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Traditional practices versus modern healthcare: Determinants of traditional medicine use after potential dog bites among dog-owning households in Nigeria. 传统做法与现代保健:尼日利亚养狗家庭在可能被狗咬伤后使用传统药物的决定因素。
IF 3.4 2区 医学
PLoS Neglected Tropical Diseases Pub Date : 2025-03-17 eCollection Date: 2025-03-01 DOI: 10.1371/journal.pntd.0012910
Philip P Mshelbwala, Kinley Wangdi, Jibrin Idris, Mohammad Mahmudul Hassan, Andrew M Adamu, Charles E Rupprecht, Nicholas J Clark
{"title":"Traditional practices versus modern healthcare: Determinants of traditional medicine use after potential dog bites among dog-owning households in Nigeria.","authors":"Philip P Mshelbwala, Kinley Wangdi, Jibrin Idris, Mohammad Mahmudul Hassan, Andrew M Adamu, Charles E Rupprecht, Nicholas J Clark","doi":"10.1371/journal.pntd.0012910","DOIUrl":"10.1371/journal.pntd.0012910","url":null,"abstract":"<p><p>Canine rabies is endemic in Nigeria, with a low dog vaccination rate. Often, dog bite victims resort to traditional remedies, which can lead to fatalities. Our study investigated factors influencing decisions to seek traditional remedies in Nigeria. We conducted a cross-sectional study in 2022 involving 4,162 dog-owning households. A joint random effect Bayesian regression model was developed to examine the role of sociodemographic, socioeconomic, and infrastructural covariates. This model included a latent variable measuring a respondent's understanding of rabies risk based on literacy levels and responses to questions about rabies epidemiology. Our results indicated that 27% (95% Confidence Interval [Cl); 26-27) of respondents would preferably seek traditional remedies following a dog bite. Male respondents were 24% more likely than female respondents to seek traditional remedies (odds ratio [OR]: 1.24; 95%, Credible Interval CrI): 1.07-1.31). Similarly, individuals residing in rural areas reported 55% higher likelihood of using traditional remedies than those in urban areas (OR: 1.55; 95% CrI: 1.43-1.67). Respondents residing in areas with no veterinary services reported 35% higher likelihood of using traditional remedies than those near such facilities (OR: 1.35; 95% CrI: 1.15-1.42). Children under 16 years reported 27% lower likelihood of using traditional remedies than adults (OR: 0.73; 95% CrI: 0.49-0.84). Private or unemployed individuals were more likely to seek traditional remedies than civil servants (OR: 1.99; 95% Crl: 1.53-2.37). Respondents with tertiary education reported 42% lower likelihood of using traditional remedies than those without formal education (OR: 0.58; 95% CrI: 0.49-0.62). Our latent variable representing understanding of rabies risk was negatively associated with the probability of seeking traditional remedies (OR: 0.67; 95% CrI: 0.54-0.73). Lastly, poverty was negatively associated with the likelihood of seeking traditional remedies (OR: 0.78; 95% CrI: 0.66-0.82). Our findings provide important insights into healthcare behaviour decisions and their possible associations with rabies outcomes in Nigeria. These results highlight the need to improve public education, enhance access to medical care, and involve traditional healers in rabies prevention and control programs.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"19 3","pages":"e0012910"},"PeriodicalIF":3.4,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
T-cell activation and senescence in asymptomatic HIV/Leishmania infantum co-infection. 无症状HIV/利什曼原虫合并感染的t细胞活化和衰老。
IF 3.4 2区 医学
PLoS Neglected Tropical Diseases Pub Date : 2025-03-17 eCollection Date: 2025-03-01 DOI: 10.1371/journal.pntd.0012848
Carolina de Oliveira Mendes-Aguiar, Manoella do Monte Alves, Amanda de Albuquerque Lopes Machado, Glória Regina de Góis Monteiro, Iara Marques Medeiros, Jose Wilton Queiroz, Iraci Duarte Lima, Eliardo G Costa, Richard D Pearson, Mary E Wilson, Marshall J Glesby, Eliana Lúcia Tomaz do Nascimento, Selma Maria Bezerra Jerônimo
