Aluminum salts have been used as adjuvants in vaccines for nearly a century, enhancing the immune response to purified antigens and ensuring durable protection against serious infectious diseases. Despite their longstanding record of safety and effectiveness, aluminum adjuvants have become a focus of public concern, with claims linking them to developmental, neurologic, allergic, and autoimmune diseases. This review summarizes the immunologic rationale for aluminum adjuvants and evaluates the evidence for proposed safety risks. Aluminum salts have consistently been demonstrated over nearly a century of use to enhance the immune responses elicited by vaccines while also being well tolerated by nearly all who take them. Pharmacokinetic studies show that aluminum released from intramuscular vaccines is slowly absorbed and efficiently cleared by the kidneys, contributing minimally to systemic levels. Large-scale clinical and epidemiologic studies consistently demonstrate no association between aluminum-adjuvanted vaccines and autism spectrum disorder, neurotoxicity, allergic disease, or autoimmune disease. Clinically, vaccines adjuvanted solely with aluminum salts generally do not result in systemic reactogenicity, although local reactions are common. Collectively, the evidence strongly supports the safety of aluminum adjuvants and their necessity in certain vaccines. Clinicians can reassure caregivers that aluminum-containing vaccines provide clear benefits, with risks largely limited to transient local reactions and no systemic toxicity signal in large clinical and epidemiologic studies.

Highly pathogenic avian influenza A(H5N1) is a global health threat due to its high historical virulence and increasing mammalian host range, as demonstrated by the 2024-2025 outbreak among U.S. dairy cattle, with 71 confirmed human infections. While human-to-human transmission has not yet been documented, limited pre-existing human immunity, and uncertainty about evolutionary barriers to human infection make H5N1 a potential pandemic threat. Expanding testing capacity for H5N1 beyond its currently limited scope would be critical for response to potential outbreaks. Thus, we developed and validated a dual-target reverse transcription PCR assay for H5 subtyping of pooled influenza A-positive samples. The assay targets two regions of the hemagglutinin (HA) gene of influenza A(H5). Using contrived samples containing inactivated bovine H5N1 virus, we determined the assay's 95% lower limit of detection for individual samples (58 copies/mL; 95% confidence interval [CI]: 50 to 66 copies/mL) and eight-sample pools (2,465 copies/mL; 95% CI: 1,969 to 3,756 copies/mL). The assay demonstrated 100% positive percent agreement, detecting H5 in all contrived H5-positive pools (32/32 pools; 95% CI: 89.1% to 100.0%) where the contrived positive samples ranged from 500,000 to 3,906 copies/mL. We observed 100% negative percent agreement in H5-negative, influenza A-positive pools (32/32; 95% CI: 89.1% to 100.0%). Though sample pooling reduced analytical sensitivity, contrived samples with H5 virus present at levels typically found in human respiratory infections were detected in eight-sample pools. This approach has the potential to increase testing capacity for influenza A (H5) while maintaining adequate sensitivity, enhancing preparedness for potential outbreaks.IMPORTANCEAvian influenza A(H5N1) poses a potential pandemic threat. H5N1 testing capacity is currently limited. We validated an influenza A (H5) subtyping RT-qPCR for testing pooled samples to increase capacity. The assay displays adequate analytical sensitivity to detect clinical respiratory infections based on prior human cases. This proactive assay validation enhances outbreak preparedness.

