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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.

A meta-analysis of infection rates of <i>Schistosoma japonicum</i> in sentinel mice associated with infectious waters in mainland China over last 40 years

PLoS Neglected Tropical Diseases News - 7 June 2019 - 9:00pm

by Chen Qiu, Hui-Ying Zou, Yao Deng, You-sheng Liang, Da-Bing Lu

Background

Schistosomiasis japonica is a zoonotic parasitic disease. After nearly 70 years of control efforts in China, Schistosomiasis transmission has been reduced to a much lower level. The absence or near absence of infections in humans or livestock, based on traditional fecal and serological tests, has made the targets and priorities of future control efforts difficult to determine. However, detection of schistosome cercariae in waters using sentinel mice could be an alternative way of identifying remaining foci of infection, or even serve as a tool for evaluation of control efficacy. This method has been employed in China over last forty years. We therefore performed a meta-analysis of the relevant research to investigate if infections in sentinel mice mirror the ongoing trend of schistosomiasis transmission in China.

Methods

We conducted a meta-analysis of studies reporting infection rates of S. japonicum in sentinel mice in China before Sep 1, 2018 in accordance with the PRISMA guidelines. We retrieved all relative studies based on five databases (CNKI, WanFang, VIP, PubMed and Web of Science) and the reference lists of resulting articles. For each individual study, the infection rate in sentinel mice is presented together with its 95% confidence interval (CI). Point estimates of the overall infection rates and their 95% CIs were calculated. Subgroup analyses were performed according to study periods, seasons or regions.

Results

We identified 90 articles, including 290 studies covering eight endemic provinces. The overall rate in sentinel mice was 12.31% (95% CI: 10.14–14.65%) from 1980 to 2018. The value of 3.66% (95% CI: 2.62–4.85%) estimated in 2004 to 2018 was significantly lower than in 1980 to 2003 (22.96%, 95% CI: 19.25–26.89%). The estimate was significantly higher in the middle and lower reaches than in the upper reaches of the Yangtze River. The highest estimates were obtained in Hunan (30.11%, 95% CI: 25.64–34.77%) followed by Anhui (26.34%, 95% CI: 12.88–42.44%) and then Jiangxi (13.73%, 95% CI: 6.71–22.56%). Unlike the other provinces in the middle and lower reaches, no significant reduction was seen in Hubei after 2003. Even in Hubei two studies carried out after 2014 reported infections in sentinel mice, although no infected snails were reported across the province. Infections were most found in April (17.40%, 95% CI: 1.13–45.49%), July (24.98%, 95% CI: 15.64–35.62%) and October (17.08%, 95% CI 5.94–32.05%). High degrees of heterogeneity were observed.

Conclusion

This meta-analysis provides a comprehensive analysis of schistosome infection in sentinel mice across China. The estimates largely mirror the ongoing trends of transmission in terms of periods and regions. Infections were most likely to occur in April, July and October. In areas where no infected snails were reported infections in sentinel mice were still observed. Due to the presence of snails and infected wildlife, detection of schistosomes in waters using such a highly sensitive method as the deployment of sentinel mice, remains of importance in schistosomiasis monitoring. We would suggest the current criteria for transmission interruption or elimination of schistosomiasis in China be adjusted by integrating the results of sentinel mice based surveys.

Host species and site of collection shape the microbiota of Rift Valley fever vectors in Kenya

PLoS Neglected Tropical Diseases News - 7 June 2019 - 9:00pm

by David P. Tchouassi, Ephantus J. Muturi, Samwel O. Arum, Chang-Hyun Kim, Christopher J. Fields, Baldwyn Torto

The composition and structure of microbial communities associated with mosquitoes remain poorly understood despite their important role in host biology and potential to be harnessed as novel strategies for mosquito-borne disease control. We employed MiSeq sequencing of the 16S rRNA gene amplicons to characterize the bacterial flora of field-collected populations of Aedes mcintoshi and Aedes ochraceus, the primary vectors of Rift Valley fever (RVF) virus in Kenya. Proteobacteria (53.5%), Firmicutes (22.0%) and Actinobacteria (10.0%) were the most abundant bacterial phyla accounting for 85.5% of the total sequences. Non-metric multi-dimensional scaling plots based on Bray-Curtis dissimilarities revealed a clear grouping of the samples by mosquito species, indicating that the two mosquito species harbored distinct microbial communities. Microbial diversity, richness and composition was strongly influenced by the site of mosquito collection and overall, Ae. ochraceus had significantly higher microbial diversity and richness than Ae. mcintoshi. Our findings suggest that host species and site of collection are important determinants of bacterial community composition and diversity in RVF virus vectors and these differences likely contribute to the spatio-temporal transmission dynamics of RVF virus.

