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Relationship between toxoplasmosis and obsessive compulsive disorder: A systematic review and meta-analysis

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

by Tooran Nayeri Chegeni, Shahabeddin Sarvi, Afsaneh Amouei, Mahmood Moosazadeh, Zahra Hosseininejad, Sargis A. Aghayan, Ahmad Daryani

Background

A few studies investigated the relationship between toxoplasmosis and mental disorders, such as obsessive compulsive disorder (OCD). However, the specific nature of the association between Toxoplasma gondii (T. gondii) infection and OCD is not yet clear. The aim of this study was to collect information on the relationship between OCD and toxoplasmosis and assess whether patients with toxoplasmosis are prone to OCD.

Methods

For the purpose of this study, 6 major electronic databases and the Internet search engine Google Scholar were searched for the published articles up to July 30th, 2018 with no restriction of language. The inverse variance method and the random effect model were used to combine the data. The values of odds ratio (OR) were estimated at 95% confidence interval (CI).

Results

A total of 9 case-control and 3 cross-sectional studies were included in our systematic review. However, 11 of these 12 articles were entered into the meta-analysis containing 9873 participants, out of whom 389 were with OCD (25.96% positive for toxoplasmosis) and 9484 were without OCD (17.12% positive for toxoplasmosis). The estimation of the random effect model indicated a significant common OR of 1.96 [95% CI: 1.32–2.90].

Conclusion

This systematic review and meta-analysis revealed that toxoplasmosis could be as an associated factor for OCD (OR = 1.96). However, further prospective investigations are highly recommended to illuminate the underlying pathophysiological mechanisms of T. gondii infection in OCD and to better investigate the relationship between OCD and T. gondii infection.

Strategies for tackling <i>Taenia solium</i> taeniosis/cysticercosis: A systematic review and comparison of transmission models, including an assessment of the wider Taeniidae family transmission models

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

by Matthew A. Dixon, Uffe C. Braae, Peter Winskill, Martin Walker, Brecht Devleesschauwer, Sarah Gabriël, Maria-Gloria Basáñez

Background

The cestode Taenia solium causes the neglected (zoonotic) tropical disease cysticercosis, a leading cause of preventable epilepsy in endemic low and middle-income countries. Transmission models can inform current scaling-up of control efforts by helping to identify, validate and optimise control and elimination strategies as proposed by the World Health Organization (WHO).

Methodology/Principal findings

A systematic literature search was conducted using the PRISMA approach to identify and compare existing T. solium transmission models, and related Taeniidae infection transmission models. In total, 28 modelling papers were identified, of which four modelled T. solium exclusively. Different modelling approaches for T. solium included deterministic, Reed-Frost, individual-based, decision-tree, and conceptual frameworks. Simulated interventions across models agreed on the importance of coverage for impactful effectiveness to be achieved.Other Taeniidae infection transmission models comprised force-of-infection (FoI), population-based (mainly Echinococcus granulosus) and individual-based (mainly E. multilocularis) modelling approaches. Spatial structure has also been incorporated (E. multilocularis and Taenia ovis) in recognition of spatial aggregation of parasite eggs in the environment and movement of wild animal host populations.

Conclusions/Significance

Gaps identified from examining the wider Taeniidae family models highlighted the potential role of FoI modelling to inform model parameterisation, as well as the need for spatial modelling and suitable structuring of interventions as key areas for future T. solium model development. We conclude that working with field partners to address data gaps and conducting cross-model validation with baseline and longitudinal data will be critical to building consensus-led and epidemiological setting-appropriate intervention strategies to help fulfil the WHO targets.

Efficacy of China-made praziquantel for treatment of Schistosomiasis haematobium in Africa: A randomized controlled trial

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

by Xin-Yao Wang, Jian He, Saleh Juma, Fatma Kabole, Jia-gang Guo, Jian-Rong Dai, Wei Li, Kun Yang

Background

In the roadmap on the neglected tropical diseases (NTD) the World Health Organization (WHO) aims at attaining at least 75% coverage of preventive chemotherapy in pre-school and school-age children by 2020. A randomized controlled trial was used to compare the effectiveness of praziquantel in treating Schistosoma haematobium in Africa using two different sources for the drug, Merck Limited Partnership (KgaA), Germany and Nanjing Pharmaceutical Factory (NPF), China.

Methods

More than 6,000 participants testing positive for S. haematobium infection were enrolled from three villages (shehias) situated in the northern, middle and southern part of Pemba Island, Zanzibar. Applying criteria of inclusion and exclusion, resulted in a study population of 152 people (84 males, 68 females). A randomized controlled trial was conducted assigning participants to either praziquantel from NPF or Merck KGaA. After one month, the cure rate of S. haematobium and adverse events were compared to evaluate effectiveness. The ratio of male to female, the ratio of light/high infection intensity, and the average value of age were calculated between the two drug manufacturers. Chi-squared test and T-test were used for consistency analysis.

