PLoS Neglected Tropical Diseases最新文献

Methods: This study enrolled 107 VL suspects who attended a health centre in Gedaref between October 2022 and June 2023. Diagnostic accuracy was assessed by comparing the performance of the new index test (INgezimLeishma-CROM) with the comparator test (IT-LEISH) and parasitological examination as reference standard.

Results: Of 107 VL suspects screened by parasitological examination, 77 VL patients were smear positive and 30 were smear negative. Independent serological testing of these patients using INgezim Leishma-CROM showed a sensitivity of 98.7% [95% CI 92.23-99.97] and specificity of 92.5% [95% CI 75.71-99.09]. For IT-LEISH, both sensitivity [95% CI 84.39-97.20] and specificity [95% CI 75.71-99.09] were 92.5%. INgezim Leishma-CROM demonstrated increased diagnostic accuracy (97.2%) compared to IT-LEISH RDT (92.5%). Both RDTs gave positive results in 2 cases from the smear negative group that were previously treated for VL. All other non-VL cases (malaria, typhoid, brucellosis) were negative in both RDTs, showing 100% specificity, while VL patients co-infected with malaria were positive in both tests. Within the smear-negative group, 3 VL symptomatic cases that had been previously treated but still show clinical signs were all positive with INgezim Leishma-CROM but only 2 cases were positive with IT-LEISH.

Neuroangiostrongyliasis is characterized by eosinophilic meningoencephalitis with a robust onset of severe neurological symptoms, by which immunological factors and peripheral metabolites have been postulated to affect the course of the disease. The gut-brain axis provides a bidirectional communication between the gut and the central nervous system, and therefore, understanding the gut microbiome may provide us with a deeper insight into the pathogenesis of angiostrongyliasis. Using 16S rRNA sequencing, we identified an increase in the abundance of different Lactobacillus species in Angiostrongylus cantonensis-infected mice, which was correlated to the disease severity. However, attempts to inoculate L. johnsonii into A. cantonensis-infected mice surprisingly revealed an improvement in neuroinflammation and prolonged survival. RNA sequencing suggested an immune-modulatory effect of L. johnsonii, which was confirmed by ELISA, showing increased levels of IL-10 and reduced levels of IL-2, IL-4, IL-5, and MCP-1 in the brain. Nevertheless, L. johnsonii-associated improvements were not associated with microbiome-related metabolites, as UHPLC-MS/MS analysis revealed no change in short-chain fatty acids, tryptophan metabolites, and bile acids. Our results suggest that while intestinal L. johnsonii appears to be linked to the progression of neuroangiostrongyliasis, these bacteria are likely attempting to modulate the dysregulated immune response to combat the disease. This is one of the first studies to investigate the gut microbiome in mice with A. cantonensis infection, which extends our knowledge from the microbiome-point-of-view of the pathogenesis of angiostrongyliasis and how the body defends against A. cantonensis. This work also extends to possible treatment approaches using L. johnsonii as probiotics.

Background: Hepatitis B virus (HBV) is highly prevalent and a major health problem in developing countries. Controversial findings are reported on the effect of schistosomiasis and HBV infection. This study aimed to describe the association of S. mansoni infection with Hepatitis B surface antigen (HBsAg) carriage rate in schistosome endemic setting.

Methods: A cross-sectional study was conducted from January to March 2024 among school children aged 7-14 years old in two primary schools of Jille Timuga district of Oromo special zone, Amhara region, Ethiopia. Demographic and health related data was collected by Kobo collect tool. Blood and stool specimens were collected to test Hepatitis B infection using rapid test kit and S.mansoni infection by kato-katz method respectively. The data was analyzed by STATA version 17 statistical software. A descriptive statistic, bivariate and multivariate logistic regression analysis was used to identify associated factors. P-value of <0.05 was used as a cut-off in reporting statistical significance.

Results: A total of 300 children participated in the study with a mean age of 10.5 years (±2) ranging from 7 to 14 years. Eighty-nine (29.6%) children were infected with S. mansoni and the sero-prevalence of hepatitis B surface antigen was 0.3%; no co-infection was observed. Children who had taken praziquantel mass treatment recently (<6 month) had higher infection rate at 34%. Likewise, highest prevalence of S. mansoni infection (39.8%) was found among 11-12 years age group. A significant association of sex with higher S.mansoni infection rate was observed where males had 2.07 increased odds of infection.

