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Recent advances in the clinical development of antifungal vaccines: a narrative review 抗真菌疫苗临床开发的最新进展:综述
Pub Date : 2024-08-08 DOI: 10.3389/fitd.2024.1446477
Das Alapan, Ojha Bisweswar, Sarkar Prasenjit, Das Prasanjit, Bandyopadhyay Arkapal
Vaccine development tools for fungal infections are undergoing transformation where newer technologies like nanotechnology and bioinformatics are used to create new and improved vaccine candidates. Immunocompromised individuals and those with multiple chronic conditions are especially vulnerable to invasive fungal infections. These patients are at increased risk of developing widespread infections and experiencing poor health outcomes. Current management of fungal infections is associated with diagnostic challenges, side effects, and resistance. Vaccination is an effective strategy to prevent infections and boost immunity. Despite the significant burden of fungal disease, there are currently no licensed fungal vaccines available. This review is focused on various vaccine development strategies, including whole-cell, subunit, and nucleic acid-based vaccines. Various challenges like safety concerns, weak and nonspecific immune response, ideal adjuvants, and the need for improved drug delivery systems are also highlighted in this review. Sustained antigenic response, addressing host immune response variability, and eliciting persistent predictable immune response are crucial for vaccine development. Standardized protocols and robust preclinical studies are essential for the clinical development of potential vaccine candidates. Exploring novel targets using advanced technologies like bioinformatics, nanotechnology, and reverse vaccinology are being rapidly explored.
针对真菌感染的疫苗开发工具正在发生转变,纳米技术和生物信息学等新技术被用于开发新的改良候选疫苗。免疫力低下的人和患有多种慢性疾病的人特别容易受到侵袭性真菌感染。这些患者发生大面积感染和健康状况恶化的风险更高。目前治疗真菌感染的方法存在诊断难题、副作用和耐药性。接种疫苗是预防感染和提高免疫力的有效策略。尽管真菌疾病造成了巨大的负担,但目前还没有获得许可的真菌疫苗。本综述重点介绍各种疫苗开发策略,包括全细胞疫苗、亚单位疫苗和核酸疫苗。本综述还强调了各种挑战,如安全性问题、弱和非特异性免疫反应、理想佐剂以及改进给药系统的必要性。持续的抗原反应、解决宿主免疫反应的可变性以及激发持久的可预测免疫反应对于疫苗开发至关重要。标准化方案和稳健的临床前研究对于候选疫苗的临床开发至关重要。利用生物信息学、纳米技术和反向疫苗学等先进技术探索新型靶点的工作正在迅速展开。
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引用次数: 0
Sustaining success through strategies for post-elimination management of neglected tropical diseases in African Union Member States 非洲联盟成员国通过被忽视热带疾病消除后管理战略保持成功
Pub Date : 2024-08-08 DOI: 10.3389/fitd.2024.1421522
Nafiisah Chotun, Julian Eaton, Ifeoma Ajegbo Anagbogu, H. Tesfahunei, Sheila Shawa, Carol Karutu, Akeem Bolarinwa, Abdulaziz Mohammed
The elimination of Neglected Tropical Diseases (NTDs) has seen significant progress, with 22 African Union Member States having successfully eliminated at least one NTD. However, post-elimination management of NTDs remains a challenge. This article provides important insights into the challenges faced by African Union Member States after eliminating NTDs, including potential financial support withdrawal and risk of disease reemergence. We also discuss comprehensive strategies for post-elimination management, emphasising the importance of robust surveillance systems, capacity building, community engagement, and the integration of mental health services. We also advocate for a multisectoral approach to sustain elimination gains, aligning with global and regional health strategies. Our analysis underscores the necessity of continuous innovation in surveillance, the critical role of community health workers, the integration of NTD post-elimination management into broader health and development frameworks such as Universal Healthcare Coverage, and the need for innovative financing and partnerships to ensure the long-term success of NTD elimination efforts.