OBJECTIVES:The adaptation of clade 2.3.4.4b influenza A(H5N1) to dozens of mammalian species, including dairy cattle, raises concerns about potential spillover into humans. If the virus develops human-to-human transmissibility, sensitive diagnostics will be critical to containment efforts. We sought to determine the lower limit of detection of commercial influenza A tests for the circulating bovine-adapted strain of H5N1. METHODS:We determined the 95% lower limit of detection (LLOD) of 4 commercial respiratory virus panels for detecting inactivated bovine H5N1 (A/bovine/Ohio/B24OSU-439/2024). Two of the tested panels provide seasonal influenza A subtyping, the BioFire Respiratory Panel 2.1 (BioFire Diagnostics/BioMérieux) and the cobas eplex respiratory pathogen panel 2 (Roche Diagnostics), while 2 panels provide pan-influenza A detection, the Xpert Xpress CoV-2/Flu/RSV plus (Cepheid), and the Panther Fusion SARS-CoV-2/Flu A/B/RSV Assay (Hologic, Inc). Serial dilutions of H5 RNA (400-25 copies/mL) were prepared in respiratory virus-negative nasopharyngeal swab matrix, and 20 replicates were tested at each concentration. The 95% LLOD for each test was calculated using probit regression. RESULTS:All 4 tests detected H5 with 95% LLODs below 1000 H5 RNA copies/mL. Xpert demonstrated the highest analytical sensitivity (50 copies/mL; 95% CI, 39-160), followed by BioFire (297 copies/mL; 95% CI, 196-3955), Panther Fusion (531 copies/mL; 95% CI, 421-792), and eplex (883 copies/mL; 95% CI, 588-2741). CONCLUSIONS:Existing commercial respiratory virus panels can effectively detect bovine H5N1. These platforms could support screening in the event of an H5N1 outbreak, followed by confirmation with specific H5 subtyping, as needed.

Current U.S. surveillance for highly pathogenic avian influenza A(H5N1) in humans prioritizes individuals with known animal exposures, potentially missing community-acquired infections. To address this gap, we implemented universal H5 subtyping of all influenza A-positive respiratory samples collected within our hospital system, regardless of patient exposure history. Between August 2024 and April 2025, we subtyped 4,488 influenza A-positive samples and identified two cases positive for H5 RNA in Alameda County, California, USA. The first case was a 14-month-old girl with mild respiratory symptoms and no H5N1 exposure risks; sequencing of the sample revealed an H5 gene closely related to clade 2.3.4.4b, genotype B3.13 viruses circulating in U.S. dairies. The second case was a 79-year-old male, also with no known exposures, whose sample reproducibly tested positive with a high cycle threshold value but could not be confirmed by public health laboratories. Both patients had evidence of co-infection with other common respiratory viruses. These findings, while requiring cautious interpretation due to low virus levels and the presence of potential confounding factors, highlight limitations in exposure-based testing and demonstrate the potential for cryptic H5N1 circulation. This report underscores that broader, geographically targeted surveillance may be a critical tool for early detection of potential community transmission of pandemic-capable pathogens.

Typbar-TCV®, a typhoid conjugate vaccine (TCV), was prequalified by the World Health Organization in 2017. We evaluated its effectiveness in a mass vaccination program targeting children 9 months to 14 years in Navi Mumbai, India, from September 2018 to July 2020. We compared laboratory-confirmed typhoid cases from six clinical sites with age-matched community controls. Of 38 cases, three (8.6%) received TCV through the campaign, compared with 53 (37%) of 140 controls. The adjusted odds ratio of typhoid fever among vaccinated children was 0.16 (95% CI: 0.05–0.55), equivalent to a vaccine effectiveness of 83.7% (95% CI: 45.0–95.3). Vaccine effectiveness of Typbar-TCV in this large public sector vaccine introduction was similar to prior randomized controlled trials, providing reassurance to policymakers that TCV effectiveness is robust in a large-scale implementation.

In 2018, the Navi Mumbai Municipal Corporation implemented phase 1 of a public sector typhoid conjugate vaccine campaign in Navi Mumbai, India, targeting all children aged 9 months to 14 years within its administrative boundaries. To assess associations with receipt of vaccine in phase 1, we used generalized estimating equations to calculate estimates of vaccination by child-, household-, and community-level demographics (child education and age; household head education, income, and occupation; community informal settlement percent). Campaign vaccine receipt was most associated with children enrolled in school (odds ratio [OR] = 3.84, 95% CI: 2.18-6.77), the lowest household income tertile when divided into three equal parts (OR = 1.64, 95% CI: 1.43-1.84), and lower community-level socioeconomic status (OR = 1.06, 95% CI: 1.04-1.08 per 10% informal settlement proportion). The campaign was successful in reaching the most underserved populations of its target communities.

