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Tag: Fever

  • Gut bacteria and tryptophan diet can play a protective role against pathogenic E. coli

    Gut bacteria and tryptophan diet can play a protective role against pathogenic E. coli

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    Gut bacteria and a diet rich in the amino acid tryptophan can play a protective role against pathogenic E. coli, which can cause severe stomach upset, cramps, fever, intestinal bleeding and renal failure, according to a study published March 13 in Nature.

    The research reveals how dietary tryptophan – an amino acid found mostly in animal products, nuts, seeds, whole grains and legumes – can be broken down by gut bacteria into small molecules called metabolites. It turns out a few of these metabolites can bind to a receptor on gut epithelial (surface) cells, triggering a pathway that ultimately reduces the production of proteins that E. coli use to attach to the gut lining where they cause infection. When E. coli fail to attach and colonize the gut, the pathogen benignly moves through and passes out of the body.

    The research describes a previously unknown role in the gut for a receptor, DRD2. DRD2 has otherwise been known as a dopamine (neurotransmitter) receptor in the central and peripheral nervous systems.

    It’s actually two completely different areas that this receptor could play a role in, which was not appreciated prior to our findings. We essentially think that DRD2 is moonlighting in the gut as a microbial metabolite sensor, and then its downstream effect is to help protect against infection.”


    Pamela Chang, associate professor of immunology in the College of Veterinary Medicine and of chemical biology in the College of Arts and Sciences

    Samantha Scott, a postdoctoral researcher in Chang’s lab, is first author of the study, “Dopamine Receptor D2 Confers Colonization Resistance via Microbial Metabolites.”

    Now that Chang, Scott and colleagues have identified a specific pathway to help prevent E. coli infection, they may now begin studying the DRD2 receptor and components of its downstream pathway for therapeutic targets.

    In the study, the researchers used mice infected with Citrobacter rodentium, a bacterium that closely resembles E. coli, since certain pathogenic E. coli don’t infect mice. Through experiments, the researchers identified that there was less pathogen and inflammation (a sign of an active immune system and infection) after mice were fed a tryptophan-supplemented diet. Then, to show that gut bacteria were having an effect, they gave the mice antibiotics to deplete microbes in the gut, and found that the mice were infected by C. rodentium in spite of eating a tryptophan diet, confirming that protection from tryptophan was dependent on the gut bacteria.

    Then, using mass spectrometry, they ran a screen to find the chemical identities of tryptophan metabolites in a gut sample, and identified three such metabolites that were significantly increased when given a tryptophan diet. Again, based on pathogen levels and inflammation, when these three metabolites alone were fed to the mice, they had the same protective effect as giving the mice a full tryptophan diet.

    Switching gears, the researchers used bioinformatics to find which proteins (and receptors) might bind to the tryptophan metabolites, and from a long list they identified three related receptors within the same family of dopamine receptors. Using a human intestinal cell line in the lab, they were able to isolate receptor DRD2 as the one that had the protective effect against infection in the presence of tryptophan metabolites.

    Having identified the metabolites and the receptor, they analyzed the downstream pathway of DRD2 in human gut epithelial cells. Ultimately, they found that when the DRD2 pathway was activated, the host’s ability to produce an actin regulatory protein was compromised. C. rodentium (and E. coli) require actin to attach themselves to gut epithelial cells, where they colonize and inject virulence factors and toxins into the cells that cause symptoms. But without actin polymerization they can’t attach and the pathogen passes through and clears.

    The experiments revealed a new role of dopamine receptor DRD2 in the gut that controls actin proteins and affects a previously unknown pathway for preventing a pathogenic bacteria’s ability to colonize the gut. 

    Jingjing Fu, a former postdoctoral researcher in Chang’s lab, is a co-author.

    The study was supported by the Arnold and Mabel Beckman Foundation, a President’s Council of Cornell Women Affinito-Stewart Grant, the National Institutes of Health and a Cornell Institute of Host-Microbe Interactions and Disease Postdoctoral Fellowship. 