消除被忽视热带病(NTDs)的工作取得了重大进展,22 个非洲联盟成员国已成功消除了至少一种 NTDs。然而,消灭非传染性疾病后的管理仍然是一项挑战。本文就非洲联盟成员国在消灭非传染性疾病后面临的挑战提供了重要见解,包括可能撤销财政支持和疾病再次爆发的风险。我们还讨论了消除后管理的综合战略,强调了强大的监测系统、能力建设、社区参与和整合心理健康服务的重要性。我们还主张采取多部门方法来保持消除工作的成果,并与全球和地区卫生战略保持一致。我们的分析强调了在监测方面不断创新的必要性、社区卫生工作者的关键作用、将消灭非传染性疾病后的管理纳入更广泛的卫生和发展框架(如全民医疗保健覆盖),以及创新融资和伙伴关系的必要性,以确保消灭非传染性疾病工作的长期成功。
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引用次数: 0
Biobanking for tropical health: leveraging collaborative initiatives in the Lusophone world 生物库促进热带健康:利用葡语世界的合作倡议
Pub Date : 2024-08-08 DOI: 10.3389/fitd.2024.1438842
A. P. Arez, Aline Souto, Manuela da Silva, C. R. S. do Nascimento, Isabel Couto, Silvana Belo, Nelson Lima
Biological collections and biobanks are essential for scientific research and innovation, supporting various scientific fields such as health sciences, biotechnology, food and agriculture. They preserve and provide diverse organisms, biological materials and their associated data, enabling the study of biodiversity, diseases, and their evolution and ecological functions. These collections are crucial for addressing global challenges like biodiversity loss, sustainable food and feed production, and human health, including understanding variations in pathogenic and etiologic agents over time. Biobanks support the development of new therapies, biomarkers, and diagnostic tests while promoting equitable benefit sharing from genetic resource utilization and developing and implementing international standards, crucial for improving research reliability and reproducibility. Collaborative networks enhance biobank operation by organizing data, exchanging biological material and facilitating trans-biobank studies and protocols standardization/harmonization. The establishment of the Lusophone Network of Biobanks and Biological Collections is a significant step toward promoting collaboration, capacity building and capacity development among Portuguese-speaking countries, many of them dealing with tropical health issues, facilitating knowledge exchange and resource sharing for scientific advancement on a global scale.
生物藏品和生物库对于科学研究和创新至关重要,为健康科学、生物技术、食品和农业等各个科学领域提供支持。它们保存并提供各种生物、生物材料及其相关数据,有助于研究生物多样性、疾病及其进化和生态功能。这些藏品对于应对生物多样性丧失、可持续粮食和饲料生产以及人类健康等全球挑战至关重要,包括了解病原体和致病因子随时间的变化。生物库支持新疗法、生物标志物和诊断测试的开发,同时促进遗传资源利用的公平惠益分享,并制定和实施对提高研究可靠性和可重复性至关重要的国际标准。合作网络通过组织数据、交换生物材料、促进跨生物库研究和协议标准化/协调,加强了生物库的运作。葡语国家生物库和生物收藏网络的建立是朝着促进葡语国家之间的合作、能力建设和能力发展迈出的重要一步,其中许多国家都在处理热带健康问题,促进知识交流和资源共享,推动全球范围内的科学进步。
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引用次数: 0
Scabies: current knowledge and future directions 疥疮:现有知识和未来方向
Pub Date : 2024-07-23 DOI: 10.3389/fitd.2024.1429266
Elke Mitchell, Miranda Wallace, Justine Marshall, Margot Whitfeld, Lucia Romani
Scabies is a global public health issue, with approximately 455 million new cases worldwide each year. Scabies is a parasitic skin disease caused by infestation with the mite Sarcoptes scabiei var. hominis that can lead to secondary skin infections such as impetigo. In 2017, scabies was added to the World Health Organization’s list of neglected tropical diseases renewing calls for effective management and control of the disease. Mass drug administration has emerged as an effective strategy to control scabies, especially in highly endemic settings. In this review, we detail scabies epidemiology and risk factors, clinical characteristics and diagnosis, as well as control options, and future areas for scabies research.
