Powerful Sequencing Tool Helps Identify Infectious Diseases in Mali

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Powerful Sequencing Tool Helps Identify Infectious Diseases in Mali

An advanced diagnostic tool used in an observational clinical study in Bamako, Mali, helped identify infectious viruses in hospital patients that normally would have required many traditional tests. Scientists, led by the National Institute of Allergy and Infectious Diseases (NIAID), designed the study to help physicians identify the causes of unexplained fever in patients and to bring awareness to new technology in a resource-limited region.

Because malaria is the most common fever-causing illness in rural sub-Saharan Africa, most medical workers in the region presume patients with a fever have malaria. But recent NIAID work has identified dengue, Zika and chikungunya viruses – like malaria, all spread by mosquitos – in some Malian residents.

The observational study of 108 patients, published recently in The American Journal of Tropical Medicine and Hygiene, added the advanced diagnostic test, known as VirCapSeq-VERT, to traditional testing methods to identify cases of measles, SARS-CoV-2, HIV, and other viral diseases in patients. Surprisingly, more than 40% of patients were found to have more than one infection.

VirCapSeq-VERT is the virome capture-sequencing platform for vertebrate viruses, a powerful DNA sequencing technique capable of finding all viruses known to infect humans and animals in specimens, such as plasma. VirCapSeq-VERT uses special probes that capture all virus DNA and RNA in a specimen, even if the researcher does not know which specific virus to look for. Scientists then sequence the captured DNA and RNA to identify viruses present to solve the mystery of which viral infection(s) a patient has.

In the study, the researchers recommend that combining VirCapSeq-VERT with traditional diagnostic tests could greatly assist physicians “in settings with large disease burdens or high rates of coinfections and may lead to better outcomes for patients.”

Scientists from NIAID’s Division of Clinical Research collaborated on the project from July 2020 to October 2022 with colleagues from the University of Sciences, Techniques, and Technologies of Bamako, Mali, and Columbia University.

Reference: A Koné, et al. Adding Virome Capture Metagenomic Sequencing to Conventional Laboratory Testing Increases Unknown Fever Etiology Determination in Bamako, Mali. The American Journal of Tropical Medicine and Hygiene DOI: https://doi.org/10.4269/ajtmh.24-0449 (2024).

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Evaluation of the Protective Efficacy of TV003 or Previous Zika Infection Against Infection With ZIKV-SJRP Challenge Compared to DENV and ZIKV-naïve Controls Against Infection With ZIKV-SJRP Challenge

The goals of this study are to find out if people who have already been infected with one type of Zika virus (ZIKV) can get infected with ZIKV a second time, and to test the ability of the TV003 dengue vaccine to prevent people from getting infected with the ZIKV-SJRP challenge virus.

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Office/Contact: Aislinn Woody, B.S.N., R.N.
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Evaluation of Two Zika Viruses for Use in Controlled Human Infection Models (CHIM)

The purpose of this study is to evaluate the clinical and virologic response to escalating doses of 2 different ZIKV strains administered subcutaneously in healthy, ZIKV and DENV-naïve, male and non-pregnant, female adult volunteers to identify the most suitable ZIKV strain and dose for use in a ZIKV CHIM.

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Office/Contact: Ruby Pritchett
Phone: 410-955-2791
Email: rpritch1@jhu.edu
 

New Research on Mosquito Odorant Receptors Advances Understanding of Feeding Behaviors

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NIAID Raises Awareness to Malaria-like Diseases in W. Africa

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NIAID Raises Awareness to Malaria-like Diseases in W. Africa

Dengue, Zika, Chikungunya Viruses in Mali; Disease Likely Misdiagnosed

NIAID scientists and colleagues have identified dengue, Zika and chikungunya viruses in the West African country of Mali, where health care providers likely misdiagnose patients with illness from those viruses due to unavailable diagnostic tools. Because malaria is the most common fever-causing illness in rural sub-Saharan Africa, most medical workers presume patients with a fever have malaria. The primary cause of all four infectious diseases is a mosquito bite.

Records from the Malian Health Information System show that about one-third of all patient visits to health care facilities are related to malaria, with 2.37 million clinical cases.

A new study from NIAID’s Rocky Mountain Laboratories and the University of Sciences, Techniques and Technologies in Mali aims to help spread information to medical workers about the existence of the additional viral diseases. Ideally, circulating the information will help them obtain the necessary diagnostics.

