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Comparison of three data mining models for prediction of advanced schistosomiasis prognosis in the Hubei province

15 February 2018 - 10:00pm

by Guo Li, Xiaorong Zhou, Jianbing Liu, Yuanqi Chen, Hengtao Zhang, Yanyan Chen, Jianhua Liu, Hongbo Jiang, Junjing Yang, Shaofa Nie

Background

In order to better assist medical professionals, this study aimed to develop and compare the performance of three models—a multivariate logistic regression (LR) model, an artificial neural network (ANN) model, and a decision tree (DT) model—to predict the prognosis of patients with advanced schistosomiasis residing in the Hubei province.

Methodology/Principal findings

Schistosomiasis surveillance data were collected from a previous study based on a Hubei population sample including 4136 advanced schistosomiasis cases. The predictive models use LR, ANN, and DT methods. From each of the three groups, 70% of the cases (2896 cases) were used as training data for the predictive models. The remaining 30% of the cases (1240 cases) were used as validation groups for performance comparisons between the three models. Prediction performance was evaluated using area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy. Univariate analysis indicated that 16 risk factors were significantly associated with a patient’s outcome of prognosis. In the training group, the mean AUC was 0.8276 for LR, 0.9267 for ANN, and 0.8229 for DT. In the validation group, the mean AUC was 0.8349 for LR, 0.8318 for ANN, and 0.8148 for DT. The three models yielded similar results in terms of accuracy, sensitivity, and specificity.

Conclusions/Significance

Predictive models for advanced schistosomiasis prognosis, respectively using LR, ANN and DT models were proved to be effective approaches based on our dataset. The ANN model outperformed the LR and DT models in terms of AUC.

Imported endemic mycoses in Spain: Evolution of hospitalized cases, clinical characteristics and correlation with migratory movements, 1997-2014

15 February 2018 - 10:00pm

by Daniel Molina-Morant, Adrián Sánchez-Montalvá, Fernando Salvador, Augusto Sao-Avilés, Israel Molina

Endemic mycoses are systemic fungal infections. Histoplasmosis is endemic in all temperate areas of the world; coccidioidomycosis and paracoccidioidomycosis are only present in the American continent. These pathogens are not present in Spain, but in the last years there has been an increase of reported cases due to migration and temporary movements. We obtained from the Spanish hospitals records clinical and demographic data of all hospitalized cases between 1997 and 2014. There were 286 cases of histoplasmosis, 94 of Coccidioidomycosis and 25 of paracoccidioidomycosis. Overall, histoplasmosis was strongly related to HIV infection, as well as with greater morbidity and mortality. For the other mycoses, we did not find any immunosuppressive condition in most of the cases. Although we were not able to obtain data about clinical presentation of all the cases, the most frequently found was pulmonary involvement. We also found a temporal correlation between the Spanish population born in endemic countries and the number of hospitalized cases along this period. This study reflects the importance of imported diseases in non-endemic countries due to migratory movements.

<i>Mycobacterium tuberculosis</i> complex genotypes circulating in Nigeria based on spoligotyping obtained from Ziehl-Neelsen stained slides extracted DNA

15 February 2018 - 10:00pm

by Barbara Molina-Moya, Michel K. Gomgnimbou, Lizania Spinasse, Joshua Obasanya, Olanrewaju Oladimeji, Russell Dacombe, Thomas Edwards, Xavier-Olessa Daragon, Lovett Lawson, Saddiq T. Abdurrahman, Luis E. Cuevas, Jose Dominguez, Christophe Sola

Methods

All State TB control programmes in Nigeria were requested to submit 25–50 smear-positive Ziehl-Neelsen (ZN) stained slides for screening during 2013–2014. DNA was extracted from 929 slides for spoligotyping and drug-resistance analysis using microbead-based flow-cytometry suspension arrays.

Results

Spoligotyping results were obtained for 549 (59.1%) of 929 samples. Lineage 4 Cameroon sublineage (L4.6.2) represented half of the patterns, Mycobacterium africanum (L5 and L6) represented one fifth of the patterns, and all other lineages, including other L4 sublineages, represented one third of the patterns. Sublineage L4.6.2 was mostly identified in the north of the country whereas L5 was mostly observed in the south and L6 was scattered. The spatial distribution of genotypes had genetic geographic gradients. We did not obtain results enabling the detection of drug-resistance mutations.

Conclusion/Significance

We present the first national snapshot of the M. tuberculosis spoligotypes circulating in Nigeria based on ZN slides. Spoligotyping data can be obtained in a rapid and high-throughput manner with DNA extracted from ZN-stained slides, which may potentially improve our understanding of the genetic epidemiology of TB.

