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GSMN-ML- a genome scale metabolic network reconstruction of the obligate human pathogen <i>Mycobacterium leprae</i>

PLoS Neglected Tropical Diseases News - 6 July 2020 - 9:00pm

by Khushboo Borah, Jacque-Lucca Kearney, Ruma Banerjee, Pankaj Vats, Huihai Wu, Sonal Dahale, Sunitha Manjari Kasibhatla, Rajendra Joshi, Bhushan Bonde, Olabisi Ojo, Ramanuj Lahiri, Diana L. Williams, Johnjoe McFadden

Leprosy, caused by Mycobacterium leprae, has plagued humanity for thousands of years and continues to cause morbidity, disability and stigmatization in two to three million people today. Although effective treatment is available, the disease incidence has remained approximately constant for decades so new approaches, such as vaccine or new drugs, are urgently needed for control. Research is however hampered by the pathogen’s obligate intracellular lifestyle and the fact that it has never been grown in vitro. Consequently, despite the availability of its complete genome sequence, fundamental questions regarding the biology of the pathogen, such as its metabolism, remain largely unexplored. In order to explore the metabolism of the leprosy bacillus with a long-term aim of developing a medium to grow the pathogen in vitro, we reconstructed an in silico genome scale metabolic model of the bacillus, GSMN-ML. The model was used to explore the growth and biomass production capabilities of the pathogen with a range of nutrient sources, such as amino acids, glucose, glycerol and metabolic intermediates. We also used the model to analyze RNA-seq data from M. leprae grown in mouse foot pads, and performed Differential Producibility Analysis to identify metabolic pathways that appear to be active during intracellular growth of the pathogen, which included pathways for central carbon metabolism, co-factor, lipids, amino acids, nucleotides and cell wall synthesis. The GSMN-ML model is thereby a useful in silico tool that can be used to explore the metabolism of the leprosy bacillus, analyze functional genomic experimental data, generate predictions of nutrients required for growth of the bacillus in vitro and identify novel drug targets.

The potential impact of human visceral leishmaniasis vaccines on population incidence

PLoS Neglected Tropical Diseases News - 2 July 2020 - 9:00pm

by Epke A. Le Rutte, Luc E. Coffeng, Stefano Malvolti, Paul M. Kaye, Sake J. de Vlas

Human visceral leishmaniasis (VL) vaccines are currently under development and there is a need to understand their potential impact on population wide VL incidence. We implement four characteristics from different human VL vaccine candidates into two published VL transmission model variants to estimate the potential impact of these vaccine characteristics on population-wide anthroponotic VL incidence on the Indian subcontinent (ISC). The vaccines that are simulated in this study 1) reduce the infectiousness of infected individuals towards sand flies, 2) reduce risk of developing symptoms after infection, 3) reduce the risk of developing post-kala-azar dermal leishmaniasis (PKDL), or 4) lead to the development of transient immunity. We also compare and combine a vaccine strategy with current interventions to identify their potential role in elimination of VL as a public health problem. We show that the first two simulated vaccine characteristics can greatly reduce VL incidence. For these vaccines, an approximate 60% vaccine efficacy would lead to achieving the ISC elimination target (<1 VL case per 10,000 population per year) within 10 years’ time in a moderately endemic setting when vaccinating 100% of the population. Vaccinating VL cases to prevent the development of PKDL is a promising tool to sustain the low incidence elimination target after regular interventions are halted. Vaccines triggering the development of transient immunity protecting against infection lead to the biggest reduction in VL incidence, but booster doses are required to achieve perduring impact. Even though vaccines are not yet available for implementation, their development should be pursued as their potential impact on transmission can be substantial, both in decreasing incidence at the population level as well as in sustaining the ISC elimination target when other interventions are halted.

<i>Schistosoma haematobium</i> infection is associated with lower serum cholesterol levels and improved lipid profile in overweight/obese individuals

PLoS Neglected Tropical Diseases News - 2 July 2020 - 9:00pm

by Jeannot F. Zinsou, Jacqueline J. Janse, Josiane Y. Honpkehedji, Jean Claude Dejon-Agobé, Noemí García-Tardón, Pytsje T. Hoekstra, Marguerite Massinga-Loembe, Paul L. A. M. Corstjens, Govert J. van Dam, Martin Giera, Peter G. Kremsner, Maria Yazdanbakhsh, Ayola A. Adegnika, Bruno Guigas

