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The Galabat-Metema cross-border onchocerciasis focus: The first coordinated interruption of onchocerciasis transmission in Africa

PLoS Neglected Tropical Diseases News - 6 February 2020 - 10:00pm

by Moses N. Katabarwa, Isam M. A. Zarroug, Nebiyu Negussu, Nabil M. Aziz, Zerihun Tadesse, Wigdan A. Elmubark, Zainab Shumo, Kadu Meribo, Hashim Kamal, Aderajew Mohammed, Yewondwossen Bitew, Tewodros Seid, Firdaweke Bekele, Abebual Yilak, Tekola Endeshaw, Mohammed Hassen, Abate Tillahun, Fikresilasie Samuel, Henok Birhanu, Tadesse Asmare, Daniel Boakye, Sindew M. Feleke, Thomas Unnasch, Rory Post, Tarig Higazi, Emily Griswold, Charles Mackenzie, Frank Richards

Background

Onchocerciasis transmission across international borders is not uncommon, yet a coordinated cross border stops mass drug administration (MDA) decision has not been documented.

Methods/Principle findings

The Galabat-Metema focus involves neighboring districts on the border between Sudan and Ethiopia. Mass drug administration (MDA) was provided once and subsequently twice per year in this focus, with twice-per-year beginning in Ethiopia’s Metema subfocus in 2016 and in the Sudan’s Galabat subfocus in 2008. Ov16 ELISA-based serosurveys were conducted in 6072 children under 10 years of age in the Metema subfocus in 2014, and 3931 in the Galabat in 2015. Between 2014 and 2016, a total of 27,583 vector Simulium damnosum flies from Metema and 9,148 flies from Galabat were tested by pool screen PCR for Onchocerca volvulus O-150 DNA. Only 8 children were Ov16 seropositive (all in the Metema subfocus); all were negative by skin snip PCR. The upper limit of the 95% confidence interval (UCL) for Ov16 seropositive was <0.1% for the overall focus and 0.14 positive fly heads per 2000 (UCL = 0.39/2000). However, an entomological ‘hotspot’ was detected on the Wudi Gemzu river in Metema district. The hotspot was confirmed when 4 more positive fly pools were found on repeat testing in 2017 (1.04 L3/2000 flies (UCL = 2.26/2000). Information exchange between the two countries led to stopping MDA in a coordinated fashion in 2018, with the exception of the hotspot at Wudi Gemzu, where MDA with ivermectin was increased to every three months to hasten interruption of transmission.

Conclusion

Coordinated stop MDA decisions were made by Sudan and Ethiopia based on data satisfying the World Health Organization’s criteria for interruption of onchocerciasis transmission. Definitions of entomological ‘hotspots’ and buffer zones around the focus are proposed.

“<i>Buruli ulcer and leprosy</i>, <i>they are intertwined</i>”: Patient experiences of integrated case management of skin neglected tropical diseases in Liberia

PLoS Neglected Tropical Diseases News - 5 February 2020 - 10:00pm

by Mateo Prochazka, Joseph Timothy, Rachel Pullan, Karsor Kollie, Emerson Rogers, Abednego Wright, Jennifer Palmer

Background

Skin neglected tropical diseases (NTDs) such as Buruli ulcer (BU) and leprosy produce significant stigma and disability. Shared clinical presentations and needs for care present opportunities for integrated case management in co-endemic areas. As global policies are translated into local integrated services, there remains a need to monitor what new configurations of care emerge and how individuals experience them.

Methods

To explore patient experiences of integrated case management for skin NTDs, in 2018, we conducted a field-based qualitative case series in a leprosy rehabilitation centre in Ganta, Liberia where BU services were recently introduced. Twenty patients with BU (n = 10) and leprosy (n = 10) participated in in-depth interviews that incorporated photography methods. We contextualised our findings with field observations and unstructured interviews with health workers.

Findings

The integration of care for BU and leprosy prompted new conceptualisations of these diseases and experiences of NTD stigma. Some patients felt anxiety about using services because they feared being infected with the other disease. Other patients viewed the two diseases as ‘intertwined’: related manifestations of the same condition. Configurations of inter-disease stigma due to fear of transmission were buffered by joint health education sessions which also appeared to facilitate social support between patients in the facility. For both diseases, medication and wound care were viewed as the cornerstones of care and appreciated as interventions that led to rehabilitation of the whole patient group through shared experiences of healing, avoidance of physical deformities and stigma reduction. Patient accounts of intense pain during wound care for BU and inability of staff to manage severe complications, however, exposed some shortcomings of medical care for the newly integrated service, as did patient fears of long-lasting disability due to lack of physiotherapy services.

Significance

Under integrated care policies, the possibility of new discourses about skin NTD identities emerging along with new configurations of stigma may have unanticipated consequences for patients' experiences of case management. The social experience of integrated medication and wound dressing has the potential to link patients within a single, supportive patient community. Control programmes with resource constraints should anticipate potential challenges of integrating care, including the need to ameliorate lasting disability and provide adequate clinical management of severe BU cases.

