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Follow-up of an Asymptomatic Chagas Disease Population of Children after Treatment with Nifurtimox (Lampit) in a Sylvatic Endemic Transmission Area of Colombia

PLoS Neglected Tropical Diseases News - 27 February 2015 - 10:00pm

by Fiorella Bianchi, Zulma Cucunubá, Felipe Guhl, Nadia Lorena González, Hector Freilij, Rubén Santiago Nicholls, Juan David Ramírez, Marleny Montilla, Astrid Carolina Flórez, Fernando Rosas, Victor Saavedra, Nubia Silva

Background

Chagas disease is an anthropozoonosis caused by Trypanosoma cruzi. Two drugs are currently used for the etiological treatment of the disease: Nifurtimox (Lampit) and Benznidazole. This study presents a quasi-experimental trial (non-control group) of sixty-two patients who were treated for Chagas disease with Nifurtimox (Lampit), and were then followed for 30 months post-treatment. The safety of Nifurtimox (Lampit) for Chagas disease in this group of children primarily between 4 and 19 years old was also evaluated.

Materials and methods

The 62 patients included in the study were selected when resulted seropositive for two out of three fundamentally different serological tests. All children were treated during two months according to protocols established by WHO. Monitoring was performed every twenty days to evaluate treatment safety. In 43 patients, two different serological tests: ELISA and IFAT; and two parasitological tests: blood culture, and real time PCR, (qPCR) were performed to assess therapeutic response, defined as post-treatment serological negativization.

Principal findings

All patients completed the treatment successfully, and six patients abandoned the post-treatment follow-up. Adverse effects occurred in 74% of patients, but only 4.8% of cases required temporary suspension to achieve 100% adherence to the 60-day treatment, and all symptoms reverted after treatment completion. Both parasite load (measured through qPCR) and antibodies (ELISA absorbance) evidenced a significant median reduction 6 months after treatment from 6.2 to 0.2 parasite equivalents/mL, and from 0.6 to 0.2 absorbance units respectively (p<0.001). Serological negativization by ELISA was evident since 6 months post-treatment, whereas by IFAT only after 18 months. Serological negativization by the two tests (ELISA and IFAT) was 41.9% (95%CI: 26.5–57.3) after 30 months post-treatment. qPCR was positive in 88.3% of patients pre-treatment and only in 12.1% of patients after 30 months. Survival analysis indicated that only 26.3% (95%CI: 15.5–44.8) persisted with negative qPCR during the whole follow-up period.

Conclusions

Nifurtimox was very well tolerated and successfully reduced parasite load and antibody titers. Re-infection, lysed parasites or a lack of anti-parasitic activity could explain these persistently positive qPCR cases.

Inter-epidemic Acquisition of Rift Valley Fever Virus in Humans in Tanzania

PLoS Neglected Tropical Diseases News - 27 February 2015 - 10:00pm

by Robert David Sumaye, Emmanuel Nji Abatih, Etienne Thiry, Mbaraka Amuri, Dirk Berkvens, Eveline Geubbels

Background

In East Africa, epidemics of Rift Valley fever (RVF) occur in cycles of 5–15 years following unusually high rainfall. RVF transmission during inter-epidemic periods (IEP) generally passes undetected in absence of surveillance in mammalian hosts and vectors. We studied IEP transmission of RVF and evaluated the demographic, behavioural, occupational and spatial determinants of past RVF infection.

Methodology

Between March and August 2012 we collected blood samples, and administered a risk factor questionnaire among 606 inhabitants of 6 villages in the seasonally inundated Kilombero Valley, Tanzania. ELISA tests were used to detect RVFV IgM and IgG antibodies in serum samples. Risk factors were examined by mixed effects logistic regression.

Findings

RVF virus IgM antibodies, indicating recent RVFV acquisition, were detected in 16 participants, representing 2.6% overall and in 22.5% of inhibition ELISA positives (n = 71). Four of 16 (25.0%) IgM positives and 11/71 (15.5%) of individuals with inhibition ELISA sero-positivity reported they had had no previous contact with host animals. Sero-positivity on inhibition ELISA was 11.7% (95% CI 9.2–14.5) and risk was elevated with age (odds ratio (OR) 1.03 per year; 95% CI 1.01–1.04), among milkers (OR 2.19; 95% CI 1.23–3.91), and individuals eating raw meat (OR 4.17; 95% CI 1.18–14.66). Households keeping livestock had a higher probability of having members with evidence of past infection (OR = 3.04, 95% CI = 1.42–6.48) than those that do not keep livestock.

