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BackgroundAlgeria like other North African countries is experiencing recurrent episodes of West Nile Virus (WNV) emergences and new health threats associated with the introduction of Aedes albopictus in 2010 are to be feared. To improve the surveillance of mosquito-borne pathogens, we performed a study using innovative tools based on multiplex molecular methods.MethodsWe combined two approaches: a high-throughput chip based on the BioMark Dynamic array system to detect arboviruses in mosquitoes, and a set of immunologic methods (ELISA, microsphere immunoassays (MIA) and virus microneutralization tests (MNT)) for serological surveys in animal hosts. We investigated two distinct regions: a first zone located in the coastal humid region and a second one in the Saharan desert region.Principal findingsWe collected a total of 1,658 mosquitoes belonging to nine different species and found predominantly Culex pipienss. l. (56.5%) and Cx. perexiguus (27.5%). From 180 pools of 10 mosquitoes, we detected four arboviruses: Banna virus (BAV), chikungunya virus (CHIKV), Sindbis virus (SINV), and Usutu virus (USUV). Moreover, we examined 389 blood samples from equids and poultry and found that 52.4% were positive for flavivirus antibodies in ELISA, while 30.8% were positive for WNV and two chickens and two equids were positive for USUV by MNT and MIA respectively.ConclusionsTo our knowledge, this is the first report of five arboviruses circulating in Algeria, with three reported for the first time (CHIKV, BAV, and USUV). Our study brings evidence that reinforcing surveillance using more discriminant tools may help in anticipating future emergences and propose adapted control measures.

BackgroundTrachoma is the leading infectious cause of blindness. Patients with trachomatous corneal opacity (TCO) are traditionally considered high-risk cases for graft failure. However, anecdotal evidence suggests that corneal transplantation may restore vision in such individuals. We wanted to review the available evidence for keratoplasty outcomes in TCO.MethodsA literature search of PubMed, MEDLINE, and Web of Science was performed using the search terms "trachoma* AND (keratoplasty OR cornea* transplant*)". The search was restricted to studies published between 1 January 1992 and 12 October 2022. All types of prospective and retrospective study designs reporting outcomes of keratoplasty in trachoma were included. The primary outcome assessed was rate of graft survival in patients with TCO who received keratoplasty. Secondary outcomes were postoperative best corrected visual acuity (BCVA) and graft rejection rates.ResultsSeven studies met our inclusion criteria. None were prospective trials; 215/302 grafts (71%) were clear at final follow-up. There was significant variability between studies in the reporting of patient characteristics, follow-up, complications, and outcomes. In data on penetrating keratoplasty (PKP), graft survival at final follow-up was observed in 161/195 eyes (83%). Studies assessing lamellar keratoplasty (LKP) reported graft survival in 18/20 eyes (90%). Rejection episodes were reported in 31/167 (19%) eyes managed with PKP and 0 of 20 eyes managed with LKP. Of 163 eyes, preoperative BCVA was ≤counting fingers in 76% and ≤6/60 in 91%. A postoperative BCVA of >6/60 was achieved in 63% of eyes.ConclusionsThere is a paucity of evidence supporting keratoplasty in TCO. However, it may hold visual rehabilitation promise for people whose needs have to date been largely ignored. More structured reporting of outcomes from centres which perform keratoplasty in TCO and a well-designed prospective study would be valuable additions to the literature.

Wolbachia pipientis (= Wolbachia) has promise as a tool to suppress virus transmission by Aedes aegypti mosquitoes. However, Wolbachia can have variable effects on mosquito-borne viruses. This variation remains poorly characterized, yet the multimodal effects of Wolbachia on diverse pathogens could have important implications for public health. Here, we examine the effects of transient somatic infection with two strains of Wolbachia (wAlbB and wMel) on the alphaviruses Sindbis virus (SINV), O'nyong-nyong virus (ONNV), and Mayaro virus (MAYV) in Ae. aegypti. We found variable effects of Wolbachia including enhancement and suppression of viral infections, with some effects depending on Wolbachia strain. Both wAlbB- and wMel-infected mosquitoes showed enhancement of SINV infection rates one week post-infection, with wAlbB-infected mosquitoes also having higher viral titers than controls. Infection rates with ONNV were low across all treatments and no significant effects of Wolbachia were observed. The effects of Wolbachia on MAYV infections were strikingly strain-specific; wMel strongly blocked MAYV infections and suppressed viral titers, while wAlbB had more modest effects. The variable effects of Wolbachia on vector competence underscore the importance of further research into how this bacterium impacts the virome of wild mosquitoes including the emergent human pathogens they transmit.

BackgroundBenzimidazole derivatives are widely used anthelmintic drugs, particularly in mass campaigns for intestinal parasitosis treatment. Despite their generally good safety profile, serious adverse reactions have been reported. This study aims to identify potential pharmacovigilance signals for benzimidazole derivatives using disproportionality analysis in the WHO database.MethodologyA case/non-case study was conducted using data from the WHO VigiBase database (2000-2023). Cases were individual case safety reports (ICSRs) where at least one suspected serious adverse event of interest was reported, while non-cases were ICSRs reporting any adverse events other than the serious adverse events of interest. Reporting Odds Ratios (RORs) and 95% confidence intervals were calculated to assess disproportionate reporting. Analyses were adjusted for potential confounding factors and a sensitivity analysis with imputed missing data was performed.Principal findingsAmong 19,068 serious reports analyzed, significant disproportionality signals were found for benzimidazole derivatives compared to other anthelmintic drugs, notably for bone marrow failure and hypoplastic anemia (adjusted ROR 9.44 [5.01-18.9]), serious leukopenia (3.89 [2.64-5.76]), serious hepatic disorders (3.10 [2.59-3.71]), hepatitis (2.88, 95% CI 2.29-3.63) and serious urticaria (2.02, 95% CI 1.36-2.99). We have also highlighted a new signal not mentioned in the summaries of product characteristics for seizures with benzimidazole derivatives. Secondary analysis revealed these signals were primarily reported with albendazole.Conclusions/significanceThis study identified potential pharmacovigilance signals for serious hematological and hepatic adverse events for benzimidazole derivatives, particularly albendazole. New signal for benzimidazole derivatives has been described for seizures. These findings underscore the need for vigilant monitoring during benzimidazole derivatives use and warrant further pharmacoepidemiologic studies to confirm these signals and investigate underlying mechanisms.

BackgroundSurgical intervention is a crucial treatment for hepatic cystic echinococcosis. However, the choice between radical and conservative surgery remains controversial. This study aimed to compare the perioperative outcomes and hospitalization costs between radical and conservative surgery for hepatic cystic echinococcosis.MethodA retrospective cohort study was conducted on patients undergoing surgical treatment at the First People's Hospital of Kashi Prefecture from July 1, 2012, to October 1, 2023. Propensity score-matching analysis was utilized to mitigate patient selection bias between the two surgical groups.ResultOf the 434 patients included, 324 underwent conservative surgery and 110 underwent radical surgery. After propensity score-matching, 182 conservative surgery and 102 radical surgery patients were compared. Radical surgery patients experienced longer operative time, higher intraoperative blood loss, increased blood transfusion, and higher costs compared to conservative surgery patients. However, no differences were observed in short-term outcomes, including overall morbidity, death, bile leak, effusion, pulmonary infection, incision infection, intestinal obstruction, ICU stay, abdominal drainage time, and postoperative hospital stays.ConclusionThis study suggests that radical surgery is associated with greater surgical complexity and higher hospitalization costs, while it doesn't offer a significant short-term advantage. Conservative surgery may be a viable option in resource-limited settings or for patients unsuitable for complex procedures. Further research with long-term follow-up is needed to determine the optimal approach.

BackgroundA specific phobia is an anxiety disorder that is characterised by persistent and excessive fear in the presence of the object of the phobia. Animal phobias are the most prevalent forms of specific phobia among humans. Fear of snakes (snake phobia) is present in non-human primates which suggests its evolutionary origins as the ability to detect the threat of snakes was critical for survival. Snake phobia is a critical factor in protecting snakes and mitigating snakebite burden. To date, only one standardised psychometric test [the Snake Questionnaire (SNAQ) developed in 1974] has been used to quantify snake phobia although this was not performed in snakebite-endemic countries. In this study, we aimed to determine snake phobia in India, where snakebites and resulting deaths, disabilities and socioeconomic impacts are high.Methodology/principal findingsA modified version of the SNAQ (i.e. SNAQ12), which has previously demonstrated internal consistency, excellent reliability, and good discrimination between phobics and non-phobics in Europe was used in this study. SNAQ12 was developed both in English and Tamil and validated by testing on several individuals. Then, the final questionnaire was disseminated to members of the public through various methods including social media and in person through academic and clinical organisations. We received a total of 2032 responses, comprising 1086 [53.4%] males and 946 [46.6%] females, and these data were analysed to determine various aspects of snake phobia in the study population.Conclusions/significanceThe results demonstrated good internal consistency in using SNAQ12 to determine the phobia amongst the tested population. The data suggests that males are more snake-phobic in all age groups than females in India, in contrast to previous research that suggested that females are usually more snake-phobic. No other critical factors contribute to snake phobia in this study population. The use of the SNAQ12 allowed us to easily discriminate between individuals with phobia and non-clinical controls. This tool can be used as part of the One Health approach to better understand the relationships between snake phobia and snakebites and their impact on the mental health and well-being of vulnerable populations.

