RSS news feeds

Error message

  • Warning: date_timezone_set() expects parameter 1 to be DateTime, boolean given in format_date() (line 2041 of /home/bizmesol/public_html/prod/drupal-7/includes/common.inc).
  • Warning: date_format() expects parameter 1 to be DateTime, boolean given in format_date() (line 2051 of /home/bizmesol/public_html/prod/drupal-7/includes/common.inc).

Amino acids serve as an important energy source for adult flukes of <i>Clonorchis sinensis</i>

PLoS Neglected Tropical Diseases News - 30 April 2020 - 9:00pm

by Shan Li, Xueqing Chen, Juanjuan Zhou, Zhizhi Xie, Mei Shang, Lei He, Pei Liang, Tingjin Chen, Qiang Mao, Chi Liang, Xuerong Li, Yan Huang, Xinbing Yu

Clonorchiasis, caused by chronic infection with Clonorchis sinensis (C. sinensis), is an important food-borne parasitic disease that seriously afflicts more than 35 million people globally, resulting in a socioeconomic burden in endemic regions. C. sinensis adults long-term inhabit the microaerobic and limited-glucose environment of the bile ducts. Energy metabolism plays a key role in facilitating the adaptation of adult flukes to crowded habitat and hostile environment. To understand energy source for adult flukes, we compared the component and content of free amino acids between C. sinensis-infected and uninfected bile. The results showed that the concentrations of free amino acids, including aspartic acid, serine, glycine, alanine, histidine, asparagine, threonine, lysine, hydroxylysine, and urea, were significantly higher in C. sinensis-infected bile than those in uninfected bile. Furthermore, exogenous amino acids could be utilized by adult flukes via the gluconeogenesis pathway regardless of the absence or presence of exogenous glucose, and the rate-limiting enzymes, such as C. sinensis glucose-6-phosphatase, fructose-1,6-bisphosphatase, phosphoenolpyruvate carboxykinase, and pyruvate carboxylase, exhibited high expression levels by quantitative real-time PCR analysis. Interestingly, no matter whether exogenous glucose was present, inhibition of gluconeogenesis reduced the glucose and glycogen levels as well as the viability and survival time of adult flukes. These results suggest that gluconeogenesis might play a vital role in energy metabolism of C. sinensis and exogenous amino acids probably serve as an important energy source that benefits the continued survival of adult flukes in the host. Our study will be a cornerstone for illuminating the biological characteristics of C. sinensis and the host-parasite interactions.

A prospective study of bloodstream infections among febrile adolescents and adults attending Yangon General Hospital, Yangon, Myanmar

PLoS Neglected Tropical Diseases News - 30 April 2020 - 9:00pm

by Tin Ohn Myat, Khine Mar Oo, Hla Kye Mone, Wah Win Htike, Ambarish Biswas, Rachel F. Hannaway, David R. Murdoch, James E. Ussher, John A. Crump

Data on causes of community-onset bloodstream infection in Myanmar are scarce. We aimed to identify etiological agents of bloodstream infections and patterns of antimicrobial resistance among febrile adolescents and adults attending Yangon General Hospital (YGH), Yangon, Myanmar. We recruited patients ≥12 years old with fever >38°C who attended YGH from 5 October 2015 through 4 October 2016. A standardized clinical history and physical examination was performed. Provisional diagnoses and vital status at discharge was recorded. Blood was collected for culture, bloodstream isolates were identified, and antimicrobial susceptibility testing was performed. Using whole-genome sequencing, we identified antimicrobial resistance mechanisms of Enterobacteriaceae and sequence types of Enterobacteriaceae and Streptococcus agalactiae. Among 947 participants, 90 (9.5%) had bloodstream infections (BSI) of which 82 (91.1%) were of community-onset. Of 91 pathogens isolated from 90 positive blood cultures, we identified 43 (47.3%) Salmonella enterica including 33 (36.3%) serovar Typhi and 10 (11.0%) serovar Paratyphi A; 20 (22.0%) Escherichia coli; 7 (7.7%) Klebsiella pneumoniae; 6 (6.6%), Staphylococcus aureus; 4 (4.4%) yeasts; and 1 (1.1%) each of Burkholderia pseudomallei and Streptococcus agalactiae. Of 70 Enterobacteriaceae, 62 (88.6%) were fluoroquinolone-resistant. Among 27 E. coli and K. pneumoniae, 18 (66.6%) were extended-spectrum beta-lactamase (ESBL)-producers, and 1 (3.7%) each were AmpC beta-lactamase- and carbapenemase-producers. Fluoroquinolone resistance was associated predominantly with mutations in the quinolone resistance-determining region. blaCTX-M-15 expression was common among ESBL-producers. Methicillin-resistant S. aureus was not detected. Fluoroquinolone-resistant, but not multiple drug-resistant, typhoidal S. enterica was the leading cause of community-onset BSI at a tertiary hospital in Yangon, Myanmar. Fluoroquinolone and extended-spectrum cephalosporin resistance was common among other Enterobactericeae. Our findings inform empiric management of severe febrile illness in Yangon and indicate that measures to prevent and control enteric fever are warranted. We suggest ongoing monitoring and efforts to mitigate antimicrobial resistance among community-onset pathogens.

