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Parasitic Diseases - Top 30 Publications

Case 1-2018. A 39-Year-Old Woman with Rapidly Progressive Respiratory Failure.

Immunization and Vaccine-related Implementation Research Advisory Committee (IVIR-AC): summary of conclusions and recommendations, 20–22 September 2017.

Talaromyces marneffei Infection.

Stably expressed APOBEC3H forms a barrier for cross-species transmission of simian immunodeficiency virus of chimpanzee to humans.

APOBEC3s (A3s) are potent restriction factors of human immunodeficiency virus type 1/simian immunodeficiency viruses (HIV-1/SIV), and can repress cross-species transmissions of lentiviruses. HIV-1 originated from a zoonotic infection of SIV of chimpanzee (SIVcpz) to humans. However, the impact of human A3s on the replication of SIVcpz remains unclear. By using novel SIVcpz reporter viruses, we identified that human APOBEC3B (A3B) and APOBEC3H (A3H) haplotype II strongly reduced the infectivity of SIVcpz, because both of them are resistant to SIVcpz Vifs. We further demonstrated that human A3H inhibited SIVcpz by deaminase dependent as well independent mechanisms. In addition, other stably expressed human A3H haplotypes and splice variants showed strong antiviral activity against SIVcpz. Moreover, most SIV and HIV lineage Vif proteins could degrade chimpanzee A3H, but no Vifs from SIVcpz and SIV of gorilla (SIVgor) lineages antagonized human A3H haplotype II. Expression of human A3H hapII in human T cells efficiently blocked the spreading replication of SIVcpz. The spreading replication of SIVcpz was also restricted by stable A3H in human PBMCs. Thus, we speculate that stably expressed human A3H protects humans against the cross-species transmission of SIVcpz and that SIVcpz spillover to humans may have started in individuals that harbor haplotypes of unstable A3H proteins.

Disseminated Nocardiosis Associated with Treatment with Infliximab in a Patient with Ulcerative Colitis.

BACKGROUND Opportunistic infections may occur when patients with inflammatory bowel disease (IBD) are treated with tumor necrosis factor (TNF)-alpha inhibitors. With the increasing use of new immunosuppressant drugs, the incidence of opportunistic or atypical infections is also increasing, including with Nocardia spp. A high level of awareness of atypical infections is warranted in immunosuppressed patients. CASE REPORT A 57-year-old female African American, with a past medical history of ulcerative colitis (UC) and arthritis, was treated with infliximab and prednisone. She presented to the emergency department with acute onset of chest pain, shortness of breath, and a two-week history of a productive cough. Examination showed hypoxia, tachypnea, decreased and coarse bilateral breath sounds, and fluctuant, tender, erythematous masses on her trunk and groin. Laboratory investigations showed a leukocytosis with a left shift. She was initially treated for presumed community-acquired pneumonia (CAP). However, blood cultures grew Nocardia farcinica and treatment with trimethoprim-sulfamethoxazole (TMP-SMX) was begun, which was complicated by severe symptomatic hyponatremia. Following recovery from infection and resolution of the hyponatremia, the patient was discharged to a senior care facility, but with continued treatment with TMP-SMX. CONCLUSIONS To our knowledge, this is the first case of disseminated nocardiosis associated with infliximab treatment in a patient with ulcerative colitis. As with other forms of immunosuppressive therapy, patients who are treated with infliximab should be followed closely due to the increased risk of atypical infections. When initiating antibiotic therapy, careful monitoring of possible side effects should be done.

Recent Advances in Type-2-Cell-Mediated Immunity: Insights from Helminth Infection.

Type-2-cell-mediated immune responses play a critical role in mediating both host-resistance and disease-tolerance mechanisms during helminth infections. Recently, type 2 cell responses have emerged as major regulators of tissue repair and metabolic homeostasis even under steady-state conditions. In this review, we consider how studies of helminth infection have contributed toward our expanding cellular and molecular understanding of type-2-cell-mediated immunity, as well as new areas such as the microbiome. By studying how these successful parasites form chronic infections without overt pathology, we are gaining additional insights into allergic and inflammatory diseases, as well as normal physiology.