Results

Out of the total of 73 cases receiving praziquantel from NPF, the cure rate achieved was 97.3% (73/75), while the 74 cases receiving the drug from Merck KgaA reached a similar cure rate (96.1% or 74/77). There was no significant difference between the two outcomes (χ2 = 0.003, P = 0.956). Among the 75 patients treat, only one (a 16-years old female student), who had received the drug made in China had slight adverse reactions manifested as dizziness, headache and abdominal pain.

Conclusion

The efficacy of China-made praziquantel does not differ significantly from praziquantel made by Merck KGaA in Germany.

Trial registration

ClinicalTrials.gov, NCT03133832

Whole cell matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for identification of <i>Leptospira</i> spp. in Thailand and Lao PDR

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

by Piengchan Sonthayanon, Janthima Jaresitthikunchai, Suthee Mangmee, Tipparat Thiangtrongjit, Vanaporn Wuthiekanun, Premjit Amornchai, Paul Newton, Rattanaphone Phetsouvanh, Nicholas PJ Day, Sittiruk Roytrakul

Leptospirosis is a zoonosis with a worldwide distribution, caused by pathogenic spirochetes of the genus Leptospira. The classification and identification of leptospires can be conducted by both genotyping and serotyping which are time-consuming and established in few reference laboratories. This study used matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) as rapid and accurate tool for the identification of leptospires. The whole cell protein spectra of 116 Leptospira isolates including 15 references Leptospira spp. (pathogenic, n = 8; intermediate, n = 2; non-pathogenic, n = 5) and 101 Leptospira spp. clinical isolates was created as an in-house MALDI-TOF MS database. Ninety-seven clinical isolates from Thailand and Laos was validated with these protein spectra and revealed 98.9% correct identification when compared with 16S rRNA gene sequences method. Moreover, MALDI-TOF MS could identify spiked leptospires whole cell in urine. Biomarkers for differentiation of leptospires phylogeny and specific protein spectra for most found Leptospira spp. in this area (L. interrogans, L. kirschneri, L. borgpetersenii) based on MALDI-MS algorithm were demonstrated.

Epidemiological features of a recent zoonotic cutaneous leishmaniasis outbreak in Zagora province, southern Morocco

PLoS Neglected Tropical Diseases News - 9 April 2019 - 9:00pm

by Adil El Hamouchi, Othmane Daoui, Mouad Ait Kbaich, Idris Mhaidi, Sofia El Kacem, Ikram Guizani, M’hammed Sarih, Meryem Lemrani

Background

Leishmania major is an endemic vector-borne disease in Morocco that causes zoonotic cutaneous leishmaniasis (ZCL), especially in arid pre-Saharan regions where its unique vector and reservoir are Phlebotomus papatasi and Meriones shawi, respectively, and may cause epidemics. In late 2017, the Zagora province, an endemic focus for ZCL in southern Morocco, had CL outbreak. The main objective of our investigation was to analyze the epidemiological features of this latest ZCL outbreak.

Methodology/Principal findings

We analyzed epidemiological features of this latest ZCL outbreak. The Regional Delegation of Health, Zagora, recorded 4,402 CL patients between October 2017 and end of March 2018. Our findings showed that 24 municipalities were affected and majority (55.1%) of infected cases belonged to the Tinzouline rural municipality. Majority of patients were females (57.2%). While all age group patients were affected, those aged <10 years were the most affected (42.1%). During this outbreak over 5 days in December 2017, we conducted a survey in Tinzouline and recruited and sampled 114 CL patients to confirm CL diagnosis by parasitological (direct examination and culture) and molecular (ITS1-PCR) methods and identify the etiological agent of infection using ITS1-PCR-RFLP and sequencing. We completed a detailed questionnaire including clinical and epidemiological data for each patient and found 72.8% of patients presenting multiple lesions (≥2), with an average number of lesions of 5.16 ± 0.5. Lesions were more prevalent in the upper limbs, with the most common type being the ulcerocrusted lesion (60.5%). We detected no associations between lesion type and patients’ sex or age.

Conclusions/Significance

Among 114 clinically diagnosed CL patients, we confirmed 90.35% and identified L. major as the species responsible for this outbreak. Self-medication using various products caused superinfection and inflammation of lesions and complicated the diagnosis and treatment. Thus, ZCL remains a major public health problem in the Zagora province, and commitment of all stakeholders is urgently required to implement a sustainable regional control program.