BackgroundUrogenital schistosomiasis is considered a Neglected Tropical Disease (NTD) by the World Health Organization (WHO). It is estimated to affect 150 million people worldwide, with a high relevance in resource-poor settings of the African continent. The gold-standard diagnosis is still direct observation of Schistosoma haematobium eggs in urine samples by optical microscopy. Novel diagnostic techniques based on digital image analysis by Artificial Intelligence (AI) tools are a suitable alternative for schistosomiasis diagnosis.MethodologyDigital images of 24 urine sediment samples were acquired in non-endemic settings. S. haematobium eggs were manually labeled in digital images by laboratory professionals and used for training YOLOv5 and YOLOv8 models, which would achieve automatic detection and localization of the eggs. Urine sediment images were also employed to perform binary classification of images to detect erythrocytes/leukocytes with the MobileNetv3Large, EfficientNetv2, and NasNetLarge models. A robotized microscope system was employed to automatically move the slide through the X-Y axis and to auto-focus the sample.ResultsA total number of 1189 labels were annotated in 1017 digital images from urine sediment samples. YOLOv5x training demonstrated a 99.3% precision, 99.4% recall, 99.3% F-score, and 99.4% mAP0.5 for S. haematobium detection. NasNetLarge has an 85.6% accuracy for erythrocyte/leukocyte detection with the test dataset. Convolutional neural network training and comparison demonstrated that YOLOv5x for the detection of eggs and NasNetLarge for the binary image classification to detect erythrocytes/leukocytes were the best options for our digital image database.ConclusionsThe development of low-cost novel diagnostic techniques based on the detection and identification of S. haematobium eggs in urine by AI tools would be a suitable alternative to conventional microscopy in non-endemic settings. This technical proof-of-principle study allows laying the basis for improving the system, and optimizing its implementation in the laboratories.

BackgroundClonorchis sinensis (C. sinensis) infection plays an important role in the progression of hepatocarcinogenesis. However, its specific role in HCC progression remains unclear. This study aimed to investigate whether C. sinensis contributes to angiogenesis in HCC.MethodsA comprehensive clinical analysis was conducted on 947 HCC patients, divided into two groups: C. sinensis (-) HCC and C. sinensis (+) HCC. Kaplan-Meier survival curves and log-rank tests were utilized to assess survival outcomes. Microvessel density (MVD) was evaluated through CD34 immunohistochemistry on hepatectomy specimens. A chemistry analyzer and blood analyzer were employed to measure the concentration of circulating angiogenesis-related biomarkers. Quantitative reverse transcription-PCR (qRT-PCR) was used to analyze the expression of angiogenesis-related genes (CD34, Ang1, Ang2, VEGF, PDGF) in HCC tissues.ResultsC. sinensis infection was associated with poorer outcomes in HCC patients, with significantly shorter overall survival (OS) (p = 0.014) and recurrence-free survival (RFS) (pConclusionC. sinensis infection is closely associated with inflammatory responses and may promote metabolic reprogramming in HCC, thereby enhancing its malignant characteristics.

The genus Prototheca (alga) comprises a unique group of achlorophyllic saprotrophic and mammalian pathogen species. Despite its rare occurrence in humans and animals, protothecosis is considered an emerging clinical entity with relevance in immunocompromised patients. In this study, the characterization of spherical structures with endospores recovered from a blood culture in an HIV patient was investigated using phenotypic and molecular methodologies. On 2% Sabouraud dextrose agar, the isolate displayed morphological and biochemical characteristics found on isolates identified as Prototheca wickerhamii. To validate these analyses, molecular phylogeny of the internal transcript space (ITS) partial gene confirmed the identity of the isolate as P. wickerhamii. This is the first case of systemic human protothecosis in Brazil. The present case of human Prototheca and those reported in the medical literature highlight the need for novel methodologies to identify pathogenic algae in the clinical laboratory, improving in this way the diagnosis and treatment of this group of neglected pathogens.

BackgroundInflammatory bowel disease (IBD) increases the risk of colorectal cancer, and it has the potential to diminish the quality of life. Clinical and experimental evidence demonstrate protective aspects of parasitic helminth infection against IBD. However, studies on the inhibition of inflammation by helminth infection have overlooked a key determinant of health: the gut microbiota. Although infection with helminths induces alterations in the host microbiota composition, the potential influence and mechanism of helminth infections induced changes in the gut microbiota on the development of IBD has not yet been elucidated. In this study, we analyzed the intersection of helminth Trichinella spiralis and gut bacteria in the regulation of colitis and related mechanisms.Methodology/principal findingsT. spiralis infected mice were treated with antibiotics or cohoused with wild type mice, then challenged with dextran sodium sulfate (DSS)-colitis and disease severity, immune responses and goblet cells assessed. Gut bacteria composition was assessed by 16S rRNA sequencing and short-chain fatty acids (SCFAs) were measured. We found that protection against disease by infection with T. spiralis was abrogated by antibiotic treatment, and cohousing with T. spiralis- infected mice suppressed DSS-colitis in wild type mice. Bacterial community profiling revealed an increase in the abundance of the bacterial genus Muribaculum and unclassified_Muribaculaceae in mice with T. spiralis infection or mice cohoused with T. spiralis- infected mice. Metabolomic analysis demonstrated significantly increased propionic acid in feces from T. spiralis- infected mice. Data also showed that the gut microbiome modulated by T. spiralis exhibited enhanced goblet cell differentiation and elevated IL-10 levels in mice.ConclusionsThese findings identify the gut microbiome as a critical component of the anti- colitic effect of T. spiralis and gives beneficial insights into the processes by which helminth alleviates colitis.

BackgroundPlasmodium vivax infection, when it occurs during pregnancy, has often been associated with serious adverse pregnancy outcomes. However, immunological alterations in pregnancy and their consequences have been little explored. We characterized the humoral immune response in pregnant women exposed to malaria by P. vivax antigens and its association with the maternal inflammatory profile and poor pregnancy outcomes.MethodsAn observational cohort study in the Brazilian Amazon was conducted between 2013 and 2015. After applying exclusion criteria, 242 mother-child pairs were included in the analysis. Data on maternal infection, gestational outcomes, and inflammatory factors were evaluated in the maternal peripheral plasma. In samples from the first infection, the presence of total IgG and its subclasses in plasma against PvMSP119 protein were also quantified.ResultsPrevious exposure to malaria, observed by anti-total IgG antibodies to the PvMSP119 antigen, increased the inflammatory response to infection when the pregnant woman had malaria during pregnancy. IL-6 and IL-10 levels were positively correlated with parasitemia and with total IgG levels; but they were negatively correlated with the gestational age at delivery from Pv-infected woman. In multivariate linear regression analyses, IgG 1, 2 and 4 was negatively and positively associated with cytokines IL-6 and IL-10, respectively, in P. vivax-infection.ConclusionsAn association between the humoral immune response and the peripheral inflammatory cytokine profile with the adverse outcomes in malaria in pregnancy by P. vivax was observed. Previous exposure to the parasite can influence the IL-6 and IL-10 response, which is associated with increased parasitemia, reduced maternal weight gain and premature delivery.

BackgroundChikungunya virus (CHIKV) is a mosquito-borne alphavirus that is responsible for Chikungunya fever, which is characterized by fever, rash, and debilitating polyarthralgia. Since its re-emergence in 2004, CHIKV has continued to spread to new regions and become a severe health threat to global public. Development of safe and single dose vaccines that provide durable protection is desirable to control the spread of virus. The recombinant adeno-associated virus (rAAV) vectors represent promising vaccine platform to provide prolonged protection with a single-dose immunization. In this study, we developed a rAAV capsid serotype 1 vector based CHIKV vaccine and evaluated its protection effect against CHIKV challenge.MethodologyThe recombinant AAV1 encoding the full-length structural proteins of CHIKV (named as rAAV1-CHIKV-SP) was generated in vitro by transfecting the plasmids of AAV helper-free system into HEK-293T cells. The safety and immunogenicity of rAAV1-CHIKV-SP were tested in 4-week-old C57BL/6 mice. The antibody responses of the mice receiving prime-boost or single-dose immunization of the vaccine were determined by ELISA and plaque reduction neutralizing test. The immunized mice were challenged with CHIKV to evaluate the protection effect of the vaccine.ConclusionsThe rAAV1-CHIKV-SP showed remarkable safety and immunogenicity in C57BL/6 mice. A single dose intramuscular injection of rAAV1-CHIKV-SP elicited high level and long-lasting antibody responses, and conferred complete protection against a heterologous CHIKV strain challenge. These results suggest rAAV1-CHIKV-SP represents a promising vaccine candidate against different CHIKV clades with a simplified immunization strategy.

BackgroundHemorrhagic fever with renal syndrome (HFRS) is a vital rodent-borne disease, and poses a serious public health threat in Hubei province. We aimed to explore the spatiotemporal distribution of HFRS in Hubei province during 2005-2022, and the effects of meteorological factors.MethodsData on HFRS cases at the county level in Hubei province during 2005-2022 were obtained from the Chinese Center for Disease Prevention and Control Information System. The monthly meteorological data at the city level was extracted from the China Meteorological Data Sharing Service System from 2016 to 2020. Descriptive analyses, joinpoint regression model, spatial correlation analyses, Geodetector model and autoregressive integrated moving average (ARIMA) model were conducted to investigate the epidemic characteristics, temporal trend, spatial distribution, influencing factors of HFRS and predict its trend.ResultsA total of 6,295 cases were reported in Hubei province during 2005-2022, with an average incidence of 6/1,000,000. Most cases were males (74.52%) and aged 40-69 years (71.87%). The monthly HFRS cases showed two seasonal peaks, which were summer (May to June) and winter (November to December). The HFRS incidence remained fluctuating at a low level during 2005-2015, followed an increasing trend during 2015-2018, and then decreased during 2018-2022. Hotspots were concentrated in the center of Hubei province in all 3 periods, including Qianjiang, Tianmen and some counties from Xiangyang, Jingmen and Jingzhou cities. The distribution of HFRS had a positive association with wind speed, while a "V"-shaped correlation with mean temperature, with an explanatory power of 3.21% and 1.03% respectively (both P ConclusionsHFRS cases showed seasonal fluctuation and spatial clustering in Hubei province. Central plain areas showed high risk of HFRS. Wind speed and mean temperature had significant effects on the transmission of HFRS in Hubei province. The results alert health authorities to conduct disease-climate surveillance and comprehensive prevention strategies, especially in high-risk counties.

