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MicroRNA-30e* Suppresses Dengue Virus Replication by Promoting NF-κB–Dependent IFN Production

PLoS Neglected Tropical Diseases News - 14 August 2014 - 9:00pm

by Xun Zhu, Zhenjian He, Yiwen Hu, Weitao Wen, Cuiji Lin, Jianchen Yu, Jing Pan, Ran Li, Haijing Deng, Shaowei Liao, Jie Yuan, Jueheng Wu, Jun Li, Mengfeng Li

MicroRNAs have been shown to contribute to a repertoire of host-pathogen interactions during viral infection. Our previous study demonstrated that microRNA-30e* (miR-30e*) directly targeted the IκBα 3′-UTR and disrupted the NF-κB/IκBα negative feedback loop, leading to hyperactivation of NF-κB. This current study investigated the possible role of miR-30e* in the regulation of innate immunity associated with dengue virus (DENV) infection. We found that DENV infection could induce miR-30e* expression in DENV-permissive cells, and such an overexpression of miR-30e* upregulated IFN-β and the downstream IFN-stimulated genes (ISGs) such as OAS1, MxA and IFITM1, and suppressed DENV replication. Furthermore, suppression of IκBα mediates the enhancing effect of miR-30e* on IFN-β-induced antiviral response. Collectively, our findings suggest a modulatory role of miR-30e* in DENV induced IFN-β signaling via the NF-κB-dependent pathway. Further investigation is needed to evaluate whether miR-30e* has an anti-DENV effect in vivo.

Disease Progression in Plasmodium knowlesi Malaria Is Linked to Variation in Invasion Gene Family Members

PLoS Neglected Tropical Diseases News - 14 August 2014 - 9:00pm

by Atique M. Ahmed, Miguel M. Pinheiro, Paul C. Divis, Angela Siner, Ramlah Zainudin, Ing Tien Wong, Chan Woon Lu, Sarina K. Singh-Khaira, Scott B. Millar, Sean Lynch, Matthias Willmann, Balbir Singh, Sanjeev Krishna, Janet Cox-Singh

Emerging pathogens undermine initiatives to control the global health impact of infectious diseases. Zoonotic malaria is no exception. Plasmodium knowlesi, a malaria parasite of Southeast Asian macaques, has entered the human population. P. knowlesi, like Plasmodium falciparum, can reach high parasitaemia in human infections, and the World Health Organization guidelines for severe malaria list hyperparasitaemia among the measures of severe malaria in both infections. Not all patients with P. knowlesi infections develop hyperparasitaemia, and it is important to determine why. Between isolate variability in erythrocyte invasion, efficiency seems key. Here we investigate the idea that particular alleles of two P. knowlesi erythrocyte invasion genes, P. knowlesi normocyte binding protein Pknbpxa and Pknbpxb, influence parasitaemia and human disease progression. Pknbpxa and Pknbpxb reference DNA sequences were generated from five geographically and temporally distinct P. knowlesi patient isolates. Polymorphic regions of each gene (approximately 800 bp) were identified by haplotyping 147 patient isolates at each locus. Parasitaemia in the study cohort was associated with markers of disease severity including liver and renal dysfunction, haemoglobin, platelets and lactate, (r = ≥0.34, p = <0.0001 for all). Seventy-five and 51 Pknbpxa and Pknbpxb haplotypes were resolved in 138 (94%) and 134 (92%) patient isolates respectively. The haplotypes formed twelve Pknbpxa and two Pknbpxb allelic groups. Patients infected with parasites with particular Pknbpxa and Pknbpxb alleles within the groups had significantly higher parasitaemia and other markers of disease severity. Our study strongly suggests that P. knowlesi invasion gene variants contribute to parasite virulence. We focused on two invasion genes, and we anticipate that additional virulent loci will be identified in pathogen genome-wide studies. The multiple sustained entries of this diverse pathogen into the human population must give cause for concern to malaria elimination strategists in the Southeast Asian region.

Molecular Xenomonitoring Using Mosquitoes to Map Lymphatic Filariasis after Mass Drug Administration in American Samoa

PLoS Neglected Tropical Diseases News - 14 August 2014 - 9:00pm

by Mark A. Schmaedick, Amanda L. Koppel, Nils Pilotte, Melissa Torres, Steven A. Williams, Stephen L. Dobson, Patrick J. Lammie, Kimberly Y. Won

Background

Mass drug administration (MDA) programs have dramatically reduced lymphatic filariasis (LF) incidence in many areas around the globe, including American Samoa. As infection rates decline and MDA programs end, efficient and sensitive methods for detecting infections are needed to monitor for recrudescence. Molecular methods, collectively termed ‘molecular xenomonitoring,’ can identify parasite DNA or RNA in human blood-feeding mosquitoes. We tested mosquitoes trapped throughout the inhabited islands of American Samoa to identify areas of possible continuing LF transmission after completion of MDA.