Improved estimates for extinction probabilities and times to extinction for populations of tsetse (<i>Glossina</i> spp)

PLoS Neglected Tropical Diseases News - 9 April 2019 - 9:00pm

by Damian Kajunguri, Elisha B. Are, John W. Hargrove

A published study used a stochastic branching process to derive equations for the mean and variance of the probability of, and time to, extinction in population of tsetse flies (Glossina spp) as a function of adult and pupal mortality, and the probabilities that a female is inseminated by a fertile male. The original derivation was partially heuristic and provided no proofs for inductive results. We provide these proofs, together with a more compact way of reaching the same results. We also show that, while the published equations hold good for the case where tsetse produce male and female offspring in equal proportion, a different solution is required for the more general case where the probability (β) that an offspring is female lies anywhere in the interval (0, 1). We confirm previous results obtained for the special case where β = 0.5 and show that extinction probability is at a minimum for β > 0.5 by an amount that increases with increasing adult female mortality. Sensitivity analysis showed that the extinction probability was affected most by changes in adult female mortality, followed by the rate of production of pupae. Because females only produce a single offspring approximately every 10 days, imposing a death rate of greater than about 3.5% per day will ensure the eradication of any tsetse population. These mortality levels can be achieved for some species using insecticide-treated targets or cattle—providing thereby a simple, effective and cost-effective method of controlling and eradicating tsetse, and also human and animal trypanosomiasis. Our results are of further interest in the modern situation where increases in temperature are seeing the real possibility that tsetse will go extinct in some areas, without the need for intervention, but have an increased chance of surviving in other areas where they were previously unsustainable due to low temperatures.

Estimating the current burden of Chagas disease in Mexico: A systematic review and meta-analysis of epidemiological surveys from 2006 to 2017

PLoS Neglected Tropical Diseases News - 9 April 2019 - 9:00pm

by Audrey Arnal, Etienne Waleckx, Oscar Rico-Chávez, Claudia Herrera, Eric Dumonteil

Background

In Mexico, estimates of Chagas disease prevalence and burden vary widely. Updating surveillance data is therefore an important priority to ensure that Chagas disease does not remain a barrier to the development of Mexico's most vulnerable populations.

Methodology/Principal findings

The aim of this systematic review and meta-analysis was to analyze the literature on epidemiological surveys to estimate Chagas disease prevalence and burden in Mexico, during the period 2006 to 2017. A total of 2,764 articles were screened and 36 were retained for the final analysis. Epidemiological surveys have been performed in most of Mexico, but with variable study scale and geographic coverage. Based on studies reporting confirmed cases (i.e. using at least 2 serological tests), and taking into account the differences of sample sizes, the national estimated seroprevalence of Trypanosoma cruzi infection was 3.38% [95%CI 2.59–4.16], suggesting that there are 4.06 million cases in Mexico. Studies focused on pregnant women, which may transmit the parasite to their newborn during pregnancy, reported an estimated seroprevalence of 2.21% [95%CI 1.46–2.96], suggesting that there are 50,675 births from T. cruzi infected pregnant women per year, and 3,193 cases of congenitally infected newborns per year. Children under 18 years had an estimated seropositivity rate of 1.51% [95%CI 0.77–2.25], which indicate ongoing transmission. Cases of T. cruzi infection in blood donors have also been reported in most states, with a national estimated seroprevalence of 0.55% [95%CI 0.43–0.66].

Conclusions/Significance

Our analysis suggests a disease burden for T. cruzi infection higher than previously recognized, highlighting the urgency of establishing Chagas disease surveillance and control as a key national public health priority in Mexico, to ensure that it does not remain a major barrier to the economic and social development of the country's most vulnerable populations.

The role of perceptions and knowledge of leprosy in the elimination of leprosy: A baseline study in Fatehpur district, northern India

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

by Anna T. van ‘t Noordende, Ida Korfage, Suchitra Lisam, Mohammed A. Arif, Anil Kumar, Wim H. van Brakel

Background

With the introduction of new interventions to prevent leprosy, such as post-exposure prophylaxis (PEP) given to contacts of leprosy patients, it is necessary to update our understanding of knowledge and perception of leprosy among the populations where these interventions will be introduced, in order to tailor communication optimally to the current situation. This study is a baseline study of the PEP++ project and aimed to assess the knowledge, attitudes and practices regarding leprosy in Fatehpur, India.

Methodology

The study used a community-based cross-sectional design with a mixed-methods approach. We assessed knowledge, attitudes, and practices with the KAP measure, and stigma with the Explanatory Model Interview Catalogue community stigma scale (EMIC-CSS) and the Social Distance Scale (SDS). In addition, semi-structured interviews and focus group discussions were conducted with all participant groups. The quantitative data were analysed using stepwise multivariate regression. The qualitative data were analysed using open, inductive coding and content analysis.

Findings

A total of 446 participants were included in the study: 100 persons affected by leprosy, 111 close contacts, 185 community members and 50 health care workers. In addition, 24 in-depth interviews were conducted and 35 people were included in focus group discussions. 12.5% of the participants had adequate knowledge of leprosy, while 22% had poor knowledge. Knowledge on cause (answered correctly by 10% of the participants), mode of transmission (5%) and symptoms of leprosy (16%) was especially poor. The mean EMIC-CSS score was 15.3 (95%CI 14.6–16.0) and mean SDS score 7.2 (95%CI 6.6–7.8). Better knowledge of leprosy was associated with lower levels of social distance towards persons affected by leprosy.