Joint ancestry and association test indicate two distinct pathogenic pathways involved in classical dengue fever and dengue shock syndrome

15 February 2018 - 10:00pm

by Marisa Oliveira, Worachart Lert-itthiporn, Bruno Cavadas, Verónica Fernandes, Ampaiwan Chuansumrit, Orlando Anunciação, Isabelle Casademont, Fanny Koeth, Marina Penova, Kanchana Tangnararatchakit, Chiea Chuen Khor, Richard Paul, Prida Malasit, Fumihiko Matsuda, Etienne Simon-Lorière, Prapat Suriyaphol, Luisa Pereira, Anavaj Sakuntabhai

Ethnic diversity has been long considered as one of the factors explaining why the severe forms of dengue are more prevalent in Southeast Asia than anywhere else. Here we take advantage of the admixed profile of Southeast Asians to perform coupled association-admixture analyses in Thai cohorts. For dengue shock syndrome (DSS), the significant haplotypes are located in genes coding for phospholipase C members (PLCB4 added to previously reported PLCE1), related to inflammation of blood vessels. For dengue fever (DF), we found evidence of significant association with CHST10, AHRR, PPP2R5E and GRIP1 genes, which participate in the xenobiotic metabolism signaling pathway. We conducted functional analyses for PPP2R5E, revealing by immunofluorescence imaging that the coded protein co-localizes with both DENV1 and DENV2 NS5 proteins. Interestingly, only DENV2-NS5 migrated to the nucleus, and a deletion of the predicted top-linking motif in NS5 abolished the nuclear transfer. These observations support the existence of differences between serotypes in their cellular dynamics, which may contribute to differential infection outcome risk. The contribution of the identified genes to the genetic risk render Southeast and Northeast Asian populations more susceptible to both phenotypes, while African populations are best protected against DSS and intermediately protected against DF, and Europeans the best protected against DF but the most susceptible against DSS.

Multiplex serology for impact evaluation of bed net distribution on burden of lymphatic filariasis and four species of human malaria in northern Mozambique

14 February 2018 - 10:00pm

by Mateusz M. Plucinski, Baltazar Candrinho, Geraldo Chambe, João Muchanga, Olinda Muguande, Graça Matsinhe, Guidion Mathe, Eric Rogier, Timothy Doyle, Rose Zulliger, James Colborn, Abu Saifodine, Patrick Lammie, Jeffrey W. Priest

Background

Universal coverage with long-lasting insecticidal nets (LLINs) is a primary control strategy against Plasmodium falciparum malaria. However, its impact on the three other main species of human malaria and lymphatic filariasis (LF), which share the same vectors in many co-endemic areas, is not as well characterized. The recent development of multiplex antibody detection provides the opportunity for simultaneous evaluation of the impact of control measures on the burden of multiple diseases.

Methodology/Principal findings

Two cross-sectional household surveys at baseline and one year after a LLIN distribution campaign were implemented in Mecubúri and Nacala-a-Velha Districts in Nampula Province, Mozambique. Both districts were known to be endemic for LF; both received mass drug administration (MDA) with antifilarial drugs during the evaluation period. Access to and use of LLINs was recorded, and household members were tested with P. falciparum rapid diagnostic tests (RDTs). Dried blood spots were collected and analyzed for presence of antibodies to three P. falciparum antigens, P. vivax MSP-119, P. ovale MSP-119, P. malariae MSP-119, and three LF antigens. Seroconversion rates were calculated and the association between LLIN use and post-campaign seropositivity was estimated using multivariate regression. The campaign covered 68% (95% CI: 58–77) of the population in Nacala-a-Velha and 46% (37–56) in Mecubúri. There was no statistically significant change in P. falciparum RDT positivity between the two surveys. Population seropositivity at baseline ranged from 31–81% for the P. falciparum antigens, 3–4% for P. vivax MSP-119, 41–43% for P. ovale MSP-119, 46–56% for P. malariae MSP-119, and 37–76% for the LF antigens. The seroconversion rate to the LF Bm33 antigen decreased significantly in both districts. The seroconversion rate to P. malariae MSP-119 and the LF Wb123 and Bm14 antigens each decreased significantly in one of the two districts. Community LLIN use was associated with a decreased risk of P. falciparum RDT positivity, P. falciparum CSP and LSA-1 seropositivity, and P. malariae MSP-119 seropositivity, but not LF antigen seropositivity.

Conclusions/Significance

The study area noted significant declines in LF seropositivity, but these were not associated with LLIN use. The MDA could have masked any impact of the LLINs on population LF seropositivity. The LLIN campaign did not reach adequately high coverage to decrease P. falciparum RDT positivity, the most common measure of P. falciparum burden. However, the significant decreases in the seroconversion rate to the P. malariae antigen, coupled with an association between community LLIN use and individual-level decreases in seropositivity to P. falciparum and P. malariae antigens show evidence of impact of the LLIN campaign and highlight the utility of using multiantigenic serological approaches for measuring intervention impact.

