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Economic analysis of dengue prevention and case management in the Maldives

27 September 2018 - 9:00pm

by Mathieu Bangert, Aishath Thimna Latheef, Shushil Dev Pant, Ibrahim Nishan Ahmed, Sana Saleem, Fathimath Nazla Rafeeq, Moomina Abdulla, Fathimath Shamah, Ahmed Jamsheed Mohamed, Christopher Fitzpatrick, Raman Velayudhan, Donald S. Shepard

As tourism is the mainstay of the Maldives’ economy, this country recognizes the importance of controlling mosquito-borne diseases in an environmentally responsible manner. This study sought to estimate the economic costs of dengue in this Small Island Developing State of 417,492 residents. The authors reviewed relevant available documents on dengue epidemiology and conducted site visits and interviews with public health offices, health centers, referral hospitals, health insurers, and drug distribution organizations. An average of 1,543 symptomatic dengue cases was reported annually from 2011 through 2016. Intensive waste and water management on a resort island cost $1.60 per occupied room night. Local vector control programs on inhabited islands cost $35.93 for waste collection and $7.89 for household visits by community health workers per person per year. Ambulatory care for a dengue episode cost $49.87 at a health center, while inpatient episodes averaged $127.74 at a health center, $1,164.78 at a regional hospital, and $1,655.50 at a tertiary referral hospital. Overall, the cost of dengue illness in the Maldives in 2015 was $2,495,747 (0.06% of gross national income, GNI, or $6.10 per resident) plus $1,338,141 (0.03% of GNI or $3.27 per resident) for dengue surveillance. With tourism generating annual income of $898 and tax revenues of $119 per resident, results of an international analysis suggest that the risk of dengue lowers the country’s gross annual income by $110 per resident (95% confidence interval $50 to $160) and its annual tax receipts by $14 per resident (95% confidence interval $7 to $22). Many innovative vector control efforts are affordable and could decrease future costs of dengue illness in the Maldives.

Genetic diversity, infection prevalence, and possible transmission routes of <i>Bartonella</i> spp. in vampire bats

27 September 2018 - 9:00pm

by Daniel J. Becker, Laura M. Bergner, Alexandra B. Bentz, Richard J. Orton, Sonia Altizer, Daniel G. Streicker

Bartonella spp. are globally distributed bacteria that cause endocarditis in humans and domestic animals. Recent work has suggested bats as zoonotic reservoirs of some human Bartonella infections; however, the ecological and spatiotemporal patterns of infection in bats remain largely unknown. Here we studied the genetic diversity, prevalence of infection across seasons and years, individual risk factors, and possible transmission routes of Bartonella in populations of common vampire bats (Desmodus rotundus) in Peru and Belize, for which high infection prevalence has previously been reported. Phylogenetic analysis of the gltA gene for a subset of PCR-positive blood samples revealed sequences that were related to Bartonella described from vampire bats from Mexico, other Neotropical bat species, and streblid bat flies. Sequences associated with vampire bats clustered significantly by country but commonly spanned Central and South America, implying limited spatial structure. Stable and nonzero Bartonella prevalence between years supported endemic transmission in all sites. The odds of Bartonella infection for individual bats was unrelated to the intensity of bat flies ectoparasitism, but nearly all infected bats were infested, which precluded conclusive assessment of support for vector-borne transmission. While metagenomic sequencing found no strong evidence of Bartonella DNA in pooled bat saliva and fecal samples, we detected PCR positivity in individual saliva and feces, suggesting the potential for bacterial transmission through both direct contact (i.e., biting) and environmental (i.e., fecal) exposures. Further investigating the relative contributions of direct contact, environmental, and vector-borne transmission for bat Bartonella is an important next step to predict infection dynamics within bats and the risks of human and livestock exposures.

Atypical leishmaniasis: A global perspective with emphasis on the Indian subcontinent

27 September 2018 - 9:00pm

by Lovlesh Thakur, Kiran K. Singh, Vinay Shanker, Ajeet Negi, Aklank Jain, Greg Matlashewski, Manju Jain

Background

Among the neglected tropical diseases, leishmaniasis continues to be prevalent in many tropical and subtropical countries despite international, national, and local efforts towards its control and elimination over the last decade. This warrants a critical evaluation of such factors as under-reporting, asymptomatic infections, post kala azar dermal leishmaniasis (PKDL) cases, and drug resistance. In this review, we highlight lesser-understood atypical presentations of the disease involving atypical parasite strains against a background of classical leishmaniasis with a focus on the Indian subcontinent.

