PLoS Neglected Tropical Diseases
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2022 ◽  
Vol 16 (1) ◽  
pp. e0010136
Author(s):  
Meng-Tao Sun ◽  
Man-Man Gu ◽  
Jie-Ying Zhang ◽  
Qiu-Fu Yu ◽  
Poppy H. L. Lamberton ◽  
...  

Background As China is moving onto schistosomiasis elimination/eradication, diagnostic methods with both high sensitivity and specificity for Schistosoma japonicum infections in humans are urgently needed. Microscopic identification of eggs in stool is proven to have poor sensitivity in low endemic regions, and antibody tests are unable to distinguish between current and previous infections. Polymerase chain reaction (PCR) technologies for the detection of parasite DNA have been theoretically assumed to show high diagnostic sensitivity and specificity. However, the reported performance of PCR for detecting S. japonicum infection varied greatly among studies. Therefore, we performed a meta-analysis to evaluate the overall diagnostic performance of variable-temperature PCR technologies, based on stool or blood, for detecting S. japonicum infections in humans from endemic areas. Methods We searched literatures in eight electronic databases, published up to 20 January 2021. The heterogeneity and publication bias of included studies were assessed statistically. The risk of bias and applicability of each eligible study were assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool (QUADAS-2). The bivariate mixed-effects model was applied to obtain the summary estimates of diagnostic performance. The hierarchical summary receiver operating characteristic (HSROC) curve was applied to visually display the results. Subgroup analyses and multivariate regression were performed to explore the source of heterogeneity. This research was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and was registered prospectively in PROSPERO (CRD42021233165). Results A total of 2791 papers were retrieved. After assessing for duplications and eligilibity a total of thirteen publications were retained for inclusion. These included eligible data from 4268 participants across sixteen studies. High heterogeneity existed among studies, but no publication bias was found. The pooled analyses of PCR data from all included studies resulted in a sensitivity of 0.91 (95% CI: 0.83 to 0.96), specificity of 0.85 (95% CI: 0.65 to 0.94), positive likelihood ratio of 5.90 (95% CI: 2.40 to 14.60), negative likelihood ratio of 0.10 (95% CI: 0.05 to 0.20) and a diagnostics odds ratio of 58 (95% CI: 19 to 179). Case-control studies showed significantly better performances for PCR diagnostics than cross-sectional studies. This was further evidenced by multivariate analyses. The four types of PCR approaches identified (convention PCR, qPCR, Digital droplet PCR and nested PCR) differed significantly, with nested PCRs showing the best performance. Conclusions Variable-temperature PCR has a satisfactory performance for diagnosing S. japonicum infections in humans in endemic areas. More high quality studies on S. japonicum diagnostic techniques, especially in low endemic areas and for the detection of dual-sex and single-sex infections are required. These will likely need to optimise a nested PCR alongside a highly sensitive gene target. They will contribute to successfully monitoring endemic areas as they move towards the WHO 2030 targets, as well as ultimately helping areas to achieve these goals.


2022 ◽  
Vol 16 (1) ◽  
pp. e0009192
Author(s):  
Michael Weingartner ◽  
Simon Stücheli ◽  
Fadi Jebbawi ◽  
Bruno Gottstein ◽  
Guido Beldi ◽  
...  

Background Echinococcus multilocularis causes alveolar echinococcosis (AE), a rising zoonotic disease in the northern hemisphere. Treatment of this fatal disease is limited to chemotherapy using benzimidazoles and surgical intervention, with frequent disease recurrence in cases without radical surgery. Elucidating the molecular mechanisms underlying E. multilocularis infections and host-parasite interactions ultimately aids developing novel therapeutic options. This study explored an involvement of unfolded protein response (UPR) and endoplasmic reticulum-stress (ERS) during E. multilocularis infection in mice. Methods E. multilocularis- and mock-infected C57BL/6 mice were subdivided into vehicle, albendazole (ABZ) and anti-programmed death ligand 1 (αPD-L1) treated groups. To mimic a chronic infection, treatments of mice started six weeks post i.p. infection and continued for another eight weeks. Liver tissue was then collected to examine inflammatory cytokines and the expression of UPR- and ERS-related genes. Results E. multilocularis infection led to an upregulation of UPR- and ERS-related proteins in the liver, including ATF6, CHOP, GRP78, ERp72, H6PD and calreticulin, whilst PERK and its target eIF2α were not affected, and IRE1α and ATF4 were downregulated. ABZ treatment in E. multilocularis infected mice reversed, or at least tended to reverse, these protein expression changes to levels seen in mock-infected mice. Furthermore, ABZ treatment reversed the elevated levels of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α and interferon (IFN)-γ in the liver of infected mice. Similar to ABZ, αPD-L1 immune-treatment tended to reverse the increased CHOP and decreased ATF4 and IRE1α expression levels. Conclusions and significance AE caused chronic inflammation, UPR activation and ERS in mice. The E. multilocularis-induced inflammation and consecutive ERS was ameliorated by ABZ and αPD-L1 treatment, indicating their effectiveness to inhibit parasite proliferation and downregulate its activity status. Neither ABZ nor αPD-L1 themselves affected UPR in control mice. Further research is needed to elucidate the link between inflammation, UPR and ERS, and if these pathways offer potential for improved therapies of patients with AE.


