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Community based cross sectional study of podoconiosis and associated factors in Dano district, Central Ethiopia

28 January 2019 - 10:00pm

by Feven Dejene, Hailu Merga, Henok Asefa

Background

Podoconiosis, affects lower limb, is an entirely preventable non-communicable tropical disease common in low income countries. Globally it is estimated that there are 4 million peoples with podoconiosis and nationally it is estimated that there are 1.56 million cases of podoconiosis. Even though nationwide mapping has been conducted including the current district under investigation, there are no studies conducted to identify factors associated with podoconiosis in the district. Hence, this study was aimed to determine the prevalence of podoconiosis and associated factors in the west Shewa of Dano district community.

Method

A community based cross sectional study was conducted from March 1 to 26, 2018. Seven kebeles out of the total of twenty-three kebeles found in the district were selected randomly. The total sample size was allocated by probability proportional to size to each kebele based on the number of households they had. Then, systematic random sampling was employed to select 652 study participants from the seven kebeles. Data was collected using interviewer administered structured questionnaire and observation. In addition, a blood sample was collected from the study subjects who had leg swelling for ruling out lymphedema due to lymphatic filarasis by using Immunochromatographic test card. Podoconiosis case was defined as bilateral but asymmetric swelling which develop first in the foot often confined to the lower leg and negative result for immune-chromatographic test (ICT card). The prevalence of podoconiosis was determined and multiple logistic regression model was fitted using SPSS version 23 to identify factors associated with podoconiosis.

Result

The prevalence of podoconiosis in Dano district was found to be 6.3% (95%CI: 5.8, 6.8). Age at first shoe wearing (AOR = 1.08,95% CI = 1.06–1.11), washing practice of feet by water only (AOR = 3.68, 95% CI = 1.47–9.24) and not wearing shoe daily (AOR = 9.32, 95% CI = 4.27–20.4) were found to be significantly associated with increased odds of podoconiosis.

Conclusion

This study revealed that there was significant burden of podoconiosis in the study area. Age at first shoe wearing, washing practice and frequency of shoe wearing were associated with the development of podoconiosis disease. Modalities to enhance the shoe wearing behaviour of the communities should be planned by high level decision makers working in the area of Health. Moreover, collaboration between local government and non-government stakeholders, and integration with existing programs addressing foot hygiene which involves washing feet with soap and water needs to be addressed.

Genetic variation and phylogeography of the <i>Triatoma dimidiata</i> complex evidence a potential center of origin and recent divergence of haplogroups having differential <i>Trypanosoma cruzi</i> and DTU infections

28 January 2019 - 10:00pm

by Angélica Pech-May, Carlos Jesús Mazariegos-Hidalgo, Amaia Izeta-Alberdi, Sury Antonio López-Cancino, Ezequiel Tun-Ku, Keynes De la Cruz-Félix, Carlos N. Ibarra-Cerdeña, Raúl E. González Ittig, Janine M. Ramsey

The population genetics of Triatoma dimidiata haplogroups was analyzed at landscape and sub-regional scales in Chiapas and regional level across the Mexican Neotropics, and phylogeography of the complex was re-analyzed across its complete geographic range. Two contiguous fragments of the ND4 gene were analyzed due to bias from differential haplogroup specificity using a previously designed sequence. At both landscape (anthropic modification gradient) and regional (demographic, fragmentation, biogeographic, climate) scales, lowest T. dimidiata genetic diversity occurs where there is greatest historical anthropic modification, and where T. cruzi infection prevalence is significantly highest. Trypanosoma cruzi prevalence was significantly higher than expected in haplogroups 1 and 3, while lower than expected in haplogroup 2. There was also a significant difference of DTUI and DTUVI infection frequencies in both haplogroups 1 and 3, while no difference of either in haplogroup 2. All haplogroups from the Mexican Neotropics had moderate to high haplotype diversity, while greatest genetic differentiation was between haplogroups 1 and 3 (above FST = 0.868, p < 0.0001). Divergence of the complex from the MRCA was estimated between 0.97 MYA (95% HPD interval = 0.55–1.53 MYA) and 0.85 MYA (95% HPD interval = 0.42–1.5 MYA) for ND4A and both concatenated fragments, respectively, with primary divergence from the MRCA of haplogroups 2 and 3. Effective population size for Mexican haplogroups 1 and 2 increased between 0.02 and 0.03 MYA. This study supports previous ecological niche evidence for the complex´s origin surrounding the Tehuantepec Isthmus, and provides evidence for recent divergence of three primary dimidiata haplogroups, with differential T. cruzi infection frequency and DTU specificity, important components of vector capacity.