{"title":"T-cell activation and senescence in asymptomatic HIV/Leishmania infantum co-infection.","authors":"Carolina de Oliveira Mendes-Aguiar, Manoella do Monte Alves, Amanda de Albuquerque Lopes Machado, Glória Regina de Góis Monteiro, Iara Marques Medeiros, Jose Wilton Queiroz, Iraci Duarte Lima, Eliardo G Costa, Richard D Pearson, Mary E Wilson, Marshall J Glesby, Eliana Lúcia Tomaz do Nascimento, Selma Maria Bezerra Jerônimo","doi":"10.1371/journal.pntd.0012848","DOIUrl":"10.1371/journal.pntd.0012848","url":null,"abstract":"<p><strong>Background: </strong>Leishmania infantum can be an opportunistic pathogen, with an immunocompromised status increasing the risk of converting asymptomatic infection to symptomatic visceral leishmaniasis (VL). VL has approximately 5% fatality rate; and HIV coinfection (AIDS/VL) increases this risk. We hypothesized that, relative to those with HIV alone, people with co-infection would have altered T cell activation which could impact on the risk of VL.</p><p><strong>Methods: </strong>A cross-sectional study was performed between 2014 and 2016 to determine the prevalence of L. infantum infection in people living with HIV (PLHIV) residing in Brazil (n = 1,372). Subsequent incident cases of VL were ascertained from a public health database through 2018 and from a cohort of families with VL. Immune status of 69 participants was evaluated and comparisons made between those with and without HIV, with latent or with active Leishmania infection and those without HIV but with active or resolved Leishmania or T cell hypersensitivity to Leishmania antigen and healthy control subjects.</p><p><strong>Results: </strong>A total of 24.2% of PLHIV had positive anti-IgG L. infantum antibodies. The relative risk of developing AIDS/VL was 2.27 (95% CI: 0.920 to 5.59; p = 0.07) to HIV/Leish coinfected subjects with positive leishmania serology compared to HIV subjects without leishmania serology. Poor adherence to antiretroviral therapy (p = 0.0008) or prior opportunistic infections (p = 0.0007) was associated with development of AIDS/VL in asymptomatic HIV/Leish. CD4+ and CD8+ T cells counts or viral load were similar between asymptomatic HIV/Leish and HIV subjects. However, activated CD8+CD38+HLA-DR+ T cells were higher in asymptomatic HIV/Leish than HIV. Likewise, senescent (CD57+) and PD1+ CD8+ T cells were higher in asymptomatic HIV/Leish than in AIDS/VL or HIV groups.</p><p><strong>Conclusion: </strong>Although asymptomatic HIV/Leish subjects had CD4+ and CD8+ T cells similar to HIV alone, their CD8+T cells had increased activation and senescence which could contribute to risk of developing VL.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"19 3","pages":"e0012848"},"PeriodicalIF":3.4,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11964262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cas10 based 7SL-sRNA diagnostic for the detection of active trypanosomosis. 基于Cas10的7SL-sRNA诊断检测活动性锥虫病
IF 3.4 2区 医学
PLoS Neglected Tropical Diseases Pub Date : 2025-03-17 eCollection Date: 2025-03-01 DOI: 10.1371/journal.pntd.0012937
Sabine Grüschow, Pieter C Steketee, Edith Paxton, Keith R Matthews, Liam J Morrison, Malcolm F White, Finn Grey
{"title":"Cas10 based 7SL-sRNA diagnostic for the detection of active trypanosomosis.","authors":"Sabine Grüschow, Pieter C Steketee, Edith Paxton, Keith R Matthews, Liam J Morrison, Malcolm F White, Finn Grey","doi":"10.1371/journal.pntd.0012937","DOIUrl":"10.1371/journal.pntd.0012937","url":null,"abstract":"<p><p>Animal Trypanosomosis (AT) is a significant disease affecting cattle across sub-Saharan Africa, Latin America, and Asia, posing a major threat to economic productivity and animal welfare. The absence of reliable diagnostic tests has led to an over-reliance on widespread pre-emptive drug treatments, which not only compromise animal health but also heighten