NIH-Sponsored Trial of Lassa Vaccine Opens

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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Fabiano Oliveira, M.D., Ph.D.

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Vector Molecular Biology Section

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Program Description

Our research focuses on the complex interactions between the human immune system and insect-derived molecules, and how these interactions can influence the outcomes of vector-borne diseases such as dengue, Zika, Chikungunya, and leishmaniasis. When an insect bites, it injects hundreds of arthropod molecules into the host's skin, alerting our immune system to these foreign agents. If the insect is infected with a pathogen, the microorganism is delivered along with these insect-derived molecules. Our immune response to these molecules over time can either help or hinder pathogen establishment, ultimately affecting the disease outcome.

Our work is conducted at two primary locations: the Laboratory of Malaria and Vector Research (LMVR) in Rockville, which is equipped with cutting-edge technologies, and the NIAID International Center of Excellence in Research (ICER) in Cambodia, where we conduct field observations and studies.

At LMVR-Rockville, we use advanced technologies and methodologies to explore the molecular and immunological mechanisms underlying the human response to arthropod bites and the pathogens they transmit. In Cambodia, at the NIAID ICER, we engage in extensive fieldwork to gather critical data and observations directly from affected populations. By integrating field data with laboratory findings, we aim to develop robust hypotheses that can lead to effective strategies for disease mitigation and control.

Our multidisciplinary approach allows us to bridge the gap between laboratory research and field applications. By understanding how the human immune system responds to arthropod molecules, we can identify potential targets for vaccines, therapeutics, and diagnostic tools. Additionally, our research contributes to the development of innovative vector control strategies that can reduce the incidence of these debilitating diseases.

Through collaboration with local communities, healthcare providers, and international partners, we strive to translate our scientific discoveries into practical solutions that can improve public health outcomes. Our ultimate goal is to reduce the burden of vector-borne diseases and enhance the quality of life for people living in endemic regions.

Our research aims to improve dengue prevention and treatment strategies for U.S. travelers, personnel in endemic areas, and regions with reported dengue cases, such as Hawaii, Florida, Texas, Puerto Rico, the U.S. Virgin Islands, and Guam. Enhanced predictive, management, diagnostic, and preventive measures for dengue outbreaks are particularly crucial for these at-risk regions. The development and use of prophylactic therapeutics targeting specific immune responses to mosquito bites could reduce the transmission of arboviruses, including eastern equine encephalitis, Jamestown Canyon, La Crosse, Powassan, St. Louis encephalitis, and West Nile viruses. Improved diagnostic capabilities for vector-borne diseases and emerging infections will lead to better patient outcomes. 

Selected Publications

Manning JE, Chea S, Parker DM, Bohl JA, Lay S, Mateja A, Man S, Nhek S, Ponce A, Sreng S, Kong D, Kimsan S, Meneses C, Fay MP, Suon S, Huy R, Lon C, Leang R, Oliveira F. Development of Inapparent Dengue Associated With Increased Antibody Levels to Aedes aegypti Salivary Proteins: A Longitudinal Dengue Cohort in Cambodia. J Infect Dis. 2022 Oct 17;226(8):1327-1337.

Guerrero D, Vo HTM, Lon C, Bohl JA, Nhik S, Chea S, Man S, Sreng S, Pacheco AR, Ly S, Sath R, Lay S, Missé D, Huy R, Leang R, Kry H, Valenzuela JG, Oliveira F, Cantaert T, Manning JE. Evaluation of cutaneous immune response in a controlled human in vivo model of mosquito bites. Nat Commun. 2022 Nov 17;13(1):7036.

Chea S, Willen L, Nhek S, Ly P, Tang K, Oristian J, Salas-Carrillo R, Ponce A, Leon PCV, Kong D, Ly S, Sath R, Lon C, Leang R, Huy R, Yek C, Valenzuela JG, Calvo E, Manning JE, Oliveira F. Antibodies to Aedes aegypti D7L salivary proteins as a new serological tool to estimate human exposure to Aedes mosquitoes. Front Immunol. 2024 May 1;15:1368066.

Guimaraes-Costa AB, Shannon JP, Waclawiak I, Oliveira J, Meneses C, de Castro W, Wen X, Brzostowski J, Serafim TD, Andersen JF, Hickman HD, Kamhawi S, Valenzuela JG, Oliveira F. A sand fly salivary protein acts as a neutrophil chemoattractant. Nat Commun. 2021 May 28;12(1):3213.