    Source:

    Journal reference:

    Scott, S. A., et al. (2024). Dopamine receptor D2 confers colonization resistance via microbial metabolites. Nature. doi.org/10.1038/s41586-024-07179-5

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  • New study highlights the urgent need for typhoid vaccination in sub-Saharan Africa

    New study highlights the urgent need for typhoid vaccination in sub-Saharan Africa

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    There is a high burden of typhoid fever in sub-Saharan African countries, according to a new study published today in The Lancet Global Health. This high burden combined with the threat of typhoid strains resistant to antibiotic treatment calls for stronger prevention strategies, including the use and implementation of typhoid conjugate vaccines (TCVs) in endemic settings along with improvements in access to safe water, sanitation, and hygiene.

    The findings from this 4-year study, the Severe Typhoid in Africa (SETA) program, offers new typhoid fever burden estimates from six countries: Burkina Faso, Democratic Republic of the Congo (DRC), Ethiopia, Ghana, Madagascar, and Nigeria, with four countries recording more than 100 cases for every 100,000 person-years of observation, which is considered a high burden. The highest incidence of typhoid was found in DRC with 315 cases per 100,000 people while children between 2-14 years of age were shown to be at highest risk across all 25 study sites.

    There are an estimated 12.5 to 16.3 million cases of typhoid every year with 140,000 deaths. However, with generic symptoms such as fever, fatigue, and abdominal pain, and the need for blood culture sampling to make a definitive diagnosis, it is difficult for governments to capture the true burden of typhoid in their countries.

    “Our goal through SETA was to address these gaps in typhoid disease burden data,” said lead author Dr. Florian Marks, Deputy Director General of the International Vaccine Institute (IVI). “Our estimates indicate that introduction of TCV in endemic settings would go to lengths in protecting communities, especially school-aged children, against this potentially deadly-;but preventable-;disease.”

    In addition to disease incidence, this study also showed that the emergence of antimicrobial resistance (AMR) in Salmonella Typhi, the bacteria that causes typhoid fever, has led to more reliance beyond the traditional first line of antibiotic treatment. If left untreated, severe cases of the disease can lead to intestinal perforation and even death. This suggests that prevention through vaccination may play a critical role in not only protecting against typhoid fever but reducing the spread of drug-resistant strains of the bacteria.

    There are two TCVs prequalified by the World Health Organization (WHO) and available through Gavi, the Vaccine Alliance. In February 2024, IVI and SK bioscience announced that a third TCV, SKYTyphoid™, also achieved WHO PQ, paving the way for public procurement and increasing the global supply.

    Alongside the SETA disease burden study, IVI has been working with colleagues in three African countries to show the real-world impact of TCV vaccination. These studies include a cluster-randomized trial in Agogo, Ghana and two effectiveness studies following mass vaccination in Kisantu, DRC and Imerintsiatosika, Madagascar.

    Through these vaccine effectiveness studies, we aim to show the full public health value of TCV in settings that are directly impacted by a high burden of typhoid fever.” He adds, “Our final objective of course is to eliminate typhoid or to at least reduce the burden to low incidence levels, and that’s what we are attempting in Fiji with an island-wide vaccination campaign.”


    Dr. Birkneh Tilahun Tadesse, Associate Director General at IVI and Head of the Real-World Evidence Department

    As more countries in typhoid endemic countries, namely in sub-Saharan Africa and South Asia, consider TCV in national immunization programs, these data will help inform evidence-based policy decisions around typhoid prevention and control.

    Source:

    International Vaccine Institute

    Journal reference:

    Marks, F., et al. (2024) Incidence of typhoid fever in Burkina Faso, Democratic Republic of the Congo, Ethiopia, Ghana, Madagascar, and Nigeria (the Severe Typhoid in Africa programme): a population-based study. The Lancet Global Health. doi.org/10.1016/S2214-109X(24)00007-X.

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  • Novel genetic link uncovered in generalized pustular psoriasis

    Novel genetic link uncovered in generalized pustular psoriasis

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    A team from Nagoya University in Japan has identified previously unidentified gene variants that are associated with the development of generalized pustular psoriasis (GPP). The team’s findings, published in the Journal of the American Academy of Dermatology, offer hope for improving diagnosis and therapy.

    GPP is rare, but its effects are often serious. People with GPP can experience recurrent flares of the disease, which include multiple erythematous lesions and sterile pustules over the whole body, often accompanied by fever and chills. This can lead to emergency treatment and even death.