Methods and findings

A literature review based on endemic areas, the nature of disease manifestation, and underlying causative parasite was performed with data collected from WHO reports for each country. Searches on PubMed included the term ‘‘leishmaniasis” and “leishmaniasis epidemiology” alone and in combination with each of the endemic countries, Leishmania species, cutaneous, visceral, endemic, non-endemic, typical, classical, atypical, and unusual with no date limit and published in English up to September 2017. Our findings portray a scenario with a wider distribution of the disease in new endemic foci, with new discoveries of parasite-driven atypical disease manifestations in different regions of the world. Unlike the classical picture, some Leishmania species are associated with more than one disease presentation, e.g., the L. donovani complex, generally associated with the visceral form, is now also associated with a cutaneous disease presentation, while L. tropica species complex, known to cause cutaneous disease, can cause viscerotropic disease. This phenomenon points towards the discovery of novel parasite variants as etiologic agents of atypical disease manifestations and represents an excellent opportunity to identify and study genes that control disease virulence and tropism.

Conclusions

The increased recognition of atypical leishmaniasis as an outcome of parasite variants has major implications for leishmaniasis control and elimination. Identifying molecular correlates of parasite isolates from distinct regions associated with different disease phenotypes is required to understand the current epidemiology of leishmaniasis in regions with atypical disease.

Standardising visual control devices for Tsetse: East and Central African Savannah species <i>Glossina swynnertoni</i>, <i>G</i>. <i>morsitans centralis</i> and <i>G</i>. <i>pallidipes</i>

25 September 2018 - 9:00pm

by Mechtilda Byamungu, Tusevo Zacarie, Alexis Makumyaviri M’Pondi, Philémon Mansinsa Diabakana, Andrew McMullin, Thomas Kröber, Steve Mihok, Patrick M. Guerin

Background

This study focused on the savannah tsetse species Glossina swynnertoni and G. morsitans centralis, both efficient vectors of human and animal trypanosomiasis in, respectively, East and Central Africa. The aim was to develop long-lasting, practical and cost-effective visually attractive devices that induce the strongest landing responses in these two species for use as insecticide-impregnated tools in population suppression.

Methods and findings

Trials were conducted in different seasons and years in Tanzania (G. swynnertoni) and in Angola and the Democratic Republic of the Congo (DRC, G. m. centralis) to measure the performance of traps (pyramidal and epsilon) and targets of different sizes, shapes and colours, with and without chemical baits, at different population densities and under different environmental conditions. Adhesive film was used to catch flies landing on devices at the remote locations to compare tsetse-landing efficiencies. Landing rates by G. m. centralis in both Angola and the DRC were highest on blue-black 1 m2 oblong and 0.5 m2 square and oblong targets but were not significantly different from landings on the pyramidal trap. Landings by G. swynnertoni on 0.5 m2 blue-black oblong targets were likewise not significantly lower than on equivalent 1 m2 square targets. The length of target horizontal edge was closely correlated with landing rate. Blue-black 0.5 m2 targets performed better than equivalents in all-blue for both G. swynnertoni and G. m. centralis, although not consistently. Baiting with chemicals increased the proportion of G. m. centralis entering pyramidal traps.

Conclusions

This study confirms earlier findings on G. swynnertoni that smaller visual targets, down to 0.5 m2, would be as efficient as using 1 m2 targets for population management of this species. This is also the case for G. m. centralis. An insecticide-impregnated pyramidal trap would also constitute an effective control device for G. m. centralis.

Impact of ivermectin administered for scabies treatment on the prevalence of head lice in Atoifi, Solomon Islands

25 September 2018 - 9:00pm

by Suny Coscione, Tommy Esau, Esau Kekeubata, Jason Diau, Rowena Asugeni, David MacLaren, Andrew C. Steer, Christian Kositz, Michael Marks

Background

Scabies and head lice are ubiquitous ectoparasitic infestations that are common across the Pacific Islands. Ivermectin is an effective treatment for both conditions, although the doses used vary. At a community level, mass drug administration (MDA) with ivermectin is an effective strategy to decrease prevalence of scabies. To what extent MDA with ivermectin will also reduce prevalence of head lice is unknown.

Methodology

Head lice prevalence was assessed before and after MDA with oral ivermectin (at a dose of 200 micrograms per kilogram of body weight) administered on day 1 and day 8. The primary outcome was the change in prevalence of head louse infestation at two weeks compared to baseline. Longer term efficacy was assessed three months after MDA.

Results

118 participants were enrolled. Baseline prevalence of active head louse infestation was 25.4% (95% CI 18.4–34.0). At three-month follow-up, prevalence was 7.5% (95% CI 2.7–12.3), a relative reduction of 70.6% (95% CI 72.7%-91.4%, p <0.001). Head louse infestation was associated with younger age (age ≤10 years: prevalence 46.7%; adjusted odds ratio compared to adults of 7.2, 95%CI 2.0–25.9) and with having at least one other member of the household with active head louse infestation (adjusted odds ratio 4.3, 95%CI 1.7–11.1).