Genetic variation in <i>Interleukin-32</i> influence the immune response against New World <i>Leishmania</i> species and susceptibility to American Tegumentary Leishmaniasis

PLoS Neglected Tropical Diseases News - 5 February 2020 - 10:00pm

by Jéssica Cristina dos Santos, Valéria Bernadete Leite Quixabeira, Muriel Vilela Teodoro Silva, Michelle S. M. A. Damen, Kiki Schraa, Martin Jaeger, Marije Oosting, Samuel T. Keating, Miriam Leandro Dorta, Sebastião Alves Pinto, Fernanda Bugalho Duarte, Ledice Inácia de Araújo Pereira, Mihai G. Netea, Fátima Ribeiro-Dias, Leo A. B. Joosten

Interleukin-32 is a novel inflammatory mediator that has been described to be important in the immunopathogenesis and control of infections caused by Leishmania parasites. By performing experiments with primary human cells in vitro, we demonstrate that the expression of IL-32 isoforms is dependent on the time exposed to L. amazonensis and L. braziliensis antigens. Moreover, for the first time we show the functional consequences of three different genetic variations in the IL32 (rs4786370, rs4349147, rs1555001) modulating IL-32γ expression, influencing innate and adaptive cytokine production after Leishmania exposure. Using a Brazilian cohort of 107 American Tegumentary Leishmaniasis patients and a control cohort of 245 healthy individuals, the IL32 rs4786370 genetic variant was associated with protection against ATL, whereas the IL32 rs4349147 was associated with susceptibility to the development of localized cutaneous and mucosal leishmaniasis. These novel insights may help improve therapeutic strategies and lead to benefits for patients suffering from Leishmania infections.

Iron trafficking in patients with Indian Post kala-azar dermal leishmaniasis

PLoS Neglected Tropical Diseases News - 5 February 2020 - 10:00pm

by Aishwarya Dighal, Debanjan Mukhopadhyay, Ritika Sengupta, Srija Moulik, Shibabrata Mukherjee, Susmita Roy, Surya Jyati Chaudhuri, Nilay K. Das, Mitali Chatterjee

Background

During infections involving intracellular pathogens, iron performs a double-edged function by providing the pathogen with nutrients, but also boosts the host’s antimicrobial arsenal. Although the role of iron has been described in visceral leishmaniasis, information regarding its status in the dermal sequel, Post Kala-azar Dermal Leishmaniasis (PKDL) remains limited. Accordingly, this study aimed to establish the status of iron within monocytes/macrophages of PKDL cases.

Methodology/Principal findings

The intramonocytic labile iron pool (LIP), status of CD163 (hemoglobin-haptoglobin scavenging receptor) and CD71 (transferrin receptor, Tfr) were evaluated within CD14+ monocytes by flow cytometry, and soluble CD163 by ELISA. At the lesional sites, Fe3+ status was evaluated by Prussian blue staining, parasite load by qPCR, while the mRNA expression of Tfr (TfR1/CD71), CD163, divalent metal transporter-1 (DMT-1), Lipocalin-2 (Lcn-2), Heme-oxygenase-1 (HO-1), Ferritin, Natural resistance-associated macrophage protein (NRAMP-1) and Ferroportin (Fpn-1) was evaluated by droplet digital PCR. Circulating monocytes demonstrated elevated levels of CD71, CD163 and soluble CD163, which corroborated with an enhanced lesional mRNA expression of TfR, CD163, DMT1 and Lcn-2. Additionally, the LIP was raised along with an elevated mRNA expression of ferritin and HO-1, as also iron exporters NRAMP-1 and Fpn-1.

Conclusions/Significance

In monocytes/macrophages of PKDL cases, enhancement of the iron influx gateways (TfR, CD163, DMT-1 and Lcn-2) possibly accounted for the enhanced LIP. However, enhancement of the iron exporters (NRAMP-1 and Fpn-1) defied the classical Ferritinlow/Ferroportinhigh phenotype of alternatively activated macrophages. The creation of such a pro-parasitic environment suggests incorporation of chemotherapeutic strategies wherein the availability of iron to the parasite can be restricted.

Impact of flavivirus vaccine-induced immunity on primary Zika virus antibody response in humans

PLoS Neglected Tropical Diseases News - 4 February 2020 - 10:00pm

by Stefan Malafa, Iris Medits, Judith H. Aberle, Stephan W. Aberle, Denise Haslwanter, Georgios Tsouchnikas, Silke Wölfel, Kristina L. Huber, Elena Percivalle, Pascal Cherpillod, Melissa Thaler, Lena Roßbacher, Michael Kundi, Franz X. Heinz, Karin Stiasny

Background

Zika virus has recently spread to South- and Central America, causing congenital birth defects and neurological complications. Many people at risk are flavivirus pre-immune due to prior infections with other flaviviruses (e.g. dengue virus) or flavivirus vaccinations. Since pre-existing cross-reactive immunity can potentially modulate antibody responses to Zika virus infection and may affect the outcome of disease, we analyzed fine-specificity as well as virus-neutralizing and infection-enhancing activities of antibodies induced by a primary Zika virus infection in flavivirus-naïve as well as yellow fever- and/or tick-borne encephalitis-vaccinated individuals.