    Until now, researchers have reported six genes associated with GPP. Although these genes are widely used for diagnosis and treatment, there remain GPP patients who do not have any variants of these genes. This suggests unknown genetic factors associated with the development of GPP.

    To address this problem, a group led by Prof. Masashi Akiyama, Takenori Yoshikawa, and Dr. Takuya Takeichi from the Department of Dermatology at Nagoya University Graduate School of Medicine used next-generation sequencing to investigate the genes of Japanese patients with GPP. They found that higher frequencies of two MEFV gene variants, p.Arg202Gln and p.Ser503Cys, were associated with GPP. In particular, 21% of the patients carried the variant p.Arg202Gln variant and 13% carried the p.Ser503Cys variant.

    Pyrin, the product of MEFV, regulates inflammatory pathways. But specific variants of pyrin induce excessive neutrophil migration to tissues, eventually triggering excessive inflammation. This finding, therefore, suggests a likely path for the disease.

    The researchers believe that therapies targeting inflammatory pathways related to MEFV are a promising therapeutic strategy for patients with these variants. According to Yoshikawa, their findings suggest a new use for a commonly used drug to treat familial Mediterranean fever (FMF).

    As these variants are associated with both FMF and GPP, treatments for FMF may also be effective for the treatment of patients with MEFV-associated GPP.”


    Takenori Yoshikawa, Nagoya University

    Source:

    Journal reference:

    Yoshikawa, T., et al. (2023) MEFV variants are a predisposing factor for generalized pustular psoriasis. Journal of the American Academy of Dermatology. doi.org/10.1016/j.jaad.2023.10.070.

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  • Global health boost as new vaccine SKYTyphoid gains WHO prequalification

    Global health boost as new vaccine SKYTyphoid gains WHO prequalification

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    SK bioscience and the International Vaccine Institute (IVI) announced today that the typhoid conjugate vaccine developed by SK bioscience with technology transfer from IVI has achieved the World Health Organization prequalification (PQ), which paves the way for public procurement of the vaccine by UN organizations and gives a boost to the global TCV supply.

    WHO PQ certifies the safety, efficacy, and GMP of a vaccine by evaluating its manufacturing process, quality, and clinical trial results according to stringent standards. WHO PQ is essential for participating in international tenders organized by UN agencies including UNICEF and the Pan American Health Organization (PAHO) and certifies the quality of the vaccine and the competitiveness of technology in the global market.

    The new vaccine SKYTyphoid™, which has received the WHO’s seal of approval this time, is a typhoid conjugate vaccine developed jointly by SK bioscience and IVI following IVI’s technology transfer with funding support from the Bill & Melinda Gates Foundation. SK bioscience was the manufacturing partner and IVI led clinical trials conducted in the Philippines and Nepal.

    The vaccine utilizes the ‘purified Vi polysaccharide-diphtheria toxoid conjugate’ method, which conjugates diphtheria toxin protein (diphtheria toxoid), which acts as a carrier, to polysaccharide of typhoid bacteria, which acts as an antigen. Adopting conjugation technology, the vaccine is safe to administer in infants and young children aged 6 months to 2 years and is expected to provide sufficient immune response and long-term protection with a single dose compared to existing oral live or polysaccharide typhoid vaccines.

    Based on clinical results, SKYTyphoid™ obtained a licensure for export from the Korean Ministry of Food and Drug Safety in 2022. A Phase 3 clinical trial conducted by SK bioscience and IVI in Nepal on 2,160 healthy individuals aged 6 months to 45 years had confirmed the excellent immunogenicity and safety of the vaccine. In the comparative study with a conventional WHO-PQed polysaccharide-protein conjugate typhoid vaccine, SKYTyphoid™ demonstrated equivalent immunogenicity and safety, without any notable side effect after administration across all age groups. The findings were published in The Lancet Infectious Diseases, a sister publication to the journal The Lancet.

    Additionally, the results of the Phase II clinical trial of SKYTyphoid™ booster shot, published in the international ‘npj (Nature Partner Journal) Vaccine,’ showed that two doses of the TCV in infants aged 6 to 23 months induced a strong immune response, with a significant increase in antibody titers in the body compared to before vaccination.