Conclusions

Head louse infestation is common in the Solomon Islands. This proof of principle study shows that oral ivermectin at a dose of 200 micrograms per kilogram can reduce the burden of active head louse infestation, offering an additional collateral benefit of MDA with ivermectin for scabies control.

Trial registration

ClinicalTrials.gov NCT03236168.

Filarial infection during pregnancy has profound consequences on immune response and disease outcome in children: A birth cohort study

25 September 2018 - 9:00pm

by Madhusmita Bal, Manoranjan Ranjit, Ashok K. Satapathy, Hemant K. Khuntia, Sanghamitra Pati

Background

Current Global Program to Eliminate Lymphatic Filariasis (GPELF) that prohibits pregnant mothers and children below two years of age from coverage targeted interruption of transmission after 5–6 rounds of annual mass drug administration (MDA). However, after more than 10 rounds of MDA in India the target has not been achieved, which poses challenge to the researchers and policy makers. Several studies have shown that in utero exposure to maternal filarial infections plays certain role in determining the susceptibility and disease outcome in children. But the mechanism of which has not been studied extensively. Therefore the present study was undertaken to understand the mechanism of immune modulation in children born to filarial infected mother in a MDA ongoing area.

Methodology and principal finding

To our knowledge this is the first study to conduct both cellular and humoral immunological assays and follow up the children until older age in a W bancrofti endemic area,where the microfilariae (Mf) rate has come down to <1% after 10 rounds of MDA. A total 57 (32: born to infected, 25: born to uninfected mother) children were followed up. The infection status of children was measured by presence of Mf and circulating filarial antigen (CFA) assay. Filaria specific IgG1, IgG2, IgG3 and IgG4 responses were measured by ELISA. Plasma level of IL-10 and IFN-γ were evaluated by using commercially available ELISA kit. The study reveals a high rate of acquisition of filarial infection among the children born to infected mother compared to uninfected mothers. A significantly high level of IgG1 and IgG4 was observed in children born to infected mother, whereas high level of IgG3 was marked in children born to uninfected mother. Significantly high level of IL-10 positively correlated with IgG4 have been observed in infected children born to infected mother, while high level of IFN-γ positively correlated with IgG3 was found in infection free children born to mother free from infection at the time of pregnancy. Moreover a negative correlation between IL-10and IFN-γ has been observed only among the infected children born to infected mother.

Significance conclusion

The study shows a causal association between maternal filarial infection and impaired or altered immune response in children more susceptible to filarial infection during early childhood. As lymphatic damage that commences in childhood during asymptomatic stage has major implications from public health point of view, understanding maternal programming of the newborn immune system could provide a basis for interventions promoting child health by implementing MDA campaigns towards all women of childbearing age and young children in achieving the target of global elimination of LF.

Development and validation of a scale to assess attitudes of health care providers towards persons affected by leprosy in southern India

25 September 2018 - 9:00pm

by Govindarajulu Srinivas, Shuba Kumar, Rani Mohanraj, Geethalakshmi Sekkizhar, Thirumugam Muthuvel, Vivek Lal, Burkard Koemm, Christa Kasang

Introduction

Assessment of attitude of health care professionals is important as negative attitude could constitute a major deterrent to care-seeking by persons affected by neglected tropical diseases (NTDs) such as leprosy. Leprosy continues to pose a major disease burden in India with an annual new case detection rate of 10.17 per 100,000 population. This paper reports on the development and validation of a culturally appropriate scale to measure attitude of health care providers (HCPs) towards persons affected by leprosy in Tamil Nadu, India.

Methodology/Principal findings

The Affective, Behavioural and Cognitive (ABC) model of attitudes guided the development of the scale. Steps in scale development included qualitative interviews and focus group discussions with medical officers and paramedical staffs selected from high prevalence districts in Tamil Nadu, India which informed the development of the draft scale. Reviews of existing attitude questionnaires in related areas further contributed to scale development and together helped to generate a large pool of items which was then subjected to Thurston’s scaling method for selection of items from this pool. Face and content validity were obtained, following which internal consistency and test, re-test reliability were assessed. Scaling exercise resulted in 11 items being discarded from an initial pool of 38, owing to the poor agreement among experts regarding relevance. Face and content validity were good with experts endorsing relevance and applicability of items. The intra-class correlation coefficient (ICC) for test re-test reliability of the 27 item scale was 0.6 (95% CI: 0.20–0.78) indicating marginal intra-class correlation. The overall Cronbach’s alpha was 0.85 while the alphas for each of the affective and behavioural components was good at 0.78 and 0.69 respectively indicating a good degree of consistency and homogeneity between items but the alpha for the cognitive component was low at 0.53.