Methodology

Antibodies in sera from convalescent Zika patients with and without vaccine-induced immunity were assessed by ELISA with respect to Zika virus-specificity and flavivirus cross-reactivity. Functional analyses included virus neutralization and infection-enhancement. The contribution of IgM and cross-reactive antibodies to these properties was determined by depletion experiments.

Principal findings

Pre-existing flavivirus immunity had a strong influence on the antibody response in primary Zika virus infections, resulting in higher titers of broadly flavivirus cross-reactive antibodies and slightly lower levels of Zika virus-specific IgM. Antibody-dependent enhancement (ADE) of Zika virus was mediated by sub-neutralizing concentrations of specific IgG but not by cross-reactive antibodies. This effect was potently counteracted by the presence of neutralizing IgM. Broadly cross-reactive antibodies were able to both neutralize and enhance infection of dengue virus but not Zika virus, indicating a different exposure of conserved sequence elements in the two viruses.

Conclusions

Our data point to an important role of flavivirus-specific IgM during the transient early stages of infection, by contributing substantially to neutralization and by counteracting ADE. In addition, our results highlight structural differences between strains of Zika and dengue viruses that are used for analyzing infection-enhancement by cross-reactive antibodies. These findings underscore the possible impact of specific antibody patterns on flavivirus disease and vaccination efficacy.

Epidemiology of Congenital Rubella Syndrome (CRS) in India, 2016-18, based on data from sentinel surveillance

PLoS Neglected Tropical Diseases News - 3 February 2020 - 10:00pm

by Manoj Murhekar, Sanjay Verma, Kuldeep Singh, Ashish Bavdekar, Naveen Benakappa, Sridhar Santhanam, Gajanan Sapkal, Rajlakshmi Viswanathan, Mini P. Singh, Vijaya Lakshmi Nag, Sadanand Naik, Munivenkatappa Ashok, Asha Mary Abraham, Devika Shanmugasundaram, R. Sabarinathan, Valsan Philip Verghese, Suji George, Ravinder Kaur Sachdeva, Jyoti Kolekar, S. Manasa, Jagat Ram, Madhu Gupta, Manoj K. Rohit, Praveen Kumar, Parul Chawla Gupta, R. K. Ratho, Sanjay Kumar Munjal, Urvashi Nehra, Daisy Khera, Neeraj Gupta, Nidhi Kaushal, Pratibha Singh, Ravisekhar Gadepalli, Neelam Vaid, Sandeep Kadam, Sanjay Shah, S. Mahantesh, Vykuntaraju K. Gowda, Pradeep Haldar, M. K. Aggarwal, Nivedita Gupta

Background

Government of India is committed to eliminate measles and control rubella/congenital rubella syndrome (CRS) by 2020. In 2016, CRS surveillance was established in five sentinel sites. We analyzed surveillance data to describe the epidemiology of CRS in India.

Methodology/Principal findings

We used case definitions adapted from the WHO-recommended standards for CRS surveillance. Suspected patients underwent complete clinical examination including cardiovascular system, ophthalmic examination and assessment for hearing impairment. Sera were tested for presence of IgM and IgG antibodies against rubella. Of the 645 suspected CRS patients enrolled during two years, 137 (21.2%) were classified as laboratory confirmed CRS and 8 (1.2%) as congenital rubella infection. The median age of laboratory confirmed CRS infants was 3 months. Common clinical features among laboratory confirmed CRS patients included structural heart defects in 108 (78.8%), one or more eye signs (cataract, glaucoma, pigmentary retinopathy) in 82 (59.9%) and hearing impairment in 51. (38.6%) Thirty-three (24.1%) laboratory confirmed CRS patients died over a period of 2 years. Surveillance met the quality indicators in terms of adequacy of investigation, adequacy of sample collection for serological diagnosis as well as virological confirmation.

Conclusions/Significance

About one fifth suspected CRS patients were laboratory confirmed, indicating significance of rubella as a persistent public health problem in India. Continued surveillance will generate data to monitor the progress made by the rubella control program in the country.