Sensitive and less invasive confirmatory diagnosis of visceral leishmaniasis in Sudan using loop-mediated isothermal amplification (LAMP)

14 February 2018 - 10:00pm

by Maowia Mukhtar, Sababil S. Ali, Salah A. Boshara, Audrey Albertini, Séverine Monnerat, Paul Bessell, Yasuyoshi Mori, Yutaka Kubota, Joseph M. Ndung’u, Israel Cruz

Background

Confirmatory diagnosis of visceral leishmaniasis (VL), as well as diagnosis of relapses and test of cure, usually requires examination by microscopy of samples collected by invasive means, such as splenic, bone marrow or lymph node aspirates. This causes discomfort to patients, with risks of bleeding and iatrogenic infections, and requires technical expertise. Molecular tests have great potential for diagnosis of VL using peripheral blood, but require well-equipped facilities and trained personnel. More user-friendly, and field-amenable options are therefore needed. One method that could meet these requirements is loop-mediated isothermal amplification (LAMP) using the Loopamp Leishmania Detection Kit, which comes as dried down reagents that can be stored at room temperature, and allows simple visualization of results.

Methodology/Principal findings

The Loopamp Leishmania Detection Kit (Eiken Chemical Co., Japan), was evaluated in the diagnosis of VL in Sudan. A total of 198 VL suspects were tested by microscopy of lymph node aspirates (the reference test), direct agglutination test-DAT (in house production) and rK28 antigen-based rapid diagnostic test (OnSite Leishmania rK39-Plus, CTK Biotech, USA). LAMP was performed on peripheral blood (whole blood and buffy coat) previously processed by: i) a direct boil and spin method, and ii) the QIAamp DNA Mini Kit (QIAgen). Ninety seven of the VL suspects were confirmed as cases by microscopy of lymph node aspirates. The sensitivity and specificity for each of the tests were: rK28 RDT 98.81% and 100%; DAT 88.10% and 78.22%; LAMP-boil and spin 97.65% and 99.01%; LAMP-QIAgen 100% and 99.01%.

Conclusions/Significance

Due to its simplicity and high sensitivity, rK28 RDT can be used first in the diagnostic algorithm for primary VL diagnosis, the excellent performance of LAMP using peripheral blood indicates that it can be also included in the algorithm for diagnosis of VL as a simple test when parasitological confirmatory diagnosis is required in settings that are lower than the reference laboratory, avoiding the need for invasive lymph node aspiration.

Promising approach to reducing Malaria transmission by ivermectin: Sporontocidal effect against <i>Plasmodium vivax</i> in the South American vectors <i>Anopheles aquasalis</i> and <i>Anopheles darlingi</i>

14 February 2018 - 10:00pm

by Yudi T. Pinilla, Stefanie C. P. Lopes, Vanderson S. Sampaio, Francys S. Andrade, Gisely C. Melo, Alessandra S. Orfanó, Nágila F. C. Secundino, Maria G. V. B. Guerra, Marcus V. G. Lacerda, Kevin C. Kobylinski, Karin S. Escobedo-Vargas, Victor M. López-Sifuentes, Craig A. Stoops, G. Christian Baldeviano, Joel Tarning, Gissella M. Vasquez, Paulo F. P. Pimenta, Wuelton M. Monteiro

Background

The mosquito resistance to the insecticides threatens malaria control efforts, potentially becoming a major public health issue. Alternative methods like ivermectin (IVM) administration to humans has been suggested as a possible vector control to reduce Plasmodium transmission. Anopheles aquasalis and Anopheles darlingi are competent vectors for Plasmodium vivax, and they have been responsible for various malaria outbreaks in the coast of Brazil and the Amazon Region of South America.

Methods

To determine the IVM susceptibility against P. vivax in An. aquasalis and An. darlingi, ivermectin were mixed in P. vivax infected blood: (1) Powdered IVM at four concentrations (0, 5, 10, 20 or 40 ng/mL). (2) Plasma (0 hours, 4 hours, 1 day, 5, 10 and 14 days) was collected from healthy volunteers after to administer a single oral dose of IVM (200 μg/kg) (3) Mosquitoes infected with P. vivax and after 4 days was provided with IVM plasma collected 4 hours post-treatment (4) P. vivax-infected patients were treated with various combinations of IVM, chloroquine, and primaquine and plasma or whole blood was collected at 4 hours. Seven days after the infective blood meal, mosquitoes were dissected to evaluate oocyst presence. Additionally, the ex vivo effects of IVM against asexual blood-stage P. vivax was evaluated.

Results

IVM significantly reduced the prevalence of An. aquasalis that developed oocysts in 10 to 40 ng/mL pIVM concentrations and plasma 4 hours, 1 day and 5 days. In An. darlingi to 4 hours and 1 day. The An. aquasalis mortality was expressively increased in pIVM (40ng/mL) and plasma 4 hours, 1, 5 10 and 14 days post-intake drug and in An. darlingi only to 4 hours and 1 day. The double fed meal with mIVM by the mosquitoes has a considerable impact on the proportion of infected mosquitoes for 7 days post-feeding. The oocyst infection prevalence and intensity were notably reduced when mosquitoes ingested blood from P. vivax patients that ingested IVM+CQ, PQ+CQ and IVM+PQ+CQ. P. vivax asexual development was considerably inhibited by mIVM at four-fold dilutions.

