Low Endemic Areas Research Articles

Comparison of four commercial serological tests for the detection of Leishmania infantum antibodies in dogs.

Early detection and treatment of cases of Leishmania infantum infection are critical in controlling the spread of the disease in dogs. Several serological methods are available to support the diagnosis of canine leishmaniosis. The immunofluorescence antibody test (IFAT) and enzyme-linked immunosorbent assay (ELISA) are the main tests used by clinicians. High antibody levels are associated with severe parasitism and disease and are diagnostic of clinical leishmaniosis. Conversely, the presence of low antibody levels is not necessarily indicative of disease and may be more difficult to detect by serological tests. The aim of this study was to evaluate and compare the diagnostic performance of four commercially available serological tests, including ELISAs (CIVTEST® CANIS LEISHMANIA short and standard protocols), LEISHMANIA-ELISA DOG®, ELISA/S7® and MegaFLUO®LEISH IFAT, for the detection of specific antibodies against L. infantum antigens in dogs in different states of infection. Canine sera samples from seropositive sick infected dogs (n = 75), seropositive apparently healthy dogs (n = 48), and seronegative apparently healthy dogs from a high endemic area (Cadiz, n = 40) and seronegative apparently healthy dogs from very low endemic area of L. infantum infection (Asturias, n = 40) were classified based on the results of an in-house UAB ELISA as a reference test. The positive percent of agreement (PPA) and negative percent of agreement (NPA) observed for each test were as follows: CIVTEST® standard (93.4 %, 100 %) on 202 samples tested, CIVTEST® short (84.4 %, 100 %) on 202 samples tested, LEISHMANIA-ELISA DOG® (81.8 %, 72.2 %) on 138 samples tested, ELISA/S7® (34.8 %, 45 %) on 195 samples tested and MegaFLUO®LEISH IFAT (100 %, 100 %) on 203 samples tested, respectively. The accuracy was as follows: CIVTEST® standard (0.96), CIVTEST® short (0.91), LEISHMANIA-ELISA DOG® (0.77), ELISA/S7® (0.39), and MegaFLUO®LEISH IFAT (1). The Cohen´s Kappa index (K) from best to worst was: MegaFLUO®LEISH IFAT (K = 1), CIVTEST® standard (K = 0.92), CIVTEST® short (K=0.81), LEISHMANIA-ELISA DOG® (K =0.54), and ELISA/S7® (K=-0.19). Finally, the area under the receiver operating characteristic curve (AUC-ROC), in the ELISAs test, ordered from the maximum to the minimum value was: CIVTEST® short (1), CIVTEST® standard (0.99), LEISHMANIA-ELISA DOG® (0.87), and S7® (0.37). In conclusion, this study demonstrated that the diagnostic performance of the commercially available ELISA tests against L. infantum antigen can vary widely. Moreover, it highlights the fact that CIVTEST® CANIS LEISHMANIA is a reliable test to support the diagnosis of canine leishmaniosis in clinical settings.

Evaluation of Synthetic Peptides from Schistosoma mansoni ATP Diphosphohydrolase 1: In Silico Approaches for Characterization and Prospective Application in Diagnosis of Schistosomiasis.

Schistosomiasis is the infection caused by Schistosoma mansoni and constitutes a worldwide public health problem. The parasitological recommended method and serological methods can be used for the detection of eggs and antibodies, respectively. However, both have limitations, especially in low endemicity areas. Thus, new approaches for the diagnosis of schistosomiasis are essential. In this study, a six-amino acid peptide and derived sequences from SmATPDase1 were synthesized for the evaluation of immunogenicity. SmATPDase1 is included in a protein group in S. mansoni tegument; therefore, its peptides could be potential candidates for diagnostic antigens. In the hypothetical SmATPDase1 three-dimensional structure, peptides are located in a region exposed and accessible to antibody binding. In addition, peptide amino acid sequences are conserved in the most relevant Schistosoma species and have low identity with human NTPDases isoforms. Swiss mice immunization resulted in significant anti-peptide polyclonal antibodies production, which recognized a 63 kDa protein in tegument and adult worm preparations. By immunofluorescence microscopy, polyclonal antibodies also identified this enzyme in cercariae. Sera of infected animals presented high seropositivity in ELISA-peptides, with an area under curve (AUC) greater than 0.96 for all peptides. In mice with low parasite burden, we observed a seropositivity AUC > 0.9. Reactivity in the prepatent period exhibited AUC values greater than 0.94 for all peptides. Anti-P1425 monoclonal antibodies were successfully produced, and mAbs recognized the integral protein in ELISA and Western blots. The data indicate that peptides from SmATPDase1 are potential biomarkers for schistosomiasis, and anti-peptide antibodies are interesting tools for the detection of the infection.