Conclusions

The ABC model of attitudes guided the development of the scale, ensured a mix of 27 items tapping into the three domains of Affect, Behaviour and Cognition which best explained the attitude construct. With good validity and alphas for each of the affective, behavioural components and overall alpha estimates, this scale can be a valuable tool to provide accurate estimates of the true attitudes held by HCPs. This, in turn, would be useful to obtain insights for appropriate intervention programmes that would help change negative attitudes of HCPs towards persons affected by leprosy. With some adaptations, the scales can be validated for other NTDs as well.

Reactive and pre-emptive vaccination strategies to control hepatitis E infection in emergency and refugee settings: A modelling study

25 September 2018 - 9:00pm

by Ben S. Cooper, Lisa J. White, Ruby Siddiqui

Background

Hepatitis E Virus (HEV) is the leading cause of acute viral hepatitis globally. Symptomatic infection is associated with case fatality rates of ~20% in pregnant women and it is estimated to account for ~10,000 annual pregnancy-related deaths in southern Asia alone. Recently, large and well-documented outbreaks with high mortality have occurred in displaced population camps in Sudan, Uganda and South Sudan. However, the epidemiology of HEV is poorly defined, and the value of different immunisation strategies in outbreak settings uncertain. We aimed to estimate the critical epidemiological parameters for HEV and to evaluate the potential impact of both reactive vaccination (initiated in response to an epidemic) and pre-emptive vaccination.

Methods

We analysed data from one of the world's largest recorded HEV epidemics, which occurred in internally-displaced persons camps in Uganda (2007–2009), using transmission dynamic models to estimate epidemiological parameters and assess the potential impact of reactive and pre-emptive vaccination strategies.

Results

Under baseline assumptions we estimated the basic reproduction number of HEV in three separate camps to range from 3.7 (95% Credible Interval [CrI] 2.8, 5.1) to 8.5 (5.3, 11.4). Mean latent and infectious periods were estimated to be 34 (95% CrI 28, 39) and 40 (95% CrI 23, 71) days respectively.Assuming 90% vaccine coverage, reactive two-dose vaccination of those aged 16–65 years excluding pregnant women (for whom vaccine is not licensed), if initiated after 50 reported cases, led to mean camp-specific reductions in mortality of 10 to 29%. Pre-emptive vaccination with two doses reduced mortality by 35 to 65%. Both strategies were more effective if coverage was extended to groups for whom the vaccine is not currently licensed. For example, two dose pre-emptive vaccination, if extended to include pregnant women, led to mean reductions in mortality of 66 to 82%.

Conclusions

HEV has a high transmission potential in displaced population settings. Substantial reductions in mortality through vaccination are expected, even if used reactively. There is potential for greater impact if vaccine safety and effectiveness can be established in pregnant women.

Nanoparticle Delivery of a Tetravalent E Protein Subunit Vaccine Induces Balanced, Type-Specific Neutralizing Antibodies to Each Dengue Virus Serotype

24 September 2018 - 9:00pm

by Stefan W. Metz, Ashlie Thomas, Alex Brackbill, Yi Xianwen, Michele Stone, Katie Horvath, Michael J. Miley, Chris Luft, Joseph M. DeSimone, Shaomin Tian, Aravinda M. de Silva

Dengue virus (DENV) is the causative agent of dengue fever and dengue hemorrhagic shock syndrome. Dengue vaccine development is challenging because of the need to induce protection against four antigenically distinct DENV serotypes. Recent studies indicate that tetravalent DENV vaccines must induce balanced, serotype-specific neutralizing antibodies to achieve durable protective immunity against all 4 serotypes. With the leading live attenuated tetravalent DENV vaccines, it has been difficult to achieve balanced and type-specific responses to each serotype, most likely because of unbalanced replication of vaccine viral strains. Here we evaluate a tetravalent DENV protein subunit vaccine, based on recombinant envelope protein (rE) adsorbed to the surface of poly (lactic-co-glycolic acid) (PLGA) nanoparticles for immunogenicity in mice. In monovalent and tetravalent formulations, we show that particulate rE induced higher neutralizing antibody titers compared to the soluble rE antigen alone. Importantly, we show the trend that tetravalent rE adsorbed to nanoparticles stimulated a more balanced serotype specific antibody response to each DENV serotype compared to soluble antigens. Our results demonstrate that tetravalent DENV subunit vaccines displayed on nanoparticles have the potential to overcome unbalanced immunity observed for leading live-attenuated vaccine candidates.

