Pathogens

14 pages, 1795 KB

Open AccessArticle

Epidemiological Trends, Statistical Correlations, and Forecasting of Notifiable Infectious Diseases in South Korea, 2001–2024: A Regression and Time Series Analysis with Projections to 2028

by Hyeran Jung and Minsun Jung

Pathogens 2026, 15(8), 780; https://doi.org/10.3390/pathogens15080780 - 23 Jul 2026

Abstract

Background: Notifiable infectious diseases impose a substantial, evolving burden on public health systems. This study characterized long-term epidemiological trends, inter-class associations, and age-stratified patterns of notifiable infectious diseases in South Korea and projected future burden through 2028. Methods: We analyzed aggregate national surveillance [...] Read more.

Background: Notifiable infectious diseases impose a substantial, evolving burden on public health systems. This study characterized long-term epidemiological trends, inter-class associations, and age-stratified patterns of notifiable infectious diseases in South Korea and projected future burden through 2028. Methods: We analyzed aggregate national surveillance data (2001–2024) from the Korea Disease Control and Prevention Agency (KDCA) via the Korean Statistical Information Service (KOSIS). Because the statutory classification changed in 2020 from a four-group (Class 1–4, gun) to a four-grade (geup) system, all inferential trend, correlation, and forecasting analyses were restricted to the internally consistent 2001–2019 group-system period, and 2020–2024 grade-system data were used descriptively. Secular trends were estimated with ordinary least squares and, for count-specific inference, negative-binomial log-linear models (annual percent change, APC); residual autocorrelation was assessed (Durbin–Watson, Ljung–Box). Structural breaks were estimated objectively (Bai–Perron least-squares). Inter-class associations were tested with Pearson/Spearman correlations and re-evaluated with partial correlation (controlling for calendar year) and first-difference detrending to guard against spurious co-trending. Forecasts used a random-walk ARIMA (identified by ADF stationarity testing, ACF/PACF, and AICc) and a damped Holt–Winters model on the H1N1-adjusted series, combined into an ensemble; performance was validated by rolling-origin cross-validation (RMSE, MAE, MAPE). Results: After handling the 2009 H1N1 pandemic outlier, total notifications rose significantly over 2001–2019 (slope = 8344 cases/year; 95% CI 6603–10,084; R² = 0.866; p < 0.001). Class 2 (respiratory/vaccine-preventable) diseases showed the strongest trend (APC = 17.2%/year; 95% CI 8.0–27.3), with an objectively estimated structural break at 2004 (supF = 10.5) separating an early variable phase from sustained growth (2005–2019: +7418 cases/year; R² = 0.94). Raw Class 1–Class 2 correlation (Pearson r = 0.569, p = 0.011) did not survive temporal adjustment (partial r = 0.13, p = 0.59; detrended r = −0.31, p = 0.21), indicating shared secular co-trending rather than a direct epidemiological association; only Class 2–Class 3 remained associated after detrending (r = 0.52, p = 0.03). Young working-age adults (30–49 years) showed the steepest Class 1 increases. Ensemble projections for the pre-COVID trajectory were 238,000 (2025) to 269,000 (2028) annual notifications, with wide prediction intervals reflecting substantial uncertainty. Conclusions: South Korean notifiable-disease epidemiology was dominated by a genuine upward Class 2 respiratory trend; several previously reported inter-class correlations were attributable to common temporal trends rather than shared transmission. Post-COVID normalization monitoring and respiratory-disease surveillance investment are priority actions. Full article

(This article belongs to the Special Issue Epidemiology of Vector-Borne Pathogens)

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8 pages, 4652 KB

Open AccessBrief Report

High Burden of Asymptomatic Malaria Among Schoolchildren in Nigeria: Diagnosis Challenges and pfhrp2 Deletions

by Irene Molina-de la Fuente, Akeem Abiodun Akindele, Thuy-Huong Ta-Tang, Alexandra Martin-Ramírez, Vicenta Gonzalez, Ibukun Temitope Sossou, Samuel Adeyinka Adedokun, Raquel Capote-Morales, Agustín Benito, Sulaiman Adebayo Nassar and Pedro Berzosa

Pathogens 2026, 15(8), 779; https://doi.org/10.3390/pathogens15080779 - 23 Jul 2026

Abstract

Background: Nigeria has a high prevalence of malaria, with asymptomatic patients being one of the possible reservoirs. In this context, accurate diagnosis is essential for malaria control. The efficacy of rapid diagnostic tests (RDTs) is being threatened by false negatives due to pfhrp2 [...] Read more.

Background: Nigeria has a high prevalence of malaria, with asymptomatic patients being one of the possible reservoirs. In this context, accurate diagnosis is essential for malaria control. The efficacy of rapid diagnostic tests (RDTs) is being threatened by false negatives due to pfhrp2 and pfhrp3 deletions. This study aims to describe malaria in asymptomatic schoolchildren in Osun State, Southwestern Nigeria and to assess the performance of malaria diagnosis, including the characterisation of pfhrp2 and pfhrp3 deletions. Methods: A total of 350 dried blood spot (DBS) samples from schoolchildren were used for malaria diagnosis using microscopy, RDTs, and polymerase chain reaction (PCR). Sensitivity and specificity were calculated for microscopy and RDTs, using PCR as the gold standard. Pfhrp2 and pfhrp3 deletions were analysed for all P. falciparum-positive samples using multiplex qPCR. Results: The P. falciparum infection frequency among asymptomatic schoolchildren in Osun State was 89%. Considering PCR as the gold standard, microscopy presented better sensitivity at 100% (86% for RDTs), but RDTs had better specificity at 76% (60% for microscopy). The deletion frequency of the pfhrp2 gene among positive samples was 16.6%, while it was 1.3% for pfhrp3 and 0.9% for double deletion. However, considering all positive samples, only 3% of samples yielded false negatives by RDT with deletion in pfhrp2. Conclusions: P. falciparum infection has a high frequency in asymptomatic schoolchildren, being a potential hotspot for malaria. The combination of RDTs and microscopy could increase the accuracy of malaria diagnosis. Deletions in pfhrp2 and pfhrp3 are highly common in Osun State, but their impact on RDT results is still limited. More surveillance studies are recommended to assess the contribution of asymptomatic children to malaria transmission and the impact of deletions. Full article