Conclusion

There is inter-epidemic acquisition of RVFV in Kilombero Valley inhabitants. In the wake of declining malaria incidence, these findings underscore the need for clinicians to consider RVF in the differential diagnosis for febrile illnesses. Several types of direct contact with livestock are important risk factors for past infection with RVFV in this study’s population. However, at least part of RVFV transmission appears to have occurred through bites of infected mosquitoes.

Sm29, but Not Sm22.6 Retains its Ability to Induce a Protective Immune Response in Mice Previously Exposed to a Schistosoma mansoni Infection

PLoS Neglected Tropical Diseases News - 27 February 2015 - 10:00pm

by Clarice Carvalho Alves, Neusa Araujo, Viviane Cristina Fernandes dos Santos, Flávia Bubula Couto, Natan R. G. Assis, Suellen B. Morais, Sérgio Costa Oliveira, Cristina Toscano Fonseca

Background

A vaccine against schistosomiasis would have a great impact in disease elimination. Sm29 and Sm22.6 are two parasite tegument proteins which represent promising antigens to compose a vaccine. These antigens have been associated with resistance to infection and reinfection in individuals living in endemic area for the disease and induced partial protection when evaluated in immunization trials using naïve mice.

Methodology/principals findings

In this study we evaluated rSm29 and rSm22.6 ability to induce protection in Balb/c mice that had been previously infected with S. mansoni and further treated with Praziquantel. Our results demonstrate that three doses of the vaccine containing rSm29 were necessary to elicit significant protection (26%–48%). Immunization of mice with rSm29 induced a significant production of IL-2, IFN-γ, IL-17, IL-4; significant production of specific antibodies; increased percentage of CD4+ central memory cells in comparison with infected and treated saline group and increased percentage of CD4+ effector memory cells in comparison with naïve Balb/c mice immunized with rSm29. On the other hand, although immunization with Sm22.6 induced a robust immune response, it failed to induce protection.

Conclusion/significance

Our results demonstrate that rSm29 retains its ability to induce protection in previously infected animals, reinforcing its potential as a vaccine candidate.

Health Economic Evaluations of Visceral Leishmaniasis Treatments: A Systematic Review

PLoS Neglected Tropical Diseases News - 27 February 2015 - 10:00pm

by Daniel S. Marinho, Carmen N. P. R. Casas, Claudia C. de A. Pereira, Iuri C. Leite

Objective

The main objective of this study was to identify, describe, classify and analyze the scientific health economic evidence of VL-related technologies.

Methods

A web search of combinations of free text and Mesh terms related to the economic evaluation of visceral leishmaniasis was conducted on scientific publication databases (Web of Science, Scopus, Medline via the Pubmed and Lilacs). A manual search of references lists of articles previously identified by the authors was also included. Articles written in English, Portuguese, Spanish or French were considered suitable for inclusion. Articles that matched the inclusion criteria were screened by at least two researchers, who extracted information regarding the epidemiologic scenario and methodological issues on a standardized form.

Results

The initial search retrieved 107 articles, whose abstracts were inspected according to the inclusion criteria leading to a first selection of 49 (46%) articles. After the elimination of duplicates, the list was reduced to 21 (20%) articles. After careful reading and application of exclusion criteria, 14 papers were eligible according to the description, classification and analysis process proposed by the study. When classified by type of economic evaluation, articles were 7 (50%) cost-effectiveness, 5 (36%) cost-minimization, 1(7%) cost-benefit, and 1(7%) budget impact. When classified by methodology, studies were mainly nested to clinical-trials (“piggy back”) 8(57%). Discount rates for outcomes and costs were present in 3 (43%) of the cost-effectiveness studies, and according to WHO's recommendations, the discount rate of 3% was used in all studies.

Conclusions

This article showed that health economic evaluations on visceral leishmaniasis used a wide range of technologies and methods. Nevertheless it is important to point out the geographic concentration of studies, which makes their transferability uncertain to different epidemiological scenarios, especially those concerning visceral leishmaniasis caused by Leishmania infantum.

A Novel Bacterial Pathogen of Biomphalaria glabrata: A Potential Weapon for Schistosomiasis Control?