2022 ◽  
Vol 16 (1) ◽  
pp. e0009772
Author(s):  
José Abraão Carneiro Neto ◽  
Cássius José Vitor de Oliveira ◽  
Sheila Nunes Ferraz ◽  
Mariele Guerra ◽  
Lívia Alves Oliveira ◽  
...  

Background While bladder dysfunction is observed in the majority of patients with human T cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy (HAM), it is also observed in patients who do not fulfill all diagnostic criteria for HAM. These patients are classified as having possible or probable HAM/TSP. However, it remains unclear whether the severity and progression of bladder dysfunction occurs similarly between these two groups. Objective Compare the severity and evolution of bladder dysfunction in HTLV-1-infected patients with possible and definite HAM/TSP. Methods The present prospective cohort study followed 90 HTLV-1 patients with possible HAM/TSP and 84 with definite HAM/TSP between April 2011 and February 2019. Bladder dysfunction was evaluated by bladder diary, overactive bladder symptoms scores (OABSS) and urodynamic studies. Bladder dysfunction progression was defined as the need for clean self-intermittent catheterization (CIC). Results At baseline, nocturia, urgency and OABSS scores were worse in definite compared to possible HAM/TSP patients. The main urodynamic finding was detrusor overactivity, present in 77.8% of the patients with definite HAM/TSP versus 58.7% of those with possible HAM/TSP (P = 0.05). Upon study conclusion, the cumulative frequency of patients requiring CIC increased in both groups, from 2 to 6 in possible HAM/TSP and from 28 to 44 in definite HAM/TSP patients. The estimated time to need for CIC was 6.7 years (95%CI 6.5–7.0) in the possible HAM/TSP group compared to 5.5 years (95%CI 4.8–6.1) in the definite HAM/TSP group. Conclusions Although both groups showed similarities in bladder dysfunction and tended to progress to requiring CIC over time, patients with possible HAM/TSP presented less severe manifestations at baseline and progressed more slowly than those with definite HAM/TSP.


2022 ◽  
Vol 16 (1) ◽  
pp. e0010109
Author(s):  
Ana Hernández-González ◽  
Belén González-Bertolín ◽  
Laura Urrea ◽  
Agnes Fleury ◽  
Elizabeth Ferrer ◽  
...  

Background Neurocysticercosis (NCC), and cystic echinococcosis (CE) are two neglected diseases caused by cestodes, co-endemic in many areas of the world. Imaging studies and serological tests are used in the diagnosis of both parasitic diseases, but cross-reactions may confound the results of the latter. The novel multiplex bead-based assay with recombinant antigens has been reported to increases the diagnostic accuracy of serological techniques. Methodology We set-up an immunoassay based on the multiplex bead-based platform (MBA), using the rT24H (against Cysticercus cellulosae, causing cysticercosis) and r2B2t (against Echinococcus granulosus sensu lato, causing CE) recombinant antigens, for simultaneous and differential diagnosis of these infections. The antigens were tested on 356 sera from 151 patients with CE, 126 patients with NCC, and 79 individuals negative for both diseases. Specificity was calculated including sera from healthy donors, other neurological diseases and the respective NCC or CE sera counterpart. The diagnostic accuracy of this assay was compared with two commercial ELISA tests, Novalisa and Ridascreen, widely used in the routine diagnosis of cysticercosis and CE, respectively. Main findings For the diagnosis of NCC, sensitivity ranged from 57.94–63.49% for the rT24H-MBA, and 40.48–46.03% for Novalisa ELISA depending on exclusion or inclusion of sera having equivocal results on ELISA from the analysis; specificities ranged from 90.87–91.30% and 70.43–76.96%, respectively. AUC values of the ROC curve were 0.783 (rT24H) and 0.619 (Novalisa) (p-value < 0.001). For the diagnosis of CE, the sensitivity of the r2B2t-MBA ranged from 68.87–69.77% and of Ridascreen ELISA from 50.00–57.62%; specificities from 92.47–92.68% and from 74.15–80.98%, respectively. AUC values were 0.717 and 0.760, respectively. Conclusions/Significance Overall, the recombinant antigens tested with the bead-based technology showed better diagnostic accuracy than the commercial assays, particularly for the diagnosis of NCC. The possibility of testing the same serum sample simultaneously for the presence of antibodies against both antigens is an added value particularly in seroprevalence studies for cysticercosis linked to control programs in endemic areas where these two parasites coexist.