BackgroundSchistosomiasis, a chronic parasitic disease, remains a public health issue in tropical and subtropical regions, especially in low and moderate-income countries lacking assured access to safe water and proper sanitation. A national prevalence survey carried out by the Brazilian Ministry of Health from 2011 to 2015 found a decrease in human infection rates to 1%, with 19 out of 26 states still classified as endemic areas. There is a risk of schistosomiasis reemerging as a public health concern in low-endemic regions. This study proposes an integrated landscape-based approach to aid surveillance and control strategies for schistosomiasis in low-endemic areas.Methodology/principal findingsIn the Middle Paranapanema river basin, specific landscapes linked to schistosomiasis were identified using a comprehensive methodology. This approach merged remote sensing, environmental, socioeconomic, epidemiological, and malacological data. A team of experts identified ten distinct landscape categories associated with varying levels of schistosomiasis transmission potential. These categories were used to train a supervised classification machine learning algorithm, resulting in a 92.5% overall accuracy and a 6.5% classification error. Evaluation revealed that 74.6% of collected snails from water collections in five key municipalities within the basin belonged to landscape types with higher potential for S. mansoni infection. Landscape connectivity metrics were also analysed.Conclusions/significanceThis study highlights the role of integrated landscape-based analyses in informing strategies for eliminating schistosomiasis. The methodology has produced new schistosomiasis risk maps covering the entire basin. The region's low endemicity can be partly explained by the limited connectivity among grouped landscape-units more prone to triggering schistosomiasis transmission. Nevertheless, changes in social, economic, and environmental landscapes, especially those linked to the rising pace of incomplete urbanization processes in the region, have the potential to increase risk of schistosomiasis transmission. This study will help target interventions to bring the region closer to schistosomiasis elimination.

Network analysis may improve the understanding of malaria epidemiology in rural areas of the Amazon region by explicitly representing the relationships between villages as a proxy for human population mobility. This study tests a comprehensive set of connectivity metrics and their relationship with malaria incidence across villages with contrasting PAMAFRO (a malaria control initiative) coverage levels in the Loreto department of Peru using data from the passive case detection reports from the Peruvian Ministry of Health between 2011 and 2018 at the village level. A total of 24 centrality metrics were computed and tested on 1608 nodes (i.e., villages/cities). Based on its consistency and stability, the betweenness centrality type outperformed other metrics. No appreciable differences in the distributions of malaria incidence were found when using different weights, including population, deforested area, Euclidian distance, or travel time. Overall, villages in the top quintile of centrality have a higher malaria incidence in comparison with villages in the bottom quintile of centrality (Mean Difference in cases per 1000 population; P. vivax = 165.78 and P. falciparum = 76.14). The mean difference between villages at the top and bottom centrality quintiles increases as PAMAFRO coverage increases for both P. vivax (Tier 1 = 155.36; Tier 2 = 176.22; Tier 3 = 326.08) and P. falciparum (Tier 1 = 48.11; Tier 2 = 95.16; Tier 3 = 139.07). The findings of this study support the shift in current malaria control strategies from targeting specific locations based on malaria metrics to strategies based on connectivity neighborhoods that include influential connected villages.

BackgroundSome regions of Spain are withdrawing their pregnancy screening program for congenital toxoplasmosis (CT). The Spanish Research Network of Congenital Toxoplasmosis (REIV-TOXO) was created to describe the current status of CT in Spain. The aims of this study were to describe the epidemiological and clinical characteristics of CT and to evaluate the effect of prenatal treatment on clinical outcomes to inform decision-making policies.MethodsAmbispective observational study including CT cases recorded in the REIV-TOXO database that includes 122 hospitals (2015-2022). Inclusion criteria were one or more of the following: positive PCR in maternal amniotic fluid; positive Toxoplasma gondii-specific IgM or IgA antibodies at birth; positive PCR in the placenta, newborn blood, urine or CSF; increase of specific IgG levels during infant follow-up; or specific IgG persistence beyond age 12 months.FindingsFifty-six newborns (54 pregnancies) were included. Prenatal screening allowed 92.8% of cases to be identified. The time of maternal infection was well documented in 90.7% of cases, with 61.1% occurring in the third trimester. A total of 66.6% (36/54) pregnant women received antiparasitic treatment: 24/36 spiramycin, 8/36 pyrimethamine, sulfadiazine, and folinic acid, and 4/36 both treatments sequentially. Most cases were asymptomatic at birth (62.5%, 35/56), and 84% (47/56) newborns completed one year of treatment. Median follow-up was 24 months (IQR = 3-72): 14.2% children exhibited new complications, mainly ocular. Newborns born to mothers treated prenatally had four-fold lower risk of CT clinical features at birth (p = 0.03) and six-fold lower risk of further complications during follow-up (p = 0.04) with no treatment-related differences during pregnancy.ConclusionsWhile diagnosis based only on neonatal assessment misses a significant number of CT cases, prenatal screening allows treatment to be started during pregnancy, with better clinical outcomes at birth and during follow-up. REIV-TOXO provides valuable information about CT in Spain, highlighting the need for universal maternal screening.

The study aimed to optimize qPCR reactions using oligonucleotides from the first Brazilian molecular diagnostic kit for leprosy on a portable platform (Q3-Plus). In addition, we sought to develop a simplified protocol for DNA extraction that met point-of-care criteria. During optimization on the Q3-Plus, optical parameters, thresholds, and cutoffs for the 16S rRNA and RLEP targets of M. leprae were established using synthetic DNA, purified DNA from M. leprae, and pre-characterized clinical samples. For the simplified extraction protocol, different lysis solutions were evaluated using chaotropic agents, and purification was carried out by transferring the lysed material to FTA cards. The complete protocol (simplified extraction + qPCR on the portable platform) was then evaluated with pre-characterized clinical skin biopsy samples and compared with standard equipment (QuantStudio-5). LOD95% for the optimized reactions was 113.31 genome-equivalents/μL for 16S rRNA and 17.70 genome-equivalents/μL for RLEP. Among the lysis solutions, the best-performing was composed of urea (2 M), which provided good dissolution of the skin fragment and a lower Ct value, indicating higher concentrations of DNA. The complete technological solution showed a sensitivity of 52% in reactions. Our results highlight the need for additional optimization to deal with paucibacillary samples, but also demonstrate the feasibility of the portable platform for the qPCR detection of M. leprae DNA in low infrastructure settings.

IntroductionLeprosy is a chronic, slowly developing infectious disease that affects the peripheral nerves, specifically Schwann cells. Individuals with the multibacillary type exhibit a propensity for developing chronic pain and a decrease in sensitivity in the plantar region, which directly interferes with balance maintenance. The evaluation of static balance in this population is made through the measurement of the center of pressure (COP) oscillations. Therefore, there is a need to investigate the association between postural control and COP oscillations using a force platform and finding accelerations of the center of mass (COM) from inertial sensors for reliable and portable balance assessment in leprosy patients.ObjectiveTo validate the application of inertial sensors for patients with leprosy by establishing a correlation with the outcomes obtained from a force platform.MethodsThis is an observational study with a case-control design, in which 30 participants with leprosy and 30 healthy participants were recruited to evaluate static balance using an inertial sensor and a force platform. Participants underwent balance assessment under two conditions (Eyes Open: OE and Eyes Closed: CE), and data from the platform and sensor were processed using Matlab computational routines. The data were quantified using four parameters: Total Displacement (TD), Area, Antero-Posterior Displacement (APdisp), and Medio-Lateral Displacement (MLdisp).ResultsThe evaluated parameters showed significantly different values between the groups, where the Leprosy group exhibited significantly higher values compared to the control group, both in the OE and CE conditions for all four parameters. The sensor corroborated the differences demonstrated by the platform and followed the same trend for medio-lateral displacements and accelerations. It can be observed that the evaluated parameters exhibited a varied correlation ranging from moderate to large between the platform and the sensor. Among the four variables, MLdisp had the lowest correlation.DiscussionThe results partially confirmed the first hypothesis of concurrent validation, showing a moderate to large correlation between the force platform and the inertial sensor. The second hypothesis of clinical validation was also partially confirmed, as not all group differences observed in the COP measurements from the force platform were reflected in the COM measurements from the inertial sensor. Specifically, the force platform indicated greater oscillations in participants with multibacillary leprosy compared to controls, a finding statistically confirmed by the sensor for all measures except MLdisp.ConclusionThis research confirmed the concurrent validity of the inertial sensor with the force platform and its clinical validation, demonstrating that this instrument can be applied in clinical settings due to its low cost and ease of use. The findings may contribute to public health by identifying postural control tools for patients with multibacillary leprosy.