Infection with parasitic helminths has been reported to improve insulin sensitivity and glucose homeostasis, lowering the risk for type 2 diabetes. However, little is known about its impact on whole-body lipid homeostasis, especially in obese individuals. For this purpose, a cross-sectional study was carried out in lean and overweight/obese adults residing in the Lambaréné region of Gabon, an area endemic for Schistosoma haematobium. Helminth infection status, peripheral blood immune cell counts, and serum metabolic and lipid/lipoprotein levels were analyzed. We found that urine S. haematobium egg-positive individuals exhibited lower serum total cholesterol (TC; 4.42 vs 4.01 mmol/L, adjusted mean difference [95%CI] -0.30 [-0.68,-0.06]; P = 0.109), high-density lipoprotein (HDL)-C (1.44 vs 1.12 mmol/L, -0.24 [-0.43,-0.06]; P = 0.009) and triglyceride (TG; 0.93 vs 0.72 mmol/L, -0.20 [-0.39,-0.03]; P = 0.022) levels than egg-negative individuals. However, when stratified according to body mass index, these effects were only observed in overweight/obese infected individuals. Similarly, significant negative correlations between the intensity of infection, assessed by serum circulating anodic antigen (CAA) concentrations, and TC (r = -0.555; P<0.001), HDL-C (r = -0.327; P = 0.068), LDL-C (r = -0.396; P = 0.025) and TG (r = -0.381; P = 0.032) levels were found in overweight/obese individuals but not in lean subjects. Quantitative lipidomic analysis showed that circulating levels of some lipid species associated with cholesterol-rich lipoprotein particles were also significantly reduced in overweight/obese infected individuals in an intensity-dependent manner. In conclusion, we reported that infection with S. haematobium is associated with improved lipid profile in overweight/obese individuals, a feature that might contribute reducing the risk of cardiometabolic diseases in such population.

<i>Anopheles sundaicus</i>  complex and the presence of <i>Anopheles epiroticus</i> in Indonesia

PLoS Neglected Tropical Diseases News - 2 July 2020 - 9:00pm

by Din Syafruddin, Yulia E. Lestari, Dendi H. Permana, Puji B. S. Asih, Brandyce St. Laurent, Siti Zubaidah, Ismail E. Rozi, Sully Kosasih, Shinta, Supratman Sukowati, Lukman Hakim, Edhi Haryanto, Wibowo Mangunwardoyo, Michael J. Bangs, Neil F. Lobo

Anopheles sundaicus s.l. is an important malaria vector primarily found in coastal landscapes of western and central Indonesia. The species complex has a wide geographical distribution in South and Southeast Asia and exhibits ecological and behavioural variability over its range. Studies on understanding the distribution of different members in the complex and their bionomics related to malaria transmission might be important guiding more effective vector intervention strategies. Female An. sundaicus s.l. were collected from seven provinces, 12 locations in Indonesia representing Sumatra: North Sumatra, Bangka-Belitung, South Lampung, and Bengkulu; in Java: West Java; and the Lesser Sunda Islands: West Nusa Tenggara and East Nusa Tenggara provinces. Sequencing of ribosomal DNA ITS2 gene fragments and two mitochondrial DNA gene markers, COI and cytb, enabled molecular identification of morphologically indistinguishable members of the complex. Findings allowed inference on the distribution of the An. sundaicus s.l. present in Indonesia and further illustrate the phylogenetic relationships of An. epiroticus within the complex. A total of 370 An. sundaicus s.l specimens were analysed for the ITS2 fragment. The ITS2 sequence alignment revealed two consistent species-specific point mutations, a T>C transition at base 479 and a G>T transversion at base 538 that differentiated five haplotypes: TG, CG, TT, CT, and TY. The TG haplotype matched published An. epiroticus–indicative sequences from Thailand, Vietnam and peninsular Malaysia. The previously described insertion event (base 603) was observed in all identified specimens. Analysis of the COI and cytb genes revealed no consistent nucleotide variations that could definitively distinguish An. epiroticus from other members in the Sundaicus Complex. The findings indicate and support the existence of An. epiroticus in North Sumatra and Bangka-Belitung archipelago. Further studies are recommended to determine the full distributional extent of the Sundaicus complex in Indonesia and investigate the role of these species in malaria transmission.

High genetic similarity between non-typhoidal <i>Salmonella</i> isolated from paired blood and stool samples of children in the Democratic Republic of the Congo

PLoS Neglected Tropical Diseases News - 2 July 2020 - 9:00pm

by Marie-France Phoba, Barbara Barbé, Benedikt Ley, Sandra Van Puyvelde, Annelies Post, Wesley Mattheus, Stijn Deborggraeve, Octavie Lunguya, Jan Jacobs

Background

Non-typhoidal Salmonella (NTS) serotypes Typhimurium and Enteritidis are a major cause of bloodstream infections in children in sub-Saharan Africa but their reservoir is unknown. We compared pairs of NTS blood and stool isolates (with the same NTS serotype recovered in the same patient) for genetic similarity.

Methods

Between November 2013 and April 2017, hospital-admitted children (29 days to 14 years) with culture-confirmed NTS bloodstream infections were enrolled in a cross-sectional study at Kisantu Hospital, DR Congo. Stool cultures for Salmonella were performed on a subset of enrolled children, as well as on a control group of non-febrile hospital-admitted children. Pairs of blood and stool NTS isolates were assessed for genetic similarity by multiple-locus variable-number of tandem repeats (MLVA) and genomics analysis.