Methodology/Principle Findings

Mosquitoes were collected using BG Sentinel traps from most of the villages on American Samoa's largest island, Tutuila, and all major villages on the smaller islands of Aunu'u, Ofu, Olosega, and Ta'u. Real-time PCR was used to detect Wuchereria bancrofti DNA in pools of ≤20 mosquitoes, and PoolScreen software was used to infer territory-wide prevalences of W. bancrofti DNA in the mosquitoes. Wuchereria bancrofti DNA was found in mosquitoes from 16 out of the 27 village areas sampled on Tutuila and Aunu'u islands but none of the five villages on the Manu'a islands of Ofu, Olosega, and Ta'u. The overall 95% confidence interval estimate for W. bancrofti DNA prevalence in the LF vector Ae. polynesiensis was 0.20–0.39%, and parasite DNA was also detected in pools of Culex quinquefasciatus, Aedes aegypti, and Aedes (Finlaya) spp.

Conclusions/Significance

Our results suggest low but widespread prevalence of LF on Tutuila and Aunu'u where 98% of the population resides, but not Ofu, Olosega, and Ta'u islands. Molecular xenomonitoring can help identify areas of possible LF transmission, but its use in the LF elimination program in American Samoa is limited by the need for more efficient mosquito collection methods and a better understanding of the relationship between prevalence of W. bancrofti DNA in mosquitoes and infection and transmission rates in humans.

Neglected Tropical Diseases: A Systematic Evaluation of Research Capacity in Nigeria

PLoS Neglected Tropical Diseases News - 14 August 2014 - 9:00pm

by Patricia N. Okorie, Moses J. Bockarie, David H. Molyneux, Louise A. Kelly-Hope

Background

Nigeria carries the highest burden and diversity of neglected tropical diseases (NTDs) in sub-Saharan Africa and is preparing to scale up its efforts to control/eliminate these diseases. To achieve this it will require a range of internal technical support and expertise for mapping, monitoring and evaluating, operational research and documenting its success. In order to begin to evaluate this potential in Nigeria, this study collated and analysed information for lymphatic filariasis (LF), onchocerciasis, schistosomiasis and soil-transmitted helminths (STH), which are currently being targeted with preventive chemotherapy through mass drug administration (MDA).

Methodology/Principal Findings

Information from 299 scientific articles published on the selected NTDs in 179 journals between January 2008 and September 2013 was extracted and systematically compiled into a geo-referenced database for analysis and mapping. The highest number of articles was from the southern geo-political zones of the country. The majority of articles focused on one specific disease, and schistosomiasis and STH were found to have the highest and most wide ranging research output. The main type of study was parasitological, and the least was biotechnological. Nigerian authors were mostly affiliated with universities, and there was a wide range of international co-authors from Africa and other regions, especially the USA and UK. The majority of articles were published in journals with no known impact factor.

Conclusions/Significance

The extensive database and series of maps on the research capacity within Nigeria produced in this study highlights the current potential that exists, and needs to be fully maximized for the control/elimination of NTDs in the country. This study provides an important model approach that can be applied to other low and middle income countries where NTDs are endemic, and NTD programmes require support from the expertise within their own country, as well as internationally, to help raise their profile and importance.

Nitric Oxide from IFNγ-Primed Macrophages Modulates the Antimicrobial Activity of β-Lactams against the Intracellular Pathogens Burkholderia pseudomallei and Nontyphoidal Salmonella

PLoS Neglected Tropical Diseases News - 14 August 2014 - 9:00pm

by Jessica Jones-Carson, Adrienne E. Zweifel, Timothy Tapscott, Chad Austin, Joseph M. Brown, Kenneth L. Jones, Martin I. Voskuil, Andrés Vázquez-Torres