<i>Aedes</i> cadherin receptor that mediates <i>Bacillus thuringiensis</i> Cry11A toxicity is essential for mosquito development

PLoS Neglected Tropical Diseases News - 3 February 2020 - 10:00pm

by Jianwu Chen, Karly G. Aimanova, Sarjeet S. Gill

Aedes cadherin (AaeCad, AAEL024535) has been characterized as a receptor for Bacillus thuringiensis subsp. israelensis (Bti) Cry11A toxins. However, its role in development is still unknown. In this study, we modified the cadherin gene using ZFN and TALEN. Even though we obtained heterozygous deletions, no homozygous mutants were viable. Because ZFN and TALEN have lower off-targets than CRISPR/Cas9, we conclude the cadherin gene is essential for Aedes development. In contrast, in lepidopteran insects loss of a homologous cadherin does not appear to be lethal, since homozygous mutants are viable. To analyze the role of AaeCad in vivo, we tagged this protein with EGFP using CRISPR-Cas9-mediated homologous recombination and obtained a homozygous AaeCad-EGFP line. Addition of Aedes Rad51 mRNA enhanced the rate of recombination. We then examined AaeCad protein expression in most tissues and protein dynamics during mosquito development. We observe that AaeCad is expressed in larval or adult midgut-specific manner and its expression pattern changed during the mosquito development. Confocal images showed AaeCad has high expression in larval caecae and posterior midgut, and also in adult midgut. Expression of AaeCad is observed primarily in the apical membranes of epithelial cells, and not in cell-cell junctions. The expression pattern observed suggests AaeCad does not appear to play a role in these junctions. However, we cannot exclude its role beyond cell-cell adhesion in the midgut. We also observed that Cry11A bound to the apical side of larval gastric caecae and posterior midgut cells exactly where AaeCad-EGFP was expressed. Their co-localization suggests that AaeCad is indeed a receptor for the Cry11A toxin. Using this mosquito line we also observed that low doses of Cry11A toxin caused the cells to slough off membranes, which likely represents a defense mechanism, to limit cell damage from Cry11A toxin pores formed in the cell membrane.

Severe <i>Strongyloides stercoralis</i> infection in kidney transplant recipients: A multicenter case-control study

PLoS Neglected Tropical Diseases News - 31 January 2020 - 10:00pm

by Lísia Miglioli-Galvão, José Osmar Medina Pestana, Guilherme Santoro Lopes, Renato Torres Gonçalves, Lúcio R. Requião Moura, Álvaro Pacheco Silva, Lígia Camera Pierrotti, Elias David Neto, Evelyne Santana Girão, Cláudia Maria Costa de Oliveira, Cely Saad Abboud, João Ítalo Dias França, Carolina Devite Bittante, Luci Corrêa, Luís Fernando Aranha Camargo

Background

Severe Strongyloides stercoralis infection in kidney transplant recipients is associated with considerable morbidity and mortality, although little is known about the risk factors for such infection.

Methodology/Principal findings

This was a retrospective, multicenter, case–control study in which we assessed the risk factors for and clinical outcomes of severe S. stercoralis infections in kidney transplant recipients in Brazil. We included 138 kidney transplant recipients: 46 cases and 92 controls. Among the cases, the median number of days from transplantation to diagnosis was 117 (interquartile range [IQR], 73.5–965) and the most common clinical findings were gastrointestinal symptoms (in 78.3%) and respiratory symptoms (in 39.1%), whereas fever and eosinophilia were seen in only 32.6% and 43.5%, respectively. The 30-day all-cause mortality among the cases was 28.3% overall and was significantly higher among the cases of infection occurring within the first three months after transplantation (47% vs. 17.2%, P = 0.04). The independent risk factors were receiving a transplant from a deceased donor (odds ratio [OR] = 6.16, 95% confidence interval [CI] = 2.05–18.5), a history of bacterial infection (OR = 3.04, 95% CI = 1.2–7.5), and a cumulative corticosteroid dose (OR = 1.005, 95% CI = 1.001–1.009). The independent predictors of mortality were respiratory failure (OR = 98.33, 95% CI = 4.46–2169.77) and concomitant bacteremia (OR = 413.00, 95% CI = 4.83–35316.61).

Conclusions/Significance

Severe S. stercoralis infections are associated with considerable morbidity and mortality after kidney transplantation. In endemic areas, such infection may occur late after transplantation, although it seems to be more severe when it occurs earlier after transplantation. Specific risk factors and clinical manifestations can identify patients at risk, who should receive prophylaxis or early treatment.

