Country-led genetic analysis of samples collected through the Republic of Congo (RoC) epidemiologic surveillance system in early 2024 showed that mpox was affecting people in parts of the country where it has not been historically reported, and point to increases in human-to-human transmission across the border with the neighboring Democratic Republic of the Congo (DRC), where a large outbreak was declared a public health emergency of international concern in August of the same year. The analysis was conducted by the RoC Laboratoire National de Santé Publique (LNSP) in Brazzaville with support and scientific partnership from NIAID and was published in The Lancet. 

There are two known types or “clades” of monkeypox virus (MPXV), which causes mpox clinical disease. Clade I is endemic in Central Africa and can cause severe illness. Clade II, endemic in West Africa, caused the global mpox outbreak that began in 2022 and tends to result in milder illness. Each clade has two known subtypes referred to as “a” and “b.” Clade Ia has been identified in RoC and DRC intermittently for decades and Clade Ib was first identified during the active DRC outbreak. Mpox is a zoonotic disease, meaning it can be spread between animals and people. MPXV has been detected in rodents that live in areas historically affected by mpox. 

Genetic sequencing of MPXV can help determine the transmission dynamics and guide the public health response to mpox, but until recently most sequencing of MPXV was done outside of affected countries like RoC, requiring costly sample transport and delaying decision-making by local health authorities. 

To better understand whether mpox in RoC was driven by spillover from local animal hosts or cross-border human-to-human transmission from DRC, a team led by the RoC LNSP analyzed 31 samples of laboratory-confirmed MPXV collected through the country’s routine epidemiologic surveillance system between January and April of 2024. Using new in-country sequencing technology, the team determined that there were diverse circulating strains of MPXV in the country, all of the Clade Ia subtype, and some showed up to 99.9% genetic similarity to MPXV sequenced from the DRC. Moreover, MPXV samples came from provinces without historical reports of mpox. 

According to the authors, the diversity of identified stains suggest MPXV has been introduced to the human population in RoC through multiple distinct events, which could be a combination of direct zoonotic transmission from local animals as well as human-to-human transmission within and across the country’s borders. They state that current epidemiological data are insufficient to definitively confirm the directionality of MPXV transmission and that further epidemiological research is needed to understand local transmission patterns and inform the public health response in RoC. Finally, they highlight that while only 31 samples met criteria for analysis in the study, it is likely these cases represent only a fraction of the RoC mpox burden at the time of collection.

This research informed the RoC’s decision to declare a national mpox epidemic in April 2024. It is part of a longstanding scientific collaboration between NIAID’s Rocky Mountain Laboratories and the Congolese government. The U.S. Embassy in RoC, the U.S. Agency for International Development, the U.S. Centers for Disease Control and Prevention, and the World Health Organization also provided technical and laboratory support for this study. 

Learn more about NIAID’s mpox research priorities. Play a video of NIAID Director Jeanne Marrazzo discussing these priorities. 

Reference:

CK Yinda, et al. Genetic sequencing analysis of monkeypox virus clade I in Republic of the Congo: a cross-sectional, descriptive study. The Lancet DOI: 10.1016/S0140-6736(24)02188-3 (2024)

Mosquitoes are considered one of the most dangerous animals on earth because of their broad distribution and the many pathogens they transmit to humans. Some of the most important human diseases in tropical and temperate regions of the planet are caused by mosquito-borne pathogens. Malaria, dengue, and filariasis, among other mosquito-borne diseases, kill or sicken millions of people worldwide every year.

Mosquito-borne pathogens are transmitted to the vertebrate host, such as a human, when the mosquito bites the host in search of blood. The proteins found in blood are essential for female mosquitoes: without it, they lack the resources to create eggs. Greater knowledge of the biological processes involved in the mosquito life cycle could lead to new or improved strategies to control mosquito populations.     

Dr. Patricia Scaraffia, Associate Professor at the Tulane University School of Public Health and Tropical Medicine, has dedicated her career to understanding the metabolism of the mosquito Aedes aegypti that carries the pathogens responsible for dengue, Zika, chikungunya, and yellow fever to humans. NIAID reached out to Dr. Scaraffia about her team’s research. 

What got you interested in studying mosquito metabolism?