the risk of drug resistance. The chronic nature of AT, characterized by cyclical low or undetectable parasite levels, and the necessity for field-applicable tests that can distinguish between active infection and prior exposure, present considerable challenges in developing effective diagnostics. In previous work, we identified a parasite-specific small RNA, 7SL-sRNA, which is detectable in the serum of infected cattle, even during the chronic stages of infection. However, existing methods for detecting sRNA require specialized equipment, making them unsuitable for field use. In this study, we have developed both a fluorescence-based and a lateral flow diagnostic test utilizing Cas10 technology for the detection of 7SL-sRNA from Trypanosoma congolense and Trypanosoma brucei. The fluorescence assay detects 10 - 100 fM T. congolense 7SL-sRNA and 1 pM T. brucei 7SL-sRNA, and the lateral flow assay showed a limit of detection of 1 - 10 pM for both species. Either assay can effectively identify active infections in cattle, including during chronic phases (with positive signals observed up to the experimental end point, 63 days post infection). This also highlights the effective use of Cas10 for small RNA detection, paving the way for a cost-effective, user-friendly, and field-deployable diagnostic test for AT, while establishing Cas10 technology for the detection of small RNAs in general.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"19 3","pages":"e0012937"},"PeriodicalIF":3.4,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143650348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
HL-IR mediates cinnamaldehyde repellency behavior in parthenogenetic Haemaphysalis longicornis. HL-IR介导孤雌长角血蜱对肉桂醛的排斥行为。
IF 3.4 2区 医学
PLoS Neglected Tropical Diseases Pub Date : 2025-03-17 eCollection Date: 2025-03-01 DOI: 10.1371/journal.pntd.0012877
Ceyan Kuang, Han Shi, Jie Cao, Yongzhi Zhou, Houshuang Zhang, Yanan Wang, Jinlin Zhou
{"title":"HL-IR mediates cinnamaldehyde repellency behavior in parthenogenetic Haemaphysalis longicornis.","authors":"Ceyan Kuang, Han Shi, Jie Cao, Yongzhi Zhou, Houshuang Zhang, Yanan Wang, Jinlin Zhou","doi":"10.1371/journal.pntd.0012877","DOIUrl":"10.1371/journal.pntd.0012877","url":null,"abstract":"<p><p>Chemical repellents against arthropods have limitations in terms of toxicity and resistance. Natural plant compounds can be utilized as alternatives for developing environmentally friendly repellents for humans and animals. A variety of plant essential oils exhibit strong repellent effects against ticks; however, the mechanisms of action against ticks remain unknown. Here, we investigated the repellency of cinnamaldehyde, a primary compound found in cinnamon oil, and demonstrated that it affected the electrophysiological responses on Haller's organs of parthenogenetic Haemaphysalis longicornis. Transcriptome data indicated that the cinnamaldehyde response was linked to ionotropic receptor (HL-IR) at various tick developmental stages. HL-IR was widely expressed in a variety of tissues and developmental stages of ticks according to RT-qPCR. In situ hybridization results showed that HL-IR was highly expressed on Haller's organs of the ticks. Microinjection of HL-IR double-stranded RNA (dsRNA) showed that reduced transcript levels led to significant decreases in the tick repellency rate from cinnamaldehyde and the EAG response of Haller's organ. Experiments using competitive fluorescence binding and mutation sites showed that 218ASN was the critical binding site for cinnamaldehyde and HL-IR. We conclude that Haller's organ of ticks expresses HL-IR, and that this interaction mediates tick-repellent behavior by binding to cinnamaldehyde.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"19 3","pages":"e0012877"},"PeriodicalIF":3.4,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11913321/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Detection of Leishmania metacyclogenesis within the sand fly vector employing a real-time PCR for sherp gene expression: A tool for Leishmania surveillance and transmission potential. 利用实时荧光定量PCR检测沙蝇载体内利什曼原虫元胞形成:一种监测利什曼原虫及其传播潜力的工具。