Lyme Disease Confirmatory Western Blot Is Redundant for Screen Negative Samples in Low Endemic Areas, British Columbia, Canada.

Background: Borrelia burgdorferi sensu stricto is the causative agent of Lyme disease (LD). Possible early symptoms include flu-like symptoms and erythema migrans and later, the risk of disruption of the nervous system, joints, and heart. A two-tiered testing method is employed for serological diagnostics. The Public Health Agency of Canada guidelines recommend that samples tested negative on first-tiered test need not be confirmed by second-tiered test. Due to the challenging nature of diagnosis leading to misconceptions among physicians about false negatives, confirmatory testing is requested despite the initial negative result. Methods: Hundred screen-negative Lyme patient samples from 2007 to 2016 were tested by Western blot (WB) second-tiered confirmatory test upon physician's request in British Columbia to study the first-tiered screening test sufficiency. Results: Those negative for first-tiered enzyme-linked immunosorbent assay were also negative by WB. Conclusion: Results demonstrate that confirmatory testing is not necessary on screen-negative samples. Hence, first-tiered test is sufficient to rule out LD.

Severe Malaria in Angola: The Clinical Profile and Disease Outcome Among Adults from a Low-Endemic Area.

Severe malaria poses a significant public health concern in Angola, particularly among adults. This study assessed the clinical manifestations and outcomes of severe Plasmodium falciparum malaria in adult patients admitted to Hospital Central Dr. António Agostinho Neto of Lubango (HCL), Angola. The study retrospectively reviewed medical records of patients over 14 years old admitted with severe malaria during the first quarter of 2021 and 2022, coinciding with the peak transmission season. The World Health Organization (WHO) criteria were used to clarify the disease severity. The cohort included 640 patients-167 in 2021 and 473 in 2022-distributed across the following departments: the Intensive Care Unit (ICU; n = 81), Medicine (MED; n = 458) and Infectiology (INF; n = 101). The median age was 26 years and 59.4% were males. Renal impairment was the most frequent severe manifestation, affecting 37.4% of cases. The mortality rate across the study period was 7%, showing a notable decrease from 10.2% in 2021 to 5.9% in 2022. The higher mortality rate in 2021 may reflect the impact of the COVID-19 pandemic, which limited hospital access and delayed care, resulting in more critical cases being admitted at a later stage. In 2022, with reduced COVID-19 pressures, earlier access to treatment may have improved outcomes, contributing to the lower mortality rate. This study emphasizes the need to assess the clinical burden of severe malaria in low-endemic regions, where shifting patterns may signal emerging threats such as antimalarial drug resistance. Further research is essential to optimize control strategies and strengthen surveillance systems, reducing morbidity and mortality.

Anti-Schistosoma mansoni antibodies detection in Indigenous communities living in low endemicity areas

Anti-Schistosoma mansoni antibodies detection in Indigenous communities living in low endemicity areas

Intermediate and definitive hosts of wild Schistosoma mansoni: ecological niche modeling of hosts in low endemicity areas

Intermediate and definitive hosts of wild Schistosoma mansoni: ecological niche modeling of hosts in low endemicity areas

Development and Application of qPCR as an Alternative for the Diagnosis and control of Schistosomiasis in Areas of Low Endemicity for the Disease

Development and Application of qPCR as an Alternative for the Diagnosis and control of Schistosomiasis in Areas of Low Endemicity for the Disease

Stability of the helminth community in Nectomys squamipes 22 years apart in a low endemic area for schistosomiasis in Brazil

Stability of the helminth community in Nectomys squamipes 22 years apart in a low endemic area for schistosomiasis in Brazil

Mapping schistosomiasis risk landscapes and implications for disease control: A case study for low endemic areas in the Middle Paranapanema river basin, São Paulo, Brazil.

