Thailand Rhoel Dinglasan
ScM Program, Department of Molecular Microbiology and Immunology, JHSPH
Malaria remains a global public health burden. Mosquito resistance to insecticides and parasite resistance to anti-malarial drugs necessitate new approaches to curb infection and transmission. One promising strategy of reducing malaria transmission is through a malaria transmission-blocking vaccine (TBV). Antibodies specific for an alanyl aminopeptidase (APN1) present on the midgut surface of several malariatransmitting mosquito vectors in the Anopheles genus have demonstrated impressive ability to block malaria parasites from invading the mosquito midgut, implicating APN1 as a promising target for a transmissionblocking vaccine antigen. However, natural parasite polymorphisms in endemic regions may limit the utilty of such TBVs that were tested against laboratory strains. In ex vivo field trials in Cameroon, anti-APN1 antibodies (IgG) exhibited sterile blocking (100%) against naturally circulating isolates of the malaria parasite Plasmodium falciparum. It is currently unknown whether anti-APN1 IgG inhibits invasion of the species Plasmodium vivax, the primary cause of malaria in South America and Southeast Asia. The goal of this project is to evaluate whether anti-APN1 IgG is effective against the malaria parasite species P. vivax and if it maintains efficacy against genetic variants of P. falciparum that have evolved in other regions of the globe. Transmission-blocking assays using the anti-APN1 antibody will be performed against Thai isolates of P. falciparum and P. vivax in Maesod, Thailand. Subsequently, genetic analysis of Plasmodium isolates will be conducted to allow for further investigation of the limits of the transmission-blocking activity of anti-APN1 IgG by members of the Dinglasan Laboratory. Personal Abstract:
“Why are you studying malaria, why not study Alzheimer’s?” a Thai man asked me in in Thon Pha Phum, a mountain town about two hours north of my field site. I laughed a little as I considered this question, ‘why not Alzheimer’s?” I assured him that I considered Alzheimer’s a worthy subject of study, and said “Well, malaria kills a lot of children who don’t even have the chance to grow old enough to be at risk for Alzheimer’s.” “Oh, you mean in poor countries, like Africa? Malaria is not a problem here in Thailand,” he said. In a sense, he’s right. Malaria is not a problem for most Thai people – those living in cities, or even towns. Since the Thai government created malaria clinics that continue to offer free diagnosis and prophylaxis since the worldwide malaria eradication in the 1950’s, the prevalence of malaria has reduced significantly throughout the country. Furthermore, the primary Thai malaria-spreading mosquito species, Anopheles dirus and Anopheles minimus, prefer heavily forested habitats with dense foliage, not exactly a typical city environment. Yet there continue to be endemic regions, and every year certain communities in these regions are infected time and again without fail. “Why is that?” I wondered. I began to understand the subtleties of these infection dynamics as I scoured the patient demographic data on the walls of the free clinics, waiting for an infected patient to come in. Certain occupations and populations seemed to have infection rates 10-fold higher than others. As I inquired about the numbers, the complex interconnection between Thai society and economics began to unravel before my eyes. Unsurprisingly, the most reproducible pattern was high infection rates of Burmese immigrants that travel to Thailand for better work and health services. Yet I also saw higher rates in farmers than monks, although both populations live close to wooded areas, and not just any kind of farmer – only the farmers in the category of ‘other.’ No one seemed to be exactly sure what this category was – some of the Thais thought it may be laborers who work on many farms, but not one particular farm. Others thought it could be farmers of fruits and vegetables. One entomologist I spoke with told me his theory was that the infection rates of the ‘other’ category were due to the newly emerging rubber industry in Thailand. Investors from the south have begun buying wooded areas in the eastern part of the country, cutting down forests and starting rubber farms (Picture 5). Rubber has recently become more lucrative than the previous crop, cassava. When this happens, deforestation displaces the Anopheles mosquito species that carries malaria, and gives them a perfect replacement home right next to human hosts: rubber trees. The moist environment and dense foliage that rubber trees provide are ideal for an Anopheles mosquito species habitat. Furthermore, this practice employs lumberjacks to cut down trees in the forest, putting these workers at risk for contracting malaria as well. Indeed, the malaria rates among lumberjacks were some of the highest in the region. Not to mention the environmental damage caused by deforestation, and the devastation on the local ecosystem from the poisonous rubber tree leaves that prevent plants from sprouting up in their environs. Yet the highest malaria rates in Thai people were in a livelihood that I had never before considered – people who make their living by finding miscellaneous items in the forest and selling them. This could be anything from bamboo shoots and precious wild mushrooms to old junk that somehow ended up along their path. Interestingly, these people explained the infection dynamics more than any other local population. We see spikes in infection just after it rains, because these scavengers wait for it to stop raining to go out into the forest, where they get infected. Living in a developed country, it is difficult to even fathom that kind of lifestyle, why do these people put themselves at risk over and over again to look for anything they can find? Because Thai people buy bamboo shoots, wild mushrooms and even pieces of junk. Just like so many problems in developing countries, transmission dynamics can be explained by a combination between societal customs and economics. And why do we foreigners care about this small population in Thailand – the Burmese immigrants, the rubber farmers and the forest scavengers – that keep going back into the forest and getting sick every year? Unfortunately Thailand is known as the ‘hotbed of resistance.’ It is where anti-malarial resistance has appeared over and over again in the past 60 years, beginning with chloroquine resistance in the 1950’s that later spread throughout Africa, up to recent reports of increased tolerance of Artemisinin. Although we cannot fully explain this phenomenon, we know there must be something about the transmission dynamics of the area that make it conducive to the appearance of drug resistance threatening malaria control everywhere. I was truly inspired by my first-hand discoveries of how the nuances of Thai society impact disease transmission patterns in Thailand and throughout the world. I now understand more than ever that malaria is not an easy problem to solve: it requires a comprehensive expertise of the biology, ecology, epidemiology, history, tradition and economics of each transmission region. Yet with the right tools and knowledge, I believe that it can be conquered and this experience has made me all the more committed to being a part of the battle. Photo Album:  | Preparing the Lumsum Malaria clinic for opening in Kanchanaburi, Thailand. |  | ‘Farm’ (a research technician in the Sattabongkot Prachumsri laboratory) draws infected Plasmodium vivax blood from a clinic patient at the Lumsum clinic. |  | Mosquitoes feeding on warmed blood infected with malaria, and mixed with the APN1 transmission-blocking vaccine candidate. |  | Mosquito collectors in the Ban Thon Ma Muang district in Kanchanaburi, Thailand. |  | Harvesting from rubber trees in Ban Thon Ma Muang district in Kanchanaburi, Thailand. The rise of rubber plantations is thought to have produced an increased malaria incidence due to the replacement of local forests with rubber trees, which create ideal environments for mosquito populations. |
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