The construction of dams and irrigation of arid areas have been a boon to rice farming in Ethiopia. While enhancing food productivity and economic development, such environmental modifications could have unforeseen detrimental effects on malaria transmiss

Credit: Guiyun Yan/UC Irvine

The construction of dams and irrigation of arid areas have been a boon to rice farming in Ethiopia. While enhancing food productivity and economic development, such environmental modifications could have unforeseen detrimental effects on malaria transmission and epidemiology.

Despite advances, malaria remains a leading global public health concern, with an estimated 212 million new cases and 429,000 deaths occurring in 2015.

In an effort to improve malaria control worldwide, University of California researchers have been awarded up to $25 million from the National Institute of Allergy & Infectious Diseases, a part of the National Institutes of Health. Of seven grants awarded, three went to UC campuses:

  • UC Irvine will receive up to $9.6 million over seven years to study the impact of environmental changes on malaria in sub-Saharan Africa.
  • UC San Diego will receive up to $8.3 million over seven years to continue to build upon malaria research efforts of the previous seven years in Amazonia.
  • UC San Francisco will receive up to about $7 million over seven years to build on previous research that has informed new guidelines to antimalarial care throughout Africa, enabling thousands of children and pregnant women to live malaria-free.

The funding establishes UC Irvine as one of the International Centers of Excellence for Malaria Research (ICEMR), which will engage in projects in Africa, Asia and Latin America. Guiyun Yan, professor of public health, leads the UC Irvine project.

“Knowledge gained from this ICEMR will be important to malaria control, not only for the two countries studied – Ethiopia and Kenya – but also for other regions of Africa,” Yan said.

He added that the overarching goal of UC Irvine’s ICEMR is to assess the effect of human-induced environmental modifications – such as dam construction, irrigation and shifting agricultural practices – on the epidemiology and transmission of malaria. Because of food insufficiencies, major investments have been made in water resource development in highly populated Kenya and Ethiopia.

Partnering internationally

To address the major knowledge gaps and challenges in malaria control and elimination in the face of drastic environmental changes in sub-Saharan Africa, the UC Irvine ICEMR is establishing a consortium with researchers from the U.S., Australia, Kenya and Ethiopia to explore scientific questions important to global anti-malaria efforts, especially in Greater Horn of Africa countries.

The ICEMR has three projects, each with multiple specific objectives:

  • Gauge the impact of environmental modifications related to water resource development on malaria epidemiology at the molecular, individual, field and population levels.
  • Examine the ramifications of environmental changes on vector ecology and transmission, the outcomes of which will inform innovative integrated vector control approaches.
  • Determine the effect of environmental modifications on malaria pathogenesis and immunity.

Expanding drug discovery efforts

Joseph Vinetz, professor of medicine and tropical disease specialist at UC San Diego School of Medicine.
Credit: UC San Diego

The Amazonian Center of Excellence for Malaria Research, headed by Joseph Vinetz, professor of medicine and tropical disease specialist at the UC San Diego School of Medicine, is one of 10 ICEMR programs established in 2010, comprising a global network of research centers in malaria-endemic settings, including Africa, Asia, the Pacific Islands and Latin America.

Except for cases contracted elsewhere and brought here, malaria has largely been eliminated in the United States. In other parts of the world, however, the disease remains persistent. While progress has been made over the past decade in reducing the global disease burden from malaria, more than 3 billion people — almost half the world’s population — remain at risk, primarily in parts of Africa, Asia and South America.

The vast majority of cases are children under the age of 5 or pregnant women. As yet, there is no vaccine and the cause of the disease — a group of parasitic microorganisms called Plasmodium sp. that are transmitted to humans by the bite of an infected mosquito — evolve constantly to resist drug treatments.

Vinetz said the role and impact of the Amazonian ICEMR has been significant, with the center collaborating extensively with American, Peruvian and Brazilian researchers and institutions.

For example, researchers have worked to identify asymptomatically infected people who do not display malarial symptoms or require treatment, but who can potentially and continually infect mosquitoes. This month, the Peruvian government announced a new “Malaria Zero 2017-2021” program, led by ICEMR investigators Alejandro Llanos-Cuentas and Dionicia Gamboa, both at the Universidad Peruana Cayetano Heredia.

Indeed, another UC San Diego effort, headed by Elizabeth A. Winzeler, professor in the School of Medicine’s pediatric division of host-microbe systems and therapeutics, received a three-year, $4.7 million supplement grant from the Bill & Melinda Gates Foundation earlier this year to advance development of improved therapies for malaria eradication and elimination. Winzeler and an international research team are trying to develop new antimalarial compounds that are less likely to provoke resistance compared to existing drugs.

Vinetz and colleagues collaborate with the Winzeler group, in particular on drug discovery efforts for Plasmodium vivax based on work at the Peruvian study site.

Building on successful work

Grant Dorsey of UC San Francisco received federal funding that will allow him to research the biology of the malaria parasite.
Credit: UC San Francisco

UCSF’s renewal award will fund researcher Grant Dorsey’s project, the Program for Resistance, Immunology, Surveillance and Modeling of Malaria in Uganda (PRISM).

“We’re extremely excited,” said Dorsey, a professor of medicine in UCSF’s Division of HIV, Infectious Diseases and Global Medicine. “We feel very fortunate to continue the work we started.”

PRISM is based in Tororo, a rural town in Eastern Uganda, and its goals are to perform surveillance of malaria in order to improve understanding and to measure the impact of population-level control interventions. With the award, Dorsey aims to build upon the work of the last seven years.

“With the initial grant, we aimed to understand epidemiology of malaria,” said Dorsey. “Now, we want to understand its biology.”

To control malaria, Dorsey and his team has primarily relied on insecticide-treated bed nets and artemisinin-based combination therapy (ACTs) for symptomatic malaria. The interventions have been extremely effective in reducing the incidence of malaria.

Between 2010 and 2015, the rate of new cases fell by 21 percent globally. In the same period, malaria mortality rates have fallen globally by nearly 30 percent. Despite these gains, the burden of disease persists in “asymptomatic” malaria – a malaria infection that doesn’t result in typical symptoms like chills, fever and sweating, yet still causes harmful health outcomes.

Dorsey is particularly interested in understanding how malaria transmission – particularly of “asymptomatic” infections – continues in a setting where malaria burden has been reduced. “In Tororo (Uganda), incidences are now low, yet we still have a significant portion of people infected with malaria parasites,” Dorsey said. “We want to understand why this is.”

Despite high hopes for eradication and elimination, Dorsey anticipates challenges ahead. “Key interventions for the malaria parasite and mosquito are drugs and insecticides,” he said. “Yet the parasite and mosquito are constantly evolving to develop resistance to interventions. I hope that our understanding of how parasites are maintained in the human population will inform the development of new interventions.”