"The mosquitoes that destroy your face". Social impact of Cutaneous Leishmaniasis in South-eastern Morocco, A qualitative study.

To document the psychosocial burden of Cutaneous Leishmaniasis (CL) in rural communities in Southeastern Morocco.

Interaction between environment, nutrient-derived metabolites and immunity: A possible role in malaria susceptibility/resistance in Fulani and Dogon of Mali.

The role of some nutrient-derived metabolites on the innate and adaptive immune responses is now established. Global research approach investigating the interplay between environment, lifestyle and the host's immune responses is crucial in the understanding of malaria susceptibility. Advanced Glycation end products (AGE), which are food-derived metabolites result from the link between reducing sugar and amino group of proteins, lipids or nucleic acids. The level of exposure to AGEs varies depending on the type of diet. The dysfunction of the immune system induced by AGE and the cellular receptors for AGEs (RAGE) in susceptibility to bacterial infection has been described. But no study has yet explored their role in susceptibility to malaria. Therefore, we aimed to evaluate systemic AGE and RAGE gene polymorphism in two sympatric populations with previously described difference of susceptibility to malaria. We measured by ELISA the plasma levels of AGEs, and their soluble receptors (sRAGE) from 170 volunteers (68 Fulani and 102 Dogon). We also determined by real-time quantitative PCR the expression of RAGE, and the -374 T/A, -429 T/C polymorphisms and 63 bp deletion by fragment length restriction polymorphism. The prevalence rate of Plasmodium in Fulani and Dogon were respectively 42.64% and 51.30% for P. falciparum, 5.88% and 6.5% for P. malariae, 0% and 2.6% for P. ovale. The average AGE was 12.65 μg/ml, and 496.48pg/ml for sRAGE. Highest levels of sRAGE were observed in Fulani (563,07pg/ml, 95% CI [547.81-580.13] vs 465.68pg/ml, 95% CI [331.19-467.51]) for Dogon, p = 0.00001. Fulani had the lowest mean of AGE (10.21μg/ml, 95% CI [8.02-10.92]) compared to Dogon (16.88μg/ml, 95% CI [13.92-17.96]; p = 0.00001. RAGE was more expressed in Dogon than Fulani (0.08 vs 0.04), P = 0.08. The -374A polymorphism vas more frequent in Fulani (32%) compared to Dogon (20%). The chronic exposure to dietary AGE could lead to immune responses impairment and polymorphism with implications in malaria susceptibility. More studies are necessary to better investigate this hypothesis.

Toxoplasmosis - Awareness and knowledge among medical doctors in Nigeria.

Toxoplasma gondii is a zoonotic parasite causing high disease burden worldwide. A One Health approach is needed to understand, prevent, and control toxoplasmosis, while knowledge gaps in the One Health aspects have been identified among medical professionals in earlier studies. As a One Health collaboration between veterinary and medical fields, we surveyed the knowledge on toxoplasmosis among medical doctors in Nigeria. The knowledge questions, which the participants answered without consulting literature and colleagues, covered epidemiological One Health aspects as well as clinical interspecialty aspects of T. gondii infections. Altogether 522 medical doctors from four tertiary hospitals completed the questionnaire. The mean number of correct answers in the knowledge questions was 7.5, and 8.4% of the participants selected at least 12 of the 17 correct answers. The proportion of medical doctors scoring such a high score was significantly higher among those who reported having seen a case of clinical toxoplasmosis than in those who did not. While 62% of the medical doctors participating in our study knew that cats can shed T. gondii in their feces, 36% incorrectly suggested that humans could do that too. That T. gondii infection can be meatborne was known by 69%, but that it can be also waterborne only by 28% of the medical doctors participating in our study. Most of the medical doctors, 78%, knew that clinical toxoplasmosis may involve the central nervous system, while only 37% answered that it can involve the eyes. Our results suggested knowledge gaps, which need to be addressed in Continuous Medical Education. The identified gaps included both intersectoral One Health aspects and interspecialty aspects: For prevention and management of toxoplasmosis, knowing the main transmission routes and that the parasite can affect several organs is relevant.