Results

A total of 299 children with NTS grown from blood cultures (Typhimurium 68.6%, Enteritidis 30.4%, other NTS 1.0%) had a stool sample processed; in 105 (35.1%) of them NTS was detected (Typhimurium 70.5%, Enteritidis 25.7%, other NTS 3.8%). A total of 87/105 (82.9%) pairs of blood and stool NTS isolates were observed (representing 29.1% of the 299 children). Among 1598 controls, the proportion of NTS stool excretion was 2.1% (p < 0.0001). MLVA types among paired isolates were identical in 82/87 (94.3%) pairs (27.4% of the 299 children; 61/66 (92.4%) in Typhimurium and 21/21 (100%) in Enteritidis pairs). Genomics analysis confirmed high genetic similarity within 41/43 (95.3%) pairs, showing a median SNP difference of 1 (range 0–77) and 1 (range 0–4) for Typhimurium and Enteritidis pairs respectively. Typhimurium and Enteritidis isolates belonged to sequence types ST313 lineage II and ST11 respectively.

Conclusion

Nearly 30% of children with NTS bloodstream infection showed stool excretion of an NTS isolate with high genetic similarity, adding to the evidence of humans as a potential reservoir for NTS.

Identifying thresholds to classify moderate-to-heavy soil-transmitted helminth intensity infections for FECPAK<sup>G2</sup>, McMaster, Mini-FLOTAC and qPCR

PLoS Neglected Tropical Diseases News - 2 July 2020 - 9:00pm

by Bruno Levecke, Piet Cools, Marco Albonico, Shaali Ame, Cécile Angebault, Mio Ayana, Jerzy M. Behnke, Jeffrey M. Bethony, Giuseppe Cringoli, Daniel Dana, Bertrand Guillard, Nguyen Thi Viet Hoa, Gagandeep Kang, Deepthi Kattula, Jennifer Keiser, Andrew C. Kotze, Leonardo F. Matoso, Maria P. Maurelli, James S. McCarthy, Zeleke Mekonnen, Greg Mirams, Antonio Montresor, Rodrigo Corrêa Oliveira, Maria V. Periago, Simone A. Pinto, Laura Rinaldi, Somphou Sayasone, Laurentine Sumo, Louis-Albert Tchuem-Tchuenté, Dang Thi Cam Thach, Eurion Thomas, Ahmed Zeynudin, Jaco J. Verweij, Johnny Vlaminck, Jozef Vercruysse

World Health Organization (WHO) has defined moderate-to-heavy intensity (M&HI) infections with soil-transmitted helminths (Ascaris lumbricoides, Trichuris trichiura and the two hookworms, Ancylostoma duodenale and Necator americanus) based on specific values of eggs per gram of stool, as measured by the Kato-Katz method. There are a variety of novel microscopy and DNA-based methods but it remains unclear whether applying current WHO thresholds on to these methods allows for a reliable classification of M&HI infections. We evaluated both WHO and method-specific thresholds for classifying the M&HI infections for novel microscopic (FECPAKG2, McMaster and Mini-FLOTAC) and DNA-based (qPCR) diagnostic methods. For this, we determined method-specific thresholds that best classified M&HI infections (defined by Kato-Katz and WHO thresholds; reference method) in two multi-country drug efficacy studies. Subsequently, we verified whether applying these method-specific thresholds improved the agreement in classifying M&HI infections compared to the reference method. When we applied the WHO thresholds, the new microscopic methods mainly misclassified M&HI as low intensity, and to a lesser extent low intensity infection as M&HI. For FECPAKG2, applying the method-specific thresholds significantly improved the agreement for Ascaris (moderate → substantial), Trichuris and hookworms (fair → moderate). For Mini-FLOTAC, a significantly improved agreement was observed for hookworms only (fair → moderate). For the other STHs, the agreement was almost perfect and remained unchanged. For McMaster, the method-specific thresholds revealed a fair to a substantial agreement but did not significantly improve the agreement. For qPCR, the method-specific thresholds based on genome equivalents per ml of DNA moderately agreed with the reference method for hookworms and Trichuris infections. For Ascaris, there was a substantial agreement. We defined method-specific thresholds that improved the classification of M&HI infections. Validation studies are required before they can be recommended for general use in assessing M&HI infections in programmatic settings.

Volunteer based approach to dog vaccination campaigns to eliminate human rabies: Lessons from Laikipia County, Kenya

PLoS Neglected Tropical Diseases News - 2 July 2020 - 9:00pm

by Adam W. Ferguson, Dishon Muloi, Dedan K. Ngatia, Wangechi Kiongo, Duncan M. Kimuyu, Paul W. Webala, Moses O. Olum, Mathew Muturi, Samuel M. Thumbi, Rosie Woodroffe, Lucy Murugi, Eric M. Fèvre, Suzan Murray, Dino J. Martins

Background

An estimated 59,000 people die from rabies annually, with 99% of those deaths attributable to bites from domestic dogs (Canis lupus familiaris). This preventable Neglected Tropical Disease has a large impact across continental Africa, especially for rural populations living in close contact with livestock and wildlife. Mass vaccinations of domestic dogs are effective at eliminating rabies but require large amounts of resources, planning, and political will to implement. Grassroots campaigns provide an alternative method to successful implementation of rabies control but remain understudied in their effectiveness to eliminate the disease from larger regions.