    The WHO licensure of SK bioscience’s TCV represents the successful conclusion of a global public-private partnership to bring a novel vaccine crucial to global public health to market. SKYTyphoid™ will diversify and expand the supply of TVCs and help improve vaccine access in the endemic countries. With SK’s commitment to make the vaccine for global public health at a competitive price, SKYTyphoid™ will play an important role in typhoid prevention globally.”


    Dr. Sushant Sahastrabuddhe, Director of IVI’s Typhoid program

    With high demand for typhoid vaccines worldwide, especially in low-income countries, SK bioscience plans to start supplying the vaccine as soon as possible and expand global supply through public procurement markets including typhoid endemic countries. According to the WHO, an estimated 11 to 20 million typhoid fever cases occur worldwide every year, and 120,000 to 160,000 die from the disease.

    Dr. Jerome Kim, Director General of IVI said, “Typhoid fever is more prevalent in warmer temperatures, and climate change and the worrying rise of antimicrobial resistance are only adding to the threat of the disease. Vaccination is critical to effective prevention and control of the disease. In collaboration with SK bioscience and other partners, IVI will continue endeavors to make this vaccine accessible to people who need them the most.”

    Mr. Jae-Yong Ahn, President of SK bioscience said, “We are pleased that our global collaboration to address the global vaccine supply imbalance and improve public health has been recognized through the WHO PQ. In addition to the WHO PQ, we will obtain additional country-specific approvals to ensure that the vaccine can be supplied quickly.” With the addition of ‘SKYtyphoid™,’ SK bioscience has now achieved WHO PQ for four vaccines, including two influenza vaccines and a chickenpox vaccine.

    Source:

    International Vaccine Institute

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  • Virginia Tech food safety expert offers tips for selecting the right charcuterie meats

    Virginia Tech food safety expert offers tips for selecting the right charcuterie meats

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    Whether it’s building out a big spread for the Super Bowl or planning a Valentine’s Day meal, lots of people will be heading to the store these next few weeks to stock up on food. One item many might be considering is charcuterie. A recent Salmonella outbreak linked to charcuterie meats has raised some concerns, but Virginia Tech food safety expert Katheryn Parraga-Estrada explains that not all charcuterie products are involved in this outbreak and offers tips for selecting the right meats.

    What do people need to know before buying charcuterie meats?

    If you plan on buying or consuming charcuterie, make sure that you do not buy products from the brands implicated in the recent outbreak until the recall is over. If you have these products at home, discard them and thoroughly wash and disinfect any surfaces that may have come into contact with the products. 

    For reference, the charcuterie products involved in the recent outbreak include:

    Busseto brand Charcuterie Sampler

    – Has prosciutto, sweet soppressata, and dry coppa

    – Sold at Sam’s Club

    – Comes in a twin-pack (2 x 9oz)

     – Any lot code

    Fratelli Beretta brand Antipasto Gran Beretta

    – Has black pepper coated dry salami, Italian dry salami, dry coppa, and prosciutto

    – Sold at Costco

    – Comes in a twin-pack (2 x 12oz)

    – Any lot code

    The duration of a CDC investigation varies depending on the outbreak, and it may be extended. Each time an individual reports symptoms, it takes 3 to 4 weeks to determine if it is linked to an outbreak. As part of your responsibility, you will need to keep informed as additional brands may be implicated in this recall.

    How can people avoid Salmonella?

    Salmonella is a bacteria that lives in the intestines of people and animals and can cause a gastrointestinal illness and fever called salmonellosis. Salmonella can contaminate food or drinking water due to poor hygiene of employees who handle the food or through cross-contamination from raw products, such as poultry products to cooked or ready-to-eat products. Every year, there are about 420 deaths due to salmonellosis and about 26,500 people get hospitalized because of this bacteria. 

    People can prevent getting sick with salmonellosis by following these recommendations:

    Wash your hands properly and sanitize them after touching pets, including poultry and reptiles, which are natural carriers of Salmonella.

    • When preparing food at home, make sure to wash and sanitize surfaces that might be contaminated with Salmonella.

    • If you have children, elderly individuals, pregnant women, or people with weakened immune systems at home, ensure you fully cook all foods, especially meats.

    What are the symptoms of Salmonella?