Schistosomiasis, a chronic parasitic disease, remains a public health issue in tropical and subtropical regions, especially in low and moderate-income countries lacking assured access to safe water and proper sanitation. A national prevalence survey carried out by the Brazilian Ministry of Health from 2011 to 2015 found a decrease in human infection rates to 1%, with 19 out of 26 states still classified as endemic areas. There is a risk of schistosomiasis reemerging as a public health concern in low-endemic regions. This study proposes an integrated landscape-based approach to aid surveillance and control strategies for schistosomiasis in low-endemic areas. In the Middle Paranapanema river basin, specific landscapes linked to schistosomiasis were identified using a comprehensive methodology. This approach merged remote sensing, environmental, socioeconomic, epidemiological, and malacological data. A team of experts identified ten distinct landscape categories associated with varying levels of schistosomiasis transmission potential. These categories were used to train a supervised classification machine learning algorithm, resulting in a 92.5% overall accuracy and a 6.5% classification error. Evaluation revealed that 74.6% of collected snails from water collections in five key municipalities within the basin belonged to landscape types with higher potential for S. mansoni infection. Landscape connectivity metrics were also analysed. This study highlights the role of integrated landscape-based analyses in informing strategies for eliminating schistosomiasis. The methodology has produced new schistosomiasis risk maps covering the entire basin. The region's low endemicity can be partly explained by the limited connectivity among grouped landscape-units more prone to triggering schistosomiasis transmission. Nevertheless, changes in social, economic, and environmental landscapes, especially those linked to the rising pace of incomplete urbanization processes in the region, have the potential to increase risk of schistosomiasis transmission. This study will help target interventions to bring the region closer to schistosomiasis elimination.

Two mosquito salivary antigens demonstrate promise as biomarkers of recent exposure to P. falciparum infected mosquito bites.

Measuring malaria transmission intensity using the traditional entomological inoculation rate is difficult. Antibody responses to mosquito salivary proteins like SG6 have been used as biomarkers of exposure to Anopheles mosquito bites. Here, we investigate four mosquito salivary proteins as potential biomarkers of human exposure to mosquitoes infected with P. falciparum: mosGILT, SAMSP1, AgSAP, and AgTRIO. We tested population-level human immune responses in longitudinal and cross-sectional plasma from individuals with known P. falciparum infection from low and moderate transmission areas in Senegal using a multiplexed magnetic bead-based assay. AgSAP and AgTRIO were the best indicators of recent exposure to infected mosquitoes. Antibody responses to AgSAP, in a moderate endemic area, and to AgTRIO in both low and moderate endemic areas, were significantly higher than responses in a healthy non-endemic control cohort (p-values = 0.0245, 0.0064, and <0.0001 respectively). No antibody responses significantly differed between the low and moderate transmission area, or between equivalent groups during and outside the malaria transmission seasons. For AgSAP and AgTRIO, reactivity peaked 2-4 weeks after clinical P. falciparum infection and declined 3 months after infection. Reactivity to AgSAP and AgTRIO peaked after infection, with no differences between transmission seasons within region or between low and moderate transmission regions. This suggests that reactivity reflects exposure to infectious mosquitoes or recent bites rather than general mosquito exposure. Kinetics suggest reactivity is relatively short-lived. AgSAP and AgTRIO are promising candidates to incorporate into multiplexed assays for serosurveillance of population-level changes in P. falciparum-infected mosquito exposure.