(This article belongs to the Special Issue Molecular Epidemiology and Host-Pathogen Interactions in Infectious Diseases)

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17 pages, 1612 KB

Open AccessArticle

Effect of Methyl Gallate on Physiological and Gut Microbiota-Associated Responses Following a Single Intramuscular Administration of Tylosin in Weaned Piglets

by Hae-Yeon Cho, Syed Al Jawad Sayem, Ga-Yeong Lee, Jonghyun Park, Eon-Bee Lee, Mi-Hyang Hwangbo and Seung-Chun Park

Pathogens 2026, 15(7), 778; https://doi.org/10.3390/pathogens15070778 - 22 Jul 2026

Abstract

Tylosin (TYL), a macrolide antibiotic, is commonly used to treat respiratory infections in weaned piglets. Despite its utility, TYL administration is associated with adverse side effects, including immune dysregulation and gut microbiota imbalance. This study evaluated whether methyl gallate (MG), a natural polyphenolic [...] Read more.

Tylosin (TYL), a macrolide antibiotic, is commonly used to treat respiratory infections in weaned piglets. Despite its utility, TYL administration is associated with adverse side effects, including immune dysregulation and gut microbiota imbalance. This study evaluated whether methyl gallate (MG), a natural polyphenolic compound with antimicrobial and immunomodulatory properties, could mitigate these side effects of TYL. Forty weaned piglets were randomly assigned to a saline control group, a TYL (10 mg/kg) group, an MG (10 mg/kg) group, and a TYL + MG (10 mg/kg each) group. Changes in body weight, hematological parameters, plasma cytokines, culturable fecal bacterial populations, and 16S rRNA-based gut microbiota composition were evaluated in all weaned piglets. There were no significant differences (p > 0.05) in ADG, ADFI, or FE among the treatment groups. Hematological analysis revealed significant changes in neutrophil and eosinophil counts, showing significant fluctuations in the MG-treated group compared with the control. TYL administration significantly decreased TNF-α and IL-1β levels while increasing IL-10 and IL-1ra concentrations, indicating immunomodulatory effects. In contrast, MG significantly increased adaptive immune-associated cytokines, including IL-2, IL-4, IL-6, and IL-12. Culture-based fecal microbiological analysis revealed that TYL reduced Lactobacillus abundance and lowered the culture-based Lactobacillus/Enterobacteriaceae ratio, suggesting acute dysbiosis. Co-administration of MG partially attenuated these microbiota-associated alterations and promoted the recovery of bacterial populations. Moreover, 16S rRNA sequencing demonstrated that similar relative abundances of Proteobacteria were observed in the TYL and TYL + MG groups. Therefore, no clear reduction in relative abundance of Proteobacteria was demonstrated under the present experimental conditions. These findings support the possibility that MG may partially attenuate selected TYL-associated immunological and gut microbiota-related changes under the conditions of the present exploratory study. A graphical summary of the study design and the principal findings is presented in the Graphical Abstract. Full article

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11 pages, 684 KB

Open AccessArticle

Two Diagnostic Challenges in Hepatitis B Serology: Low HBsAg S/CO Values and Isolated Anti-HBc Positivity

by Şerife Yılmaz Gürbüz, Oğuzhan Yağdı and Erhan Başar

Pathogens 2026, 15(7), 777; https://doi.org/10.3390/pathogens15070777 - 22 Jul 2026

Abstract

Hepatitis B surface antigen (HBsAg) signal-to-cutoff (S/CO) values and isolated anti-HBc positivity represent two significant diagnostic challenges in hepatitis B virus (HBV) serology. This retrospective study, conducted in Karabük between 2021 and 2025, aimed to evaluate the correlation between these profiles and HBV [...] Read more.

Hepatitis B surface antigen (HBsAg) signal-to-cutoff (S/CO) values and isolated anti-HBc positivity represent two significant diagnostic challenges in hepatitis B virus (HBV) serology. This retrospective study, conducted in Karabük between 2021 and 2025, aimed to evaluate the correlation between these profiles and HBV DNA positivity to determine the optimal S/CO thresholds for confirmatory testing and clarify the clinical relevance of isolated anti-HBc reactivity. Among 17,356 patients screened for anti-HBc, isolated anti-HBc positivity was identified in 506 patients (2.9%), of whom 3.2% had detectable HBV DNA. Positivity was significantly higher in patients older than 50 years and in the Gastroenterology department. Separately, 213 specimens with HBsAg S/CO values between 1.0 and 10.0 underwent HBV DNA confirmation testing. ROC analysis yielded an excellent area under the curve of 0.937, with an S/CO threshold of ≥3.04, achieving 100% sensitivity for HBV DNA detection. All specimens with S/CO values between 1.0 and 3.0 were HBV DNA-negative. In this study population, no serum HBV DNA positivity was detected among samples with S/CO values below 3.04, suggesting that HBV DNA testing may help avoid unnecessary confirmatory work-up in this range. Anti-HBc screening should be prioritized in older patients. S/CO-based confirmatory algorithm using HBV DNA testing may improve diagnostic accuracy and reduce unnecessary clinical interventions in routine hepatitis B screening programs. Full article

12 pages, 375 KB

Open AccessArticle

High Prevalence of Occult Hepatitis B Virus Co-Infection Identified in Treponema Pallidum-Positive Blood Donations: Implications for HBV Risk Reduction

by Xianlin Ye, Xiaoxuan Xu, Jinfeng Zeng, He Xie, Jujun Sun, Baoren He and Limin Chen

Pathogens 2026, 15(7), 776; https://doi.org/10.3390/pathogens15070776 - 22 Jul 2026

Abstract

Over the past decade, the incidence of infectious syphilis has been on the rise in the general Chinese population. Consequently, Treponema Pallidum (TP) testing has been proposed as a surrogate marker for sexually transmitted pathogens and for monitoring risky sexual behaviors among blood [...] Read more.