An <i>Anopheles aquasalis</i> GATA factor Serpent is required for immunity against <i>Plasmodium</i> and bacteria

24 September 2018 - 9:00pm

by Ana C. Bahia, Marina S. Kubota, Jayme A. Souza-Neto, Leonardo B. Koerich, Ana Beatriz Barletta, Helena R. C. Araújo, Caroline M. Gonçalves, Cláudia M. Ríos-Velásquez, Paulo F. P. Pimenta, Yara M. Traub-Csekö

Innate immunity is an ancient and conserved defense system that provides an early effective response against invaders. Many immune genes of Anopheles mosquitoes have been implicated in defense against a variety of pathogens, including plasmodia. Nevertheless, only recent work identified some immune genes of Anopheles aquasalis mosquitoes upon P. vivax infection. Among these was a GATA transcription factor gene, which is described here. This is an ortholog of GATA factor Serpent genes described in Drosophila melanogaster and Anopheles gambiae. Gene expression analyses showed an increase of GATA-Serpent mRNA in P. vivax-infected A. aquasalis and functional RNAi experiments identified this transcription factor as an important immune gene of A. aquasalis against both bacteria and P. vivax. Besides, we were able to identify an effect of GATA-Serpent knockdown on A. aquasalis hemocyte proliferation and differentiation. These findings expand our understanding of the poorly studied A. aquasalis-P. vivax interactions and uncover GATA-Serpent as a key player of the mosquito innate immune response.

Evaluation of antigen-specific immune responses for leprosy diagnosis in a hyperendemic area in China

24 September 2018 - 9:00pm

by Xiaohua Chen, Yuan-Gang You, You-Hua Yuan, Lian Chao Yuan, Ying Zhang, Wen Yan

Objective

To evaluate antigen-specific immune responses for leprosy diagnosis in a hyperendemic area in China.

Methods

Eighty-three leprosy patients and 161 non-leprosy controls were enrolled from Hani-yi Autonomous Prefecture of Honghe, Yunnan Province, China. Leprosy patients were divided into multibacillary (MB, n = 38), paucibacillary (PB, n = 23), and post-multi-drug therapy (MDT, n = 22) groups. Controls were divided into the following groups: healthy household contacts (HHC, n = 119), tuberculosis (TB, n = 11), and endemic controls (EC, n = 31). The NDO-LID Rapid Test, M. leprae antigen-specific ELISA and antigen-specific IFN-γ secretion in a whole blood assay (WBA) were used to evaluate these subjects.

Results

The NDO-LID Rapid Test achieved higher positive response rates in MB than in PB patients[94.7%(36/38) vs 65.2%(15/23)], and these rates were higher than those observed by ELISA using anti-LID-1[92.1%(35/38) vs 52.2%(12/23)], anti-NDO-LID[92.1%(35/38) vs 47.8% (11/23)], and anti-ND-O-BSA[89.5%(34/38) vs 60.9%(14/23)]. However, the NDO-LID Rapid Test also showed a higher positive response rate in the EC group (33.3%,10/31), which was higher than the rates observed for anti-NDO-LID (12.9%,4/31) and anti-ND-O-BSA (16.1%,5/31). M. leprae antigen-specific ELISA demonstrated relatively high specificity (86.84–97.37%) but low sensitivity (15.97–72.73%) in discriminating between leprosy patients and non-leprosy controls by ROC curve analysis. In contrast, M. leprae antigen-specific IFN-γ secretion detection achieved higher positive response rates in PB than in MB patients (positive ratio of MB vs PB: 40% vs 56% for LID-1, 28.6% vs 47.8% for ML89, 31.4% vs 60.7% for ML2044, and 31.4 vs 47.8% for ML2028) and could distinguish MB from EC when stimulated with ML89(AUC = 0.6664) and PB fromTB when stimulated with ML2044 and ML2028(AUC = 0.7549 and 0.7372, respectively).

Conclusion

The NDO-LID Rapid Test and M. leprae antigen-specific ELISA are useful tools to assist in the diagnosis of leprosy patients, especially MB patients, although the former had higher sensitivity but lower specificity than the latter. M. leprae antigen-specific IFN-γ release assessed by WBA has diagnostic value for distinguishing PB from TB but not for distinguishing PB from HHC or EC. Screening novel M. leprae-specific antigens, combining different M. leprae antigens and a multi-cytokine analyte model may be needed for more effective diagnosis of leprosy.