Knowledge, attitudes, and practices regarding malaria transmission and prevention in an indigenous Maijuna community: a qualitative study in the Peruvian Amazon

BackgroundPeru is a low-endemic transmission area for malaria, where the majority (84%) of incident malaria cases are localized to the department of Loreto, which is composed of several geographically isolated rural communities. Recent intervention efforts targeting at-risk Indigenous populations that live in riverine communities in Loreto place emphasis on preventive behaviours to decrease transmission. However, malaria related behaviour change is often dependent upon local knowledge, beliefs, and practices, especially in areas where malaria is viewed an embedded and unavoidable aspect of life.MethodsThis exploratory case study used semi-structured interviews conducted in Spanish between February and March of 2019 to examine the knowledge, attitudes, and practices related to malaria prevention among the Indigenous Maijuna people of Sucusari, Loreto, Peru. Participants who consented were also administered a rapid diagnostic test (RDT) upon the time of interview.ResultsA total of 33 community members were interviewed, and 31 were tested via malaria rapid diagnostic tests, with RDT filter paper subsequently tested using PCR. All test results were negative for malaria. Themes that emerged included: varying knowledge of methods to prevent malaria, reports of observed changes in malaria incidence over time, confusion surrounding malaria transmission, treatment-seeking as a common behaviour, the belief that medications are effective, and the acceptance of bed nets which were viewed as a lifestyle norm.ConclusionThese shared narratives should be used as a foundation for further studies and health interventions among communities in the Peruvian Amazon with limited access to health services where culturally resonant, community-based health programming is essential to improving health. Takeaways regarding confusion surrounding malaria transmission should also be considered.

Molecular epidemiology and population genetics of Schistosoma mansoni infecting school-aged children situated along the southern shoreline of Lake Malawi, Malawi.

In areas of low disease endemicity, highly sensitive diagnostic tools to identify, diagnose, and monitor intestinal schistosomiasis transmission are needed to reliably measure the burden and risk of infection. Here, we used highly sensitive molecular diagnostic methods to investigate Schistosoma mansoni prevalence and transmission along the southern shoreline of Lake Malawi, five years post-disease outbreak. Faecal and urine samples were provided by school-aged children situated along the southern shoreline of Lake Malawi. Kato-Katz faecal-egg microscopy and point-of-care circulating cathodic antigen (POC-CCA) rapid diagnostic tests were then performed to diagnose infection with S. mansoni. Urine-egg microscopy was also used to diagnose infection with Schistosoma haematobium. In addition, Schistosoma miracidia were isolated from faecal material using a standard miracidium hatching technique. A two-step real-time PCR approach was then used to diagnose infection with S. mansoni using DNA isolated from faecal samples. Furthermore, isolated miracidia were genotyped to species level through PCR and Sanger sequencing. Phylogenetic analyses were then carried out to identify which previously defined S. mansoni cox1 lineage group S. mansoni miracidia were most closely related to. The measured prevalence of S. mansoni infection varied considerably depending on which diagnostic assay was used. When compared to real-time PCR, faecal-egg microscopy had a sensitivity of 9% and a specificity of 100%. When POC-CCA 'trace' results were considered positive, POC-CCA had a sensitivity of 73% and a specificity of 81% when compared to real-time PCR. However, when considered negative, POC-CCA sensitivity was reduced to 56%, whereas specificity was increased to 90%. In addition, a high degree of S. haematobium DNA was detected in DNA isolated from faecal samples and motile S. haematobium miracidia were recovered from faecal samples. Schistosoma mansoni miracidia were closely related to two independent cox1 lineage groups, suggesting multiple recent introduction and colonisation events originating from surrounding east African countries. Intestinal schistosomiasis is now highly prevalent along the southern shoreline of Lake Malawi just five years post-disease outbreak. In addition, a high prevalence of urogenital schistosomiasis persists. The revision of ongoing schistosomiasis control programmes in this area is therefore recommended. Our study also highlights the need for reliable diagnostic assays capable of distinguishing between Schistosoma species in multispecies co-endemic areas.

Trends and Age-Period-Cohort Effect on Acute Hepatitis B Incidence - China, 2005-2021.