Over the past decade, the incidence of infectious syphilis has been on the rise in the general Chinese population. Consequently, Treponema Pallidum (TP) testing has been proposed as a surrogate marker for sexually transmitted pathogens and for monitoring risky sexual behaviors among blood donors globally. In addition, sexual contact with individuals chronically infected with hepatitis B virus (HBV) is recognized as one of the primary routes of HBV transmission. Blood donors may acquire HBV infection through sexual contact with chronically infected partners, particularly with occult hepatitis B infections (OBIs), which are characterized by intermittent and extremely low viral loads. Therefore, the prevalence of OBIs among syphilis-positive blood donations and the corresponding risks to blood safety require further investigation. This study aimed to investigate the prevalence of OBIs among syphilis-positive blood donors and assess the surrogate value of TP testing for evaluating OBI-related risks to blood supply. After routine screening using serological assays and nucleic acid testing (NAT), blood donation samples with positive anti-TP enzyme-linked immunosorbent assay (ELISA) results were collected and further confirmed by the Treponema Pallidum Particle Agglutination Assay (TPPA). For blood donations confirmed positive for syphilis, further tests were performed to characterize whether the donations had HBV co-infection, including electrochemiluminescence immunoassay (ECLI) for the detection of hepatitis B surface antigen (HBsAg), anti-hepatitis B surface antibody (anti-HBs), hepatitis B e antigen (HBeAg), anti-hepatitis B e antibody (anti-HBe), and anti-hepatitis B core antibody (anti-HBc). Additionally, quantitative real-time polymerase chain reaction (qPCR) was used for HBV DNA quantification, and nested PCRs for the S and basal core promoter/precore (BCP/PC) region were conducted in combination with high-volume nucleic acid extraction. Subsequently, molecular characterization of HBV DNA in these co-infected samples was carried out by DNA sequencing to analyze the viral genetic features. Of 252 anti-TP ELISA+ donations screened from 64,871 blood samples, 138 (138/250, 55.2%) donations were confirmed syphilis-positive but NAT−, among which 78 (78/138, 56.5%) were anti-HBc-positive, and 88 (88/138, 63.7%) had anti-HBs. Notably, seven donations (7/138, 5.1%) were diagnosed as OBI co-infections, and available sequence analysis revealed that three cases were genotype B and one case was genotype C. In addition, several mutations in the S region of the HBV genome were identified, including Q101R, K122R, Q129H, T131N, M133T, G145R, and Y161F mutations. Furthermore, nucleotide mutations such as T1719G, A1752T, G1896A, and A1762T/G1764A in the BCP/PC regions were also detected in these OBI donations. These mutations may contribute to the extremely low HBV viral loads and/or failure in HBsAg detection, collectively leading to OBIs. These data indicate that syphilis screening of blood donors has potential to serve as an additional safeguard measure for excluding donations co-infected with OBIs. The high prevalence of undetected OBIs in syphilis-positive blood donors further supports that syphilis screening has the potential to serve as a surrogate marker for HBV-related risks in the blood supply. Full article

(This article belongs to the Special Issue Advances in the Epidemiology of Human Infectious Diseases)

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19 pages, 15582 KB

Open AccessArticle

Distribution and Genetic Diversity of Borrelia from Lyme Borreliosis and Relapsing Fever Groups in Ixodidae Ticks in the Russian Far East

by Yuliya Sabitova, Vera Rar, Valeria Fedorets, Yana Igolkina, Tamara Epikhina, Aleksey Nikitin, Yulia Verzhutskaya, Valentina Kolesnikova, Natalia Gordeiko, Natalya Pukhovskaya and Nina Tikunova

Pathogens 2026, 15(7), 775; https://doi.org/10.3390/pathogens15070775 - 22 Jul 2026

Abstract

Ixodidae ticks are vectors of pathogenic spirochetes from the Borrelia burgdorferi sensu lato (s.l.) complex and the relapsing fever (RF) group. The Russian Far East is endemic for borrelioses, yet data on the distribution and genetic diversity of Borrelia spp. in this region [...] Read more.

Ixodidae ticks are vectors of pathogenic spirochetes from the Borrelia burgdorferi sensu lato (s.l.) complex and the relapsing fever (RF) group. The Russian Far East is endemic for borrelioses, yet data on the distribution and genetic diversity of Borrelia spp. in this region remain scarce. We examined 3107 Ixodidae ticks (Ixodes spp., Haemaphysalis spp., and Dermacentor silvarum), collected from two mainland provinces and five islands of the Russian Far East in 2005–2023. A total of 86 Borrelia afzelii, 297 Borrelia bavariensis, 81 Borrelia garinii, 44 Borrelia miyamotoi, and 33 unclassified RF borreliae were identified. Borrelia burgdorferi s.l. and B. miyamotoi were strongly associated with Ixodes spp., whereas unclassified RF borreliae were associated with Haemaphysalis spp. Among B. burgdorferi s.l. isolates, B. afzelii and B. bavariensis were found significantly more frequently in I. persulcatus compared to I. pavlovskyi, whereas B. garinii was significantly more common in I. pavlovskyi. Genetic characterization of B. burgdorferi s.l. revealed high haplotypic diversity, particularly within B. bavariensis and B. garinii. Among RF borreliae, all B. miyamotoi isolates were highly conserved and belonged to the Asian type. In contrast, unclassified RF borreliae were genetically variable and clustered with RF borreliae previously found in Haemaphysalis and Rhipicephalus ticks. The obtained results expand the understanding of the distribution and genetic diversity of Borrelia spp. in the Russian Far East. Full article

(This article belongs to the Special Issue Ticks and Tick-Borne Pathogens in a Changing World)

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17 pages, 15663 KB

Open AccessCase Report

Mycobacterium tuberculosis and Mycobacterium avium Complex Cutaneous Co-Infection: Diagnostic and Therapeutic Challenges

by Minhua Weng, Guizhong Zhou, Qiuping Wu, Qiong Chen, Jiabin Li, Zheng Wang and Wenting Li

Pathogens 2026, 15(7), 774; https://doi.org/10.3390/pathogens15070774 - 22 Jul 2026

Abstract

Cutaneous co-infection with Mycobacterium tuberculosis (MTB) and Mycobacterium avium complex (MAC) is extremely rare and easily missed due to overlapping histopathological features. We report a previously healthy, HIV-negative middle-aged woman who presented with a progressive destructive mass in the left inguinal-perineal region. Imaging [...] Read more.