Phylogeography and demographic history of the Chagas disease vector <i>Rhodnius nasutus</i> (Hemiptera: Reduviidae) in the Brazilian Caatinga biome

24 September 2018 - 9:00pm

by Tatiana Peretolchina, Márcio G. Pavan, Jessica Corrêa-Antônio, Rodrigo Gurgel-Gonçalves, Marli M. Lima, Fernando A. Monteiro

Background

Rhodnius nasutus, a vector of the etiological agent Trypanosoma cruzi, is one of the epidemiologically most relevant triatomine species of the Brazilian Caatinga, where it often colonizes rural peridomestic structures such as chicken coops and occasionally invades houses. Historical colonization and determination of its genetic diversity and population structure may provide new information towards the improvement of vector control in the region. In this paper we present thoughtful analyses considering the phylogeography and demographic history of R. nasutus in the Caatinga.

Methodology/Principal findings

A total of 157 R. nasutus specimens were collected from Copernicia prunifera palm trees in eight geographic localities within the Brazilian Caatinga biome, sequenced for 595-bp fragment of the mitochondrial cytochrome b gene (cyt b) and genotyped for eight microsatellite loci. Sixteen haplotypes were detected in the cyt b sequences, two of which were shared between different localities. Molecular diversity indices exhibited low diversity and a haplotype network revealed low divergence among R. nasutus sequences, with two central haplotypes shared by five of the eight populations analyzed. The demographic model that better represented R. nasutus population dynamics was the exponential growth model. Results of the microsatellite data analyses indicated that the entire population is comprised of four highly differentiated groups, with no obvious contemporary geographic barriers that could explain the population substructure detected. A complex pattern of migration was observed, in which a western Caatinga population seems to be the source of emigrants to the eastern populations.

Conclusions/Significance

R. nasutus that inhabit C. prunifera palms do not comprise a species complex. The species went through a population expansion at 12–10 ka, during the Holocene, which coincides with end of the largest dry season in South America. It colonized the Caatinga in a process that occurred from west to east in the region. R. nasutus is presently facing an important ecological impact caused by the continuous deforestation of C. prunifera palms in northeast Brazil. We hypothesize that this ecological disturbance might contribute to an increase in the events of invasion and colonization of human habitations.

Anti-parasitic effect of vitamin C alone and in combination with benznidazole against <i>Trypanosoma cruzi</i>

21 September 2018 - 9:00pm

by Vanesa Puente, Agostina Demaria, Fernanda M. Frank, Alcira Batlle, Maria Elisa Lombardo

Background

Drugs currently used for the treatment of Chagas’ disease, nifurtimox and benznidazole, have a limited effectiveness and toxic side effects. With the aim of finding new therapeutic approaches, in vitro and in vivo anti-Trypanosoma cruzi activity of vitamin C alone and combined with benznidazole were investigated.

Methodology/Principal findings

The trypanocidal activity on epimastigote and trypomastigote forms was evaluated by counting parasites in a Neubauer chamber after treatment with the compounds. For the amastigote stage, transgenic parasites expressing β-galactosidase were used and quantified by measuring the β-galactosidase activity. The cytotoxicity of compounds was tested on Vero cells. The redox state of the parasite was evaluated by determining the reduced thiol levels (spectrophotometric assay) and the intracellular oxidative state (by flow cytometry). The in vivo trypanocidal activity was evaluated on a murine model of Chagas’ disease. The trypanocidal activity of vitamin C and benznidazole was similar for the three parasite forms. When combining both drugs, vitamin C did not induce any change in the antiparasitic activity of benznidazole on trypomastigotes; however, on mammal cells, vitamin C diminished the cytotoxicity degree of benznidazole. Two mechanisms of action may be postulated for vitamin C: a lethal pro-oxidant effect on the parasite when used alone, and an antioxidant effect, when combined with benznidazole. A similar behavior was observed on infected mice; i.e., parasite counts in infected mice treated with vitamin C were lower than that of the control group. Animals treated with benznidazole presented lower parasitemia levels, as compared with those treated with vitamin C alone. Again, vitamin C did not cause any effect on the antiparasitic profile of benznidazole. Even though a combined treatment was employed, the antioxidant effect of vitamin C on the host was evidenced; a 100% survival was observed and the weight loss occurring during the acute phase of the infection was reduced.

Conclusions/Significance

Based on these results, the combination of vitamin C with benznidazole could be considered as an alternative treatment for Chagas’ disease. These preliminary results encourage further research to improve the treatment of Chagas’ disease.

