PLoS Neglected Tropical Diseases最新文献

Background: Outbreaks of Aedes-borne diseases in temperate areas are not frequent, and limited in number of cases. We investigate the associations between habitat factors and temperature on individuals' risk of chikungunya (CHIKV) in a non-endemic area by spatially analyzing the data from the 2017 Italian outbreak.

Methodology/principal findings: We adopted a case-control study design to analyze the association between land-cover variables, temperature, and human population density with CHIKV cases. The observational unit was the area, at different scales, surrounding the residence of each CHIKV notified case. The statistical analysis was conducted considering the whole dataset and separately for the resort town of Anzio and the metropolitan city of Rome, which were the two main foci of the outbreak. In Rome, a higher probability for the occurrence of CHIKV cases is associated with lower temperature (OR = 0.72; 95% CI: 0.61-0.85) and with cells with higher vegetation coverage and human population density (OR = 1.03; 95% CI: 1.00-1.05). In Anzio, CHIKV case occurrence was positively associated with human population density (OR = 1.03; 95% CI: 1.00-1.06) but not with habitat factors or temperature.

Conclusion/significance: Using temperature, human population density and vegetation coverage data as drives for CHIKV transmission, our estimates could be instrumental in assessing spatial heterogeneity in the risk of experiencing arboviral diseases in non-endemic temperate areas.

Snakebite envenoming is a globally important public health issue that has devastating consequences on human health and well-being, with annual mortality rates between 81,000 and 138,000. Snake venoms may cause different pathological effects by altering normal physiological processes such as nervous transfer and blood coagulation. In addition, snake venoms can cause severe (local) tissue damage that may result in life-long morbidities, with current estimates pointing towards an additional 450,000 individuals that suffer from permanent disabilities such as amputations, contractions and blindness. Despite such high morbidity rates, research to date has been mainly focusing on neurotoxic and haemotoxic effects of snake venoms and considerably less on venom-induced tissue damage. The molecular mechanisms underlaying this pathology include membrane disruption and extracellular matrix degradation. This research describes methods used to study the (molecular) mechanisms underlaying venom-induced cell- and tissue damage. A selection of cellular bioassays and fluorescent microscopy were used to study cell-damaging activities of snake venoms in multi-well plates, using both crude and fractionated venoms. A panel of 10 representative medically relevant snake species was used, which cover a large part of the geographical regions most heavily affected by snakebite. The study comprises both morphological data as well as quantitative data on cell metabolism and viability, which were measured over time. Based on this data, a distinction could be made in the ways by which viper and elapid venoms exert their effects on cells. We further made an effort to characterise the bioactive compounds causing these effects, using a combination of liquid chromatography methods followed by bioassaying and protein identification using proteomics. The outcomes of this study might prove valuable for better understanding venom-induced cell- and tissue-damaging pathologies and could be used in the process of developing and improving snakebite treatments.

Not all pit viper species are present in every state of Malaysia and their distribution varies according to altitude. There is limited information on pit viper bite incidence and its geographical distribution. This was a cross-sectional study of confirmed pit viper bite cases referred to Remote Envenomation Consultancy Services (RECS) from January 2017 to December 2020. Data was collected following the approval of institutional research ethics committee. Universal sampling methods were used. Confirmed pit viper bite cases in each state, geographical location and the antivenom used were reported. A total of 523 confirmed pit viper bite injuries occurred over the 4-year study period. The majority were Malaysians, male and young adults. Most were non-occupational related (83.9%) and involved the upper limbs (46.8%). The commonest pit viper species involved was Trimeresurus purpureomaculatus (23.7%). Green pit viper antivenom (GPAV) was the most frequent antivenom used (n = 51) with the majority of patients requiring only one dose (3 vials). This study provides a better appreciation of indigenous pit viper species distribution for each state and reflects the requirement of appropriate antivenom to be stocked in each state or district hospital.

Background: Since its first record in urban areas of Central-Africa in the 2000s, the invasive mosquito, Aedes albopictus, has spread throughout the region, including in remote villages in forested areas, causing outbreaks of Aedes-borne diseases, such as dengue and chikungunya. Such invasion might enhance Ae. albopictus interactions with wild animals in forest ecosystems and favor the spillover of zoonotic arboviruses to humans. The aim of this study was to monitor Ae. albopictus spread in the wildlife reserve of La Lopé National Park (Gabon), and evaluate the magnitude of the rainforest ecosystem colonization.

Methodology: From 2014 to 2018, we used ovitraps, larval surveys, BG-Sentinel traps, and human landing catches along an anthropization gradient from La Lopé village to the natural forest in the Park.

Conclusions: We detected Ae. albopictus in gallery forest up to 15 km away from La Lopé village. However, Ae. albopictus was significantly more abundant at anthropogenic sites than in less anthropized areas. The number of eggs laid by Ae. albopictus decreased progressively with the distance from the forest fringe up to 200m inside the forest. Our results suggested that in forest ecosystems, high Ae. albopictus density is mainly observed at interfaces between anthropized and natural forested environments. Additionally, our data suggested that Ae. albopictus may act as a bridge vector of zoonotic pathogens between wild and anthropogenic compartments.