Cutaneous co-infection with Mycobacterium tuberculosis (MTB) and Mycobacterium avium complex (MAC) is extremely rare and easily missed due to overlapping histopathological features. We report a previously healthy, HIV-negative middle-aged woman who presented with a progressive destructive mass in the left inguinal-perineal region. Imaging revealed sinus tract formation, osteolytic bone lesions, and chronic inflammation in the right middle lobe of the lung. Initial metagenomic next-generation sequencing (mNGS) detected 3756 reads of the Mycobacterium tuberculosis complex (MTBC) and 111 reads of Mycobacterium intracellulare (M. intracellulare); the latter was interpreted as possible colonization or contamination because of its low abundance. Empirical anti-tuberculosis therapy produced only transient partial improvement, followed by paradoxical worsening, local recurrence, and new bone destruction. After a high suspicion of mixed infection, a MAC-directed combination regimen (including azithromycin and a short course of amikacin) was added, leading to complete clinical cure; subsequent repeat cultures confirmed the presence of MAC. This is the first report of cutaneous MTB-MAC co-infection in the inguinal-perineal region of an adult without overt immune abnormalities, accompanied by disseminated bone lesions. This case highlights that in regions where nontuberculous mycobacteria (NTM) are co-endemic, atypical destructive skin lesions with paradoxical worsening despite initial response to anti-tuberculosis therapy should raise suspicion of MAC co-infection. The combination of mNGS and conventional culture facilitates identification of mixed infections and guides precision therapy, but mNGS results must be interpreted cautiously in the clinical context. Full article

(This article belongs to the Section Bacterial Pathogens)

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15 pages, 689 KB

Open AccessArticle

Investigation of the Anti-Toxoplasma gondii Potential of Loratadine

by Stephanie Ortega Alves, Ingrid de Oliveira Dias, Gabriel Candido Moura, Samuel Cota Teixeira and Juliana Quero Reimão

Pathogens 2026, 15(7), 773; https://doi.org/10.3390/pathogens15070773 - 22 Jul 2026

Abstract

Toxoplasmosis remains a major global health concern, particularly in immunocompromised individuals and pregnant women, while currently available therapies are associated with significant toxicity and limited efficacy against chronic infection. Drug repurposing represents an attractive strategy for the identification of safer and more effective [...] Read more.

Toxoplasmosis remains a major global health concern, particularly in immunocompromised individuals and pregnant women, while currently available therapies are associated with significant toxicity and limited efficacy against chronic infection. Drug repurposing represents an attractive strategy for the identification of safer and more effective anti-Toxoplasma gondii agents. This study investigated the antiparasitic potential of loratadine, a second-generation antihistamine, using an integrated in silico, in vitro, and in vivo approach. The anti-T. gondii activity of loratadine was evaluated through β-galactosidase-based proliferation assays, reversibility assays, and experiments using pretreated tachyzoites. In vivo efficacy was assessed in murine models of acute and chronic toxoplasmosis. Disease progression, survival, parasite burden, and cerebral cyst formation were analyzed following treatment. Loratadine inhibited the intracellular proliferation of T. gondii tachyzoites in a concentration-dependent manner and induced partially irreversible effects on parasite viability after drug withdrawal. Pretreatment of extracellular tachyzoites produced limited effects, suggesting that loratadine predominantly acts during the intracellular stage of infection. In the acute toxoplasmosis model, loratadine treatment delayed disease progression, prolonged animal survival, and significantly reduced the number of tachyzoites recovered from the peritoneal cavity. In the chronic infection model, treatment significantly decreased both the number and size of cerebral cysts, although these findings do not demonstrate cyst eradication or direct bradyzoite killing. Despite its measurable biological activity, loratadine exhibited a relatively low in vitro selectivity index, highlighting the need for further optimization. These exploratory findings identify loratadine as a promising lead compound (hit) for further optimization rather than an immediately translatable therapeutic candidate. Additional medicinal chemistry, pharmacokinetic, mechanistic, and confirmatory preclinical studies will be required to determine its potential for anti-T. gondii drug development. Full article

(This article belongs to the Special Issue Discovery of Novel Antiprotozoal Agents: Current Status and Future Perspectives)

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12 pages, 1403 KB

Open AccessArticle

Acaricidal Activity of Liquid Culture Filtrates from Nematophagous Fungi Against Rhipicephalus microplus Ticks

by Oscar Guadalupe Barrón-Bravo, Pedro Mendoza-de Gives, César Andrés Ángel-Sahagún, Ricardo Avilés-Ruiz, Rubén D. Garza-Cedillo, José L. Arispe-Vázquez, Juan Patishtan-Pérez and Gustavo Pérez-Anzúrez

Pathogens 2026, 15(7), 772; https://doi.org/10.3390/pathogens15070772 - 22 Jul 2026

Abstract

Rhipicephalus microplus ticks harm cattle health and productivity. Frequent use of ixodicides can result in resistant tick populations and environmental contamination, as residues enter soil. Nematophagous (NF) and entomopathogenic fungi (EF) are natural enemies of nematodes and insect pests. This study tested the [...] Read more.

Rhipicephalus microplus ticks harm cattle health and productivity. Frequent use of ixodicides can result in resistant tick populations and environmental contamination, as residues enter soil. Nematophagous (NF) and entomopathogenic fungi (EF) are natural enemies of nematodes and insect pests. This study tested the in vitro lethal effects of liquid culture filtrates (LCFs) from selected NF on R. microplus. Fungi were grown in Czapek-Dox broth for 30 days at room temperature to obtain LCFs, which were tested using the immersion method. Experimental groups included: (1) Arthrobotrys musiformis, (2) Purpureocillium lilacinum, (3) Flavocillium subprimulinum, (4) Lecanicillium psalliotae, (5) ixodicide mixture (permethrin and chlorpyrifos), (6) negative control (water), and (7) negative control (Czapek-Dox broth). Differences in tick mortality among filtrate treatments starting on day 10 were observed. Filtrates from L. psalliotae and A. musiformis caused the highest mortality, with A. musiformis reaching 40% and L. psalliotae 33.3% on days 14, 16, and 18 (p < 0.01). We anticipated that combining ixodicides would lead to substantial tick mortality; however, the ixodicidal compounds (chlorpyrifos and permethrin) resulted in 33.3% mortality by day 18, which was similar to that observed for L. psalliotae during the same period. Filtrates from P. lilacinum and F. subprimulinum had no effect. The ixodicide treatment led to a significant reduction in oviposition, averaging 69.8% (p < 0.05). LCFs of selected NF could be used against either nematodes or R. microplus ticks. Full article