2022 ◽  
Vol 16 (1) ◽  
pp. e0010000
Author(s):  
Priyanka Rai ◽  
Dhiraj Saha

Introduction Lymphatic filariasis causes long term morbidity and hampers the socio-economic status. Apart from the available treatments and medication, control of vector population Culex quinquefasciatus Say through the use of chemical insecticides is a widely applied strategy. However, the unrestrained application of these insecticides over many decades has led to resistance development in the vectors. Methods In order to determine the insecticide susceptibility/resistance status of Cx. quinquefasciatus from two filariasis endemic districts of West Bengal, India, wild mosquito populations were collected and assayed against six different insecticides and presence of L1014F; L1014S kdr mutations in the voltage-gated sodium channel gene was also screened along with the use of synergists to evaluate the role of major detoxifying enzymes in resistance development. Results The collected mosquito populations showed severe resistance to insecticides and the two synergists used–PBO (piperonyl butoxide) and TPP (triphenyl phosphate), were unable to restore the susceptibility status of the vector thereupon pointing towards a minor role of metabolic enzymes. kdr mutations were present in the studied populations in varying percent with higher L1014F frequency indicating its association with the observed resistance to pyrethroids and DDT. This study reports L1014S mutation in Cx. quinquefasciatus for the first time.


2022 ◽  
Vol 16 (1) ◽  
pp. e0010038
Author(s):  
Naomi D. de Bruijne ◽  
Kedir Urgesa ◽  
Abraham Aseffa ◽  
Kidist Bobosha ◽  
Anne Schoenmakers ◽  
...  

Background Delay in case detection is a risk factor for developing leprosy-related impairments, leading to disability and stigma. The objective of this study was to develop a questionnaire to determine the leprosy case detection delay, defined as the period between the first signs of the disease and the moment of diagnosis, calculated in total number of months. The instrument was developed as part of the PEP4LEP project, a large-scale intervention study which determines the most effective way to implement integrated skin screening and leprosy post-exposure prophylaxis with a single-dose of rifampicin (SDR-PEP) administration in Ethiopia, Mozambique and Tanzania. Methodology/Principal findings A literature review was conducted and leprosy experts were consulted. The first draft of the questionnaire was developed in Ethiopia by exploring conceptual understanding, item relevance and operational suitability. Then, the first draft of the tool was piloted in Ethiopia, Mozambique and Tanzania. The outcome is a questionnaire comprising nine questions to determine the case detection delay and two annexes for ease of administration: a local calendar to translate the patient’s indication of time to number of months and a set of pictures of the signs of leprosy. In addition, a body map was included to locate the signs. A ‘Question-by-Question Guide’ was added to the package, to provide support in the administration of the questionnaire. The materials will be made available in English, Oromiffa (Afaan Oromo), Portuguese and Swahili via https://www.infolep.org. Conclusions/Significance It was concluded that the developed case detection delay questionnaire can be administered quickly and easily by health workers, while not inconveniencing the patient. The instrument has promising potential for use in future leprosy research. It is recommended that the tool is further validated, also in other regions or countries, to ensure cultural validity and to examine psychometric properties like test-retest reliability and interrater reliability.


2022 ◽  
Vol 16 (1) ◽  
pp. e0009889
Author(s):  
Shaoyun Cheng ◽  
Bingkuan Zhu ◽  
Fang Luo ◽  
Xiying Lin ◽  
Chengsong Sun ◽  
...  