Background: Previous qualitative studies on attitudes towards schistosomiasis demonstrated inconclusive results on the extent of stigma towards schistosomiasis in endemic communities around the world. The Explanatory Model Interview Catalogue-Community Stigma Scale (EMIC-CSS) has been used and validated for the assessment of public stigma across numerous countries in various health conditions. This study tested the performance of the scale in the context of stigma related to schistosomiasis in twelve communities in the three districts of Magu, Nyamagana and Ilemela in Mwanza region, Tanzania.

Methodology/principal findings: The 15-item-version of the EMC-CSS was first translated to Kiswahili language. The translation was discussed within the research team to retain the meaning of the items and implement cultural adaptations. Validation of the adapted EMIC-CSS scale was conducted following the framework of Herdman and Fox- Rushby. A pilot study with 41 participants from two communities provided the basis for testing the performance of each item and assessing the semantic and operational equivalence of the scales. In addition, eight qualitative focus group discussions (FGDs) were conducted to evaluate the conceptional equivalence of the EMIC-CSS. Finally, the performance of the adjusted scale was tested on 200 participants with a 50:50 male-female ratio from ten communities. The mean score of the EMIC-CSS M = 8.35 (SD = 6.63) shows clear indications for public stigma towards schistosomiasis. The EMIC-CSS demonstrated a good internal consistency with Cronbach's alpha α = .857 and no floor and ceiling effects.

Conclusion/significance: The results demonstrate that the EMIC-CSS is a useful instrument in assessing public stigma towards schistosomiasis and allow a clear recommendation of the EMIC-CSS for schistosomiasis in the Tanzanian culture. However, future studies are additionally recommended to address specific aspects and forms of the disease and how they contribute to the development of stigma towards schistosomiasis.

The South African bont tick Amblyomma hebraeum is a hematophagous vector for the heartwater disease pathogen Ehrlichia ruminantium in southern Africa. During feeding, the tick's enterocytes express proteins that perform vital functions in blood digestion, including proteins that may be involved in E. ruminantium acquisition, colonization or immunity. To delineate the molecular mechanism of midgut response to E. ruminantium infection, we performed comparative analyses of midgut transcriptomes of E. ruminantium infected engorged A. hebraeum nymphs, and infected adult male and female ticks with their corresponding matched uninfected controls, before and during feeding. A total of 102,036 unigenes were annotated in public databases and their expression levels analyzed for engorged nymphs as well as unfed and partly-fed adult ticks. There were 2,025 differentially expressed genes (DEGs) in midguts, of which 1,225 unigenes were up-regulated and 800 unigenes were down-regulated in the midguts of infected ticks. Annotation of DEGs revealed an increase in metabolic and cellular processes among E. ruminantium infected ticks. Notably, among the infected ticks, there was up-regulation in the expression of genes involved in tick immunity, histone proteins and oxidative stress responses. We also observed up-regulation of glycoproteins that E. ruminantium could potentially use as docking sites for host cell entry. Insights uncovered in this study offer a platform for further investigations into the molecular interaction between E. ruminantium and A. hebraeum.

Mycetoma is one of the six Neglected Tropical Diseases that are prevalent in Turkana County (northwest Kenya). The aim of the study was to estimate the prevalence of mycetoma in the county, as well as to describe the main causative agents involved in the disease using methods affordable locally. Based on the data collected by the team of cooperative medicine Cirugia en Turkana (Surgery in Turkana), a specific study for mycetoma was started during the 16th humanitarian medicine campaign in February 2019. Patients with suspected mycetoma were studied at the Lodwar County Referral Hospital (LCRH). After informing the patient and getting their consent, the lesions were examined and sampled (mainly by biopsy) and clinical data were recorded. Samples were washed in sterile saline solution and cut in fragments. Some of these were inoculated on Sabouraud Dextrose Agar, Malt Extract Agar, and diluted Nutrient Agar plates. One fragment of each sample was used for DNA extraction. The DNA and the rest of the fragments of samples were kept at -20°C. All cultures were incubated at room temperature at the LCRH laboratory. The DNA obtained from clinical samples was submitted to PCR amplification of the ITS-5.8S and the V4-V5 16S rRNA gene region, for the detection and identification of fungi and bacteria respectively. From February 2019 till February 2022, 60 patients were studied. Most of them were men (43, 74,1%) between 13 and 78 y.o. (mean age 37). Half of the patients were herdsmen but, among women 40% (6) were housewives and 26.7% (4) charcoal burners. Lesions were mainly located at the feet (87.9%) and most of the patients (54; 93.1%) reported discharge of grains in the exudate, being 27 (46.6%) yellow or pale colored and 19 (32.8%) of them dark grains. Culture of clinical samples yielded 35 fungal and bacterial putative causative agents. Culture and molecular methods allowed the identification of a total of 21 causative agents of mycetoma (39.6% of cases studied). Most of them (17) corresponded to fungi causing eumycetoma (80.9%) being the most prevalent the genus Madurella (7; 41.2%), with two species involved (M. mycetomatis and M. fahalii), followed by Aspergillus (2; 11.8%). Other minority genera detected were Cladosporium, Fusarium, Acremonium, Penicillium, and Trichophyton (5.9% each of them). Actinobacteria were detected in 19.1% of samples, but only Streptomyces somaliensis was identified as a known agent of mycetoma, the rest being actinobacteria not previously described as causative agents of the disease, such as Cellulosimicrobium cellulans detected in two of the patients. Although Kenya is geographically located in the mycetoma belt, to our knowledge this is the first report on mycetoma in this country from 1973, and the first one for Turkana County.