High cholera vaccination coverage following emergency campaign in Haiti: Results from a cluster survey in three rural Communes in the South Department, 2017

PLoS Neglected Tropical Diseases News - 31 January 2020 - 10:00pm

by Ashley Sharp, Alexandre Blake, Jérôme Backx, Isabella Panunzi, Robert Barrais, Fabienne Nackers, Francisco Luquero, Yves Gaston Deslouches, Sandra Cohuet

Oral cholera vaccine (OCV) has increasingly been used as an outbreak control measure, but vaccine shortages limit its application. A two-dose OCV campaign targeting residents aged over 1 year was launched in three rural Communes of Southern Haiti during an outbreak following Hurricane Matthew in October 2016. Door-to-door and fixed-site strategies were employed and mobile teams delivered vaccines to hard-to-reach communities. This was the first campaign to use the recently pre-qualified OCV, Euvichol. The study objective was to estimate post-campaign vaccination coverage in order to evaluate the campaign and guide future outbreak control strategies. We conducted a cluster survey with sampling based on random GPS points. We identified clusters of five households and included all members eligible for vaccination. Local residents collected data through face-to-face interviews. Coverage was estimated, accounting for the clustered sampling, and 95% confidence intervals calculated. 435 clusters, 2,100 households and 9,086 people were included (99% response rate). Across the three communes respectively, coverage by recall was: 80.7% (95% CI:76.8–84.1), 82.6% (78.1–86.4), and 82.3% (79.0–85.2) for two doses and 94.2% (90.8–96.4), 91.8% (87–94.9), and 93.8% (90.8–95.9) for at least one dose. Coverage varied by less than 9% across age groups and was similar among males and females. Participants obtained vaccines from door-to-door vaccinators (53%) and fixed sites (47%). Most participants heard about the campaign through community ‘criers’ (58%). Despite hard-to-reach communities, high coverage was achieved in all areas through combining different vaccine delivery strategies and extensive community mobilisation. Emergency OCV campaigns are a viable option for outbreak control and where possible multiple strategies should be used in combination. Euvichol will help alleviate the OCV shortage but effectiveness studies in outbreaks should be done.

Evidence of hybridization, mitochondrial introgression and biparental inheritance of the kDNA minicircles in <i>Trypanosoma cruzi I</i>

PLoS Neglected Tropical Diseases News - 31 January 2020 - 10:00pm

by Fanny Rusman, Noelia Floridia-Yapur, Paula G. Ragone, Patricio Diosque, Nicolás Tomasini

Background

Genetic exchange in Trypanosoma cruzi is controversial not only in relation to its frequency, but also to its mechanism. Parasexual genetic exchange has been proposed based on laboratory hybrids, but population genomics strongly suggests meiosis in T. cruzi. In addition, mitochondrial introgression has been reported several times in natural isolates although its mechanism is not fully understood yet. Moreover, hybrid T. cruzi DTUs (TcV and TcVI) have inherited at least part of the kinetoplastic DNA (kDNA = mitochondrial DNA) from both parents.

Methodology/Principal findings

In order to address such topics, we sequenced and analyzed fourteen nuclear DNA fragments and three kDNA maxicircle genes in three TcI stocks which are natural clones potentially involved in events of genetic exchange. We also deep-sequenced (a total of 6,146,686 paired-end reads) the minicircle hypervariable region (mHVR) of the kDNA in such three strains. In addition, we analyzed the DNA content by flow cytometry to address cell ploidy. We observed that most polymorphic sites in nuclear loci showed a hybrid pattern in one cloned strain and the other two cloned strains were compatible as parental strains (or nearly related to the true parents). The three clones had almost the same ploidy and the DNA content was similar to the reference strain Sylvio (a nearly diploid strain). Despite maxicircle genes evolve faster than nuclear housekeeping ones, we detected no polymorphisms in the sequence of three maxicircle genes showing mito-nuclear discordance. Lastly, the hybrid stock shared 66% of its mHVR clusters with one putative parent and 47% with the other one; in contrast, the putative parental stocks shared less than 30% of the mHVR clusters between them.

Conclusions/significance

The results suggest a reductive division, a natural hybridization, biparental inheritance of the minicircles in the hybrid and maxicircle introgression. The models including such phenomena and explaining the relationships between these three clones are discussed.

Post-elimination surveillance in formerly onchocerciasis endemic focus in Southern Mexico

PLoS Neglected Tropical Diseases News - 30 January 2020 - 10:00pm

by Nadia A. Fernández-Santos, Thomas R. Unnasch, Isabel C. Rodríguez-Luna, Francisco Gibert Prado-Velasco, Adebiyi A. Adeniran, Humberto Martínez-Montoya, Mario A. Rodríguez-Pérez

Background

All formerly endemic communities of the Southern Chiapas focus of onchocerciasis in Mexico were treated with ivermectin until parasite transmission was eliminated by 2015. Transmission of onchocerciasis did not resume during a period of three years (2012–2014) following the final distribution of ivermectin in 2011; it was thus concluded that transmission remained undetectable without intervention. WHO thus declared the elimination of transmission of onchocerciasis from Mexico in 2015.