A single-dose ChAdOx1-vectored vaccine provides complete protection against Nipah Bangladesh and Malaysia in Syrian golden hamsters

PLoS Neglected Tropical Diseases News - 6 June 2019 - 9:00pm

by Neeltje van Doremalen, Teresa Lambe, Sarah Sebastian, Trenton Bushmaker, Robert Fischer, Friederike Feldmann, Elaine Haddock, Michael Letko, Victoria A. Avanzato, Ilona Rissanen, Rachel LaCasse, Dana Scott, Thomas A. Bowden, Sarah Gilbert, Vincent Munster

Nipah virus (NiV) is a highly pathogenic re-emerging virus that causes outbreaks in South East Asia. Currently, no approved and licensed vaccine or antivirals exist. Here, we investigated the efficacy of ChAdOx1 NiVB, a simian adenovirus-based vaccine encoding NiV glycoprotein (G) Bangladesh, in Syrian hamsters. Prime-only as well as prime-boost vaccination resulted in uniform protection against a lethal challenge with NiV Bangladesh: all animals survived challenge and we were unable to find infectious virus either in oral swabs, lung or brain tissue. Furthermore, no pathological lung damage was observed. A single-dose of ChAdOx1 NiVB also prevented disease and lethality from heterologous challenge with NiV Malaysia. While we were unable to detect infectious virus in swabs or tissue of animals challenged with the heterologous strain, a very limited amount of viral RNA could be found in lung tissue by in situ hybridization. A single dose of ChAdOx1 NiVB also provided partial protection against Hendra virus and passive transfer of antibodies elicited by ChAdOx1 NiVB vaccination partially protected Syrian hamsters against NiV Bangladesh. From these data, we conclude that ChAdOx1 NiVB is a suitable candidate for further NiV vaccine pre-clinical development.

Disruption of the NlpD lipoprotein of the plague pathogen <i>Yersinia pestis</i> affects iron acquisition and the activity of the twin-arginine translocation system

PLoS Neglected Tropical Diseases News - 6 June 2019 - 9:00pm

by Avital Tidhar, Yinon Levy, Ayelet Zauberman, Yaron Vagima, David Gur, Moshe Aftalion, Ofir Israeli, Theodor Chitlaru, Naomi Ariel, Yehuda Flashner, Anat Zvi, Emanuelle Mamroud

We have previously shown that the cell morphogenesis NlpD lipoprotein is essential for virulence of the plague bacteria, Yersinia pestis. To elucidate the role of NlpD in Y. pestis pathogenicity, we conducted a whole-genome comparative transcriptome analysis of the wild-type Y. pestis strain and an nlpD mutant under conditions mimicking early stages of infection. The analysis suggested that NlpD is involved in three phenomena: (i) Envelope stability/integrity evidenced by compensatory up-regulation of the Cpx and Psp membrane stress-response systems in the mutant; (ii) iron acquisition, supported by modulation of iron metabolism genes and by limited growth in iron-deprived medium; (iii) activity of the twin-arginine (Tat) system, which translocates folded proteins across the cytoplasmic membrane. Virulence studies of Y. pestis strains mutated in individual Tat components clearly indicated that the Tat system is central in Y. pestis pathogenicity and substantiated the assumption that NlpD essentiality in iron utilization involves the activity of the Tat system. This study reveals a new role for NlpD in Tat system activity and iron assimilation suggesting a modality by which this lipoprotein is involved in Y. pestis pathogenesis.

