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Transmission of Zika virus through breast milk and other breastfeeding-related bodily-fluids: A systematic review

PLoS Neglected Tropical Diseases News - 10 April 2017 - 9:00pm

by Susannah Colt, Maria N. Garcia-Casal, Juan Pablo Peña-Rosas, Julia L. Finkelstein, Pura Rayco-Solon, Zita C. Weise Prinzo, Saurabh Mehta

Background

Zika virus (ZIKV) infection is an emerging mosquito-borne disease, which is associated with an increase in central nervous system malformations and newborn microcephaly cases. This review investigated evidence of breastfeeding transmission from ZIKV-infected mothers to their children and the presence of ZIKV infection in breastfeeding-related fluids.

Methodology/Principal findings

We conducted a systematic review of observational studies, case studies, and surveillance reports involving breastfeeding women with ZIKV infection in several international databases. Data extraction and analysis were conducted following a PROSPERO-registered protocol. From 472 non-duplicate records, two case reports met criteria for inclusion. We reviewed three cases of ZIKV infection among lactating mothers near the time of delivery. Two of the three (2/3) associated newborns had evidence of ZIKV infection. ZIKV was detected in breast milk of all three mothers. Breast milk detection results were positive in all mothers (3/3) by RT-PCR, one was positive by culture (1/3), and none was tested for ZIKV-specific antibodies. Serum samples were ZIKV positive in all mothers (3/3), and sweat was not tested for ZIKV.

Conclusions/Significance

We describe three cases of ZIKV-infected breastfeeding mothers who were symptomatic within three days of delivery, and two cases with ZIKV-infected newborns. While ZIKV was detected in the breast milk of all three mothers, the data are not sufficient to conclude ZIKV transmission via breastfeeding. More evidence is needed to distinguish breastfeeding transmission from other perinatal transmission routes.

Seroprevalence of Q fever among human and animal in Iran; a systematic review and meta-Analysis

PLoS Neglected Tropical Diseases News - 10 April 2017 - 9:00pm

by Ashraf Mohabbati Mobarez, Fahimeh Bagheri Amiri, Saber Esmaeili

Background

Q fever is a main zoonotic disease around the world. The aim of this meta-analysis was to estimate the overall seroprevalence of Coxiella burnetii among human and animal population in Iran.

Methods

Major national and international databases were searched from 2005 up to August 2016. We extracted the prevalence of Q fever antibodies (IgG) as the main primary outcome. We reported the prevalence of the seropositivity as point and 95% confidence intervals.

Results

The overall seroprevalence of IgG phase I and II antibodies of Q fever in human was 19.80% (95% CI: 16.35–23.25%) and 32.86% (95% CI: 23.80–41.92%), respectively. The herd and individual prevalence of C. burnetii antibody in goat were 93.42% (95% CI: 80.23–100.00) and 31.97% (95% CI: 20.96–42.98%), respectively. The herd and individual prevalence of Q fever antibody in sheep's were 96.07% (95% CI: 89.11–100.00%) and 24.66% (95% CI: 19.81–29.51%), respectively. The herd and individual prevalence of C. burnetii antibody in cattle were 41.37% (95% CI: 17.88–64.86%) and 13.30% (95% CI: 2.98–23.62%), respectively. Individual seropositivity of Q fever in camel and dog were 28.26% (95% CI: 21.47–35.05) and 0.55% (0.03–2.68), respectively.

Conclusion

Seroprevalence of Q fever among human and domestic animals is considerable. Preventative planning and control of C. burnetii infections in Iran is necessary. Active surveillance and further research studies are recommended, to more clearly define the epidemiology and importance of C. burnetii infections in animals and people in Iran.

Loss in lung volume and changes in the immune response demonstrate disease progression in African green monkeys infected by small-particle aerosol and intratracheal exposure to Nipah virus

PLoS Neglected Tropical Diseases News - 7 April 2017 - 9:00pm

by Yu Cong, Margaret R. Lentz, Abigail Lara, Isis Alexander, Christopher Bartos, J. Kyle Bohannon, Dima Hammoud, Louis Huzella, Peter B. Jahrling, Krisztina Janosko, Catherine Jett, Erin Kollins, Matthew Lackemeyer, Daniel Mollura, Dan Ragland, Oscar Rojas, Jeffrey Solomon, Ziyue Xu, Vincent Munster, Michael R. Holbrook