Familial assimilation in transmission of raw-freshwater fish-eating practice leading to clonorchiasis

PLoS Neglected Tropical Diseases News - 30 April 2020 - 9:00pm

by Men-Bao Qian, Zhi-Hua Jiang, Chang-Hai Zhou, Tao Ge, Xin Wang, Xiao-Nong Zhou

Clonorchiasis is caused by raw-freshwater fish-eating practice and causes high burden in Asia. Transmission mechanism of this behavior hasn’t been illuminated, which hinders the adoption of sustainable control activities. A cross-sectional survey was implemented in students from four endemic provinces in China. Data with 23,222 students aged 9–18 and their parents were eligible. Familial clustering of raw-eating practice, impact of parents’ practice on children, interaction of spouses’ practice was analyzed. Raw-eating practice met β-binomial distribution (χ2 = 0.8, p>0.05). Clustering coefficient increased by students’ age (R2 = 0.82, p<0.001) and was higher in those families with boys compared to girls (t = 4.1, p<0.01). The proportion of students with raw-eating practice increased yearly by 8.9% in girls and 10.5% in boys. Compared to those without parents’ raw-eating practice, adjusted odds ratio of students’ raw-eating practice was 10.5 (95% confidential intervals (95% CI): 9.4–11.7) in those with fathers’ practice, 33.6 (95% CI: 26.3–42.9) in those with mothers’ practice and 47.1 (95% CI: 42.0–52.8) in those with both parents’ practice. There exists interaction between spouses’ practice (χ2 = 6713.1, p<0.001) and the impact from husband on his wife was higher than that from wife on her husband. Familial assimilation characterizes the transmission of raw-freshwater fish-eating practice, consisted of vertical intergenerational assimilation from parents to their children and horizontal martial assimilation between spouses. A sustainable strategy against clonorchiasis should interrupt the transmission of raw-freshwater fish-eating practice. Additionally, further studies are expected to explore more information, e.g. the frequency in raw-eating practice and type of raw freshwater fish, infection status of C. sinensis in participants, as well as direct collection of parents’ eating information from themselves.

Investigating barriers and challenges to the integrated management of neglected tropical skin diseases in an endemic setting in Nigeria

PLoS Neglected Tropical Diseases News - 30 April 2020 - 9:00pm

by Kingsley N. Ukwaja, Chukwuka Alphonsus, Chinwe C. Eze, Linda Lehman, Ngozi Ekeke, Charles C. Nwafor, Joy Ikebudu, Moses C. Anyim, Joseph N. Chukwu

Background

There is a dearth of experience in and evidence for cost-effective integrated community-based management of skin neglected tropical diseases (NTDs). The objective of this study was to assess the knowledge, attitude and care-seeking practices including self-care with a view to introducing appropriate community-based interventions for skin NTDs in an endemic setting in Southern Nigeria.

Methods/Principal findings

This exploratory study adopted a mixed-methods design consisting of cross-sectional surveys of community members and health workers using interviewer-administered questionnaires; and focus group discussions (FGDs) with community members, health care workers and patients with NTDs in Anambra State, Nigeria. The survey was completed by 353 community members (61.8% female) and 15 health care workers (100.0% female). A total of 52 individuals participated in six FGDs. Of the community members, 236 (66.9%) had heard or seen a case of leprosy; 324 (91.8%) and 131 (37.5%) had heard or seen a case of Buruli ulcer and lymphatic filariasis, respectively. Again, 213 (60.3%) of the respondents reported that the diseases were caused by witchcraft or curse. As regards prevention, 241 (68.3%) suggested avoiding handshake with affected persons. Up to 223 (63.2%) of respondents strongly agreed to the seriousness of skin NTDs in their community. Meanwhile, 272 (77.1%) of the respondents believed that the transmission of these skin NTDs can be prevented. Furthermore, 324 (91.7%) desired active community engagement for control of skin NTDs. Regarding community care seeking practices, 197 (55.8%) would first visit the health centre/hospital, followed by 91 (25.8%) traditional healer/herbalist and 35 (9.9%) pharmacy/patent medicine vendor if they develop a skin NTD. Overall, 332 (94.1%) of respondents expressed interest in being taught self-care practices for skin NTDs. Out of 15 healthcare workers, 13 (86.7%) were able to correctly diagnose two of these skin NTDs and 10 (66.7%) would encourage patients to practice self-care. Prominent themes in the FGDs were belief in witchcraft and herbal remedies; as well as the occurrence of physical, social and economic distress.

Conclusions

Our study helped quantify the information gaps that need to be addressed in order to create demand for integrated skin NTDs services in an endemic setting in Nigeria. Individual, structural and socioeconomic challenges to access and delivery of services were identified. Community and health care workers’ empowerment and engagement through outreach and regular training, respectively may alleviate these challenges.