High association of Cryptosporidium spp. infection with colon adenocarcinoma in Lebanese patients.

The association between Cryptosporidium and human colon cancer has been reported in different populations. However, this association has not been well studied. In order to add new strong arguments for a probable link between cryptosporidiosis and colon human cancer, the aim of this study was to determine prevalence and to identify species of Cryptosporidium among Lebanese patients.

Bacteremia due to Kingella denitrificans in a child followed-up for bone marrow failure syndrome.

Kingella denitrificans is a non-pathogenic micro-organism present in oropharyngeal flora. This germ has been recently recognized as responsible for opportunistic invasive infections mainly affecting immunosuppressed patients. We here report the case of a child aged 3 years and 7 months followed-up since the age of one year for bone marrow failure syndrome associated with pancytopenia of undetermined origin who had bacteremia due to Kingella denitrificans, a group of difficult to culture gram-negative bacteria rarely described in the literature. Clinicians and microbiologists should suspect the presence of this germ especially in immunosuppressed patients. The use of blood culture bottle contributes in a significant way to the detection of this germ.

Assessing the ownership, usage and knowledge of Insecticide Treated Nets (ITNs) in Malaria Prevention in the Hohoe Municipality, Ghana.

Malaria remains one of the top five killer diseases in sub-Saharan Africa (SSA) and its burden is skewed towards pregnant women and children under five. Insecticide Treated Bed-Net (ITN) usage is considered one of the most cost-effective, preventive interventions against malaria. This study sought to assess ownership, usage, effectiveness, knowledge, access and availability of ITNs among mothers with children under five in the Hohoe municipality.

The interruption of Onchocerca volvulus and Wuchereria bancrofti transmission by integrated chemotherapy in the Obongi focus, North Western Uganda.

Few studies have documented the interruption of onchocerciasis and Lymphatic Filariasis (LF) by integrated chemotherapy in Uganda. The study describes the interruption of transmission of the two diseases co-endemic in Obongi focus, north western Uganda. Base line data for Onchocerciasis and LF were collected in 1994 and 2006, respectively. Annual mass drug administration for onchocerciasis (Ivermectin) and Lymphatic Filariasis (Ivermectin + albendazole) was conducted for 20 and 6 years, respectively. Thereafter, assessments by skin snip, larval searches in rivers and human landing catches were performed. Children <10 years were screened for IgG4 antibodies using Ov16 ELISA technique in 2013. LF Pre-TAS and TAS1 were conducted in sentinel sites. ITN coverage and utilization for the implementation unit was also reported.

High prevalence of Angiostrongylus cantonensis (rat lungworm) on eastern Hawai'i Island: A closer look at life cycle traits and patterns of infection in wild rats (Rattus spp.).

The nematode Angiostrongylus cantonensis is a zoonotic pathogen and the etiological agent of human angiostrongyliasis or rat lungworm disease. Hawai'i, particularly east Hawai'i Island, is the epicenter for angiostrongyliasis in the USA. Rats (Rattus spp.) are the definitive hosts while gastropods are intermediate hosts. The main objective of this study was to collect adult A. cantonensis from wild rats to isolate protein for the development of a blood-based diagnostic, in the process we evaluated the prevalence of infection in wild rats. A total of 545 wild rats were sampled from multiple sites in the South Hilo District of east Hawai'i Island. Adult male and female A. cantonensis (3,148) were collected from the hearts and lungs of humanely euthanized Rattus rattus, and R. exulans. Photomicrography and documentation of multiple stages of this parasitic nematode in situ were recorded. A total of 45.5% (197/433) of rats inspected had lung lobe(s) (mostly upper right) which appeared granular indicating this lobe may serve as a filter for worm passage to the rest of the lung. Across Rattus spp., 72.7% (396/545) were infected with adult worms, but 93.9% (512/545) of the rats were positive for A. cantonensis infection based on presence of live adult worms, encysted adult worms, L3 larvae and/or by PCR analysis of brain tissue. In R. rattus we observed an inverse correlation with increased body mass and infection level of adult worms, and a direct correlation between body mass and encysted adult worms in the lung tissue, indicating that larger (older) rats may have developed a means of clearing infections or regulating the worm burden upon reinfection. The exceptionally high prevalence of A. cantonensis infection in Rattus spp. in east Hawai'i Island is cause for concern and indicates the potential for human infection with this emerging zoonosis is greater than previously thought.