疥疮是一个全球性的公共卫生问题,全世界每年新增病例约 4.55 亿例。疥疮是一种由疥螨变种引起的寄生性皮肤病,可导致脓疱疮等继发性皮肤感染。2017 年,疥疮被世界卫生组织列入被忽视的热带疾病名单,再次呼吁对该疾病进行有效管理和控制。大规模用药已成为控制疥疮的有效策略,尤其是在疥疮高度流行的环境中。在这篇综述中,我们将详细介绍疥疮的流行病学和风险因素、临床特征和诊断、控制方案以及疥疮研究的未来领域。
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引用次数: 0
Natural occurrence of Wolbachia in Anopheles sp. and Aedes aegypti populations could compromise the success of vector control strategies 按蚊和埃及伊蚊种群中自然存在的沃尔巴克氏体可能会影响病媒控制战略的成功实施
Pub Date : 2024-07-22 DOI: 10.3389/fitd.2024.1329015
O. Gnankiné, R. Dabiré
Wolbachia is a maternally inherited bacterium commonly detected in approximately 50% of arthropod species, including mosquito vector species. Wolbachia species have been detected in different mosquito vectors, but in most malaria vectors, their occurrence in natural populations were reported 10 years ago. Aedes aegypti, the main vector of dengue virus, is generally uninfected by Wolbachia, and records of infection are rare and only include a few populations. This bacterium impacts the biology, ecology, and evolution of vector populations. Wolbachia has attracted considerable interest because of its role in reducing disease transmission. Moreover, this bacterium is known to manipulate insect reproduction by inducing cytoplasmic incompatibility (CI), thus providing new avenues for vector control strategies. Interestingly, wMel or wAlbB Wolbachia infections in Aedes populations exhibit a stable high frequency in most areas and contribute to the reduction of local dengue transmission. In natural populations of Anopheles, although Wolbachia was found, little is known about its role and effect on Plasmodium. If the incompatible insect technique (IIT) and population replacement strategy resulted in significant decreases in the dengue transmission in endemic countries such as the USA, Taiwan, Australia, and Brazil, natural Wolbachia detection in mosquitoes may pose a threat to these vector control strategies, raising the following question: “Does the natural occurrence of Wolbachia in Anopheles sp. and Ae. aegypti populations compromise the success of vector control strategies? This review presents recent achievements of Wolbachia in natural Anopheles and Ae. aegypti populations in terms of prevalence and provides guidelines for the development of Wolbachia-based vector control.
沃尔巴克氏菌是一种母系遗传的细菌,通常在大约 50%的节肢动物物种(包括蚊媒物种)中检测到。沃尔巴克氏菌已在不同的蚊媒中检测到,但在大多数疟疾病媒中,其在自然种群中出现的报道是在 10 年前。埃及伊蚊是登革热病毒的主要传播媒介,一般不受沃尔巴克氏菌感染,感染记录很少,而且只包括少数几个种群。这种细菌影响着病媒种群的生物学、生态学和进化。沃尔巴克氏菌在减少疾病传播方面的作用引起了人们的极大兴趣。此外,这种细菌还能通过诱导细胞质不相容(CI)来操纵昆虫的繁殖,从而为病媒控制策略提供了新的途径。有趣的是,在大多数地区,伊蚊种群中的wMel或wAlbB沃尔巴克氏体感染表现出稳定的高频率,并有助于减少登革热在当地的传播。虽然在按蚊的自然种群中发现了沃尔巴克氏体,但人们对其对疟原虫的作用和影响知之甚少。如果不相容昆虫技术(IIT)和种群替代策略导致登革热流行国家(如美国、台湾、澳大利亚和巴西)的登革热传播显著减少,那么在蚊子中检测到的天然沃尔巴克氏体可能会对这些病媒控制策略构成威胁,这就提出了以下问题:"按蚊和埃及伊蚊种群中自然存在的沃尔巴克氏体是否会影响病媒控制策略的成功?本综述介绍了沃尔巴克氏体在按蚊和埃及蝇自然种群中的流行率方面的最新成果,并为制定基于沃尔巴克氏体的病媒控制提供了指导。
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引用次数: 0
Predicting malaria hyper endemic zones in West Africa using a regional scale dynamical malaria model 利用区域尺度动态疟疾模型预测西非疟疾高流行区
Pub Date : 2024-07-16 DOI: 10.3389/fitd.2024.1322502
E. Olaniyan, A. Tompkins, Cyril Caminade
Due to the continuing large number of malaria-related deaths in tropical Africa, the need to develop a robust Malaria Early Warning System (MEWS) for effective action is growing to guide cost-effective implementation of interventions. This study employs a two-stage hierarchical evaluation technique to evaluate the ability of the VECTRI malaria model to simulate malaria dynamics at seasonal time scale (1 - 7 months) over Nigeria and West Africa. Two sets of malaria simulations are considered. The first set is based on VECTRI simulations driven by observed rainfall and temperature datasets (hereafter referred to as control run). The second is based on malaria simulations driven by the European Centre for Medium-Range Weather Forecasting (ECMWF) System5 ensemble seasonal forecasting system (hereafter referred to as Forecast run). Different metrics are employed to assess the skill of the VECTRI malaria model. Results based on the control run indicate that the model can reproduce