Our investigations show that nonlethal concentrations of nitric oxide (NO) abrogate the antibiotic activity of β-lactam antibiotics against Burkholderia pseudomallei, Escherichia coli and nontyphoidal Salmonella enterica serovar Typhimurium. NO protects B. pseudomallei already exposed to β-lactams, suggesting that this diatomic radical tolerizes bacteria against the antimicrobial activity of this important class of antibiotics. The concentrations of NO that elicit antibiotic tolerance repress consumption of oxygen (O2), while stimulating hydrogen peroxide (H2O2) synthesis. Transposon insertions in genes encoding cytochrome c oxidase-related functions and molybdenum assimilation confer B. pseudomallei a selective advantage against the antimicrobial activity of the β-lactam antibiotic imipenem. Cumulatively, these data support a model by which NO induces antibiotic tolerance through the inhibition of the electron transport chain, rather than by potentiating antioxidant defenses as previously proposed. Accordingly, pharmacological inhibition of terminal oxidases and nitrate reductases tolerizes aerobic and anaerobic bacteria to β-lactams. The degree of NO-induced β-lactam antibiotic tolerance seems to be inversely proportional to the proton motive force (PMF), and thus the dissipation of ΔH+ and ΔΨ electrochemical gradients of the PMF prevents β-lactam-mediated killing. According to this model, NO generated by IFNγ-primed macrophages protects intracellular Salmonella against imipenem. On the other hand, sublethal concentrations of imipenem potentiate the killing of B. pseudomallei by NO generated enzymatically from IFNγ-primed macrophages. Our investigations indicate that NO modulates the antimicrobial activity of β-lactam antibiotics.

Dissemination of Orientia tsutsugamushi and Inflammatory Responses in a Murine Model of Scrub Typhus

PLoS Neglected Tropical Diseases News - 14 August 2014 - 9:00pm

by Christian A. Keller, Matthias Hauptmann, Julia Kolbaum, Mohammad Gharaibeh, Melanie Neumann, Markus Glatzel, Bernhard Fleischer

Central aspects in the pathogenesis of scrub typhus, an infection caused by Orientia (O.) tsutsugamushi, have remained obscure. Its organ and cellular tropism are poorly understood. The purpose of this study was to analyze the kinetics of bacterial dissemination and associated inflammatory responses in infected tissues in an experimental scrub typhus mouse model, following infection with the human pathogenic strain Karp. We provide a thorough analysis of O. tsutsugamushi infection in inbred Balb/c mice using footpad inoculation, which is close to the natural way of infection. By a novel, highly sensitive qPCR targeting the multi copy traD genes, we quantitatively monitored the spread of O. tsutsugamushi Karp from the skin inoculation site via the regional lymph node to the internal target organs. The highest bacterial loads were measured in the lung. Using confocal imaging, we also detected O. tsutsugamushi at the single cell level in the lung and found a predominant macrophage rather than endothelial localization. Immunohistochemical analysis of infiltrates in lung and brain revealed differently composed lesions with specific localizations: iNOS-expressing macrophages were frequent in infiltrative parenchymal noduli, but uncommon in perivascular lesions within these organs. Quantitative analysis of the macrophage response by immunohistochemistry in liver, heart, lung and brain demonstrated an early onset of macrophage activation in the liver. Serum levels of interferon (IFN)-γ were increased during the acute infection, and we showed that IFN-γ contributed to iNOS-dependent bacterial growth control. Our data show that upon inoculation to the skin, O. tsutsugamushi spreads systemically to a large number of organs and gives rise to organ-specific inflammation patterns. The findings suggest an essential role for the lung in the pathogenesis of scrub typhus. The model will allow detailed studies on host-pathogen interaction and provide further insight into the pathogenesis of O. tsutsugamushi infection.

Is Plasmodium vivax Malaria a Severe Malaria?: A Systematic Review and Meta-Analysis

PLoS Neglected Tropical Diseases News - 14 August 2014 - 9:00pm

by Cho Naing, Maxine A. Whittaker, Victor Nyunt Wai, Joon Wah Mak

Background

Plasmodium vivax is one of the major species of malaria infecting humans. Although emphasis on P. falciparum is appropriate, the burden of vivax malaria should be given due attention. This study aimed to synthesize the evidence on severe malaria in P. vivax infection compared with that in P. falciparum infection.