A delayed diagnosis of X-linked hyper IgM syndrome complicated with toxoplasmic encephalitis in a child: A case report and literature review.

The X-linked hyper-immunoglobulin M syndrome (XHIGM) is an uncommon primary combined immunodeficiency disease caused by CD40L gene mutations. A delayed or missed diagnosis of XHIGM is common and concerning, owing to atypical immunoglobulin profile and phenotype of some patients, low recognition, and limited knowledge of clinicians on XHIGM in some underdeveloped areas. Opportunistic infections are a prominent clinical feature of XHIGM. However, toxoplasma encephalitis occurs sporadically and is extremely rare in patients with XHIGM.

Severe infections in sarcoidosis: Incidence, predictors and long-term outcome in a cohort of 585 patients.

Sarcoidosis is associated with cell-mediated immunodeficiency and treatment of symptomatic sarcoidosis usually includes systemic immunosuppressants. Data relative to incidence, prognosis factors, and outcome of infections are scarce.Retrospective cohort study of 585 patients with biopsy proven sarcoidosis in a tertiary referral specialist clinic, with a nested case-control analysis. Twenty nine patients (4.9%) with severe infections were compared to 116 controls subjects with sarcoidosis, matched according to their gender, ethnicity, age at diagnosis, and treatment with corticosteroids.After a median follow-up of 8 years [range; 1-46], 38 severe infections [mycobacterial infections (n = 14), fungal infections (n = 10), bacterial (n = 8), viral (n = 3) and parasitic (n = 1)] were observed in 30 patients. The incidence of severe infections was 0.71% persons-year (CI 95% 0.5-0.98) and 0.43% persons-year (CI 95% 0.27-0.66). Patients with severe infection were more frequently of male gender (60% vs 46%) and were more likely treated by ≥ 3 immunosuppressive agents (OR = 3.8, IC 95% [1.5-9.64], P = .005) and by cyclophosphamide (OR = 5.55, IC 95% [1.9-16.1], P = .002), and with neurological (OR = 3.36 CI 95% [1.37-8.25], P = .008), or cardiac (OR = 2.65 CI 95% [1.09-6.43], P = .031) involvement of the sarcoidosis, compared to the controls. Two patients died within the 6 months following infection, due to progressive multifocal leucoencephalopathy (n = 1), and of peritonitis (n = 1).Severe infections are observed in 5.1% of our patients with sarcoidosis after a median follow-up of 8 years. Risk factors for severe infections included neurological or cardiac involvement of sarcoidosis, the use of immunosuppressive agents and mainly cyclophosphamide.

Characterization of Toxoplasma DegP, a rhoptry serine protease crucial for lethal infection in mice.

During the infection process, Apicomplexa discharge their secretory organelles called micronemes, rhoptries and dense granules to sustain host cell invasion, intracellular replication and to modulate host cell pathways and immune responses. Herein, we describe the Toxoplasma gondii Deg-like serine protein (TgDegP), a rhoptry protein homologous to High temperature requirement A (HtrA) or Deg-like family of serine proteases. TgDegP undergoes processing in both types I and II strains as most of the rhoptries proteins. We show that genetic disruption of the degP gene does not impact the parasite lytic cycle in vitro but affects virulence in mice. While in a type I strain DegPI appears dispensable for the establishment of an infection, removal of DegPII in a type II strain dramatically impairs the virulence. Finally, we show that KO-DegPII parasites kill immunodeficient mice as efficiently as the wild-type strain indicating that the protease might be involved in the complex crosstalk that the parasite engaged with the host immune response. Thus, this study unravels a novel rhoptry protein in T. gondii important for the establishment of lethal infection.

