Probe in DR Congo unexplained illness cluster shifts toward chemical or meningitis causes

An ongoing investigation into an unexplained illness cluster in the Democratic Republic of the Congo (DRC) Equateur province suggests chemical poisoning or rapid-onset bacterial meningitis might be causing the sudden onset of deaths in a village, especially in young men, the World Health Organization (WHO) said yesterday in an outbreak notice.

There have been two unexplained illness clusters in Equateur Province, a smaller one in Bolomba Health Zone that began in January and a larger one in Basankusu Health Zone that began in early February, with a report of 24 unexplained deaths from a single village. The WHO said the epidemiological investigation doesn’t show a link between outbreaks at the two locations, which are about 100 miles apart and separated by dense forests and poor infrastructure.

Fever was one of the symptoms in a broad case definition, and initial fears of Marburg or Ebola virus were ruled out in earlier testing.
Most deaths occurred within a day or two of illness onset

Of the now 53 deaths reported from Basankusu, most were reported from the same village. Time of symptom onset to death in the initial cluster was 1 day, with symptoms that included fever, chills, headaches, muscle aches, abdominal pains, diarrhea, sweating, dizziness, shortness of breath, agitation, and others. Adolescent and young adult males were disproportionately affected. With a rapidly declining incidence, suggesting that the event is not spreading in time or place, the WHO said.

Enhanced surveillance using the broad case definition identified 1,318 suspected cases, which the WHO said makes the information difficult to interpret and probably covers a range of febrile illnesses, including malaria. About 50% tested positive on rapid tests, which the WHO said isn’t usual in an area where malaria is endemic.

More samples, including cerebrospinal fluid, have been collected, and environmental samples have been collected to test for chemical causes, such as organophosphate contamination. “The definitive cause of illness remains undetermined. Further testing and field investigations are ongoing to better characterize the cases and deaths,” the group added.

Website: International Conference on Infectious Diseases

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Researchers uncover how hepatitis B virus can persist in liver cells

Researchers have discovered a key mechanism that allows the hepatitis B virus (HBV) to infect and persist in liver cells, in a new study that may pave the way for potential treatments for people with chronic hepatitis B infection.

Specifically, they found the virus infects liver cells by hijacking protein complexes that package DNA in order to activate its own genes. With these findings, researchers were able to successfully disrupt HBV’s ability to infect lab-grown human liver cells using a compound already in clinical trials as a potential cancer treatment.
Potential cure’

“If these results are confirmed through additional study, we are optimistic the approach could be used to treat chronic infections for the first time — and therefore could represent a potential cure,” Robert Schwartz, MD, PhD, who co-led the study at Weill Cornell Medicine, in New York, said in a university news story.

The study, “A nucleosome switch primes hepatitis B virus infection,” was published in the journal Cell.

Liver inflammation in hepatitis B is caused by an infection with the hepatitis B virus. Although HBV infections often clear up on their own, some will become chronic, lasting six months or more, which can lead to serious liver damage and liver cancer.

Current antiviral therapies for hepatitis B can lower circulating levels of the virus, but they cannot completely stop it from replicating its DNA.

“One of the main challenges with treating hepatitis B is that the existing treatments can stop the virus from making new copies of itself [viral replication], but they don’t fully clear the virus from infected cells, allowing the virus to persist in the liver and maintain chronic infection,” Schwartz said.


When HBV infects liver cells, its DNA is transported to the cell’s nucleus, where it forms rings of genetic material called covalently closed circular DNA (cccDNA). When combined with host histones, or proteins that package DNA like a thread on a spool, cccDNA becomes a minichromosome that serves as a template for producing four viral proteins — C, P, S, and X — needed for HBV replication.

Protein X is known to be produced immediately upon infection to degrade a host protein complex that blocks cccDNA as a defense mechanism against the virus. This viral protein also degrades host proteins involved with DNA repair, making infected cells more prone to accumulate DNA errors, eventually leading to cancer.

However, protein X is not found in the virus and must be made from cccDNA in newly infected liver cells.

“This raises a classic chicken-and-egg question that has puzzled scientists for decades,” said Yael David, PhD, a study co-lead at Memorial Sloan Kettering Cancer Center, in New York. “How does the virus produce enough X protein to drive viral gene [activity] and establish infection?”
To find out, the team created a model for HBV infection in vitro, or under laboratory conditions outside of living organisms. Experiments confirmed that the in vitro HBV minichromosome closely resembled how HBV’s DNA organizes in infected liver cells.