Methods/Principal Findings

We searched relevant studies in electronic databases. The main outcomes required for inclusion in the review were mortality, severe malaria (SM) and severe anaemia (SA). The methodological quality of the included studies was assessed using the Newcastle-Ottawa Scale. Overall, 26 studies were included. The main meta-analysis was restricted to the high quality studies. Eight studies (n = 27490) compared the incidence of SM between P. vivax infection and P. falciparum mono-infection; a comparable incidence was found in infants (OR: 0.45, 95% CI:0.04–5.68, I2:98%), under 5 year age group (OR: 2.06, 95% CI: 0.83–5.1, I2:83%), the 5–15 year-age group (OR: 0.6, 95% CI: 0.31–1.16, I2:81%) and adults (OR: 0.83, 95% CI: 0.67–1.03, I2:25%). Six studies reported the incidences of SA in P. vivax infection and P. falciparum mono-infection; a comparable incidence of SA was found among infants (OR: 3.47, 95%:0.64–18.94, I2: 92%), the 5–15 year-age group (OR:0.71, 95% CI: 0.06–8.57, I2:82%). This was significantly lower in adults (OR:0.75, 95% CI: 0.62–0.92, I2:0%). Five studies (n = 71079) compared the mortality rate between vivax malaria and falciparum malaria. A lower rate of mortality was found in infants with vivax malaria (OR:0.61, 95% CI:0.5–0.76, I2:0%), while this was comparable in the 5–15 year- age group (OR: 0.43, 95% CI:0.06–2.91, I2:84%) and the children of unspecified-age group (OR: 0.77, 95% CI:0.59–1.01, I2:0%).

Conclusion

Overall, the present analysis identified that the incidence of SM in patients infected with P. vivax was considerable, indicating that P. vivax is a major cause of SM. Awareness of the clinical manifestations of vivax malaria should prompt early detection. Subsequent treatment and monitoring of complications can be life-saving.

Effects of a Post-Deworming Health Hygiene Education Intervention on Absenteeism in School-Age Children of the Peruvian Amazon

PLoS Neglected Tropical Diseases News - 14 August 2014 - 9:00pm

by François L. Thériault, Mathieu Maheu-Giroux, Brittany Blouin, Martin Casapía, Theresa W. Gyorkos

Soil-transmitted helminth (STH) infections are a leading cause of disability and disease burden in school-age children of worm-endemic regions. Their effect on school absenteeism, however, remains unclear. The World Health Organization currently recommends delivering mass deworming and health hygiene education through school-based programs, in an effort to control STH-related morbidity. In this cluster-RCT, the impact of a health hygiene education intervention on absenteeism was measured. From April to June 2010, all Grade 5 students at 18 schools in a worm-endemic region of the Peruvian Amazon were dewormed. Immediately following deworming, nine schools were randomly assigned to the intervention arm of the trial using a matched-pair design. The Grade 5 students attending intervention schools (N = 517) received four months of health hygiene education aimed at increasing knowledge of STH prevention. Grade 5 students from the other nine schools (N = 571) served as controls. Absenteeism was measured daily through teachers' attendance logs. After four months of follow-up, overall absenteeism rates at intervention and control schools were not statistically significantly different. However, post-trial non-randomized analyses have shown that students with moderate-to-heavy Ascaris infections and light hookworm infections four months after deworming had, respectively, missed 2.4% (95% CI: 0.1%, 4.7%) and 4.6% (95% CI: 1.9%, 7.4%) more schooldays during the follow-up period than their uninfected counterparts. These results provide empirical evidence of a direct effect of STH infections on absenteeism in school-age children.

Long-term Sonographic and Serological Follow-up of Inactive Echinococcal Cysts of the Liver: Hints for a “Watch-and-Wait” Approach

PLoS Neglected Tropical Diseases News - 14 August 2014 - 9:00pm

by Luca Piccoli, Francesca Tamarozzi, Federico Cattaneo, Mara Mariconti, Carlo Filice, Antonella Bruno, Enrico Brunetti

Human cystic echinococcosis is a chronic, complex and neglected infection. Its clinical management has evolved over decades without adequate evaluation of efficacy. Recent expert opinion recommends that uncomplicated inactive cysts of the liver should be left untreated and solely monitored over time (“watch-and-wait” approach). However, clinical data supporting this approach are still scant and published mostly as conference proceedings. In this study, we report our experience with long-term sonographic and serological follow-up of inactive cysts of the liver. From March 1994 to October 2013, 38 patients with 47 liver cysts, diagnosed as inactive without any previous treatment history, were followed with ultrasound and serology at 6–12 months intervals for a period of at least 24 months (median follow-up 51.95 months) in our outpatient clinic. In 97.4% of patients, the cysts remained inactive over time and in only one case was reactivation of the cyst detected. No complications occurred during the time of monitoring. During follow-up, serology tests for CE were negative at diagnosis or became negative in 74.1% and were positive or became positive in 25.9% of cases. Patients with inactive cysts on ultrasound but positive serological tests were also investigated by CT scan (chest and abdomen) to rule out extra-hepatic cyst localization. This study confirms the importance of a stage-specific approach to the management of cystic echinococcosis and supports the use of a monitoring-only approach to inactive, uncomplicated cysts of the liver. It also confirms that serology plays only an ancillary role in the clinical management of these patients, compared to ultrasound and other imaging techniques. The implications of these findings for clinical management and natural history of cystic echinococcosis are discussed.