Conclusion

In conclusion, whole blood spiked with IVM reduced the infection rate of P. vivax in An. aquasalis and An. darlingi, and increased the mortality of mosquitoes. Plasma from healthy volunteers after IVM administration affect asexual P. vivax development. These findings support that ivermectin may be used to decrease P. vivax transmission.

Prevalence of trachoma in the Kayes region of Mali eight years after stopping mass drug administration

12 February 2018 - 10:00pm

by Lamine Traoré, Benoit Dembele, Modibo Keita, Steven Reid, Mahamadou Dembéle, Bréhima Mariko, Famolo Coulibaly, Whitney Goldman, Dramane Traoré, Daouda Coulibaly, Boubacar Guindo, Joe Amon, Marily Knieriemen, Yaobi Zhang

Background

In 2009, three years after stopping mass treatment with azithromycin, a trachoma impact survey in four health districts in the Kayes region of Mali found a prevalence of trachomatous inflammation—follicular (TF) among children aged 1 to 9 years of >5% and a trachomatous trichiasis (TT) prevalence within the general population (≥1-year-old) of <1%. As a result, the government’s national trachoma program expanded trichiasis surgery and related activities required to achieve trachoma elimination.

Methodology/Principal findings

In 2015, to assess progress towards elimination, a follow-up impact survey was conducted in the Kayes, Kéniéba, Nioro and Yélimané health districts. The survey used district level two-stage cluster random sampling methodology with 20 clusters of 30 households in each evaluation unit. Subjects were eligible for examination if they were ≥1 year. TF and TT cases were identified and confirmed by experienced ophthalmologists. In total 14,159 people were enumerated and 11,620 (82%) were examined. TF prevalence (95% confidence interval (CI)) was 0.5% (0.3–1%) in Kayes, 0.8% (0.4–1.7%) in Kéniéba, 0.2% (0–0.9%) in Nioro and 0.3% (0.1–1%) in Yélimané. TT prevalence (95% CI) was 0.04% (0–0.25%) in Kayes, 0.29% (0.11–0.6%) in Kéniéba, 0.04% (0–0.25%) in Nioro and 0.07% (0–0.27%) in Yélimané.

Conclusions/Significance

Eight years after stopping MDA and intensifying trichiasis surgery outreach campaigns, all four districts reached the TF elimination threshold of <5% and three of four districts reached the TT elimination threshold of <0.1%.

Submicroscopic placental infection by non-<i>falciparum Plasmodium</i> spp.

12 February 2018 - 10:00pm

by Justin Y. A. Doritchamou, Richard A. Akuffo, Azizath Moussiliou, Adrian J. F. Luty, Achille Massougbodji, Philippe Deloron, Nicaise G. Tuikue Ndam

Background

Among the Plasmodium species that infect humans, adverse effects of P. falciparum and P. vivax have been extensively studied and reported with respect to poor outcomes particularly in first time mothers and in women living in areas with unstable malaria transmission. Although, other non-falciparum malaria infections during pregnancy have sometimes been reported, little is known about the dynamics of these infections during pregnancy.

Methods and findings

Using a quantitative PCR approach, blood samples collected from Beninese pregnant women during the first antenatal visit (ANV) and at delivery including placental blood were screened for Plasmodium spp. Risk factors associated with Plasmodium spp. infection during pregnancy were assessed as well as the relationships with pregnancy outcomes.P. falciparum was the most prevalent Plasmodium species detected during pregnancy, irrespective either of parity, of age or of season during which the infection occurred. Although no P. vivax infections were detected in this cohort, P. malariae (9.2%) and P. ovale (5.8%) infections were observed in samples collected during the first ANV. These non-falciparum infections were also detected in maternal peripheral blood (1.3% for P. malariae and 1.2% for P. ovale) at delivery. Importantly, higher prevalence of P. malariae (5.5%) was observed in placental than peripheral blood while that of P. ovale was similar (1.8% in placental blood). Among the non-falciparum infected pregnant women with paired peripheral and placental samples, P. malariae infections in the placental blood was significantly higher than in the peripheral blood, suggesting a possible affinity of P. malariae for the placenta. However, no assoctiation of non-falciparum infections and the pregnancy outcomes was observed

Conclusions

Overall this study provided insights into the molecular epidemiology of Plasmodium spp. infection during pregnancy, indicating the lack association of non-falciparum infections with adverse pregnancy outcomes.

Estimation of the number of women of reproductive age in need of preventive chemotherapy for soil-transmitted helminth infections

12 February 2018 - 10:00pm

by Denise Mupfasoni, Alexei Mikhailov, Pamela Mbabazi, Jonathan King, Theresa W. Gyorkos, Antonio Montresor

Background

Soil-transmitted helminth infections are among the most common infections in developing countries. Globally, as many as 2 billion people are considered to be at risk for soil-transmitted-helminth (STH) infections. Preschool children (PSAC), school-age children (SAC) and women of reproductive age (WRA) are at high risk of STH-attributable morbidity and preventive chemotherapy (PC) for STH is recommended by the World health Organization (WHO).