Methodology/Principal Findings

We report on the development, implementation, and effectiveness of a grassroots mass dog rabies vaccination campaign in Kenya, the Laikipia Rabies Vaccination Campaign. During 2015–2017, a total of 13,155 domestic dogs were vaccinated against rabies in 17 communities covering approximately 1500 km2. Based on an estimated population size of 34,275 domestic dogs, percent coverages increased across years, from 2% in 2015 to 24% in 2017, with only 3 of 38 community-years of vaccination exceeding the 70% target. The average cost of vaccinating an animal was $3.44 USD with in-kind contributions and $7.44 USD without in-kind contributions.

Conclusions/Significance

The evolution of the Laikipia Rabies Vaccination Campaign from a localized volunteer-effort to a large-scale program attempting to eliminate rabies at the landscape scale provides a unique opportunity to examine successes, failures, and challenges facing grassroots campaigns. Success, in the form of vaccinating more dogs across the study area, was relatively straightforward to achieve. However, lack of effective post-vaccination monitoring and education programs, limited funding, and working in diverse community types appeared to hinder achievement of 70% coverage levels. These results indicate that grassroots campaigns will inevitably be faced with a philosophical question regarding the value of local impacts versus their contributions to a larger effort to eliminate rabies at the regional, country, or global scale.

Post kala-azar dermal leishmaniasis: A threat to elimination program

PLoS Neglected Tropical Diseases News - 2 July 2020 - 9:00pm

by Mallikarjuna Rao Gedda, Bhawana Singh, Dhiraj Kumar, Abhishek Kumar Singh, Prasoon Madhukar, Shreya Upadhyay, Om Prakash Singh, Shyam Sundar

Leishmaniasis remains a public health concern around the world that primarily affects poor folks of the developing world spanning across 98 countries with mortality of 0.2 million to 0.4 million annually. Post kala-azar dermal leishmaniasis (PKDL) is the late skin manifestation of visceral leishmaniasis (VL). It has been reported that about 2.5% to 20% of patients recovered from VL develop PKDL having stilted macular or nodular lesions with parasites. In the Indian subcontinent (ISC), it manifests a few months after recovery from VL, though in Africa it can occur simultaneously with VL or a little later. New cases of PKDL are also observed without prior VL in the ISC. These individuals with PKDL represent an important but largely neglected reservoir of infection that perpetuates anthroponotic Leishmania donovani transmission in the ISC and can jeopardize the VL elimination program as these cases can infect the sand flies and spread the endemic. Therefore, it becomes imperative to eradicate PKDL as a part of the VL elimination program. With the limited treatment options besides little knowledge on PKDL, this review stands out in focusing on different aspects that should be dealt for sustained VL elimination.

Future schistosome hybridizations: Will all <i>Schistosoma haematobium</i> hybrids please stand-up!

PLoS Neglected Tropical Diseases News - 2 July 2020 - 9:00pm

by J. Russell Stothard, Sekeleghe A. Kayuni, Mohammad H. Al-Harbi, Janelisa Musaya, Bonnie L. Webster

Knowledge, attitudes and bite prevention practices and estimation of productivity of vector breeding sites using a Habitat Suitability Score (HSS) among households with confirmed dengue in the 2014 outbreak in Dar es Salaam, Tanzania

PLoS Neglected Tropical Diseases News - 2 July 2020 - 9:00pm

by Daniel Msellemu, Tegemeo Gavana, Hassan Ngonyani, Yeromin P. Mlacha, Prosper Chaki, Sarah J. Moore

Background

The frequency and magnitude of dengue epidemics has increased dramatically throughout the tropics in the past 40 years due to unplanned urbanization, globalization and lack of effective mosquito control. The commercial capital of Tanzania, Dar es Salaam, is now experiencing regular dengue outbreaks. Three dengue serotypes have been detected in Dar es Salaam (DNV 1, 2 and 3). Without adequate vector monitoring and control, further outbreaks will certainly occur.

Methods/Findings

A case series study followed 97 individuals with confirmed dengue fever (NS1 and/or IgM on rapid diagnostic test and/or PCR positive) to their households in Kinondoni, Dar es Salaam during the 2014 outbreak from a random sample of 202 confirmed cases at Mwananyamala Hospital. Kinondoni wards of Manzese, Mwananyamala, Tandale and Mabibo had the highest number of confirmed cases: 18, 13, 13 and 9 respectively. Individuals were interviewed by questionnaire on dengue prevention practices and houses were inspected for mosquito breeding sites to validate a Habitat Suitability Score (HSS). This is a tool devised to predict the productivity of any potential breeding habitats (PBHs) before the rains begin.There were 12 /312 positive Aedes breeding habitats. Drums/barrels, flowerpots and tyres were the most common breeding habitats. The HSS correctly identified 9/12 of Aedes breeding habitats. Larviciding is already conducted in urban Tanzania for malaria control and the HSS may be a useful means to train individuals on productive Aedes aegypti breeding sites should this program be extended to include dengue control.The population remains poorly informed about dengue transmission and prevention: 22% of respondents said dengue is spread from one person to another and 60% first heard about dengue when already sick. Less than 20% of respondents used personal protection and >80% thought bednets protected against dengue. Mobile phones were owned by almost all individuals followed up and have the potential of being the prime medium for dissemination of information on dengue prevention.