This study analyzed long-term trends in the incidence of acute hepatitis B (AHB) in China, focusing on age, period, and cohort effects on incidence. Data on AHB from 2005 to 2021 were extracted from the National Notifiable Disease Reporting System (NNDRS) of China for analysis. Incidences of AHB were calculated by gender and age group using population denominators from the 2000, 2010, and 2020 censuses. Joinpoint regression was employed to evaluate trends, and an age-period-cohort model was used to assess the age, period, and cohort effects. The annual average incidence of reported AHB in children aged 14 years and below in low, intermediate, and high endemic areas decreased from 1.65, 2.33, and 2.56 per 100,000 in 2005-2010 to 0.56, 0.58, and 0.48 per 100,000 in the 2016-2021 period. The 15-39-year age group in high endemic areas exhibited the most significant decline in incidence, dropping from 23.14 per 100,000 in 2005 to 4.59 per 100,000 in 2021 among males and from 10.62 per 100,000 to 3.21 per 100,000 among females. Age-period-cohort analysis indicated decreasing age, period, and cohort effects for reported AHB incidence in each endemic area, except for a slight upward trend in the 15-19-year age group and in the cohort born between 1951 and 1955. This study demonstrated a rapid decline in AHB incidence across various endemic areas since 2005. Children aged 14 years and below exhibited very low AHB incidences, while the incidence among individuals over 15 years was higher. To further reduce AHB incidence, hepatitis B vaccine (HepB) coverage should be enhanced among adolescents and adults.

Unravelling heterogeneous malaria transmission dynamics in the Peruvian Amazon: insights from a cross-sectional survey

BackgroundMalaria remains a global health challenge, particularly in Peru's Loreto region. Despite ongoing efforts, high infection rates and asymptomatic cases perpetuate transmission. The Peruvian Ministry of Health’s “Zero Malaria Plan” targets elimination. This novel study combines microscopic, molecular, and serological techniques to assess transmission intensity, identify epidemiological risk factors, and characterize species-specific patterns across villages. The findings aim to inform targeted interventions and support broader malaria elimination efforts in line with the Zero Malaria Plan initiative.MethodsA cross-sectional malaria survey was conducted in the Zungarococha community, comprising the villages Llanchama (LL), Ninarumi (NI), Puerto Almendra (PA), and Zungarococha (ZG), using microscopic, molecular, and serological techniques to evaluate malaria transmission intensity. Statistical analysis, including multivariate-adjusted analysis, seroprevalence curves, and spatial clustering analysis, were performed to assess malaria prevalence, exposure, and risk factors.ResultsThe survey revealed a high prevalence of asymptomatic infections (6% by microscopy and 18% by PCR), indicating that molecular methods are more sensitive for detecting asymptomatic infections. Seroprevalence varied significantly between villages, reflecting the heterogeneous malaria transmission dynamics. Multivariate analysis identified age, village, and limited bed net use as significant risk factors for malaria infection and species-specific exposure. Seroprevalence curves demonstrated community-specific patterns, with Llanchama and Puerto Almendra showing the highest seroconversion rates for both Plasmodium species.ConclusionsThe study highlights the diverse nature of malaria transmission in the Loreto region, particularly nothing the pronounced heterogeneity as transmission rates decline, especially in residual malaria scenarios. The use of molecular and serological techniques enhances the detection of current infections and past exposure, aiding in the identification of epidemiological risk factors. These findings underscore the importance of using molecular and serological tools to characterize malaria transmission patterns in low-endemic areas, which is crucial for planning and implementing targeted interventions and elimination strategies. This is particularly relevant for initiatives like the Zero Malaria Plan in the Peruvian Amazon.

Schistosomiasis in areas of low endemicity: an overly neglected disease. The example of Schistosoma monsoni in BrazilEsquistossomose em áreas de baixa endemicidade, uma doença muito negligenciada. O exemplo de Schistosoma mansoni no Brasil

