for combating parasitic diseases.
The recent publications of the genome sequences for the P. falciparum parasite, its vector and its human host have set the stage for researchers to perform genome-wide studies of malaria disease pathogenesis. Genomic and genetic analysis tools represent the technological advances needed to achieve this goal. They enable researchers to extract, analyze, and interpret genomic data in a cost-effective and high-throughput fashion.
These tools have significantly improved our understanding of the basic biology and microbiology of the malaria parasite. Post-genomic research on the genetic diversity between strains of P. falciparum has allowed scientists to identify drug sensitive and drug resistant strains of parasite. Such research and information may help guide diagnostic test research, identify critical mechanisms for protective immunity, and contribute to identifying targets for malaria vaccine development. Genetic analysis tools can also be used for drug resistance surveillance and epidemiological studies which will inform public health policy recommendations regarding drug treatment regimens.
The background section of this website presents a summary of recent advances in genomic research for the P. falciparum parasite, with a particular emphasis on genetic variation associated with drug resistance. It is important to note that this research represents only a fraction of the genomic research that is currently ongoing in the malaria scientific community. A significant body of literature exists regarding genetic variation within the mosquito vector, Anopheles gambiae, and its impact on malaria disease pathogenesis. For example, discovery-based research in the Anopheles vector is aimed at identifying potential gene targets for insecticide resistance. Many of the same genetic analysis tools that are used for P. falciparum experiments are applicable to the study of the Anopheles genome.
In summary, a new research paradigm has emerged during the postgenomic era. The availability of annotated, genome sequences for parasites of public health importance, their vectors and the human host sets the stage for significant advancements in parasitic research. Efforts are currently underway to sequence the genomes of parasites involved in toxoplasma (Toxoplasma gondii), cryptosporidiosis (Cryptosporidium hominis), amebiasis (Entamoebahistolytica), African sleeping sickness (Trypanosoma brucei), and schistosomiasis (Schistosoma mansoni), among others.
Genetic analysis tools, which can be used for discovery research, diagnostic applications, and genetic surveillance efforts, can be universally applied to the study of these parasitic diseases. Knowledge gained from the use of genetic analysis tools can drive the scientific community toward a clearer understanding of parasitic disease pathogenesis and stimulate the development of effective public health approaches toward the treatment and prevention of parasitic diseases.
Challenges and Issues - Can genomic tools be used in the developing world?
In order to obtain the full-benefit of genomic tools, a well-established scientific infrastructure is necessary. Observations of Africa’s current fledgling health systems reveal challenges to implementing genomic tools in endemic countries with nonexistent or emerging scientific infrastructures. The African clinical laboratory system is comprised of large, centralized national laboratories, district hospitals and periphery clinics. Non-governmental organizations, such as the African Medical and Research Foundation (AMREF), help to support the national laboratories. For example, AMREF staffs a central laboratory in Nairobi, Kenya, and also helps to perform Quality Assurance testing for district hospitals and dispensary (periphery) clinics. At the district level, a small number of doctors and physicians often serve a wide region of the community. Periphery clinics do not contain laboratories and might consist only of one nurse who is able to do rapid diagnostic tests. These “bush” facilities often contain rudimentary facilities and lack staff with formal training.
Challenge 1: Cost
An initial challenge of the use of these genomic tools in developing countries is the cost issue. Certain genomic and genetic analysis tools, such as microarrays, require up-front infrastructure, equipment and supply expenses. Many resource-poor research laboratories therefore cannot afford or use these tools. Nevertheless, one possible solution to alleviate costs is offered by the Malaria Research and Reference Reagent Resource Center (MR4). MR4 remarkably provides quality-controlled malaria-related agents to the international malaria research community. Endemic laboratories in developing countries may receive materials and resources, such as oligonucleotides and antibodies that are hard to produce locally, at no cost(33). Such open sharing of material may be of great value to resource-poor researchers.
Challenge 2: Under-equipped facilities
The use of genomic tools may also be impractical for many under-equipped laboratories in Africa. Many district and remote facilities lack running water and refrigeration. Taking extreme heat of the environment into consideration, it is impractical to use genomic tools that depend on thermo-sensitive genetic reagents. Given such shortcomings of in-country scientific infrastructure, the solution to this challenge is strategic placement in the use of genomic tools. Genomic tools have the most value for centralized clinical laboratories that have necessary resources to maintain these tools. More tools may be implemented in lower laboratories as scientific and health infrastructures develop.
