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The extent, nature, and pathogenic consequences of helminth polyparasitism in humans: A meta-analysis

PLoS Neglected Tropical Diseases News - 18 June 2019 - 9:00pm

by Rose E. Donohue, Zoë K. Cross, Edwin Michael

Background

Individual helminth infections are ubiquitous in the tropics; geographical overlaps in endemicity and epidemiological reports suggest areas endemic for multiple helminthiases are also burdened with high prevalences of intestinal protozoan infections, malaria, tuberculosis (TB), and human immunodeficiency virus (HIV). Despite this, pathogens tend to be studied in isolation, and there remains a need for a better understanding of the community ecology and health consequences of helminth polyparasitism to inform the design of effective parasite control programs.

Methodology

We performed meta-analyses to (i) evaluate the commonality of polyparasitism for helminth-helminth, helminth-intestinal protozoa, helminth-malaria, helminth-TB, and helminth-HIV co-infections, (ii) assess the potential for interspecies interactions among helminth-helminth and helminth-intestinal protozoan infections, and (iii) determine the presence and magnitude of association between specific parasite pairs. Additionally, we conducted a review of reported health consequences of multiply-infected individuals compared to singly- or not multiply-infected individuals.

Principal findings

We found that helminth-helminth and helminth-intestinal protozoan multiple infections were significantly more common than single infections, while individuals with malaria, TB, and HIV were more likely to be singly-infected with these infections than co-infected with at least one helminth. Most observed species density distributions significantly differed from the expected distributions, suggesting the potential presence of interspecies interactions. All significant associations between parasite pairs were positive in direction, irrespective of the combination of pathogens. Polyparasitized individuals largely exhibited lower hemoglobin levels and higher anemia prevalence, while the differences in growth-related variables were mostly statistically insignificant.

Conclusions

Our findings confirm that helminth polyparasitism and co-infection with major diseases is common in the tropics. A multitude of factors acting at various hierarchical levels, such as interspecies interactions at the within-host infra-parasite community level and environmental variables at the higher host community level, could explain the observed positive associations between pathogens; there remains a need to develop new frameworks which can consider these multilevel factors to better understand the processes structuring parasite communities to accomplish their control.

Refinement strategy for antivenom preparation of high yield and quality

PLoS Neglected Tropical Diseases News - 17 June 2019 - 9:00pm

by Tihana Kurtović, Maja Lang Balija, Marija Brgles, Dora Sviben, Monika Tunjić, Hrvoje Cajner, Martina Marchetti-Deschmann, Günter Allmaier, Beata Halassy

Antivenoms from hyperimmune animal plasma are the only specific pharmaceuticals against snakebites. The improvement of downstream processing strategies is of great interest, not only in terms of purity profile, but also from yield-to-cost perspective and rational use of plasma of animal origin. We report on development of an efficient refinement strategy for F(ab')2-based antivenom preparation. Process design was driven by the imperative to keep the active principle constantly in solution as a precautionary measure to preserve stability of its conformation (precipitation of active principle or its adsorption to chromatographic stationary phase has been completely avoided). IgG was extracted from hyperimmune horse plasma by 2% (V/V) caprylic acid, depleted from traces of precipitating agent and digested by pepsin. Balance between incomplete IgG fraction breakdown, F(ab')2 over-digestion and loss of the active principle's protective efficacy was achieved by adjusting pepsin to substrate ratio at the value of 4:300 (w/w), setting pH to 3.2 and incubation period to 1.5 h. Final polishing was accomplished by a combination of diafiltration and flow-through chromatography. Developed manufacturing strategy gave 100% pure and aggregate-free F(ab')2 preparation, as shown by size-exclusion HPLC and confirmed by MS/MS. The overall yield of 75% or higher compares favorably to others so far reported. This optimised procedure looks also promising for large-scale production of therapeutic antivenoms, since high yield of the active drug and fulfillment of the regulatory demand considering purity was achieved. The recovery of the active substance was precisely determined in each purification step enabling accurate estimation of the process cost-effectiveness.

<i>Giardia lamblia</i> miRNAs as a new diagnostic tool for human giardiasis

PLoS Neglected Tropical Diseases News - 17 June 2019 - 9:00pm

by Tal Meningher, Daniel Boleslavsky, Iris Barshack, Hila Tabibian-Keissar, Refael Kohen, Devorah Gur-Wahnon, Iddo Z. Ben-Dov, Yechezkel Sidi, Dror Avni, Eli Schwartz

Background

Giardia lamblia is a very common cause of gastrointestinal symptoms worldwide. There are several methods for the diagnosis of Giardia infection, however none are ideal. We aim to find a new, microRNA-based method that will improve the currently available diagnostic methods for giardiasis.

Methods

Deep-sequence profiling of Giardia small-RNA revealed that miR5 and miR6 are highly expressed in Giardia. These miRNAs were tested by qRT-PCR in duodenal biopsies of patients with giardiasis who were positive by microscopic pathological evaluation. The gastric biopsies of the same patients served as negative control tissues. Additionally, these miRNAs were evaluated in stool samples of patients with proven giardiasis.