(This article belongs to the Section Parasitic Pathogens)

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14 pages, 1590 KB

Open AccessArticle

Salmonella enterica in Northern Italy: Insights from a Historical Collection

by Priscilla Pasutto, Antonella Amendola, Maria Gori, Clara Fappani, Marta Gusmeroli, Daniela Colzani, Elisa Borghi, Mirella Pontello, Elisabetta Tanzi and Silvia Bianchi

Pathogens 2026, 15(7), 771; https://doi.org/10.3390/pathogens15070771 - 22 Jul 2026

Abstract

Historical microbiological collections linked to epidemiological and clinical metadata represent a valuable resource for retrospective investigation of long-term changes in pathogen populations. In this retrospective study, we analyzed the epidemiological, clinical, and microbiological information recorded in the datasheets accompanying Salmonella enterica isolates archived [...] Read more.

Historical microbiological collections linked to epidemiological and clinical metadata represent a valuable resource for retrospective investigation of long-term changes in pathogen populations. In this retrospective study, we analyzed the epidemiological, clinical, and microbiological information recorded in the datasheets accompanying Salmonella enterica isolates archived in a historical collection assembled in Lombardy, Italy, between 2001 and 2016. Overall, metadata associated with 6624 salmonellosis cases with confirmed serovar identification were included to describe serovar distribution, bloodstream infections, and antimicrobial resistance (AMR) patterns within the collection. Four serovars (S. Typhimurium, S. Enteritidis, S. 1,4,[5],12:i:-, S. Napoli) accounted for approximately 80% of all cases. The relative representation of S. Napoli increased over the study period, whereas S. Choleraesuis showed the highest proportion of bloodstream isolates and predominantly affected adults. Overall, resistance to penicillins (46.9%) and tetracyclines (48.0%) was common, whereas resistance to fluoroquinolones (2.9%) and third-generation cephalosporins (<2%) remained low. Among invasive non-typhoidal Salmonella (iNTS) infections, 69.3% of isolates were resistant to at least one antimicrobial class, and 34.7% exhibited multidrug resistance (MDR), with fluoroquinolone resistance increasing to 13.9%. These findings highlight the value of historical microbiological collections and their associated metadata for documenting long-term changes in serovar distribution, invasive infections, and AMR, while emphasizing their importance as a resource for future molecular epidemiology and One Health surveillance. Full article

(This article belongs to the Section Bacterial Pathogens)

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15 pages, 1773 KB

Open AccessArticle

Low-Dose Interleukin-2 Enhances Activated Suppressor Regulatory T Cells and CTLA-4 and HLA-DR Expression in Chronic Chikungunya Arthritis

by Sarah R. Tritsch, Jose Forero Mejia, Evelyn Mendoza-Torres, Alfonso Sucerquia, Abebawork Adem, Juan David Alzate-Alvarez, Rimjhim Agarwal, Daniela Weiskopf, Edna Acosta, Estefanie Osorio-Llanes, Andres Orozco González, Alberto Panza Pallares, Marianna Carrillo Encinales, Victor Cañas Paez, Maria Jose Viera Contreras, Maria Jose Sarmiento Alvarez, Nicolle Suarez Otero, Diego Garcia Bañol, Lin Tan Kuang, Lucia Suárez Maestre, Belkis Meneses Rueda, Camilo Badel, Gary L. Simon, Gary S. Firestein, Liliana Encinales, Christopher Mores, Andres Cadena and Aileen Y. Chang Show full author list Hide full author list

Pathogens 2026, 15(7), 770; https://doi.org/10.3390/pathogens15070770 - 22 Jul 2026

Abstract

Chronic chikungunya arthritis is a debilitating post-viral inflammatory arthritis with no established evidence-based therapy. Regulatory T cell (Treg) dysfunction may contribute to persistent inflammation, and low-dose interleukin-2 (IL-2) may restore immune regulation. We evaluated the immunomodulatory effects of low-dose IL-2 using peripheral blood [...] Read more.

Chronic chikungunya arthritis is a debilitating post-viral inflammatory arthritis with no established evidence-based therapy. Regulatory T cell (Treg) dysfunction may contribute to persistent inflammation, and low-dose interleukin-2 (IL-2) may restore immune regulation. We evaluated the immunomodulatory effects of low-dose IL-2 using peripheral blood mononuclear cells from adults with laboratory-confirmed chronic chikungunya arthritis in Atlántico, Colombia. Cells were treated ex vivo with recombinant IL-2 or an IL-2/anti-IL-2 monoclonal antibody complex in the presence of CD2/CD3/CD28 stimulation beads, followed by flow cytometric assessment of effector T cells and Tregs. Low-dose IL-2 treatments ex vivo did not increase total Treg frequency but selectively increased activated suppressor Tregs while decreasing activated T effector cells, enhancing Treg CTLA-4 and HLA-DR expression, and reducing Ki67 expression in effector T cells. IL-2 complex treatment decreased cytokine-secreting Tregs, and IL-10 and TGF-β were not associated with IL-2 treatment status or with Teff/Treg balance, suggesting limited utility as pharmacodynamic biomarkers of low-dose IL-2 treatments. These findings support the use of activated suppressor Tregs, Treg CTLA-4, and HLA-DR expression as candidate biologic endpoints for evaluation in future trials of low-dose IL-2 in chikungunya arthritis. Full article

(This article belongs to the Special Issue Emerging Arboviruses and Novel Viral Threats: Detection, Surveillance, and Mitigation Strategies)

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8 pages, 389 KB

Open AccessBrief Report

Effect of Cup Material on S-Methoprene Bioavailability and Susceptibility Estimates in Larval Mosquito Bioassays

by Sarah S. Wheeler, Kara Kelley and Mario Novelo

Pathogens 2026, 15(7), 769; https://doi.org/10.3390/pathogens15070769 - 22 Jul 2026

Abstract

Mosquito control programs rely on larvicides such as S-methoprene to suppress vector populations and prevent mosquito-borne diseases including West Nile virus (WNV). Resistance surveillance is essential for maintaining the long-term effectiveness of larvicide active ingredients and is typically conducted using cup bioassays to [...] Read more.