Application of system dynamics and participatory spatial group model building in animal health: A case study of East Coast Fever interventions in Lundazi and Monze districts of Zambia.

East Coast Fever (ECF) is the most economically important production disease among traditional beef cattle farmers in Zambia. Despite the disease control efforts by the government, donors, and farmers, ECF cases are increasing. Why does ECF oscillate over time? Can alternative approaches such as systems thinking contribute solutions to the complex ECF problem, avoid unintended consequences, and achieve sustainable results? To answer these research questions and inform the design and implementation of ECF interventions, we qualitatively investigated the influence of dynamic socio-economic, cultural, and ecological factors. We used system dynamics modelling to specify these dynamics qualitatively, and an innovative participatory framework called spatial group model building (SGMB). SGMB uses participatory geographical information system (GIS) concepts and techniques to capture the role of spatial phenomenon in the context of complex systems, allowing stakeholders to identify spatial phenomenon directly on physical maps and integrate such information in model development. Our SGMB process convened focus groups of beef value chain stakeholders in two distinct production systems. The focus groups helped to jointly construct a series of interrelated system dynamics models that described ECF in a broader systems context. Thus, a complementary objective of this study was to demonstrate the applicability of system dynamics modelling and SGMB in animal health. The SGMB process revealed policy leverage points in the beef cattle value chain that could be targeted to improve ECF control. For example, policies that develop sustainable and stable cattle markets and improve household income availability may have positive feedback effects on investment in animal health. The results obtained from a SGMB process also demonstrated that a "one-size-fits-all" approach may not be equally effective in policing ECF in different agro-ecological zones due to the complex interactions of socio-ecological context with important, and often ignored, spatial patterns.

In vitro anthelmintic effects of Spigelia anthelmia protein fractions against Haemonchus contortus.

Gastrointestinal nematodes are a significant concern for animal health and well-being, and anthelmintic treatment is mainly performed through the use of chemical products. However, bioactive compounds produced by plants have shown promise for development as novel anthelmintics. The aim of this study is to assess the anthelmintic activity of protein fractions from Spigelia anthelmia on the gastrointestinal nematode Haemonchus contortus. Plant parts were separated into leaves, stems and roots, washed with distilled water, freeze-dried and ground into a fine powder. Protein extraction was performed with sodium phosphate buffer (75 mM, pH 7.0). The extract was fractionated using ammonium sulfate (0-90%) and extensively dialyzed. The resulting fractions were named LPF (leaf protein fraction), SPF (stem protein fraction) and RPF (root protein fraction), and the protein contents and activities of the fractions were analyzed. H. contortus egg hatching (EHA), larval exsheathment inhibition (LEIA) and larval migration inhibition (LMIA) assays were performed. Proteomic analysis was conducted, and high-performance liquid chromatography (HPLC) chromatographic profiles of the fractions were established to identify proteins and possible secondary metabolites. S. anthelmia fractions inhibited H. contortus egg hatching, with LPF having the most potent effects (EC50 0.17 mg mL-1). During LEIA, SPF presented greater efficiency than the other fractions (EC50 0.25 mg mL-1). According to LMIA, the fractions from roots, stems and leaves also reduced the number of larvae, with EC50 values of 0.11, 0.14 and 0.21 mg mL-1, respectively. Protein analysis indicated the presence of plant defense proteins in the S. anthelmia fractions, including protease, protease inhibitor, chitinase and others. Conversely, secondary metabolites were absent in the S. anthemia fractions. These results suggest that S. anthelmia proteins are promising for the control of the gastrointestinal nematode H. contortus.