Efficacy and Safety of Praziquantel, Tribendimidine and Mebendazole in Patients with Co-infection of Clonorchis sinensis and Other Helminths

PLoS Neglected Tropical Diseases News - 14 August 2014 - 9:00pm

by Li-Li Xu, Bin Jiang, Ji-Hui Duan, Shi-Feng Zhuang, Yong-Chun Liu, Shi-Qiao Zhu, Li-Ping Zhang, Hao-Bing Zhang, Shu-Hua Xiao, Xiao-Nong Zhou

Background

Both tribendimidine and mebendazole are broad-spectrum drugs for anti-intestinal nematodes. We aim to assess the efficacy and safety of tribendimidine and mebendazole in patients with co-infection of Clonorchis sinensis and other helminths.

Method

We performed a randomized open-label trial in Qiyang, People's Republic of China. Eligible participants were randomly assigned to one of four groups: (i) a single dose of 400 mg tribendimidine, (ii) 200 mg tribendimidine twice daily, (iii) 75 mg/kg praziquantel divided in four doses within 2 days, and (iv) a single dose of 400 mg mebendazole. Cure rates and egg reduction rates were assessed, and adverse events were monitored after treatments. Uncured patients accepted the second treatment with the same drugs after the first treatment.

Results

156 patients were eligible for the study. Results from the first treatment showed that the cure rates of single-dose tribendimidine and praziquantel against C. sinensis were 50% and 56.8%, respectively; the single-dose tribendimidine achieved the cure rate of 77.8% in the treatment for hookworm, which was significantly higher than that of praziquantel; Low cure rates were obtained in the treatment of single-dose tribendimidine against Ascaris lumbricoides and Trichuris trichiura (28.6% and 23.1%). Results of the second treatment illustrated the cure rates of tribendimidine and praziquantel against C. sinensis were 78.1% and 75%, respectively. Most adverse events were mild and transient. Adverse events caused by tribendimidine were significantly less than praziquantel.

Conclusion

Single-dose tribendimidine showed similar efficacy against C. sinensis as praziquantel with less adverse events, and achieved significantly higher cure rate in the treatment for hookworm than those of praziquantel and mebendazole. Low cure rates, which were still higher than other drugs, were obtained in the treatment of single-dose tribendimidine against Ascaris lumbricoides and Trichuris trichiura.

Trial Registration

Controlled-Trials.com ISRCTN55086560

Primary Amoebic Meningoencephalitis Caused by Naegleria fowleri: An Old Enemy Presenting New Challenges

PLoS Neglected Tropical Diseases News - 14 August 2014 - 9:00pm

by Ruqaiyyah Siddiqui, Naveed Ahmed Khan

First discovered in 1899, Naegleria fowleri is a protist pathogen, known to infect the central nervous system and produce primary amoebic meningoencephalitis. The most distressing aspect is that the fatality rate has remained more than 95%, despite our advances in antimicrobial chemotherapy and supportive care. Although rare worldwide, most cases have been reported in the United States, Australia, and Europe (France). A large number of cases in developing countries go unnoticed. In particular, religious, recreational, and cultural practices such as ritual ablution and/or purifications, Ayurveda, and the use of neti pots for nasal irrigation can contribute to this devastating infection. With increasing water scarcity and public reliance on water storage, here we debate the need for increased awareness of primary amoebic meningoencephalitis and the associated risk factors, particularly in developing countries.

Vaccine Strategies for the Control and Prevention of Japanese Encephalitis in Mainland China, 1951–2011

PLoS Neglected Tropical Diseases News - 14 August 2014 - 9:00pm

by Xiaoyan Gao, Xiaolong Li, Minghua Li, Shihong Fu, Huanyu Wang, Zhi Lu, Yuxi Cao, Ying He, Wuyang Zhu, Tingting Zhang, Ernest A. Gould, Guodong Liang

Japanese encephalitis (JE) is arguably one of the most serious viral encephalitis diseases worldwide. China has a long history of high prevalence of Japanese encephalitis, with thousands of cases reported annually and incidence rates often exceeding 15/100,000. In global terms, the scale of outbreaks and high incidence of these pandemics has almost been unique, placing a heavy burden on the Chinese health authorities. However, the introduction of vaccines, developed in China, combined with an intensive vaccination program initiated during the 1970s, as well as other public health interventions, has dramatically decreased the incidence from 20.92/100,000 in 1971, to 0.12/100,000 in 2011. Moreover, in less readily accessible areas of China, changes to agricultural practices designed to reduce chances of mosquito bites as well as mosquito population densities have also been proven effective in reducing local JE incidence. This unprecedented public health achievement has saved many lives and provided valuable experience that could be directly applicable to the control of vector-borne diseases around the world. Here, we review and discuss strategies for promotion and expansion of vaccination programs to reduce the incidence of JE even further, for the benefit of health authorities throughout Asia and, potentially, worldwide.