ABSTRACTBackgroundThe WHO recommends vaccines for prevention and control of typhoid fever, especially where antimicrobial-resistant typhoid circulates. In 2018 the Navi Mumbai Municipal Corporation (NMMC), implemented a TCV campaign. The campaign targeted all children aged 9-months through 14-years within NMMC boundaries (∼320,000 children) over 2 vaccination phases. The phase 1 campaign occurred from July 14-August 25, 2018 (71% coverage, ∼113,420 children). We evaluated the campaign’s programmatic effectiveness in reducing typhoid cases at the community level.MethodsWe established prospective, blood culture-based surveillance at 6 hospitals in Navi Mumbai, offering blood cultures to children presenting with fever for at least 3 days. We employed a cluster-randomized test-negative design to estimate the effectiveness of the vaccination campaign on pediatric typhoid cases. We matched culture-confirmed typhoid cases with up to 3 culture-negative controls by age and date of blood culture and assessed community vaccine campaign phase as an exposure using conditional logistic regression.ResultsBetween September 1, 2018–March 31, 2021, we identified 81 typhoid cases and matched these with 238 controls. Cases were 0.44 times as likely to live in vaccine campaign communities (campaign effectiveness, 56%, 95%CI: 25%-74%, p=0.002). Cases ≥ 5-years-old were 0.37 times as likely (95% CI: 0.19-0.70; p-value = 0.002) and cases during the first year of surveillance were 0.30 times as likely (95% CI: 0.14-0.64; p-value = 0.002) to live in vaccine campaign communities.ConclusionsOur findings support the use of TCV mass vaccination campaigns as effective population-based tools to combat typhoid fever.SummaryIn 2018, the Navi Mumbai Municipal Corporation conducted a typhoid conjugate vaccine campaign in half of its communities. Utilizing a test-negative design, we estimate that this campaign reduced typhoid risk by 56% (25-74%) in vaccinated communities compared to non-campaign communities.

The twenty-first century has been marked by a surge in viral epidemics and pandemics, highlighting the global health challenge posed by emerging and re-emerging pediatric viral diseases. This review article explores the complex dynamics contributing to this challenge, including climate change, globalization, socio-economic interconnectedness, geopolitical tensions, vaccine hesitancy, misinformation, and disparities in access to healthcare resources. Understanding the interactions between the environment, socioeconomics, and health is crucial for effectively addressing current and future outbreaks. This scoping review focuses on emerging and re-emerging viral infectious diseases, with an emphasis on pediatric vulnerability. It highlights the urgent need for prevention, preparedness, and response efforts, particularly in resource-limited communities disproportionately affected by climate change and spillover events. Adopting a One Health/Planetary Health approach, which integrates human, animal, and ecosystem health, can enhance equity and resilience in global communities. Impact We provide a scoping review of emerging and re-emerging viral threats to global pediatric populations This review provides an update on current pediatric viral threats in the context of the COVID-19 pandemic This review aims to sensitize clinicians, epidemiologists, public health practitioners, and policy stakeholders/decision-makers to the role these viral diseases have in persistent pediatric morbidity and mortality