The study, published in The American Journal of Tropical Medicine and Hygiene, involved 600 residents, 200 from each of the southern Malian communities of Soromba, Bamba and Banzana. The scientists detected antibodies to dengue virus in the blood of 77.2% of the residents tested; to Zika virus in 31.2%, and to chikungunya virus in 25.8%. They detected at least one of the three viruses in 84.9% of participants, meaning just 15.1% tested negative to any of the three viruses.

Evidence of the parasites that cause malaria was found in 44.5% of those tested. Unlike malaria, however, where most cases are found in children under age 14, residents over age 50 were most likely to have been exposed to dengue, Zika or chikungunya viruses. 

“Despite the high exposure risk to dengue virus in southern Mali, dengue fever cases have rarely been reported,” the researchers write. “This is likely due to the lack of diagnostic testing and the biased clinical focus on malaria in the region. Awareness of dengue virus as a cause of febrile illness needs to be urgently established in medical communities as an important public health measure.”

The scientists are hoping data from a more in-depth clinical study that just ended will provide additional details about the prevalence of these viruses in Mali. They also are planning to examine patients who have undiagnosed fevers to establish infection rates.

NIAID scientists are investigating dengue, Zika and chikungunya viruses to try and develop preventive and therapeutic treatment options, none of which exist.

Reference: S Bane, et alSeroprevalence of Arboviruses in a Malaria Hyperendemic Area in Southern MaliThe American Journal of Tropical Medicine and Hygiene DOI: 10.4269/ajtmh.23-0803 (2024).

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New Synthetic Biomarker Technology Differentiates Between Prior Zika and Dengue Infections

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How Does Zika Virus Replicate and Transmit from Mother to Fetus?

NIAID and Cuban Scientists Gather to Discuss Global Health Challenges

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Recent arbovirus outbreaks – specifically dengue, chikungunya, and Zika in the Americas – led NIAID and the Instituto de Medicina Tropical “Pedro Kouri” in Cuba to co-host a joint scientific meeting on Addressing Global Health Challenges Through Scientific Innovation and Biomedical Research. The meeting was held Feb. 14-16 in Havana.

The arbovirus cases, atop the COVID-19 pandemic, are reminders that emerging and re-emerging infectious diseases can quickly become research priorities and pose global health threats.

Though infectious disease was prominent in conference discussions, the scientific agenda sought to highlight biomedical research areas of mutual and global priority. These topics are becoming increasingly interconnected in the U.S. and worldwide. As such, the conference brought together researchers to review current science and discuss ways to develop effective interventions to control epidemics in the Americas and globally. 

The bilateral technical scientific research meeting convened subject matter experts on infectious and non-communicable diseases, including arboviruses, pandemic preparedness, cancer, neurological disorders, and long-term health concerns. The agenda also included cross-cutting biomedical research areas, such as immunology, genomics, and precision medicine.

The Cuban Academy of Sciences (ACC) provided a meeting highlight by honoring two U.S. scientists for their longstanding and innovative contributions to global arbovirus and neurological disorders research. Each scientist was granted the designation of Corresponding Academic to the ACC.

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NIH Awards Priya Shah $2.8 Million to Research How Zika Virus Causes Brain-Related Birth Defects

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World Mosquito Day 2023—How Mathematical Modeling Reveals the Link Between Climate Change and Mosquito-Borne Diseases

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Mosquito-borne diseases include some of the most important human diseases worldwide, such as malaria and dengue. With global temperatures increasing because of climate change, mosquitoes and the pathogens they transmit are expanding their range. For example, the Centers for Disease Control and Prevention recently reported a number of malaria and dengue cases transmitted within the United States in Texas and Florida. Therefore, it has become more urgent to understand the interactions between climate, mosquitoes, and the pathogens mosquitoes transmit to humans.

The National Institutes of Health (NIH) Climate Change and Health Initiative is a collaborative effort across NIH Institutes and Centers to reduce the public health impact of climate change. As part of the Initiative’s Scholars Program, NIH brings climate and health scientists from outside the U.S. federal government to work with NIH staff to share knowledge and help build expertise in the scientific domains outlined in the Initiative’s Strategic Framework. 

Luis Chaves, Ph.D., is a 2023 Scholar working with NIAID. Dr. Chaves is an associate professor in the Department of Environmental and Occupational Health in the School of Public Health-Bloomington, Indiana University, and was previously an associate scientist at the Instituto Gorgas in Panama. His research focuses on understanding the impacts of environmental change on the ecology of insect vectors and the diseases they transmit. Over the last 20 years, he has combined field studies and modeling approaches, both statistical and mathematical, to address how insect vectors respond to changes in the environment and how these changes impact the transmission of diseases, such as malaria and dengue. NIAID spoke with Dr. Chaves about his work. 