Schistosoma japonicum is prevalent in Asia with a wide mammalian host range, which leads to highly harmful zoonotic parasitic diseases. Most previous transcriptomic studies have been performed on this parasite, but mainly focus on stages inside the mammalian host. Moreover, few larval transcriptomic data are available in public databases. Here we mapped the detailed transcriptome profiles of four S. japonicum larval stages including eggs, miracidia, sporocysts and cercariae, providing a comprehensive development picture outside of the mammalian host. By analyzing the stage-specific/enriched genes, we identified functional genes associated with the biological characteristic at each stage: e.g. we observed enrichment of genes necessary for DNA replication only in sporocysts, while those involved in proteolysis were upregulated in sporocysts and/or cercariae. This data indicated that miracidia might use leishmanolysin and neprilysin to penetrate the snail, while elastase (SjCE2b) and leishmanolysin might contribute to the cercariae invasion. The expression profile of stem cell markers revealed potential germinal cell conversion during larval development. Additionally, our analysis indicated that tandem duplications had driven the expansion of the papain family in S. japonicum. Notably, all the duplicated cathepsin B-like proteases were highly expressed in cercariae. Utilizing our 3rd version of S. japonicum genome, we further characterized the alternative splicing profiles throughout these four stages. Taken together, the present study provides compressive gene expression profiles of S. japonicum larval stages and identifies a set of genes that might be involved in intermediate and definitive host invasion.


2022 ◽  
Vol 16 (1) ◽  
pp. e0010040
Author(s):  
David Horn

The parasitic trypanosomatids cause lethal and debilitating diseases, the leishmaniases, Chagas disease, and the African trypanosomiases, with major impacts on human and animal health. Sustained research has borne fruit by assisting efforts to reduce the burden of disease and by improving our understanding of fundamental molecular and cell biology. But where has the research primarily been conducted, and which research areas have received the most attention? These questions are addressed below using publication and citation data from the past few decades.


2022 ◽  
Vol 16 (1) ◽  
pp. e0010009
Author(s):  
Imane El Idrissi Saik ◽  
Chaimaa Benlabsir ◽  
Hassan Fellah ◽  
Meryem Lemrani ◽  
Myriam Riyad

Cutaneous leishmaniasis (CL) due to Leishmania tropica is a neglected tropical disease characterized by a wide geographical distribution in the Mediterranean basin and is endemic in several of its countries. In addition, the vector Phlebotomus sergenti is abundantly present all around the basin. Its transmission cycle is still subject to debate. In some countries, the presence of an animal reservoir has been confirmed. In Morocco, CL due to L. tropica has risen since the 1980s and has spread widely to become the most abundant form of leishmaniasis in the territory. However, the anthroponotic transmission is so far the only recognized mode, despite recordings of L. tropica infection in animal hosts. In this review article, we assess the situation of CL due to L. tropica in the Mediterranean basin with a focus on Morocco and gather knowledge about any potential zoonotic transmission in the country. A concomitant zoonotic transmission could explain the persistence of the disease in areas where human protective measures combined with vector management did not help reduce the disease burden.


2022 ◽  
Vol 16 (1) ◽  
pp. e0010101
Author(s):  
Hao Li ◽  
Luqi Wang ◽  
Mengxi Zhang ◽  
Yihan Lu ◽  
Weibing Wang

Many countries implemented measures to control the COVID-19 pandemic, but the effects of these measures have varied greatly. We evaluated the effects of different policies, the prevalence of dominant variants (e.g., Delta), and vaccination on the characteristics of the COVID-19 pandemic in eight countries. We quantified the lag times of different non-pharmaceutical interventions (NPIs) and vaccination using a distributed lag non-linear model (DLNM). We also tested whether these lag times were reasonable by analyzing changes in daily cases and the effective reproductive number (Rt)over time. Our results indicated that the response to vaccination in countries with continuous vaccination programs lagged by at least 40 days, and the lag time for a response to NPIs was at least 14 days. A rebound was most likely to occur during the 40 days after the first vaccine dose. We also found that the combination of school closure, workplace closure, restrictions on mass gatherings, and stay-at-home requirements were successful in containing the pandemic. Our results thus demonstrated that vaccination was effective, although some regions were adversely affected by new variants and low vaccination coverage. Importantly, relaxation of NPIs soon after implementation of a vaccination program may lead to a rebound.


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