IF 3.4 2区 医学
PLoS Neglected Tropical Diseases Pub Date : 2025-03-17 eCollection Date: 2025-03-01 DOI: 10.1371/journal.pntd.0012915
Chukwunonso O Nzelu, Somayeh Bahrami, Phillip G Lawyer, Nathan C Peters
{"title":"Detection of Leishmania metacyclogenesis within the sand fly vector employing a real-time PCR for sherp gene expression: A tool for Leishmania surveillance and transmission potential.","authors":"Chukwunonso O Nzelu, Somayeh Bahrami, Phillip G Lawyer, Nathan C Peters","doi":"10.1371/journal.pntd.0012915","DOIUrl":"10.1371/journal.pntd.0012915","url":null,"abstract":"<p><p>Surveillance of infected insect vectors of vector-transmitted diseases has been recognized for its ability to estimate pathogen prevalence and transmission potential. Classically restricted to microscopic dissection and examination of individual insects, the potential of entomological monitoring has grown due to the advent of rapid molecular DNA detection methods with high specificity and sensitivity. Despite such advancement, a recurring question concerning DNA detection of parasitic pathogens is related to the fact that DNA amplification, by itself, does not differentiate between insects carrying infectious versus dead, non- or poorly-infectious life-cycle stages, thereby limiting it's programmatic usefulness for accurately measuring the transmission potential of infected insects in endemic areas or within experimentally infected populations. Herein, we developed a quantitative real-time PCR with Reverse Transcription (RT-qPCR) based sherp (small hydrophilic endoplasmic reticulum-associated protein) detection assay employing a novel set of sherp-RT-qPCR primers to detect and quantify infectious Leishmania parasites in infected vector sand flies. The sherp RT-qPCR showed significantly increased expression of sherp transcripts in infectious Leishmania metacyclic versus non-metacyclic promastigotes or mammalian-derived amastigotes. The assay displayed detection performance ranging from 106 to 1 parasite and could reliably quantify parasites within infected sand flies without the need for dissection. Sherp transcripts were also successfully amplified from flies stored in ethanol at room temperature, a practical and economical method of sample preservation in resource-limited field settings. Lastly, in conjunction with an established RT-qPCR assay for Leishmania kinetoplast DNA minicircles, we were able to calculate a score for the degree of metacyclogenesis within infected sand flies, a known predictor of transmission potential. These results highlight the potential of the sherp-RT-qPCR assay to identify hotspots of potential transmission, areas of re-emergence, vector competence, and the transmission potential of infected sand fly populations.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"19 3","pages":"e0012915"},"PeriodicalIF":3.4,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11942415/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Unraveling the dynamics of dengue in Metahara town, East Shewa, Oromia, Ethiopia, 2023. 揭示2023年埃塞俄比亚奥罗米亚州东谢瓦Metahara镇登革热动态
IF 3.4 2区 医学
PLoS Neglected Tropical Diseases Pub Date : 2025-03-17 eCollection Date: 2025-03-01 DOI: 10.1371/journal.pntd.0012908
Bikila Negesa Gobena, Teshome Kabeta Dadi, Gemechu Chemeda Feyisa, Birhanu Kenate, Gemechu Shumi, Fantahun Workie, Haimanot Workie, Ebise Djirata, Dabesa Gobena