Spatial distribution of <i>Taenia solium</i> exposure in humans and pigs in the Central Highlands of Vietnam

20 September 2018 - 9:00pm

by Dinh Ng-Nguyen, Rebecca Justine Traub, Van-Anh Thi Nguyen, Kathleen Breen, Mark Anthony Stevenson

Background

Taenia solium, a pork-borne parasitic zoonosis, is the cause of taeniasis and cysticercosis in humans. In Vietnam, poor sanitation, the practice of outdoor defecation and consumption of raw/undercooked pork have been associated with infection/exposure to T. solium in both humans and pigs. The broad-scale geographic distribution of the prevalence of T. solium varies throughout the country with infection restricted to isolated foci in the north and a more sporadic geographic distribution in the Central Highlands and the south. While cross-sectional studies have allowed the broad-scale geographic distribution of T. solium to be described, details of the geographic distribution of T. solium at finer spatial scales have not been described in detail. This study provides a descriptive spatial analysis of T. solium exposure in humans and pigs and T. solium taeniasis in humans within individual households in village communities of Dak Lak in the Central Highlands of Vietnam.

Methodology/Principal findings

We used Ripley’s K-function to describe spatial dependence in T. solium exposure positive and negative human and pig households and T. solium taeniasis exposure positive and negative households in villages within the districts of Buon Don, Krong Nang and M’Drak of Dak Lak province in the Central Highlands of Vietnam. The prevalence of exposure to T. solium in pigs in Dak Lak province was 9 (95% CI 5 to 17) cases per 1000 pigs at risk. The prevalence of exposure to the parasite in humans was somewhat higher at 5 (95% CI 3 to 8) cases per 100 individuals at risk. Spatial aggregations of T. solium exposure-positive pig and human households occurred in some, but not all of the villages in the three study districts. Human exposure-positive households were found to be aggregated within a distance of 200 to 300 m in villages in Krong Nang district compared with distances of up to 1200 m in villages in M’Drak district. Although this study demonstrated the aggregation of households in which either T. solium exposure- or taeniasis-positive individuals were present, we were unable to identify an association between the two due to the very low number of T. solium taeniasis-positive households.

Conclusions

Spatial aggregations of T. solium exposure-positive pig and human households occurred in some, but not all of the villages in the three study districts. We were unable to definitively identify reasons for these findings but speculate that they were due to a combination of demographic, anthropological and micro-environmental factors. To more definitively identify characteristics that increase cysticercosis risk we propose that cross-sectional studies similar in design to that described in this paper should be applied in other provinces of Vietnam.

Detection and distribution of Sca autotransporter protein antigens in diverse isolates of <i>Orientia tsutsugamushi</i>

20 September 2018 - 9:00pm

by Munegowda C. Koralur, Arunachalam Ramaiah, Gregory A. Dasch

Orientia tsutsugamushi (Ots) frequently causes severe scrub typhus infections in the Asia-Pacific region. Korean investigators have demonstrated that Ots encodes five different autotransporter domain (ATD) proteins (ScaA-ScaE). ScaA functions as an adhesin and confers protective immunity in a lethal mouse model of Ots infection. Specific antibodies are detected against ScaA and ScaC in Korean scrub typhus patients. However, there is limited data on the distribution of the Sca protein genes in diverse isolates of Ots. By BLAST analysis with the conserved beta barrel autotransporter domain (ATD) regions of the sca proteins, we discovered a sixth gene scaF among 3 of 10 new partial Ots genome sequences available at NCBI GenBank (Sido, Karp, AFSC7). We designed two to seven specific TaqMan assays to detect the ATD for each of the six sca genes. The TaqMan assays among those for each sca gene which gave the greatest sensitivity and linearity with DNA log dilutions were then used for screening DNAs from Ots isolates grown in L929 mouse cells for sca genes. The sca prevalence survey was performed for all six sca genes with 178 DNAs from isolates from 12 countries. The survey results were confirmed by conventional PCR with primers from conserved regions of the passenger domains (PD) and ATD of the sca proteins. The ATD was highly conserved between the DNAs of different genotypes compared to the sca PD but each TaqMan assay was sca specific. The percentage positivity for 56 kDa and scaA genes in the 178 DNAs using Ha primers was 59.6% and 62.4%, respectively. Our scaA conventional ATD PCR assay was positive in 98.3% but scaA was present in all 178 DNAs (100%) by ATD TaqMan. scaB, scaC, scaD, scaE and scaF were detected in 33.7%, 97.8%, 93.8%, 97.2% and 43.3% isolates by ATD TaqMan, respectively. The ATDs of Ots sca genes are thus sufficiently conserved between different genotypes for molecular assay design. Four sca genes are widely distributed among diverse Ots isolates from diverse geographical areas. scaB and scaF were detected in fewer Ots isolates and absent from some available genome sequences. Whether the utility of the ScaA, ScaC, ScaD, and ScaE antigenic passenger protein domains exceeds that of the mixed 56 kDa type surface antigens of Ots now used in combination diagnostic assays needs to be determined before they can be considered as suitable alternative serological antigens for diagnosis of scrub typhus.