Host genetic susceptibility to mycetoma

PLoS Neglected Tropical Diseases News - 30 April 2020 - 9:00pm

by Rayan S. Ali, Melanie J. Newport, Sahar Mubarak Bakhiet, Muntaser E. Ibrahim, Ahmed Hassan Fahal

Mycetoma is one of the badly neglected tropical diseases, characterised by subcutaneous painless swelling, multiple sinuses, and discharge containing aggregates of the infecting organism known as grains. Risk factors conferring susceptibility to mycetoma include environmental factors and pathogen factors such as virulence and the infecting dose, in addition to host factors such as immunological and genetic predisposition. Epidemiological evidence suggests that host genetic factors may regulate susceptibility to mycetoma and other fungal infections, but they are likely to be complex genetic traits in which multiple genes interact with each other and environmental factors, as well as the pathogen, to cause disease. This paper reviews what is known about genetic predisposition to fungal infections that might be relevant to mycetoma, as well as all studies carried out to explore host genetic susceptibility to mycetoma. Most studies were investigating polymorphisms in candidate genes related to the host immune response. A total of 13 genes had allelic variants found to be associated with mycetoma, and these genes lie in different pathways and systems such as innate and adaptive immune systems, sex hormone biosynthesis, and some genes coding for host enzymes. None of these studies have been replicated. Advances in genomic science and the supporting technology have paved the way for large-scale genome-wide association and next generation sequencing (NGS) studies, underpinning a new strategy to systematically interrogate the genome for variants associated with mycetoma. Dissecting the contribution of host genetic variation to susceptibility to mycetoma will enable the identification of pathways that are potential targets for new treatments for mycetoma and will also enhance the ability to stratify ‘at-risk’ individuals, allowing the possibility of developing preventive and personalised clinical care strategies in the future.

Mycetoma in Uganda: A neglected tropical disease

PLoS Neglected Tropical Diseases News - 29 April 2020 - 9:00pm

by Richard Kwizera, Felix Bongomin, David B. Meya, David W. Denning, Ahmed H. Fahal, Robert Lukande

Mycetoma is considered a neglected tropical disease globally. However, data on its burden and the associated complications in Uganda are limited. Hence we aimed to estimate its burden in Uganda. Firstly, a systematic PubMed search for all studies of any design on mycetoma in Uganda without restriction to the year of publication was conducted. A retrospective review of all the biopsy reports at the Pathology Reference Laboratory, Department of Pathology, Makerere University, Kampala, Uganda from January 1950 to September 2019 was conducted to identify any reports on mycetoma histological diagnosis. During the 70-years study period, 30 cases were identified by the literature review, with 249 additional cases identified by review of biopsy reports (total of 279 cases). The average incidence was estimated at 0.32/100,000 persons and prevalence of 8.32/100,000 persons per decade. However, there was a general decline in the number of cases detected recently. Males and the age group of 21–30 years were the most affected by mycetoma in Uganda, and only 7% of the cases were children. The highest number of cases was recorded from Kampala (n = 30) and Jinja (n = 19) districts. The majority of the cases (68%) were referred from surgical units. The foot was the most affected part of the body (72%). Ten per cent of the cases had bone involvement of which 58% required amputation. Fungi were the most common causative agents (89%) followed by Nocardia species (5%) and Actinomycetes (4%). The index of clinical suspicion of mycetoma was low (45%) with a very large differential diagnosis. Mycetoma is a relatively rare disease in Uganda, mostly caused by fungi, and there is a big gap in data and epidemiological studies. More systematic studies are warranted to define the true burden of mycetoma in Uganda.

New estimates of the Zika virus epidemic attack rate in Northeastern Brazil from 2015 to 2016: A modelling analysis based on Guillain-Barré Syndrome (GBS) surveillance data

PLoS Neglected Tropical Diseases News - 29 April 2020 - 9:00pm

by Daihai He, Shi Zhao, Qianying Lin, Salihu S. Musa, Lewi Stone

Background

Between January 2015 and August 2016, two epidemic waves of Zika virus (ZIKV) disease swept the Northeastern (NE) region of Brazil. As a result, two waves of Guillain-Barré Syndrome (GBS) were observed concurrently. The mandatory reporting of ZIKV disease began region-wide in February 2016, and it is believed that ZIKV cases were significantly under-reported before that. The changing reporting rate has made it difficult to estimate the ZIKV infection attack rate, and studies in the literature vary widely from 17% to > 50%. The same applies to other key epidemiological parameters. In contrast, the diagnosis and reporting of GBS cases were reasonably reliable given the severity and easy recognition of the disease symptoms. In this paper, we aim to estimate the real number of ZIKV cases (i.e., the infection attack rate) and their dynamics in time, by scaling up from GBS surveillance data in NE Brazil.

Methodology

A mathematical compartmental model is constructed that makes it possible to infer the true epidemic dynamics of ZIKV cases based on surveillance data of excess GBS cases. The model includes the possibility that asymptomatic ZIKV cases are infectious. The model is fitted to the GBS surveillance data and the key epidemiological parameters are inferred by using a plug-and-play likelihood-based estimation. We make use of regional weather data to determine possible climate-driven impacts on the reproductive number R 0, and to infer the true ZIKV epidemic dynamics.

Findings and conclusions

The GBS surveillance data can be used to study ZIKV epidemics and may be appropriate when ZIKV reporting rates are not well understood. The overall infection attack rate (IAR) of ZIKV is estimated to be 24.1% (95% confidence interval: 17.1%—29.3%) of the population. By examining various asymptomatic scenarios, the IAR is likely to be lower than 33% over the two ZIKV waves. The risk rate from symptomatic ZIKV infection to develop GBS was estimated as ρ = 0.0061% (95% CI: 0.0050%—0.0086%) which is significantly less than current estimates. We found a positive association between local temperature and the basic reproduction number, R 0. Our analysis revealed that asymptomatic infections affect the estimation of ZIKV epidemics and need to also be carefully considered in related modelling studies. According to the estimated effective reproduction number and population wide susceptibility, we comment that a ZIKV outbreak would be unlikely in NE Brazil in the near future.