hyper-endemic zones and the evolution of malaria cases, particularly the observed increase in cases with decreasing population density. Despite having significant biases and low correlation, the model successfully predicts annual anomalies in malaria cases across Nigeria, particularly in the savannah region that experience large malaria burden. Annual correlations between the VECTRI Forecast run and the VECTRI Control run are relatively low at all lead times (LT) and for each start date (SD) across West Africa, although correlation generally increases from the Gulf of Guinea to the Sahel. Despite low correlations, the Rank Probability Skill Score (RPSS) reveals that the model has a statistically significant skill in predicting malaria occurrences across all categories of malaria cases, regardless of start date or lead time. While the Guinea Forest has the strongest RPSS, the increase or decrease in skill from the first to seventh lead time varies significantly across the region. In addition, the VECTRI malaria model has a good ability to discriminate variability in malaria cases across all regions, with an average Area Under the Relative Operating Characteristics (ROC) Curve (AUC) of approximately 0.62. Our findings suggest that the VECTRI malaria model could be used as a reliable Malaria Early Warning System (MEWS), particularly for identifying malaria hyper-endemic zones in West Africa at seasonal time scale.
由于非洲热带地区与疟疾相关的死亡人数居高不下,因此越来越需要开发一个强大的疟疾早期预警系统(MEWS)来采取有效行动,以指导实施具有成本效益的干预措施。本研究采用两阶段分层评估技术,评估 VECTRI 疟疾模型模拟尼日利亚和西非季节性时间尺度(1 - 7 个月)疟疾动态的能力。我们考虑了两组疟疾模拟。第一组是基于观测到的降雨量和温度数据集进行的 VECTRI 模拟(以下称为对照运行)。第二组是基于欧洲中期天气预报中心(ECMWF)System5 集合季节性预报系统(以下简称 "预报运行")驱动的疟疾模拟。采用不同的指标来评估 VECTRI 疟疾模式的技能。基于对照运行的结果表明,该模型可以再现疟疾高流行区和疟疾病例的演变,特别是观察到的病例随人口密度下降而增加的情况。尽管存在明显偏差且相关性较低,但该模型成功预测了尼日利亚各地疟疾病例的年度异常情况,尤其是在疟疾负担较重的热带草原地区。VECTRI 预测运行和 VECTRI 控制运行之间的年度相关性在西非的所有提前期(LT)和每个开始日期(SD)都相对较低,但从几内亚湾到萨赫勒地区,相关性普遍上升。尽管相关性较低,但等级概率技能得分(RPSS)显示,无论起始日期或准备时间如何,该模型在预测所有类别疟疾病例发生率方面都具有显著的统计技能。虽然几内亚森林的 RPSS 值最高,但从第一个到第七个前导时间的技能增减在各地区差异很大。此外,VECTRI 疟疾模型对各地区疟疾病例的变化具有良好的判别能力,其相对工作特征曲线(ROC)下的平均面积(AUC)约为 0.62。我们的研究结果表明,VECTRI 疟疾模型可用作可靠的疟疾预警系统(MEWS),特别是用于在季节时间尺度上识别西非疟疾高流行区。
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引用次数: 0
Verification of the reactivity of immunoglobulins in dried blood spots collected for onchocerciasis sero-surveillance by an Escherichia coli ELISA 用大肠杆菌酶联免疫吸附试验验证盘尾丝虫病血清监测采集的干血斑中免疫球蛋白的反应性
Pub Date : 2024-07-10 DOI: 10.3389/fitd.2024.1419166
H. Hassan, Kristi Miley, T. Unnasch
The World Health Organization guidelines for verification of onchocerciasis elimination include demonstrating that the prevalence of exposure to the parasite in individuals born since transmission was interrupted needs to be less than 0.1%. The guidelines recommend using seropositivity to an Onchocerca volvulus specific antigen (Ov16) for this purpose. Ov16 seropositivity has most often been assessed using the Ov16 ELISA assay. Currently, the Ov16 ELISA assay includes internal positive and negative controls to monitor for proper assay performance but does not control for the quality of the dried blood spots (DBS) being tested. Previous studies have reported a high prevalence of antibodies recognizing Escherichia coli in children. Through the development of an ELISA assay to detect antibodies recognizing E. coli, a common commensal in humans, DBS may be prescreened for quality assurance prior to testing for Ov16. Results demonstrated antibodies to E. coli were detected in 100% of randomly selected serum samples collected from O. volvulus infected individuals residing in an onchocerciasis hyperendemic area. Furthermore, when DBS were improperly stored, the E. coli antibodies were found to decay over a period of one week, while remaining unchanged over the same period in properly stored samples. Similarly, E. coli antibodies were detected in 100% of a batch of field collected properly stored DBS, while being present only in 5% of a batch of improperly stored spots. This study demonstrates the value of E. coli ELISA for DBS quality control testing and validation of proper storage of collections of DBS for the Ov16 ELISA.