Conclusion

This study revealed poor knowledge regarding leprosy and high levels of stigma and fear and desire to keep social distance towards persons affected by leprosy. Community education that takes cultural beliefs, knowledge gaps and fears into consideration could improve knowledge, reduce misconceptions and positively influence the perception of leprosy.

Vector competence of Australian <i>Aedes aegypti</i> and <i>Aedes albopictus</i> for an epidemic strain of Zika virus

PLoS Neglected Tropical Diseases News - 4 April 2019 - 9:00pm

by R. Leon E. Hugo, Liesel Stassen, Jessica La, Edward Gosden, O’mezie Ekwudu, Clay Winterford, Elvina Viennet, Helen M. Faddy, Gregor J. Devine, Francesca D. Frentiu

Background

Recent epidemics of Zika virus (ZIKV) in the Pacific and the Americas have highlighted its potential as an emerging pathogen of global importance. Both Aedes (Ae.) aegypti and Ae. albopictus are known to transmit ZIKV but variable vector competence has been observed between mosquito populations from different geographical regions and different virus strains. Since Australia remains at risk of ZIKV introduction, we evaluated the vector competence of local Ae. aegypti and Ae. albopictus for a Brazilian epidemic ZIKV strain. In addition, we evaluated the impact of daily temperature fluctuations around a mean of 28°C on ZIKV transmission and extrinsic incubation period.

Methodology/Principal findings

Mosquitoes were orally challenged with a Brazilian ZIKV strain (8.8 log CCID50/ml) and maintained at either 28°C constant or fluctuating temperature conditions. At 3, 7 and 14 days post-infection (dpi), ZIKV RNA copies were quantified in mosquito bodies, as well as wings and legs, using qRT-PCR, while virus antigen in saliva (a proxy for transmission) was detected using a cell culture ELISA. Despite high body and disseminated infection rates in both vectors, the transmission rates of ZIKV in saliva of Ae. aegypti (50–60%) were significantly higher than in Ae. albopictus (10%) at 14 dpi. Both species supported a high viral load in bodies, with no significant differences between constant and fluctuating temperature conditions. However, a significant difference in viral load in wings and legs between species was observed, with higher titres in Ae. aegypti maintained at constant temperature conditions. For ZIKV transmission to occur in Ae. aegypti, a disseminated virus load threshold of 7.59 log10 copies had to be reached.

Conclusions/Significance

Australian Ae. aegypti are better able to transmit a Brazilian ZIKV strain than Ae. albopictus. The results are in agreement with the global consensus that Ae. aegypti is the major vector of ZIKV.

The Role of Interleukin-1 cytokine family (IL-1β, IL-37) and interleukin-12 cytokine family (IL-12, IL-35) in eumycetoma infection pathogenesis

PLoS Neglected Tropical Diseases News - 4 April 2019 - 9:00pm

by Amir Abushouk, Amre Nasr, Emad Masuadi, Gamal Allam, Emmanuel E. Siddig, Ahmed H. Fahal

Mycetoma is a neglected tropical disease, endemic in many tropical and subtropical regions, characterised by massive deformity and disability and can be fatal if untreated early and appropriately. Interleukins (IL) -35 and IL-37 are newly discovered cytokines that play an important role in suppressing the immune system. However, the expression of these interleukins in patients with Madurella mycetomatis (M. mycetomatis) induced eumycetoma has not yet been explored. The aim of this study is to determine the levels of IL-1 family (IL-1β, IL-37) and IL-12 family (IL-12, IL-35) in a group of these patients and the association between these cytokines levels and the patients’ demographic characteristics. The present, case-control study was conducted at the Mycetoma Research Centre, Soba University Hospital, University of Khartoum, Sudan and it included 140 individuals. They were divided into two groups; group I: healthy controls [n = 70; median age 25 years (range 12 to 70 years)]. Group II: mycetoma patients [n = 70 patients; median age 25 (range 13 to 70 years)]. Cytokines levels were measured in sera using enzyme linked immunosorbent assay (ELISA). There was a significant negative correlation between IL-1β and IL-12 levels and lesion size and disease duration, while IL-37 and IL-35 levels were significantly positively correlated with both lesion size and disease duration. The analysis of the risk factors of higher circulatory levels of IL-37 in patients of mycetoma showed a negative significant association with IL-1β cytokine, where a unit increment in IL-1β will decrease the levels of IL-37 by 35.28 pg/ml. The levels of IL-37 among the patients with a duration of mycetoma infection ≤ 1 year were significantly low by an average of 18.45 pg/ml compared to patients with a mycetoma infection’s duration of ≥ 5years (reference group). Furthermore, the risk factors of higher levels of IL-35 in mycetoma patients revealed a negative significant association with IL-12, as a unit increment in IL-12 decreases the levels of IL-35 by 8.99 pg/ml (p < 0.001). Levels of IL-35 among the patients with duration of mycetoma infection ≤ one year were significantly low on average by 41.82 pg/ml (p value = 0.002) compared to patients with a duration of mycetoma infection ≥ 5 years (reference group). In conclusion, this study indicates that both IL-35 and IL-37 are negatively associated with the levels of IL-1β and IL-12 in eumycetoma mycetoma infection; and high levels of IL-37 and IL-35 may have a negative impact on disease progression.