PLoS Neglected Tropical Diseases News - 26 February 2015 - 10:00pm

by David Duval, Richard Galinier, Gabriel Mouahid, Eve Toulza, Jean François Allienne, Julien Portela, Christophe Calvayrac, Anne Rognon, Nathalie Arancibia, Guillaume Mitta, André Théron, Benjamin Gourbal

Background

Schistosomiasis is the second-most widespread tropical parasitic disease after malaria. Various research strategies and treatment programs for achieving the objective of eradicating schistosomiasis within a decade have been recommended and supported by the World Health Organization. One of these approaches is based on the control of snail vectors in endemic areas. Previous field studies have shown that competitor or predator introduction can reduce snail numbers, but no systematic investigation has ever been conducted to identify snail microbial pathogens and evaluate their molluscicidal effects.

Methodology/Principal findings

In populations of Biomphalaria glabrata snails experiencing high mortalities, white nodules were visible on snail bodies. Infectious agents were isolated from such nodules. Only one type of bacteria, identified as a new species of Paenibacillus named Candidatus Paenibacillus glabratella, was found, and was shown to be closely related to P. alvei through 16S and Rpob DNA analysis. Histopathological examination showed extensive bacterial infiltration leading to overall tissue disorganization. Exposure of healthy snails to Paenibacillus-infected snails caused massive mortality. Moreover, eggs laid by infected snails were also infected, decreasing hatching but without apparent effects on spawning. Embryonic lethality was correlated with the presence of pathogenic bacteria in eggs.

Conclusions/Significance

This is the first account of a novel Paenibacillus strain, Ca. Paenibacillus glabratella, as a snail microbial pathogen. Since this strain affects both adult and embryonic stages and causes significant mortality, it may hold promise as a biocontrol agent to limit schistosomiasis transmission in the field.

Minipool Caprylic Acid Fractionation of Plasma Using Disposable Equipment: A Practical Method to Enhance Immunoglobulin Supply in Developing Countries

PLoS Neglected Tropical Diseases News - 26 February 2015 - 10:00pm

by Magdy El-Ekiaby, Mariángela Vargas, Makram Sayed, George Gorgy, Hadi Goubran, Mirjana Radosevic, Thierry Burnouf

Background

Immunoglobulin G (IgG) is an essential plasma-derived medicine that is lacking in developing countries. IgG shortages leave immunodeficient patients without treatment, exposing them to devastating recurrent infections from local pathogens. A simple and practical method for producing IgG from normal or convalescent plasma collected in developing countries is needed to provide better, faster access to IgG for patients in need.

Methodology/Principal Findings

IgG was purified from 10 consecutive minipools of 20 plasma donations collected in Egypt using single-use equipment. Plasma donations in their collection bags were subjected to 5%-pH5.5 caprylic acid treatment for 90 min at 31°C, and centrifuged to remove the precipitate. Supernatants were pooled, then dialyzed and concentrated using a commercial disposable hemodialyzer. The final preparation was filtered online by gravity, aseptically dispensed into storage transfusion bags, and frozen at <-20°C. The resulting preparation had a mean protein content of 60.5 g/L, 90.2% immunoglobulins, including 83.2% IgG, 12.4% IgA, and 4.4% IgM, and residual albumin. There was fourfold to sixfold enrichment of anti-hepatitis B and anti-rubella antibodies. Analyses of aggregates (<3%), prekallicrein (5-7 IU/mL), plasmin (26.3 mU/mL), thrombin (2.5 mU/mL), thrombin-like activity (0.011 U/g), thrombin generation capacity (< 223 nM), and Factor XI (<0.01 U/mL) activity, Factor XI/XIa antigen (2.4 ng/g) endotoxin (<0.5 EU/mL), and general safety test in rats showed the in vitro safety profile. Viral validation revealed >5 logs reduction of HIV, BVDV, and PRV infectivity in less than 15 min of caprylic acid treatment.

Conclusions/Significance

90% pure, virally-inactivated immunoglobulins can be prepared from plasma minipools using simple disposable equipment and bag systems. This easy-to-implement process could be used to produce immunoglobulins from local plasma in developing countries to treat immunodeficient patients. It is also relevant for preparing hyperimmune IgG from convalescent plasma during infectious outbreaks such as the current Ebola virus episode.

The Gulf of Mexico: A “Hot Zone” for Neglected Tropical Diseases?