Regulatory T cells and IgE expression in duodenal mucosa of <i>Strongyloides stercoralis</i> and human T lymphotropic virus type 1 co-infected patients

PLoS Neglected Tropical Diseases News - 6 June 2019 - 9:00pm

by Luis Malpica, A. Clinton White Jr., Cristina Leguia, Natalia Freundt, Nicolas Barros, Cesar Chian, E. Antonio Antunez, Martin Montes

Background

Strongyloides stercoralis is an intestinal nematode unique in its ability to replicate in the human host, allowing ongoing cycles of autoinfection, persisting for decades within the same host. Although usually asymptomatic, overwhelming infections can occur in Strongyloides and HTLV-1 co-infected individuals (SS/HTLV-1). Regulatory T cells (Tregs) are able to blunt specific Th2 responses necessary to control the parasite. We previously reported that peripheral blood Tregs are increased in SS/HTLV-1 and correlate with low Th2 responses. We hypothesized that Tregs are also increased at the site of infection in duodenal mucosa.

Methods

Paraffin embedded duodenal biopsies were obtained from 10 SS/HTLV-1 patients, 3 controls with non-parasitic chronic duodenitis, and 2 healthy controls. Immunohistochemistry was performed using monoclonal antibodies against human CD3, CD8, IgE and FoxP3. The number of cells were counted using a conventional light microscope. The number of CD3+, CD8+, FP3+ and IgE positive cells per 0.35 mm2 was measured using ImagePro Plus software comparing areas adjacent or distant from parasite material.

Results

In patients with SS/HTLV-1, T lymphocyte counts and CD8+ cells were lower in areas adjacent to the parasite compared to non-adjacent areas (CD3+: adjacent: 6.5 [Interquartile range (IQR: 2.8–12.3)]; non-adjacent: 24.5 [IQR: 20.9–34.4]; Mann-Whitney p = 0.0003; CD8+: adjacent: 4.5 [IQR: 2.3–11.8]; non-adjacent: 21 [IQR: 15.3–42.9]; Mann-Whitney p = 0.0011). Tregs cells in the intestines (FoxP3+ expressing cells) were increased in patients with SS/HTLV-1 compared with patients with chronic duodenitis (SS/HTLV-1: 1.5 [IQR: 0.7–2.3]; duodenitis controls: 0 [range 0–0.7]; healthy controls: 0; Mann-Whitney p = 0.034). There was also a trend towards fewer eosinophils adjacent to the parasites. Among SS/HTLV-1 patients the number of IgE expressing cells was increased for in areas not adjacent to the parasite compared to non-adjacent areas (ANOVA, p = 0.001).

Conclusions

Our data shows increased Treg cell numbers localized adjacent to the parasites in the duodenum SS/HTLV-1 patients. In addition, other T lymphocytes and IgE expressing cells were decreased adjacent to the parasites, suggesting an important role for Tregs in down-regulating local parasite effector responses.

Increased growth ability and pathogenicity of American- and Pacific-subtype Zika virus (ZIKV) strains compared with a Southeast Asian-subtype ZIKV strain

PLoS Neglected Tropical Diseases News - 6 June 2019 - 9:00pm

by Yasuhiro Kawai, Eri Nakayama, Kenta Takahashi, Satoshi Taniguchi, Ken-ichi Shibasaki, Fumihiro Kato, Takahiro Maeki, Tadaki Suzuki, Shigeru Tajima, Masayuki Saijo, Chang-Kweng Lim

We investigated the growth properties and virulence in mice of three Zika virus (ZIKV) strains of Asian/American lineage, PRVABC59, ZIKV/Hu/Chiba/S36/2016 (ChibaS36), and ZIKV/Hu/NIID123/2016 (NIID123), belonging to the three distinct subtypes of this lineage. The American-subtype strain, PRVABC59, showed the highest growth potential in vitro, whereas the Southeast Asian-subtype strain, NIID123, showed the lowest proliferative capacity. Moreover, PRVABC59- and NIID123-infected mice showed the highest and lowest viremia levels and infectious virus levels in the testis, respectively, and the rate of damaged testis in PRVABC59-infected mice was higher than in mice infected with the other two strains. Lastly, ZIKV NS1 antigen was detected in the damaged testes of mice infected with PRVABC59 and the Pacific-subtype strain, ChibaS36, at 2 weeks post-inoculation and in the epididymides of PRVABC59-infected mice at 6 weeks post-inoculation. Our results indicate that PRVABC59 and ChibaS36 exhibit increased abilities to grow in vitro and in vivo and to induce testis damage in mice.