Results

All histologically proven duodenal biopsies of patients with Giardia infection were positive for Giardia miR5, with a mean threshold cycle (Ct) of 23.7, as well as for Giardia DNA qPCR (16S-like gene, mean Ct 26.3). Gastric biopsies which were tested as a control all were negative. Stool evaluation of miR6 in patients with giardiasis showed 90% specificity but only 66% sensitivity, and a lower accuracy rate was obtained with miR5.

Conclusion

Giardia miR5 testing in duodenal biopsies may be a new method for the diagnosis of giardiasis. It seems to be more sensitive when compared with testing for Giardia DNA by qPCR in duodenal biopsies. It will be important to investigate the contribution of routine Giardia miRNA testing in duodenal biopsies from patients with persistent abdominal symptoms

Identification of high-risk habitats of <i>Oncomelania hupensis</i>, the intermediate host of <i>schistosoma japonium</i> in the Poyang Lake region, China: A spatial and ecological analysis

PLoS Neglected Tropical Diseases News - 17 June 2019 - 9:00pm

by Congcong Xia, Yi Hu, Michael P. Ward, Henry Lynn, Si Li, Jun Zhang, Jian Hu, Shuang Xiao, Chengfang Lu, Shizhu Li, Ying Liu, Zhijie Zhang

Background

Identifying and eliminating snail habitats is the key measure for schistosomiasis control, critical for the nationwide strategy of eliminating schistosomiasis in China. Here, our aim was to construct a new analytical framework to predict high-risk snail habitats based on a large sample field survey for Oncomelania hupensis, providing guidance for schistosomiasis control and prevention.

Methodology/Principal findings

Ten ecological models were constructed based on the occurrence data of Oncomelania hupensis and a range of variables in the Poyang Lake region of China, including four presence-only models (Maximum Entropy Models, Genetic Algorithm for rule-set Production, Bioclim and Domain) and six presence-absence models (Generalized Linear Models, Multivariate Adaptive Regression Splines, Flexible Discriminant Analysis, as well as machine algorithmic models–Random Forest, Classification Tree Analysis, Generalized Boosted Model), to predict high-risk snail habitats. Based on overall predictive performance, we found Presence-absence models outperformed the presence-only models and the models based on machine learning algorithms of classification trees showed the highest accuracy. The highest risk was located in the watershed of the River Fu in Yugan County, as well as the watershed of the River Gan and the River Xiu in Xingzi County, covering an area of 52.3 km2. The other high-risk areas for both snail habitats and schistosomiasis were mainly concentrated at the confluence of Poyang Lake and its five main tributaries.

Conclusions/Significance

This study developed a new distribution map of snail habitats in the Poyang Lake region, and demonstrated the critical role of ecological models in risk assessment to directing local field investigation of Oncomelania hupensis. Moreover, this study could also contribute to the development of effective strategies to prevent further spread of schistosomiasis from endemic areas to non-endemic areas.

Development and validation of a multiplexed-tandem qPCR tool for diagnostics of human soil-transmitted helminth infections

PLoS Neglected Tropical Diseases News - 17 June 2019 - 9:00pm

by Katharina Stracke, Naomi Clarke, Camille V. Awburn, Susana Vaz Nery, Virak Khieu, Rebecca J. Traub, Aaron R. Jex

Soil-transmitted helminths (STH) are a major cause of morbidity in tropical developing countries with a global infection prevalence of more than one billion people and disease burden of around 3.4 million disability adjusted life years. Infection prevalence directly correlates to inadequate sanitation, impoverished conditions and limited access to public health systems. Underestimation of infection prevalence using traditional microscopy-based diagnostic techniques is common, specifically in populations with access to benzimidazole mass treatment programs and a predominance of low intensity infections. In this study, we developed a multiplexed-tandem qPCR (MT-PCR) tool to identify and quantify STH eggs in stool samples. We have assessed this assay by measuring infection prevalence and intensity in field samples of two cohorts of participants from Timor-Leste and Cambodia, which were collected as part of earlier epidemiological studies. MT-PCR diagnostic parameters were compared to a previously published multiplexed qPCR for STH detection. The MT-PCR assay agreed strongly with qPCR data and showed a diagnostic specificity of 99.60–100.00% (sensitivity of 83.33–100.00%) compared to qPCR and kappa agreement exceeding 0.85 in all tests. In addition, the MT-PCR has the added advantage of distinguishing Ancylostoma spp. species, namely Ancylostoma duodenale and Ancylostoma ceylanicum. This semi-automated platform uses a standardized, manufactured reagent kit, shows excellent run-to-run consistency/repeatability and supports high-throughput detection and quantitation at a moderate cost.

Identification of <i>Burkholderia thailandensis</i> with novel genotypes in the soil of central Sierra Leone

PLoS Neglected Tropical Diseases News - 14 June 2019 - 9:00pm

by Emma Birnie, Senne van ’t Hof, Anne Bijnsdorp, Yembeh Mansaray, Erdi Huizenga, Arie van der Ende, Floor Hugenholtz, Martin P. Grobusch, W. Joost Wiersinga

Background

The soil-dwelling bacillus Burkholderia pseudomallei is the etiological-agent of the neglected and life-threatening emerging infection melioidosis. The distribution of B. pseudomallei in West Africa is unknown. In the present study we aimed to determine whether B. pseudomallei and B. thailandensis are present in the environment of central Sierra Leone.