{"title":"Unraveling the dynamics of dengue in Metahara town, East Shewa, Oromia, Ethiopia, 2023.","authors":"Bikila Negesa Gobena, Teshome Kabeta Dadi, Gemechu Chemeda Feyisa, Birhanu Kenate, Gemechu Shumi, Fantahun Workie, Haimanot Workie, Ebise Djirata, Dabesa Gobena","doi":"10.1371/journal.pntd.0012908","DOIUrl":"10.1371/journal.pntd.0012908","url":null,"abstract":"<p><strong>Background: </strong>Since 2013, dengue cases have shown a marked increase in Ethiopia. The current suspected outbreak occurring in Metahara town, Oromia Regional State, began in July 2023. This study aimed to confirm and characterize the outbreak, identify risk factors, and implement control measures.</p><p><strong>Methods: </strong>We conducted a descriptive study and an unmatched case-control design, using a one-to-two ratio of cases to controls. We collected data on the dengue outbreak using line lists, laboratory test results, environmental observations, home visits, and entomological examinations. We selected a total of 50 cases using simple random sampling from the line list and purposively chose 100 controls from the same block. We applied community-based face-to-face interviews with 150 participants. After gathering data through Kobo Collect, we analyzed it using Statistical Package for the Social Sciences (SPSS) version 26 and summarized the findings in Microsoft Excel 2013. A binary logistic regression model was employed to identify significant variables, with p-values ≤ 0.25 in bivariate analysis considered for the final model. Crude and adjusted odds ratios (OR and AOR) were used to measure associations, with p-values ≤ 0.05 indicating significance.</p><p><strong>Results: </strong>The investigation confirmed 342 dengue cases, corresponding to an attack rate of 7.1 per 1,000 population and a case fatality rate of 0.88%. Significant risk factors included not using long-lasting insecticide nets during the daytime (9-fold increased likelihood) and having open water containers (5-fold increased likelihood. Respondents lacking disease awareness were 25 times more likely to be infected, while wearing long-sleeved clothing conferred a protective effect of 75% reduction in risk.</p><p><strong>Conclusion: </strong>The dengue outbreak in Metahara town was driven by epidemiological, entomological, and environmental factors, with Aedes aegypti as the primary vector. The ongoing circulation of DENV-3, coupled with insufficient vector control measures, poses a serious public health threat. Key contributing factors to the outbreak include the lack of utilization of long-lasting insecticide nets (LLINs) during the daytime, improper water storage practices, insufficient public knowledge regarding transmission and prevention strategies, and inadequate protective clothing choices that increase vulnerability to mosquito bites. Strategies including vector control, community education, promotion of protective clothing, and improved surveillance were recommended.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"19 3","pages":"e0012908"},"PeriodicalIF":3.4,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Exploring the genomic landscape of the GP63 family in Trypanosoma cruzi: Evolutionary dynamics and functional peculiarities. 探索克氏锥虫GP63家族的基因组景观:进化动力学和功能特性。
IF 3.4 2区 医学
PLoS Neglected Tropical Diseases Pub Date : 2025-03-17 eCollection Date: 2025-03-01 DOI: 10.1371/journal.pntd.0012950
Luisa Berná, María Laura Chiribao, Sebastián Pita, Fernando Alvarez-Valin, Adriana Parodi-Talice
{"title":"Exploring the genomic landscape of the GP63 family in Trypanosoma cruzi: Evolutionary dynamics and functional peculiarities.","authors":"Luisa Berná, María Laura Chiribao, Sebastián Pita, Fernando Alvarez-Valin, Adriana Parodi-Talice","doi":"10.1371/journal.pntd.0012950","DOIUrl":"10.1371/journal.pntd.0012950","url":null,"abstract":"<p><p>Members of the GP63 metalloprotease family play crucial roles in parasite-host interactions, immune evasion, and pathogenesis. Although it has been widely studied in Leishmania spp., less is known about its function and diversity in Trypanosoma cruzi. This study focuses on characterizing the complete repertoire of GP63 sequences in the T. cruzi genome, refining gene annotations, and