Identification of divergent <i>Leishmania</i> (<i>Viannia</i>) <i>braziliensis</i> ecotypes derived from a geographically restricted area through whole genome analysis

PLoS Neglected Tropical Diseases News - 6 June 2019 - 9:00pm

by Bruna S. L. Figueiredo de Sá, Antonio M. Rezende, Osvaldo P. de Melo Neto, Maria Edileuza F. de Brito, Sinval P. Brandão Filho

Leishmania braziliensis, the main etiological agent of cutaneous leishmaniasis (CL) in Latin America, is characterized by major differences in basic biology in comparison with better-known Leishmania species. It is also associated with a high phenotypic and possibly genetic diversity that need to be more adequately defined. Here we used whole genome sequences to evaluate the genetic diversity of ten L. braziliensis isolates from a CL endemic area from Northeastern Brazil, previously classified by Multi Locus Enzyme Electrophoresis (MLEE) into ten distinct zymodemes. These sequences were first mapped using the L. braziliensis M2904 reference genome followed by identification of Single Nucleotide Polymorphisms (SNPs). A substantial level of diversity was observed when compared with the reference genome, with SNP counts ranging from ~95,000 to ~131,000 for the different isolates. When the genome data was used to infer relationship between isolates, those belonging to zymodemes Z72/Z75, recovered from forested environments, were found to cluster separately from the others, generally associated with more urban environments. Among the remaining isolates, those from zymodemes Z74/Z106 were also found to form a separate group. Phylogenetic analyses were also performed using Multi-Locus Sequence Analysis from genes coding for four metabolic enzymes used for MLEE as well as the gene sequence coding for the Hsp70 heat shock protein. All 10 isolates were firmly identified as L. braziliensis, including the zymodeme Z26 isolate previously classified as Leishmania shawi, with the clustering into three groups confirmed. Aneuploidy was also investigated but found in general restricted to chromosome 31, with a single isolate, from zymodeme Z27, characterized by extra copies for other chromosomes. Noteworthy, both Z72 and Z75 isolates are characterized by a much reduced heterozygosity. Our data is consistent with the existence of distinct evolutionary groups in the restricted area sampled and a substantial genetic diversity within L. braziliensis.

Genetic changes associated with the temporal shift in invasive non-typhoidal <i>Salmonella</i> serovars in Bamako Mali

PLoS Neglected Tropical Diseases News - 6 June 2019 - 9:00pm

by Kristin Bornstein, Sharon M. Tennant, Tracy H. Hazen, John D. Sorkin, Milagritos D. Tapia, Samba O. Sow, Uma Onwuchekwa, Myron M. Levine, David A. Rasko

Background

Invasive non-typhoidal Salmonella (iNTS) serovars S. Typhimurium and S. Enteritidis are major etiologic agents of invasive bacterial disease among infants and young children in sub-Saharan Africa, including in Mali. Early studies of iNTS serovars in several countries indicated that S. Typhimurium was more prevalent than S. Enteritidis, including in Mali before 2008. We investigated genomic and associated phenotypic changes associated with an increase in the relative proportion of iNTS caused by S. Enteritidis versus S. Typhimurium in Bamako, Mali, during the period 2002–2012.

Methodology/Principal findings

Comparative genomics studies identified homologs of tetracycline resistance and arsenic utilization genes that were associated with the temporal shift of serovars causing iNTS shift, along with several hypothetical proteins. These findings, validated through PCR screening and phenotypic assays, provide initial steps towards characterizing the genomic changes consequent to unknown evolutionary pressures associated with the shift in serovar prevalence.

Conclusions/Significance

This work identified a shift to S. Enteritidis from the more classic S. Typhimurium, associated with iNTS in Bamako, Mali, during the period 2002–2012. This type of shift in underlying iNTS pathogens are of great importance to pediatric public health in endemic regions of sub-Saharan Africa. Additionally, this work demonstrates the utility of combining epidemiologic data, whole genome sequencing, and functional characterization in the laboratory to identify and characterize genomic changes in the isolates that may be involved with the observed shift in circulating iNTS agents.