“This platform became a powerful tool not only to study the virus’s biochemistry but also to analyze, in detail, what happens in the critical first hours of an infection,” David said.

The team showed that for protein X to be made, the viral DNA needs to be organized into DNA-histone complexes called nucleosomes, like beads on a string. Nucleosomes are the building blocks of chromatin, the material that forms chromosomes.

“Conventional wisdom says that packaging a gene’s DNA into nucleosomes would block or slow down the cell’s ability to read out that gene to make [working] proteins, like protein X,” said Viviana Risca, PhD, who co-led the study at The Rockefeller University, in New York. “But in complex organisms like humans and in the viruses that infect us, gene regulation is not always so straightforward. We found that to be the case for the HBV gene encoding protein X — the presence of nucleosomes on the viral genome is necessary for the [process] that gives rise to [working] protein X.”

Building on these findings, the researchers tested five small molecules known to disrupt chromatin formation. They found the CBL137 molecule, an anticancer drug candidate, significantly suppressed chromatin organization of the X gene and blocked HBV replication in lab-grown human liver cells. Notably, CBL137 worked at very low concentrations, affecting the virus but not human cells.

“This made us very optimistic about the possibility of developing a treatment approach while preventing or limiting side effects,” David said.

The researchers noted CBL137 might be helpful in treating other chromatin-associated viruses, such as herpesviruses, papillomaviruses, and adenoviruses.

“Our results shed light on a long-standing paradox and represent a potential therapeutic approach for the treatment of chronic HBV infection,” they wrote.

Website: International Conference on Infectious Diseases

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Preparing for Disease X

December 3, 2024, the Ministry of Health of Democratic Republic of Congo (DRC) reported 406 cases and 31 fatalities from an "undiagnosed illness" that appeared in the Panzi health zone, which is located in Kwango Province, in the southwest of the country. The outbreak, which first emerged in late October, primarily affected children under 5, who also accounted for more than 90% of deaths. Symptoms resembled those of common viral diseases—fever, headache, cough, runny nose, and body aches. The rapid rate of transmission, combined with a lack of diagnostic and treatment resources, made it difficult for local health authorities to contain the outbreak. Although Disease X has since been identified as severe malaria complicated by malnutrition, the process by which the outbreak was reported and contained offers lessons for future pathogens.

Challenges Making Sense of the Strange Situation

From the start of the outbreak, experts emphasized the need for laboratory diagnostics to rule out known pathogens such as COVID-19, measles, influenza, and malaria. Panzi's limited health-care capacity and resources, along with its poor infrastructure, however, posed significant logistical hurdles. The lack of local laboratory diagnostics in the region required patient samples to be shipped to Kinshasa, but unpaved roads delayed those samples from reaching the capital by nearly five weeks, hindering timely intervention and response efforts.

The region's poorly equipped primary care systems, including comprehensive curative, promotive, and preventive services, also created the conditions for Disease X to spread. At the time of the outbreak, 54% of Kwango village suffered from malnutrition. Despite limited data on childhood vaccination coverage, experts suggest that a lack of immunity could have left the population susceptible to disease spread. Hence the intersection of a weak health-care system and challenging local conditions intensified vulnerabilities and complicated rapid response efforts to the situation in early December.

National and Global Response Efforts

The global health community uses the term Disease X to denote a hypothetical unknown pathogen that could potentially cause a pandemic. The possibility of a Disease X scenario prompted national and global public health responses to shift into high alert, especially given that DRC is still grappling with an mpox emergency—having reported 43,862 suspected cases in 2024 alone. The simultaneous emergence of mpox and a potential Disease X in DRC raised concern over the possibilities of overwhelming public health authorities and posing a significant international threat.

To get ahead of that dual threat, the National Public Health Institute of DRC, Africa Centers for Disease Control and Prevention (Africa CDC), and the World Health Organization (WHO) dispatched rapid response teams of doctors, epidemiologists, lab technicians, and infection control experts to the Panzi region. Their mission was twofold: to provide immediate care to the infected population and to collect critical data to diagnose the illness. Samples were collected from patients and transferred to a laboratory in Kinshasa for analysis. At the time, the WHO warned that the illness could be a new respiratory pathogen, a mix of known ones such as influenza, COVID-19, malaria, or measles, or a completely unidentified disease.