Female genital schistosomiasis and HIV/AIDS: Reversing the neglect of girls and women

PLoS Neglected Tropical Diseases News - 4 April 2019 - 9:00pm

by Peter J. Hotez, Wendy Harrison, Alan Fenwick, Amaya L. Bustinduy, Camilla Ducker, Pamela Sabina Mbabazi, Dirk Engels, Eyrun Floerecke Kjetland

Application of long read sequencing to determine expressed antigen diversity in <i>Trypanosoma brucei</i> infections

PLoS Neglected Tropical Diseases News - 3 April 2019 - 9:00pm

by Siddharth Jayaraman, Claire Harris, Edith Paxton, Anne-Marie Donachie, Heli Vaikkinen, Richard McCulloch, James P. J. Hall, John Kenny, Luca Lenzi, Christiane Hertz-Fowler, Christina Cobbold, Richard Reeve, Tom Michoel, Liam J. Morrison

Antigenic variation is employed by many pathogens to evade the host immune response, and Trypanosoma brucei has evolved a complex system to achieve this phenotype, involving sequential use of variant surface glycoprotein (VSG) genes encoded from a large repertoire of ~2,000 genes. T. brucei express multiple, sometimes closely related, VSGs in a population at any one time, and the ability to resolve and analyse this diversity has been limited. We applied long read sequencing (PacBio) to VSG amplicons generated from blood extracted from batches of mice sacrificed at time points (days 3, 6, 10 and 12) post-infection with T. brucei TREU927. The data showed that long read sequencing is reliable for resolving variant differences between VSGs, and demonstrated that there is significant expressed diversity (449 VSGs detected across 20 mice) and across the timeframe of study there was a clear semi-reproducible pattern of expressed diversity (median of 27 VSGs per sample at day 3 post infection (p.i.), 82 VSGs at day 6 p.i., 187 VSGs at day 10 p.i. and 132 VSGs by day 12 p.i.). There was also consistent detection of one VSG dominating expression across replicates at days 3 and 6, and emergence of a second dominant VSG across replicates by day 12. The innovative application of ecological diversity analysis to VSG reads enabled characterisation of hierarchical VSG expression in the dataset, and resulted in a novel method for analysing such patterns of variation. Additionally, the long read approach allowed detection of mosaic VSG expression from very few reads–the earliest in infection that such events have been detected. Therefore, our results indicate that long read analysis is a reliable tool for resolving diverse gene expression profiles, and provides novel insights into the complexity and nature of VSG expression in trypanosomes, revealing significantly higher diversity than previously shown and the ability to identify mosaic gene formation early during the infection process.

A Plant like Cytochrome P450 Subfamily <i>CYP710C1</i> Gene in <i>Leishmania donovani</i> Encodes Sterol C-22 Desaturase and its Over-expression Leads to Resistance to Amphotericin B

PLoS Neglected Tropical Diseases News - 3 April 2019 - 9:00pm

by Ruby Bansal, Shib Sankar Sen, Rohini Muthuswami, Rentala Madhubala

Background

Leishmania donovani is a protozoan parasite, a primary causative agent of visceral leishmaniasis. Sterol produced via the mevalonate pathway, show differences in composition across biological kingdoms. The specific occurrence of Δ22-unsaturated sterols, containing a double bond at the C-22 position in the side chain occurs in fungi as ergosterol and as stigmasterol in plants. In the present study, we report the identification and functional characterization of a plant-like Cytochrome P450 subfamily CYP710C1 in L. donovani as the Leishmania C-22 desaturase.

Methodology

In silico analysis predicted the presence of a plant like CYP710C1 gene that encodes a sterol C-22 desaturase, a key enzyme in stigmasterol biosynthesis. The enzymatic function of recombinant CYP710C1 as C-22 desaturase was determined. To further study the physiological role of CYP710C1 in Leishmania, we developed and characterized an overexpressing strain and a gene deletion mutant. C-22 desaturase activity and stigmasterol levels were estimated in the wild-type, overexpressing promastigotes and heterozygous mutants.

Conclusion

We for the first time report the presence of a CYP710C1 gene that encodes a plant like sterol C-22 desaturase leading to stigmasterol biosynthesis in Leishmania. The recombinant CYP710C1 exhibited C-22 desaturase activity by converting β-sitosterol to stigmasterol. Axenic amastigotes showed higher expression of CYP710C1 mRNA, protein and stigmasterol levels compared to the promastigotes. Sterol profiling of CYP710C1 overexpressing L. donovani and heterozygous mutant parasites demonstrated that CYP710C1 was responsible for stigmasterol production. Most importantly, we demonstrate that these CYP710C1 overexpressing promastigotes are resistant to amphotericin B, a drug of choice for use against leishmaniasis. We report that Leishmania sterol biosynthesis pathway has a chimeric organisation with characteristics of both plant and fungal pathways.