Pharmacological inhibition of lysine-specific demethylase 1 (LSD1) induces global transcriptional deregulation and ultrastructural alterations that impair viability in <i>Schistosoma mansoni</i>

PLoS Neglected Tropical Diseases News - 1 July 2020 - 9:00pm

by Vitor Coutinho Carneiro, Isabel Caetano de Abreu da Silva, Murilo Sena Amaral, Adriana S. A. Pereira, Gilbert Oliveira Silveira, David da Silva Pires, Sergio Verjovski-Almeida, Frank J. Dekker, Dante Rotili, Antonello Mai, Eduardo José Lopes-Torres, Dina Robaa, Wolfgang Sippl, Raymond J. Pierce, M. Teresa Borrello, A. Ganesan, Julien Lancelot, Silvana Thiengo, Monica Ammon Fernandez, Amanda Roberta Revoredo Vicentino, Marina Moraes Mourão, Fernanda Sales Coelho, Marcelo Rosado Fantappié

Treatment and control of schistosomiasis still rely on only one effective drug, praziquantel (PZQ) and, due to mass treatment, the increasing risk of selecting for schistosome strains that are resistant to PZQ has alerted investigators to the urgent need to develop novel therapeutic strategies. The histone-modifying enzymes (HMEs) represent promising targets for the development of epigenetic drugs against Schistosoma mansoni. In the present study, we targeted the S. mansoni lysine-specific demethylase 1 (SmLSD1), a transcriptional corepressor, using a novel and selective synthetic inhibitor, MC3935, which was used to treat schistosomula and adult worms in vitro. By using cell viability assays and optical and electron microscopy, we showed that treatment with MC3935 affected parasite motility, egg-laying, tegument, and cellular organelle structures, culminating in the death of schistosomula and adult worms. In silico molecular modeling and docking analysis suggested that MC3935 binds to the catalytic pocket of SmLSD1. Western blot analysis revealed that MC3935 inhibited SmLSD1 demethylation activity of H3K4me1/2. Knockdown of SmLSD1 by RNAi recapitulated MC3935 phenotypes in adult worms. RNA-Seq analysis of MC3935-treated parasites revealed significant differences in gene expression related to critical biological processes. Collectively, our findings show that SmLSD1 is a promising drug target for the treatment of schistosomiasis and strongly support the further development and in vivo testing of selective schistosome LSD1 inhibitors.

Genome-wide mapping using new AFLP markers to explore intraspecific variation among pathogenic <i>Sporothrix</i> species

PLoS Neglected Tropical Diseases News - 1 July 2020 - 9:00pm

by Jamile Ambrósio de Carvalho, Ferry Hagen, Matthew C. Fisher, Zoilo Pires de Camargo, Anderson Messias Rodrigues

Sporotrichosis is a chronic subcutaneous mycosis caused by Sporothrix species, of which the main aetiological agents are S. brasiliensis, S. schenckii, and S. globosa. Infection occurs after a traumatic inoculation of Sporothrix propagules in mammals’ skin and can follow either a classic route through traumatic inoculation by plant debris (e.g., S. schenckii and S. globosa) or an alternative route through zoonotic transmission from animals (e.g., S. brasiliensis). Epizootics followed by a zoonotic route occur in Brazil, with Rio de Janeiro as the epicenter of a recent cat-transmitted epidemic. DNA-based markers are needed to explore the epidemiology of these Sporothrix expansions using molecular methods. This paper reports the use of amplified-fragment-length polymorphisms (AFLP) to assess the degree of intraspecific variability among Sporothrix species. We used whole-genome sequences from Sporothrix species to generate 2,304 virtual AFLP fingerprints. In silico screening highlighted 6 primer pair combinations to be tested in vitro. The protocol was used to genotype 27 medically relevant Sporothrix. Based on the overall scored AFLP markers (97–137 fragments), the values of polymorphism information content (PIC = 0.2552–0.3113), marker index (MI = 0.002–0.0039), effective multiplex ratio (E = 17.8519–35.2222), resolving power (Rp = 33.6296–63.1852), discriminating power (D = 0.9291–0.9662), expected heterozygosity (H = 0.3003–0.3857), and mean heterozygosity (Havp = 0.0001) demonstrated the utility of these primer combinations for discriminating Sporothrix. AFLP markers revealed cryptic diversity in species previously thought to be the most prevalent clonal type, such as S. brasiliensis, responsible for cat-transmitted sporotrichosis, and S. globosa responsible for large sapronosis outbreaks in Asia. Three combinations (#3 EcoRI-FAM-GA/MseI-TT, #5 EcoRI-FAM-GA/MseI-AG, and #6 EcoRI-FAM-TA/MseI-AA) provide the best diversity indices and lowest error rates. These methods make it easier to track routes of disease transmission during epizooties and zoonosis, and our DNA fingerprint assay can be further transferred between laboratories to give insights into the ecology and evolution of pathogenic Sporothrix species and to inform management and mitigation strategies to tackle the advance of sporotrichosis.