Mosquito control programs rely on larvicides such as S-methoprene to suppress vector populations and prevent mosquito-borne diseases including West Nile virus (WNV). Resistance surveillance is essential for maintaining the long-term effectiveness of larvicide active ingredients and is typically conducted using cup bioassays to evaluate larval susceptibility. Disposable Styrofoam cups are commonly used for these assays because they minimize adsorption of S-methoprene under standard testing conditions. However, recent restrictions on expanded polystyrene products in California necessitated the identification and evaluation of suitable replacement cup materials for larval resistance bioassays. Four alternative cup materials, high-density polyethylene (HDPE), polyethylene terephthalate (PET), polypropylene (PP), and paper cups, were compared to Styrofoam cups. Cup bioassays were conducted using a laboratory colony of Culex quinquefasciatus exposed to S-methoprene concentrations of 1–40 ppb. Emergence inhibition data were analyzed using probit regression to estimate the concentrations causing 50% and 90% emergence inhibition (LC₅₀ and LC₉₀, respectively) for each cup type. Cup material significantly affected concentration-response relationships. HDPE and paper cups produced significantly higher LC₅₀ and LC₉₀ estimates than Styrofoam, whereas PET and PP produced responses more comparable to the Styrofoam reference. Concentration-response slopes were similar among cup materials, indicating that cup material primarily shifted the concentration required to achieve a given level of emergence inhibition. These findings demonstrate that cup material can significantly influence estimated S-methoprene LC values. Replacement assay cups should therefore be validated before implementation in larval resistance monitoring programs. Full article

(This article belongs to the Special Issue Advances in Mosquito Insecticide Resistance, Vector Competence and Control Strategies)

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19 pages, 1474 KB

Open AccessBrief Report

Genetic Determinants Analysis of PB1 and PB2 Genes in H5N1 Avian Influenza Strains from Romania

by Maria Rodica Gurău, Florica Bărbuceanu, Alexandru Gligor, Cosmin Șonea, Georgeta Ștefan, Doina Daneș, Elena Negru, Iosif Nicodim Fiț, Kalmár Zsuzsa, Doru Valentin Hristescu, Vlad Barbu Vuță, Raluca Burlacu, Ionica Iancu, Viorel Herman and Stelian Bărăităreanu

Pathogens 2026, 15(7), 768; https://doi.org/10.3390/pathogens15070768 - 21 Jul 2026

Abstract

Avian influenza is a highly contagious viral disease affecting domestic and wild birds, caused by influenza A viruses of the family Orthomyxoviridae. Continuous genetic surveillance is essential for monitoring viral evolution and identifying molecular determinants associated with pathogenicity and host adaptation. In this [...] Read more.

Avian influenza is a highly contagious viral disease affecting domestic and wild birds, caused by influenza A viruses of the family Orthomyxoviridae. Continuous genetic surveillance is essential for monitoring viral evolution and identifying molecular determinants associated with pathogenicity and host adaptation. In this study, the PB1 and PB2 polymerase genes of highly pathogenic avian influenza (HPAI) H5N1 viruses detected in Romania between 2017 and 2024 were genetically characterized. A total of 18 organ samples collected from domestic and wild birds in several Romanian counties were analyzed by real-time RT-PCR, followed by conventional RT-PCR, Sanger sequencing, mutational analysis, and phylogenetic reconstruction. High-quality sequence data were obtained for six PB1 and eight PB2 gene fragments. Sequence analysis revealed a high degree of conservation within the PB1 gene, particularly across regions involved in viral replication, indicating strong evolutionary constraints. In contrast, the PB2 gene exhibited several amino acid substitutions, including changes at positions 464 and 678 in selected isolates. Notably, all analyzed strains lacked the mammalian adaptation marker E627K. Phylogenetic analysis clustered the Romanian isolates within Eurasian H5N1 lineages and demonstrated close genetic relationships with contemporary strains circulating in Eastern Europe and Russia. These findings highlight the genetic stability of PB1, the ongoing diversification of PB2, and the importance of continuous molecular surveillance for the early detection of viral variants with potential implications for host adaptation and zoonotic risk. Full article

(This article belongs to the Special Issue Pathogenesis, Epidemiology, and Control of Animal Influenza Viruses—2nd Edition)

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19 pages, 13107 KB

Open AccessSystematic Review

Clinical Predictors of Mortality in Severe Fever with Thrombocytopenia Syndrome: An Updated Systematic Review and Meta-Analysis

by Ke-Xin Wang, Guo-Mei Xia, Yu-Han Liu, Shuai-Ru Jiao, Yu-Feng Gao and Sheng-Qun Deng

Pathogens 2026, 15(7), 767; https://doi.org/10.3390/pathogens15070767 - 21 Jul 2026

Abstract

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease with a high case fatality rate and no specific treatment. Identifying robust clinical predictors of mortality is crucial for improving patient outcomes. This systematic review and meta-analysis aimed to comprehensively evaluate the [...] Read more.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease with a high case fatality rate and no specific treatment. Identifying robust clinical predictors of mortality is crucial for improving patient outcomes. This systematic review and meta-analysis aimed to comprehensively evaluate the association of underlying diseases, hemorrhagic symptoms, neurological signs, and complications with fatal outcomes in SFTS patients. We systematically searched PubMed, Web of Science, CNKI, and Wan Fang databases up to 1 March 2026 for observational studies. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using fixed- or random-effects models. Forty-five studies, encompassing 8078 patients (1729 deaths), were included. Underlying diabetes (OR = 1.77) and hypertension (OR = 2.38) were significant risk factors. Among hemorrhagic symptoms, systemic manifestations (OR = 4.19), melena (OR = 4.26), and petechiae (OR = 3.20) were strong predictors. Neurological symptoms, particularly coma (OR = 55.07), were the most powerful predictors of death. Complications like multiple organ dysfunction syndrome (MODS, OR = 19.77) and disseminated intravascular coagulation (DIC, OR = 12.02) also significantly increased mortality risk. The findings confirm that a range of clinical features, from underlying conditions to severe neurological and organ complications, are strongly associated with SFTS mortality. These predictors can guide clinicians in early risk stratification and intensive monitoring, especially in high-risk patients, to potentially reduce the high case-fatality rate. Full article

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15 pages, 5313 KB

Open AccessPerspective

Hiding in Plain Sight: HIV-1 Membraneless Organelles as Nuclear Hubs—Host Hijacking, Replication, Immune Evasion, and Drug-Access Implications

by Francesco Broccolo, Alessandro Sannino, Mauro Pollini, Federica Paladini, Thierry Mourer and Francesca Di Nunzio

Pathogens 2026, 15(7), 766; https://doi.org/10.3390/pathogens15070766 - 21 Jul 2026

Abstract

Theories on the early steps of the HIV-1 life cycle have been radically revised over the past five years. The long-held assumption that the capsid fully disassembles in the cytoplasm has given way to a more nuanced view: Cytoplasmic disassembly does occur and, [...] Read more.