    Symptoms can develop within 6 hours to 6 days after consuming the food contaminated or swallowing the bacteria. While healthy individuals typically recover without treatment after 4 to 7 days, those with weakened immune systems, children under 5 years old, and adults above 65 years old may experience more severe symptoms requiring medical treatment or hospitalization.

    If you experience these symptoms, make sure to keep hydrated by drinking fluids and getting rest. Dehydration can occur due to diarrhea; if symptoms are severe (bloody diarrhea, severe diarrhea for more than 3 days, high fever (>102 °F), vomiting, signs of dehydration), contact your doctor. In some cases, antibiotics may be prescribed.

    About Parraga-Estrada

    Katheryn Parraga-Estrada joined the faculty at Virginia Seafood Agricultural Research and Extension Center and Virginia Tech’s Department of Food Science and Technology in September of 2021. Her extension work focuses on improving the understanding and application of food safety research through education, training, and technical guidance for the production of safe and quality foods. In addition, she is an active member of the International Association of Food Protection, Gamma Sigma Delta Honor Society, and Phi Tau Sigma Honor Society.

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  • Study reveals high insomnia rates in non-hospitalized COVID-19 survivors

    Study reveals high insomnia rates in non-hospitalized COVID-19 survivors

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    In a recent study published in Frontiers in Public Health, researchers investigated insomnia prevalence and its association with anxiety and depression in the non-hospitalized coronavirus disease 2019 (COVID-19)-recovered community.

    Study: Sleep quality among non-hospitalized COVID-19 survivors: a national cross-sectional study. Image Credit: Stock-Asso/Shutterstock.com
    Study: Sleep quality among non-hospitalized COVID-19 survivors: a national cross-sectional study. Image Credit: Stock-Asso/Shutterstock.com

    Background

    The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has afflicted millions globally since late 2019, with most cases resolved by mid-2023. Common symptoms include coughing, weariness, fever, dyspnea, musculoskeletal issues, gastrointestinal complaints, anosmia, dysgeusia, and vertigo. Post-infection and long-term physical and psychological difficulties are serious public health concerns.

    Insomnia is a prevalent complaint, particularly among hospitalized COVID-19 patients. High-risk variables include being female, younger, and more educated, as well as having anxiety, depression, or post-traumatic stress disorder. Poor mental health is associated with insufficient sleep, and chronic disorders such as obstructive sleep apnea (OSA) can affect glycemic control, neurocognitive impairment, and aberrant functional pulmonary alterations.

    About the study

    In the current nationwide cross-sectional study, researchers investigated insomnia prevalence among COVID-19 survivors with no or moderate symptoms who did not require hospitalization throughout the recovery period (six months) and discovered relevant variables.

    Between June and September 2022, the team conducted a web-based survey among 1,056 COVID-19-recovered individuals who recovered within six months of acute SARS-CoV-2 infection and did not need hospitalization. They used the Depression Anxiety and Stress Scale-14 (DASS-14) and the Insomnia Severity Index (ISI). They obtained data on demographics such as age, marital status, sex, educational attainment, occupation, employment status, and comorbidities.

    The team asked the respondents to rate their SARS-CoV-2 infection severity and duration (days from the initial SARS-CoV-2-positive to the initial SARS-CoV-2-negative report). In addition, the respondents compared their sleep quality, sleep initiation, and total sleep duration in the previous two weeks with the time before confirming the SARS-CoV-2 infection.

    The team used multivariate logistic regressions to determine odds ratios (OR) for the relationships between anxiety and depression scores and insomnia levels among the survey respondents. They included adult COVID-19 survivors (who recovered as confirmed using polymerase chain reaction (PCR) within six months and did not require COVID-19-associated hospitalization) in Vietnam’s general population. They excluded individuals diagnosed with insomnia or psychological disorders before the study.

    Results

    The study included 1,056 individuals, with the majority being married (64%), female (69%), and having attended university (69%). After the SARS-CoV-2 infection, almost a third of respondents reported shorter sleep duration, worsened sleep quality, and more difficulties falling asleep, and half of them reported more nocturnal awakenings. Insomnia prevalence was 76%, with 23% of patients reporting severe insomnia.

    Individuals with anxiety (OR, 3.9) or depression (OR, 3.5) had a significantly increased risk of having insomnia. Other characteristics that increased the likelihood of sleeplessness included higher educational attainment and pre-existing medical conditions, but COVID-19 duration and symptoms had no significant relationship.