Reservoirs and transmission routes of leprosy; A systematic review

PLoS Neglected Tropical Diseases News - 27 April 2020 - 9:00pm

by Thomas Ploemacher, William R. Faber, Henk Menke, Victor Rutten, Toine Pieters

Leprosy is a chronic infectious disease caused by Mycobacterium leprae (M. leprae) and the more recently discovered Mycobacterium lepromatosis (M. lepromatosis). The two leprosy bacilli cause similar pathologic conditions. They primarily target the skin and the peripheral nervous system. Currently it is considered a Neglected Tropical Disease, being endemic in specific locations within countries of the Americas, Asia, and Africa, while in Europe it is only rarely reported. The reason for a spatial inequality in the prevalence of leprosy in so-called endemic pockets within a country is still largely unexplained. A systematic review was conducted targeting leprosy transmission research data, using PubMed and Scopus as sources. Publications between January 1, 1945 and July 1, 2019 were included. The transmission pathways of M. leprae are not fully understood. Solid evidence exists of an increased risk for individuals living in close contact with leprosy patients, most likely through infectious aerosols, created by coughing and sneezing, but possibly also through direct contact. However, this systematic review underscores that human-to-human transmission is not the only way leprosy can be acquired. The transmission of this disease is probably much more complicated than was thought before. In the Americas, the nine-banded armadillo (Dasypus novemcinctus) has been established as another natural host and reservoir of M. leprae. Anthroponotic and zoonotic transmission have both been proposed as modes of contracting the disease, based on data showing identical M. leprae strains shared between humans and armadillos. More recently, in red squirrels (Sciurus vulgaris) with leprosy-like lesions in the British Isles M. leprae and M. lepromatosis DNA was detected. This finding was unexpected, because leprosy is considered a disease of humans (with the exception of the armadillo), and because it was thought that leprosy (and M. leprae) had disappeared from the United Kingdom. Furthermore, animals can be affected by other leprosy-like diseases, caused by pathogens phylogenetically closely related to M. leprae. These mycobacteria have been proposed to be grouped as a M. leprae-complex. We argue that insights from the transmission and reservoirs of members of the M. leprae-complex might be relevant for leprosy research. A better understanding of possible animal or environmental reservoirs is needed, because transmission from such reservoirs may partly explain the steady global incidence of leprosy despite effective and widespread multidrug therapy. A reduction in transmission cannot be expected to be accomplished by actions or interventions from the human healthcare domain alone, as the mechanisms involved are complex. Therefore, to increase our understanding of the intricate picture of leprosy transmission, we propose a One Health transdisciplinary research approach.

Molecular characterization of a <i>Trichinella spiralis</i> aspartic protease and its facilitation role in larval invasion of host intestinal epithelial cells

PLoS Neglected Tropical Diseases News - 27 April 2020 - 9:00pm

by Jia Xu, Ruo Dan Liu, Sheng Jie Bai, Hui Nan Hao, Wen Wen Yue, Yang Xiu Yue Xu, Shao Rong Long, Jing Cui, Zhong Quan Wang

Background

T. spiralis aspartic protease has been identified in excretion/secretion (ES) proteins, but its roles in larval invasion are unclear. The aim of this study was to characterize T. spiralis aspartic protease-2 (TsASP2) and assess its roles in T. spiralis invasion into intestinal epithelial cells (IECs) using RNAi.

Methodology/Principal findings

Recombinant TsASP2 (rTsASP2) was expressed and purified. The native TsASP2 of 43 kDa was recognized by anti-rTsASP2 serum in all worm stages except newborn larvae (NBL), and qPCR indicated that TsASP2 transcription was highest at the stage of intestinal infective larvae (IIL). IFA results confirmed that TsASP2 was located in the hindgut, midgut and muscle cells of muscle larvae (ML) and IIL and intrauterine embryos of the female adult worm (AW), but not in NBL. rTsASP2 cleaved several host proteins (human hemoglobin (Hb), mouse Hb, collagen and IgM). The proteolytic activity of rTsASP2 was host-specific, as it hydrolyzed mouse Hb more efficiently than human Hb. The enzymatic activity of rTsASP2 was significantly inhibited by pepstatin A. The expression levels of TsASP2 mRNA and protein were significantly suppressed by RNAi with 5 μM TsASP2-specific siRNA. Native aspartic protease activity in ML crude proteins was reduced to 54.82% after transfection with siRNA. Larval invasion of IECs was promoted by rTsASP2 and inhibited by anti-rTsASP2 serum and siRNA. Furthermore, cell monolayer damage due to larval invasion was obviously alleviated when siRNA-treated larvae were used. The adult worm burden, length of adult worms and female fecundity were clearly reduced in mice challenged using siRNA-treated ML relative to the PBS group,

Conclusions

rTsASP2 possesses the enzymatic activity of native aspartic protease and facilitates T. spiralis invasion of host IECs.