First identification of genotypes of <i>Enterocytozoon bieneusi</i> (Microsporidia) among symptomatic and asymptomatic children in Mozambique

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

by Aly S. Muadica, Augusto E. Messa Jr., Alejandro Dashti, Sooria Balasegaram, Mónica Santin, Filomena Manjate, Percina Chirinda, Marcelino Garrine, Delfino Vubil, Sozinho Acácio, Pamela C. Köster, Begoña Bailo, Tacilta Nhampossa, Rafael Calero-Bernal, Jason M. Mwenda, Inácio Mandomando, David Carmena

Enterocytozoon bieneusi is a human pathogen with a broad range of animal hosts. Initially, E. bieneusi was considered an emerging opportunistic pathogen in immunocompromised, mainly HIV-infected patients, but it has been increasingly reported in apparently healthy individuals globally. As in other African countries, the molecular epidemiology of E. bieneusi in Mozambique remains completely unknown. Therefore, we undertook a study to investigate the occurrence and genetic diversity of E. bieneusi infections in children with gastrointestinal symptoms as well as in asymptomatic children in Mozambique. Individual stool specimens were collected from 1,247 children aged between 0 and 14 years-old living in urban and rural settings in Zambézia (n = 1,097) and Maputo (n = 150) provinces between 2016 and 2019. Samples were analysed for E. bieneusi by nested-PCR targeting the internal transcribed spacer (ITS) region of the rRNA gene. All positive amplicons were confirmed and genotyped. Penalised logistic regression (Firth) was used to evaluate risk associations. The overall prevalence of E. bieneusi in this children population was 0.7% (9/1,247). A 10-fold higher prevalence was found in Maputo (4.0%; 6/150) than in Zambézia (0.3%; 3/1,097). All E. bieneusi-positive samples were from children older than 1-year of age, and most (8/9) from asymptomatic children. Nucleotide sequence analysis of the ITS region revealed the presence of four genotypes, three previously reported (Peru11, n = 1; Type IV, n = 2, and S2, n = 2) and a novel genotype (named HhMzEb1, n = 4). Novel genotype HhMzEb1 was identified in both asymptomatic (75%, 3/4) and symptomatic (25%, 1/4) children from a rural area in Maputo province in southern Mozambique. Genotypes HhMzEb1, Peru11, S2, and Type IV belonged to the Group 1 that includes genotypes with low host specificity and the potential for zoonotic and cross-species transmission. Being infected by enteric protozoan parasites and no handwashing were identified as risk associations for E. bieneusi infection. This study reports the first investigation of E. bieneusi genotypes in Mozambique with the identification of three previously reported genotypes in humans as well as a novel genotype (HhMzEb1). Findings highlight the need to conduct additional research to elucidate the epidemiology of E. bieneusi in the country, especially in rural areas where poor hygiene conditions still prevail. Special attention should be paid to the identification of suitable animal and environmental reservoirs of this parasite and to the characterization of transmission pathways.

Etiology of acute Gastroenteritis among children less than 5 years of age in Bucaramanga, Colombia: A case-control study

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

by Ana E. Farfán-García, Aamer Imdad, Chengxian Zhang, Mónica Y. Arias-Guerrero, Nayibe T. Sánchez-Álvarez, Junaid Iqbal, Adriana E. Hernández-Gamboa, James C. Slaughter, Oscar G. Gómez-Duarte

Background

Acute gastroenteritis (AGE) is a major cause of morbidity and mortality in children aged less than 5 years in low- and middle-income countries where limited access to potable water, poor sanitation, deficient hygiene, and food product contamination are prevalent. Research on the changing etiology of AGE and associated risk factors in Latin America, including Colombia, is essential to understand the epidemiology of these infections. The primary objectives of this study were to describe etiology of moderate to severe AGE in children less than 5 years of age from Bucaramanga, Colombia, a middle-income country in Latin American, and to identify the presence of emerging E. coli pathotypes.

Methodology/Principal findings

This was a prospective, matched for age, case-control study to assess the etiology of moderate to severe AGE in children less than 5 years of age in Bucaramanga, Colombia, South America. We tested for 24 pathogens using locally available diagnostic testing, including stool culture, polymerase chain reaction, microscopy and enzyme-linked immunoassay. Adjusted attributable fractions were calculated to assess the association between AGE and each pathogen in this study population. The study included 861 participants, 431 cases and 430 controls. Enteric pathogens were detected in 71% of cases and in 54% of controls (p = <0.001). Co-infection was identified in 28% of cases and in 14% of controls (p = <0.001). The adjusted attributable fraction showed that Norovirus GII explained 14% (95% CI: 10–18%) of AGE, followed by rotavirus 9.3% (6.4–12%), adenovirus 3% (1–4%), astrovirus 2.9% (0.6–5%), enterotoxigenic Escherichia coli (ETEC) 2.4% (0.4–4%), Cryptosporidium sp. 2% (0.5–4%), Campylobacter sp. 2% (0.2–4%), and Salmonella sp.1.9% (0.3 to 3.5%). Except for Cryptosporidium, all parasite infections were not associated with AGE. Three emergent diarrheagenic E. coli pathotypes were identified in cases (0.7%), including an enteroaggregative/enterotoxigenic E.coli (EAEC/ETEC), an enteroaggregative/enteropathogenic E.coli (EAEC/EPEC), and an emergent enteroinvasive E. coli with a rare O96:H19. No deaths were reported among cases or controls.