I have studied the metabolism of insects that are vectors of pathogens causing human diseases since I was a graduate student at the Universidad Nacional de Cordoba, in Argentina. My Ph.D. dissertation was focused on the energy metabolism in Triatomine insects, vectors of Trypanosoma cruzi, the etiological agent of Chagas´ disease. After my dissertation, I participated as a speaker in a two-week course for PhD students entitled Biochemistry and molecular biology of insects of importance for public health. During the course, Argentinian professors encouraged me to contact the late Dr. Michael A. Wells, a leader in insect metabolism, and apply for a postdoctoral training in his lab. Soon after, I joined Dr. Wells´s lab at the University of Arizona as a research associate and opened a new line of investigation in his lab. Since then, I have never stopped working on A. aegypti mosquito metabolism. I am passionate and curious about the tremendous complexity of mosquito metabolism. It is a fascinating puzzle to work on. It constantly challenges me and my research team to think outside the box when trying to decipher the unknowns related to mosquito metabolism.

Dr. Patricia Scaraffia's work focuses on the secrets of mosquito metabolism.

Credit: Dr. Patricia Scaraffia

What are the metabolic challenges faced by mosquitoes after feeding on blood?

Female mosquitoes are a very captivating biological system. It is during blood feeding that female mosquitoes can transmit dangerous, and sometimes lethal, pathogens to humans. Interestingly, the blood that the females take could be twice their body weight, which is impressive. Female mosquitoes have evolved efficient mechanisms to digest blood meals, eliminate excess water, absorb and transport nutrients, synthesize new molecules, metabolize excess nitrogen, remove nitrogen waste, and successfully lay eggs within 72 hours! Despite significant progress in understanding how females overcome these metabolic challenges, we have not yet fully elucidated the intricate metabolic pathways, networks, and signaling cascades, nor the molecular and biochemical bases underlying the multiple regulatory mechanisms that may exist in blood-fed female mosquitoes. 

What are the greatest potential benefits of understanding mosquito metabolism?

Metabolism is a complicated process that involves the entire set of chemical transformations present in an organism. A metabolic challenge faced by mosquitoes is how to break down ammonia that results from digesting a blood meal and is toxic to the mosquito. With NIAID support, we found that in the absence of a functional metabolic cycle to detoxify ammonia, A. aegypti mosquitoes use specific metabolic pathways that were believed to be non-existent in insects. This discovery has opened a new field of study. 

A better understanding of mosquito metabolism and its mechanisms of regulation in A. aegypti and other mosquito species could lead us to the discovery of common and novel metabolic targets and/or metabolic regulators. It would also provide a strong foundation for the development and implementation of more effective biological, chemical and/or genetic strategies to control mosquito populations around the world. 

What are the biggest challenges to studying mosquito metabolism?

We have often observed that genetic silencing or knockdown—a technique to prevent or reduce gene expression—of one or more genes encoding specific proteins involved in mosquito nitrogen metabolism results in a variety of unpredictable phenotypes based on our knowledge of vertebrate nitrogen metabolism. Notably, female mosquitoes get control of the deficiency of certain key proteins by downregulating or upregulating one or multiple metabolic pathways simultaneously and at a very high speed. This highlights the tremendous adaptive capacity of blood-fed mosquitoes to avoid deleterious effects and survive.

We have been collaborating closely with scientists that work at the University of Texas MD Anderson Cancer Center Metabolomics Core Facility, and more recently, with bioanalytical chemists that work in the Microbiome Center’s Metabolomics and Proteomics Mass Spectrometry Laboratory in Texas Children’s Hospital in Houston. Our projects are not turn-key type of projects with quick turn-round times. We have to invest considerable time and effort to successfully develop and/or optimize methods before analyzing mosquito samples. Despite these challenges, our research work keeps motivating us to unlock the metabolic mysteries that female mosquitoes hold.

Your research has focused on Aedes aegypti, the main vector of dengue, Zika, etc.  Why did you choose to study this mosquito species rather than others that are also important vectors of malaria and other diseases?

My research has focused on Aedes aegypti not only because it is a vector of pathogens that pose public health threats, but also because it is genetically one of the best-characterized insect species. The availability of the Aedes aegypti genome is a great resource for a wide range of investigations. In addition, Aedes aegypti is relatively simple to rear and maintain in the lab. In my lab, we are interested in expanding our metabolic studies to other mosquito species by working in collaboration with scientists with expertise in the biology of different vectors.