Note: responses to the questions have been edited for clarity and brevity.

In what ways have you seen climate changes impact vectors and disease transmission?
There is very strong evidence that climate change has affected vector-borne diseases. This includes mosquito-borne diseases, like malaria and dengue, but also other diseases like leishmaniasis, which is transmitted by sandflies. Changes in temperature and rainfall affect the spread of disease vectors and impact their breeding behavior. For example, there is evidence of the impact of El Niño weather events on malaria transmission. Higher temperatures and more rainfall make a more suitable habitat for mosquito breeding, causing an increase in disease transmission. In other areas, El Niño weather patterns are associated with droughts, which may reduce disease transmission but cause food shortages. These weather patterns have been known and studied before, but climate change has generated more extreme conditions resulting in more extreme weather events. So, we can see that there is robust evidence that climate change is having a massive impact on human health and wellbeing.


What sparked your interest in examining how socio-economic conditions impact vector-borne disease transmission and control? 
I remember the first encounter I had with Chagas disease was visiting an uncle who lived in a rural setting. I was told not to visit a neighbor’s house because they had Chagas disease. There were lots of discussions about how his neighbor got Chagas because his home was made from mud, which is why kissing bugs, the vectors of Chagas disease, got inside. That was the first time I observed an increased prevalence of diseases in places with social exclusion and poverty. More generally, infectious diseases cannot be put out of the social and economic context where they emerge and are transmitted. If you have people with substandard housing, is that a choice, or a constraint because of the underlying socio-economic inequities? It is impossible to learn about the ecology of disease transmission without understanding that the ecology of transmission is not only ecological and environmental but also social. 


What are the advantages of using mathematical modeling to study vector-borne diseases?
Mathematical and quantitative modeling have been incredibly useful to expand the ways in which the relations shaping disease patterns can be studied This ability to understand interactions advances our capacity to engage in more relational science, where factors aren’t understood as fixed and independent forces, but as dynamic and interdependent. Relations between variables can’t be described by a fixed constant proportion, but by nonlinearities that can be easily grasped by machine learning algorithms and other data science tools.  Computers have made it easier to collect, process and analyze larger datasets. The automation of data assimilation using pipelines that integrate different data sources and algorithms can lead to robust “boosted” predictions about where and when to expect the transmission of some vector-borne diseases. Mathematical models also show how the stability of natural systems can collapse following small changes in the environment, and that has clear implications about why we need to worry as climate change continues its current course.   


What limitations do you see in the use of data science?
Data science poses ethical dilemmas, because not everyone mining freely available data is likely to do so with altruistic aims, nor is it clear how communities and individuals could benefit from the data they generated when someone profits from that or how communities, and even individuals, are protected from potential misuse.  I also think there is a need to always consider the context in which data are generated, as this approximation allows us to see what else is out there. The more nuanced our knowledge is, the more likely we can generate actionable knowledge that improves human health and wellbeing. That’s why it’s so important to include information on how data is collected (metadata) and how to use it.  The nuances don’t come from just looking at the data. They require experience, observation, and immersion in nature to create a clearer picture of vector-borne disease transmission. 


How has your work influenced vector control and prevention activities?
My research at the Costa Rican Institute for Research and Training in Nutrition and Health’s (INCIENSA) and the Costa Rican Vector Control Program was centered around developing insect vector maps and training people working in vector control about the impacts of climate change. This also involved evaluating past policies and their impact on parasitic and neglected tropical diseases. For example, comparing how different public health strategies like Mass Drug Administration versus vector control might impact malaria transmission and elimination. These activities increased the awareness about the importance of climate change, particularly among vector control inspectors, with whom I interacted closely on their work.  My research has also supported a focus on Mass Drug Administration as a major tool to eliminate malaria in Costa Rica.


What impact do you hope your research will have?
I’ll be happy if my research can serve, at least, the communities where the research is being done. As long as my research can lead to diminishing transmission of infectious pathogens or reducing the populations of vectors, then I will be happy. If that eventually leads to the elimination of those diseases, I’ll be even happier. I want to be able to provide resources for the local communities, so they can understand health problems or health threats within their local environment. For example, one of the nicest experiences I have had as a researcher was in Panama, where at least three or four studies on leishmaniasis have been done in the same community. In that community, we have seen how people come up with their own solutions, partly based on what they learn from when you did research in that location. You see how they modify their houses and look for changes in incidence of new cases. When they tell you that cases of leishmaniasis have gone down, that newborns and children aren´t getting the disease, that is very fulfilling.                     

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