Human schistosomiasis is a parasitic disease caused by an infection with trematodes of the genus Schistosoma. The disease mainly affects impoverished populations. Around 800 million people are exposed to the infection, which is a public health problem in the tropical and subtropical regions of Africa, Asia, the Caribbean and South America. In Brazil, Schistosoma mansoni is the only species that causes schistosomiasis and the disease is widely distributed. Conventional diagnosis of the disease is carried out by detecting eggs using parasitological methods, such as the Kato-Katz test. Schistosomiasis has been reported in all regions of Brazil and is characterized as endemic in seven states in the Northeast Region and two states in the Southeast Region. In 2015, 78,7% of all cases reported in Brazil occurred in the Northeast Region. It is estimated that 1,5 million people is infected with this disease in Brazil and more than 25 millions live in areas with a high risk of transmission. Despite the reduction in mortality and morbidity, schistosomiasis was responsible for 8,756 deaths between 2000 and 2011 and 2,517 deaths between 2015 and 2019 in Brazil and it remains an important public health problem. In the state of Rio de Janeiro, some areas have low endemicity or isolated foci of Schistosoma mansoni and the majority of infected individuals have mild infections. The last survey of the disease in the state of Rio de Janeiro was carried out between 2010 and 2015 in students aged 7 to 17.Schistosomiasis was reported in 10 of the 21 municipalities studied. Of the 5,111 school children screened for S. mansoni infection, 46 (1,65%) were tested positive. Studies carried out in areas of low endemicity in Rio de Janeiro showed that among the 205 patients infected by S. mansoni in Sumidouro, around 84% were aged 14 or over and all, except one individual, had the intestinal form (91,2%) or hepato-intestinal (8,3%) of schistosomiasis. Another study carried out in Sumidouro showed that with tests based on patent Schistosoma egg infection determined by the Kato-Katz test, active infections were diagnosed in eight (8/108) individuals. The intensity of infection expressed by parasite loads ranged from 6 to 72 eggs per gram of feces/individual. The results showed DNA amplification in 32 of the 100 individuals tested by real-time PCR. All individuals with patent ovo infection showed positive DNA amplification. These studies showed that if we only analyzed school-age children using the Kato-Katz test, the majority of the infected population would never be diagnosed with S. mansoni infection. In situations of low endemicity, with low intensities of infection, with low severity in the population and in the most affected age groups, schistosomiasis requires a more sensitive diagnostic approach (e.g. screening by PCR rather than Kato test), otherwise many infected individuals will remain invisible to the healthcare system.

Effectiveness, Safety, and Acceptability of Primaquine Mass Drug Administration in Low-Endemicity Areas in Southern Thailand: Proof-of-Concept Study.

A challenge in achieving the malaria-elimination target in the Greater Mekong Subregion, including Thailand, is the predominance of Plasmodium vivax malaria, which has shown extreme resilience to control measures. This proof-of-concept study aimed to provide evidence for implementing primaquine mass drug administration (pMDA) as a strategy for P. vivax elimination in low-endemicity settings. The study employed a mixed-methods trial to thoroughly evaluate the effectiveness, safety, acceptability, and community engagement of pMDA. The quantitative part was designed as a 2-period cluster-crossover randomized controlled trial. The intervention was pMDA augmented to the national prevention and control standards with directly observed treatment (DOT) by village health volunteers. The qualitative part employed in-depth interviews and brainstorming discussions. The study involved 7 clusters in 2 districts of 2 southern provinces in Thailand with persistently low P. vivax transmission. In the quantitative part, 5 cross-sectional blood surveys were conducted in both the pMDA and control groups before and 3 months after pMDA. The effectiveness of pMDA was determined by comparing the proportions of P. vivax infections per 1000 population between the 2 groups, with a multilevel zero-inflated negative binomial model adjusted for cluster and time as covariates and the interaction. The safety data comprised adverse events after drug administration. Thematic content analysis was used to assess the acceptability and engagement of stakeholders. In the pre-pMDA period, the proportions of P. vivax infections in the pMDA (n=1536) and control (n=1577) groups were 13.0 (95% CI 8.2-20.4) and 12.0 (95% CI 7.5-19.1), respectively. At month 3 post-pMDA, these proportions in the pMDA (n=1430) and control (n=1420) groups were 8.4 (95% CI 4.6-15.1) and 5.6 (95% CI 2.6-11.5), respectively. No statistically significant differences were found between the groups. The number of malaria cases reduced in all clusters in both groups, and thus, the impact of pMDA was inconclusive. There were no major safety concerns. Acceptance among the study participants and public health care providers at local and national levels was high, and they believed that pMDA had boosted awareness in the community. pMDA was associated with high adherence, safety, and tolerability, but it may not significantly impact P. vivax transmission. As this was a proof-of-concept study, we decided not to scale up the intervention with larger clusters and samples. An alternative approach involving a targeted primaquine treatment strategy with primaquine and DOT is currently being implemented. We experienced success regarding effective health care workforces at point-of-care centers, effective collaborations in the community, and commitment from authorities at local and national levels. Our efforts boosted the acceptability of the malaria-elimination initiative. Community engagement is recommended to achieve elimination targets. Thai Clinical Trials Registry TCTR20190806004; https://www.thaiclinicaltrials.org/show/TCTR20190806004.