exploring the evolutionary dynamics that shape the diversity of these proteins. Eleven GP63 groups were identified, which are sharply defined and have a higher intra- than inter-group sequence identity. These GP63 groups display some distinctive features. First, two groups lack an essential amino acid in the active site, indicating that they are enzymatically inactive. Second, GP63 groups show strong preference for different genomic compartments. Moreover, genes from groups located in the core genome compartment of T. cruzi, are often arranged as tandem arrays (of larger genomic fragments that generally include a SIRE retroposon), whereas genes from groups located in the disruptive compartment tend to be surrounded by genes encoding other surface proteins (such as MASP, mucins and trans-sialidases). Transcription patterns across different life cycle stages are not homogenous. Instead, some GP63 groups have higher mRNA levels in the infective trypomastigote stage, suggesting a potential role in host invasion. To get a wider picture of the evolutionary dynamics of these proteins, a phylogenetic analysis was conducted that included species representative of kinetoplastid diversity. It was found that 10 out of 11 GP63 T. cruzi groups are specific to the Trypanosoma genus, suggesting that the diversification of these subfamilies took place before speciation of the genus, followed by other species-specific expansions. Additionally, there are other GP63 groups that are absent in T. cruzi. Notably, the processes of expansion and diversification of GP63 in Leishmania is independent of that of trypanosomes. This suggests that these proteins may have evolved under species-specific selective (functional) pressures, resulting in unique amplifications in each parasite species.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"19 3","pages":"e0012950"},"PeriodicalIF":3.4,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Development of a virulent O'nyong'nyong challenge model to determine heterologous protection mediated by a hydrogen peroxide-inactivated chikungunya virus vaccine. 过氧化氢灭活基孔肯雅病毒疫苗介导的异源保护性强毒O'nyong'nyong攻毒模型的建立。
IF 3.4 2区 医学
PLoS Neglected Tropical Diseases Pub Date : 2025-03-17 eCollection Date: 2025-03-01 DOI: 10.1371/journal.pntd.0012938
Whitney C Weber, Zachary J Streblow, Takeshi F Andoh, Michael Denton, Hans-Peter Raué, Ian J Amanna, Dawn K Slifka, Craig N Kreklywich, Irene Arduino, Gauthami Sulgey, Magdalene M Streblow, Mark T Heise, Mark K Slifka, Daniel N Streblow
{"title":"Development of a virulent O'nyong'nyong challenge model to determine heterologous protection mediated by a hydrogen peroxide-inactivated chikungunya virus vaccine.","authors":"Whitney C Weber, Zachary J Streblow, Takeshi F Andoh, Michael Denton, Hans-Peter Raué, Ian J Amanna, Dawn K Slifka, Craig N Kreklywich, Irene Arduino, Gauthami Sulgey, Magdalene M Streblow, Mark T Heise, Mark K Slifka, Daniel N Streblow","doi":"10.1371/journal.pntd.0012938","DOIUrl":"10.1371/journal.pntd.0012938","url":null,"abstract":"<p><p>O'nyong-nyong virus (ONNV) is a mosquito-transmitted alphavirus identified in Uganda in 1959. The virus has potential for enzootic and urban transmission cycles, and in humans, ONNV infection manifests as fever, rash, and joint/muscle pain that can persist. There are currently no specific vaccines or antiviral treatments for ONNV. Since highly passaged alphaviruses often lose pathogenic features, we constructed an infectious clone for ONNV-UVRI0804 (ONNV0804), a 2017 isolate from a febrile patient in Uganda. Viral replication for ONNV0804 was compared to the highly passaged strain, ONNVUgMP30, and ONNVUgMP30 replicated to higher levels in human dermal fibroblasts and Vero cells, but both viruses replicated similarly in C6/36 and mouse embryonic fibroblast cells. We performed a head-to-head comparison of in vivo virulence in both immunocompetent C57BL/6 mice and interferon