Inhibition of merozoite invasion and transient de-sequestration by sevuparin in humans with Plasmodium falciparum malaria.

Even with the best available treatment, the mortality from severe Plasmodium falciparum malaria remains high. Typical features at death are high parasite loads and obstructed micro- vasculature. Infected erythrocytes (IE) containing mature parasites bind to the host receptor heparan sulfate, which is also an important receptor for merozoite invasion. To block merozoite invasion has not previously been proposed as an adjunctive therapeutic approach but it may preclude the early expansion of an infection that else leads to exacerbated sequestration and death.

Cost-effectiveness analysis of introducing malaria diagnostic testing in drug shops: A cluster-randomised trial in Uganda.

Private sector drug shops are an important source of malaria treatment in Africa, yet diagnosis without parasitological testing is common among these providers. Accurate rapid diagnostic tests for malaria (mRDTs) require limited training and present an opportunity to increase access to correct diagnosis. The present study was a cost-effectiveness analysis of the introduction of mRDTs in Ugandan drug shops.

Drug resistance and treatment failure in leishmaniasis: A 21st century challenge.

Reevaluation of treatment guidelines for Old and New World leishmaniasis is urgently needed on a global basis because treatment failure is an increasing problem. Drug resistance is a fundamental determinant of treatment failure, although other factors also contribute to this phenomenon, including the global HIV/AIDS epidemic with its accompanying impact on the immune system. Pentavalent antimonials have been used successfully worldwide for the treatment of leishmaniasis since the first half of the 20th century, but the last 10 to 20 years have witnessed an increase in clinical resistance, e.g., in North Bihar in India. In this review, we discuss the meaning of "resistance" related to leishmaniasis and discuss its molecular epidemiology, particularly for Leishmania donovani that causes visceral leishmaniasis. We also discuss how resistance can affect drug combination therapies. Molecular mechanisms known to contribute to resistance to antimonials, amphotericin B, and miltefosine are also outlined.

The self-curing phenomenon of schistosome infection in rhesus macaques: insight from in vitro studies.

A reduction in the burden of schistosomiasis is potentially achievable by integrating a schistosomiasis vaccine with current control measures. Here, we determine parasite-specific in vitro responses of B, T, and NK cells from naive uninfected rhesus macaques to Schistosoma mansoni (Sm) egg (SmEA) and worm antigen (SmWA) preparations isolated from infected baboons. Pronounced B cell responses to SmEA and NK cell responses to both SmEA and SmWA were observed. High levels of IL-2 and IL-21 responses against Sm antigens were observed in T and non-T cells of lymph nodes (LNs) and gut lamina propria-derived lymphocytes (LPLs). Data analysis showed multifunctionality of LN-derived CD4+ , CD8+ , and CD4+ CD8+ double positive T cells against either SmWA or SmWA+SmEA antigen preparations. Distinct SmEA-specific multifunctional responses were observed in gut LPLs, suggesting simultaneous responses against egg antigens. These data provide insight into the immune effectors involved in schistosome responses by rhesus macaques.

Tubular Opacities in the Gastrointestinal Tract.

Antischistosomal agents: state of art and perspectives.

Praziquantel has remained the drug of choice for schistosomiasis chemotherapy for almost 40 years. The pressing need to develop a new antischistosomal drug may necessitate exploring and filtering chemotherapeutic history to search for the most promising ones. In this context, this review attempts to summarize all progress made in schistosomiasis chemotherapy from the early 20th century (mid-1910s) to 2016. We gathered almost 100 compounds providing information on therapeutic action, specifically covering at least first in vivo studies in animal model and in vitro. Pharmacokinetic and toxicity profiles of antischistosomal agents were also described. Preclinical studies indicate a handful of promising future candidates.

Chagas disease vector blood meal sources identified by protein mass spectrometry.