Nipah virus (NiV) is a paramyxovirus (genus Henipavirus) that emerged in the late 1990s in Malaysia and has since been identified as the cause of sporadic outbreaks of severe febrile disease in Bangladesh and India. NiV infection is frequently associated with severe respiratory or neurological disease in infected humans with transmission to humans through inhalation, contact or consumption of NiV contaminated foods. In the work presented here, the development of disease was investigated in the African Green Monkey (AGM) model following intratracheal (IT) and, for the first time, small-particle aerosol administration of NiV. This study utilized computed tomography (CT) and magnetic resonance imaging (MRI) to temporally assess disease progression. The host immune response and changes in immune cell populations over the course of disease were also evaluated. This study found that IT and small-particle administration of NiV caused similar disease progression, but that IT inoculation induced significant congestion in the lungs while disease following small-particle aerosol inoculation was largely confined to the lower respiratory tract. Quantitative assessment of changes in lung volume found up to a 45% loss in IT inoculated animals. None of the subjects in this study developed overt neurological disease, a finding that was supported by MRI analysis. The development of neutralizing antibodies was not apparent over the 8–10 day course of disease, but changes in cytokine response in all animals and activated CD8+ T cell numbers suggest the onset of cell-mediated immunity. These studies demonstrate that IT and small-particle aerosol infection with NiV in the AGM model leads to a severe respiratory disease devoid of neurological indications. This work also suggests that extending the disease course or minimizing the impact of the respiratory component is critical to developing a model that has a neurological component and more accurately reflects the human condition.

Poor performance of the rapid test for human brucellosis in health facilities in Kenya

PLoS Neglected Tropical Diseases News - 7 April 2017 - 9:00pm

by William A. de Glanville, Raquel Conde-Álvarez, Ignacio Moriyón, John Njeru, Ramón Díaz, Elizabeth A. J. Cook, Matilda Morin, Barend M. de C. Bronsvoort, Lian F. Thomas, Samuel Kariuki, Eric M. Fèvre

Human brucellosis is considered to be an important but typically under-diagnosed cause of febrile illness in many low and middle-income countries. In Kenya, and throughout East Africa, laboratory diagnosis for the disease is based primarily on the febrile antigen Brucella agglutination test (FBAT), yet few studies of the diagnostic accuracy of this test exist. Assessment of the performance of the FBAT is essential for its appropriate clinical use, as well as for evaluating surveillance data reported by public health systems. To assess FBAT performance, we collected sera from people with symptoms compatible with brucellosis attending two health facilities in Busia County, Kenya. Sera were tested using the FBAT and results compared with those from the Rose Bengal Test (RBT), an assay with well-known performance characteristics. Positives on either test were confirmed using the classical serum agglutination test (SAT)-Coombs test combination and a rapid IgM/IgG lateral flow immunochromatography assay (LFA). A questionnaire focussing on known risk factors for exposure to Brucella spp. was also conducted, and relationships with FBAT positivity examined using logistic regression. Out of 825 recruited individuals, 162 (19.6%) were classified as positive using the FBAT. In contrast, only eight (1.0%) were positive using the RBT. Of the 162 FBAT positives, one (0.62%) had an atypical agglutination in SAT and three (1.9%) showed low Coombs titres. Out of 148 FBAT positive individuals tested using the LFA, five (3.4%) were IgM positive and none were IgG positive. Poor or no correlation was observed between FBAT results and most established risk factors for Brucella infection. We observed substantial disagreement between the FBAT and a number of well-known serological tests, with the majority of reactive FBAT results appearing to be false positives. Poor FBAT specificity, combined with a lack of confirmatory testing, strongly suggests overdiagnosis of brucellosis is common in this low prevalence setting. This is expected to have important economic impacts on affected patients subjected to the long and likely unnecessary courses of multiple antibiotics required for treatment of the disease.

Development of a glycoconjugate vaccine to prevent invasive <i>Salmonella</i> Typhimurium infections in sub-Saharan Africa

PLoS Neglected Tropical Diseases News - 7 April 2017 - 9:00pm

by Scott M. Baliban, Mingjun Yang, Girish Ramachandran, Brittany Curtis, Surekha Shridhar, Rachel S. Laufer, Jin Y. Wang, John Van Druff, Ellen E. Higginson, Nicolas Hegerle, Kristen M. Varney, James E. Galen, Sharon M. Tennant, Andrew Lees, Alexander D. MacKerell Jr., Myron M. Levine, Raphael Simon

Invasive infections associated with non-typhoidal Salmonella (NTS) serovars Enteritidis (SE), Typhimurium (STm) and monophasic variant 1,4,[5],12:i:- are a major health problem in infants and young children in sub-Saharan Africa, and currently, there are no approved human NTS vaccines. NTS O-polysaccharides and flagellin proteins are protective antigens in animal models of invasive NTS infection. Conjugates of SE core and O-polysaccharide (COPS) chemically linked to SE flagellin have enhanced the anti-COPS immune response and protected mice against fatal challenge with a Malian SE blood isolate. We report herein the development of a STm glycoconjugate vaccine comprised of STm COPS conjugated to the homologous serovar phase 1 flagellin protein (FliC) with assessment of the role of COPS O-acetyls for functional immunity. Sun-type COPS conjugates linked through the polysaccharide reducing end to FliC were more immunogenic and protective in mice challenged with a Malian STm blood isolate than multipoint lattice conjugates (>95% vaccine efficacy [VE] versus 30–43% VE). Immunization with de-O-acetylated STm-COPS conjugated to CRM197 provided significant but reduced protection against STm challenge compared to mice immunized with native STm-COPS:CRM197 (63–74% VE versus 100% VE). Although OPS O-acetyls were highly immunogenic, post-vaccination sera that contained various O-acetyl epitope-specific antibody profiles displayed similar in vitro bactericidal activity when equivalent titers of anti-COPS IgG were assayed. In-silico molecular modeling further indicated that STm OPS forms a single dominant conformation, irrespective of O-acetylation, in which O-acetyls extend outward and are highly solvent exposed. These preclinical results establish important quality attributes for an STm vaccine that could be co-formulated with an SE-COPS:FliC glycoconjugate as a bivalent NTS vaccine for use in sub-Saharan Africa.