BackgroundTsetse flies (Glossina) transmit species of Trypanosoma which cause human African trypanosomiasis (HAT) and animal African trypanosomiasis (AAT). Understanding the epidemiology of this disease and controlling the vector rationally requires analysis of the abundance, age structure, infection rates and feeding patterns of tsetse populations.MethodsWe analysed a population of G. fuscipes fuscipes in the Koboko district of Uganda. Seasonal variation in the abundance of tsetse was assessed from the numbers of tsetse caught in pyramidal traps. The age structure of the population was assessed by dissecting female tsetse to estimate their ovarian categories. Classical and PCR-based methods were utilised to determine the presence of the three major pathogenic species of salivarian trypanosomes: T. vivax, T. congolense and T. brucei in a subset (n = 2369) of flies. Further, bloodmeal analysis was carried out using PCR to amplify and sequence a portion of the vertebrate cytb gene.ResultsThe abundance and age structure of tsetse populations were relatively stable and a slight seasonal four-fold variation in abundance appeared to be correlated with rainfall. Analyses of age structure suggests a low natural daily mortality of 1.75% (1.62-1.88). Infection rates estimated were significantly greater (1.9-9.3 times) using the PCR-based method compared to the classical dissection-based method. Positive rates for T. brucei sl, T. congolense and T. vivax were 1.6% (1.32-2.24), 2.4% (1.83-3.11and 2.0% (1.46-2.63), respectively by PCR. The majority of bloodmeals were identified as cattle (39%, 30.5-47.8) and human (37%, 28.4-45.6).ConclusionThe seasonally stable abundance, low mortality rate and high proportion of bloodmeals from humans may explain, in part, why this district has historically been a focus of sleeping sickness. Additionally, the high rates of cattle feeding indicate insecticide treated cattle may prove to be a useful vector control strategy in the area.

BackgroundIn 2008-2010, Malaysia experienced a nationwide chikungunya virus (CHIKV) outbreak caused by the Indian Ocean lineage E1-226V (valine) variant, adapted to Aedes albopictus. In 2017-2022, transition to an E1-226A (alanine) variant occurred. Ae. albopictus prevails in rural areas, where most cases occurred during the E1-226V outbreak, while Ae. aegypti dominates urban areas. The shift in circulating CHIKV variants from E1-226V to E1-226A (2009-2022) was hypothesized to result in a transition from rural to urban CHIKV distribution, driven by differences in Ae. aegypti vector competence for the two variants. This study aimed to: (1) map the spatiotemporal spread of CHIKV cases in Malaysia between 2009-2022; and (2) compare replication of E1-226A and E1-226V variants in the midguts and head/thoraxes of Ae. aegypti.Methodology/principal findingsSpatiotemporal analysis of national notified CHIKV case addresses was performed. Between 2009-2022, 12,446 CHIKV cases were reported, with peaks in 2009 and 2020, and a significant shift from predominantly rural cases in 2009-2011 (85.1% rural), to urban areas in 2017-2022 (86.1% urban; pConclusions/significanceThis study revealed that a change in circulating CHIKV variants can be associated with changes in vector competence and outbreak epidemiology. Continued genomic surveillance of arboviruses is important.

We conducted a large-scale survey of arboviruses in mosquitoes and biting midges to assess the presence and spread of mosquito-borne pathogens currently circulating on Hainan Island, China. RT-PCR assays were used to detect the arbovirus species, distribution, and infection rates in mosquitoes and biting midges. Cell inoculation and high throughput sequencing were performed to isolate the viruses and assemble full viral genomes. Phylogenetic analysis was conducted to identify the viral genotypes and evolutionary relationships with known viruses. During 2019-2023, 32,632 mosquitoes and 21,000 biting midges were collected from 14 of 18 cities/counties on Hainan Island. Japanese encephalitis virus (JEV) was detected in Culex mosquitoes from five cities/counties, where the minimum infection rate (MIR) was 1.6 (0.6-2.6) per 1,000 females tested. Tembusu virus (TMUV) was detected in Culex mosquitoes from three cities/counties with MIR1.0 (0-2.2) per 1,000. Getah virus (GETV) was detected in Armigeres mosquitoes from Qionghai city with MIR 7.1 (0-15.2) per 1,000. Oya virus (OYAV) and Bluetongue virus (BTV) were detected in biting midges from Wanning city with MIRs of 0.4 (0-1.2) and 0.1 (0-10.2) per 1,000, respectively. Three JEV strains were isolated and clustered within the genotype I group, which is presently the dominant genotype in China. Three TMUV strains were isolated for the first time on Hainan Island that belonged to Cluster 3. Three isolated GETVs were identified as Group 3. BTV was reported for the first time on Hainan Island, and the complete genome for one BTV strain was successfully assembled, which was classified as serotype 1 based on the sequences of segment 2. These results stress the need to develop adequate surveillance plan measures to better control the public health threat of arboviruses carried by mosquitoes and biting midges in local regions.

BackgroundAedes albopictus (Skuse 1894) mosquitoes can transmit deadly arboviruses and are globally invasive due to their ability to survive in both tropical and temperate climates. Although adults cannot survive harsh winters, females are capable of anticipating seasonal change and producing overwintering diapause (DP) eggs that remain in a state of arrested development over the winter and hatch when favorable conditions return in the spring. While low temperatures can facilitate DP entry under short photoperiods, temperature signals alone are not sufficient to induce DP.Methodology/principal findingsTo identify maternal phenotypes predictive of DP egg production in laboratory conditions, we characterized aspects of maternal physiology and behavior to identify those that correlate with DP egg production and changes in photoperiod, versus changes in temperature. Neither changes in temperature nor photoperiod impacted protein preference, blood meal consumption, or total number of eggs produced per female. Egg retention and oviposition timing were influenced by temperature, independent of DP egg production. However, females housed under short photoperiod conditions showed increased starvation resistance, despite showing similar levels of locomotor activity and internal stores of triacylglycerols, glucose, glycogen, and trehalose compared to females housed in long photoperiods.Conclusions/significanceThese results suggest that temperature and photoperiod differentially affect maternal phenotypes and identify starvation resistance as a maternal phenotype that is influenced by photoperiod and correlates with DP egg status.

Diarrheal disease is the second leading cause of death among children under five in developing communities, despite active interventions to improve access to water, sanitation, and hygiene resources. Even interventions with high fidelity and compliance saw minimal improvements in health outcomes, necessitating a need for looking beyond traditionally targeted exposure pathways. This study focuses on the pathogen exposure a young child may receive while playing in the public spaces of informal settlements, where animal feces, human feces, and garbage are frequently observed. The study utilized 79 soil samples previously collected across ten cluster sites in Corail, Haiti and processed using DelAgua cultural assays and quantitative Polymerase Chain Reaction methods. Molecular assays screened for Aeromonas, Vibrio cholera, and several pathogenic Escherichia coli species. Behavioral observations of young children (

Bacillus thuringiensis crystal (Cry) proteins have been expressed in commercial transgenic crops for nearly 30 years, providing safe and effective control of insect pests and significantly reducing the application of hazardous chemical pesticides. B. thuringiensis crystal proteins have also been shown to target parasitic nematodes, including plant parasitic nematodes. Recently, transgenic soybean crops expressing Cry14Ab have been shown to provide control against the soybean cyst nematode Heterodera glycines, marking the first time a crystal protein is being commercialized in transgenic crops for control of a nematode pest. However, apart from H. glycines and the free-living nematode, Caenorhabditis elegans, the breadth of nematode activity of Cry14Ab, e.g., against gastrointestinal parasitic nematodes (GINs), has not been reported. Here we study the efficacy of Cry14Ab against a wide range of gastrointestinal nematode parasites (GINs) in vitro and in vivo. We find that Cry14Ab is effective in vitro against the barber's pole worm Haemonchus contortus larvae, small strongyles cyathostomin larvae, the hookworm Ancylostoma ceylanicum adults, the roundworm Ascaris suum L4 larvae, and the whipworm Trichuris muris adults. In rodents infected with GIN parasites, Cry14Ab is effective as an in vivo anthelmintic against the hookworms A. ceylanicum and N. americanus, against the mouse parasite Heligmosomoides polygyrus bakeri, and against the roundworm A. suum. Cry14Ab also variably reduces the reproduction of the whipworm T. muris in vivo. Using optimized profile Markov Models, we looked for other putative anthelmintic Cry proteins and, within this list, identified a Bt crystal protein, GenBank accession no. MF893203, that we produced and demonstrated intoxicated GINs. This protein, with 90% amino acid identity to Cry14Ab, is active against C. elegans, A. ceylanicum adults, and A. suum L4 larvae in vitro. MF893203 was given the official designation of Cry14Ac. Cry14Ac is also an effective in vivo anthelmintic against A. ceylanicum hookworms in hamsters and intestinal A. suum in mice. Taken together, our results demonstrate that Cry14Ab and Cry14Ac have wide therapeutic utility against GINs.

BackgroundSchistosoma mansoni was introduced from Africa to the Americas during the transatlantic slave trade and remains a major public health problem in parts of South America and the Caribbean. This study presents a comprehensive comparative analysis of three S. mansoni strains with different geographical origins-from Liberia, Belo Horizonte and Puerto Rico. We demonstrated significant variation in virulence and host-parasite interactions.MethodsWe investigated the phenotypic characteristics of the parasite and its eggs, as well as the immunopathologic effects on laboratory mouse organ systems.ResultsOur results show significant differences in worm morphology, worm burden, egg size, and pathologic organ changes between these strains. The Puerto Rican strain showed the highest virulence, as evidenced by marked liver and spleen changes and advanced liver fibrosis indicated by increased collagen content. In contrast, the strains from Liberia and Belo Horizonte had a less pathogenic profile with less liver fibrosis. We found further variations in granuloma formation, cytokine expression and T-cell dynamics, indicating different immune responses.ConclusionOur study emphasizes the importance of considering intra-specific variations of S. mansoni for the development of targeted therapies and public health strategies. The different virulence patterns, host immune responses and organ pathologies observed in these strains provide important insights for future research and could inform region-specific interventions for schistosomiasis control.