Chagas disease is a complex vector borne parasitic disease involving blood feeding Triatominae (Hemiptera: Reduviidae) insects, also known as kissing bugs, and the vertebrates they feed on. This disease has tremendous impacts on millions of people and is a global health problem. The etiological agent of Chagas disease, Trypanosoma cruzi (Kinetoplastea: Trypanosomatida: Trypanosomatidae), is deposited on the mammalian host in the insect's feces during a blood meal, and enters the host's blood stream through mucous membranes or a break in the skin. Identifying the blood meal sources of triatomine vectors is critical in understanding Chagas disease transmission dynamics, can lead to identification of other vertebrates important in the transmission cycle, and aids management decisions. The latter is particularly important as there is little in the way of effective therapeutics for Chagas disease. Several techniques, mostly DNA-based, are available for blood meal identification. However, further methods are needed, particularly when sample conditions lead to low-quality DNA or to assess the risk of human cross-contamination. We demonstrate a proteomics-based approach, using liquid chromatography tandem mass spectrometry (LC-MS/MS) to identify host-specific hemoglobin peptides for blood meal identification in mouse blood control samples and apply LC-MS/MS for the first time to Triatoma dimidiata insect vectors, tracing blood sources to species. In contrast to most proteins, hemoglobin, stabilized by iron, is incredibly stable even being preserved through geologic time. We compared blood stored with and without an anticoagulant and examined field-collected insect specimens stored in suboptimal conditions such as at room temperature for long periods of time. To our knowledge, this is the first study using LC-MS/MS on field-collected arthropod disease vectors to identify blood meal composition, and where blood meal identification was confirmed with more traditional DNA-based methods. We also demonstrate the potential of synthetic peptide standards to estimate relative amounts of hemoglobin acquired when insects feed on multiple blood sources. These LC-MS/MS methods can contribute to developing Ecohealth control strategies for Chagas disease transmission and can be applied to other arthropod disease vectors.

Lack of association between serum syndecan-4, myocardial fibrosis and ventricular dysfunction in subjects with chronic Chagas disease.

Syndecan-4 is a transmembrane glycoprotein associated with inflammation and fibrosis. Increased syndecan-4 levels were previously detected after acute myocardial infarction and in subjects with heart failure. However, the levels of syndecan-4 in subjects with Chagas disease have not so far been investigated. The aim of this study was to investigate the potential role of serum sydencan-4 as a novel biomarker for myocardial fibrosis and cardiac dysfunction in subjects with Chagas disease.

More than the eyes can see: The worrying scenario of canine leishmaniasis in the Brazilian side of the triple border.

A cross-sectional epidemiological study in the extreme-west of the state of Paraná was carried out to access the prevalence, distribution, and risk variables of canine Visceral Leishmaniases (cVL). This study was conducted in three areas, two cities of far west of Parana state: Foz do Iguaçu (FI) and Santa Terezinha de Itaipu (STI), and along two transects between these two municipalities. To sample the entire urban area, the cities (FI and STI) were divided into a grid of squares of 400 m2 (patch). Among the 526 patches, 123 in FI, 40 in the transects and 33 in STI were selected according to the 'worst scenario' criterion. In the transect areas, in each 0.86 km five dogs from houses were surveyed to leishmaniasis. In each patch, blood of five dogs from houses (and from neighborhood when necessary) in the areas that seemed to be the most appropriate for the proliferation of vector were surveyed. The infection of the dogs by cVL were assessed using two serological tests were used (cELISA and TR-DPP®), and, for those seropositive for both methods, the PCR method were used. Moreover, dogs presenting clinical signs or cutaneous lesions were sampled to PCR. The identification of Leishmania species was confirmed using PCR-RFLP followed by DNA sequencing. Micro, meso and macro scale environmental variables were also surveyed and statistically analyzed. The prevalence rate Leishmania infantum was 23.8% in FI, 4.7% in STI and 9.1% in the transects areas. Among the extrinsic variables analysed, the number of vectors and the presence of infected dogs in neighbouring were positively correlated with the occurrence of infected dogs. Dog size was positively correlated with cVL infection, while the quality of the dog's nutrition affected cVL negatively. As for cutaneous leishmaniasis (CL), the first registry of dogs infected with L. braziliensis in the region shows that there is potential for transmission in peri-urban areas, since environmental conditions allow the proliferation of vectors capable of transmitting this species of parasite. cVL is widely spread in FI, with high prevalence. This supports the hypothesis that the parasite has been present in the region for longer than previously believed, despite the fact that the presence of leishmaniais in the region has only been recognized recently. It is important to control the population of dogs infected with L. infantum (parasite and non-antibodies) to prevent the spread of the disease to other dogs and also to people in the region.