世界卫生组织的消除盘尾丝虫病验证准则包括:证明自传播中断后出生的个体中接触寄生虫的流行率需低于 0.1%。指导方针建议使用盘尾丝虫特异性抗原(Ov16)血清阳性来达到这一目的。Ov16血清阳性通常使用Ov16 ELISA检测法进行评估。目前,Ov16 酶联免疫吸附测定法包括内部阳性和阴性对照,用于监测测定结果的正确性,但不能控制被测干血斑点(DBS)的质量。先前的研究报告显示,儿童体内识别大肠杆菌的抗体流行率很高。通过开发一种酶联免疫吸附试验(ELISA)来检测大肠杆菌(一种人类常见的共生菌)抗体,可以在检测 Ov16 之前对干血斑进行预筛,以保证质量。结果表明,在盘尾丝虫病高发区随机采集的大肠杆菌感染者血清样本中,100%都能检测到大肠杆菌抗体。此外,当 DBS 储存不当时,大肠杆菌抗体会在一周内衰减,而正确储存的样本在同一时期内则保持不变。同样,在一批现场采集并妥善保存的 DBS 样品中,100% 都能检测到大肠杆菌抗体,而在一批保存不当的样本中,只有 5% 的样本能检测到大肠杆菌抗体。这项研究证明了大肠杆菌酶联免疫吸附试验在 DBS 质量控制检测中的价值,并验证了 Ov16 酶联免疫吸附试验中 DBS 的正确储存。
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引用次数: 0
Editorial: Latest advances in the biological control of vectors of human tropical diseases 社论:人类热带疾病病媒生物防治的最新进展
Pub Date : 2024-07-05 DOI: 10.3389/fitd.2024.1430944
Juan Venegas, Slavica Vaselek, M. Yasnot
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引用次数: 0
Disease X in the Tropics, preventing the next pandemic: how to accelerate spillover prevention and vaccine preparedness? 热带地区的 X 疾病,预防下一次大流行:如何加快外溢预防和疫苗准备?