Febrile temperatures increase <i>in vitro</i> antibody affinity for malarial and dengue antigens

PLoS Neglected Tropical Diseases News - 3 April 2019 - 9:00pm

by Razvan C. Stan, Katia S. Françoso, Rubens P. S. Alves, Luís Carlos S. Ferreira, Irene S. Soares, Maristela M. de Camargo

Fever is a regulated increase of the body temperature resulting from both infectious and non-infectious causes. Fever is known to play a role in modulating immune responses to infection, but the potential of febrile temperatures in regulating antigen binding affinity to antibodies has not been explored. Here we investigated this process under in vitro conditions using Isothermal titration calorimetry and ELISA. We used selected malarial and dengue antigens against specific monoclonal antibodies, and observed a marked increase in the affinity of these antibody-antigen complexes at 40°C, compared to physiological (37°C) or pathophysiological temperatures (42°C). Induced thermal equilibration of the protein partners at these temperatures in vitro, prior to measurements, further increased their binding affinity. These results suggest another positive and adaptive role for fever in vivo, and highlight the favourable role of thermal priming in enhancing protein-protein affinity for samples with limited availability.

<i>Culex</i> species diversity, susceptibility to insecticides and role as potential vector of Lymphatic filariasis in the city of Yaoundé, Cameroon

PLoS Neglected Tropical Diseases News - 3 April 2019 - 9:00pm

by Elysee Nchoutpouen, Abdou Talipouo, Borel Djiappi-Tchamen, Landre Djamouko-Djonkam, Edmond Kopya, Carmene Sandra Ngadjeu, Patricia Doumbe-Belisse, Parfait Awono-Ambene, Sevilor Kekeunou, Charles Sinclair Wondji, Christophe Antonio-Nkondjio

Background

Culex species are widespread across Cameroon and responsible for high burden of nuisance in most urban settings. However, despite their high nuisance, they remain less studied compared to anophelines. The present study aimed to assess Culex species distribution, susceptibility to insecticide, bionomics and role in Lymphatic Filariasis (LF) transmission in the city of Yaoundé.

Methods

Mosquito collections were conducted from March to December 2017 using Centre for Disease Control light traps (CDC-LT), human landing catches (HLC) and larval collections. Mosquitoes were identified using morphological identification keys. Mosquitoes from the Culex pipiens complex were further identified using Polymerase Chain Reaction (PCR) to assess the presence of sibling species. Bioassays were conducted with 2–5 day-old unfed females to assess mosquito susceptibility to DDT, permethrin, deltamethrin and bendiocarb following WHO guidelines. Dead, control and surviving mosquitoes from bioassays were screened by PCR to detect the presence of knockdown resistance (kdr) alleles. Pools of mosquitoes were examined by PCR to detect the presence of Wuchereria bancrofti.

Results

A total of 197,956 mosquitoes belonging to thirteen species were collected. The density of mosquito collected varied according to the collection methods, districts and seasons. Culex quinquefasciatus emerged as the most abundant and the only species of the Culex pipiens complex in Yaoundé. Culex species were found breeding in different types of breeding sites including polluted and unpolluted sites. All Culex species including Cx antennatus, Cx duttoni, Cx perfuscus and Cx tigripes were found to be highly resistant to permethrin, deltamethrin and DDT. Culex quinquefasciatus was also found to be resistant to bendiocarb. A high frequency of the West Africa kdr allele was recorded in resistant Cx. quinquefasciatus. Out of the 247 pooled samples of 25 Culex spp. examined for the presence of Wuchereria bancrofti, none was found infected.

Conclusion

The study confirms the high adaptation of Culex species particularly Culex quinquefasciatus to the urban environment and no implication of this species in the transmission of LF in Yaoundé Cameroon. Culex species predominance in urban settings highlight potential transmission risk of West Nile and rift valley fever in Yaoundé.

Connexin 43 plays an important role in the transformation of cholangiocytes with <i>Clonochis sinensis</i> excretory-secretory protein and <i>N</i>-nitrosodimethylamine

PLoS Neglected Tropical Diseases News - 3 April 2019 - 9:00pm

by Eun-Min Kim, Young Mee Bae, Min-Ho Choi, Sung-Tae Hong

Background

Clonorchis sinensis is a group I bio-carcinogen responsible for cholangiocarcinoma (CHCA) in humans. However, the mechanism by which C. sinensis promotes carcinogenesis is unclear.