We performed whole-genome sequencing of 174 Salmonella Typhi and 54 Salmonella Paratyphi A isolates collected through prospective surveillance in the context of a phased typhoid conjugate vaccine introduction in Navi Mumbai, India. We investigate the temporal and geographical patterns of emergence and spread of antimicrobial resistance. We evaluated the relationship between the spatial distance between households and genetic clustering of isolates. Most isolates were non-susceptible to fluoroquinolones, with nearly 20% containing ≥3 quinolone resistance-determining region mutations. Two H58 isolates carried an IncX3 plasmid containing blaSHV-12, associated with ceftriaxone resistance, suggesting that the ceftriaxone-resistant isolates from India independently evolved on multiple occasions. Among S. Typhi, we identified two main clades circulating (2.2 and 4.3.1 [H58]); 2.2 isolates were closely related following a single introduction around 2007, whereas H58 isolates had been introduced multiple times to the city. Increasing geographic distance between isolates was strongly associated with genetic clustering (odds ratio [OR] = 0.72 per km; 95% credible interval [CrI]: 0.66-0.79). This effect was seen for distances up to 5 km (OR = 0.65 per km; 95% CrI: 0.59-0.73) but not seen for distances beyond 5 km (OR = 1.02 per km; 95% CrI: 0.83-1.26). There was a non-significant reduction in odds of clustering for pairs of isolates in vaccination communities compared with non-vaccination communities or mixed pairs compared with non-vaccination communities. Our findings indicate that S. Typhi was repeatedly introduced into Navi Mumbai and then spread locally, with strong evidence of spatial genetic clustering. In addition to vaccination, local interventions to improve water and sanitation will be critical to interrupt transmission. IMPORTANCE Enteric fever remains a major public health concern in many low- and middle-income countries, as antimicrobial resistance (AMR) continues to emerge. Geographical patterns of typhoidal Salmonella spread, critical to monitoring AMR and planning interventions, are poorly understood. We performed whole-genome sequencing of S. Typhi and S. Paratyphi A isolates collected in Navi Mumbai, India before and after a typhoid conjugate vaccine introduction. From timed phylogenies, we found two dominant circulating lineages of S. Typhi in Navi Mumbai-lineage 2.2, which expanded following a single introduction a decade prior, and 4.3.1 (H58), which had been introduced repeatedly from other parts of India, frequently containing "triple mutations" conferring high-level ciprofloxacin resistance. Using Bayesian hierarchical statistical models, we found that spatial distance between cases was strongly associated with genetic clustering at a fine scale (<5 km). Together, these findings suggest that antimicrobial-resistant S. Typhi frequently flows between cities and then spreads highly locally, which may inform surveillance and prevention strategies.

BACKGROUND AND AIM: Exposure to heavy metals during pregnancy has been associated with an increased risk of adverse birth outcomes, including stillbirth. Our study aims to investigate the sources of exposure to select metals (arsenic, lead, and cadmium) during pregnancy among women residing Faridpur and adjacent districts, namely Madaripur, Rajbari, Jhenaida, Magura, Gopalganj, Kushtia and Dhaka, Bangladesh. METHOD: We have enrolled women who experience stillbirths (N=31) and live births (N=33) at Bangabandhu Sheikh Mujib Medical College Hospital, Faridpur in Bangladesh, with 64 participants enrolled to date. Samples of drinking and cooking water, rice, courtyard and agricultural soil, and turmeric were collected from homes where participants resided for at least two trimesters of pregnancy. Concentrations of lead, cadmium, and arsenic in turmeric and soil were measured using a handheld X-ray fluorescence analyzer. RESULTS: Turmeric lead concentrations exceeded the Bangladesh standard (2.5 μg/g.) in approximately 10% of turmeric samples, with a maximum concentration of 46 μg/g. Arsenic was not detected in these samples. Out of 64 participant households, 27 had agricultural land and provided agrarian soil samples. None of the courtyard or agricultural soil samples had lead concentrations exceeding the threshold of 400 μg/g set by the US EPA. Only one courtyard was found to have soil arsenic concentrations exceeding the threshold level for arsenic (20 μg/g); however, over 40% of agricultural soil samples had arsenic concentrations above 20 μg/g, with an average concentration of 16.8 μg/g (±12.1 μg/g). Cadmium was not detected in the courtyard or agricultural soil samples. CONCLUSIONS: Pregnant women residing in Faridpur and adjacent districts of Bangladesh may face a potential risk of exposure to high concentrations of lead in turmeric as well as arsenic in agricultural soil or output. Our continued research will evaluate associations between heavy metal exposure and stillbirth in this community.