BackgroundDiarrhoea is one of the leading causes of disability-adjusted life years (DALYs) among children below five years, though the proportion of the burden occurring amongst those aged over 70 is increasing. The cost of treating and managing diarrhoea can place a burden on individuals, their households, and society in general. The cost can be high but is often undocumented, and many studies focus on children or hospitalised patients only. This study aimed to estimate the economic cost per case of diarrhoea amongst individuals of any age in Uvira, Democratic Republic of the Congo.MethodsThe study was cross-sectional and retrospective, and based on a household survey approximately representative of the city undertaken in September 2021. Data on quantities and prices of resources were collected in the survey, as well as from interviews with staff at the Cholera Treatment Centre in the Uvira general hospital and their records on resource use and patient numbers. Direct and indirect costs were measured from the societal perspective, and generalised linear regression used to identify factors associated with higher costs.ResultsOf 2,820 members of the 528 households surveyed, 175 people (6.2%) were reported to have had diarrhoea in the previous seven days. The majority sought care (91%) of which most (64%) visited a pharmacy. The average economic cost of illness (COI) for an episode of diarrhoea was 33,816 Congolese Francs (CDF) (US$ 17.0) in 2021 prices. The median was CDF 14,000 (US$ 7.0). The average out of pocket COI to patients was CDF 15,579 (US$ 7.8), representing 9% of the estimated average monthly income of households. On average caregivers and patients lost 4 days per episode. A concentration index suggested a lower economic COI among poorer households (p=0.099). A regression analysis identified that being older than 5 years (p=0.001) or being water insecure (p=0.032) were associated with higher COI.ConclusionHouseholds in Uvira experience many diarrhoeal episodes per year, and the COI is an important burden for them and society. These costs could be avoided if diarrhoea were prevented through public health interventions to reduce prevalence and care-seeking was better managed to avert this public health burden.

BackgroundThe prevalence of intestinal schistosomiasis remains a challenge despite government efforts to eliminate the disease. This study aims to assess the prevalence of intestinal schistosomiasis in school-age children living in the villages surrounding Lake Chamo in southern Rift Valley of Ethiopia.Methodology/principal findingsA cross-sectional study was conducted from January to July 2023 in Shele Mela Kebele in Gamo Zone, South Ethiopia. Stool samples were collected from 597 school-age children. A singe Kato-Katz for helminths and formalin-ether concentration technique for protozoan parasites were used to process the samples. The intensity of Schistosoma mansoni infection among school-age children was determined by counting the number of eggs per gram of stool. Of the 597 children screened, 52.3% (95% CI: 48.4.4-56.4) were positive for Schistosoma mansoni. These findings showed that 55% of the infections were light, 30.3% were moderate, and 14.7% were heavy. The mean egg count of S. mansoni parasites was 182.1 eggs per gram. The prevalence of other intestinal parasites (Hymenolopis nana, Ascaris lumbricoides, Hookworm, Taenia species, Giardia lamblia and Entamoeba histolytica) was found to be 7.7% (46/597). The overall prevalence of S. mansoni co-infection with other intestinal parasites was 5.0% (30/597). Specifically, the co-infection rates were 1.5% for A. lumbricoides, 1.3% for H. nana, 1.0% for Taenia species, 0.2% for Hookworm, 0.2% for E. histolytica, and 0.2% for G. lamblia.Conclusions/significancesThe study showed a high rate of S. mansoni infection among school-age children. This calls for immediate action, such as school-based deworming, to protect these children from the disease and reduce the burden. Further research is needed to understand the transmission of the infection by the intermediate host.

Nipah virus (NiV) is a highly pathogenic Paramyxovirus associated with outbreaks in Malaysia, Bangladesh, and India with high mortality rates. NiV infection causes fatal respiratory and neurological disease. The majority of survivors suffer from long-term neurological sequelae or late onset and relapsed encephalitis. The pathogenesis of neurological disease is complex and has not been able to be studied in current animal models as they are skewed towards the development of lethal respiratory disease rather than neurological disease. Although NiV neurological disease can be observed in animal models, there is currently no model where the majority of animals consistently develop neurological disease. Here, we developed a new Syrian hamster (Mesocricetus auratus) model to mimic neurological disease in humans. Hamsters were inoculated intracranially in the cerebellomedullary cistern with different doses of NiV, strain Malaysia. Intracranial NiV inoculation in the cerebellomedullary cistern resulted in a rapid progression towards severe neurological disease requiring euthanasia. High Nipah viral loads were detected in the brains, and NiV spread from the CNS to the lungs. Histopathologic examination of the brain showed ischemic necrosis, often accompanied by marked edema and hemorrhage. NiV antigen was detected primarily in meninges and cerebellum, but rarely observed in brain parenchyma. These histological lesions were different from the typical lesions observed in NiV-infected humans. Thus, despite the consistent development of neurological disease, intracranial inoculation does not result in a model representative of NiV neurological disease.

BackgroundPlasmodium vivax is the dominant Plasmodium spp. causing malaria throughout tropical and sub-tropical countries. Humoral immunity is induced during P. vivax infection. However, data on longevity of antibody and memory B cell (MBC) responses is lacking. Follicular helper T cells (Tfh) are drivers of high-affinity and long-lived antibody responses. Understanding of Tfh-mediated immunity against malaria is valuable for vaccine development.Methodology/principal findingsWe enrolled 31 acutely infected P. vivax patients in low malaria transmission areas of Thailand to detect frequencies, phenotypes and kinetics of different subsets of circulating Tfh (cTfh) and MBCs, and to evaluate their association with humoral immunity following natural P. vivax infection. Expansion of cTfh2 cells, activated and atypical MBCs were shown during acute malaria. To relate increased cTfh2 cells to humoral immunity, P. vivax-specific MBCs and antibodies were assessed. High anti-PvCSP and -PvDBPII seropositivity was detected and most subjects produced MBCs specific to these antigens. The increased cTfh2 cells were positively related to atypical MBCs, plasmablasts/plasma cells, and anti-PvDBPII IgM and IgG levels. Distributions of memory cTfh cell subsets were altered from central memory (CM) to effector memory (EM) during infection. The highest ratios of cTfh-EM/cTfh-CM were represented in cTfh2 cells. Positive correlation of cTfh17-EM with activated and atypical MBCs was observed, while cTfh2-CM and cTfh17-CM cells were positively related to PvDBPII-specific MBCs and IgM levels.Conclusions/significancePresent study demonstrated that P. vivax infection induced cTfh polarization into cTfh2 subset, and alteration of memory cTfh2 phenotype from CM to EM phase. These P. vivax-induced cTfh responses significantly associated with generation of MBCs and antibody responses. Therefore, cTfh2 cells might possibly influence humoral immunity by inducing expansion of activated and atypical MBCs, and by generating P. vivax-specific MBCs and antibody responses following natural infection.

BackgroundIn 2007, the first outbreak of Chikungunya in Italy generated great alarm, highlighting the health risks caused by exotic species recently introduced in Europe and the need to strengthen control actions against the vectors. Besides health risks, mosquitoes cause nuisance, and citizens are required to adopt control measures. While the economic aspects of mosquito control by public agencies have been investigated, the scientific literature on the costs of mosquito protection incurred by families is scarce. This study assessed the households' expenditure on protective measures against mosquitoes in Emilia-Romagna, a region in Northern Italy.Methodology/principal findingsA phone questionnaire survey was conducted to collect data on the annual expenditure incurred by households for self-protection against mosquitos in relation to the perceived level of nuisance and the household and dwelling characteristics. Univariate and multivariate analyses were conducted to identify the main determinants influencing such expenditure, which resulted affected by dwelling characteristics, presence of children under 6 years of age, and health concerns of family members. The average annual household expenditure was estimated at 84.63 euros, about 30 times higher than the expenditure per household supported by regional and local administrations for interventions against mosquitoes in public areas, as calculated in a previous study.Conclusion/significanceHousehold expenditure is mainly aimed at providing a direct defense against mosquito bites (mosquito nets, adulticides, skin-on repellents, etc.) while spending for more effective measures addressed to reduce mosquito density results marginal: e.g., only 3.5% of the total expenditure was dedicated to larval control. Control activities that lower the mosquito density in both private and public areas could reduce the use of household insecticides in urban environments and the related costs, and the risk of spread of imported arboviruses as well.

Burkholderia pseudomallei (Bpm) is the causative agent of the disease melioidosis. As a facultative intracellular pathogen, Bpm has a complex lifestyle that culminates in cell-to-cell fusion and multinucleated giant cells (MNGCs) formation. The virulence factor responsible for MNGC formation is the type 6 secretion system (T6SS), a contractile nanomachine. MNGC formation is a cell-to-cell spread strategy that allows the bacteria to avoid the extracellular immune system and our previous data highlighted cell death, apoptosis, and inflammation as pathways significantly impacted by T6SS activity. Thusly, we investigated how the T6SS influences these phenotypes within the macrophage and pulmonary models of infection. Here we report that the T6SS is responsible for exacerbating apoptotic cell death during infection in both macrophages and the lungs of infected mice. We also demonstrate that although the T6SS does not influence differential macrophage polarization, the M2 polarization observed is potentially beneficial for Bpm pathogenesis and replication. Finally, we show that the T6SS contributes to the severity of inflammatory nodule formation in the lungs, which might be potentially connected to the amount of apoptosis that is triggered by the bacteria.