deficient AG129 mice. In both mouse strains, ONNV0804 was substantially more pathogenic than ONNVUgMP30. Unlike ONNVUgMP30, ONNV0804 caused significant footpad swelling and broader tissue distribution with higher vRNA loads at both 5- and 43-days post-infection (dpi) relative to ONNVUgMP30. This finding indicates that ONNV can persist in joint and muscle tissues for long periods of time, which has been associated with chronic arthritogenic human disease. In AG129 mice, ONNV0804 caused a more rapid onset of disease, higher viremia, and a >800-fold increase in virulence. Previous studies have shown that CHIKV infection or vaccination can provide cross-reactive immunity to ONNV. To determine if a CHIKV vaccine can protect against the more virulent ONNV0804 strain, we vaccinated mice with a hydrogen peroxide-inactivated CHIKV vaccine, HydroVax-CHIKV. Neutralizing antibody titers were determined against ONNV0804 and CHIKV and animals were challenged with ONNV0804. An optimized two-dose vaccination regimen of HydroVax-CHIKV protected against lethal infection and reduced virus-associated arthritogenic disease. These data indicate that we have developed new and robust models for studying severe ONNV disease and that HydroVax-CHIKV vaccination can protect against infection with a highly pathogenic contemporary strain of ONNV.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"19 3","pages":"e0012938"},"PeriodicalIF":3.4,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11964224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Diagnosis of Indian Big Four and monocled Cobra snakebites in envenomed plasma using smartphone-based digital imaging colourimetry method. 使用基于智能手机的数字成像比色法诊断被毒蛇咬伤的血浆中的印度大四眼镜蛇和独角眼镜蛇。
IF 3.4 2区 医学
PLoS Neglected Tropical Diseases Pub Date : 2025-03-14 eCollection Date: 2025-03-01 DOI: 10.1371/journal.pntd.0012913
Upasana Puzari, Mojibur R Khan, Ashis K Mukherjee
{"title":"Diagnosis of Indian Big Four and monocled Cobra snakebites in envenomed plasma using smartphone-based digital imaging colourimetry method.","authors":"Upasana Puzari, Mojibur R Khan, Ashis K Mukherjee","doi":"10.1371/journal.pntd.0012913","DOIUrl":"10.1371/journal.pntd.0012913","url":null,"abstract":"<p><strong>Background: </strong>Venomous or dry bites can result from snake envenomation. Therefore, developing a detection test for venomous snakebites in envenomed patients can prevent from unnecessary antivenom therapy for dry bites, thereby, saving them from adverse effects and cost of antivenom therapy.</p><p><strong>Methodology: </strong>This study demonstrates a method for the diagnosis of medically significant 'Big Four' Indian snake venoms (Naja naja, Bungarus caeruleus, Daboia russelii, Echis carinatus) in the plasma of experimentally envenomed animals (envenomed under laboratory conditions). Rabbit polyclonal antibodies (PAbs) were produced by generating modified bespoke peptides identified by computational analysis from the antigenic sites of the main toxins found in the proteome of India's 'Big Four' venomous snakes. The polyclonal antibody formulation (FPAb) prepared by mixing the five representative PAbs in the ratio of 1:1:1:1:1 demonstrated synergistic immune recognition of the 'Big Four' snakes and Naja kaouthia venoms. The recognition for these venoms under in vitro and in vivo conditions by FPAb was significantly higher (p<0.05) than commercial polyvalent antivenom produced against native venom toxins. The FPAb was tested to detect the venoms in subcutaneously envenomed rat plasmas until 240 minutes post-injection. Fourier-transform infrared spectroscopy, zeta potential, transmission electron microscopy, and atomic force microscopy characterised gold nanoparticles (AuNP) conjugated with FPAb. The FPAb-conjugated AuNP demonstrated aggregation upon interaction with venom toxins, changing the colour from red through burgundy to blue, monitored using a smartphone. From the digital image colourimetry analysis of the images, calibration curves for venoms were obtained, and each venom in the envenomed plasma at different time intervals was quantified using these curves.