A low technology emanator treated with the volatile pyrethroid transfluthrin confers long term protection against outdoor biting vectors of lymphatic filariasis, arboviruses and malaria

PLoS Neglected Tropical Diseases News - 7 April 2017 - 9:00pm

by Sheila B. Ogoma, Arnold S. Mmando, Johnson K. Swai, Sebastian Horstmann, David Malone, Gerry F. Killeen

Background

The vapor phase of the volatile pyrethroid transfluthrin incapacitates mosquitoes and prevents them from feeding. Although existing emanator products for delivering volatile pyrethroids protect against outdoor mosquito bites, they are too short-lived to be practical or affordable for routine use in low-income settings. New transfluthrin emanators, comprised simply of treated hessian fabric strips, have recently proven highly protective against outdoor-biting vectors of lymphatic filariasis, arboviruses and malaria, but their full protective lifespan, minimum dose requirements, and range of protection have not previously been assessed.

Methodology

The effects of transfluthrin-treated hessian strips upon mosquito biting exposure of users and nearby non-users, as well as dependence of protection upon treatment dose, were measured outdoors in rural Tanzania using human landing catches (HLC).

Principal findings

Strips treated with 10ml of transfluthrin prevented at least three quarters (p < 0.001) of outdoor bites by Anopheles arabiensis, Culex spp. and Mansonia spp. mosquitoes, and >90% protection against bites on warmer nights with higher evaporation rates, for at least one year. Strips treated with this high dose also reduced biting exposure of non-users at a distance of up to 5m from the strips for An. arabiensis (p < 0.001) and up to 2m for Mansonia spp. (p = 0.008), but provided no protection to non-users against Culex spp. No evidence of increased risk for non-users, caused by diversion of mosquitoes to unprotected individuals, was found at any distance within an 80m radius. A dose of only 1ml provided equivalent protection to the 10ml dose against An. arabiensis, Culex spp. and Mansonia spp. mosquitoes over 6 months (p < 0.001).

Conclusions/Significance

Transfluthrin-treated hessian emanators provide safe, affordable, long-term protection against several different pathogen-transmitting mosquito taxa that attack humans outdoors, where they are usually active and cannot be protected by bed nets or residual sprays with conventional, solid-phase insecticides.

Cost-effectiveness of meglumine antimoniate versus miltefosine caregiver DOT for the treatment of pediatric cutaneous leishmaniasis

PLoS Neglected Tropical Diseases News - 6 April 2017 - 9:00pm

by Brandon A. Berger, Alexandra Cossio, Nancy Gore Saravia, Maria del Mar Castro, Sergio Prada, Allison H. Bartlett, Mai T. Pho

Background

Oral miltefosine has been shown to be non-inferior to first-line, injectable meglumine antimoniate (MA) for the treatment of cutaneous leishmaniasis (CL) in children. Miltefosine may be administered via in-home caregiver Directly Observed Therapy (cDOT), while patients must travel to clinics to receive MA. We performed a cost-effectiveness analysis comparing miltefosine by cDOT versus MA for pediatric CL in southwest Colombia.

Methodology/Principle findings

We developed a Monte Carlo model comparing the cost-per-cure of miltefosine by cDOT compared to MA from patient, government payer, and societal perspectives (societal = sum of patient and government payer perspective costs). Drug effectiveness and adverse events were estimated from clinical trials. Healthcare utilization and costs of travel were obtained from surveys of providers and published sources. The primary outcome was cost-per-cure reported in 2015 USD. Treatment efficacy, costs, and adherence were varied in sensitivity analysis to assess robustness of results. Treatment with miltefosine resulted in substantially lower cost-per-cure from a societal and patient perspective, and slightly higher cost-per-cure from a government payer perspective compared to MA. Mean societal cost-per-cure were $531 (SD±$239) for MA and $188 (SD±$100) for miltefosine, a mean cost-per-cure difference of +$343. Mean cost-per-cure from a patient perspective were $442 (SD ±$233) for MA and $30 (SD±$16) for miltefosine, a mean difference of +$412. Mean cost-per-cure from a government perspective were $89 (SD±$55) for MA and $158 (SD±$98) for miltefosine, with a mean difference of -$69. Results were robust across a variety of assumptions in univariate and multi-way analysis.

Conclusions/Significance

Treatment of pediatric cutaneous leishmaniasis with miltefosine via cDOT is cost saving from patient and societal perspectives, and moderately more costly from the government payer perspective compared to treatment with MA. Results were robust over a range of sensitivity analyses. Lower drug price for miltefosine could result in cost saving from a government perspective.