Guillain-Barré syndrome related to Zika virus infection: A systematic review and meta-analysis of the clinical and electrophysiological phenotype

PLoS Neglected Tropical Diseases News - 27 April 2020 - 9:00pm

by Sonja E. Leonhard, Cristiane C. Bresani-Salvi, Joanna D. Lyra Batista, Sergio Cunha, Bart C. Jacobs, Maria Lucia Brito Ferreira, Maria de Fatima P. Militão de Albuquerque

Background

The Zika virus (ZIKV) has been associated with Guillain-Barré syndrome (GBS) in epidemiological studies. Whether ZIKV-associated GBS is related to a specific clinical or electrophysiological phenotype has not been established. To this end, we performed a systematic review and meta-analysis of all published studies on ZIKV-related GBS.

Methods

We searched Pubmed, EMBASE and LILACS, and included all papers, reports or bulletins with full text in English, Spanish or Portuguese, reporting original data of patients with GBS and a suspected, probable or confirmed recent ZIKV infection. Data were extracted according to a predefined protocol, and pooled proportions were calculated.

Results

Thirty-five studies were included (13 single case reports and 22 case series, case-control or cohort studies), reporting on a total of 601 GBS patients with a suspected, probable or confirmed ZIKV infection. Data from 21 studies and 587 cases were available to be summarized. ZIKV infection was confirmed in 21%, probable in 22% and suspected in 57% of cases. ZIKV PCR was positive in 30% (95%CI 15–47) of tested patients. The most common clinical features were: limb weakness 97% (95%CI 93–99), diminished/absent reflexes 96% (95%CI 88–100), sensory symptoms 82% (95%CI 76–88), and facial palsy 51% (95%CI 44–58). Median time between infectious and neurological symptoms was 5–12 days. Most cases had a demyelinating electrophysiological subtype and half of cases were admitted to the Intensive Care Unit (ICU). Heterogeneity between studies was moderate to substantial for most variables.

Conclusions

The clinical phenotype of GBS associated with ZIKV infection reported in literature is generally a sensorimotor demyelinating GBS with frequent facial palsy and a severe disease course often necessitating ICU admittance. Time between infectious and neurological symptoms and negative PCR in most cases suggests a post-infectious disease mechanism. Heterogeneity between studies was considerable and results may be subject to reporting bias. This study was registered on the international Prospective Register of Systematic Reviews (CRD42018081959).

Assessing expanded community wide treatment for schistosomiasis: Baseline infection status and self-reported risk factors in three communities from the Greater Accra region, Ghana

PLoS Neglected Tropical Diseases News - 27 April 2020 - 9:00pm

by Lucas J. Cunningham, Suzy J. Campbell, Samuel Armoo, Artemis Koukounari, Victoria Watson, Pamela Selormey, J. Russell Stothard, Bright Idun, Manfred Asiedu, Yvonne Ashong, Emily R. Adams, Mike Yaw Osei-Atweneboana

Background

This paper reports on the baseline prevalence and associated risk factor findings of a pilot, longitudinal study exploring community-wide treatment of schistosomiasis and soil-transmitted helminthiasis, using albendazole plus praziquantel in the Greater Accra region of Ghana.

Method

From three communities, at least, 658 individuals were enrolled into the study via random household selection. Prevalence and intensity of schistosomiasis and STH infection were determined from stool and urine samples with a questionnaire being administered in order to explore other morbidities and risk factors. Factor analysis of household demographic variables was undertaken to generate a socioeconomic score; this was then further categorised into tertiles. Proportional-odds cumulative logit generalised estimating equation (GEE) models were used to investigate categorical ordinal intensity of infection associations with morbidity. Separately, logistic GEE models were used to investigate risk factor associations with infection prevalence.

Results

Both Schistosoma haematobium and S. mansoni were prevalent in the three communities, with the prevalence of S. haematobium ranging from 3.3% (24/679; 95% CI = 1.9–4.7) to 19% (114/632; 95% CI = 15.8–22.2) and S. mansoni ranging from 30% (202/679; 95% CI = 26.5–33.5) to 78.3% (409/536; 95% CI = 74.7–81.9). The total prevalence of STH across all three sites was negligible at 1.3% (24/1847; 95% CI = 0.8–1.9) comprising mainly hookworm (10/1847). Multivariable statistical models indicated males to be 2.3 (95% CI = 1.7–3.3) times more likely to have a high intensity S. mansoni infection and 1.5 (95% CI = 1.1–2) times more likely to have a high intensity of S. haematobium infection compared to females. There was no significant difference in the likelihood of infection with S. mansoni between adults and school age children (SAC), however S. haematobium infections were found to be 2.5 (95% CI = 1.8–3.5) times more likely to occur in school age children than in adults.Multivariable statistical models (adjusted for age and sex) indicated an association between schistosomiasis and a number of self-reported morbidity indicators (notably diarrhoea and blood in stool and urine). Low socio-economic status was also associated with SCH infection (OR: 2; 95% CI = 1.3–3.2).

Conclusion

The communities targeted by this study showed a range of Schistosoma prevalence’s of infection, from hypo-endemic through to meso-endemic and hyper-endemic. The prevalence of SCH across the different age groups in the study locations highlights the large number of individuals currently being left out of the standard morbidity control method of annual treatment of the SAC.