By December 27—more than three weeks after the public health alert—the WHO announced that the mystery Disease X was Plasmodium falciparum malaria combined with common viral respiratory infections, all compounded by high rates of acute malnutrition. Response teams continue to work in the Panzi zone to treat affected individuals. In addition, efforts are under way to address food insecurity and improve surveillance and health resources for future outbreaks.

Lessons from Past Pandemics

Although Disease X has been identified, the critical question remains: If a mysterious pathogen were to appear again, are health systems ready to swiftly identify the disease, deploy medical countermeasures, and increase the surge capacity of epidemiologists and other experts?

Given the history of pandemics and the frequency of current outbreaks, the question is not whether Disease X will occur again, but when. Three interventions are therefore needed to enhance preparedness for such an event.

Strengthen primary health-care systems, the health-care workforce, and surveillance for effective infection prevention and control

The DRC outbreak highlights the urgent need for a robust primary care framework. In Panzi, inadequate childhood vaccinations and nutrition have worsened malnutrition and vulnerability to illness. Additionally, inadeqate access to essential medications, lack of funding for free health care, and a shortage of medical personnel have all impeded timely responses, hindering effective treatment for common symptoms and limiting access to care for vulnerable populations.

A well-functioning primary care system should include trained health professionals, access to all essential medications, and comprehensive vaccination programs to prevent outbreaks. Given the challenges in rural areas, including a lack of funding for health-care resources and scarcity of medical providers, innovative solutions are needed to improve access. Community health workers can fill gaps in the health-care workforce and set up medical tents or mobile clinics in remote locations. In rural Kenya, community health workers have used mobile clinics to bridge gaps in HIV care and expand access to antiviral treatment for rural populations.

In addition, the use of mobile clinics connected to urban centers can also provide early supportive care and basic treatments, and isolation tents can help contain infectious diseases. Finding ways to effectively integrate telehealth with physical clinics can enhance diagnosis and care in out-of-hospital settings, preventing the spread of disease to more populated areas. In rural Uganda, telehealth has enabled community health workers to identify, refer, and care for COVID-19 patients, playing a crucial role in the country's pandemic response.

Strengthen infectious disease tracking systems

The delayed response in Panzi highlights the need for improved data infrastructure and reliable surveillance capabilities. Investing in local data interoperability and quality can enable quicker reporting from rural areas and more effective national policy actions.

Strategically locating laboratories to serve multiple rural areas can facilitate routine diagnostics and rapid testing for emerging diseases. For example, DRC, Nigeria, Senegal, and Uganda have previously linked laboratory reporting systems across districts with local health ministry data to track and store information on COVID-19 infections. Given increased funding and investments, solar-powered versatile testing equipment can be used in rural areas of Africa to expedite clinical and surveillance efforts. Ensuring that testing is conducted within 24 to 48 hours is vital because the effectiveness of a surveillance system hinges on swift turnaround times.

Use military personnel to manage pandemic outbreaks effectively

One proven strategy to overcome poor infrastructure is to leverage the military, which excels in rapid logistics and capabilities to access remote regions to significantly enhance epidemic management. Investment in joint simulations with military personnel for epidemic response in rural areas like Panzi is a low-cost, high-impact strategy to prepare countries for swift action in acute treatment of victims, sample collection, and diagnostic testing. Military medical professionals and logistic experts can facilitate rapid deployment of response teams at outbreak sites, as demonstrated during the 2014–15 Ebola outbreak in West Africa and, more recently, during the COVID-19 outbreaks in Ghana. The military there now operates a former COVID-19 intensive care center to conduct surveillance, collect and transport samples, and treat critical illness to ensure rapid response and prevention of outbreaks.

Website: International Conference on Infectious Diseases

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Scientists Discover How Engineered Bacteria Supercharge the Immune System to Kill Cancer

For decades, scientists have explored the potential of bacteria in fighting cancer, but safety and efficacy barriers have stood in the way. Now, a research team has cracked the code behind how genetically engineered bacteria, specifically DB1, can selectively target and eliminate tumors.

A team of researchers, led by Prof. Chenli Liu from the Shenzhen Institutes of Advanced Technology at the Chinese Academy of Sciences (CAS) and Prof. Yichuan Xiao from the Shanghai Institute of Nutrition and Health at CAS, has uncovered the key mechanism behind bacterial cancer therapy using a genetically engineered bacterial strain. Their findings were published today (March 3) in the scientific journal Cell.

The idea of using bacteria to fight cancer dates back to the 1860s. However, despite its long history, bacterial-based cancer therapy has struggled to gain clinical traction due to concerns about safety and effectiveness.