Theories on the early steps of the HIV-1 life cycle have been radically revised over the past five years. The long-held assumption that the capsid fully disassembles in the cytoplasm has given way to a more nuanced view: Cytoplasmic disassembly does occur and, in several myeloid systems, is increasingly linked to cytosolic cDNA sensing and to abortive infection. However, a substantial fraction of intact or nearly intact capsid cores instead traverse the nuclear pore complex (NPC) and, upon interacting with the host factor CPSF6, induce liquid–liquid phase separation. This leads to the formation of biomolecular condensates, termed HIV-1 membraneless organelles (HIV-1-MLOs), which subsequently merge with nuclear speckles (NSs). In this Perspective we read these condensates along five interlocking axes. First, the virus drives the host phase separation of cleavage and polyadenylation specificity factor 6 (CPSF6), which quickly fuses with another MLO: the NS composed of the speckle scaffold factors, SON and SRRM2. Second, the resulting condensate behaves as a catalytic site that concentrates the reverse-transcription machinery and thereby promotes integration of the viral DNA into speckle-associated chromatin (SPADs). Third, the same compartment is the final layer of a stratified programme of innate immune evasion, shielding nascent double-stranded DNA from cGAS–STING after cytoplasmic restriction factors and sensors have been outmanoeuvred. Fourth, although demonstrated only in vitro, stable HIV-1-MLOs can maintain the viral RNA genome in the presence of a reverse-transcription inhibitor. Upon removal of the inhibitor, reverse transcription resumes, mirroring, to some extent, the situation in individuals undergoing interruption of antiretroviral therapy and suggesting that these structures may act as a pre-integration reservoir. Fifth, and still largely unexplored, the sanctuary has a pharmacological dimension: anatomical lymphoid compartments, and possibly the condensate itself through selective small-molecule partitioning, may limit antiretroviral drug access. We situate HIV-1-MLOs within the convergent condensate strategies of SARS-CoV-2 and other viruses, and we discuss the clinical, diagnostic, therapeutic, and vaccine implications, including capsid inhibitors as “block-and-expose” tools. Full article

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15 pages, 1363 KB

Open AccessArticle

Machine Learning-Based Detection of Anaplasma spp. Using Dielectric Properties of Host Cells

by Hossein Valishirin, Sai Deepika Reddy Yaram, Negar Farhang Doost, Soumya K. Srivastava and Shira L. Broschat

Pathogens 2026, 15(7), 765; https://doi.org/10.3390/pathogens15070765 - 21 Jul 2026

Abstract

Tick-borne bacterial infections such as those caused by Anaplasma phagocytophilum are difficult to diagnose, particularly at early stages, because they rely on specialized laboratory tests. Dielectric-based measurements provide a label-free way to probe cellular state and may offer useful information. In this study, [...] Read more.

Tick-borne bacterial infections such as those caused by Anaplasma phagocytophilum are difficult to diagnose, particularly at early stages, because they rely on specialized laboratory tests. Dielectric-based measurements provide a label-free way to probe cellular state and may offer useful information. In this study, we explored whether A. phagocytophilum-infected and uninfected HL-60 human promyelocytic leukemia cells can be distinguished using dielectric measurements collected under controlled in vitro conditions. Measurements were performed at two medium conductivities (100 and 300 µS/cm), and three dielectric properties were examined: cytoplasmic conductivity, specific membrane conductance, and specific membrane capacitance. We used exploratory analysis, statistical tests, and interpretable linear classifiers, with performance evaluated using leave-one-out cross-validation. Membrane-related properties, especially specific membrane conductance, showed the clearest separation between infection states and were consistently the most informative across models. Both classification performance and effect sizes were stronger at the higher medium conductivity condition. These results are encouraging, but because the sample size was small and consisted only of technical replicates, they should be interpreted as preliminary measurement-level evidence. This study is intended as a pilot and supports further work with larger datasets, additional cell types, and broader experimental conditions. Full article

(This article belongs to the Special Issue Tick-Borne Pathogens: Advanced Identification, Characterization, Transmission, and Prevalence Studies)

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19 pages, 3020 KB

Open AccessArticle

Bovine Brucellosis in Dairy Herds in Mali and Niger, 2024: Apparent Seroprevalence and Epidemiological Factors

by Abel S. Biguezoton, Chaka Traore, Haladou Gagara, Der Dabire, Zakaria Bengaly, Mahaman Maaouia Abdou Moussa, Raïssa Bakinahe Ntamukunzi, Kader Issoufou, Maïmouna Ousmane, Claude Saegerman and Marcella Mori

Pathogens 2026, 15(7), 764; https://doi.org/10.3390/pathogens15070764 - 21 Jul 2026

Abstract

As part of the PRISMA project, which promotes research and innovation for productive, resilient, and healthy agro-pastoral systems in West Africa, a cross-sectional survey was conducted to assess the apparent seroprevalence and investigate epidemiological factors associated with bovine brucellosis in dairy herds. The [...] Read more.