Conclusions: The observed prevalence of S. mansoni infection (29.6%) was high in view of the ongoing preventive chemotherapy using praziquantel. The low, 0.3%, prevalence of HBV in the setting of higher S.mansoni prevalence underscore non well defined association of HBSAg carriage with schistosomiasis. However, a larger, well-controlled further research is recommended. The infection rate of S. mansoni was higher among children who recently took praziquantel which highlight the limitations of mass drug administration (MDA) program and possibility of re-infection. These emphasize the need for integrated schistosomiasis control programs, combining mass drug administration with other supportive intervention measures such as snail control.

Background: A school-based preventive chemotherapy (PC) program has operated since 2013 for soil-transmitted helminths (STHs) and 2014 for schistosomiasis in Huambo, Uige and Zaire provinces, Angola. This program was informed by a prevalence survey in 2014 and evaluated in 2021, demonstrating limited impact in reducing provincial-level prevalence. This geospatial analysis aims to provide granular estimates of the geographic distribution of schistosomiasis and STHs to target control strategies.

Methods: Parasitological data on schistosomiasis and STHs were obtained from school-based prevalence surveys conducted in 2014 and 2021. These data were supplemented with open access environmental and climatic data to develop risk prediction maps for each parasite at each time point. Variables for the final risk prediction models were selected through non-spatial multivariable regression analyses and residual spatial autocorrelation was investigated using semivariograms. Risk prediction maps were then developed using either non-spatial or spatial (using the Matérn covariance) geostatistical models depending on the presence of residual spatial autocorrelation.

Results: The 2014 survey included 17,093 schoolchildren (575 schools) for schistosomiasis and 3,649 schoolchildren (121 schools) for STHs, and the 2021 survey included 17,880 schoolchildren (599 schools) for schistosomiasis and 6,461 schoolchildren (214 schools) for STHs. Our analyses indicated that in Huambo province, there are small areas of high schistosomiasis risk in the north and south, and a centrally located STH hotspot, with no discernible change in predicted risk for either infection over time. In Uige, there has been a reduction in schistosomiasis hotspots in the southwest corner but an overall increase in predicted risk throughout the province, whilst there is a concerning trend for expanding areas of high predicted STH risk throughout. In Zaire, there are increasing areas of higher risk for schistosomiasis and STHs, with co-endemic hotspots.

Conclusion: These risk prediction maps importantly identify higher risk areas for schistosomiasis and STHs within large geographic regions that should be prioritised for control with tailored decisions for future PC delivery.

Background: Pythiosis caused by Pythium insidiosum, is a rare but deadly infectious disease that is often underrecognized. The disease has high morbidity and mortality rates, particularly in vascular forms where surgical resection is necessary. A previous study demonstrated low awareness and knowledge of vascular pythiosis among Thai medical personnel. There is an urgent need to improve disease recognition given that vascular pythiosis is very prevalent in Thailand.

Methods: This study aimed to enhance knowledge and disease recognition about vascular pythiosis among Thai medical personnel and the public through a self-paced, asynchronous, open-access online course. The course included seven video lessons and was available from February to July 2023. Participants' knowledge was assessed using pretest and posttest analysis.

Results: A total of 428 participants completed the course. Participants showed significant knowledge improvement, with mean posttest scores substantially higher than pretest scores, 6.77 vs. 3.46 (p-value < 0.01). Higher educational level had a positive impact with higher pretest and posttest scores, but the delta scores between the posttest and pretest of all groups were comparable. Moreover, 80% of participants demonstrated knowledge gain. However, participants of all groups scored the lowest on the posttest in diagnostic investigation field.

Conclusions: Very low pretest scores underline the neglected problem of vascular pythiosis. This asynchronous online course successfully enhanced participants' knowledge about vascular pythiosis. Future efforts should focus on collaborative initiatives at the government and university levels to emphasize disease recognition.

Background: The Neglected Tropical Diseases (NTDs) represent a global public health problem. Telemedicine uses telecommunications to deliver remote healthcare services when patients and providers are separated by distance. Using digital health technologies to offer medical care remotely to NTDs can be an important strategy for reducing inequalities in access but is challenging in low-and middle-income settings. The objective of the current review was to identify and summarize international evidence on the use of telemedicine for clinical care of patients with NTDs around the world based on a scoping review protocol.