ABSTRACT. India has one of the highest estimated burdens of enteric fever globally. Prior to the implementation of Typbar-TCV typhoid conjugate vaccine (TCV) in a public sector pediatric immunization campaign in Navi Mumbai, India, we conducted a retrospective review of blood culture-confirmed cases of typhoid and paratyphoid fevers to estimate the local burden of disease. This review included all blood cultures processed at a central microbiology laboratory, serving multiple hospitals, in Navi Mumbai (January 2014–May 2018) that tested positive for either Salmonella Typhi or Salmonella Paratyphi A. Of 40,670 blood cultures analyzed, 1,309 (3.2%) were positive for S. Typhi (1,201 [92%]) or S. Paratyphi A (108 [8%]). Culture positivity was highest in the last months of the dry season (April–June). Our findings indicate a substantial burden of enteric fever in Navi Mumbai and support the importance of TCV immunization campaigns and improved water, sanitation, and hygiene.

Typhoid fever caused by infection with Salmonella enterica subspecies enterica serotype Typhi (S. Typhi), an important public health problem in many low- and middle-income countries, is transmitted by ingestion of water or food contaminated by feces or urine from individuals with acute or chronic S. Typhi infection. Most chronic S. Typhi carriers (shedding for ≥12 months) harbor infection in their gallbladder wherein preexisting pathologies, particularly cholelithiasis, provide an environment that fosters persistence. Much less appreciated is the existence of non-gallbladder hepatobiliary chronic S. Typhi carriers and urinary carriers. The former includes parasitic liver flukes as a chronic carriage risk factor. Chronic urinary carriers typically have pathology of their urinary tract, with or without renal or bladder stones. Even as the prevalence of multidrug-resistant and extensively drug-resistant S. Typhi strains is rising, global implementation of highly effective typhoid vaccines is increasing. There is also renewed interest in identifying, monitoring, and (where possible) treating chronic carriers who comprise the long-term reservoir of S. Typhi.

Approximately 90% of chronic typhoid carriers with persistent Salmonella enterica serovar Typhi (S. Typhi) gallbladder infection have gallstones. In Samoa, where typhoid fever has been endemic for many decades, risk factors predisposing to the development of gallstones are increasing among adults. The Samoa Typhoid Fever Control Program dispatches a "Typhoid Epidemiologic SWAT Team" to perform a household investigation of every blood culture-confirmed case of acute typhoid fever. Investigations include screening household contacts to detect chronic carriers. Following limited training, two nonexpert ultrasound operators performed point-of-care ultrasound (POCUS) on 120 Samoan adults from August to September 2019 to explore the feasibility of POCUS to detect individuals with gallstones during household investigations and community screenings. POCUS scans from 120 Samoan adults in three cohorts (28 food handlers, two typhoid cases and their 18 household contacts, and 72 attendees at an ambulatory clinic) were reviewed by a board-certified radiologist who deemed 96/120 scans (80%) to be interpretable. Compared with the radiologist (gold standard), the nonexpert operators successfully detected 6/7 Samoans with gallstones (85.7% sensitivity) and correctly identified 85/89 without gallstones (95.5% specificity). The proportion (24/120) of uninterpretable scans from this pilot that used minimally trained clinicians (who are neither radiologists nor ultrasound technicians) indicates the need for additional training of POCUS operators. Nevertheless, this pilot feasibility study engenders optimism that in the Samoan setting nonexperts can be trained to use POCUS to diagnose cholelithiasis, thereby helping (along with stool cultures and Vi serology) to identify possible chronic S. Typhi carriers.

We report persistent severe acute respiratory syndrome coronavirus 2 infection in a patient with HIV/AIDS; the virus developed spike N terminal domain and receptor binding domain neutralization resistance mutations. Our findings suggest that immunocompromised patients can harbor emerging variants of severe acute respiratory syndrome coronavirus 2.