Methodology/Principal findings

Over the last five years, PC coverage in PSAC and SAC has gradually increased, while coverage in WRA has lagged. Estimating the numbers of WRA in each endemic country would inform scale-up in this group. A two-step process was used: 1) total numbers of girls and women between 15 and 49 years of age were obtained from the United Nations World Population Prospects 2015 database; and 2) the proportion in need of PC was obtained primarily from extrapolation from the WHO PC Databank. WRA were divided into four sub-groups reflecting different reproductive life stages, each having a potentially different interface with the health care system and, consequently, presenting different opportunities for intervention strategies.Worldwide, we estimated that 688 million WRA in 102 countries were in need of PC for STH in 2015. The South-East Asia (49%) and Africa regions (26%) had the highest numbers. Adolescent girls accounted for 16%, while pregnant and lactating women each represented 10%. Over 25 million pregnant women alone were estimated living in areas where the prevalence of hookworm and T. trichiura infection was ≥ 20%. Approximately 20% of at-risk WRA had received deworming with albendazole through the Global Programme to Eliminate Filariasis.

Conclusions/Significance

To close current gaps in coverage, numbers of WRA in need of PC for STH are essential for operational strategies to control STH infection.

Forecasting the spatial and seasonal dynamic of <i>Aedes albopictus</i> oviposition activity in Albania and Balkan countries

12 February 2018 - 10:00pm

by Clément Tisseuil, Enkelejda Velo, Silvia Bino, Perparim Kadriaj, Kujtim Mersini, Ada Shukullari, Artan Simaku, Elton Rogozi, Beniamino Caputo, Els Ducheyne, Alessandra della Torre, Paul Reiter, Marius Gilbert

The increasing spread of the Asian tiger mosquito, Aedes albopictus, in Europe and US raises public health concern due to the species competence to transmit several exotic human arboviruses, among which dengue, chikungunya and Zika, and urges the development of suitable modeling approach to forecast the spatial and temporal distribution of the mosquito. Here we developed a dynamical species distribution modeling approach forecasting Ae. albopictus eggs abundance at high spatial (0.01 degree WGS84) and temporal (weekly) resolution over 10 Balkan countries, using temperature times series of Modis data products and altitude as input predictors. The model was satisfactorily calibrated and validated over Albania based observed eggs abundance data weekly monitored during three years. For a given week of the year, eggs abundance was mainly predicted by the number of eggs and the mean temperature recorded in the preceding weeks. That is, results are in agreement with the biological cycle of the mosquito, reflecting the effect temperature on eggs spawning, maturation and hatching. The model, seeded by initial egg values derived from a second model, was then used to forecast the spatial and temporal distribution of eggs abundance over the selected Balkan countries, weekly in 2011, 2012 and 2013. The present study is a baseline to develop an easy-handling forecasting model able to provide information useful for promoting active surveillance and possibly prevention of Ae. albopictus colonization in presently non-infested areas in the Balkans as well as in other temperate regions.

Microexon gene transcriptional profiles and evolution provide insights into blood processing by the <i>Schistosoma japonicum</i> esophagus

12 February 2018 - 10:00pm

by Xiao-Hong Li, Ricardo DeMarco, Leandro X. Neves, Sally R. James, Katherine Newling, Peter D. Ashton, Jian-Ping Cao, R. Alan Wilson, William Castro-Borges

Background

Adult schistosomes have a well-developed alimentary tract comprising an oral sucker around the mouth, a short esophagus and a blind ending gut. The esophagus is not simply a muscular tube for conducting blood from the mouth to gut but is divided into compartments, surrounded by anterior and posterior glands, where processing of ingested blood is initiated. Self-cure of rhesus macaques from a Schistosoma japonicum infection appears to operate by blocking the secretory functions of these glands so that the worms cease feeding and slowly starve to death. Here we use subtractive RNASeq to characterise the genes encoding the principal secretory products of S. japonicum esophageal glands, preparatory to evaluating their relevance as targets of the self-cure process.

Methodology/Principal findings

The heads and a small portion of the rear end of male and female S. japonicum worms were separately enriched by microdissection, for mRNA isolation and library construction. The sequence reads were then assembled de novo using Trinity and those genes enriched more than eightfold in the head preparation were subjected to detailed bioinformatics analysis. Of the 62 genes selected from the male heads, more than one third comprised MEGs encoding secreted or membrane-anchored proteins. Database searching using conserved motifs revealed that the MEG-4 and MEG-8/9 families had counterparts in the bird schistosome Trichobilharzia regenti, indicating an ancient association with blood processing. A second group of MEGs, including a MEG-26 family, encoded short peptides with amphipathic properties that most likely interact with ingested host cell membranes to destabilise them. A number of lysosomal hydrolases, two protease inhibitors, a secreted VAL and a putative natterin complete the line-up. There was surprisingly little difference between expression patterns in males and females despite the latter processing much more blood.