<i>Plasmodium vivax</i> gametocytes in the bone marrow of an acute malaria patient and changes in the erythroid miRNA profile

PLoS Neglected Tropical Diseases News - 6 April 2017 - 9:00pm

by Barbara Baro, Katrien Deroost, Tainá Raiol, Marcelo Brito, Anne C. G. Almeida, Armando de Menezes-Neto, Erick F. G. Figueiredo, Aline Alencar, Rodrigo Leitão, Fernando Val, Wuelton Monteiro, Anna Oliveira, Maria del Pilar Armengol, Carmen Fernández-Becerra, Marcus V. Lacerda, Hernando A. del Portillo

Viral hemorrhagic fevers in the Tihamah region of the western Arabian Peninsula

PLoS Neglected Tropical Diseases News - 6 April 2017 - 9:00pm

by Fathiah Zakham, Mohammed Al-habal, Rola Taher, Altaf Alaoui, Mohammed El Mzibri

Viral hemorrhagic fever (VHF) refers to a group of diseases characterized by an acute febrile syndrome with hemorrhagic manifestations and high mortality rates caused by several families of viruses that affect humans and animals. These diseases are typically endemic in certain geographical regions and sometimes cause major outbreaks. The history of hemorrhagic fever in the Arabian Peninsula refers to the 19th century and most outbreaks were reported in the Tihamah region—the Red Sea coastal plain of the Arabian Peninsula in the west and southwest of Saudi Arabia and Yemen. Herein, we describe the agents that cause VHFs and their epidemiology in Tihamah, the history of the diseases, transmission, species affected, and clinical signs. Finally, we address challenges in the diagnosis and control of VHFs in this region.

In the hunt for genomic markers of metabolic resistance to pyrethroids in the mosquito <i>Aedes aegypti</i>: An integrated next-generation sequencing approach

PLoS Neglected Tropical Diseases News - 5 April 2017 - 9:00pm

by Frederic Faucon, Thierry Gaude, Isabelle Dusfour, Vincent Navratil, Vincent Corbel, Waraporn Juntarajumnong, Romain Girod, Rodolphe Poupardin, Frederic Boyer, Stephane Reynaud, Jean-Philippe David

Background

The capacity of Aedes mosquitoes to resist chemical insecticides threatens the control of major arbovirus diseases worldwide. Until alternative control tools are widely deployed, monitoring insecticide resistance levels and identifying resistance mechanisms in field mosquito populations is crucial for implementing appropriate management strategies. Metabolic resistance to pyrethroids is common in Aedes aegypti but the monitoring of the dynamics of resistant alleles is impeded by the lack of robust genomic markers.

Methodology/Principal findings

In an attempt to identify the genomic bases of metabolic resistance to deltamethrin, multiple resistant and susceptible populations originating from various continents were compared using both RNA-seq and a targeted DNA-seq approach focused on the upstream ATG regions of detoxification genes. Multiple detoxification enzymes were over transcribed in resistant populations, frequently associated with an increase in their gene copy number. Targeted sequencing identified potential promoter variations associated with their over transcription. Non-synonymous variations affecting detoxification enzymes were also identified in resistant populations.

Conclusion /Significance

This study not only confirmed the role of gene copy number variations as a frequent cause of the over expression of detoxification enzymes associated with insecticide resistance in Aedes aegypti but also identified novel genomic resistance markers potentially associated with their cis-regulation and modifications of their protein structure conformation. As for gene transcription data, polymorphism patterns were frequently conserved within regions but differed among continents confirming the selection of different resistance factors worldwide. Overall, this study paves the way of the identification of a comprehensive set of genomic markers for monitoring the spatio-temporal dynamics of the variety of insecticide resistance mechanisms in Aedes aegypti.

Catalase protects <i>Aedes aegypti</i> from oxidative stress and increases midgut infection prevalence of Dengue but not Zika

PLoS Neglected Tropical Diseases News - 5 April 2017 - 9:00pm

by José Henrique M. Oliveira, Octávio A. C. Talyuli, Renata L. S. Gonçalves, Gabriela Oliveira Paiva-Silva, Marcos Henrique F. Sorgine, Patricia Hessab Alvarenga, Pedro L. Oliveira

Background

Digestion of blood in the midgut of Aedes aegypti results in the release of pro-oxidant molecules that can be toxic to the mosquito. We hypothesized that after a blood meal, the antioxidant capacity of the midgut is increased to protect cells against oxidative stress. Concomitantly, pathogens present in the blood ingested by mosquitoes, such as the arboviruses Dengue and Zika, also have to overcome the same oxidative challenge, and the antioxidant program induced by the insect is likely to influence infection status of the mosquito and its vectorial competence.