Peripheral immune response in the African green monkey model following Nipah-Malaysia virus exposure by intermediate-size particle aerosol

PLoS Neglected Tropical Diseases News - 5 June 2019 - 9:00pm

by Abigail Lara, Yu Cong, Peter B. Jahrling, Mark Mednikov, Elena Postnikova, Shuiqing Yu, Vincent Munster, Michael R. Holbrook

The ability to appropriately mimic human disease is critical for using animal models as a tool for understanding virus pathogenesis. In the case of Nipah virus (NiV), infection of humans appears to occur either through inhalation, contact with or consumption of infected material. In two of these circumstances, respiratory or sinusoidal exposure represents a likely route of infection. In this study, intermediate-size aerosol particles (~7 μm) of NiV-Malaysia were used to mimic potential routes of exposure by focusing viral deposition in the upper respiratory tract. Our previous report showed this route of exposure extended the disease course and a single animal survived the infection. Here, analysis of the peripheral immune response found minimal evidence of systemic inflammation and depletion of B cells during acute disease. However, the animal that survived infection developed an early IgM response with rapid development of neutralizing antibodies that likely afforded protection. The increase in NiV-specific antibodies correlated with an expansion of the B cell population in the survivor. Cell-mediated immunity was not clearly apparent in animals that succumbed during the acute phase of disease. However, CD4+ and CD8+ effector memory cells increased in the survivor with correlating increases in cytokines and chemokines associated with cell-mediated immunity. Interestingly, kinetic changes of the CD4+ and CD8bright T cell populations over the course of acute disease were opposite from animals that succumbed to infection. In addition, increases in NK cells and basophils during convalescence of the surviving animal were also evident, with viral antigen found in NK cells. These data suggest that a systemic inflammatory response and “cytokine storm” are not major contributors to NiV-Malaysia pathogenesis in the AGM model using this exposure route. Further, these data demonstrate that regulation of cell-mediated immunity, in addition to rapid production of NiV specific antibodies, may be critical for surviving NiV infection.

Linear growth in preschool children treated with mass azithromycin distributions for trachoma: A cluster-randomized trial

PLoS Neglected Tropical Diseases News - 5 June 2019 - 9:00pm

by Jeremy D. Keenan, Sintayehu Gebresillasie, Nicole E. Stoller, Berhan A. Haile, Zerihun Tadesse, Sun Y. Cotter, Kathryn J. Ray, Kristen Aiemjoy, Travis C. Porco, E. Kelly Callahan, Paul M. Emerson, Thomas M. Lietman

Background

Mass azithromycin distributions have been shown to reduce mortality among pre-school children in sub-Saharan Africa. It is unclear what mediates this mortality reduction, but one possibility is that antibiotics function as growth promoters for young children.

Methods and findings

24 rural Ethiopian communities that had received biannual mass azithromycin distributions over the previous four years were enrolled in a parallel-group, cluster-randomized trial. Communities were randomized in a 1:1 ratio to either continuation of biannual oral azithromycin (20mg/kg for children, 1 g for adults) or to no programmatic antibiotics over the 36 months of the study period. All community members 6 months and older were eligible for the intervention. The primary outcome was ocular chlamydia; height and weight were measured as secondary outcomes on children less than 60 months of age at months 12 and 36. Study participants were not masked; anthropometrists were not informed of the treatment allocation. Anthropometric measurements were collected for 282 children aged 0–36 months at the month 12 assessment and 455 children aged 0–59 months at the month 36 assessment, including 207 children who had measurements at both time points. After adjusting for age and sex, children were slightly but not significantly taller in the biannually treated communities (84.0 cm, 95%CI 83.2–84.8, in the azithromycin-treated communities vs. 83.7 cm, 95%CI 82.9–84.5, in the untreated communities; mean difference 0.31 cm, 95%CI -0.85 to 1.47, P = 0.60). No adverse events were reported.

Conclusions

Periodic mass azithromycin distributions for trachoma did not demonstrate a strong impact on childhood growth.

Trial registration

The TANA II trial was registered on clinicaltrials.gov #NCT01202331.

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