Methodology

Using the human cholangiocyte line H69, we investigated cell proliferation and gap junction protein expression after stimulation with the hepatotoxin N-nitrosodimethylamine (NDMA) and/or excretory-secretory products (ESP) of C. sinensis, which induce inflammation. NDMA and ESP treatment increased proliferation by 146% and the proportion of cells in the G2/M phase by 37%. Moreover, the expression of the cell proliferation-related proteins E2F1, Ki-67, and cancer related protein cytokeratin 19 and Cox-2 increased in response to combined treatment with NDMA and ESP. The gap-junction proteins connexin (Cx) 43 and Cx26 increased. In contrast, Cx32 expression decreased in cells treated with NDMA and ESP. Silencing of Cx43 reduced cell proliferation and significantly suppressed Cx26 and Cox-2 expression.

Conclusions

These results suggest that Cx43 is an important factor in CHCA induced by C. sinensis ESP and NDMA and further investigations targeting this pathway may allow prevention of this deadly disease.

A community-based knowledge, attitude, and practice survey on rabies among cattle owners in selected areas of Bhutan

PLoS Neglected Tropical Diseases News - 1 April 2019 - 9:00pm

by Sangay Rinchen, Tenzin Tenzin, David Hall, Frank van der Meer, Basant Sharma, Kinzang Dukpa, Susan Cork

Rabies remains a disease of significant zoonotic and economic concern in rabies endemic areas of Bhutan. Rabies outbreaks in livestock threaten the livelihoods of subsistent farming communities and pose a potential public health threat. As a part of identifying approaches to prevent rabies in cattle, a Knowledge, Attitude, and Practice (KAP) survey was conducted among cattle owners in selected rural areas of the southern rabies high-risk zone and low-risk zone in eastern Bhutan. Between March and April 2017, 562 cattle owners (281 in the east and 281 in the south) were interviewed using a questionnaire. Eighty-eight percent of the participants had heard of rabies but only 39% of the participants who had heard of rabies had adequate knowledge about rabies. Multivariable logistic regression analysis showed that residing in the south [OR = 9.25 (95% CI: 6.01–14.53)] and having seen a rabies case [OR = 2.46 (95% CI: 1.6–3.82)] were significantly associated with having adequate knowledge about rabies. Based on our scoring criteria, 65% of the total participants who had heard of rabies had a favorable attitude towards rabies control and prevention programs. The participants residing in the east were two times more likely to have a favourable attitude than their counterparts in the south [OR = 2.08 (95% CI: 1.43–3.05)]. More than 70% of the participants reported engaging in farm activities such as examining the oral cavity of sick cattle and assisting cattle during parturition. Only 25% of the participants reported using personal protective equipment while undertaking these activities. Despite a high level of rabies awareness, we observed that there is a lack of comprehensive knowledge about rabies regarding susceptible hosts, transmission routes, the health outcome of rabies infection in humans, and appropriate health-seeking behaviours. This study highlights the need to strengthen rabies education programs in rural communities to address the knowledge gaps that have been identified.

Blackflies in the ointment: <i>O</i>. <i>volvulus</i> vector biting can be significantly reduced by the skin-application of mineral oil during human landing catches

PLoS Neglected Tropical Diseases News - 1 April 2019 - 9:00pm

by Túllio Romão Ribeiro da Silva, James Lee Crainey, Felipe Arley Costa Pessoa, Yago Vinícius Serra dos Santos, Jordam William Pereira-Silva, Lorena Ferreira de Oliveira Leles, Ana Carolina Vicente, Sérgio Luiz Bessa Luz

Background

Standard human landing catches (sHLCs) have historically been a key component of Onchocerca volvulus transmission monitoring, but expose health-workers to potentially hazardous vector bites. Novel human-bait-free trapping methods have been developed, but do not always work where they are needed and may not generate O. volvulus surveillance data that is directly comparable with historic data.

Methodology

Simuliid sHLCs and mineral-oil protected HLCs (mopHLCs) were performed in a rural village of Amazonas state, Brazil. A four-hour direct comparisons of sHLCs and mopHLCs was carried-out using six vector collectors, each of whom used one leg for a HLC and one for a mopHLC. Two-person collection teams then exclusively performed either mopHLCs or sHLCs for a further set of 12 four-hour collections. Following the completion of all collections, simuliid-bite mark estimates were made from legs used exclusively in sHLCs and legs used exclusively in mopHLCs.

Principal findings

All of the 1669 captured simuliids were identified as the O. volvulus vector Simulium oyapockense. Overall, mopHLC simuliids captured per hour (S/H) rates were lower than those obtained with sHLC trapping (15.5 S/H versus 20 S/H). Direct comparisons of simuliid capture rates found that vector-collectors captured simuliids significantly more efficiently (x¯: 20.5 S/H) with mopHLC trapping than with sHLC trapping (x¯: 16.4 S/H): P-value = 0.002. MopHLCs performed in isolation were, however, observed to capture vectors less efficiently (x¯: 13.4 S/H) than sHLCs performed under similar conditions (x¯: 19.98 S/H). All six vector collectors had significantly higher simuliid capture per counted bite mark (SC/CBM) rates using mopHLCs than they were observe to have using sHLCs (x¯: 21 SC/CBM versus x¯: 1 SC/CBM; p-value = 0.03125).