Methodology/Principal findings

We found that blood-induced catalase mRNA and activity in the midgut peaked 24 h after feeding and returned to basal levels after the completion of digestion. RNAi-mediated silencing of catalase (AAEL013407-RB) reduced enzyme activity in the midgut epithelia, increased H2O2 leakage and decreased fecundity and lifespan when mosquitoes were fed H2O2. When infected with Dengue 4 and Zika virus, catalase-silenced mosquitoes showed no alteration in infection intensity (number of plaque forming units/midgut) 7 days after the infectious meal. However, catalase knockdown reduced Dengue 4, but not Zika, infection prevalence (percent of infected midguts).

Conclusion/Significance

Here, we showed that blood ingestion triggers an antioxidant response in the midgut through the induction of catalase. This protection facilitates the establishment of Dengue virus in the midgut. Importantly, this mechanism appears to be specific for Dengue because catalase silencing did not change Zika virus prevalence. In summary, our data suggest that redox balance in the midgut modulates mosquito vectorial competence to arboviral infections.

Detecting and enumerating soil-transmitted helminth eggs in soil: New method development and results from field testing in Kenya and Bangladesh

PLoS Neglected Tropical Diseases News - 5 April 2017 - 9:00pm

by Lauren Steinbaum, Laura H. Kwong, Ayse Ercumen, Makeda S. Negash, Amira J. Lovely, Sammy M. Njenga, Alexandria B. Boehm, Amy J. Pickering, Kara L. Nelson

Globally, about 1.5 billion people are infected with at least one species of soil-transmitted helminth (STH). Soil is a critical environmental reservoir of STH, yet there is no standard method for detecting STH eggs in soil. We developed a field method for enumerating STH eggs in soil and tested the method in Bangladesh and Kenya. The US Environmental Protection Agency (EPA) method for enumerating Ascaris eggs in biosolids was modified through a series of recovery efficiency experiments; we seeded soil samples with a known number of Ascaris suum eggs and assessed the effect of protocol modifications on egg recovery. We found the use of 1% 7X as a surfactant compared to 0.1% Tween 80 significantly improved recovery efficiency (two-sided t-test, t = 5.03, p = 0.007) while other protocol modifications—including different agitation and flotation methods—did not have a significant impact. Soil texture affected the egg recovery efficiency; sandy samples resulted in higher recovery compared to loamy samples processed using the same method (two-sided t-test, t = 2.56, p = 0.083). We documented a recovery efficiency of 73% for the final improved method using loamy soil in the lab. To field test the improved method, we processed soil samples from 100 households in Bangladesh and 100 households in Kenya from June to November 2015. The prevalence of any STH (Ascaris, Trichuris or hookworm) egg in soil was 78% in Bangladesh and 37% in Kenya. The median concentration of STH eggs in soil in positive samples was 0.59 eggs/g dry soil in Bangladesh and 0.15 eggs/g dry soil in Kenya. The prevalence of STH eggs in soil was significantly higher in Bangladesh than Kenya (chi-square, χ2 = 34.39, p < 0.001) as was the concentration (Mann-Whitney, z = 7.10, p < 0.001). This new method allows for detecting STH eggs in soil in low-resource settings and could be used for standardizing soil STH detection globally.

Isolation of dengue virus from the upper respiratory tract of four patients with dengue fever

PLoS Neglected Tropical Diseases News - 5 April 2017 - 9:00pm

by Nai-Ming Cheng, Bao-Chen Chen, Tsi-Shu Huang, Cheng Len Sy, Susan Shin-Jung Lee, Yao-Shen Chen

Background

Dengue fever is an important arboviral disease. The clinical manifestations vary from a mild non-specific febrile syndrome to severe life-threatening illness. The virus can usually be detected in the blood during the early stages of the disease. Dengue virus has also has been found in isolated cases in the cerebrospinal fluid, urine, nasopharyngeal sections and saliva. In this report, we describe the isolation of dengue virus from the upper respiratory tract of four confirmed cases of dengue.

Methods

We reviewed all laboratory reports of the isolation of dengue virus from respiratory specimens at the clinical microbiology laboratory of the Kaohsiung Veterans General Hospital during 2007 to 2015. We then examined the medical records of the cases from whom the virus was isolated to determine their demographic characteristics, family contacts, clinical signs and symptoms, course of illness and laboratory findings.

Results

Dengue virus was identified in four patients from a nasopharyngeal or throat culture. Two were classified as group A dengue (dengue without warning signs), one as group B (dengue with warning signs) and one as group C (severe dengue). All had respiratory symptoms. Half had family members with similar respiratory symptoms during the period of their illnesses. All of the patients recovered uneventfully.

Conclusions

The isolation of dengue virus from respiratory specimens of patients with cough, rhinorrhea and nasal congestion, although rare, raises the possibility that the virus is capable of transmission by the aerosol route among close contacts. This concept is supported by studies that show that the virus can replicate in cultures of respiratory epithelium and can be transmitted through mucocutaneous exposure to blood from infected patients. However, current evidence is insufficient to prove the hypothesis of transmission through the respiratory route. Further studies will be needed to determine the frequency of respiratory colonization, viable virus titers in respiratory secretions and molecular genetic evidence of transmission among close contacts.