As part of the PRISMA project, which promotes research and innovation for productive, resilient, and healthy agro-pastoral systems in West Africa, a cross-sectional survey was conducted to assess the apparent seroprevalence and investigate epidemiological factors associated with bovine brucellosis in dairy herds. The survey was carried out in Mali (Bamako, Koulikoro, Mopti, and Sikasso regions) and Niger (Tahoua, Dosso, and Tillabéry regions). A total of 1230 animals from 82 herds were tested, including 645 animals from 43 herds in Mali and 585 animals from 39 herds in Niger. At the herd level, apparent seroprevalence was significantly higher in Mali than in Niger (37.21% vs. 15.38%). Within each country, animal-level seroprevalence varied across region, with the highest levels observed in Bamako (11.11%) and Mopti (7.62%) in Mali, and Dosso (6.67%) in Niger. High within-herd prevalence (>20%) was identified in only one herd per country. The higher overall herd-level seroprevalence in Mali was primarily driven by a greater number of herds with low (≤10%) within-herd seroprevalence. Univariate risk factor analysis at the animal level identified a borderline trend toward higher odds of seropositivity in crossbred cattle than other breeds (OR = 1.95, 95% CI: 1.00–3.81, p = 0.0503). In addition, a classification tree analysis highlighted seven exploratory signals of the positive herd status. These included four animal/management-level factors—herd region, environmental disposal of aborted placentas, the number of lactating cows (as a proxy for animal density), and reported herd abortions—as well as three human-level signals within the household: a history of miscarriage, experiencing heavy night sweats, and suffering from undulant fever. In conclusion, this survey provides new insights into bovine brucellosis and its epidemiology in dairy herds in Mali and Niger, confirming established high-prevalence areas such as Bamako and identifying new zones of concern, such as Mopti and Dosso. Our findings underscore that bovine brucellosis remains an important public health and economic threat in both countries. Given that the identified positive regions are hubs for milk production and consumption, these data may support health authorities in implementing targeted surveillance, control, and prevention strategies under a One Health approach. Full article

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12 pages, 667 KB

Open AccessArticle

An Evaluation of Novel Inflammatory Biomarkers in Children with Kingella kingae Osteoarticular Infections

by Matteo Fortunato, Anne Tabard-Fougère, Giacomo De Marco, Oscar Vazquez, Christina Steiger, Elio Paris, Ardian Ramadani, Andreas Tsoupras, Romain Dayer and Dimitri Ceroni

Pathogens 2026, 15(7), 763; https://doi.org/10.3390/pathogens15070763 - 20 Jul 2026

Abstract

Kingella kingae is now recognised as the leading cause of osteoarticular infections (OAIs) in young children. Because these infections typically produce mild symptoms and a weak inflammatory response, early diagnosis remains challenging. Complete blood count-derived immune-inflammatory biomarkers (IIBs) have recently gained interest as [...] Read more.

Kingella kingae is now recognised as the leading cause of osteoarticular infections (OAIs) in young children. Because these infections typically produce mild symptoms and a weak inflammatory response, early diagnosis remains challenging. Complete blood count-derived immune-inflammatory biomarkers (IIBs) have recently gained interest as accessible, low-cost indicators of systemic inflammation, with potential diagnostic value in several fields, including oncology, rheumatology, cardiology, and infectious diseases. This study therefore aimed to assess whether IIBs could support the screening of K. kingae OAIs. We retrospectively reviewed the medical records of 209 children admitted to our hospital between 2007 and 2025 with confirmed or highly suspected K. kingae OAIs. Complete blood counts were analysed for each patient, including leukocyte subtypes such as neutrophils, lymphocytes, monocytes, eosinophils, and basophils. We then calculated biomarkers (NLR, MLR, PLR, SII, SIRI, and PIV) and interpreted them using age-adjusted reference values. As expected, most children were younger than 48 months, and septic arthritis was the predominant clinical presentation. Classical acute-phase reactants (WBC, CRP, and ESR) were frequently normal or only mildly elevated. Likewise, most IIBs remained within or near reference ranges; the platelet-to-lymphocyte ratio was the most commonly abnormal marker, exceeding the threshold in only 59.3% of patients. These results indicate that, like conventional inflammatory markers, CBC-derived IIBs have limited standalone screening utility for K. kingae OAIs. Further studies are needed to determine whether systemic IIBs can help distinguish OAIs caused by K. kingae from those caused by pyogenic bacteria. Full article

(This article belongs to the Special Issue Infections and Bone Damage—2nd Edition)

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20 pages, 798 KB

Open AccessArticle

Autonomic Dysfunction in Patients with Bartonella henselae IgM Seroreactivity: A Cross-Sectional Study

by Branislav Milovanović, Nikola Marković, Elizabeta Ristanović, Nikoleta Đorđevski, Sonja Atanasievska Kujović, Sulin Bulatović, Vasko Žugić, Maša Petrović and Milovan Bojić

Pathogens 2026, 15(7), 762; https://doi.org/10.3390/pathogens15070762 - 20 Jul 2026

Abstract

Background: Bartonella henselae infection has been associated with a broad spectrum of neurological and autonomic manifestations, although its impact on autonomic nervous system function remains insufficiently characterized, and the aim of this study was to evaluate autonomic function in patients with polymorphic [...] Read more.

Background: Bartonella henselae infection has been associated with a broad spectrum of neurological and autonomic manifestations, although its impact on autonomic nervous system function remains insufficiently characterized, and the aim of this study was to evaluate autonomic function in patients with polymorphic symptoms and Bartonella henselae IgM seroreactivity. Methods: In this cross-sectional study, 75 patients were compared with 75 age- and sex-matched healthy controls, and all participants underwent cardiovascular autonomic reflex testing, short-term (5 min) and long-term (24 h) heart rate variability analysis, and 24 h ambulatory blood pressure monitoring, while head-up tilt testing was performed in the Bartonella group. Results: Abnormal autonomic reflex tests were significantly more frequent in the Bartonella IgM-seroreactive group, particularly those reflecting parasympathetic function, while heart rate variability analysis demonstrated reduced high-frequency components and lower long-term variability indices, and head-up tilt testing revealed heterogeneous hemodynamic responses including orthostatic hypotension and pronounced blood pressure variability, with ambulatory monitoring additionally showing higher nighttime blood pressure values and reduced nocturnal dipping. Conclusions: These findings indicate a consistent pattern of autonomic imbalance characterized predominantly by parasympathetic impairment and altered blood pressure regulation in patients with Bartonella henselae IgM seroreactivity, although further studies are required to clarify underlying mechanisms and clinical implications. Full article

(This article belongs to the Special Issue Flea-Borne Pathogens and Their Impact on Infectious Diseases)

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