Methodology/Principal findings

From 2016 to the present, post-elimination surveillance (PES) based on examination for suspected onchocercomas was performed in the former Southern Chiapas focus. Each year, over 60% of the total population (range = 85,347–104,106 individuals) of the formerly endemic communities were examined for onchocercomas. Thirty-four individuals were found harboring suspected onchocercomas in the PES surveys conducted from 2016–2019. Of these, one female of 7 years of age who had immigrated from a formerly endemic focus, harbored an infertile (sterile) female in the suspected onchocercoma; all others were negative. Skin biopsy assessments were performed from March through May 2017 in three communities where the female resided. None of the 83 individuals of the three communities examined by skin biopsy were mf positive. Similarly, none of the biopsies from the individuals were found to contain parasite DNA when tested by polymerase chain reaction-enzyme-linked immunosorbent assay (PCR-ELISA).

Conclusions/Significance

These provide support to the conclusion that onchocerciasis has been eliminated from Mexico.

What constitutes a neglected tropical disease?

PLoS Neglected Tropical Diseases News - 30 January 2020 - 10:00pm

by Peter J. Hotez, Serap Aksoy, Paul J. Brindley, Shaden Kamhawi

The World Health Organization (WHO) currently classifies 20 diseases and conditions as neglected tropical diseases (NTDs). However, since its inception in 2007, PLOS Neglected Tropical Diseases has considered an expanded list that includes additional diseases with the chronic and/or debilitating, and poverty-promoting features of NTDs. Described here is an update of our current scope, which attempts to embrace all of the NTDs, and a discussion of the status of some of the more debated medical conditions in terms of whether or not they constitute an NTD.

Determinants of intentions to prevent triatomine infestation based on the health belief model: An application in rural southern Ecuador

PLoS Neglected Tropical Diseases News - 30 January 2020 - 10:00pm

by Benjamin R. Bates, Anita G. Villacís, Angela Mendez-Trivino, Luis E. Mendoza, Mario J. Grijalva

Introduction

Control of triatomine infestation is a key strategy for the prevention of Chagas disease (CD). To promote this strategy, it is important to know which antecedents to behavioral change are the best to emphasize when promoting prevention.

Objective

The aim of this study was to determine predictors for intention to prevent home infestation based on the Health Belief Model (HBM), a commonly used health intervention planning theory.

Materials & methods

A cross-sectional study was conducted with 112 heads of household in six communities with endemic and high rates of triatomine infestation in Loja province, Ecuador. The data was collected by a questionnaire including perceived severity, susceptibility, benefits to action, barriers to action, and self-efficacy. These data were also used to predict actual infestation of homes.

Results

Community members reported strong intentions to prevent home infestation. HBM constructs predicted about 14% of the observed variance in intentions. Perceived susceptibility and severity did not predict behavioral intention well; perceived barriers to small-scale action that reduce likelihood of infestation and self-efficacy in participating in surveillance systems did. Self-efficacy and perception of barriers were equally powerful predictors. The HBM constructs, however, did not predict well actual infestation.

Conclusion

The findings supported the HBM as a way to predict intentions to prevent infestation of the home by triatomine bugs. The findings highlight that messages emphasizing self-efficacy in participating in surveillance systems and overcoming barriers to small-scale action that reduce likelihood of infestation, rather than a focus on risk, should be central messages when designing and implementing educational interventions for CD. The gap between behavioral intention and actual infestation reveals the need to assess home practices and their actual efficacy to fully enact and apply the HBM.

Ruling out early trimester pregnancy when implementing community-based deworming programs

PLoS Neglected Tropical Diseases News - 30 January 2020 - 10:00pm

by Kariane St-Denis, Brittany Blouin, Elham Rahme, Martin Casapia, Antonio Montresor, Denise Mupfasoni, Pamela Sabina Mbabazi, Theresa W. Gyorkos

Background

Large-scale deworming programs have, to date, mostly targeted preschool- and school-age children. As community-based deworming programs become more common, deworming will be offered to women of reproductive age. The World Health Organization recommends preventive chemotherapy be administered to pregnant women only after the first trimester. It is therefore important for deworming programs to be able to identify women in early pregnancy. Our objective was to validate a short questionnaire which could be used by deworming program managers to identify and screen out women in early pregnancy.

Methodology/Principal findings

In May and June 2018, interviewers administered a questionnaire, followed by a pregnancy test, to 1,203 adult women living in the Peruvian Amazon. Regression analyses were performed to identify questions with high predictive properties (using the pregnancy test as the gold standard). Test parameters were computed at different decision tree nodes (where nodes represented questions). With 106 women confirmed to be pregnant, the positive predictive value of asking the single question ‘Are you pregnant?’ was 100%, at a ‘cost’ of a false negative rate of 1.9% (i.e. 21 women were incorrectly identified as not pregnant when they were truly pregnant). Additional questions reduced the false negative rate, but increased the false positive rate. Rates were dependent on both the combination and the order of questions.

Conclusions/Significance

To identify women in early pregnancy when deworming programs are community-based, both the number and order of questions are important. The local context and cultural acceptability of different questions should inform this decision. When numbers are manageable and resources are available, pregnancy tests can be considered at different decision tree nodes to confirm pregnancy status. Trade-offs in terms of efficiency and misclassification rates will need to be considered to optimize deworming coverage in women of reproductive age.