Methodology/principal findings: A total of 422 articles were extracted from the databases MEDLINE/PubMed, Web of Science and Scopus, and after removing 129 duplicates, 285 studies were excluded because they did not meet the eligibility criteria. A total of 8 articles were included for data extraction, half of them published after 2021 (n=4). Four studies were focused on dermatological diseases, like leprosy and leishmaniasis, and the other diseases found were dengue (n=2), trachoma (n=1) and cysticercosis (n=1). Most telemedicine interventions in NTDs involved Primary Health Care teams (n=5). Studies that evaluated the accuracy of remote diagnosis demonstrated good effectiveness for leprosy, trachoma and complications of neurocysticercosis. There was a reduction in the need for specialized in-person medical consultations with telemedicine for the care of dengue fever and some dermatological NTDs; and an improvement in the quality of clinical monitoring of cutaneous leishmaniasis using mobile health was demonstrated.

Conclusions/significance: Although we observed a small recent increase in academic research on the theme, there is a gap in recommendations for the clinical management of NTDs through telemedicine in the literature. The feasibility and potential for telemedicine-based NTDs diagnosis and treatment have been demonstrated in only a few settings/countries, revealing that this resource is still largely underutilized.

Cryptococcal meningitis is one of the top causes of morbidity and mortality in people living with HIV/AIDS. In high prevalence regions, current recommendations are to screen individuals with blood CD4+ T cell counts less than 200 cells/µl for serum cryptococcal antigen (CrAg) and then preemptively treat those who test positive for presumed cryptococcosis. However, in many low-resource settings, including Monrovia, Liberia, flow cytometric CD4 assays are not readily available. We tested subjects with known HIV infection using a lateral flow assay (LFA), which provides a semi-quantitative determination of whether the blood CD4+ T cell count is ≤200 cells/µl. Subjects with counts ≤200 cells/µl were then tested with an LFA that detects CrAg. Of the 500 HIV+ subjects tested, 201 (40.2%) had blood CD4+ T cell count ≤200. Of those, 82/201 (40.7%) were serum CrAg+. Subjects who were serum CrAg+ were more likely to have a Glasgow Coma Score <15, whereas subjects who were CrAg- were more likely to be HIV-2+. Lumbar punctures were performed on 61 serum CrAg+ subjects; 30/61 (49.2%) subjects were cerebrospinal fluid CrAg+. Thus, sequential point-of-care testing enabled the diagnosis of cryptococcosis in HIV+ individuals with blood CD4 T cell counts ≤200 cells/µl. As diagnostic testing informs life-saving therapies, it is imperative that these assays are made readily available in resource-poor settings.

Background: Strongyloidiasis is a serious public health issue affecting millions of people worldwide particularly in tropical and subtropical regions. The laboratory diagnosis of strongyloidiasis is often serologically based, typically by enzyme linked immunosorbent assays (ELISA). However, the use of these assays at the point of care requires significantly different approaches for serologic measurements. We sought to determine the diagnostic performance of 2 prototype lateral flow tests alongside the Strongy Detect ELISAs (IgG and IgG4) that uses a cocktail of 2 Ss-specific recombinant antigens, Ss-NIE and Ss-IR.

Methods: The diagnostic performance of the Rapid Diagnostic Tests (RDTs) and ELISAs was determined by using stored serum samples from 17 healthy volunteers, 77 individuals known to be stool positive for Strongyloides stercoralis (Ss), 44 Ss stool-negative individuals but positive for Loa loa (n=32), or other helminths (n=12) (hookworm infection, Schistosoma mansoni, or Wuchereria bancrofti). Concordance between the RDTs and ELISAs was calculated with the Cohen's kappa statistic (κ).