Methodology/Principal findings

In June-July 2017, we conducted an environmental surveillance study–designed in accordance with existing consensus guidelines—in central Sierra Leone. A total of 1,000 soil samples (100 per site) were collected and cultured. B. pseudomallei was not identified in the soil, but we identified seven novel B. thailandensis sequence types with multi-locus sequence typing (MLST) and 16S rRNA gene sequence analyses.

Conclusions/Significance

The presence of B. pseudomallei was not demonstrated, however, multiple novel B. thailandensis sequence types were identified. More environmental and sequencing studies are needed to further understand the genetic diversity, evolution and virulence of these emerging organisms.

Downgrading disease transmission risk estimates using terminal importations

PLoS Neglected Tropical Diseases News - 14 June 2019 - 9:00pm

by Spencer J. Fox, Steven E. Bellan, T. Alex Perkins, Michael A. Johansson, Lauren Ancel Meyers

As emerging and re-emerging infectious arboviruses like dengue, chikungunya, and Zika threaten new populations worldwide, officials scramble to assess local severity and transmissibility, with little to no epidemiological history to draw upon. Indirect estimates of risk from vector habitat suitability maps are prone to great uncertainty, while direct estimates from epidemiological data are only possible after cases accumulate and, given environmental constraints on arbovirus transmission, cannot be widely generalized beyond the focal region. Combining these complementary methods, we use disease importation and transmission data to improve the accuracy and precision of a priori ecological risk estimates. We demonstrate this approach by estimating the spatiotemporal risks of Zika virus transmission throughout Texas, a high-risk region in the southern United States. Our estimates are, on average, 80% lower than published ecological estimates—with only six of 254 Texas counties deemed capable of sustaining a Zika epidemic—and they are consistent with the number of autochthonous cases detected in 2017. Importantly our method provides a framework for model comparison, as our mechanistic understanding of arbovirus transmission continues to improve. Real-time updating of prior risk estimates as importations and outbreaks arise can thereby provide critical, early insight into local transmission risks as emerging arboviruses expand their global reach.

Prevalence of trachoma within refugee camps serving South Sudanese refugees in White Nile State, Sudan: Results from population-based surveys

PLoS Neglected Tropical Diseases News - 13 June 2019 - 9:00pm

by Angelia M. Sanders, Zeinab Abdalla, Belgesa E. Elshafie, Andrew W. Nute, Elizabeth F. Long, Nabil Aziz, Paul Weiss, E. Kelly Callahan, Scott D. Nash

Background

The world is witnessing mass displacement of populations which could impact global efforts to eliminate neglected tropical diseases such as trachoma. On the African continent, South Sudan has experienced high levels of population displacement. Population based baseline trachoma surveys were conducted among refugee camps in two Sudanese localities hosting South Sudanese refugee populations to determine whether the SAFE strategy was warranted.

Methodology/Principal findings

Cross-sectional, multi-stage, cluster-random surveys were conducted within refugee camps in each of two Sudanese localities, Al Salam and Al Jabalain. For survey sampling, multiple camps within each locality were combined to form the sampling frame for that locality. Household water, sanitation and hygiene indicators were assessed, and trachoma signs were graded by trained and certified graders. The prevalence of trachomatous inflammation-follicular (TF) in children aged one to nine years was 15.7% (95%CI: 12.1–20.2) in Al Salam and 10.6% (95%CI: 7.9–14.0) in Al Jabalain. The prevalence of trachomatous trichiasis (TT) in those 15 years above was 2.9% (95%CI: 1.8–4.8) in Al Salam and 5.0% (95%CI: 3.8–6.6) in Al Jabalain. The presence of water and sanitation was high in both survey units.

Conclusion/ Significance

Sudan has made progress in reducing the prevalence of trachoma within the country; however, the presence of over one million refugees from a neighboring trachoma hyper-endemic country could impact this progress. These surveys were the first step in addressing this important issue. The results demonstrate that at least three years of mass drug administration with azithromycin and tetracycline is needed in addition to the provision of TT surgical services. Additionally, it highlights that non-endemic or formerly endemic localities may have to adopt new strategies to provide services for refugee populations originating from hyper-endemic regions to ensure elimination of trachoma as a public health problem for all populations.

B1 cells protect against <i>Schistosoma japonicum</i>–induced liver inflammation and fibrosis by controlling monocyte infiltration

PLoS Neglected Tropical Diseases News - 13 June 2019 - 9:00pm

by Liang Yong, Yuanyuan Tang, Cuiping Ren, Miao Liu, Jijia Shen, Xin Hou

During Schistosoma infection, lack of B cells results in more severe granulomas, inflammation, and fibrosis in the liver, but the mechanisms underlying this pathology remain unclear. This study was to clarify the mechanisms underpinning the immunomodulation of B cells in mice infected with Schistosoma japonicum (S. japonicum). We found that B cell deficiency led to aggravated liver pathology, as demonstrated by increases in the size of the egg-associated granulomas, alanine transaminase levels, and collagen deposition. Compared with infected wild-type (WT) mice, infected B cell-deficient (μMT) mice showed increased infiltration of Ly6Chi monocytes and higher levels of proinflammatory cytokines and chemokines. Furthermore, B1 cells were increased significantly in the liver of WT mice following S. japonicum infection. Adoptively transferring B1 cells, but not B2 cells, to μMT mice significantly reduced liver pathology and liver infiltration of Ly6Chi monocytes. Additionally, secretion of IL-10 from hepatic B cells increased significantly in infected WT mice and this IL-10 was mainly derived from B1 cells. Adoptively transferring B1 cells purified from WT mice, but not from IL-10-deficient mice, to μMT mice significantly reduced liver pathology and liver infiltration of Ly6Chi monocytes. These reductions were accompanied by decreases in the expression levels of chemokines and inflammatory cytokines. Taken together, these data indicated that after S. japonicum infection, an increased number of hepatic B1 cells secrete IL-10, which inhibits the expression of chemokines and cytokines and suppresses the infiltration of Ly6Chi monocytes into the liver thereby alleviating liver early inflammation and late fibrosis.