Molecular characterization and phylogenetic analysis of dengue viruses imported into Taiwan during 2011-2016

20 September 2018 - 9:00pm

by Cheng-Fen Yang, Shu-Fen Chang, Tung-Chien Hsu, Chien-Ling Su, Tzy-Chen Wang, Shih-Hung Lin, Su-Lin Yang, Chien-Chou Lin, Pei-Yun Shu

A total of 1,596 laboratory-confirmed imported dengue cases were identified in Taiwan during 2011–2016. Most of the imported cases arrived from Southeast Asia as well as the Indian subcontinent, the Pacific region, Latin America, Australia and Africa. Phylogenetic analyses of the complete envelope protein gene sequences from 784 imported dengue virus (DENV) isolates were conducted, and the results suggest that the DENV-1 genotype I and DENV-2 Cosmopolitan genotype comprise the predominant serotype/genotype of DENV strains circulating in Southeast Asia. The DENV-1 genotype III, DENV-3 genotype III and DENV-4 genotype I and II strains were found to be newly emerging in several Southeast Asian countries. Our results also showed that geographical restrictions of DENV-1 genotype I, DENV-1 genotype III and DENV-2 Cosmopolitan genotype are becoming blurred, indicating the extensive introductions and continuous expansions of DENV strains between nations in Southeast Asia. In this study, we present the geographic distribution and dynamic transmission of DENV strains circulating in Southeast Asian countries. In addition, we demonstrated local dengue epidemics caused by several imported DENV strains in Taiwan during 2011–2016.

Health preparedness plan for dengue detection during the 2020 summer Olympic and Paralympic games in Tokyo

20 September 2018 - 9:00pm

by Naoki Yanagisawa, Koji Wada, John D. Spengler, Ramon Sanchez-Pina

Background

Participants in mass gathering events are at risk of acquiring imported and locally endemic infectious diseases. The 2014 dengue outbreak in Tokyo gathered attention since it was the first time in 70 years for Japan to experience an autochthonous transmission. Preparation for emerging infectious threats is essential even in places where these outbreaks have been largely unknown. The aim of this study is to identify strategies for early detection and prevention of dengue infection during the 2020 summer Olympics and Paralympics in Tokyo.

Methodology/Principal findings

We modified and adapted the failure mode and effect analysis (FMEA) methodology, generally used in industrial manufacturing, to examine the current controls for dengue detection and assessment. Information on existing controls were obtained from publicly available resources. Our analysis revealed that the national infectious disease control system to detect dengue in Japan is robust. However, in the case of large assemblies of international visitors for special events when the spread of communicable and vector-borne diseases increases, there are three main gaps that could be reinforced. First, cyclical training or a certification program on tropical disease management is warranted for physicians, especially those working in non-infectious disease-designated hospitals or clinics. Second, multi-language communication methods need to be strengthened especially in the health and hospitality sector. Third, owners of accommodations should consider incorporating a formal tropical disease-training program for their staff members and have a contingency plan for infectious disease-suspected travelers.

Conclusions/Significance

Our findings may facilitate physicians and public health officials where new controls would be beneficial for the 2020 summer Olympics and Paralympics. The FMEA framework has the potential to be applied to other infectious diseases, not just dengue.

Coinfections and comorbidities in African health systems: At the interface of infectious and noninfectious diseases

20 September 2018 - 9:00pm

by Derick Nii Mensah Osakunor, David Moinina Sengeh, Francisca Mutapi

There is a disease epidemiological transition occurring in Africa, with increasing incidence of noninfectious diseases, superimposed on a health system historically geared more toward the management of communicable diseases. The persistence and sometimes emergence of new pathogens allows for the occurrence of coinfections and comorbidities due to both infectious and noninfectious diseases. There is therefore a need to rethink and restructure African health systems to successfully address this transition. The historical focus of more health resources on infectious diseases requires revision. We hypothesise that the growing burden of noninfectious diseases may be linked directly and indirectly to or further exacerbated by the existence of neglected tropical diseases (NTDs) and other infectious diseases within the population. Herein, we discuss the health burden of coinfections and comorbidities and the challenges to implementing effective and sustainable healthcare in Africa. We also discuss how existing NTD and infectious disease intervention programs in Africa can be leveraged for noninfectious disease intervention. Furthermore, we explore the potential for new technologies—including artificial intelligence and multiplex approaches—for diagnosis and management of chronic diseases for improved health provision in Africa.

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