Background: Deep learning, which is a part of a broader concept of artificial intelligence (AI) and/or machine learning has achieved remarkable success in vision tasks. While there is growing interest in the use of this technology in diagnostic support for skin-related neglected tropical diseases (skin NTDs), there have been limited studies in this area and fewer focused on dark skin. In this study, we aimed to develop deep learning based AI models with clinical images we collected for five skin NTDs, namely, Buruli ulcer, leprosy, mycetoma, scabies, and yaws, to understand how diagnostic accuracy can or cannot be improved using different models and training patterns.

Methodology: This study used photographs collected prospectively in Côte d'Ivoire and Ghana through our ongoing studies with use of digital health tools for clinical data documentation and for teledermatology. Our dataset included a total of 1,709 images from 506 patients. Two convolutional neural networks, ResNet-50 and VGG-16 models were adopted to examine the performance of different deep learning architectures and validate their feasibility in diagnosis of the targeted skin NTDs.

Principal findings: The two models were able to correctly predict over 70% of the diagnoses, and there was a consistent performance improvement with more training samples. The ResNet-50 model performed better than the VGG-16 model. A model trained with PCR confirmed cases of Buruli ulcer yielded 1-3% increase in prediction accuracy across all diseases, except, for mycetoma, over a model which training sets included unconfirmed cases.

Conclusions: Our approach was to have the deep learning model distinguish between multiple pathologies simultaneously-which is close to real-world practice. The more images used for training, the more accurate the diagnosis became. The percentages of correct diagnosis increased with PCR-positive cases of Buruli ulcer. This demonstrated that it may be better to input images from the more accurately diagnosed cases in the training models also for achieving better accuracy in the generated AI models. However, the increase was marginal which may be an indication that the accuracy of clinical diagnosis alone is reliable to an extent for Buruli ulcer. Diagnostic tests also have their flaws, and they are not always reliable. One hope for AI is that it will objectively resolve this gap between diagnostic tests and clinical diagnoses with the addition of another tool. While there are still challenges to be overcome, there is a potential for AI to address the unmet needs where access to medical care is limited, like for those affected by skin NTDs.

Background: Acanthamoeba and Klebsiella pneumoniae are both environmental commensals. Recently, clinical harm caused by hypermucoviscous K. pneumoniae has been observed. However, the interaction between these microbes and the origin of hypermucoviscous K. pneumoniae have not been reported.

Methodology/principal findings: Here, we report that the bacterial capsule is enlarged when co-cultured with Acanthamoeba using India ink staining, and this effect depends on the number of parasites present. This interaction results in an enhancement of capsular polysaccharide production in the subsequent generations of K. pneumoniae, even without co-culturing with Acanthamoeba. The hypermucoviscosity of the capsule was examined using the sedimentation assay and string test. We also screened other K. pneumoniae serotypes, including K1, K2, K5, and K20, for interaction with Acanthamoeba using India ink staining, and found the same interaction effect.

Conclusions/significance: These findings suggest that the interaction between Acanthamoeba and K. pneumoniae could lead to harmful consequences in public health and nosocomial disease control, particularly hypermucoviscous K. pneumoniae infections.

Background: Human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) is one of the pillars of a combination prevention strategy for reducing the risk of new infections caused by HIV. The daily use of antiretroviral drugs by individuals who are not infected with HIV is required to prevent infection. Although its efficacy has been well established in the literature, in recent years, the decreased supply of antiretroviral drugs has been associated with an increase in the incidence of sexually transmitted infections (STI) and changes in the social determinants of health. An ecological study was conducted covering a five-year period (2018-2022), starting from the year of initiation of PrEP administration in Brazilian state capitals.

Principal findings: Descriptive analysis was performed, and the spatial distribution of study data was taken into account. Correlation analysis was used to assess the association between PrEP administration, the incidence and detection rate of STI, and socioeconomic data. The southern region showed the highest incidence rates of STI, but the northern and northeastern regions demonstrated the worst socioeconomic indicators, especially those related to illiteracy and basic sanitation. PrEP administration was significantly correlated with illiteracy (ρ = -0.658), per capita income (ρ = 0.622), public garbage collection (ρ = 0.612), syphilis (ρ = 0.628) and viral hepatitis (ρ = 0.419) incidences. Further, all STI were significantly associated with illiteracy and per capita income.

Significance: Our findings highlight the need to continue exploring PrEP use and rising syphilis rates. In terms of policy, PrEP administration appears to be inversely associated with regions of greater social vulnerability. Further efforts should focus on the social determinants and health needs of this population to improve access to PrEP and reduce social disparities.