Distribution of Schistosomiasis and Soil Transmitted Helminthiasis in Zimbabwe: Towards a National Plan of Action for Control and Elimination

PLoS Neglected Tropical Diseases News - 14 August 2014 - 9:00pm

by Nicholas Midzi, Takafira Mduluza, Moses J. Chimbari, Clement Tshuma, Lincoln Charimari, Gibson Mhlanga, Portia Manangazira, Shungu M. Munyati, Isaac Phiri, Susan L. Mutambu, Stanley S. Midzi, Anastancia Ncube, Lawrence P. Muranzi, Simbarashe Rusakaniko, Francisca Mutapi

Background

Schistosomiasis and STH are among the list of neglected tropical diseases considered for control by the WHO. Although both diseases are endemic in Zimbabwe, no nationwide control interventions have been implemented. For this reason in 2009 the Zimbabwe Ministry of Health and Child Care included the two diseases in the 2009–2013 National Health Strategy highlighting the importance of understanding the distribution and burden of the diseases as a prerequisite for elimination interventions. It is against this background that a national survey was conducted.

Methodology

A countrywide cross-sectional survey was carried out in 280 primary schools in 68 districts between September 2010 and August 2011. Schistosoma haematobium was diagnosed using the urine filtration technique. Schistosoma mansoni and STH (hookworms, Trichuris trichiura, Ascaris lumbricoides) were diagnosed using both the Kato Katz and formol ether concentration techniques.

Main findings

Schistosomiasis was more prevalent country-wide (22.7%) than STH (5.5%). The prevalence of S. haematobium was 18.0% while that of S. mansoni was 7.2%. Hookworms were the most common STH with a prevalence of 3.2% followed by A. lumbricoides and T. trichiura with prevalence of 2.5% and 0.1%, respectively. The prevalence of heavy infection intensity as defined by WHO for any schistosome species was 5.8% (range 0%–18.3% in districts). Only light to moderate infection intensities were observed for STH species. The distribution of schistosomiasis and STH varied significantly between provinces, districts and schools (p<0.001). Overall, the prevalence of co-infection with schistosomiasis and STH was 1.5%. The actual co-endemicity of schistosomiasis and STH was observed in 43 (63.2%) of the 68 districts screened.

Conclusion and recommendations

This study provided comprehensive baseline data on the distribution of schistosomiasis and STH that formed the basis for initiating a national control and elimination programme for these two neglected tropical diseases in Zimbabwe.

Strongyloidiasis—An Insight into Its Global Prevalence and Management

PLoS Neglected Tropical Diseases News - 14 August 2014 - 9:00pm

by Santhosh Puthiyakunnon, Swapna Boddu, Yiji Li, Xiaohong Zhou, Chunmei Wang, Juan Li, Xiaoguang Chen

Background

Strongyloides stercoralis, an intestinal parasitic nematode, infects more than 100 million people worldwide. Strongyloides are unique in their ability to exist as a free-living and autoinfective cycle. Strongyloidiasis can occur without any symptoms or as a potentially fatal hyperinfection or disseminated infection. The most common risk factors for these complications are immunosuppression caused by corticosteroids and infection with human T-lymphotropic virus or human immunodeficiency virus. Even though the diagnosis of strongyloidiasis is improved by advanced instrumentation techniques in isolated and complicated cases of hyperinfection or dissemination, efficient guidelines for screening the population in epidemiological surveys are lacking.

Methodology and Results

In this review, we have discussed various conventional methods for the diagnosis and management of this disease, with an emphasis on recently developed molecular and serological methods that could be implemented to establish guidelines for precise diagnosis of infection in patients and screening in epidemiological surveys. A comprehensive analysis of various cases reported worldwide from different endemic and nonendemic foci of the disease for the last 40 years was evaluated in an effort to delineate the global prevalence of this disease. We also updated the current knowledge of the various clinical spectrum of this parasitic disease, with an emphasis on newer molecular diagnostic methods, treatment, and management of cases in immunosuppressed patients.