BackgroundSchistosomiasis japonica is a serious threat to human health. It causes damage to the intestine and liver. Probiotic therapy has been shown to be effective in alleviating intestinal diseases and improving host health. Previous studies have found that Bacillus amyloliquefaciens could alleviate the pathological symptoms of schistosomiasis japonica, but the regulatory mechanism of alleviating schistosomiasis japonica is still unknown.Principal findingsThis study analyzed the dynamic changes of intestinal microbiome in mice infected with Schistosoma japonicum after the intervention of B. amyloliquefaciens and its connection to host metabolism by multi-omics sequencing technology. B. amyloliquefaciens was found to significantly regulate the homeostasis of intestinal microbiota by promoting the growth of beneficial bacteria and inhibiting potential pathogenic bacteria and protect the number of core microbes. Meanwhile, the genes related to the metabolism of glycerophospholipids and amino acid from intestinal microbiome changed significantly, and were shown to be significantly positively correlated with the associated metabolites of microbial origin. Moreover, host metabolism (lipid metabolism and steroid hormone biosynthesis) was also found to be significantly regulated.ConclusionsThe recovery of intestinal microbial homeostasis and the regulation of host metabolism revealed the potential probiotic properties of B. amyloliquefaciens, which also provided new ideas for the prevention and adjuvant treatment of schistosomiasis japonica.

BackgroundIn September 2022, Uganda experienced an outbreak of Sudan virus disease (SVD), mainly in central Uganda. As a result of enhanced surveillance activities for Ebola disease, samples from several patients with suspected viral hemorrhagic fever (VHF) were sent to the VHF Program at Uganda Virus Research Institute (UVRI), Entebbe, Uganda, and identified with infections caused by other viral etiologies. Herein, we report the epidemiologic and laboratory findings of Crimean-Congo hemorrhagic fever (CCHF) cases that were detected during the SVD outbreak response.MethodologyWhole blood samples from VHF suspected cases were tested for Sudan virus (SUDV) by real-time reverse transcription-polymerase chain reaction (RT-PCR); and if negative, were tested for CCHF virus (CCHFV) by RT-PCR. CCHFV genomic sequences generated by metagenomic next generation sequencing were analyzed to ascertain strain relationships.Principal findingsBetween September 2022 and January 2023, a total of 2,626 samples were submitted for VHF testing at UVRI. Overall, 13 CCHF cases (including 7 deaths; case fatality rate of 53.8%), aged 4 to 60 years, were identified from 10 districts, including several districts affected by the SVD outbreak. Four cases were identified within the Ebola Treatment Unit (ETU) at Mubende Hospital. Most CCHF cases were males engaged in livestock farming or had exposure to wildlife (n = 8; 61.5%). Among confirmed cases, the most common clinical symptoms were hemorrhage (n = 12; 92.3%), fever (n = 11; 84.6%), anorexia (n = 10; 76.9%), fatigue (n = 9; 69.2%), abdominal pain (n = 9; 69.2%) and vomiting (n = 9; 69.2%). Sequencing analysis showed that the majority of identified CCHFV strains belonged to the Africa II clade previously identified in Uganda. Two samples, however, were identified with greater similarity to a CCHFV strain that was last reported in Uganda in 1958, suggesting possible reemergence.Conclusions/significanceIdentifying CCHFV from individuals initially suspected to be infected with SUDV emphasizes the need for comprehensive VHF testing during filovirus outbreak responses in VHF endemic countries. Without expanded testing, CCHFV-infected patients would have posed a risk to health care workers and others while receiving treatment after a negative filovirus diagnosis, thereby complicating response dynamics. Additionally, CCHFV-infected cases could acquire an Ebola infection while in the ETU, and upon release because of a negative Ebola virus result, have the potential to spread these infections in the community.

Clonorchis sinensis infection is an important risk factor for cholangiocarcinoma (CCA). It has been reported that extracellular vesicles (EVs) are involved in the parasite-host interaction, and EVs of C. sinensis (CsEVs) can contribute to biliary injuries and inflammation. However, uncertainty surrounds the function of CsEVs in the progression of CCA. In this study, differential ultracentrifugation was used to separate CsEVs from the culture supernatant of C. sinensis adult worms, and they were then identified by transmission electron microscopy, nanoparticle tracking analysis and proteome assays. CCK8, EdU-488 and colony formation assays were used to explore the effect of CsEVs on the proliferation of CCA cells in vitro. Wound healing assays, transwell assays and in vivo lung metastasis model were conducted to evaluate the migration and invasion abilities. Moreover, the involvement of EMT process, as well as NF-κB and ERK signaling pathway was assessed. Results showed that CsEVs were successfully isolated and could be taken up by CCA cells, which promoted proliferation by accelerating cell cycle progression. In addition, CsEVs could facilitate cell metastasis by triggering the epithelial-mesenchymal transition (EMT). Mechanistically, activation of NF-κB signaling pathway was involved in the CsEVs-mediated EMT, which could be reversed partly by BAY 11-7082 (an inhibitor of NF-κB). In conclusion, these findings suggested that CsEVs could induce the aberrant proliferation and metastasis of CCA cells by stimulating the NF-κB/EMT axis, providing a novel theoretical explanation for liver fluke-associated CCA.

BackgroundCystic Echinococcosis (CE) is a zoonotic disease causing fibrosis and necrosis of diseased livers caused by infection with Echinococcus granulosus (E.g). There is evidence that E.g is susceptible to immune escape and tolerance when host expression of immunoinflammation and fibrosis is suppressed, accelerating the progression of CE. Ghrelin has the effect of suppressing immunoinflammation and fibrosis, and whether it is involved in regulating the progression of E.g-infected liver lesions is not clear.MethodsSerum and hepatic Ghrelin levels were observed in E.g-infected mice (4, 12 and 36 weeks) and compared with healthy control groups. Co-localization analysis is performed between protein expression of Ghrelin in and around the hepatic lesions of E.g-infected 12-week mice and protein expression of different hepatic histiocytes by mIHC. HepG2 cells and protoscoleces (PSCs) protein were co-cultured in vitro, as well as PSCs were alone in vitro, followed by exogenously administered of Ghrelin and its receptor blocker, [D-Lys3]-GHRP-6, to assess their regulatory effects on immunoinflammation, fibrosis and survival rate of PSCs.ResultsSerum Ghrelin levels were increased in E.g-infected 4- and 12-week mice, and reduced in 36-week mice. E.g-infected mice consistently recruited Ghrelin in and around the hepatic lesions, which was extremely strongly co-localized with the protein expression of hepatic stellate cells (HSCs), T cells and the TGF-β1/Smad3 pathway. The secretion of Ghrelin was increased with increasing concentrations of PSCs protein in HepG2 cells culture medium. Moreover, Ghrelin could significantly inhibit the secretion of IL-2, INF-γ and TNF-α, as well as the expression of Myd88/NF-κB and TGF-β1/Smad3 pathway protein, and promoted the secretion of IL-4 and IL-10. Blocking Ghrelin receptor could significantly inhibit PSCs growth in in vitro experiment.ConclusionGhrelin is highly expressed in the early stages of hepatic E.g infection and may be involved in regulating the progression of liver lesions by suppression immunoinflammation and fibrosis.

BackgroundTicks carry and transmit a wide range of pathogens (bacteria, viruses, and protozoa) that pose significant threats to human and animal health worldwide. Only few meta-analyses have been conducted on the distribution of ticks and tick-borne spotted fever group rickettsia (SFGR). Therefore, this study aims to examine the tick species and SFGR positivity in China in order to provide support for further research and improvements in the prevention and control of tick-borne diseases.MethodologyThis systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Relevant Chinese and English studies were retrieved from PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), VIP database, Chinese Biomedical literature database (CBM) and Wanfang database from inception to January 9, 2023. Pooled SFGR positive rate was meta-analyzed using a random effects model and heterogeneity was assessed by the I2 index. Publication bias was also evaluated by funnel plot and Egger's test. The meta-analysis was performed on R studio 4.0.4.Principal findingsMeta-analysis of 57 studies published between 2000 and 2022 involving 39,380 ticks revealed a pooled SFGR positive rate of 21.4% (Q = 6423.74, I2 = 99%, Q-pConclusionsThis study examined the distribution of tick-borne SFGR in China. Our findings revealed that the main tick species were D. silvarum, I. persulcatus and H. iongicornis, and the common SFGR species were R. raoultii, R. heilongjiangiensis, and some uncultured species. Further studies are warranted to identify the potential vectors of SFGR and to better understand the epidemiology and pathogenesis of tick-borne diseases in China.