Significance/Conclusions

The mixture of approximately 40 proteins specifically secreted by the esophageal glands is responsible for initiating blood processing in the adult worm esophagus. They comprise the potential targets for the self-cure process in the rhesus macaque, and thus represent a completely new cohort of secreted proteins that can be investigated as vaccine candidates.

Vector-borne disease risk indexes in spatially structured populations

12 February 2018 - 10:00pm

by Jorge Velázquez-Castro, Andrés Anzo-Hernández, Beatriz Bonilla-Capilla, Moisés Soto-Bajo, Andrés Fraguela-Collar

There are economic and physical limitations when applying prevention and control strategies for urban vector borne diseases. Consequently, there are increasing concerns and interest in designing efficient strategies and regulations that health agencies can follow in order to reduce the imminent impact of viruses like Dengue, Zika and Chikungunya. That includes fumigation, abatization, reducing the hatcheries, picking up trash, information campaigns. A basic question that arise when designing control strategies is about which and where these ones should focus. In other words, one would like to know whether preventing the contagion or decrease vector population, and in which area of the city, is more efficient. In this work, we propose risk indexes based on the idea of secondary cases from patch to patch. Thus, they take into account human mobility and indicate which patch has more chance to be a corridor for the spread of the disease and which is more vulnerable, i.e. more likely to have cases?. They can also indicate the neighborhood where hatchery control will reduce more the number of potential cases. In order to illustrate the usefulness of these indexes, we run a set of numerical simulations in a mathematical model that takes into account the urban mobility and the differences in population density among the areas of a city. If we label by i a particular neighborhood, the transmission risk index (TRi) measures the potential secondary cases caused by a host in that neighborhood. The vector transmission risk index (VTRi) measures the potential secondary cases caused by a vector. Finally, the vulnerability risk index (VRi) measures the potential secondary cases in the neighborhood. Transmission indexes can be used to give geographical priority to some neighborhoods when applying prevention and control measures. On the other hand, the vulnerability index can be useful to implement monitoring campaigns or public health investment.

Community knowledge, perceptions and attitudes regarding leprosy in rural Cameroon: The case of Ekondotiti and Mbonge health districts in the South-west Region

12 February 2018 - 10:00pm

by Earnest Njih Tabah, Dickson Shey Nsagha, Anne-Cecile Zoung-Kanyi Bissek, Theophilus Ngeh Njamnshi, Irine Ngani-Nformi Njih, Gerd Pluschke, Alfred Kongnyu Njamnshi

Background

Although leprosy is one of the oldest diseases known to humanity, it remains largely misunderstood. Misconceptions about leprosy leads to stigma towards people with the disease. This study aimed at exploring the knowledge, perceptions and attitudes regarding leprosy in rural Cameroon.

Methods

We carried out a cross-sectional community survey of 233 respondents aged 15–75 years, free from leprosy, and living in two rural health districts of the South-west Region of Cameroon. A questionnaire designed to evaluate knowledge, perceptions and attitudes about leprosy was used. Binary logistic regression was used to determine independent predictors of negative attitudes.

Results

About 82% of respondents had heard about, and 64.4% knew someone with leprosy. Information on leprosy was mainly from community volunteers (40.6%), friends (38.0%), and the media (24%). Only 19.7% of respondents knew the cause of leprosy, and a considerable proportion linked it to a spell (25.3%), unclean blood (15.5%) and heredity (14.6%). About 72% knew that leprosy is curable and 86.3% would advise medical treatment. Attitudes towards leprosy patients were generally negative. Only 42% would shake hands, 32.6% would share the same plate, and 28.3% and 27% respectively, would allow their child to play or marry with a person with leprosy. Furthermore, only 33.9% approved of participation of leprosy patients, and 42.9% of their employment. Independent predictors of negative attitudes were: the belief that leprosy is a curse; is caused by a germ; and having seen a leprosy patient. The negative attitudes were dampened by: the beliefs that leprosy is a punishment, is hereditary and is due to poor personal hygiene.

Conclusion

An awareness intervention using community volunteers and the media, with information on the cause of leprosy, its clinical manifestations and curability, and sensitization messages correcting the misconceptions and beliefs regarding leprosy, could improve the community knowledge and attitudes towards leprosy. This would ultimately contribute to the reduction of leprosy burden in the community.

The impact of insecticide applications on the dynamics of resistance: The case of four <i>Aedes aegypti</i> populations from different Brazilian regions

12 February 2018 - 10:00pm

by Gabriela de Azambuja Garcia, Mariana Rocha David, Ademir de Jesus Martins, Rafael Maciel de Freitas, Jutta Gerlinde Birggitt Linss, Simone Costa Araújo, José Bento Pereira Lima, Denise Valle

Background

In the tropics, the utilization of insecticides is still an important strategy for controlling Aedes aegypti, the principle vector of dengue, chikungunya and Zika viruses. However, increasing insecticide resistance in Ae. aegypti populations might hinder insecticide efficacy on a long-term basis. It will be important to understand the dynamics and evolution of insecticide resistance by assessing its frequency and the mechanisms by which it occurs.