Conclusions

Vector collectors captured significantly more simuliids per counted bite mark with mopHLCs than with sHLCs. Further investigations into the utility of mopHLCs for onchocerciasis xenomonitoring and beyond are merited.

Severe fever with thrombocytopenia syndrome can masquerade as hemorrhagic fever with renal syndrome

PLoS Neglected Tropical Diseases News - 29 March 2019 - 9:00pm

by Rui Qi, Xiang-rong Qin, Ling Wang, Hui-ju Han, Feng Cui, Hao Yu, Jian-wei Liu, Xue-jie Yu

Background

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging viral hemorrhagic fever with a high fatality rate and high frequency of person-to-person transmission and is caused by SFTSV, a tick-borne Phlebovirus. Because SFTS has similar clinical manifestations and epidemic characters (such as spatial and temporal distributions) with hemorrhagic fever with renal syndrome (HFRS) in China, we reason that SFTS patients might be misdiagnosed as HFRS.

Methodology/principal findings

Acute-phase sera of 128 clinically diagnosed HFRS patients were retrospectively analyzed for Hantavirus IgM antibodies with ELISA. Hantavirus-negative patients’ sera were further analyzed for SFTSV IgM antibodies with ELISA. ELISA showed that 73 of 128 (57.0%) of clinically diagnosed HFRS patients were IgM antibody positive to Hantaviruses. Among the 55 Hantavirus-IgM negative patients, four (7.3%) were IgM antibody positive to SFTSV. The results indicated that the four SFTS patients were misdiagnosed as HFRS. The misdiagnosed SFTS patients had clinical manifestations common to HFRS and were unable to be differentiated from HFRS clinically.

Conclusions

Our study showed that SFTS patients could be clinically misdiagnosed as HFRS. The misdiagnosis of SFTS as HFRS causes particular concern because it may increase the risk of death of SFTS patients and person-to-person transmission of SFTSV without proper care for and isolation of SFTS patients.

Voltage-gated sodium channel intron polymorphism and four mutations comprise six haplotypes in an <i>Aedes aegypti</i> population in Taiwan

PLoS Neglected Tropical Diseases News - 29 March 2019 - 9:00pm

by Han-Hsuan Chung, I-Cheng Cheng, Yen-Chi Chen, Cheo Lin, Takashi Tomita, Hwa-Jen Teng

Background

Knockdown resistance (kdr) to dichlorodiphenyltrichloroethane (DDT) and pyrethroids is known to link amino acid substitutions in the voltage-gated sodium channel (VGSC) in Aedes aegypti. Dengue fever primarily transmitted by Ae. aegypti is an annual public health issue in Taiwan. Accordingly, pyrethroid insecticides have been heavily used for decades to control mosquito populations in the summer and autumn. In Taiwan, an Ae. aegypti population with two VGSC mutations, V1016G and D1763Y, was described previously.

Methodology/Principal finding

Aedes aegypti (G0) were collected in Tainan and Kaohsiung in southern Taiwan. The VGSC gene polymorphisms of the kdr mutations and the intron flanked by exons 20 and 21 were verified. The first generation offspring (G1) were used to measure the resistance level to cypermethrin, a pyrethroid insecticide currently used in Taiwan. In addition to V1016G and D1763Y, we describe two new mutations, S989P and F1534C, which have not been reported in Taiwan. Moreover, we also identify two types (groups A and B) of introns between exons 20 and 21. Intriguingly, the kdr mutations S989P, V1016G and D1763Y are strictly located on the haplotype harboring the group A intron, whereas F1534C links to the group B intron. When those data were taken together, we proposed the following six haplotypes for VGSC genes in Taiwan today: (i)S989-intron A-V1016-F1534-D1763, (ii)S989-intron A-V1016G-F1534-D1763, (iii)S989P-intron A-V1016G-F1534-D1763, (iv)S989-intron A-V1016G-F1534-D1763Y, (v)S989-intron B-V1016-F1534-D1763 and (vi)S989-intron B-V1016-F1534C-D1763. Triple heterozygous mutations of either S989P/V1016G/F1534C or V1016G/F1534C/D1763Y can be found in one single Ae. aegypti mosquito. The proportions of the VGSC mutations were relevant to cypermethrin resistance. Notably, the presence of S989P and V1016G in the population could be a helpful reference to predict the resistance level to cypermethrin. This is the first study to demonstrate the coexistence of four kdr mutations in a population of Ae. aegypti.

Conclusions/Significance

Four kdr mutations (S989P, V1016G, F1534C and D1763Y) and two intron forms (Group A and B) were commonly found in local Ae. aegypti populations in Taiwan.

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