Risk factors for therapeutic failure to meglumine antimoniate and miltefosine in adults and children with cutaneous leishmaniasis in Colombia: A cohort study

PLoS Neglected Tropical Diseases News - 5 April 2017 - 9:00pm

by Maria del Mar Castro, Alexandra Cossio, Carlos Velasco, Lyda Osorio

Introduction

Reports of therapeutic failure to meglumine antimoniate (MA) and miltefosine in cutaneous leishmaniasis (CL) varies between species, populations and geographic regions. This study aimed to determine the clinical, drug-related factors, and Leishmania species associated with treatment failure in children and adults with cutaneous leishmaniasis.

Methods

A cohort study was performed with children (2–12 years old) and adults (18–65 years old) with CL, who have participated in clinical studies at CIDEIM Cali, Tumaco and Chaparral. Incidence of therapeutic failure was estimated by treatment and age groups. Descriptive, bivariate, and multiple logistic regression analyses were performed for the complete cohort and pediatric patients.

Results

Two hundred and thirty patients were included (miltefosine: 112; MA: 118), of which 60.4% were children and 83.9% were infected with L.V. panamensis. Overall incidence of therapeutic failure was 15.65% (95%CI: 10.92–20.38), and was lower for miltefosine than for MA (8.92%, 95%CI: 3.59–14.26 versus 22.03%, 95%CI:14.48–29.58, p = 0.006). Treatment failure was associated with age ≤8 years (OR: 3.29; 95%CI: 1.37–7.89), disease duration ≤1 month (OR: 3.29; 95%CI: 1.37–7.89), regional lymphadenopathy (OR: 2.72; 95%CI: 1.10–6.70), treatment with MA (OR: 3.98; 95%CI: 1.66–9.50), and adherence <90% (OR: 3.59; 95%CI: 1.06–12.11). In children, higher Z-score of height/age was a protective factor (OR: 0.58; 95%CI: 0.36–0.93), while treatment with MA was a risk factor (OR: 40.82; 95%CI: 2.45–677.85), demonstrating significant interaction with age (p = 0.03).

Conclusions

Clinical and drug-related factors determine therapeutic failure in CL. High risk of failure in children treated with MA indicates the need to reconsider this drug as first line treatment in this population.

Trial registration

Clinical trial registration: NCT00487253Clinical trial registration: NCT01462500Clinical trial registration: NCT01464242

Unraveling Chagas disease transmission through the oral route: Gateways to <i>Trypanosoma cruzi</i> infection and target tissues

PLoS Neglected Tropical Diseases News - 5 April 2017 - 9:00pm

by Danielle Silva-dos-Santos, Juliana Barreto-de-Albuquerque, Bárbara Guerra, Otacilio C. Moreira, Luiz Ricardo Berbert, Mariana Tavares Ramos, Barbara Angelica S. Mascarenhas, Constança Britto, Alexandre Morrot, Déa M. Serra Villa-Verde, Luciana Ribeiro Garzoni, Wilson Savino, Vinícius Cotta-de-Almeida, Juliana de Meis

Oral transmission of Trypanosoma cruzi, the causative agent of Chagas disease, is the most important route of infection in Brazilian Amazon and Venezuela. Other South American countries have also reported outbreaks associated with food consumption. A recent study showed the importance of parasite contact with oral cavity to induce a highly severe acute disease in mice. However, it remains uncertain the primary site of parasite entry and multiplication due to an oral infection. Here, we evaluated the presence of T. cruzi Dm28c luciferase (Dm28c-luc) parasites in orally infected mice, by bioluminescence and quantitative real-time PCR. In vivo bioluminescent images indicated the nasomaxillary region as the site of parasite invasion in the host, becoming consistently infected throughout the acute phase. At later moments, 7 and 21 days post-infection (dpi), luminescent signal is denser in the thorax, abdomen and genital region, because of parasite dissemination in different tissues. Ex vivo analysis demonstrated that the nasomaxillary region, heart, mandibular lymph nodes, liver, spleen, brain, epididymal fat associated to male sex organs, salivary glands, cheek muscle, mesenteric fat and lymph nodes, stomach, esophagus, small and large intestine are target tissues at latter moments of infection. In the same line, amastigote nests of Dm28c GFP T. cruzi were detected in the nasal cavity of 6 dpi mice. Parasite quantification by real-time qPCR at 7 and 21 dpi showed predominant T. cruzi detection and expansion in mouse nasal cavity. Moreover, T. cruzi DNA was also observed in the mandibular lymph nodes, pituitary gland, heart, liver, small intestine and spleen at 7 dpi, and further, disseminated to other tissues, such as the brain, stomach, esophagus and large intestine at 21 dpi. Our results clearly demonstrated that oral cavity and adjacent compartments is the main target region in oral T. cruzi infection leading to parasite multiplication at the nasal cavity.