Methodology/Principal findings

The insecticide resistance status of four Brazilian Ae. aegypti populations was monitored. Quantitative bioassays with the major insecticides employed in the country was performed: the adulticide deltamethrin (a pyrethroid—PY) and the larvicides, temephos (an organophosphate) and diflubenzuron (a chitin synthesis inhibitor). Temephos resistance was detected in all populations although exhibiting a slight decrease over time probably due to the interruption of field use. All vector populations were susceptible to diflubenzuron, recently introduced in the country to control Ae. aegypti. Resistance against deltamethrin was extremely high in three populations. Molecular assays investigated substitutions in the voltage gated sodium channel (NaV), the PY target site, at positions 1011, 1016 and 1534. Elevated frequencies of substitutions Val1016Ile and Phe1534Cys related to high PY resistance levels were identified. Biochemical assays detected alterations in the activities of two detoxifying enzyme classes related to metabolic resistance, glutathion-S-transferases and esterases. The results obtained were evaluated in the context of both recent insecticide use and the records of dengue incidence in each locality.

Conclusions/Significance

The four Ae. aegypti populations evaluated were resistant to the neurotoxic insecticides, temephos and deltamethrin. However, they were still susceptible to diflubenzuron. A probable correlation between adult insect resistance to PY and the domestic application of insecticides is discussed, pointing to the need for awareness measures regarding the correct utilization by citizens. This work aims to contribute to the efficient and rational management of Ae. aegypti control of both larvae and adults.

Endogenous overexpression of an active phosphorylated form of DNA polymerase β under oxidative stress in <i>Trypanosoma cruzi</i>

12 February 2018 - 10:00pm

by Diego A. Rojas, Fabiola Urbina, Sandra Moreira-Ramos, Christian Castillo, Ulrike Kemmerling, Michel Lapier, Juan Diego Maya, Aldo Solari, Edio Maldonado

Trypanosoma cruzi is exposed during its life to exogenous and endogenous oxidative stress, leading to damage of several macromolecules such as DNA. There are many DNA repair pathways in the nucleus and mitochondria (kinetoplast), where specific protein complexes detect and eliminate damage to DNA. One group of these proteins is the DNA polymerases. In particular, Tc DNA polymerase β participates in kinetoplast DNA replication and repair. However, the mechanisms which control its expression under oxidative stress are still unknown. Here we describe the effect of oxidative stress on the expression and function of Tc DNA polymerase β To this end parasite cells (epimastigotes and trypomastigotes) were exposed to peroxide during short periods of time. Tc DNA polymerase β which was associated physically with kinetoplast DNA, showed increased protein levels in response to peroxide damage in both parasite forms analyzed. Two forms of DNA polymerase β were identified and overexpressed after peroxide treatment. One of them was phosphorylated and active in DNA synthesis after renaturation on polyacrylamide electrophoresis gel. This phosphorylated form showed 3-4-fold increase in both parasite forms. Our findings indicate that these increments in protein levels are not under transcriptional control because the level of Tc DNA polymerase β mRNA is maintained or slightly decreased during the exposure to oxidative stress. We propose a mechanism where a DNA repair pathway activates a cascade leading to the increment of expression and phosphorylation of Tc DNA polymerase β in response to oxidative damage, which is discussed in the context of what is known in other trypanosomes which lack transcriptional control.

The spectrum of neurological disease associated with Zika and chikungunya viruses in adults in Rio de Janeiro, Brazil: A case series

12 February 2018 - 10:00pm

by Ravi Mehta, Cristiane Nascimento Soares, Raquel Medialdea-Carrera, Mark Ellul, Marcus Tulius Texeira da Silva, Anna Rosala-Hallas, Marcia Rodrigues Jardim, Girvan Burnside, Luciana Pamplona, Maneesh Bhojak, Radhika Manohar, Gabriel Amorelli Medeiros da Silva, Marcus Vinicius Adriano, Patricia Brasil, Rita Maria Ribeiro Nogueira, Carolina Cardoso Dos Santos, Lance Turtle, Patricia Carvalho de Sequeira, David W. Brown, Michael J. Griffiths, Ana Maria Bispo de Filippis, Tom Solomon

Background

During 2015–16 Brazil experienced the largest epidemic of Zika virus ever reported. This arthropod-borne virus (arbovirus) has been linked to Guillain-Barré syndrome (GBS) in adults but other neurological associations are uncertain. Chikungunya virus has caused outbreaks in Brazil since 2014 but associated neurological disease has rarely been reported here. We investigated adults with acute neurological disorders for Zika, chikungunya and dengue, another arbovirus circulating in Brazil.

Methods

We studied adults who had developed a new neurological condition following suspected Zika virus infection between 1st November 2015 and 1st June 2016. Cerebrospinal fluid (CSF), serum, and urine were tested for evidence of Zika, chikungunya, and dengue viruses.