</p><p><strong>Conclusion: </strong>A method for detection of venomous snakebites has been reported. The formulation of polyclonal antibodies generated against toxins of 'Big Four' venomous snakes of India immune-recognise venoms of 'Big Four' venomous snakes of India and N. kaouthia venoms under both in vitro and in vivo conditions. The antibody formulation conjugated to AuNP detected the venoms in envenomed plasma. This method of detection has potential to be useful for snakebite management in clinical settings.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"19 3","pages":"e0012913"},"PeriodicalIF":3.4,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11936222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Genomic epidemiology of Plasmodium knowlesi reveals putative genetic drivers of adaptation in Malaysia. 诺氏疟原虫的基因组流行病学揭示了马来西亚适应的假定遗传驱动因素。
IF 3.4 2区 医学
PLoS Neglected Tropical Diseases Pub Date : 2025-03-12 eCollection Date: 2025-03-01 DOI: 10.1371/journal.pntd.0012885
Jacob A F Westaway, Ernest Diez Benavente, Sarah Auburn, Michal Kucharski, Nicolas Aranciaga, Sourav Nayak, Timothy William, Giri S Rajahram, Kim A Piera, Kamil Braima, Angelica F Tan, Danshy A Alaza, Bridget E Barber, Chris Drakeley, Roberto Amato, Edwin Sutanto, Hidayat Trimarsanto, Jenarun Jelip, Nicholas M Anstey, Zbynek Bozdech, Matthew Field, Matthew J Grigg
{"title":"Genomic epidemiology of Plasmodium knowlesi reveals putative genetic drivers of adaptation in Malaysia.","authors":"Jacob A F Westaway, Ernest Diez Benavente, Sarah Auburn, Michal Kucharski, Nicolas Aranciaga, Sourav Nayak, Timothy William, Giri S Rajahram, Kim A Piera, Kamil Braima, Angelica F Tan, Danshy A Alaza, Bridget E Barber, Chris Drakeley, Roberto Amato, Edwin Sutanto, Hidayat Trimarsanto, Jenarun Jelip, Nicholas M Anstey, Zbynek Bozdech, Matthew Field, Matthew J Grigg","doi":"10.1371/journal.pntd.0012885","DOIUrl":"10.1371/journal.pntd.0012885","url":null,"abstract":"<p><p>Sabah, Malaysia, has amongst the highest burden of human Plasmodium knowlesi infection in the world, associated with increasing encroachment on the parasite's macaque host habitat. However, the genomic make-up of P. knowlesi in Sabah was previously poorly understood. To inform on local patterns of transmission and putative adaptive drivers, we conduct population-level genetic analyses of P. knowlesi human infections using 52 new whole genomes from Sabah, Malaysia, in combination with publicly available data. We identify the emergence of distinct geographical subpopulations within the macaque-associated clusters using identity-by-descent-based connectivity analysis. Secondly, we report on introgression events between the clusters, which may be linked to differentiation of the subpopulations, and that overlap genes critical for survival in human and mosquito hosts. Using village-level locations from P. knowlesi infections, we also identify associations between several introgressed regions and both intact forest perimeter-area ratio and mosquito vector habitat suitability. Our findings provide further evidence of the complex role of changing ecosystems and sympatric macaque hosts in Malaysia driving distinct genetic changes seen in P. knowlesi populations. Future expanded analyses of evolving P. knowlesi genetics and environmental drivers of transmission will be important to guide public health surveillance and control strategies.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"19 3","pages":"e0012885"},"PeriodicalIF":3.4,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11932472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143617378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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