The novel nematicide wact-86 interacts with aldicarb to kill nematodes

PLoS Neglected Tropical Diseases News - 5 April 2017 - 9:00pm

by Andrew R. Burns, Rachel Bagg, May Yeo, Genna M. Luciani, Michael Schertzberg, Andy G. Fraser, Peter J. Roy

Parasitic nematodes negatively impact human and animal health worldwide. The market withdrawal of nematicidal agents due to unfavourable toxicities has limited the available treatment options. In principle, co-administering nematicides at lower doses along with molecules that potentiate their activity could mitigate adverse toxicities without compromising efficacy. Here, we screened for new small molecules that interact with aldicarb, which is a highly effective treatment for plant-parasitic nematodes whose toxicity hampers its utility. From our collection of 638 worm-bioactive compounds, we identified 20 molecules that interact positively with aldicarb to either kill or arrest the growth of the model nematode Caenorhabditis elegans. We investigated the mechanism of interaction between aldicarb and one of these novel nematicides called wact-86. We found that the carboxylesterase enzyme GES-1 hydrolyzes wact-86, and that the interaction is manifested by aldicarb’s inhibition of wact-86’s metabolism by GES-1. This work demonstrates the utility of C. elegans as a platform to search for new molecules that can positively interact with industrial nematicides, and provides proof-of-concept for prospective discovery efforts.

Rapid mapping of urinary schistosomiasis: An appraisal of the diagnostic efficacy of some questionnaire-based indices among high school students in Katsina State, northwestern Nigeria

PLoS Neglected Tropical Diseases News - 3 April 2017 - 9:00pm

by Tolulope Ebenezer Atalabi, Taiwo Oluwakemi Adubi, Umar Lawal

Background

In sub-Saharan Africa, over 200 million individuals are estimated to be infected with urinary and intestinal schistosomiasis. In a bid to lay a foundation for effective future control programme, this study was carried out with the aim of assessing the diagnostic efficacy of some questionnaire-based rapid assessment indices of urinary schistosomiasis.

Methodology

A total number of 1,363 subjects were enrolled for the study. Questionnaires were administered basically in English and Hausa languages by trained personnel. Following informed consent, terminal urine samples were collected between 09:40 AM and 2:00 PM using clean 20 ml capacity universal bottles. 10μl of each urine residue was examined for the eggs of S. haematobium using x10 objective nose of Motic Binocular Light Microscope (China).

Principal findings

The average age ± Standard Deviation (SD) of school children examined was 15.30 ± 2.30 years and 40.87% were females. The overall prevalence and geometric mean intensity of S. haematobium infection were 26.41% (24.10─28.85) and 6.59 (5.59─7.75) eggs / 10 ml of urine respectively. Interestingly, a questionnaire equivalence of the prevalence obtained in this survey was 26.41% (24.10─28.85) for Rapid Assessment Procedure based on self-reported blood in urine. The results of correlation analyses demonstrated significant associations between the prevalence of S. haematobium infection and contact with potentially infested open water sources (r = 0.741; P = 0.006). By regression model, cases of respondents with self-reported blood in urine are expected to rise to 24.75% if prevalence of the infection shoots up to 26.5%.

Conclusions/Significance

The best RAP performance was obtained with self-reported blood in urine. Based on the overall prevalence value, the study area was at a “moderate-risk” of endemicity for urinary schistosomiasis. Chemotherapeutic intervention with Praziquantel, the rationale behind rapid assessment procedure for schistosomiasis, has been recommended to be carried out once in every 2 years for such communities.

Defining the next generation of <i>Plasmodium vivax</i> diagnostic tests for control and elimination: Target product profiles

PLoS Neglected Tropical Diseases News - 3 April 2017 - 9:00pm

by Xavier C. Ding, Maria Paz Ade, J. Kevin Baird, Qin Cheng, Jane Cunningham, Mehul Dhorda, Chris Drakeley, Ingrid Felger, Dionicia Gamboa, Matthias Harbers, Socrates Herrera, Naomi Lucchi, Alfredo Mayor, Ivo Mueller, Jetsumon Sattabongkot, Arsène Ratsimbason, Jack Richards, Marcel Tanner, Iveth J. González

The global prevalence of malaria has decreased over the past fifteen years, but similar gains have not been realized against Plasmodium vivax because this species is less responsive to conventional malaria control interventions aimed principally at P. falciparum. Approximately half of all malaria cases outside of Africa are caused by P. vivax. This species places dormant forms in human liver that cause repeated clinical attacks without involving another mosquito bite. The diagnosis of acute patent P. vivax malaria relies primarily on light microscopy. Specific rapid diagnostic tests exist but typically perform relatively poorly compared to those for P. falciparum. Better diagnostic tests are needed for P. vivax. To guide their development, FIND, in collaboration with P. vivax experts, identified the specific diagnostic needs associated with this species and defined a series of three distinct target product profiles, each aimed at a particular diagnostic application: (i) point-of-care of acutely ill patients for clinical care purposes; (ii) point-of-care asymptomatic and otherwise sub-patent residents for public health purposes, e.g., mass screen and treat campaigns; and (iii) ultra-sensitive not point-of-care diagnosis for epidemiological research/surveillance purposes. This report presents and discusses the rationale for these P. vivax-specific diagnostic target product profiles. These contribute to the rational development of fit-for-purpose diagnostic tests suitable for use the clinical management, control and elimination of P. vivax malaria.