PLoS Neglected Tropical Diseases News - 26 February 2015 - 10:00pm

by Peter J. Hotez, Maria Elena Bottazzi, Eric Dumonteil, Pierre Buekens

Serology for Trachoma Surveillance after Cessation of Mass Drug Administration

PLoS Neglected Tropical Diseases News - 25 February 2015 - 10:00pm

by Diana L. Martin, Rhiannon Bid, Frank Sandi, E. Brook Goodhew, Patrick A. Massae, Augustin Lasway, Heiko Philippin, William Makupa, Sandra Molina, Martin J. Holland, David C. W. Mabey, Chris Drakeley, Patrick J. Lammie, Anthony W. Solomon

Background

Trachoma, caused by Chlamydia trachomatis (Ct), is the leading infectious cause of blindness worldwide. Yearly azithromycin mass drug administration (MDA) plays a central role in efforts to eliminate blinding trachoma as a public health problem. Programmatic decision-making is currently based on the prevalence of the clinical sign “trachomatous inflammation-follicular” (TF) in children. We sought to test alternative tools for trachoma surveillance based on serology in the 12-year cohort of Kahe Mpya, Rombo District, Tanzania, where ocular chlamydial infection was eliminated with azithromycin MDA by 2005.

Methodology and Principal Findings

The present study was a community-based cross-sectional survey in Kahe Mpya. Of 989 residents, 571 people aged 6 months to 87 years were enrolled: 58% of the total population and 73% of 1–9 year olds, the key WHO indicator age group. Participants were examined for TF, had conjunctival swabs collected for nucleic acid amplification test (NAAT)-based detection of Ct, and blood collected for analysis of antibodies to the Ct antigens pgp3 and CT694 by multiplex bead-based immunoassay. Seroconversion rate was used to estimate changes in the force of infection in a reversible catalytic model. No conjunctival swabs tested positive for Ct infection by NAAT. Among 1–9 year olds, TF prevalence was 6.5%, whereas only 3.5% were seropositive. Force of infection modelling indicated a 10-fold decrease in seroconversion rate at a time corresponding to MDA commencement. Without baseline serological data, the inferences we can make about antibody status before MDA and the longevity of the antibody response are limited, though our use of catalytic modelling overcomes some of these limitations.

Conclusions/Significance

Serologic tests support NAAT findings of very low to zero prevalence of ocular Ct in this community and have potential to provide objective measures of transmission and useful surveillance tools for trachoma elimination programs.

Species-Specific Antimonial Sensitivity in Leishmania Is Driven by Post-Transcriptional Regulation of AQP1

PLoS Neglected Tropical Diseases News - 25 February 2015 - 10:00pm

by Goutam Mandal, Srotoswati Mandal, Mansi Sharma, Karen Santos Charret, Barbara Papadopoulou, Hiranmoy Bhattacharjee, Rita Mukhopadhyay

Leishmania is a digenetic protozoan parasite causing leishmaniasis in humans. The different clinical forms of leishmaniasis are caused by more than twenty species of Leishmania that are transmitted by nearly thirty species of phlebotomine sand flies. Pentavalent antimonials (such as Pentostam or Glucantime) are the first line drugs for treating leishmaniasis. Recent studies suggest that pentavalent antimony (Sb(V)) acts as a pro-drug, which is converted to the more active trivalent form (Sb(III)). However, sensitivity to trivalent antimony varies among different Leishmania species. In general, Leishmania species causing cutaneous leishmaniasis (CL) are more sensitive to Sb(III) than the species responsible for visceral leishmaniasis (VL). Leishmania aquaglyceroporin (AQP1) facilitates the adventitious passage of antimonite down a concentration gradient. In this study, we show that Leishmania species causing CL accumulate more antimonite, and therefore exhibit higher sensitivity to antimonials, than the species responsible for VL. This species-specific differential sensitivity to antimonite is directly proportional to the expression levels of AQP1 mRNA. We show that the stability of AQP1 mRNA in different Leishmania species is regulated by their respective 3’-untranslated regions. The differential regulation of AQP1 mRNA explains the distinct antimonial sensitivity of each species.