    Individuals who were divorced or widowed, female, had postgraduate education, were not actively employed, or suffered from chronic medical conditions had higher mean ISI ratings than their peers. Concerning COVID-19, 92% of infected individuals experienced symptoms (mean, 11 weeks). Although these symptomatic individuals showed higher ISI scores (15.2), there was no significant difference compared to individuals without symptoms.

    The mean scores for anxiety and depression were 7.6 and 6.4, respectively, with 439 (42%) and 291 (28%) individuals reporting relevant symptoms, respectively. Individuals with symptoms of anxiety (18.7) and depression (19.1) scored significantly higher on the ISI compared to those without (12.4 and 13.5, respectively). Participants experiencing insomnia scored higher on anxiety (9.2) and depression (7.8) than the overall group mean.

    In univariate analysis, those who were wedded and had a university degree were significantly less likely to experience insomnia than single and formally-educated individuals. Students were significantly more likely to experience insomnia compared to healthcare workers. Individuals with a history of chronic medical conditions were significantly more likely to suffer from insomnia following COVID-19 compared to healthy individuals. After controlling for variables, healthcare professionals had a significantly increased likelihood of insomnia (OR, 1.6) than workers in other professions; however, there were no differences compared to those who did not work or were students.

    Conclusion

    Overall, the study findings highlighted insomnia prevalence among COVID-19 survivors, with more than 75% reporting it. This percentage is much higher than that of the general population (10% to 20%) and hospitalized survivors (12% to 47%). Individuals with chronic medical conditions are more likely to suffer from insomnia, which is underreported. Public health researchers should anticipate a greater frequency of insomnia and sleep disorders in this group, which can last for one-third of healed patients up to one year after infection.

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  • Has a decade of maternal pertussis vaccination reduced its effectiveness?

    Has a decade of maternal pertussis vaccination reduced its effectiveness?

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    In a recent modeling and meta-analysis study published in the journal Nature Communications, researchers evaluated if maternal immunization against pertussis, a highly contagious bacterial respiratory infection, experienced reduced efficacy (‘blunting’) due to prolonged use. They reviewed four studies with up to six years of follow-up and designed a novel mathematical model to evaluate immunization’s short- and long-term effects on disease transmission dynamics. While incapable of ruling out minor reductions in vaccine effectiveness (VE), their findings highlight that maternal immunizations are (and will continue to be) essential in preventing pertussis transmission and, more importantly, saving the lives of unvaccinated newborns.

    Study: Maternal pertussis immunization and the blunting of routine vaccine effectiveness: a meta-analysis and modeling study. Image Credit: Kateryna Kon / ShutterstockStudy: Maternal pertussis immunization and the blunting of routine vaccine effectiveness: a meta-analysis and modeling study. Image Credit: Kateryna Kon / Shutterstock

    Pertussis and the results of global immunization efforts

    Pertussis, colloquially called ‘whooping cough,’ is a highly contagious respiratory illness caused by the bacteria Bordetella pertussis. Its symptoms included chronic or severe cough, general fatigue and fever, nausea, and difficulty breathing. It is characterized by its severe hacking cough from which the name “whooping” is obtained. Pertussis infections are most severe in children, especially newborns, and were a significant cause of childhood mortality before the 1940s.

    Thankfully, pertussis is easily preventable via vaccines. Global large-scale immunization efforts in the 1940s reduced transmission rates by 90% in most countries. Unfortunately, for reasons hitherto unknown, pertussis has been staging a comeback over the past two decades. This has prompted a resurgence into pertussis-centric research aimed at evaluating the mechanisms underpinning rising transmission rates.

    Infants, especially newborns, are the cohort most vulnerable to the disease, given their suboptimal immune development and lack of immunization. To counter this, numerous nations (since 2012) and the World Health Organization (since 2015) have recommended and initiated maternal immunization programs. Vaccinating women during the gestation period has been clinically revealed to transfer its protective effects to their unborn infants, resulting in an estimated 70% reduction in newborn mortality.

    “However, the downstream consequences of maternal immunization, when infants receive their routine pertussis vaccines, are poorly understood. Specifically, there has been long-standing concern regarding potential immunological blunting, i.e., the interference of maternally transferred antibodies with the infant immune response.”