Home improvement and system-based health promotion for sustainable prevention of Chagas disease: A qualitative study

PLoS Neglected Tropical Diseases News - 13 June 2019 - 9:00pm

by Claudia Nieto-Sanchez, Benjamin R. Bates, Darwin Guerrero, Sylvia Jimenez, Esteban G. Baus, Koen Peeters Grietens, Mario J. Grijalva

Background

Human transmission of Chagas disease (CD) most commonly occurs in domiciliary spaces where triatomines remain hidden to feed on blood sources during inhabitants’ sleep. Similar to other neglected tropical diseases (NTDs), sustainable control of CD requires attention to the structural conditions of life of populations at risk, in this case, the conditions of their living environments. Considering socio-cultural and political dynamics involved in dwellings’ construction, this study aimed to explore social factors that contribute or limit sustainability of CD’s prevention models focused on home improvement.

Methods and main findings

Using Healthy Homes for Healthy Living (HHHL)—a health promotion strategy focused on improvement of living environments and system-based health promotion—as a reference, a qualitative study was conducted. Research participants were selected from three rural communities of a CD endemic region in southern Ecuador involved in HHHL’s refurbishment and reconstruction interventions between 2013 and 2016. Folowing an ethnographic approach, data were collected through interviews, participant observation, informal conversations and document analysis. Our results indicate that the HHHL model addressed risk factors for CD at the household level, while simultaneously promoting wellbeing at emotional, economic and social levels in local communities. We argue that sustainability of the CD prevention model proposed by HHHL is enhanced by the confluence of three factors: systemic improvement of families’ quality of life, perceived usefulness of control measures, and flexibility to adapt to emerging dynamics of the context.

Conclusion

HHHL’s proposed home improvement, facilitated through system-based rather than disease specific health promotion processes, enhances agency in populations at risk and facilitates community partnerships forged around CD prevention. Although an independent analysis of cost-effectiveness is recommended, structural poverty experienced by local families is still the most important factor to consider when evaluating the sustainability and scalability of this model.

Estimating undetected Ebola spillovers

PLoS Neglected Tropical Diseases News - 13 June 2019 - 9:00pm

by Emma E. Glennon, Freya L. Jephcott, Olivier Restif, James L. N. Wood

The preparedness of health systems to detect, treat, and prevent onward transmission of Ebola virus disease (EVD) is central to mitigating future outbreaks. Early detection of outbreaks is critical to timely response, but estimating detection rates is difficult because unreported spillover events and outbreaks do not generate data. Using three independent datasets available on the distributions of secondary infections during EVD outbreaks across West Africa, in a single district (Western Area) of Sierra Leone, and in the city of Conakry, Guinea, we simulated realistic outbreak size distributions and compared them to reported outbreak sizes. These three empirical distributions lead to estimates for the proportion of detected spillover events and small outbreaks of 26% (range 8–40%, based on the full outbreak data), 48% (range 39–62%, based on the Sierra Leone data), and 17% (range 11–24%, based on the Guinea data). We conclude that at least half of all spillover events have failed to be reported since EVD was first recognized. We also estimate the probability of detecting outbreaks of different sizes, which is likely less than 10% for single-case spillover events. Comparing models of the observation process also suggests the probability of detecting an outbreak is not simply the cumulative probability of independently detecting any one individual. Rather, we find that any individual’s probability of detection is highly dependent upon the size of the cluster of cases. These findings highlight the importance of primary health care and local case management to detect and contain undetected early stage outbreaks at source.

Towards harmonisation of entomological surveillance in the Mediterranean area

PLoS Neglected Tropical Diseases News - 13 June 2019 - 9:00pm

by Frédéric Jourdain, Abdallah M. Samy, Afrim Hamidi, Ali Bouattour, Bülent Alten, Chafika Faraj, David Roiz, Dušan Petrić, Elisa Pérez-Ramírez, Enkeledja Velo, Filiz Günay, Golubinka Bosevska, Ibrahim Salem, Igor Pajovic, Jelena Marić, Khalil Kanani, Lusine Paronyan, Maria-Grazia Dente, Marie Picard, Marija Zgomba, M'hammed Sarih, Nabil Haddad, Oleksandr Gaidash, Roena Sukhiasvili, Silvia Declich, Taher Shaibi, Tatiana Sulesco, Zoubir Harrat, Vincent Robert