Leishmania infantum Amastigotes Trigger a Subpopulation of Human B Cells with an Immunoregulatory Phenotype

PLoS Neglected Tropical Diseases News - 24 February 2015 - 10:00pm

by Guadalupe Andreani, Michel Ouellet, Rym Menasria, Alejandro Martin Gomez, Corinne Barat, Michel J. Tremblay

Visceral leishmaniasis is caused by the protozoan parasites Leishmania infantum and Leishmania donovani. This infection is characterized by an uncontrolled parasitization of internal organs which, when left untreated, leads to death. Disease progression is linked with the type of immune response generated and a strong correlation was found between disease progression and serum levels of the immunosuppressive cytokine IL-10. Other studies have suggested a role for B cells in the pathology of this parasitic infection and the recent identification of a B-cell population in humans with regulatory functions, which secretes large amounts of IL-10 following activation, have sparked our interest in the context of visceral leishmaniasis. We report here that incubation of human B cells with Leishmania infantum amastigotes resulted in upregulation of multiple cell surface activation markers and a dose-dependent secretion of IL-10. Conditioned media from B cells incubated with Leishmania infantum amastigotes were shown to strongly inhibit CD4+ T-cell activation, proliferation and function (i.e. as monitored by TNF and IFNγ secretion). Blockade of IL-10 activity using a soluble IL-10 receptor restored only partially TNF and IFNγ production to control levels. The parasite-mediated IL-10 secretion was shown to rely on the activity of Syk, phosphatidylinositol-3 kinase and p38, as well as to require intracellular calcium mobilization. Cell sorting experiments allowed us to identify the IL-10-secreting B-cell subset (i.e. CD19+CD24+CD27-). In summary, exposure of human B cells to Leishmania infantum amastigotes triggers B cells with regulatory activities mediated in part by IL-10, which could favor parasite dissemination in the organism.

Rapid Diagnostic Tests for Dengue Virus Infection in Febrile Cambodian Children: Diagnostic Accuracy and Incorporation into Diagnostic Algorithms

PLoS Neglected Tropical Diseases News - 24 February 2015 - 10:00pm

by Michael J. Carter, Kate R. Emary, Catherine E. Moore, Christopher M. Parry, Soeng Sona, Hor Putchhat, Sin Reaksmey, Ngoun Chanpheaktra, Nicole Stoesser, Andrew D. M. Dobson, Nicholas P. J. Day, Varun Kumar, Stuart D. Blacksell

Background

Dengue virus (DENV) infection is prevalent across tropical regions and may cause severe disease. Early diagnosis may improve supportive care. We prospectively assessed the Standard Diagnostics (Korea) BIOLINE Dengue Duo DENV rapid diagnostic test (RDT) to NS1 antigen and anti-DENV IgM (NS1 and IgM) in children in Cambodia, with the aim of improving the diagnosis of DENV infection.

Methodology and principal findings

We enrolled children admitted to hospital with non-localised febrile illnesses during the 5-month DENV transmission season. Clinical and laboratory variables, and DENV RDT results were recorded at admission. Children had blood culture and serological and molecular tests for common local pathogens, including reference laboratory DENV NS1 antigen and IgM assays. 337 children were admitted with non-localised febrile illness over 5 months. 71 (21%) had DENV infection (reference assay positive). Sensitivity was 58%, and specificity 85% for RDT NS1 and IgM combined. Conditional inference framework analysis showed the additional value of platelet and white cell counts for diagnosis of DENV infection. Variables associated with diagnosis of DENV infection were not associated with critical care admission (70 children, 21%) or mortality (19 children, 6%). Known causes of mortality were melioidosis (4), other sepsis (5), and malignancy (1). 22 (27%) children with a positive DENV RDT had a treatable other infection.

Conclusions

The DENV RDT had low sensitivity for the diagnosis of DENV infection. The high co-prevalence of infections in our cohort indicates the need for a broad microbiological assessment of non-localised febrile illness in these children.

Bartonella spp. in Fruit Bats and Blood-Feeding Ectoparasites in Madagascar

PLoS Neglected Tropical Diseases News - 23 February 2015 - 10:00pm

by Cara E. Brook, Ying Bai, Andrew P. Dobson, Lynn M. Osikowicz, Hafaliana C. Ranaivoson, Qiyun Zhu, Michael Y. Kosoy, Katharina Dittmar