Sustaining visceral leishmaniasis elimination in Bangladesh - Could a policy brief help?

Bangladesh has made significant progress towards elimination of visceral leishmaniasis, and is on track to achieve its target of less than one case per 10,000 inhabitants in each subdistrict in 2017. As the incidence of disease falls, it is likely that the political capital and financial resources dedicated towards the elimination of visceral leishmaniasis may decrease, raising the prospect of disease resurgence. Policy memos may play a crucial role during the transition of the elimination plan from the 'attack' to the 'consolidation' and 'maintenance' phases, highlighting key stakeholders and areas where ongoing investment is crucial. An example of a policy brief is outlined in this paper. The background to the current elimination efforts is highlighted, with emphasis on remaining uncertainties including the impact of disease reservoirs and sustainable surveillance strategies. A stakeholder map is provided outlining the current and projected future activities of key bodies. Identification of key stakeholders subsequently frames the discussion of three key policy recommendations in the Bangladeshi context for the transition to the consolidation and maintenance phases of the elimination program. Recommendations include determining optimal vector control and surveillance strategies, shifting the emphasis towards horizontal integration of disease programs, and prioritising remaining research questions with a focus on operational and technical capacity. Achieving elimination is as much a political as a scientific question. Integrating the discussion of key stakeholders with policy priorities and the research agenda provides a novel insight into potential pathways forwards in the elimination of visceral leishmaniasis in Bangladesh and in the rest of the Indian subcontinent.

Detection of duo-schistosome infection from filtered urine samples from school children in Zambia after MDA.

Schistosomiasis is one of the major Neglected Tropical Diseases (NTDs) in sub-Saharan Africa. In sub-Saharan Africa, two major human schistosome species namely Schistosoma mansoni and S. haematobium often occur sympatrically largely affecting children. Recognizing the public health impact of Schistosomiasis, the World Health Organization (WHO) is urging member states to regularly treat at least 75% and up to 100%, of all school-aged children at risk of morbidity. For control strategies based on targeted mass drug administration (MDA) to succeed it is essential to have a simple and sensitive test for monitoring the success of these interventions. Current available diagnostic tests, such as egg detection in stool by Kato-Katz (KK) for S. mansoni and detection of eggs or blood (hematuria) in urine for S. haematobium have reduced sensitivity in low intensity settings. The objective of the study was to evaluate active single or duo schistosome infections in school children following MDA using molecular diagnostics (PCR) on filtered urine samples and comparing that against traditional diagnostic tests. This cross-sectional study was conducted among 111 school children aged 7-15 years in Chongwe and Siavonga Districts in Zambia. Species-specific cell-free repeat DNA fragment were amplified from 111 filtered urine samples. Our approach detected eight times more positive cases (total 77) than by KK (9) for S. mansoni and six times more (total 72) than by hematuria (11) for S. haematobium and even more against urine filtration (77 compared to only 6). The same pattern was observed when stratified for age group and sex specific analysis with 100% sensitivity and specificity devoid of any cross amplification. In addition, 69 individuals (62%) were co-infected by both parasites. We have demonstrated a significantly higher prevalence of both species than indicated by the traditional tests and the persistent maintenance of reservoir of infection after MDA. Our approach is an effective means of detecting low intensity infection, which will enhance the effectiveness of surveillance and assess the impact of MDA control programs against schistosomiasis.