    Understanding if current vaccination protocols are resulting in immunization blunting, and if so, to what extent, will allow for the revision of present immunization policies and may require an overhaul of the vaccines used or the process itself.

    About the study

    In the present study, researchers conducted a meta-analysis to investigate if prolonged (2012 to 2023) maternal immunization has reduced vaccine effectiveness (VE). The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

    Data collection was initiated by collating relevant publications from three online databases (PubMed, Web of Science, and Scopus) from database initiation till August 25, 2023. This search revealed 374 articles across databases, 146 of which were duplicate records. Of the 228 remaining publications, abstract screening revealed 69 potential articles, which full-text screening further narrowed down to the final sample set – four.

    “To be included in our review, studies had to provide an estimate of the relative risk (RR) of pertussis in infants having received at least one dose of their primary immunization from vaccinated vs. unvaccinated mothers. We selected only those studies that used laboratory-confirmed diagnosis of pertussis.”

    Each of the four included studies reported at least five pertussis relative risk estimates in comparing vaccinated and unvaccinated mothers. Study analyses were carried out using two steps – Firstly, to account for different metrics used in the included studies, standard relative risks were calculated and applied to each included metric. Secondly, the meta-analyses were carried out. The meta-regression used herein was corrected to account for ‘population’ as a random intercept.

    Finally, researchers devised a novel mathematical model based on the Susceptible-Exposed-Infected-Recovery (SEIR) model, explicitly testing for VE accounting for immunization blunting. The model had two outcome measures – 1. failure in “take” (if the primary vaccine failed), and 2. failure in duration (loss or reduction of vaccine protection). The model works in a hierarchical compartmentalization framework comprising three levels, each with their own ‘paths.’

    Level 1: “These three possible paths or compartments start from their mother’s immunization status during pregnancy, followed by an infant immunization schedule that resembles that of the empirical studies.” Level 2: “…newborns can be born in three possible compartments: from vaccinated mothers whose immunization succeeded, mothers whose immunization failed (i.e., who received the vaccine but whose infant remained unprotected), or unvaccinated mothers.” Level 3: “Each of the three compartments is followed by a compartment for successful primary infant immunization and a compartment for failed primary infant immunization, thereby becoming susceptible, or no immunization thereby also becoming susceptible.”

    Study findings

    Exploring the historical landscape of VE in infant pertussis via the novel model revealed that infant (maternal) immunization substantially decreased disease incidence. However, consistent with global reports, this was followed by a gradual rebound in pertussis persistence. This is consistent with the previously described “end-of-honeymoon” effect and is expected in most diseases managed using imperfect yet highly efficient vaccines. These results validate model reliability.

    Analyzing the sample dataset using this model revealed that the first vaccine dose in infants following maternal immunization is highly effective against pertussis contraction, but the second and third doses are much more uncertain, consistent with previous uncertainty regarding blunting effects. The model demonstrated the presence of a decade-long lag phase following the introduction of maternal immunization, during which time blunting effects are liable to be underestimated in trial studies.

    Encouragingly, quantifying the blunting effects suggests that they are minor and pale compared to the infant mortality-saving that maternal immunization provides. These findings support the public health decisions of many countries (55 as of 2021) to continue maternal immunization efforts and recommend that other nations follow suit.

    Conclusions

    The present study conducted a meta-regression analysis of four epidemiological publications to investigate the potential blunting effect of decade-long maternal immunization efforts. They further devised and implemented a mathematical model to interpret pertussis relative risk while explicitly accounting for vaccine efficacy blunting.

    Their findings reveal the presence of a transient decade-long lag phase following maternal immunization, characterized by the masking and underestimation of blunting effects, thereby explaining previous inconsistencies in the literature. More importantly, the study highlights that while moderate levels of VE loss via blunting do exist, they are far outweighed by the infant mortality savings that maternal vaccination provides.

    Journal reference:

    • Briga, M., Goult, E., Brett, T. S., & Rohani, P. (2024). Maternal pertussis immunization and the blunting of routine vaccine effectiveness: A meta-analysis and modeling study. Nature Communications, 15(1), 1-11., DOI – 10.1038/s41467-024-44943-7, https://www.nature.com/articles/s41467-024-44943-7

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