Reassessing therapeutic antibodies for neglected and tropical diseases

PLoS Neglected Tropical Diseases News - 30 January 2020 - 10:00pm

by Rob Hooft van Huijsduijnen, Somei Kojima, Dee Carter, Hisafumi Okabe, Akihide Sato, Wataru Akahata, Timothy N. C. Wells, Kei Katsuno

In the past two decades there has been a significant expansion in the number of new therapeutic monoclonal antibodies (mAbs) that are approved by regulators. The discovery of these new medicines has been driven primarily by new approaches in inflammatory diseases and oncology, especially in immuno-oncology. Other recent successes have included new antibodies for use in viral diseases, including HIV. The perception of very high costs associated with mAbs has led to the assumption that they play no role in prophylaxis for diseases of poverty. However, improvements in antibody-expression yields and manufacturing processes indicate this is a cost-effective option for providing protection from many types of infection that should be revisited. Recent technology developments also indicate that several months of protection could be achieved with a single dose. Moreover, new methods in B cell sorting now enable the systematic identification of high-quality antibodies from humanized mice, or patients. This Review discusses the potential for passive immunization against schistosomiasis, fungal infections, dengue, and other neglected diseases.

Comparative specificity and sensitivity of NS1-based serological assays for the detection of flavivirus immune response

PLoS Neglected Tropical Diseases News - 29 January 2020 - 10:00pm

by Erick Mora-Cárdenas, Chiara Aloise, Valentina Faoro, Nataša Knap Gašper, Miša Korva, Ilaria Caracciolo, Pierlanfranco D’Agaro, Tatjana Avšič-Županc, Alessandro Marcello

Flaviviruses are relevant animal and human pathogens of increasing importance worldwide. The similarities of the initial clinical symptoms and the serological cross-reactivity of viral structural antigens make a laboratory diagnosis of flavivirus infection problematic. The main aim of the present study was the comparative specificity and sensitivity analysis of the non-structural protein NS1 as an antigen to detect flavivirus antibodies in sera from exposed individuals. A strategy for the purification of native recombinant non-structural protein 1 of representative flaviviruses including tick-borne encephalitis, West Nile, Zika and dengue virus was developed. The immunological properties of the purified antigens were analyzed using sera of immunized mice and of infected individuals in comparison with standard commercial assays. Recombinant NS1 protein was confirmed as a valuable option for the detection of flavivirus antibodies with reduced cross-reactivity and high sensitivity offering additional advantages for the detection of vaccine breakthrough cases.

World neglected tropical diseases day

PLoS Neglected Tropical Diseases News - 29 January 2020 - 10:00pm

by Peter J. Hotez, Serap Aksoy, Paul J. Brindley, Shaden Kamhawi

January 30, 2020 is the first-ever World Neglected Tropical Diseases Day (World NTD Day), a day when we celebrate the achievements made towards control of the world’s NTDs, yet recognize the daunting challenges we face in the control and elimination of these conditions.

Male predominance in reported Visceral Leishmaniasis cases: Nature or nurture? A comparison of population-based with health facility-reported data

PLoS Neglected Tropical Diseases News - 29 January 2020 - 10:00pm

by Kristien Cloots, Sakib Burza, Paritosh Malaviya, Epco Hasker, Sangeeta Kansal, Guy Mollett, Jaya Chakravarty, Nurpur Roy, Bibek Kumar Lal, Suman Rijal, Shyam Sundar, Marleen Boelaert

Background

Bangladesh, India, and Nepal aim for the elimination of Visceral Leishmaniasis (VL), a systemic parasitic infectious disease, as a public health problem by 2020. For decades, male patients have comprised the majority of reported VL cases in this region. By comparing this reported VL sex ratio to the one observed in population-based studies conducted in the Indian subcontinent, we tested the working hypothesis that mainly socio-cultural gender differences in healthcare-seeking behavior explain this gender imbalance.

Methodology/Principal findings

We compared the observed sex ratio of male versus female among all VL cases reported by the health system in Nepal and in the two most endemic states in India with that observed in population-based cohort studies in India and Nepal. Also, we assessed male sex as a potential risk factor for seroprevalence at baseline, seroconversion, and VL incidence in the same population-based data. The male/female ratio among VL cases reported by the health systems was 1.40 (95% CI 1.37–1.43). In the population cohort data, the age- and study site-adjusted male to female risk ratio was 1.27 (95% CI 1.08–1.51). Also, males had a 19% higher chance of being seropositive at baseline in the population surveys (RR 1.19; 95% CI 1.11–1.27), while we observed no significant difference in seroconversion rate between both sexes at the DAT cut-off titer defined as the primary endpoint.

Conclusions/Significance

Our population-based data show that male sex is a risk factor for VL, and not only as a socio-cultural determinant. Biological sex-related differences likely play an important role in the pathogenesis of this disease.