Machine-learning-based risk assessment tool to rule out empirical use of ESBL-targeted therapy in endemic areas

Antimicrobial stewardship focuses on identifying patients who require extended-spectrum beta-lactamase (ESBL)-targeted therapy. 'Rule-in' tools have been researched extensively in areas of low endemicity; however, such tools are inadequate for areas with high prevalence of ESBL-producing pathogens, as almost all patients will be selected. To develop a machine-learning-based 'rule-out' tool suitable for areas with high levels of resistance. Gradient-boosted decision trees were used to train and validate a risk prediction model on data from 17,913 (45% ESBL) patients with Escherichia coli and Klebsiella pneumoniae in urine cultures. The predictive power of different sets of variables was evaluated using Shapley values to evaluate the contributions of variables. The model successfully identified patients with low risk of ESBL resistance in ESBL-endemic areas (area under receiver operating characteristic curve 0.72). When used to select the 30% of patients with the lowest predicted risk, the model yielded a negative predictive value ≥0.74. A simplified model with seven input features was found to perform nearly as well as the full model. This simplified model is freely accessible as a web application. This study found that a risk calculator for antibiotic resistance can be a viable 'rule-out' strategy to reduce the use of ESBL-targeted therapy in ESBL-endemic areas. The robust performance of a version of the model with limited features makes the clinical use of such a tool feasible. This tool provides an important alternative in an era with growing rates of ESBL-producing pathogens, where some experts have called for empirical use of carbapenems as first-line therapy for all patients in areas with high prevalence of ESBL-producing pathogens.

Low toxicity contributes to Sporothrix globosa invade the skin of patients in low-epidemic areas of China.

This study aims to assess the clinical characteristics of sporotrichosis in low-endemic areas of China, including the prevalence geography, genotypic traits of patients, clinical manifestations, and strain virulence and drug sensitivities. The objective is to improve the currently used clinical management strategies for sporotrichosis. Retrospective data were collected from patients diagnosed with sporotrichosis through fungal culture identification. The isolates from purified cultures underwent identification using CAL (Calmodulin) gene sequencing. Virulence of each strain was assessed using a Galleria mellonella (G. mellonella) larvae infection model. Invitro susceptibility testing against commonly used clinical antifungal agents for sporotrichosis was conducted following CLSI criteria. In our low-endemic region for sporotrichosis, the majority of cases (23) were observed in middle-aged and elderly women with a history of trauma, with a higher incidence during winter and spring. All clinical isolates were identified as Sporothrix globosa (S. globosa). The G. mellonella larvae infection model indicated independent and dose-dependent virulence among strains, with varying toxicity levels demonstrated by the degree of melanization of the G. mellonella. Surprisingly, lymphocutaneous types caused by S. globosa exhibited lower invitro virulence but were more common in affected skin. In addition, all S.globosa strains displayed high resistances to fluconazole, while remaining highly susceptible to terbinafine, itraconazole and amphotericin B. Given the predominance of elderly women engaged in agricultural labour in our region, which is a low-epidemic areas, they should be considered as crucial targets for sporotrichosis monitoring. S. globosa appears to be the sole causative agent locally. However, varying degrees of melanization in larvae were observed among these isolates, indicating a divergence in their virulence. Itraconazole, terbinafine and amphotericin B remain viable first-line antifungal options for treating S.globosa infection.