We captured, ectoparasite-combed, and blood-sampled cave-roosting Madagascan fruit bats (Eidolon dupreanum) and tree-roosting Madagascan flying foxes (Pteropus rufus) in four single-species roosts within a sympatric geographic foraging range for these species in central Madagascar. We describe infection with novel Bartonella spp. in sampled Eidolon dupreanum and associated bat flies (Cyclopodia dubia), which nest close to or within major known Bartonella lineages; simultaneously, we report the absence of Bartonella spp. in Thaumapsylla sp. fleas collected from these same bats. This represents the first documented finding of Bartonella infection in these species of bat and bat fly, as well as a new geographic record for Thaumapsylla sp. We further relate the absence of both Bartonella spp. and ectoparasites in sympatrically sampled Pteropus rufus, thus suggestive of a potential role for bat flies in Bartonella spp. transmission. These findings shed light on transmission ecology of bat-borne Bartonella spp., recently demonstrated as a potentially zoonotic pathogen.

Comparison of Two Quantitative Real Time PCR Assays for Rickettsia Detection in Patients from Tunisia

PLoS Neglected Tropical Diseases News - 23 February 2015 - 10:00pm

by Abir Znazen, Hanen Sellami, Emna Elleuch, Zouhour Hattab, Laroussi Ben Sassi, Fatma Khrouf, Hassen Dammak, Amel Letaief, Mounir Ben Jemaa, Adnene Hammami

Background and objectives

Quantitative real time PCR (qPCR) offers rapid diagnosis of rickettsial infections. Thus, successful treatment could be initiated to avoid unfavorable outcome. Our aim was to compare two qPCR assays for Rickettsia detection and to evaluate their contribution in early diagnosis of rickettsial infection in Tunisian patients.

Patients and methods

Included patients were hospitalized in different hospitals in Tunisia from 2007 to 2012. Serology was performed by microimmunofluorescence assay using R. conorii and R. typhi antigens. Two duplex qPCRs, previously reported, were performed on collected skin biopsies and whole blood samples. The first duplex amplified all Rickettsia species (PanRick) and Rickettsia typhi DNA (Rtt). The second duplex detected spotted fever group Rickettsiae (RC00338) and typhus group Rickettsiae DNA (Rp278).

Results

Diagnosis of rickettsiosis was confirmed in 82 cases (57.7%). Among 44 skin biopsies obtained from patients with confirmed diagnosis, the first duplex was positive in 24 samples (54.5%), with three patients positive by Rtt qPCR. Using the second duplex, positivity was noted in 21 samples (47.7%), with two patients positive by Rp278 qPCR. Among79 whole blood samples obtained from patients with confirmed diagnosis, panRick qPCR was positive in 5 cases (6.3%) among which two were positive by Rtt qPCR. Using the second set of qPCRs, positivity was noted in four cases (5%) with one sample positive by Rp278 qPCR. Positivity rates of the two duplex qPCRs were significantly higher among patients presenting with negative first serum than those with already detectable antibodies.

Conclusions

Using qPCR offers a rapid diagnosis. The PanRick qPCR showed a higher sensitivity. Our study showed that this qPCR could offer a prompt diagnosis at the early stage of the disease. However, its implementation in routine needs cost/effectiveness evaluation.

Screening Diagnostic Candidates for Schistosomiasis from Tegument Proteins of Adult Schistosoma japonicum Using an Immunoproteomic Approach

PLoS Neglected Tropical Diseases News - 23 February 2015 - 10:00pm

by Min Zhang, Zhiqiang Fu, Changjian Li, Yanhui Han, Xiaodan Cao, Hongxiao Han, Yantao Liu, Ke Lu, Yang Hong, Jiaojiao Lin

Background

Schistosomiasis is one of the world’s most prevalent zoonotic diseases and a serious worldwide public health problem. Since the tegument (TG) of Schistosoma japonicum is in direct contact with the host and induces a host immune response against infection, the identification of immune response target molecules in the schistosome TG is crucial for screening diagnostic antigens for this disease.

Methodology/Principal Findings

In this study, an immunoproteomics approach used TG proteins as screening antigens to identify potential diagnostic molecules of S. japonicum. Ten spots corresponding to six proteins were identified that immunoreacted with sera from S. japonicum-infected rabbits but not sera from uninfected rabbits and their specific IgG antibody levels declined quickly after praziquantel treatment. Recombinant phosphoglycerate mutase (PGM) and UV excision repair protein RAD23 homolog B (RAD23) proteins were expressed and their diagnostic potential for schistosomiasis was evaluated and compared with schistosome soluble egg antigen (SEA) using ELISA. The results showed high sensitivity and specificity and low crossreactivity when rSjPGM-ELISA and rSjRAD23-ELISA were used to detect water buffalo schistosomiasis. Moreover, antibodies to rSjPGM and rSjRAD23 might be short-lived since they declined quickly after chemotherapy.