What important questions remain unanswered about mosquito metabolism?

Many important questions remain unanswered about mosquito metabolism. I’d like to highlight a few of them that may help us enhance our knowledge of the mosquito as a whole organism rather than as a linear sum of its parts. For example, what are the genetic and biochemical mechanisms that drive metabolic fluxes in mosquitoes in response to internal or external alterations? How do key proteins interact with each other, and how are they post-translationally regulated to maintain mosquito metabolism? How are the metabolic networks regulated in noninfected and pathogen-infected mosquitoes? What are the critical regulatory points within the mosquito metabolism and the vector-host-pathogen interface? 

While basic science will continue to be crucial in answering these questions, to successfully fight against mosquitoes, we must work together as part of a multidisciplinary team of scientists to tightly coordinate our efforts and close the gap between basic and applied science. 

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 al. Seroprevalence of Arboviruses in a Malaria Hyperendemic Area in Southern Mali. The American Journal of Tropical Medicine and Hygiene DOI: 10.4269/ajtmh.23-0803 (2024).

NIAID-developed Test Could Be Used to Find Hot Spots for Disease-spreading Mosquitoes

Not all mosquitoes are the same. Some carry pathogens that cause diseases in the people they bite. Scientists at NIAID developed a new tool to help identify geographic hot spots for Aedes mosquitoes, a type of mosquito that can spread diseases such as dengue, Zika and chikungunya. The tool uses a marker from blood serum to identify people bitten by Aedes mosquitoes. Monitoring for this marker in blood samples could help find sites where disease-carrying mosquitoes live, allowing for targeted interventions against dengue and other diseases.

Nearly half of the world’s population lives in areas affected by dengue, a viral disease spread by Aedes mosquitoes, primarily of the species Aedes aegypti and Aedes albopictus. The disease symptoms include fever, head and body aches, nausea and rash, and severe cases of dengue can be fatal. Each year, between 100 and 400 million people develop the disease, resulting in approximately 40,000 deaths. In places where dengue is common, it is often a major cause of illness. However, vaccines against dengue are not widely available throughout the world. For these reasons, mosquito control is an important strategy for preventing the disease in these regions.

When a person or animal is bitten by a mosquito, saliva from the mosquito is injected into the skin. The saliva is what causes the bite to itch—and it can also contain pathogens such as viruses and parasites that cause disease. The immune system reacts to a mosquito bite, producing antibodies against the proteins contained in mosquito saliva. People who have been bitten by Aedes mosquitoes carry antibodies against these proteins in their blood. Although a mixture of mosquito salivary gland proteins can be used in the lab to test whether a person has been bitten by Aedes mosquitoes, the test can be expensive, time-consuming, and difficult to standardize among different labs.

A team of researchers led by Dr. Fabiano Oliveira in NIAID’s Laboratory of Malaria and Vector Research aimed to develop a test suitable for large-scale monitoring of Aedes mosquito exposure in people. The researchers tested blood serum from children in Cambodia who had enrolled in a study conducted by the NIAID International Center for Excellence in Research, Cambodia. The researchers compared the levels of several mosquito saliva proteins in the blood of children who had and had not developed dengue. They found that most of the children who had developed the mosquito-borne disease had higher levels of antibodies against two proteins, AeD7L1 and AeD7L2, which are from the saliva of the Ae. aegypti mosquito. Based on these findings, the scientists developed a test that uses lab-produced versions of the proteins. They found that the test could detect antibodies produced by Aedes mosquito bites without detecting exposure to other types of mosquitoes, such as some Culex and Anopheles species.

The researchers note that the new test could be a valuable tool for public health programs, such as for identifying where mosquito control measures could have the greatest effect in areas with limited access to resources. However, they say that additional development is needed to ensure that the test produces consistent results in different populations, including adults. They note that the test uses reagents that are inexpensive, could be standardized among different labs, and would need only a drop of blood for analysis, making it a promising means to help prevent the spread of dengue and other mosquito-borne diseases.

Reference: 

S. Chea and L. Willen, et al., “Antibodies to Aedes aegypti D7L salivary proteins as a new serological tool to estimate human exposure to Aedes mosquitoes.” Frontiers in Immunology, May 1, 2024. [DOI: 10.3389/fimmu.2024.1368066]

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.