Conclusion

Strongyloidiasis is considered a neglected tropical disease and is probably an underdiagnosed parasitic disease due to its low parasitic load and uncertain clinical symptoms. Increased infectivity rates in many developed countries and nonendemic regions nearing those in the most prevalent endemic regions of this parasite and the increasing transmission potential to immigrants, travelers, and immunosuppressed populations are indications for initiating an integrated approach towards prompt diagnosis and control of this parasitic disease.

Cystic Echinococcosis in the Province of Álava, North Spain: The Monetary Burden of a Disease No Longer under Surveillance

PLoS Neglected Tropical Diseases News - 7 August 2014 - 9:00pm

by Hélène Carabin, Francisco J. Balsera-Rodríguez, José Rebollar-Sáenz, Christine T. Benner, Aitziber Benito, Juan C. Fernández-Crespo, David Carmena

Cystic echinococcosis (CE) is endemic in Spain but has been considered non-endemic in the province of Álava, Northern Spain, since 1997. However, Álava is surrounded by autonomous regions with some of the highest CE prevalence proportions in the nation, casting doubts about the current classification. The purpose of this study is to estimate the frequency of CE in humans and animals and to use this data to determine the societal cost incurred due to CE in the Álava population in 2005. We have identified epidemiological and clinical data from surveillance and hospital records, prevalence data in intermediate (sheep and cattle) host species from abattoir records, and economical data from national and regional official institutions. Direct costs (diagnosis, treatment, medical care in humans and condemnation of offal in livestock species) and indirect costs (productivity losses in humans and reduction in growth, fecundity and milk production in livestock) were modelled using the Latin hypercube method under five different scenarios reflecting different assumptions regarding the prevalence of asymptomatic cases and associated productivity losses in humans. A total of 13 human CE cases were reported in 2005. The median total cost (95% credible interval) of CE in humans and animals in Álava in 2005 was estimated to range between €61,864 (95%CI%: €47,304–€76,590) and €360,466 (95%CI: €76,424–€752,469), with human-associated losses ranging from 57% to 93% of the total losses, depending on the scenario used. Our data provide evidence that CE is still very well present in Álava and incurs important cost to the province every year. We expect this information to prove valuable for public health agencies and policy-makers, as it seems advisable to reinstate appropriate surveillance and monitoring systems and to implement effective control measures that avoid the spread and recrudescence of the disease.

Toxocara Seroprevalence among Clinically Healthy Individuals, Pregnant Women and Psychiatric Patients and Associated Risk Factors in Shandong Province, Eastern China

PLoS Neglected Tropical Diseases News - 7 August 2014 - 9:00pm

by Wei Cong, Xiao-Xuan Zhang, Na Zhou, Chang-Zheng Yu, Jia Chen, Xiang-Yang Wang, Bing Li, Ai-Dong Qian, Xing-Quan Zhu

Background

Toxocarosis is a widespread zoonosis caused by the ascarid nematodes Toxocara canis and Toxocara cati, which primarily infect dogs and cats, respectively. Most human infections with Toxocara are asymptomatic; however, some infected individuals may develop a serious illness and even death. Nevertheless, epidemiological knowledge regarding the prevalence and risks associated with Toxocara infection is limited in China. Therefore, we performed a cross-sectional pilot study and estimated the seroprevalence of Toxocara infection in humans in Shandong Province, eastern China for the first time, from June 2011 to July 2013, involving clinically healthy individuals, pregnant women and psychiatric patients, aiming to attract public attention to Toxocara infection.

Methodology/Principle Findings

Seroprevalence of Toxocara was determined using an enzyme-linked immunosorbent assay based on a cross-sectional study conducted in Qingdao and Weihai, Shandong Province, eastern China. Factors potentially associated with Toxocara infection were identified by logistic regression analysis. The overall Toxocara seroprevalence among the study population (n = 2866) was 12.25%, and a significantly higher seroprevalence in psychiatric patients (16.40%, 73/445) than that in clinically healthy individuals (13.07%, 187/1431) and pregnant women (9.19%, 91/990) was revealed. Univariate analyses suggested that keeping dogs at home (OR = 0.06, 95% CI 0.05–0.08, P<0.001), contact with cats and dogs (OR = 0.42, 95% CI 0.33–0.53, P<0.001) and exposure with soil (OR = 0.37, 95% CI 0.28–0.49, P<0.001) were risk factors associated with Toxocara infection.

Conclusions/Significance

The present study revealed, for the first time, that human infection with Toxocara is common in eastern China, posing a significant public health concern. Increasing human and dog populations, population movements and climate change all will serve to increase the importance of this zoonosis. Further studies under controlled conditions are necessary to define potential morbidity associated with Toxocara infection.