Results: The sensitivity and specificity of the IgG RDT was 95% (95% CI; 87.84 to 98.64%) and 94% (95% CI; 84.99 to 98.30%) respectively. The IgG4 RDT showed a sensitivity of 86.5% (95% CI; 77.63 to 92.83%) with 100% (95% CI; 94.13 to 100%) specificity. The IgG-based ELISA showed 100% (95% CI; 95.6-100%) sensitivity and 96% specificity (95% CI; 91.7-98%), whereas the IgG4-based ELISA revealed a 90% (95% CI; 81-94.3%) sensitivity with 100% (95% CI; 97.8-100%) specificity. Concordance between the RDTs and the ELISAs was excellent with κ = 0.94 (95% CI; 0.88-1.0%) for the IgGs and κ = 0.89 (95% CI; 0.81-0.97%) for IgG4 assays.

Conclusion: Given the high degree of sensitivity and specificity of both the IgG- and IgG4-based RDT, either of these would be useful in assessing Ss seropositivity in population-based studies and in screening patients at the point of contact.

There are limited control measures for the disease schistosomiasis, despite the fact that infection with parasitic blood flukes affects hundreds of millions of people worldwide. The current treatment, praziquantel, has been in use since the 1980's and there is a concern that drug resistance may emerge with continued monotherapy. Given the need for additional antischistosomal drugs, we have re-visited an old lead, meclonazepam. In comparison to praziquantel, there has been relatively little work on its antiparasitic mechanism. Recent findings indicate that praziquantel and meclonazepam act through distinct receptors, making benzodiazepines a promising chemical series for further exploration. Previous work has profiled the transcriptional changes evoked by praziquantel treatment. Here, we examine in detail schistosome phenotypes evoked by in vitro and in vivo meclonazepam treatment. These data confirm that meclonazepam causes extensive tegument damage and directly kills parasites, as measured by pro-apoptotic caspase activation. In vivo meclonazepam exposure results in differential expression of many genes that are divergent in parasitic flatworms, as well as several gene products implicated in blood feeding and regulation of hemostasis in other parasites. Many of these transcripts are also differentially expressed with praziquantel exposure, which may reflect a common schistosome response to the two drugs. However, despite these similarities in drug response, praziquantel-resistant parasites retain susceptibility to meclonazepam's schistocidal effects. These data provide new insight into the mechanism of antischistosomal benzodiazepines, resolving similarities and differences with the current frontline therapy, praziquantel.

Background: Necator americanus is the predominant species causing hookworm infections in humans. Despite advancements in prevention strategies, mild cases of infection still occur, highlighting the need for improved detection technology. Recombinase Polymerase Amplification (RPA) is an isothermal molecular diagnostic known for its sensitivity, speed, portability, and widespread application in detecting various pathogens. Although several molecular assays are available for N. americanus, they have limitations in detecting mild N. americanus infections.

Methods: Fluorescent RPA primers and probes targeting the N. americanus internal transcribed spacer 2 (ITS2) gene were developed. The method's detection limit was assessed via serial dilution of genomic DNA. Specificity was confirmed against Clonorchis sinensis, Schistosoma japonicum, Fasciola hepatica, Ascaris lumbricoides, Enterobius vermicularis and Ancylostoma duodenale. Thirty samples identified as positive by Kato-Katz, along with 11 samples identified as negative by the method, were tested to evaluate the sensitivity and specificity of fluorescent RPA. Additionally, 287 field samples were tested for validation with these methods. All positive samples were identified as either N. americanus or A. duodenale.

Results: This study successfully developed a fluorescent RPA assay targeting the ITS2 gene of N. americanus. The length of the amplified fragment was 237 bp. Optimized conditions were achieved, resulting in a minimum detection limit of 1fg/µL, with no cross-reactivity with other pathogens. In laboratory validation, the fluorescent RPA assay demonstrated 100% sensitivity (30/30) and 100% specificity (11/11) compared to the Kato-Katz, and 100% sensitivity (29/29) and 91.7% specificity (11/12) when compared to the semi-nested PCR. In field validation using human fecal samples, the fluorescent RPA assay showed a sensitivity of 90.0% (36/40) and a specificity of 91.1% (225/247) compared to the Kato-Katz. And the sensitivity of the fluorescent RPA method compared to the semi-nested PCR method was 100% (34/34), while the specificity was 90.5% (229/252).

Conclusions: The fluorescent RPA assay presents a rapid and dependable method for detecting N. americanus in fecal samples. Its high sensitivity and specificity provide significant utility for field surveillance and early identification of N. americanus infections. This advancement could facilitate the rapid molecular diagnosis of N. americanus disease in hookworm-endemic regions.