Oliveira F, Rowton E, Aslan H, Gomes R, Castrovinci PA, Alvarenga PH, Abdeladhim M, Teixeira C, Meneses C, Kleeman LT, Guimarães-Costa AB, Rowland TE, Gilmore D, Doumbia S, Reed SG, Lawyer PG, Andersen JF, Kamhawi S, Valenzuela JG. A sand fly salivary protein vaccine shows efficacy against vector-transmitted cutaneous leishmaniasis in nonhuman primates. Sci Transl Med. 2015 Jun 3;7(290):290ra90.

Manning JE, Oliveira F, Coutinho-Abreu IV, Herbert S, Meneses C, Kamhawi S, Baus HA, Han A, Czajkowski L, Rosas LA, Cervantes-Medina A, Athota R, Reed S, Mateja A, Hunsberger S, James E, Pleguezuelos O, Stoloff G, Valenzuela JG, Memoli MJ. Safety and immunogenicity of a mosquito saliva peptide-based vaccine: a randomised, placebo-controlled, double-blind, phase 1 trial. Lancet. 2020 Jun 27;395(10242):1998-2007.

Visit PubMed for a complete publication listing.

Major Areas of Research
  • Characterization of human immune response to ticks, mosquito, and sand fly saliva in the context of medically significant vector-borne diseases (Lyme disease, Powassan, dengue, malaria, and leishmaniasis)
  • Clinical and field epidemiology of the impact of mosquito saliva immunity on the outcome of dengue, Zika, and other diseases carried by mosquitos
  • Strategies to block vector-borne diseases by targeting the arthropod vector and interruption transmission to the human host

NIH-Funded Clinical Trial Will Evaluate New Dengue Therapeutic

A Phase 2 clinical trial will test the safety and efficacy of an experimental treatment for dengue, a viral disease transmitted by mosquitoes.

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Neglected tropical diseases (NTDs), such as dengue, lymphatic filariasis, trachoma, and leishmaniasis, are called "neglected," because they generally afflict the world's poor and historically have not received as much attention as other diseases. NTDs tend to thrive in developing regions of the world, where water quality, sanitation, and access to health care are substandard. However, some of these diseases also are found in areas of the United States with high rates of poverty.

Why Is the Study of Neglected Tropical Diseases a Priority for NIAID?

Neglected tropical diseases, take a tremendous toll on global health. The World Health Organization estimates that more than one billion people — approximately one-sixth of the world's population — suffer from at least one NTD. While NTDs rarely lead to death, they can cause significant disability that persists for a lifetime, including fatigue, blindness, and disfigurement. Sufferers miss school, are unable to work, or are too embarrassed to seek medical care. By diminishing quality of life and opportunities to succeed, NTDs can reinforce the cycle of poverty among the world's disadvantaged populations.

How Is NIAID Addressing This Critical Topic?

NIAID has a robust program of research devoted to better understanding, preventing, and treating NTDs. Studies conducted and supported by NIAID have led to important new discoveries about the microbes that cause NTDs, the identification of targets for potential new drugs and vaccines, and the development of strategies for controlling the organisms that transmit NTD-causing agents to humans. Learn more about the NIAID role in neglected tropical disease research.

Aedes mosquito larvae.
detailed photo of an aedes mosquito on a colorful background

Colorized image of an Aedes mosquito

Credit: NIAID
Neglected Tropical Diseases
Page Summary
Neglected tropical diseases (NTDs), such as dengue, lymphatic filariasis, trachoma, and leishmaniasis, are called "neglected," because they generally afflict the world's poor and historically have not received as much attention as other diseases.
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LJI Professor Sujan Shresta Wins New Funding
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New Dengue Virus Naming System Will Help Identify and Track Variants

Natural History of Treated Neurocysticercosis and Long-Term Outcomes

The purpose of this protocol is to follow participants with cysticercosis during and after completion of treatment, to characterize the disease course during both short- and long-term follow-up, assess biomarkers associated with infection and response to treatment, improve diagnostic assays, and explore host-parasite interactions.

Diagnosis and Treatment of Leishmania Infections

This study will examine the natural history of Leishmanial infections and their treatments. It will provide an opportunity for NIAID staff to learn more about leishmaniasis and perhaps to improve diagnostic tests for these infections.