Conclusions/Significance

Norovirus and rotavirus explained the major proportion of moderate to severe AGE in this study. Higher proportion of infection in cases, in the form of single infections or co-infections, showed association with AGE. Three novel E. coli pathotypes were identified among cases in this geographic region.

Detection of arboviruses in mosquitoes: Evidence of circulation of chikungunya virus in Iran

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

by Hasan Bakhshi, Laurence Mousson, Sara Moutailler, Marie Vazeille, Géraldine Piorkowski, Sedigheh Zakeri, Abbasali Raz, Xavier de Lamballerie, Navid Dinparast-Djadid, Anna-Bella Failloux

Mosquitoes are vectors of viruses affecting animal and human health. In Iran, the prevalence of mosquito-borne viruses remains poorly investigated. Once infected, mosquito females are infected for all their life making virus detections possible at early steps before infections are reported in vertebrate hosts. In this study, we used a recently developed high-throughput chip based on the BioMark Dynamic arrays system capable of detecting more than 50 arboviruses in a single experiment. A total of 1,212 mosquitoes collected in Mazandaran, North-Khorasan, and Fars provinces of Iran were analyzed. Eighteen species were identified, belonging to five genera; the most prevalent species were Anopheles maculipennis s.l. (42.41%), Culex pipiens (19.39%), An. superpictus (11.72%), and Cx. tritaeniorhynchus (10.64%). We detected chikungunya virus (CHIKV) of the Asian genotype in six mosquito pools collected in North Khorasan and Mazandaran provinces. To our knowledge, this is the first report of mosquitoes infected with CHIKV in Iran. Our high-throughput screening method can be proposed as a novel epidemiological surveillance tool to identify circulating arboviruses and to support preparedness to an epidemic in animals and humans.

<i>Opisthorchis felineus</i> infection, risks, and morbidity in rural Western Siberia, Russian Federation

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

by Olga S. Fedorova, Marina M. Fedotova, Olga I. Zvonareva, Sofia V. Mazeina, Yulia V. Kovshirina, Tatiana S. Sokolova, Ekaterina A. Golovach, Anna E. Kovshirina, Uliana V. Konovalova, Ivan L. Kolomeets, Sergey S. Gutor, Vyacheslav A. Petrov, Jan Hattendorf, Ludmila M. Ogorodova, Peter Odermatt

Background

The liver fluke, Opisthorchis felineus, is widely distributed throughout Europe and large parts of the Russian Federation. In Western Siberia, information about opisthorchiasis is lacking although infection may lead to severe liver and bile duct diseases. We aimed to assess the current prevalence of O. felineus infection along with associated risk factors and morbidity in rural Western Siberia.

Methods

We conducted a community-based, cross-sectional study in the rural Shegarskiy district, Tomsk Oblast, Russian Federation. All household members (≥ 7 years) present on the survey day were enrolled (n = 600). Two stool samples per person were examined for helminth eggs, using PARASEP (DiaSys Ltd, UK). The number of eggs per gram (EPG) of feces was recorded. Each study participant was interviewed to determine risk factors, using a pre-tested questionnaire. An abdominal ultrasonography examination of liver and bile ducts was performed with a mobile, high resolution ultrasound device. In total, 488 persons completed assessments (two stool samples, completed questionnaires); of those, 436 individuals had an US examination.

Results

We observed a prevalence of O. felineus infection of 60.2%. Significant risk factors for infection were the consumption of river fish (odds ratio [OR] 2.4, 95% CI 1.52–3.95, p<0.001), particularly stock fish (OR from multivariable analysis [mOR] 3.2, 95% CI 2.63–3.80, p<0.001), smoked fish (mOR 1.5, 95% CI 1.24–1.72, p<0.001), frozen fish (mOR 1.6, 95% CI 1.29–2.02, p<0.001), and raw fish (mOR 1.4, 95% CI 1.05–1.84, p = 0.022); and fishing activities (mOR 1.2, 95% CI 1.03–1.43, p = 0.019). Women had a higher risk of infection than men. Infection was associated positively with age and negatively with socio-economic status. The respondents’ general awareness of opisthorchiasis was quite high (93.2%), but their knowledge about infection transmission and prevention was insufficient. Children aged 7–18 years old had a lower level of awareness compared to adults. The abdominal ultrasonography results demonstrated a strong association between O. felineus infection and gallbladder stones (mOR 2.8, 95% CI 1.33–6.04, p = 0.007) and periductal fibrosis of intrahepatic bile ducts (mOR 1.9, 95% CI 1.08–3.46, p = 0.026).