Pub Date : 2024-07-04 DOI: 10.3389/fitd.2024.1417065
C. Possas, Ernesto T. A. Marques, Suresh V. Kuchipudi, Prashant Kumar, Jerome H. Kim, Akira Homma
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引用次数: 0
Challenges in the diagnosis and control of female genital schistosomiasis in sub-Saharan Africa: an exemplar case report associated with mixed and putative hybrid schistosome infection in Nsanje District, Southern Malawi 撒哈拉以南非洲女性生殖器血吸虫病诊断和控制方面的挑战:马拉维南部恩桑杰地区与混合和假定混合血吸虫感染有关的典型病例报告
Pub Date : 2024-06-11 DOI: 10.3389/fitd.2024.1354119
S. Kayuni, Lucas J. Cunningham, Dingase Kumwenda, Bright Mainga, D. Lally, P. Chammudzi, D. Kapira, G. Namacha, Bessie Ntaba, Alice Chisale, Tereza Nchembe, Luis Kinley, Ephraim Chibwana, A. Juhász, Sam Jones, J. Archer, P. Makaula, John Chiphwanya, E. J. LaCourse, J. Musaya, J. R. Stothard
Female genital schistosomiasis (FGS) remains an often overlooked chronic complication of urogenital schistosomiasis in adolescent girls and women. Moreover, the role of zoonotic or hybrid schistosome infection(s) is poorly appreciated, but is increasingly becoming an emerging public health concern in sub-Saharan Africa. In Southern Malawi, during the “Hybridization in UroGenital Schistosomiasis (HUGS)” study visit, we describe the case of a 33-year-old woman with suspected FGS who partook in a detailed external assessment with internal cervical examination using a portable colposcope. She provided several biological samples for analysis with traditional and molecular parasitological methods—urine, cervicovaginal lavage (CVL), cervical swabs, and external mass and cervical biopsies—alongside provision of detailed demographic information after a thorough medical history questionnaire and an in-depth interview. These samples were screened for the presence of Schistosoma ova on microscopy and DNA genotyping using a novel real-time PCR assay in parallel to pre-published probe-based PCR assays capable of identifying and discriminating up to six named Schistosoma species. A further molecular screen of sexually transmitted infections (STIs) including Trichomonas vaginalis, Chlamydia spp., and human papilloma virus (HPV) was conducted on her genital swab and CVL. Overt FGS was diagnosed on clinical colposcopy alongside inspection of the cervical biopsy by microscopy, real-time PCR, and histopathology. The urine filtration, microscopy and real-time PCR of the CVL and swab were negative. This evidences the typical diagnostic challenge, and cases such as this will pose an unmet need in satisfactory patient management. In addition to Schistosoma haematobium, the presence of the zoonotic species Schistosoma mattheei and concurrent STIs raise questions as to the long-term effectiveness of the current control strategies of the National Control Programme to eliminate schistosomiasis as a public health problem. Improved availability of and regular accessibility to praziquantel treatment for women at risk such as this are urgently needed. Furthermore, targeted health education, increased community awareness, and dovetailing of synergistic activities and strategies with other health stakeholders such as those in sexual and reproductive health, as well as HIV/AIDS programs in the Ministry of Health, are needed here and in neighboring countries.
女性生殖器血吸虫病(FGS)仍然是少女和妇女泌尿系统血吸虫病的一种经常被忽视的慢性并发症。此外,人畜共患病或血吸虫杂交感染的作用也未得到充分认识,但这一问题正日益成为撒哈拉以南非洲地区新出现的公共卫生问题。在马拉维南部进行的 "泌尿生殖器血吸虫病杂交(HUGS)"研究访问期间,我们描述了一例 33 岁的疑似 FGS 女性病例,她接受了详细的外部评估,并使用便携式阴道镜进行了宫颈内部检查。她提供了多份生物样本供传统和分子寄生虫学方法分析--尿液、宫颈阴道灌洗液(CVL)、宫颈拭子、外部肿块和宫颈活组织检查--同时在详细的病史问卷和深入访谈后提供了详细的人口统计学信息。在显微镜下对这些样本进行筛查,并使用一种新型实时 PCR 检测方法进行 DNA 基因分型,该方法与预先公布的探针式 PCR 检测方法并行,能够识别和区分多达六种血吸虫。对她的生殖器拭子和 CVL 进行了进一步的性传播感染 (STI) 分子筛查,包括阴道毛滴虫、衣原体属和人类乳头瘤病毒 (HPV)。临床阴道镜检查和宫颈活组织检查通过显微镜、实时 PCR 和组织病理学检查确诊为外阴癌。CVL 和拭子的尿液过滤、显微镜检查和实时 PCR 均为阴性。这证明了典型的诊断难题,此类病例将为满意的患者管理带来尚未满足的需求。除血吸虫外,人畜共患病种马氏血吸虫和并发性传播感染的存在也让人怀疑国家控制计划当前的控制策略能否长期有效地消除血吸虫病这一公共卫生问题。像这样的高危妇女急需更好地获得吡喹酮治疗,并定期接受治疗。此外,还需要在这里和邻国开展有针对性的健康教育,提高社区认识,并与卫生部的性健康和 生殖健康以及艾滋病毒/艾滋病方案等其他健康利益攸关方开展协同活动和战略。
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Frontiers in tropical diseases
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