Background. Typhoid fever has been endemic on the island nation of Samoa (2016 population, 195979) since the 1960s and has persisted through 2019, despite economic development and improvements in water supply and sanitation. Methods. Salmonella enterica serovar Typhi isolates from the 2 hospitals with blood culture capability and matched patient demographic and clinical data from January 2008 through December 2019 were analyzed. Denominators to calculate incidence by island, region, and district came from 2011 and 2016 censuses and from 2017-2019 projections from Samoa's Bureau of Statistics. Data were analyzed to describe typhoid case burden and incidence from 2008 to 2019 by time, place, and person. Results. In sum, 53-193 blood culture-confirmed typhoid cases occurred annually from 2008 to 2019, without apparent seasonality. Typhoid incidence was low among children age<48 months (17.6-27.8/10(5)), rose progressively in ages 5-9 years (54.0/10(5)), 10-19 years (60.7-63.4/10(5)), and 20-34 years (61.0-79.3/10(5)), and then tapered off; 93.6% of cases occurred among Samoans<50 years of age. Most typhoid cases and the highest incidence occurred in Northwest Upolu, but Apia Urban Area (served by treated water supplies) also exhibited moderate incidence. The proportion of cases from short-cycle versus long-cycle transmission is unknown. Samoan S. Typhi are pansusceptible to traditional first-line antibiotics. Nevertheless, enhanced surveillance in 2019 detected 4 (2.9%) deaths among 140 cases. Conclusions .Typhoid has been endemic in Samoa in the period 2008-2019. Interventions, including mass vaccination with a Vi-conjugate vaccine coadministered with measles vaccine are planned.

A 64-year-old African American man, with a history of prostate adenocarcinoma treated in 2009 and a greater than 50-pack-year tobacco smoking history, presented with 2–3 weeks of non-productive cough, frontal headache and generalised myalgias and arthralgias. CT was positive for diffuse, miliary opacities in bilateral lung fields. He was diagnosed with stage four lung adenocarcinoma, negative for epidermal growth factor receptor (EGFR) gene mutation. The patient was unable to tolerate therapy and passed away approximately 4 months after his diagnosis. Previous case reports and research have suggested an association between EGFR gene mutation and miliary patterned lung metastases in non-small cell lung cancer. This case suggests that the mechanism by which miliary patterned metastases occur is more complex than purely mutation of the EGFR gene. Further study may elucidate novel molecular targets for treatment, especially in patients with rapidly progressive disease such as the patient we describe.

Background New interventions are required to optimally and sustainably control the Anopheles sp. mosquitoes that transmit malaria and filariasis. The mosquito olfactory system is important in host seeking (transmission) and mate finding (reproduction). Understanding olfactory function could lead to development of control strategies based on repelling parasite-carrying mosquitoes or attracting them into a fatal trap. Findings Our initial focus is on odorant binding proteins with differential transcript accumulation between female and male mosquitoes. We report that the odorant binding protein, OBP2 (AGAP003306), had increased expression in the antennae of female vs. male Anopheles gambiae sensu stricto (G3 strain). The increased expression in antennae of females of this gene by quantitative RT-PCR was 4.2 to 32.3 fold in three independent biological replicates and two technical replicate experiments using A. gambiae from two different laboratories. OBP2 is a member of the vast OBP superfamily of insect odorant binding proteins and belongs to the predominantly dipteran clade that includes the Culex oviposition kairomone-binding OBP1. Phylogenetic analysis indicates that its orthologs are present across culicid mosquitoes and are likely to play a conserved role in recognizing a molecule that might be critical for female behavior. Conclusions OBP2 has increased mRNA transcript accumulation in the antennae of female as compared to male A. gambiae . This molecule and related molecules may play an important role in female mosquito feeding and breeding behavior. This finding may be a step toward providing a foundation for understanding mosquito olfactory requirements and developing control strategies based on reducing mosquito feeding and breeding success.

The role of light exposure on the final stages of development of Anopheles stephensi larvae to pupae and adult mosquitoes was explored. We demonstrated a significant reduction in the development of adult mosquitoes when larvae were bred in the absence of light compared with the control group bred in alternating 12 h of light and 12 h of dark. To correlate these findings at the molecular level, RNA levels of the visual arrestin gene were examined. Arrestins are an important gene family that play a role in the vectorial capacity of Anopheles and mediate neurotransmission as well as olfactory and visual sensory reception in insects. Semiquantitative polymerase chain reaction showed a reduction in the expression of the visual arrestin gene in pupae that developed from larvae in the absence of light compared with larvae bred under normal conditions.