Challenges and Innovations in Synthetic Biology

Recent advancements in synthetic biology have led to the creation of novel antitumor bacteria, opening new possibilities in immuno-oncology. Yet, one major challenge has remained: understanding how these bacteria evade the body’s immune system while simultaneously activating an antitumor response.

In this study, researchers developed an engineered bacterial strain called Designer Bacteria 1 (DB1). This strain is designed to thrive in tumor tissue while being eliminated from healthy tissue, achieving both a highly targeted approach to tumors and an effective tumor-clearing effect.

Unraveling the Role of CD8+ TRM Cells

To understand how DB1 simultaneously achieves these effects, researchers investigated the interactions between the bacteria and tumors. They discovered that DB1’s antitumor efficacy is closely linked to tissue-resident memory (TRM) CD8+ T cells within the tumor, which are reinvigorated and expanded following DB1 therapy. Interleukin-10 (IL-10) plays a crucial role in mediating this effect, with efficacy depending on the high expression of interleukin-10 receptor (IL-10R) on CD8+ TRM cells.
The IL-10 Feedback Loop and Tumor Memory

To investigate the molecular mechanisms underlying the high expression of IL-10R on CD8+ TRM cells, researchers conducted a series of computational and quantitative experiments. They found that IL-10 binds to IL-10R on CD8+ TRM cells, activating the STAT3 protein and further promoting IL-10R expression. This established a positive feedback loop, enabling cells to bind more IL-10 and creating a nonlinear hysteretic effect, whereby CD8+ TRM cells “memorize” previous IL-10 stimulation during tumorigenesis. The high expression of IL-10R on CD8+ TRM cells was exploited by a bacteria-induced IL-10 surge, which activated and expanded CD8+ TRM cells to clear tumor cells.
Tumor Microenvironment and Immune System Modulation

To examine the source of IL-10 within the tumor microenvironment (TME) after bacterial therapy, researchers found that tumor-associated macrophages (TAMs) upregulate IL-10 expression following DB1 stimulation via the Toll-like Receptor 4 (TLR4) signaling pathway. Interestingly, IL-10 reduced the migration speed of tumor-associated neutrophils (TANs), aiding DB1 in evading rapid clearance. These processes depended on high IL-10R expression in tumor-associated immune cells, highlighting the critical role of IL-10R hysteresis.

A New Path for Bacterial Cancer Therapy

“Our findings illuminate a crucial, yet previously unresolved mechanism in bacterial cancer therapy. The elucidated IL-10R hysteresis mechanism not only provides valuable insights but also serves as a guiding principle for the design of engineered bacteria, enhancing safety and efficacy,” said Prof. Liu.

Reference: “Bacterial immunotherapy leveraging IL-10R hysteresis for both phagocytosis evasion and tumor immunity revitalization” 3 March 2025, Cell.

Website: International Conference on Infectious Diseases

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Antimicrobial Coating for Orthopedic Implants Prevents Dangerous Infections

Biomedical engineers and surgeons at Duke University and UCLA have demonstrated an antibiotic coating that can be applied to orthopedic implants minutes before surgery that eliminates the chances of an infection around the implant.

In early trials in mice, the coating prevented all subsequent infections, even without infusions of antibiotics into the bloodstream, which is the current standard of care. After 20 days, the coating did not reduce the bone’s ability to fuse with the implant and was completely absorbed by the body. The results appeared in the journal Nature Communications.

The project began when Tatiana Segura, professor of biomedical engineering at Duke, met Nicholas Bernthal, interim chair and executive medical director at the David Geffen School of Medicine at UCLA, who specializes in pediatric orthopedic oncology and surgery. He told Segura that many children being treated for bone cancer have large portions of bone removed, which then requires orthopedic implants. But because the patients are usually also undergoing chemotherapy, their immune systems are weak, and they are especially vulnerable to bacteria colonizing the surface of the implant.

“These kids face the choice of having chemotherapy versus saving their limb or even sometimes needing amputations to survive, which sounds horrific to me,” Segura said. “All they really need is something to rub on the implant to stop an infection from taking hold, because preventing an infection is much easier than treating one. So, we came up with this coating technology that we hope will provide a solution.”

Implant infections aren’t unique to children or to cancer patients, however. For joint replacement surgeries, for example, infection occurs in 1 percent of primary and up to 7 percent of revision surgeries, which requires repeated revision surgeries and prolonged intravenous antibiotics. Treatment doesn’t always work, however, as these patients have a higher five-year mortality risk than those diagnosed with HIV/AIDS or breast cancer. Implant infections are estimated to cost the healthcare system more than $8.6 billion annually in the United States alone.