Background

The Mediterranean Basin is historically a hotspot for trade, transport, and migration. As a result, countries surrounding the Mediterranean Sea share common public health threats. Among them are vector-borne diseases, and in particular, mosquito-borne viral diseases are prime candidates as (re)emerging diseases and are likely to spread across the area. Improving preparedness and response capacities to these threats at the regional level is therefore a major issue.The implementation of entomological surveillance is, in particular, of utmost importance. Guidance in designing entomological surveillance systems is critical, and these systems may pursue different specific objectives depending on the disease.The purpose of the proposed review is to draw up guidelines for designing effective and sustainable entomological surveillance systems in order to improve preparedness and response. However, we make it clear that there is no universal surveillance system, so the thinking behind harmonisation is to define evidence-based standards in order to promote best practises, identify the most appropriate surveillance activities, and optimise the use of resources.Such guidance is aimed at policymakers and diverse stakeholders and is intended to be used as a framework for the implementation of entomological surveillance programmes. It will also be useful to collaborate and share information with health professionals involved in other areas of disease surveillance. Medical entomologists and vector control professionals will be able to refer to this report to advocate for tailored entomological surveillance strategies.The main threats targeted in this review are the vectors of dengue virus, chikungunya virus, Zika virus, West Nile virus, and Rift Valley fever virus. The vectors of all these arboviruses are mosquitoes.

Methods

Current knowledge on vector surveillance in the Mediterranean area is reviewed. The analysis was carried out by a collaboration of the medical entomology experts in the region, all of whom belong to the MediLabSecure network, which is currently funded by the European Union and represents an international effort encompassing 19 countries in the Mediterranean and Black Sea region.

Findings

Robust surveillance systems are required to address the globalisation of emerging arboviruses. The prevention and management of mosquito-borne viral diseases must be addressed in the prism of a One Health strategy that includes entomological surveillance as an integral part of the policy. Entomological surveillance systems should be designed according to the entomological and epidemiological context and must have well-defined objectives in order to effect a tailored and graduated response. We therefore rely on different scenarios according to different entomological and epidemiological contexts and set out detailed objectives of surveillance. The development of multidisciplinary networks involving both academics and public authorities will provide resources to address these health challenges by promoting good practises in surveillance (identification of surveillance aims, design of surveillance systems, data collection, dissemination of surveillance results, evaluation of surveillance activities) and through the sharing of effective knowledge and information. These networks will also contribute to capacity building and stronger collaborations between sectors at both the local and regional levels. Finally, concrete guidance is offered on the vector of the main arbovirus based on the current situation in the area.

Outcomes of Third-Generation Cephalosporin Plus Ciprofloxacin or Doxycycline Therapy in Patients with <i>Vibrio vulnificus</i> Septicemia: A Propensity Score-Matched Analysis

PLoS Neglected Tropical Diseases News - 12 June 2019 - 9:00pm

by Seong Eun Kim, Sung Un Shin, Tae Hoon Oh, Uh Jin Kim, Kalifa Sanneh Darboe, Seung-Ji Kang, Hee-Chang Jang, Sook-In Jung, Hee-Young Shin, Kyung-Hwa Park

Background

Combination therapy with a third-generation cephalosporin (TGC) and a tetracycline analogue is recommended for Vibrio vulnificus infection. The combination of a TGC and ciprofloxacin has synergistic in vitro bactericidal activity against V. vulnificus. No clinical study has compared the standard regimen with TGC plus ciprofloxacin therapy for V. vulnificus infection.

Methods

Patients with a confirmed V. vulnificus infection at two medical centers in Korea from 1991 to 2016 were enrolled in this study. The patients were grouped according to the type of antibiotic administered. A retrospective propensity-score-matched case-control study of patients treated with TGC plus doxycycline or TGC plus ciprofloxacin was performed. The clinical characteristics and outcomes of the patients were analyzed.

Results

A total of 218 patients were confirmed to have V. vulnificus septicemia during the study, and the 30-day survival rate was 39% (85/218). The patients were classified into the following six treatment groups: TGC monotherapy (n = 82), TGC plus doxycycline therapy (n = 42), TGC plus ciprofloxacin therapy (n = 39), ciprofloxacin monotherapy (n = 14), other β-lactam monotherapy (n = 10), and other (n = 31). The survival rates of these groups were as follows: TGC monotherapy (35%), TGC plus doxycycline (38%), TGC plus ciprofloxacin (54%), ciprofloxacin monotherapy (29%), other β-lactam (20%), and other (39%). The 30-day survival rate showed no significant difference between the TGC plus doxycycline and TGC plus ciprofloxacin groups (log-rank test, P = 0.18). Among the 81 patients treated with TGC plus doxycycline or TGC plus ciprofloxacin, 12 per treatment group were selected by propensity-score matching. There was no significant difference in the baseline characteristics or the frequency of fasciotomy between the two groups. The 30-day survival rate showed no significant difference between the TGC plus doxycycline (50%) and TGC plus ciprofloxacin (67%) groups (log-rank test, P = 0.46).

Conclusion

Our data suggest that the outcome of TGC plus ciprofloxacin therapy was comparable to that of TGC plus doxycycline therapy in patients with V. vulnificus septicemia.