The detection of anti-dengue virus IgM in urine in participants enrolled in an acute febrile illness study in Puerto Rico

PLoS Neglected Tropical Diseases News - 29 January 2020 - 10:00pm

by Elba Caraballo, B. Katherine Poole-Smith, Kay M. Tomashek, Brenda Torres-Velasquez, Luisa I. Alvarado, Olga D. Lorenzi, Carmen Ramos, Jessica Carrión, Elizabeth Hunsperger

Background

Dengue is an important arboviral disease with about 100 million dengue cases per year, of which, ~5% result in severe disease. Clinical differentiation of dengue from other acute febrile illnesses (AFI) is difficult, and diagnostic blood tests are costly. We evaluated the utility of anti-DENV IgM in urine to identify dengue cases among AFI patients enrolled in a clinical study.

Methods

Between May 2012-March 2013, 1538 study participants with fever for ≤7 days were enrolled, a medical history was obtained, and serum and urine specimens were collected. Serum was tested for DENV RNA and anti-DENV IgM. Urine was tested for anti-DENV IgM, and its sensitivity and specificity to detect sera laboratory-positive dengue cases were calculated. We evaluated if urine anti-DENV IgM positivity early (≤5 days post-illness onset [DPO]) and late (6–14 DPO) in the clinical course was associated with dengue severity.

Results

Urine anti-DENV IgM sensitivity and specificity were 47.4% and 98.5%, respectively, when compared with serum anti-DENV IgM ELISA results, and 29.7% and 91.1% when compared with serum rRT-PCR results. There was no correlation between urine anti-DENV IgM positivity and patient sex or pre-existing chronic disease. Early in the clinical course, a significantly higher proportion of those who developed dengue with warning signs had anti-DENV IgM in their urine when compared to those without warning signs (20.4% vs. 4.3%). There was no difference in the proportion with urine anti-DENV IgM positivity between severity groups late in the clinical course.

Conclusion

While detection of urine anti-DENV IgM lacked adequate diagnostic sensitivity, it is a highly specific marker for laboratory-positive dengue, and its presence early in the clinical course may distinguish those with more severe disease. Further assessment of urine anti-DENV IgM by DPO is warranted to determine its utility as an early diagnostic (and possibly prognostic) marker for dengue.

<i>Anisakis</i> Sensitization in the Croatian Fish Processing Workers: Behavioral Instead of Occupational Risk Factors?

PLoS Neglected Tropical Diseases News - 27 January 2020 - 10:00pm

by Ana Jerončić, Diana Nonković, Anamarija Vrbatović, Jerko Hrabar, Ivana Bušelić, Victoria Martínez-Sernández, Santiago A. Lojo Rocamonde, Florencio M. Ubeira, Sonja Jaman, Esma Čečuk Jeličić, Marco Amati, Maria Angeles Gomez Morales, Boris Lukšić, Ivona Mladineo

We undertook the first study systematically evaluating the risk of Anisakis-sensitization in Croatian fish-processing workers and potential genetic susceptibility to anisakiasis. Anti-Anisakis IgE seroprevalence and risk factors for 600 employees of Croatian fish processing facilities and 466 blood donor controls, were assessed by indirect ELISA targeted with: recombinant Ani s 1 and Ani s 7 allergens, an Anisakis crude extract, the commercial ImmunoCAP kit, and questionnaires. Genetic susceptibility to anisakiasis was evaluated by genotypisation of human leukocytes alleles (HLA). Anti-Anisakis seropositive and a fraction of negative subjects were also assessed by ELISA and Western Blot (WB) for IgG seroprevalence to Trichinella spp. Overall, the observed anti-Anisakis seroprevalence inferred by indirect ELISA was significantly higher in fish processing workers (1.8%, 95% CI 0.9–3.3%) compared to the controls (0%, 0–0.8%). Seven out of 11 Ani s 1 and Ani s 7-positives and none of selected 65 negative sera, tested positive on whole-Anisakis extract (ImmunoCAP), whereas Anisakis crude extract ELISA detected 3.9% (2.4–6.0%) seropositives in fish processing workers, three (14%) of which showed IgE reactivity to milk proteins. The highest risk associated with Anisakis-sensitization among workers was fishing in the free time, rather than any of attributes related to the occupational exposure. Although no association was observed between anti-Anisakis seropositivity and wearing gloves or protective goggles, the majority of workers (92%) wore protective gloves, minimizing the risk for Anisakis sensitization via skin contact. Six HLA alleles within DRB1 gene were significantly associated with seropositivity under dominant, allelic or recessive models. All sera confirmed negative for anti-Trichinella spp. IgG. The study exhaustively covered almost all marine fish processing workers in Croatia, reflecting real-time Anisakis sensitization status within the industry, already under the influence of wide array of allergens.

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