Clinicopathological aspects and proviral load of adulthood infective dermatitis associated with HTLV-1: Comparison between juvenile and adulthood forms

PLoS Neglected Tropical Diseases News - 24 April 2020 - 9:00pm

by Lucca Santos Souza, Thadeu Santos Silva, Maria de Fátima Paim de Oliveira, Lourdes Farre, Achiléa Lisboa Bittencourt

Background

Infective dermatitis associated with human T-cell lymphotropic virus type-1 (HTLV-1), (IDH), is a chronic eczema occurring in HTLV-1 infected children. Rare cases of adulthood IDH have been reported and no study until now aimed to compare juvenile and adulthood IDH.

Methodology/Principal findings

Twelve cases of adulthood IDH followed for a mean time of 7.5 years were analyzed according to clinicopathological and molecular aspects, comparing them to juvenile IDH cases. Diagnosis was based on the modified major criteria used for juvenile IDH. Proviral load (PVL) assessment was performed by real-time PCR technique. Adulthood IDH presented similar clinicopathological and molecular aspects compared to juvenile IDH. The morphology of lesions and areas of involvement were similar, except for the involvement of the ankles and inframammary folds in the adulthood form. HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) occurred in six adulthood IDH patients, with almost equal frequency. However, at least in two patients, HAM/TSP appeared prior to IDH, differently from what was observed in juvenile IDH.

Conclusions/Significance

Adulthood IDH is similar to juvenile IDH according to clinicopathological aspects and PVL levels. Therefore, the same modified major diagnostic criteria for juvenile IDH can be applied to both forms.

Seroprevalence of leptospiral antibodies in rodents from riverside communities of Santa Fe, Argentina

PLoS Neglected Tropical Diseases News - 24 April 2020 - 9:00pm

by Tamara Ricardo, Paulina Jacob, Yosena Chiani, María Fernanda Schmeling, Paula Cornejo, Agustina Alejandra Ojeda, Pablo Vicente Teta, Norma Bibiana Vanasco, María Andrea Previtali

Background

Leptospirosis is a zoonotic disease that can be transmitted by contact with the urine of infected mammals. Rodents play a mayor role in the transmission of leptospires to humans. The province of Santa Fe reports the greatest number of cases in Argentina. Yet, in this region, there are still knowledge gaps regarding the diversity of rodent species that may be hosts of pathogenic leptospires. The aims of this study were to evaluate the presence of leptospiral antibodies in rodents from three riverside communities of Santa Fe, and to identify factors associated with leptospiral infection.

Methodology/Principal findings

Each community was divided into three environmental settings based on the level of human disturbance, and sampled during two springs (Sep-Oct 2014 and 2015) and one autumn (Mar-Apr 2015). Serum samples of captured sigmodontine and murine rodents were tested for leptospiral antibodies by enzyme-linked immunosorbent assay (ELISA), and microagglutination test (MAT) was used to assess the infecting serovar in seropositive individuals. Factors influencing seropositivity were analyzed using logistic regression models. We caught 119 rodents, of which 101 serums were suitable for analysis. Most frequently trapped species were Scapteromys aquaticus, Akodon azarae and Oligoryzomys spp., with seroprevalences of 41.3%, 42.9% and 55% respectively. Seropositivity was higher in individuals with an average body condition score and in those that were sexually mature, but in the latter the differences were marginally significant.

Conclusions/Significance

Our results suggest that native rodents may be playing a role in the environmental circulation of pathogenic leptospires and provide relevant information for public health policies in the area.

Comparison of multi-parallel qPCR and double-slide Kato-Katz for detection of soil-transmitted helminth infection among children in rural Bangladesh

PLoS Neglected Tropical Diseases News - 24 April 2020 - 9:00pm

by Jade Benjamin-Chung, Nils Pilotte, Ayse Ercumen, Jessica R. Grant, Jacqueline R. M. A. Maasch, Andrew M. Gonzalez, Ashanta C. Ester, Benjamin F. Arnold, Mahbubur Rahman, Rashidul Haque, Alan E. Hubbard, Stephen P. Luby, Steven A. Williams, John M. Colford Jr

There is growing interest in local elimination of soil-transmitted helminth (STH) infection in endemic settings. In such settings, highly sensitive diagnostics are needed to detect STH infection. We compared double-slide Kato-Katz, the most commonly used copromicroscopic detection method, to multi-parallel quantitative polymerase chain reaction (qPCR) in 2,799 stool samples from children aged 2–12 years in a setting in rural Bangladesh with predominantly low STH infection intensity. We estimated the sensitivity and specificity of each diagnostic using Bayesian latent class analysis. Compared to double-slide Kato-Katz, STH prevalence using qPCR was almost 3-fold higher for hookworm species and nearly 2-fold higher for Trichuris trichiura. Ascaris lumbricoides prevalence was lower using qPCR, and 26% of samples classified as A. lumbricoides positive by Kato-Katz were negative by qPCR. Amplicon sequencing of the 18S rDNA from 10 samples confirmed that A. lumbricoides was absent in samples classified as positive by Kato-Katz and negative by qPCR. The sensitivity of Kato-Katz was 49% for A. lumbricoides, 32% for hookworm, and 52% for T. trichiura; the sensitivity of qPCR was 79% for A. lumbricoides, 93% for hookworm, and 90% for T. trichiura. Specificity was ≥ 97% for both tests for all STH except for Kato-Katz for A. lumbricoides (specificity = 68%). There were moderate negative, monotonic correlations between qPCR cycle quantification values and eggs per gram quantified by Kato-Katz. While it is widely assumed that double-slide Kato-Katz has few false positives, our results indicate otherwise and highlight inherent limitations of the Kato-Katz technique. qPCR had higher sensitivity than Kato-Katz in this low intensity infection setting.