Conclusion/Significance

Therefore, the two schistosome TG proteins SjPGM and SjRAD23 were identified as potential diagnostic markers for the disease. The two recombinant proteins might have the potential to evaluate the effectiveness of drug treatments and for distinguishing between current and past infection.

High Prevalence of Tropheryma whipplei in Lao Kindergarten Children

PLoS Neglected Tropical Diseases News - 20 February 2015 - 10:00pm

by Alpha Kabinet Keita, Audrey Dubot-Pérès, Koukeo Phommasone, Bountoy Sibounheuang, Manivanh Vongsouvath, Mayfong Mayxay, Didier Raoult, Paul N. Newton, Florence Fenollar

Background

Tropheryma whipplei is a bacterium commonly found in feces of young children in Africa, but with no data from Asia. We estimated the prevalence of T. whipplei carriage in feces of children in Lao PDR (Laos).

Methods/Principal Findings

Using specific quantitative real-time PCR, followed by genotyping for each positive specimen, we estimated the prevalence of T. whipplei in 113 feces from 106 children in Vientiane, the Lao PDR (Laos). T. whipplei was detected in 48% (51/106) of children. Those aged ≤4 years were significantly less frequently positive (17/52, 33%) than older children (34/54, 63%; p< 0.001). Positive samples were genotyped. Eight genotypes were detected including 7 specific to Laos. Genotype 2, previously detected in Europe, was circulating (21% of positive children) in 2 kindergartens (Chompet and Akad). Genotypes 136 and 138 were specific to Chompet (21% and 15.8%, respectively) whereas genotype 139 was specific to Akad (10.55%).

Conclusions/Significance

T. whipplei is a widely distributed bacterium, highly prevalent in feces of healthy children in Laos. Further research is needed to identify the public health significance of this finding.

Repurposing Auranofin as a Lead Candidate for Treatment of Lymphatic Filariasis and Onchocerciasis

PLoS Neglected Tropical Diseases News - 20 February 2015 - 10:00pm

by Christina A. Bulman, Chelsea M. Bidlow, Sara Lustigman, Fidelis Cho-Ngwa, David Williams, Alberto A. Rascón, Jr, Nancy Tricoche, Moses Samje, Aaron Bell, Brian Suzuki, K. C. Lim, Nonglak Supakorndej, Prasit Supakorndej, Alan R. Wolfe, Giselle M. Knudsen, Steven Chen, Chris Wilson, Kean-Hooi Ang, Michelle Arkin, Jiri Gut, Chris Franklin, Chris Marcellino, James H. McKerrow, Anjan Debnath, Judy A. Sakanari

Two major human diseases caused by filariid nematodes are onchocerciasis, or river blindness, and lymphatic filariasis, which can lead to elephantiasis. The drugs ivermectin, diethylcarbamazine (DEC), and albendazole are used in control programs for these diseases, but are mainly effective against the microfilarial stage and have minimal or no effect on adult worms. Adult Onchocerca volvulus and Brugia malayi worms (macrofilariae) can live for up to 15 years, reproducing and allowing the infection to persist in a population. Therefore, to support control or elimination of these two diseases, effective macrofilaricidal drugs are necessary, in addition to current drugs. In an effort to identify macrofilaricidal drugs, we screened an FDA-approved library with adult worms of Brugia spp. and Onchocerca ochengi, third-stage larvae (L3s) of Onchocerca volvulus, and the microfilariae of both O. ochengi and Loa loa. We found that auranofin, a gold-containing drug used for rheumatoid arthritis, was effective in vitro in killing both Brugia spp. and O. ochengi adult worms and in inhibiting the molting of L3s of O. volvulus with IC50 values in the low micromolar to nanomolar range. Auranofin had an approximately 43-fold higher IC50 against the microfilariae of L. loa compared with the IC50 for adult female O. ochengi, which may be beneficial if used in areas where Onchocerca and Brugia are co-endemic with L. loa, to prevent severe adverse reactions to the drug-induced death of L. loa microfilariae. Further testing indicated that auranofin is also effective in reducing Brugia adult worm burden in infected gerbils and that auranofin may be targeting the thioredoxin reductase in this nematode.