Vector competence of <i>Aedes aegypti</i> for different strains of Zika virus in Argentina

PLoS Neglected Tropical Diseases News - 12 June 2019 - 9:00pm

by Melisa Berenice Bonica, Silvina Goenaga, María Laura Martin, Mariel Feroci, Victoria Luppo, Evangelina Muttis, Cintia Fabbri, María Alejandra Morales, Delia Enria, María Victoria Micieli, Silvana Levis

The importance of Zika virus (ZIKV) has increased noticeably since the outbreak in the Americas in 2015, when the illness was associated with congenital disorders. Although there is evidence of sexual transmission of the virus, the mosquito Aedes aegypti is believed to be the main vector for transmission to humans. This species of mosquito has not only been found naturally infected with ZIKV, but also has been the subject of study in many vector competence assays that employ different strains of ZIKV around the world. In Argentina, the first case was reported in February 2016 and a total of 278 autochthonous cases have since been confirmed, however, ZIKV virus has not been isolated from any mosquito species yet in Argentina. In order to elucidate if Argentinian Ae. aegypti populations could be a possible vector of ZIKV, we conducted vector competence studies that involved a local strain of ZIKV from Chaco province, and a Venezuelan strain obtained from an imported case. For this purpose, Ae. aegypti adults from the temperate area of Argentina (Buenos Aires province) were fed with infected blood. Body, legs and saliva were harvested and tested by plaque titration on plates of Vero cells for ZIKV at 7, 11 and 14 days post infection (DPI) in order to calculate infection, transmission, and dissemination rates, respectively. Both strains were able to infect mosquitoes at all DPIs, whereas dissemination and transmission were observed at all DPIs for the Argentinian strain but only at 14 DPI for the Venezuelan strain. This study proves the ability of Ae. aegypti mosquitoes from Argentina to become infected with two different strains of ZIKV, both belonging to the Asian lineage, and that the virus can disseminate to the legs and salivary glands.

Associated-risk determinants for anthroponotic cutaneous leishmaniasis treated with meglumine antimoniate: A cohort study in Iran

PLoS Neglected Tropical Diseases News - 12 June 2019 - 9:00pm

by Mohammad Reza Aflatoonian, Iraj Sharifi, Behnaz Aflatoonian, Mehdi Bamorovat, Amireh Heshmatkhah, Zahra Babaei, Pooya Ghasemi Nejad Almani, Mohammad Ali Mohammadi, Ehsan Salarkia, Abbas Aghaei Afshar, Hamid Sharifi, Fatemeh Sharifi, Ahmad Khosravi, Mehrdad Khatami, Nasir Arefinia, Alireza Fekri, Saeideh Farajzadeh, Ali Khamesipour, Mehdi Mohebali, Mohammad Mehdi Gouya, Mohammad Reza Shirzadi, Rajender S. Varma

Background

The control of cutaneous leishmaniasis (CL) is facilitated by knowledge of factors associated with the treatment failures in endemic countries. The aim of this evaluation was to identify the potential risk determinants which might affect the significance of demographic and clinical characteristics for the patients with anthroponotic CL (ACL) and the outcome of meglumine antimoniate (MA) (Glucantime) treatment.

Methodology/Principal findings

This current was executed as a cohort spanning over a period of 5 years which centered in southeastern part of Iran. Altogether, 2,422 participants were evaluated and 1,391 eligible volunteer patients with ACL caused by Leishmania tropica were included. Overall, 1,116 (80.2%) patients received MA intraleisionally (IL), once a week for 12 weeks along with biweekly cryotherapy, while 275 (19.8%) patients received MA alone (20 mg/kg/day for 3 weeks) (intramuscular, IM). The treatment failure rate in ACL patients was 11% using IL combined with cryotherapy plus IM alone, whilst 9% and 18.5% by IL along with cryotherapy or IM alone, respectively. Multivariate logistic regression model predicted 5 major associated-risk determinants including male (odds ratio (OR) = 1.54, confidence interval (CI) = 1.079–2.22, p = 0.018), lesion on face (OR = 1.574, CI = 1.075–2.303, p = 0.02), multiple lesions (OR = 1.446, CI = 1.008–2.075, p = 0.045), poor treatment adherence (OR = 2.041, CI = 1.204–3.46, p = 0.008) and disease duration > 4 months (OR = 2.739, CI = 1.906–3.936, p≤0.001).

Conclusions/Significance

The present study is the original and largest cohort of ACL patients who treated with MA. A comprehensive intervention and coordinated action by the health authorities and policy-makers are crucial to make sure that patients strictly follow medical instructions. Early detection and effective therapy < 4 months following the onset of the lesion is critical for successful treatment of the patients. Since a significant number of patients are still refractory to MA, reducing man-vector exposure and development of new effective alternative drugs are essential measures against ACL due to L. tropica.

Maternal, placental and cord blood cytokines and the risk of adverse birth outcomes among pregnant women infected with <i>Schistosoma japonicum</i> in the Philippines

PLoS Neglected Tropical Diseases News - 12 June 2019 - 9:00pm

by Ajibola I. Abioye, Emily A. McDonald, Sangshin Park, Ayush Joshi, Jonathan D. Kurtis, Hannah Wu, Sunthorn Pond-Tor, Surendra Sharma, Jan Ernerudh, Palmera Baltazar, Luz P. Acosta, Remigio M. Olveda, Veronica Tallo, Jennifer F. Friedman

Background

The objectives of this study were to 1) evaluate the influence of treatment with praziquantel on the inflammatory milieu in maternal, placental, and cord blood, 2) assess the extent to which proinflammatory signatures in placental and cord blood impacts birth outcomes, and 3) evaluate the impact of other helminths on the inflammatory micro environment.