Role of asymptomatic and symptomatic humans as reservoirs of visceral leishmaniasis in a Mediterranean context

PLoS Neglected Tropical Diseases News - 23 April 2020 - 9:00pm

by Ricardo Molina, Maribel Jiménez, Jesús García-Martínez, Juan Víctor San Martín, Eugenia Carrillo, Carmen Sánchez, Javier Moreno, Fabiana Alves, Jorge Alvar

Background

In the Mediterranean basin, Leishmania infantum is the causative agent of visceral leishmaniasis (VL), a zoonosis in which the dog is the primary domestic reservoir, although wildlife may have a leading role in the sylvatic cycle of the disease in some areas. Infections without disease are very frequent. There is limited information regarding the role that VL patients and asymptomatic infected individuals could be playing in the transmission of L. infantum. Xenodiagnosis of leishmaniasis has been used in this descriptive study to explore the role of symptomatic and asymptomatic infected individuals as reservoirs in a recent focus of leishmaniasis in southwestern Madrid, Spain.

Methodology and main findings

Asymptomatic blood donors (n = 24), immunocompetent patients who were untreated (n = 12) or treated (n = 11) for visceral leishmaniasis (VL), and immunocompromised patients with VL (n = 3) were enrolled in the study. Their infectivity to Phlebotomus perniciosus was studied by indirect xenodiagnosis on peripheral blood samples. Quantitative polymerase chain reaction of blood samples from immunocompetent patients untreated for VL and immunocompromised untreated, treated and under secondary prophylaxis for VL was performed. Antibodies against Leishmania were studied by indirect fluorescent antibody and rK39-immunochromatographic tests. A lymphoproliferative assay with a soluble Leishmania antigen was used to screen for leishmaniasis infection in the healthy population. Sixty-two xenodiagnostic tests were carried out and 5,080 sand flies were dissected. Positive xenodiagnosis was recorded in four patients, with different sand fly infection rates: 1 immunosuppressed HIV / L. infantum coinfected asymptomatic patient, 1 immunosuppressed patient with multiple myeloma and symptomatic active VL, and 2 immunocompetent patients with untreated active VL. All blood donors were negative for both xenodiagnosis and conventional PCR.

Conclusions / Significance

There is no consensus amongst authors on the definition of an ‘asymptomatic case’ nor on the tools for screening; we, therefore, have adopted one for the sake of clarity. Immunocompetent subjects, both infected asymptomatics and those treated for VL, are limited in number and appear to have no epidemiological relevance. The impact is limited for immunocompetent patients with untreated active VL, whilst immunosuppressed individuals undergoing immunosuppressive therapy and immunosuppressed individuals HIV / L. infantum coinfected were the most infectious towards sand flies. It is noteworthy that the HIV / L. infantum coinfected patient with asymptomatic leishmaniasis was easily infectious to sand flies for a long time, despite being under continuous prophylaxis for leishmaniasis. Accordingly, screening for latent Leishmania infection in HIV-infected patients is recommended in scenarios where transmission occurs. In addition, screening for VL in HIV-infected patients who have spent time in VL-endemic areas should also be implemented in non-endemic areas. More research is needed to better understand if asymptomatic coinfected individuals contribute to transmission as ‘super-spreaders’.

Urine-based antigen detection assay for diagnosis of visceral leishmaniasis using monoclonal antibodies specific for six protein biomarkers of <i>Leishmania infantum / Leishmania donovani</i>

PLoS Neglected Tropical Diseases News - 23 April 2020 - 9:00pm

by Claudia Abeijon, Fabiana Alves, Séverine Monnerat, Jane Mbui, Agostinho G. Viana, Raquel M. Almeida, Lilian L. Bueno, Ricardo T. Fujiwara, Antonio Campos-Neto

The development of an accurate protein-based antigen detection assay for diagnosis of active visceral leishmaniasis (VL) would represent a major clinical advance. VL is a serious and fatal disease caused by the parasites Leishmania infantum and Leishmania donovani. The gold standard confirmatory diagnostic test for VL is the demonstration of parasites or their DNA from aspirates from spleen, lymph node, and bone marrow or from blood buffy coats (DNA tests). Here we describe the production and use of monoclonal antibodies (mAbs) for the development of a sensitive and specific antigen detection capture ELISA for VL diagnosis. This test simultaneously detects six leishmania protein biomarkers that we have previously described (Li-isd1, Li-txn1, Li-ntf2, Ld-mao1, Ld-ppi1 and Ld-mad1). The initial clinical validation of this new mAb-based multiplexed capture ELISA showed a sensitivity of ≥93%. The test was negative with 35 urine samples from healthy control subjects as well as with 30 patients with confirmed non-VL tropical diseases (cutaneous leishmaniasis, n = 6; Chagas disease, n = 6; schistosomiasis, n = 6; and tuberculosis, n = 12). These results strongly support the possible utility of this mAb-based multiplexed capture ELISA as a promising diagnostic test for active VL as well as for monitoring the treatment efficacy of this disease. The test is ready for upscaling and validation for clinical use.