Part of the challenge of treating these infections is that bacteria colonize the surface of the implants themselves. This means that there are no blood vessels flowing through the bacterial colonies to deliver the antibiotics coursing through a patient’s veins.

The only recourse is often the removal of the original implant, which is usually the best of what are only bad options.

Some doctors have taken to their own solutions, such as using antibiotic powder when closing the surgical wound or infusing the bone cement used to hold the implant in place with antibiotics. Neither of these tactics have been proven to be clinically effective. There is also the option of implant manufacturers adding antibiotic properties to their devices. But this would greatly reduce the product’s shelf life and also require a long and complicated process of FDA approval, since the implants would then be in a new classification.

“We’ve shown that a point-of-care, antibiotic-releasing coating protects implants from bacterial challenge and can be quickly and safely applied in the operating room without the need to modify existing implants,” said Christopher Hart, a Resident Physician in UCLA Orthopaedic Surgery who helped conduct the experiments.

The new antimicrobial coating is made of two polymers, one that repels water and one that mixes well with water. Both are combined in a solution with an antibiotic of the physician’s choosing and then applied directly to the orthopedic implant by dipping, painting or spraying. When exposed to a bright ultraviolet light, the two polymers couple together and self-assemble into a gridlike structure that traps the antibiotics.

The reaction is an example of click chemistry, which is a general way of describing reactions that happen quickly at room temperature, produce only a single reaction product, have an extremely high yield, and occur within a single container.

“This study is a great example of the power of click chemistry in biomedical applications,” said Weixian Xi, now a Senior Scientist at Illumina, who was a postdoctoral researcher at UCLA during the study. “This ‘smart’ and ‘clickable’ polymeric coating enables protections of implants from bacterial infection and makes a personalized approach possible.”

The click chemistry polymer grid also has an affinity for metal. Tests involving various types of implants showed that the coating was very difficult to rub off during surgical procedures. Once inside the body, however, the conditions cause the polymer to degrade, slowly releasing the antibiotics over the course of two to three weeks.

In the study, researchers rigorously tested the coating in mice with either leg or spine implants. After 20 days, the coating did not inhibit the bone’s growth into the implant and prevented 100 percent of infections. This time period, the researchers say, is long enough to prevent the vast majority of these types of infections from occurring.

The researchers have not yet tested their coating on larger animals. Since larger animals, such as humans, have larger bones and need larger implants, there is much more surface area to protect against bacterial infections. But the researchers are confident that their invention is up to the task and plan to pursue the steps needed to commercialize the product.

Website: International Conference on Infectious Diseases

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2019 Antibiotic Resistance Threats Report

Overview

CDC's 2019 AR Threats Report includes national death and infection estimates that underscore the continued threat of AR in the United States. More than 2.8 million antimicrobial-resistant infections occur in the U.S. each year, and more than 35,000 people die as a result. When C. diff is added to these, the U.S. toll of all the threats in the report exceeds 3 million infections and 48,000 deaths.

The germs are listed in three categories—urgent, serious and concerning—based on level of concern to human health. The report also includes a Watch List with three threats that have not spread widely in the U.S. but could become common without continued aggressive action.

The 2019 AR Threats Report is intended to:Serve as a reference for information on AR.
Provide the latest AR burden estimates for human health in the U.S.
Highlight emerging areas of concern and additional action needed.

The 2019 report also emphasizes progress in combating AR. However, CDC's 2022 special report highlighting the impact of COVID-19 on antimicrobial resistance in the U.S. found that much of that progress was lost, in large part, due to the effects of the pandemic. The pandemic pushed healthcare facilities, health departments and communities near their breaking points in 2020, making it very hard to maintain the progress in combating AR.

CDC's previous antimicrobial resistance threats reports, published in 2013 and 2019, were important resources to guide U.S. policy for and investments in combating antimicrobial resistance. Starting in 2025, CDC will release estimates for at least 19 antimicrobial resistance threats and an update on the U.S. burden of antimicrobial resistance, by pathogen, in a new electronic format. Going forward, CDC will release new estimates for the burden of these threats at least every two years. Data are critical to guide efforts to combat antimicrobial resistance, and CDC is committed to providing the high-quality data required to steer this important work.

Website: International Conference on Infectious Diseases

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