Rapid diagnostic tests duo as alternative to conventional serological assays for conclusive Chagas disease diagnosis

PLoS Neglected Tropical Diseases News - 3 April 2017 - 9:00pm

by Karina E. Egüez, Julio Alonso-Padilla, Carolina Terán, Zenobia Chipana, Wilson García, Faustino Torrico, Joaquín Gascón, Daniel Lozano, María-Jesús Pinazo

Chagas disease is caused by the parasite Trypanosoma cruzi. It affects several million people, mainly in Latin America, and severe cardiac and/or digestive complications occur in ~30% of the chronically infected patients. Disease acute stage is mostly asymptomatic and infection goes undiagnosed. In the chronic phase direct parasite detection is hampered due to its concealed presence and diagnosis is achieved by serological methods, like ELISA or indirect hemagglutination assays. Agreement in at least two tests must be obtained due to parasite wide antigenic variability. These techniques require equipped labs and trained personnel and are not available in distant regions. As a result, many infected people often remain undiagnosed until it is too late, as the two available chemotherapies show diminished efficacy in the advanced chronic stage. Easy-to-use rapid diagnostic tests have been developed to be implemented in remote areas as an alternative to conventional tests. They do not need electricity, nor cold chain, they can return results within an hour and some even work with whole blood as sample, like Chagas Stat-Pak (ChemBio Inc.) and Chagas Detect Plus (InBIOS Inc.). Nonetheless, in order to qualify a rapidly diagnosed positive patient for treatment, conventional serological confirmation is obligatory, which might risk its start. In this study two rapid tests based on distinct antigen sets were used in parallel as a way to obtain a fast and conclusive Chagas disease diagnosis using whole blood samples. Chagas Stat-Pak and Chagas Detect Plus were validated by comparison with three conventional tests yielding 100% sensitivity and 99.3% specificity over 342 patients seeking Chagas disease diagnosis in a reference centre in Sucre (Bolivia). Combined used of RDTs in distant regions could substitute laborious conventional serology, allowing immediate treatment and favouring better adhesion to it.

Reaching endpoints for lymphatic filariasis elimination- results from mass drug administration and nocturnal blood surveys, South Gujarat, India

PLoS Neglected Tropical Diseases News - 3 April 2017 - 9:00pm

by Anjali Modi, Sukesha Gamit, Bharat S. Jesalpura, George Kurien, Jayendra K. Kosambiya

Background

Following the World Health Assembly resolution on Elimination of lymphatic filariasis (ELF) as a public health problem by the year 2020, a Global Program (GPELF) was launched in 1997 to help endemic countries to initiate national programs. The current strategy to interrupt transmission of LF, is administration of once-yearly, single-dose, two-drug regimen (Albendazole with Diethylcarbamazine (DEC) to be used in endemic areas with the goal of reaching 65% epidemiological coverage for 4–6 years. We report findings of independent assessment from year 2010 to 2015 for last six rounds, after initial five rounds of Mass Drug Administration (MDA) since 2005 for ELF in endemic area of Gujarat.

Methods

Independent assessment of MDA was performed to find coverage and compliance indicators, reasons for non-coverage and non-compliance in five Implementation Units (IUs). Pre, during and post MDA evaluations were done in three phases. The impact of MDA was measured by microfilaraemia survey. A total of eight sites, four random and four fixed sentinel sites were selected to calculate microfilaria rate (MF) per IUs per year. In years 2010 to 2015, we report results from 125,936 nocturnal blood smears and 17,405 population in 120 selected clusters. Four clusters were selected per year in each of the five IUs for assessment of MDA round.

Result

Post MDA survey showed drug coverage between 81%-88% and epidemiological coverage 77%-89% across years. Main reasons for non-coverage were drug administrator related (the team did not visit or missed people) while non-compliance was population related (fear of side effects, sickness, people forgot or absent). During MDA findings show that the directly observed consumption is considerably improved from 58% in 2010 to 82% in 2015. The knowledge about benefits of drug provided also increased from 59% to 90% over the years. The current MF rate is less than one in all IUs with an overall 68% percent decrease from baseline year 2005 to year 2015. The average MF rate of Gujarat is 0.44 for year 2015.

Conclusions

The findings show that achieving adequate epidemiological and drug coverage is possible by actual field level operation of the program in large endemic areas. The results and feedback from independent assessment, performed regularly, could guide the policymakers and program managers for mid-term corrections and to frame strategies to enhance program. Monitoring of coverage and impact indicator together informs decisions for reaching end-point of MDA. The impact indicator- microfilaria rate in all IUs of South Gujarat Region has reached and remained less than one percent signaling end-points of MDA. Post MDA stringent monitoring in form of TAS is recommended to keep vigil on maintenance of elimination achieved.

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