Conclusion

O. felineus infection is highly prevalent in rural regions of Western Siberia, and associated with severe hepatobiliary pathology. Identified risk factors will be used to develop a comprehensive targeted O. felineus infection control program.

Linking longitudinal and cross-sectional biomarker data to understand host-pathogen dynamics: <i>Leptospira</i> in California sea lions (<i>Zalophus californianus</i>) as a case study

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

by K. C. Prager, Michael G. Buhnerkempe, Denise J. Greig, Anthony J. Orr, Eric D. Jensen, Forrest Gomez, Renee L. Galloway, Qingzhong Wu, Frances M. D. Gulland, James O. Lloyd-Smith

Confronted with the challenge of understanding population-level processes, disease ecologists and epidemiologists often simplify quantitative data into distinct physiological states (e.g. susceptible, exposed, infected, recovered). However, data defining these states often fall along a spectrum rather than into clear categories. Hence, the host-pathogen relationship is more accurately defined using quantitative data, often integrating multiple diagnostic measures, just as clinicians do to assess their patients. We use quantitative data on a major neglected tropical disease (Leptospira interrogans) in California sea lions (Zalophus californianus) to improve individual-level and population-level understanding of this Leptospira reservoir system. We create a “host-pathogen space” by mapping multiple biomarkers of infection (e.g. serum antibodies, pathogen DNA) and disease state (e.g. serum chemistry values) from 13 longitudinally sampled, severely ill individuals to characterize changes in these values through time. Data from these individuals describe a clear, unidirectional trajectory of disease and recovery within this host-pathogen space. Remarkably, this trajectory also captures the broad patterns in larger cross-sectional datasets of 1456 wild sea lions in all states of health but sampled only once. Our framework enables us to determine an individual’s location in their time-course since initial infection, and to visualize the full range of clinical states and antibody responses induced by pathogen exposure. We identify predictive relationships between biomarkers and outcomes such as survival and pathogen shedding, and use these to impute values for missing data, thus increasing the size of the useable dataset. Mapping the host-pathogen space using quantitative biomarker data enables more nuanced understanding of an individual’s time course of infection, duration of immunity, and probability of being infectious. Such maps also make efficient use of limited data for rare or poorly understood diseases, by providing a means to rapidly assess the range and extent of potential clinical and immunological profiles. These approaches yield benefits for clinicians needing to triage patients, prevent transmission, and assess immunity, and for disease ecologists or epidemiologists working to develop appropriate risk management strategies to reduce transmission risk on a population scale (e.g. model parameterization using more accurate estimates of duration of immunity and infectiousness) and to assess health impacts on a population scale.

Impact of the social context on the prognosis of Chagas disease patients: Multilevel analysis of a Brazilian cohort

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

by Ariela Mota Ferreira, Éster Cerdeira Sabino, Lea Campos de Oliveira, Cláudia Di Lorenzo Oliveira, Clareci Silva Cardoso, Antônio Luiz Pinho Ribeiro, Renata Fiúza Damasceno, Maria do Carmo Pereira Nunes, Desirée Sant’ Ana Haikal

The present study aims to investigate how the social context contributes to the prognosis of Chagas disease (CD). This is a multilevel study that considered individual and contextual data. Individual data came from a Brazilian cohort study that followed 1,637 patients who lived in 21 municipalities to which CD is endemic, over two years. Contextual data were collected from official Brazilian government databases. The dependent variable was the occurrence of cardiovascular events in CD during the two-year follow-up, defined from the grouping of three possible combined events: death, development of atrial fibrillation, or pacemaker implantation. Analysis was performed using multilevel binary logistic regression. Among the individuals evaluated, 205 (12.5%) manifested cardiovascular events in CD during two years of follow-up. Individuals living in municipalities with a larger rural population had protection for these events (OR = 0.5; 95% CI = 0.4–0.7), while those residing in municipalities with fewer physicians per thousand inhabitants (OR = 1.6; 95% CI = 1.2–2.5) and those living in municipalities with lower Primary Health Care (PHC) coverage (OR = 1.4; 95% CI = 1.1–2.1) had higher chances of experiencing cardiovascular events. Among the individual variables, the probability of experiencing cardiovascular events was higher for individuals aged over 60 years (OR = 1.4; 95% CI = 1.01–2.2), with no stable relationship (OR = 1.4; 95% CI = 0.98–2.1), without previous treatment with Benznidazole (OR = 1.5; 95% CI = 0.98–2.9), with functional class limitation (OR = 2.0; 95% CI = 1.4–2.9), with a QRS complex duration longer than 120 ms (OR = 1.5; 95% CI = 1.1–2.3), and in individuals with high NT-proBNP levels (OR = 6.4; 95% CI = 4.3–9.6). CONCLUSION: The present study showed that the occurrence of cardiovascular events in individuals with CD is determined by individual conditions that express the severity of cardiovascular involvement. However, these individual characteristics are not isolated protagonists of this outcome, and the context in which individuals live, are also determining factors for a worse clinical prognosis.

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