Rapid Treponema pallidum Clearance from Blood and Ulcer Samples following Single Dose Benzathine Penicillin Treatment of Early Syphilis

PLoS Neglected Tropical Diseases News - 20 February 2015 - 10:00pm

by Craig Tipple, Rachael Jones, Myra McClure, Graham Taylor

Currently, the efficacy of syphilis treatment is measured with anti-lipid antibody tests. These can take months to indicate cure and, as a result, syphilis treatment trials require long periods of follow-up. The causative organism, Treponema pallidum (T. pallidum), is detectable in the infectious lesions of early syphilis using DNA amplification. Bacteraemia can likewise be identified, typically in more active disease. We hypothesise that bacterial clearance from blood and ulcers will predict early the standard serology-measured treatment response and have developed a qPCR assay that could monitor this clearance directly in patients with infectious syphilis. Patients with early syphilis were given an intramuscular dose of benzathine penicillin. To investigate the appropriate sampling timeframe samples of blood and ulcer exudate were collected intensively for T. pallidum DNA (tpp047 gene) and RNA (16S rRNA) quantification. Sampling ended when two consecutive PCRs were negative. Four males were recruited. The mean peak level of T. pallidum DNA was 1626 copies/ml whole blood and the mean clearance half-life was 5.7 hours (std. dev. 0.53). The mean peak of 16S rRNA was 8879 copies/ml whole blood with a clearance half-life of 3.9 hours (std. dev. 0.84). From an ulcer, pre-treatment, 67,400 T. pallidum DNA copies and 7.08x107 16S rRNA copies were detected per absorbance strip and the clearance half-lives were 3.2 and 4.1 hours, respectively. Overall, T. pallidum nucleic acids were not detected in any sample collected more than 56 hours (range 20–56) after treatment. All patients achieved serologic cure. In patients with active early syphilis, measuring T. pallidum levels in blood and ulcer exudate may be a useful measure of treatment success in therapeutic trials. These laboratory findings need confirmation on a larger scale and in patients receiving different therapies.

Epidemiology and Molecular Characterization of Cryptosporidium spp. in Humans, Wild Primates, and Domesticated Animals in the Greater Gombe Ecosystem, Tanzania

PLoS Neglected Tropical Diseases News - 20 February 2015 - 10:00pm

by Michele B. Parsons, Dominic Travis, Elizabeth V. Lonsdorf, Iddi Lipende, Dawn M. Anthony Roellig, Shadrack Kamenya, Hongwei Zhang, Lihua Xiao, Thomas R. Gillespie

Cryptosporidium is an important zoonotic parasite globally. Few studies have examined the ecology and epidemiology of this pathogen in rural tropical systems characterized by high rates of overlap among humans, domesticated animals, and wildlife. We investigated risk factors for Cryptosporidium infection and assessed cross-species transmission potential among people, non-human primates, and domestic animals in the Gombe Ecosystem, Kigoma District, Tanzania. A cross-sectional survey was designed to determine the occurrence and risk factors for Cryptosporidium infection in humans, domestic animals and wildlife living in and around Gombe National Park. Diagnostic PCR revealed Cryptosporidium infection rates of 4.3% in humans, 16.0% in non-human primates, and 9.6% in livestock. Local streams sampled were negative. DNA sequencing uncovered a complex epidemiology for Cryptosporidium in this system, with humans, baboons and a subset of chimpanzees infected with C. hominis subtype IfA12G2; another subset of chimpanzees infected with C. suis; and all positive goats and sheep infected with C. xiaoi. For humans, residence location was associated with increased risk of infection in Mwamgongo village compared to one camp (Kasekela), and there was an increased odds for infection when living in a household with another positive person. Fecal consistency and other gastrointestinal signs did not predict Cryptosporidium infection. Despite a high degree of habitat overlap between village people and livestock, our results suggest that there are distinct Cryptosporidium transmission dynamics for humans and livestock in this system. The dominance of C. hominis subtype IfA12G2 among humans and non-human primates suggest cross-species transmission. Interestingly, a subset of chimpanzees was infected with C. suis. We hypothesize that there is cross-species transmission from bush pigs (Potaochoerus larvatus) to chimpanzees in Gombe forest, since domesticated pigs are regionally absent. Our findings demonstrate a complex nature of Cryptosporidium in sympatric primates, including humans, and stress the need for further studies.

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