Suppressing Dengue-2 Infection by Chemical Inhibition of Aedes aegypti Host Factors

PLoS Neglected Tropical Diseases News - 7 August 2014 - 9:00pm

by Seokyoung Kang, Alicia R. Shields, Natapong Jupatanakul, George Dimopoulos

Dengue virus host factors (DENV HFs) that are essential for the completion of the infection cycle in the mosquito vector and vertebrate host represent potent targets for transmission blocking. Here we investigated whether known mammalian DENV HF inhibitors could influence virus infection in the arthropod vector A. aegypti. We evaluated the potency of bafilomycin (BAF; inhibitor of vacuolar H+-ATPase (vATPase)), mycophenolic acid (MPA; inhibitor of inosine-5′-monophosphate dehydrogenase (IMPDH)), castanospermine (CAS; inhibitor of glucosidase), and deoxynojirimycin (DNJ; inhibitor of glucosidase) in blocking DENV infection of the mosquito midgut, using various treatment methods that included direct injection, ingestion by sugar feeding or blood feeding, and silencing of target genes by RNA interference (RNAi). Injection of BAF (5 µM) and MPA (25 µM) prior to feeding on virus-infected blood inhibited DENV titers in the midgut at 7 days post-infection by 56% and 60%, and in the salivary gland at 14 days post-infection by 90% and 83%, respectively, while treatment of mosquitoes with CAS or DNJ did not affect susceptibility to the virus. Ingestion of BAF and MPA through a sugar meal or together with an infectious blood meal also resulted in various degrees of virus inhibition. RNAi-mediated silencing of several vATPase subunit genes and the IMPDH gene resulted in a reduced DENV infection, thereby indicating that BAF- and MPA-mediated virus inhibition in adult mosquitoes most likely occurred through the inhibition of these DENV HFs. The route and timing of BAF and MPA administration was essential, and treatment after exposure to the virus diminished the antiviral effect of these compounds. Here we provide proof-of-principle that chemical inhibition or RNAi-mediated depletion of the DENV HFs vATPase and IMPDH can be used to suppress DENV infection of adult A. aegypti mosquitoes, which may translate to a reduction in DENV transmission.

Empiric Deworming and CD4 Count Recovery in HIV-Infected Ugandans Initiating Antiretroviral Therapy

PLoS Neglected Tropical Diseases News - 7 August 2014 - 9:00pm

by Alexander J. Lankowski, Alexander C. Tsai, Michael Kanyesigye, Mwebesa Bwana, Jessica E. Haberer, Megan Wenger, Jeffrey N. Martin, David R. Bangsberg, Peter W. Hunt, Mark J. Siedner

Background

There is conflicting evidence on the immunologic benefit of treating helminth co-infections (“deworming”) in HIV-infected individuals. Several studies have documented reduced viral load and increased CD4 count in antiretroviral therapy (ART) naïve individuals after deworming. However, there are a lack of data on the effect of deworming therapy on CD4 count recovery among HIV-infected persons taking ART.

Methodology/Principal Findings

To estimate the association between empiric deworming therapy and CD4 count after ART initiation, we performed a retrospective observational study among HIV-infected adults on ART at a publicly operated HIV clinic in southwestern Uganda. Subjects were assigned as having received deworming if prescribed an anti-helminthic agent between 7 and 90 days before a CD4 test. To estimate the association between deworming and CD4 count, we fit multivariable regression models and analyzed predictors of CD4 count, using a time-by-interaction term with receipt or non-receipt of deworming. From 1998 to 2009, 5,379 subjects on ART attended 21,933 clinic visits at which a CD4 count was measured. Subjects received deworming prior to 668 (3%) visits. Overall, deworming was not associated with a significant difference in CD4 count in either the first year on ART (β = 42.8; 95% CI, −2.1 to 87.7) or after the first year of ART (β = −9.9; 95% CI, −24.1 to 4.4). However, in a sub-analysis by gender, during the first year of ART deworming was associated with a significantly greater rise in CD4 count (β = 63.0; 95% CI, 6.0 to 120.1) in females.

Conclusions/Significance

Empiric deworming of HIV-infected individuals on ART conferred no significant generalized benefit on subsequent CD4 count recovery. A significant association was observed exclusively in females and during the initial year on ART. Our findings are consistent with recent studies that failed to demonstrate an immunologic advantage to empirically deworming ART-naïve individuals, but suggest that certain sub-populations may benefit.

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