Methods/Findings

This was a secondary analysis of samples from 369 mother-infant pairs participating in a randomized controlled trial of praziquantel given at 12–16 weeks’ gestation. We performed regression analysis to address our study objectives. In maternal peripheral blood, the concentrations of CXCL8, and TNF receptor I and II decreased from 12 to 32 weeks’ gestation, while IL-13 increased. Praziquantel treatment did not significantly alter the trajectory of the concentration of any of the cytokines examined. Hookworm infection was associated with elevated placental IL-1, CXCL8 and IFN-γ. The risk of small-for-gestational age increased with elevated IL-6, IL-10, and CXCL8 in cord blood. The risk of prematurity was increased when cord blood sTNFRI and placental IL-5 were elevated.

Conclusions

Our study suggests that fetal cytokines, which may be related to infectious disease exposures, contribute to poor intrauterine growth. Additionally, hookworm infection influences cytokine concentrations at the maternal-fetal interface.

Clinical Trial Registry number and website

ClinicalTrials.gov (NCT00486863).

Zebra skin odor repels the savannah tsetse fly, <i>Glossina pallidipes</i> (Diptera: Glossinidae)

PLoS Neglected Tropical Diseases News - 10 June 2019 - 9:00pm

by Olabimpe Y. Olaide, David P. Tchouassi, Abdullahi A. Yusuf, Christian W. W. Pirk, Daniel K. Masiga, Rajinder K. Saini, Baldwyn Torto

Background

African trypanosomosis, primarily transmitted by tsetse flies, remains a serious public health and economic challenge in sub-Saharan Africa. Interventions employing natural repellents from non-preferred hosts of tsetse flies represent a promising management approach. Although zebras have been identified as non-preferred hosts of tsetse flies, the basis for this repellency is poorly understood. We hypothesized that zebra skin odors contribute to their avoidance by tsetse flies.

Methodology/Principal findings

We evaluated the effect of crude zebra skin odors on catches of wild savannah tsetse flies (Glossina pallidipes Austen, 1903) using unbaited Ngu traps compared to the traps baited with two known tsetse fly management chemicals; a repellent blend derived from waterbuck odor, WRC (comprising geranylacetone, guaiacol, pentanoic acid and δ-octalactone), and an attractant comprising cow urine and acetone, in a series of Latin square-designed experiments. Coupled gas chromatography-electroantennographic detection (GC/EAD) and GC-mass spectrometry (GC/MS) analyses of zebra skin odors identified seven electrophysiologically-active components; 6-methyl-5-hepten-2-one, acetophenone, geranylacetone, heptanal, octanal, nonanal and decanal, which were tested in blends and singly for repellency to tsetse flies when combined with Ngu traps baited with cow urine and acetone in field trials. The crude zebra skin odors and a seven-component blend of the EAD-active components, formulated in their natural ratio of occurrence in zebra skin odor, significantly reduced catches of G. pallidipesby 66.7% and 48.9% respectively, and compared favorably with the repellency of WRC (58.1%– 59.2%). Repellency of the seven-component blend was attributed to the presence of the three ketones 6-methyl-5-hepten-2-one, acetophenone and geranylacetone, which when in a blend caused a 62.7% reduction in trap catch of G. pallidipes.

Conclusions/Significance

Our findings reveal fundamental insights into tsetse fly ecology and the allomonal effect of zebra skin odor, and potential integration of the three-component ketone blend into the management toolkit for tsetse and African trypanosomosis control.

Seasonal and geographic variation in insecticide resistance in <i>Aedes aegypti</i> in southern Ecuador

PLoS Neglected Tropical Diseases News - 10 June 2019 - 9:00pm

by Sadie J. Ryan, Stephanie J. Mundis, Alex Aguirre, Catherine A. Lippi, Efraín Beltrán, Froilán Heras, Valeria Sanchez, Mercy J. Borbor-Cordova, Rachel Sippy, Anna M. Stewart-Ibarra, Marco Neira

Insecticide resistance (IR) can undermine efforts to control vectors of public health importance. Aedes aegypti is the main vector of resurging diseases in the Americas such as yellow fever and dengue, and recently emerging chikungunya and Zika fever, which have caused unprecedented epidemics in the region. Vector control remains the primary intervention to prevent outbreaks of Aedes-transmitted diseases. In many high-risk regions, like southern Ecuador, we have limited information on IR. In this study, Ae. aegypti IR was measured across four cities in southern Ecuador using phenotypic assays and genetic screening for alleles associated with pyrethroid IR. Bottle bioassays showed significant inter-seasonal variation in resistance to deltamethrin, a pyrethroid commonly used by the Ministry of Health, and alpha-cypermethrin, as well as between-city differences in deltamethrin resistance. There was also a significant difference in phenotypic response to the organophosphate, Malathion, between two cities during the second sampling season. Frequencies of the resistant V1016I genotype ranged from 0.13 to 0.68. Frequencies of the resistant F1534C genotype ranged from 0.63 to 1.0, with sampled populations in Machala and Huaquillas at fixation for the resistant genotype in all sampled seasons. In Machala and Portovelo, there were statistically significant inter-seasonal variation in genotype frequencies for V1016I. Resistance levels were highest in Machala, a city with hyperendemic dengue transmission and historically intense insecticide use. Despite evidence that resistance alleles conferred phenotypic resistance to pyrethroids, there was not a precise correspondence between these indicators. For the F1534C gene, 17.6% of homozygous mutant mosquitoes and 70.8% of heterozygotes were susceptible, while for the V1016I gene, 45.6% homozygous mutants and 55.6% of heterozygotes were susceptible. This study shows spatiotemporal variability in IR in Ae. aegypti populations in southern coastal Ecuador, and provides an initial examination of IR in this region, helping to guide vector control efforts for Ae. aegypti.