BackgroundEpigenetic modifications, such as DNA methylation and histone modifications, are pivotal in regulating gene expression pathways related to inflammation and cancer. While there is substantial research on epigenetic markers in cholangiocarcinoma (CCA), Opisthorchis viverrini-induced cholangiocarcinoma (Ov-CCA) is overlooked as a neglected tropical disease (NTD) with limited representation in the literature. Considering the distinct etiological agent, pathogenic mechanisms, and pathological manifestations, epigenetic research plays a pivotal role in uncovering markers and potential targets related to the cancer-promoting and morbidity-inducing liver fluke parasite prevalent in the Great Mekong Subregion (GMS). Emerging studies highlight a predominant hypermethylation phenotype in Opisthorchis viverrini (O. viverrini) tumor tissues, underscoring the significance of abnormal DNA methylation and histone modifications in genes and their promoters as reliable targets for Ov-CCA.Principal findingsRelevant published literature was identified by searching major electronic databases using targeted search queries. This process retrieved a total of 81 peer-reviewed research articles deemed eligible for inclusion, as they partially or fully met the pre-defined selection criteria. These eligible articles underwent a qualitative synthesis and were included in the scoping review. Within these, 11 studies specifically explored Ov-CCA tissues to investigate potential epigenetic biomarkers and therapeutic targets. This subset of 11 articles provided a foundation for exploring the applications of epigenetics-based therapies and biomarkers for Ov-CCA. These articles delved into various epigenetic modifications, including DNA methylation and histone modifications, and examined genes with aberrant epigenetic changes linked to deregulated signalling pathways in Ov-CCA progression.ConclusionsThis review identified epigenetic changes and Wnt/β-catenin pathway deregulation as key drivers in Ov-CCA pathogenesis. Promoter hypermethylation of specific genes suggests potential diagnostic biomarkers and dysregulation of Wnt/β-catenin-modulating genes contributes to pathway activation in Ov-CCA progression. Reversible epigenetic changes offer opportunities for dynamic disease monitoring and targeted interventions. Therefore, this study underscores the importance of these epigenetic modifications in Ov-CCA development, suggesting novel therapeutic targets within disrupted signalling networks. However, additional validation is crucial for translating these novel insights into clinically applicable strategies, enhancing personalised Ov-CCA management approaches.

BackgroundRadical cure of Plasmodium vivax infections is key to the control of vivax malaria. However, the standard doses of 8-aminoquinoline drugs used for radical cure can cause severe haemolysis in G6PD-deficient patients. The availability of near-patient G6PD tests could increase use of primaquine (PQ), however direct evidence of the impacts that G6PD testing has on downstream patient outcomes, such as haemolysis and recurrence is lacking.Methodology/principle findingsA linked-evidence model was created to investigate changes in the number of severe haemolysis events and P. vivax recurrences within 6 months of treatment when qualitative G6PD testing was used to guide PQ treatment (0.25mg/kg/day for 14 days and 0.5mg/kg/day for 7 days), compared to prescribing 14-day PQ with no G6PD testing. In the model patients identified as G6PD-deficient received 8-week PQ (0.75mg/kg/week). The model was used to simulate scenarios with 1%, 5% and 10% prevalence of G6PD-deficiency (G6PDd) in theoretical populations of 10,000 male and female P. vivax patients and initially assumed 100% adherence to the prescribed PQ regiment. Results illustrate that G6PD testing to guide the 14-day PQ regiment reduced severe haemolysis by 21-80% and increased recurrences by 3-6%, compared to applying the 14-day PQ regiment without G6PD testing. Results for the 7-day PQ regiment informed by G6PD testing were mixed, dependent on G6PDd prevalence and sex. When adherence to the PQ regiments was less than perfect the model predicted reductions in the number of recurrences at all prevalence levels, provided adherence to 7-day PQ was 5-10% higher than adherence to the 14-day regiment.Conclusions/significanceIntroduction of G6PD testing to guide PQ treatment reduces severe haemolysis events for the 14-day regiment, and the 7-day regiment in higher G6PDd prevalence settings, compared to use of 14-day PQ without G6PD testing when all patients adhere to the prescribed PQ treatment. At a population level, there were increases in recurrences, but this could be resolved when the 7-day regiment was used and had superior adherence compared to the 14-day regiment.

The formamidase (FMD) enzyme plays an important role in fungal thriving by releasing a secondary nitrogen source as a product of its activity. In Paracoccidioides species, previous studies have demonstrated the upregulation of this enzyme in a wide range of starvation and infective-like conditions. However, Paracoccidioides lutzii formamidase has not yet been defined as a virulence factor. Here, by employing in vivo infections using an fmd-silenced strain in Galleria mellonella larvae model, we demonstrate the influence of formamidase in P. lutzii's immune stimulation and pathogenicity. The formamidase silencing resulted in improper arrangement of the nodules, poor melanogenesis and decreased fungal burden. Thus, we suggest that formamidase may be a piece composing the process of molecular recognition by Galleria immune cells. Furthermore, formamidase silencing doubled the observed survival rate of the larvae, demonstrating its importance in fungal virulence in vivo. Therefore, our findings indicate that formamidase contributes to Galleria's immune incitement and establishes the role of this enzyme as a P. lutzii virulence factor.

Metagenomic next generation metagenomic sequencing (mNGS) has proven to be a useful tool in the diagnosis and identification of novel human pathogens and pathogens not identified on routine clinical microbiologic tests. In this study, we applied mNGS to characterize plasma RNA isolated from 42 study participants with unexplained acute febrile illness (AFI) admitted to tertiary referral hospitals in Mubende and Arua, Uganda. Study participants were selected based on clinical criteria suggestive of viral infection (i.e., thrombocytopenia, leukopenia). The study population had a median age of 28 years (IQR:24 to 38.5) and median platelet count of 114 x103 cells/mm3 (IQR:66,500 to 189,800). An average of 25 million 100 bp reads were generated per sample. We identified strong signals from diverse virus, bacteria, fungi, or parasites in 10 (23.8%) of the study participants. These included well recognized pathogens like Helicobacter pylori, human herpes virus-8, Plasmodium falciparum, Neisseria gonorrhoeae, and Rickettsia conorii. We further confirmed Rickettsia conorii infection, the cause of Mediterranean Spotted Fever (MSF), using PCR assays and Sanger sequencing. mNGS was a useful addition for detection of otherwise undetected pathogens and well-recognized non-pathogens. This is the first report to describe the molecular confirmation of a hospitalized case of MSF in sub-Saharan Africa (SSA). Further studies are needed to determine the utility of mNGS for disease surveillance in similar settings.

IntroductionAscaris lumbricoides has dual effects on the immune system of infected hosts. The IgE response to this parasite has been thoroughly studied, but little is known about cellular responses induced by infection. This study aims to explore the interplay between A. lumbricoides infection and B cell responses, especially B regulatory cells.MethodsParticipants from Santa Catalina, Bolívar, Colombia, a helminth-endemic town, were screened for soil-transmitted helminthiasis (STH) using stool examinations. Eighteen A. lumbricoides-infected and 11 non-infected subjects were selected. Blood samples were analyzed for Breg cells and related cytokines, and immunoglobulins specific to the A. lumbricoides excretory/secretory product, ABA-1.ResultsInfected subjects exhibited higher frequencies of Breg cells, especially those with a higher A. lumbricoides egg burden. Higher frequencies of different Breg subsets were observed in infected individuals, with CD25+CD71+CD73- B cells being notably increased in strongly infected individuals. Additionally, A. lumbricoides infection was associated with reduced levels of circulating ABA-1-specific IgG1 and IgE. IL-10+ B cell frequencies correlated inversely with ABA-1-specific IgE.ConclusionsA. lumbricoides infection has a significant impact on the immune response, particularly on Breg cell populations and antibody responses. Our findings suggest that A. lumbricoides infection mediates a dose-dependent immunosuppressive response characterized by an increase in Breg cells and concomitant suppression of ABA-1-specific humoral responses.

BackgroundLeptospirosis is a priority zoonotic disease in Kenya, but an in-depth review of its presence in humans, animals and the environment is lacking. Therefore, we conducted this systematic review and meta-analysis to understand the epidemiological situation to date.MethodologyWe searched for literature in African journals online, AGRIS, Embase, the Leptospira WOAH reference laboratory library, ProMED-mail, PubMed, Scopus, Web of Science, and the institutional repositories of 33 academic institutions and included 66 publications on leptospirosis in Kenya which spanned from 1951 to 2022. The review was registered on the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY).FindingsMost investigations were done in rural and urban areas in western, southern, central, and coastal areas in Kenya and the largely pastoral eastern and northern areas were under-represented. A wide host range of domestic animals and wildlife was revealed, and occupational exposure was an important risk factor for humans. The microscopic agglutination test (MAT) was the most frequent test, particularly common in studies conducted during the 1980s and 1990s. However, varying MAT panels and cut-off titres were observed. The overall seroprevalence in cattle was 28.2% (95% confidence intervals [CI]: 12.0-53.0; heterogeneity: I2 = 96.7%, τ2 = 1.4), and 11.0% in goats (95% CI: 5.4-21.2; heterogeneity: I2 = 78.8%, τ2 = 0.4). Molecular tests were seldom used to determine species and illustrate strain diversity. There was a lack of awareness of leptospirosis among farmers and health practitioners.ConclusionThe widespread presence of leptospires and inadequate diagnostic capacity demonstrate that leptospirosis is a common but underreported disease in Kenya. Raising awareness and boosting the country's diagnostic capacity is crucial to timely detection and disease control.

Genomics, transcriptomics, and proteomics have significantly advanced our understanding of obligately host-associated microbes, where interrogation of the biology is often limited by the complexity of the biological system and limited tools. This includes the causative agents of many neglected tropical diseases, including filarial nematodes. Therefore, numerous transcriptomics studies have been undertaken on filarial nematodes. Most of these transcriptomics studies focus on Brugia malayi, which causes lymphatic filariasis and is a laboratory model for human filarial disease. Here, we undertook a meta-analysis of the publicly available B. malayi transcriptomics data enabling the direct cross comparison of samples from almost a dozen studies. This reanalysis highlights the consistency of transcriptomics results across many different studies and experimental designs from across the globe for over a decade of research, across many different generations of a sequencing technology, library preparation protocols, and differential expression tools. Males and microfilariae across samples had similar expression profiles. However, female samples were clustered into two differential expression patterns that were significantly different from one another. Largely, we confirm previous results for all studies reanalyzed including tissue-specific gene expression and anti-Wolbachia doxycycline treatment of microfilaria. However, we did not detect previously reported differential expression upon in vitro or in vivo treatment with ivermectin, albendazole, and DEC, instead identifying a consistent lack of transcriptomic change upon exposure to these anthelminthic drugs. Updated annotation has been provided that denotes poorly supported genes including those overlapping rRNAs.