Diagnostic tests for human Schistosoma mansoni and Schistosoma haematobium infection: a systematic review and meta-analysis

Accurate diagnosis is pivotal for implementing strategies for surveillance, control, and elimination of schistosomiasis. Despite their low sensitivity in low-endemicity areas, microscopy-based urine filtration and the Kato-Katz technique are considered as reference diagnostic tests for Schistosoma haematobium and Schistosoma mansoni infections, respectively. We aimed to collate all available evidence on the accuracy of other proposed diagnostic techniques. In this systematic review and meta-analysis, we searched PubMed, Embase, the Cochrane Library, and LILACS for studies published from database inception to Dec 31, 2022, investigating the sensitivity and specificity of diagnostic tests for S haematobium and S mansoni infections against Kato-Katz thick smears or urine microscopy (reference tests) involving adults (aged ≥18 years), school-aged children (aged 7 to 18 years), or preschool-aged children (aged 1 month to 7 years). We extracted raw data on true positives, true negatives, false positives, and false negatives for the diagnostic tests and data on the number of participants, study authors, publication year, journal, study design, participants' age and sex, prevalence of Schistosoma infection, and treatment status. To account for imperfect reference tests, we used a hierarchical Bayesian latent class meta-analysis to model test accuracy. Overall, we included 121 studies, assessing 28 different diagnostic techniques. Most studies (103 [85%] of 121) were done in Africa, 14 (12%) in South America, one (1%) in Asia, and one (1%) in an unknown country. Compared with the reference test, Kato-Katz thick smears, circulating cathodic antigen urine cassette assay version 1 (CCA1, 36 test comparisons) had excellent sensitivity (95% [95% credible interval 88-99]) and reasonable specificity (74% [63-83]) for S mansoni. ELISA-based tests had a performance comparable to circulating cathodic antigen, but there were few available test comparisons. For S haematobium, proteinuria (42 test comparisons, sensitivity 73% [62-82]; specificity 94% [89-98]) and haematuria (75 test comparisons, sensitivity 85% [80-90]; specificity 96% [92-99]) reagent strips showed high specificity, with haematuria reagent strips having better sensitivity. Despite limited data, nucleic acid amplification tests (NAATs; eg, PCR or loop-mediated isothermal amplification [LAMP]) showed promising results with sensitivity estimates above 90%. We found an unclear risk of bias of about 70% in the use of the reference or index tests and of 50% in patient selection. All analyses showed substantial heterogeneity (I2>80%). Although NAATs and immunological diagnostics show promise, the limited information available precludes drawing definitive conclusions. Additional research on diagnostic accuracy and cost-effectiveness is needed before the replacement of conventional tests can be considered. WHO and Luxembourg Institute of Health.

Accuracy of commercial ELISA and ICT for screening schistosomiasis infections at a low endemicity area in Brazil.

Control interventions recommended by the World Health Organization have successfully resulted in low-intensity schistosomiasis transmission areas. To achieve elimination of transmission, new diagnostic screening tools are needed to overcome less than adequate sensitivity of the currently used Kato-Katz faecal thick smear method. Ideally, in-house serological tests should be avoided due to not having a continuous supply of kits as would be necessary for large population studies. Quality assurance provided by manufacturers and proper performance evaluations are also needed. We evaluated the accuracy of two commercially available serology tests as screening methods for detecting light schistosomiasis infections. Serum samples were collected in 2015 from individuals living in a low-endemicity locality in northeastern Brazil and deposited in a biorepository. We evaluated immunoglobulin G (IgG) and IgM enzyme-linked immunosorbent assays (ELISAs) and an immunochromatographic test (ICT). The Helmintex method was used to define true-positive samples. Overall sensitivity was close to 90% for both the IgG ELISA and ICT, yet specificity was 28% and 18%, respectively. For the IgM ELISA, the values were estimated to be 55% and 43%, respectively. Poor specificity and positive predictive values prevent these tests from being recommended for screening populations in low-intensity schistosomiasis-endemic areas.