Pregnancy outcomes and mother-to-child transmission rate in HTLV-1/2 infected women attending two public hospitals in the metropolitan area of Rio de Janeiro

PLoS Neglected Tropical Diseases News - 10 June 2019 - 9:00pm

by Danielle Bittencourt Sodré Barmpas, Denise Leite Maia Monteiro, Stella Regina Taquette, Nádia Cristina Pinheiro Rodrigues, Alexandre José Baptista Trajano, Juliana de Castro Cunha, Camila Lattanzi Nunes, Lucia Helena Cavalheiro Villela, Sérgio A. M. Teixeira, Denise Cardoso das Neves Sztajnbok, Márcio Neves Bóia

HTLV-1/2 are transmitted sexually, by whole cell blood products and from mother-to-child (MTC), mainly through breastfeeding. HTLV-1/2 prevalence in pregnant women is high in Rio de Janeiro, however there were no local studies addressing the rate of adverse pregnancy outcomes (APO) and MTC transmission. The aim was to study sociodemographic characteristics which may be associated to HTLV-1/2 infection and describe pregnancy outcomes and MTC transmission in HTLV-1/2-positive women. The cross-sectional study screened 1,628 pregnant women in of Rio de Janeiro (2012–2014) and found 12 asymptomatic carrier mothers (prevalence = 0.74%). Pregnancy outcome information was retrieved from medical records. Sociodemographic characteristics were similar between the positive and negative groups except for maternal age, which was higher in carrier mothers. The incidence of adverse pregnancy outcomes was similar in infected and non-infected patients (p = 0.33), however there was a high rate of premature rupture of membranes (PROM) amid infected mothers (3/12). Multilevel logistic regression found that for each additional year of age, the chance of being HTLV-1/2-positive increased 11% and that having another sexually transmitted infection (STI) increased 9 times the chance of being infected. Carrier mothers had more antenatal visits (OR = 5.26). Among the children of HTLV-1/2-positive mothers there was one fetal death, one infant death and one loss of follow-up. After two years of follow-up there was one case of MTC transmission (1/9). The mother reported breastfeeding for one month only. Knowledge about factors associated to HTLV-1/2 infection, its impact on pregnancy outcomes and the MTC transmission rate is important to guide public health policies on antenatal screening and management.

A novel integrated molecular and serological analysis method to predict new cases of leprosy amongst household contacts

PLoS Neglected Tropical Diseases News - 10 June 2019 - 9:00pm

by Rafael Silva Gama, Márcio Luís Moreira de Souza, Euzenir Nunes Sarno, Milton Ozório de Moraes, Aline Gonçalves, Mariane M. A. Stefani, Raúl Marcel González Garcia, Lucia Alves de Oliveira Fraga

Background

Early detection of Mycobacterium leprae is a key strategy for disrupting the transmission chain of leprosy and preventing the potential onset of physical disabilities. Clinical diagnosis is essential, but some of the presented symptoms may go unnoticed, even by specialists. In areas of greater endemicity, serological and molecular tests have been performed and analyzed separately for the follow-up of household contacts, who are at high risk of developing the disease. The accuracy of these tests is still debated, and it is necessary to make them more reliable, especially for the identification of cases of leprosy between contacts. We proposed an integrated analysis of molecular and serological methods using artificial intelligence by the random forest (RF) algorithm to better diagnose and predict new cases of leprosy.

Methods

The study was developed in Governador Valadares, Brazil, a hyperendemic region for leprosy. A longitudinal study was performed, including new cases diagnosed in 2011 and their respective household contacts, who were followed in 2011, 2012, and 2016. All contacts were diligently evaluated by clinicians from Reference Center for Endemic Diseases (CREDEN-PES) before being classified as asymptomatic. Samples of slit skin smears (SSS) from the earlobe of the patients and household contacts were collected for quantitative polymerase chain reaction (qPCR) of 16S rRNA, and peripheral blood samples were collected for ELISA assays to detect LID-1 and ND-O-LID.

Results

The statistical analysis of the tests revealed sensitivity for anti-LID-1 (63.2%), anti-ND-O-LID (57.9%), qPCR SSS (36.8%), and smear microscopy (30.2%). However, the use of RF allowed for an expressive increase in sensitivity in the diagnosis of multibacillary leprosy (90.5%) and especially paucibacillary leprosy (70.6%). It is important to report that the specificity was 92.5%.

Conclusion

The proposed model using RF allows for the diagnosis of leprosy with high sensitivity and specificity and the early identification of new cases among household contacts.

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