<i>Helicobacter pylori</i> infection is associated with fecal biomarkers of environmental enteric dysfunction but not with the nutritional status of children living in Bangladesh

PLoS Neglected Tropical Diseases News - 23 April 2020 - 9:00pm

by Shah Mohammad Fahim, Subhasish Das, Md. Amran Gazi, Md. Ashraful Alam, Md. Mehedi Hasan, Md. Shabab Hossain, Mustafa Mahfuz, M Masudur Rahman, Rashidul Haque, Shafiqul Alam Sarker, Ramendra Nath Mazumder, Tahmeed Ahmed

Background

Because Helicobacter pylori (H. pylori) infection and Environmental Enteric Dysfunction (EED) follow a similar mode of transmission, there can be a complex interplay between H. pylori infection and EED, both of which can influence childhood growth. We sought to investigate the factors associated with H. pylori infection and identify its relationship with the fecal biomarkers of EED including Myeloperoxidase (MPO), Neopterin (NEO), Calprotectin, Reg1B and Alpha-1 antitrypsin (AAT), and nutritional status of the children.

Methodology

Data from an on-going community-based nutrition intervention study was used for this analysis. Total 319 children aged between 12–18 months were evaluated at enrolment and at the end of a 90-day nutrition intervention. Multivariable linear regression with generalized estimating equations was done to examine the association of H. pylori infection with stool biomarker of EED and nutritional status of the children.

Principal findings

One-fifth of the participants had H. pylori infection at both the time points, with 13.8% overall persistence. Children living in crowded households had higher odds of being infected by H. pylori (AOR = 2.02; 95% CI = 1.02, 4.10; p-value = 0.045). At enrolment, 60%, 99%, 69% and 85% of the stool samples were elevated compared to the reference values set for MPO, NEO, AAT and Calprotectin in the non-tropical western countries. The proportions reduced to 52%, 99%, 67%, and 77% for the same biomarkers after the nutrition intervention. Infection with H. pylori had significant positive association with fecal AAT concentrations (Coefficient = 0.26; 95% CI = 0.02, 0.49; p-value = 0.03) and inverse relationship with Reg1B concentrations measured in the stool samples (Coefficient = -0.32; 95% CI = -0.59, -0.05; p-value = 0.02). However, H. pylori infection was not associated with the indicators of childhood growth.

Conclusions

The study findings affirmed that the acquisition and persistence of H. pylori infection in the early years of life may exert an adverse impact on intestinal health, induce gut inflammation and result in increased intestinal permeability.

Study of Usutu virus neuropathogenicity in mice and human cellular models

PLoS Neglected Tropical Diseases News - 23 April 2020 - 9:00pm

by Marion Clé, Jonathan Barthelemy, Caroline Desmetz, Vincent Foulongne, Lina Lapeyre, Karine Bolloré, Edouard Tuaillon, Nejla Erkilic, Vasiliki Kalatzis, Sylvie Lecollinet, Cécile Beck, Nelly Pirot, Yaël Glasson, Fabien Gosselet, Maria Teresa Alvarez Martinez, Philippe Van de Perre, Sara Salinas, Yannick Simonin

Usutu virus (USUV), an African mosquito-borne flavivirus closely related to West Nile virus, was first isolated in South Africa in 1959. USUV emerged in Europe two decades ago, causing notably massive mortality in Eurasian blackbirds. USUV is attracting increasing attention due to its potential for emergence and its rapid spread in Europe in recent years. Although mainly asymptomatic or responsible for mild clinical signs, USUV was recently described as being associated with neurological disorders in humans such as encephalitis and meningoencephalitis, highlighting the potential health threat posed by the virus. Despite this, USUV pathogenesis remains largely unexplored. The aim of this study was to evaluate USUV neuropathogenicity using in vivo and in vitro approaches. Our results indicate that USUV efficiently replicates in the murine central nervous system. Replication in the spinal cord and brain is associated with recruitment of inflammatory cells and the release of inflammatory molecules as well as induction of antiviral-responses without major modulation of blood-brain barrier integrity. Endothelial cells integrity is also maintained in a human model of the blood-brain barrier despite USUV replication and release of pro-inflammatory cytokines. Furthermore, USUV-inoculated mice developed major ocular defects associated with inflammation. Moreover, USUV efficiently replicates in human retinal pigment epithelium. Our results will help to better characterize the physiopathology related to USUV infection in order to anticipate the potential threat of USUV emergence.

Target product profile for a test for the early assessment of treatment efficacy in Chagas disease patients: An expert consensus

PLoS Neglected Tropical Diseases News - 23 April 2020 - 9:00pm

by Julio Alonso-Padilla, Marcelo Abril, Belkisyolé Alarcón de Noya, Igor C. Almeida, Andrea Angheben, Tania Araujo Jorge, Eric Chatelain, Monica Esteva, Joaquim Gascón, Mario J. Grijalva, Felipe Guhl, Alejandro Marcel Hasslocher-Moreno, Manuel Carlos López, Alejandro Luquetti, Oscar Noya, María Jesús Pinazo, Janine M. Ramsey, Isabela Ribeiro, Andres Mariano Ruiz, Alejandro G. Schijman, Sergio Sosa-Estani, M. Carmen Thomas, Faustino Torrico, Maan Zrein, Albert Picado

Pages