Results

Of 35 patients studied, 22 had evidence of recent arboviral infection. Twelve had positive PCR or IgM for Zika, five of whom also had evidence for chikungunya, three for dengue, and one for all three viruses. Five of them presented with GBS; seven had presentations other than GBS, including meningoencephalitis, myelitis, radiculitis or combinations of these syndromes. Additionally, ten patients positive for chikungunya virus, two of whom also had evidence for dengue virus, presented with a similar range of neurological conditions.

Conclusions

Zika virus is associated with a wide range of neurological manifestations, including central nervous system disease. Chikungunya virus appears to have an equally important association with neurological disease in Brazil, and many patients had dual infection. To understand fully the burden of Zika we must look beyond GBS, and also investigate for other co-circulating arboviruses, particularly chikungunya.

Clinical findings and prognosis of patients hospitalized for acute decompensated heart failure: Analysis of the influence of Chagas etiology and ventricular function

12 February 2018 - 10:00pm

by Caíque Bueno Terhoch, Henry Fukuda Moreira, Silvia Moreira Ayub-Ferreira, Germano Emilio Conceição-Souza, Vera Maria Cury Salemi, Paulo Roberto Chizzola, Mucio Tavares Oliveira Jr, Silvia Helena Gelas Lage, Edimar Alcides Bocchi, Victor Sarli Issa

Aims

Explore the association between clinical findings and prognosis in patients with acute decompensated heart failure (ADHF) and analyze the influence of etiology on clinical presentation and prognosis.

Methods and results

Prospective cohort of 500 patients admitted with ADHF from Aug/2013-Feb/2016; patients were predominantly male (61.8%), median age was 58 (IQ25-75% 47–66 years); etiology was dilated cardiomyopathy in 141 (28.2%), ischemic heart disease in 137 (27.4%), and Chagas heart disease in 113 (22.6%). Patients who died (154 [30.8%]) or underwent heart transplantation (53[10.6%]) were younger (56 years [IQ25-75% 45–64 vs 60 years, IQ25-75% 49–67], P = 0.032), more frequently admitted for cardiogenic shock (20.3% vs 6.8%, P<0.001), had longer duration of symptoms (14 days [IQ25-75% 4–32.8 vs 7.5 days, IQ25-75% 2–31], P = 0.004), had signs of congestion (90.8% vs 76.5%, P<0.001) and inadequate perfusion more frequently (45.9% vs 28%, P<0.001), and had lower blood pressure (90 [IQ25-75% 80–100 vs 100, IQ25-75% 90–120], P<0.001). In a logistic regression model analysis, systolic blood pressure (P<0.001, OR 0.97 [95%CI 0.96–0.98] per mmHg) and jugular distention (P = 0.004, OR 1.923 [95%CI 1.232–3.001]) were significant. Chagas patients were more frequently admitted for cardiogenic shock (15%) and syncope/arrhythmia (20.4%). Pulmonary congestion was rare among Chagas patients and blood pressure was lower. The rate of in-hospital death or heart transplant was higher among patients with Chagas (50.5%).

Conclusions

A physical exam may identify patients at higher risk in a contemporaneous population. Our findings support specific therapies targeted at Chagas patients in the setting of ADHF.

<i>In vitro</i> studies of <i>Rickettsia</i>-host cell interactions: Confocal laser scanning microscopy of <i>Rickettsia helvetica</i>-infected eukaryotic cell lines

12 February 2018 - 10:00pm

by Stephanie Speck, Tanja Kern, Karin Aistleitner, Meik Dilcher, Gerhard Dobler, Sandra Essbauer

Rickettsia (R.) helvetica is the most prevalent rickettsia found in Ixodes ricinus ticks in Germany. Several studies reported antibodies against R. helvetica up to 12.5% in humans investigated, however, fulminant clinical cases are rare indicating a rather low pathogenicity compared to other rickettsiae. We investigated growth characteristics of R. helvetica isolate AS819 in two different eukaryotic cell lines with focus on ultra-structural changes of host cells during infection determined by confocal laser scanning microscopy. Further investigations included partially sequencing of rickA, sca4 and sca2 genes, which have been reported to encode proteins involved in cell-to-cell spread and virulence in some rickettsiae. R. helvetica grew constantly but slowly in both cell lines used. Confocal laser scanning microscopy revealed that the dissemination of R. helvetica AS819 in both cell lines was rather mediated by cell break-down and bacterial release than cell-to-cell spread. The cytoskeleton of both investigated eukaryotic cell lines was not altered. R. helvetica possesses rickA, but its expression is not sufficient to promote actin-based motility as demonstrated by confocal laser scanning microscopy. Hypothetical Sca2 and Sca4 proteins were deduced from nucleotide gene sequences but the predicted amino acid sequences were disrupted or truncated compared to other rickettsiae most likely resulting in non-functional proteins. Taken together, these results might give a first hint to the underlying causes of the reduced virulence and pathogenicity of R. helvetica.

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