BackgroundMaternal-foetal transmission of Chagas disease (CD) affects newborns worldwide. Although Benznidazole and Nifurtimox therapies are the standard treatments, their use during pregnancy is contra-indicated. The effectiveness of trypanocidal medications in preventing congenital Chagas Disease (cCD) in the offsprings of women diagnosed with CD was highly suggested by other studies.MethodsWe performed a systematic review and meta-analysis of studies evaluating the effectiveness of treatment for CD in women of childbearing age and reporting frequencies of cCD in their children. PubMed, Scopus, Web of Science, Cochrane Library, and LILACS databases were systematically searched. Statistical analysis was performed using Rstudio 4.2 using DerSimonian and Laird random-effects models. Heterogeneity was examined with the Cochran Q test and I2 statistics. A p-value of ResultsSix studies were included, comprising 744 children, of whom 286 (38.4%) were born from women previously treated with Benznidazole or Nifurtimox, trypanocidal agents. The primary outcome of the proportion of children who were seropositive for cCD, confirmed by serology, was signigicantly lower among women who were previously treated with no congenital transmission registered (OR 0.05; 95% Cl 0.01-0.27; p = 0.000432; I2 = 0%). In women previously treated with trypanocidal drugs, the pooled prevalence of cCD was 0.0% (95% Cl 0-0.91%; I2 = 0%), our meta-analysis confirms the excellent effectiveness of this treatment. The prevalence of adverse events in women previously treated with antitrypanocidal therapies was 14.01% (95% CI 1.87-26.14%; I2 = 80%), Benznidazole had a higher incidence of side effects than Nifurtimox (76% vs 24%).ConclusionThe use of trypanocidal therapy in women at reproductive age with CD is an effective strategy for the prevention of cCD, with a complete elimination of congenital transmission of Trypanosoma cruzi in treated vs untreated infected women.

BackgroundHemorrhagic fever with renal syndrome (HFRS) is a severe public health problem in Jiangxi province, China. Previous studies reported genetic variants of Orthohantavirus hantanense (Hantaan virus, HTNV) in rodents in this area. However, the relationship between HTNV variants and human infection needs to be confirmed. This study aimed to identify the HTNV variants in patients and to understand the clinical characteristics of HFRS caused by these variants.MethodsSamples were collected from hospitalized suspected cases of HFRS during the acute phase. HFRS cases were confirmed using quantitative real-time RT-PCR. Peripheral blood mononuclear cells (PBMC) from patients with HFRS were inoculated into Vero-E6 cells for viral isolation. The genomic sequences of HTNV from patients were obtained by amplicon-based next-generation sequencing. A retrospective analysis was conducted on the clinical characteristics of the patients.ResultsHTNV RNA was detected in 53 of 183 suspected HFRS patients. Thirteen HTNVs were isolated from 32 PBMCs of HFRS cases. Whole genome sequences of 14 HTNVs were obtained, including 13 isolates in cell culture from 13 patients, and one from plasma of the fatal case which was not isolated successfully in cell culture. Genetic analysis revealed that the HTNV sequence from the 14 patients showed significant variations in nucleotide and amino acid to the HTNV strains found in other areas. Fever (100%, 53/53), thrombocytopenia (100%, 53/53), increased serum aspartate aminotransferase (100%, 53/53), and increased lactate dehydrogenase (96.2%, 51/53) were the most common characteristics. Severe acute kidney injury was observed in 13.2% (7/53) of cases. Clinical symptoms, such as pain, petechiae, and gastrointestinal or respiratory symptoms were uncommon.ConclusionThe HTNV genetic variants cause human infections in Jiangxi. The clinical symptoms of HFRS caused by the HTNV genetic variant during the acute phase are atypical. In addition to renal dysfunction, attention should be paid to the common liver injuries caused by these genetic variants.

Talaromycosis is a fungal infection caused by an opportunistic dimorphic fungus Talaromyces marneffei. During infection, T. marneffei resides inside phagosomes of human host macrophages where the fungus encounters nutrient scarcities and host-derived oxidative stressors. Previously, we showed that the deletion of acuK, a gene encoding Zn(2)Cys(6) transcription factor, caused a decreased ability for T. marneffei to defend against macrophages, as well as a growth impairment in T. marneffei on both low iron-containing medium and gluconeogenic substrate-containing medium. In this study, a paralogous gene acuM was deleted and characterized. The ΔacuM mutant showed similar defects with the ΔacuK mutant, suggesting their common role in gluconeogenesis and iron homeostasis. Unlike the pathogenic mold Aspergillus fumigatus, the ΔacuK and ΔacuM mutants unexpectedly exhibited normal siderophore production and did not show lower expression levels of genes involved in iron uptake and siderophore synthesis. To identify additional target genes of AcuK and AcuM, RNA-sequencing analysis was performed in the ΔacuK and ΔacuM strains growing in a synthetic dextrose medium with 1% glucose at 25 °C for 36 hours. Downregulated genes in both mutants participated in iron-consuming processes, especially in mitochondrial metabolism and anti-oxidative stress. Importantly, the ΔacuM mutant was sensitive to the oxidative stressors menadione and hydrogen peroxide while the ΔacuK mutant was sensitive to only hydrogen peroxide. The yeast form of both mutants demonstrated a more severe defect in antioxidant properties than the mold form. Moreover, ribosomal and ribosomal biogenesis genes were expressed at significantly lower levels in both mutants, suggesting that AcuK and AcuM could affect the protein translation process in T. marneffei. Our study highlighted the role of AcuK and AcuM as global regulators that control multiple cellular adaptations under various harsh environmental conditions during host infection. These transcription factors could be potentially exploited as therapeutic targets for the treatment of this neglected infectious disease.

Mycetoma is a debilitating neglected tropical disease that affects individuals worldwide, particularly in regions where there is poverty and limited health care access. The Mycetoma Research Center (MRC), based in Khartoum, Sudan, provides a sustainable, holistic approach to patient care as the only World Health Organization collaborating center for mycetoma. We describe MRC activities that align with the United Nations' Sustainable Development Goals to control mycetoma in Sudan and globally.

BackgroundOpisthorchis-like eggs are a public health problem in northern and northeastern Thailand. However, the genetic epidemiology and structure of these parasites in northern Thailand are unknown. Thus, this study investigated their population genetic structure using cytochrome c oxidase subunit 1 (cox1) and NADH dehydrogenase subunit 1 (nad1) nucleotide sequences.Methodology/principal findingsA study was conducted in the hill tribe regions of Chiang Mai Province, northern Thailand. Internal transcribed spacer 2 polymerase chain reaction and restriction fragment length polymorphism were used to distinguish 205 positive feces samples for Opisthorchis-like eggs. The results showed that the prevalence of O. viverrini and Haplorchis taichui was 10.5% and 38.2%, respectively, and the co-infection rate was 37.2%. To determine the genetic structure of O. viverrini and H. taichui using cox1 and nad1 genes, genetic analysis was performed using 30 randomly chosen fecal samples for Opisthorchis-like eggs. Pairwise FST analysis indicated that O. viverrini and H. taichui displayed nonsignificant genetic differentiation within Chiang Mai Province and between interpopulations from different geographic areas. Moreover, within the intrapopulation in Chiang Mai Province, cox1 presented higher gene flow than nad1 in O. viverrini, while nad1 demonstrated higher gene flow than cox1 in H. taichui. The neutrality tests based on Fu's Fs indicated population expansion and selective sweep from bottleneck or hitchhiking in O. viverrini and H. taichui populations, supported by haplotype network patterns. Phylogenetic tree analysis based on cox1 and nad1 revealed the monophyly of O. viverrini and H. taichui and genetic relationships with other isolates collected from Thailand, Lao People's Democratic Republic (PDR), and Vietnam.Conclusions/significanceThis study investigated the molecular discrimination and genetic structure of Opisthorchis-like eggs in northern Thailand. The genetic information derived from this study could be associated with the background, molecular epidemiology, and disease severity of these parasites.

Mosquito-borne Zika virus (ZIKV) from sub-Saharan Africa has recently gained attention due to its epidemic potential and its capacity to be highly teratogenic. To improve our knowledge on currently circulating strains of African ZIKV, we conducted protein sequence alignment and identified contemporary West Africa NS1 (NS1CWA) protein as a highly conserved viral protein. Comparison of NS1CWA with the NS1 of the historical African ZIKV strain MR766 (NS1MR766), revealed seven amino acid substitutions. The effects of NS1 mutations on protein expression, virus replication, and innate immune activation were assessed in human cells using recombinant NS1 proteins and a chimeric viral clone MR766 with NS1CWA replacing NS1MR766. Our data indicated higher secretion efficiency of NS1CWA compared to NS1MR766 associated with a change in subcellular distribution. A chimeric MR766 virus with NS1CWA instead of authentic protein displayed a greater viral replication efficiency, leading to more pronounced cell death compared to parental virus. Enhanced viral growth was associated with reduced activation of innate immunity. Our data raise questions of the importance of NS1 protein in the pathogenicity of contemporary ZIKV from sub-Saharan Africa and point to differences within viral strains of African lineage.