For example, the AMREF-sponsored central laboratory in Nairobi, Kenya holds great promise for the use of genomic and genetic analysis tools. This laboratory is well-equipped to perform public health research and is one of the more sophisticated labs in Africa. In addition to performing tests for Kenya, this laboratory also serves as the public health reference lab for Southern Sudan and Somalia, regions and governments that lack adequate public health systems with the capacity for scientific research.
Recently, the AMREF-sponsored central laboratory in Nairobi received a PCR machine as part of a significant $60,000 investment. Such an open reception to a relatively basic genomic tool reveals how much developing countries desire and need higher scientific technology. Nevertheless, it also suggests that more expensive and sophisticated genomic tools such as microarrays are impractical and unfeasible, given current conditions. The fact that it was a significant event for the central laboratory to receive its first PCR machine underscores the current challenges facing the use of genomic tools for discovery research in peripheral or even district facilities.
With the ever increasing rise of drug costs and drug resistance, it becomes all the more necessary to be able to diagnose the specific strains of malaria in individuals. However, genomic tools are impractical for field diagnostics because they are not affordable and are not equipment-free, which are shortcomings according to the ASSURED ideal diagnostic test criteria(34). According to Dr. Sarah Volkman, more useful tests in remote areas are conventional rapid diagnostic tests such as dipsticks or blood smears.
These tests are more suitable to village level diagnosis than laboratory-based tests, since not all patients return to receive lab results. On the other hand, as mentioned in the Background section, genomics can be used to identify novel diagnostic targets for use in diagnostics development(34). As mentioned before, genomic tools can be used for understanding pathogens, and therefore they are more useful for discovery research in central laboratories, rather than field diagnostics in the periphery.
Challenge 3: Open access to scientific information
Central laboratories in malaria endemic countries have the potential to conduct significant and relevant malaria research. For genomic tools to be useful in these laboratories, another challenge to address is ensuring its open access to scientific information. Traditionally, there has been limited collaboration between endemic (Africa) scientists and domestic (U.S.) scientists on a research level. Many past global health programs have taken the paternalistic approach of industrialized countries making scientific and health decisions for developing countries from the outside(35). Nevertheless, such a trend may be reversed since data obtained from genetic analyses can be published publicly on PlasmoDB, which hosts genomic and proteomic data for different species of the Plasmodium parasite. The site serves as a central, publicly available repository for data from numerous international and domestic laboratories. Publicly available genomic information and resources may help to stimulate research collaborations between domestic groups and scientists from endemic countries, which may encourage more local scientists to be involved in tackling malaria.
Challenge 4: Training and sustainability
For the genetic tools to be used properly, another challenge to address is the training of personnel. Genomic tools, data, and resources may be useless if developing countries do not have the research capacity and the human resources to receive such technology. Insufficient training that plagues district and periphery clinics becomes an obstacle for effective use of genetic tools and resources. Receiving free genomic tools and information through MR4 is a critical first step toward addressing the training gap issue for endemic country scientists and laboratory personnel. MR4 also offers training on technology platforms and laboratory techniques which is designed to help local scientists strengthen their scientific infrastructure.
Although partnerships between industrialized nations and developing countries may be established through outside investments, more scientific analysts recently have shifted the focus to the issue of sustainability. AMREF acknowledges the many sociopolitical factors involved in malaria and believes that strengthening health systems is “the only way to achieve long term sustainability (36).” Long-term solutions to health problems can be achieved if research capacities are built and fortified within these endemic developing countries. Trained local researchers within developing countries are better able to address indigenous public health challenges faster and more cost-effectively than if they were approached from the outside(35). These local researchers are more able to understand the cultural contexts of disease and the socio-political conditions that influence how that disease manifests in communities. These local researchers can also interact more effectively with researchers from industrialized countries, allowing better cooperation, and therefore even more effective use of MR4 resources.
While the impact of genomic and genetic analysis tools on scientific research is undisputed, the use of these tools in unequipped labs seems unfeasible and impractical since these labs will not be able to maintain them. In establishing in-country research capacity, genomic tools have the most value for centralized clinical laboratories. More genetic tools may be implemented as scientific and health infrastructures develop.