A novel cell-free method to culture <i>Schistosoma mansoni</i> from cercariae to juvenile worm stages for <i>in vitro</i> drug testing

28 January 2019 - 10:00pm

by Sören Frahm, Anisuzzaman Anisuzzaman, Fabien Prodjinotho, Nermina Vejzagić, Admar Verschoor, Clarissa Prazeres da Costa

Background

The arsenal in anthelminthic treatment against schistosomiasis is limited and relies almost exclusively on a single drug, praziquantel (PZQ). Thus, resistance to PZQ could constitute a major threat. Even though PZQ is potent in killing adult worms, its activity against earlier stages is limited. Current in vitro drug screening strategies depend on newly transformed schistosomula (NTS) for initial hit identification, thereby limiting sensitivity to new compounds predominantly active in later developmental stages. Therefore, the aim of this study was to establish a highly standardized, straightforward and reliable culture method to generate and maintain advanced larval stages in vitro. We present here how this method can be a valuable tool to test drug efficacy at each intermediate larval stage, reducing the reliance on animal use (3Rs).

Methodology/Principal findings

Cercariae were mechanically transformed into skin-stage (SkS) schistosomula and successfully cultured for up to four weeks with no loss in viability in a commercially available medium. Under these serum- and cell-free conditions, development halted at the lung-stage (LuS). However, the addition of human serum (HSe) propelled further development into liver stage (LiS) worms within eight weeks. Skin and lung stages, as well as LiS, were submitted to 96-well drug screening assays using known anti-schistosomal compounds such as PZQ, oxamniquine (OXM), mefloquine (MFQ) and artemether (ART). Our findings showed stage-dependent differences in larval susceptibility to these compounds.

Conclusion

With this robust and highly standardized in vitro assay, important developmental stages of S. mansoni up to LiS worms can be generated and maintained over prolonged periods of time. The phenotype of LiS worms, when exposed to reference drugs, was comparable to most previously published works for ex vivo harvested adult worms. Therefore, this in vitro assay can help reduce reliance on animal experiments in search for new anti-schistosomal drugs.

Knowledge, attitudes and practices (KAP) towards rabies and free-roaming dogs (FRD) in Shirsuphal village in western India: A community based cross-sectional study

25 January 2019 - 10:00pm

by Harish Kumar Tiwari, Abi Tamim Vanak, Mark O’Dea, Ian Duncan Robertson

The lack of awareness about dog-bite related rabies in the rural population of developing countries, including India, is a major impediment to controlling the incidence of disease in humans. A survey of 127 rural residents was undertaken in Shirsuphal village in western India using a structured questionnaire to assess the influence of demographic and pet/livestock owning characteristics on the knowledge, attitudes and practices of the respondents towards rabies and free roaming dogs (FRD). Multivariable logistic regression models were constructed and the knowledge of the rural residents of Shirsuphal village was found to be significantly influenced by family size (OR 2.1, 95%CI 1.0–4.6, p = 0.04) and poultry ownership (OR 2.3, 95%CI 1.1–4.9, p = 0.03), while their attitudes towards FRD was significantly influenced by age of the respondents (OR 2.6, 95% CI 1.2–5.8) and ownership of cattle/buffalo (OR 2.2, 95% CI 1.1–5.5). Although the knowledge score about rabies was high, a comprehensive understanding of the disease was lacking. Concerted efforts to widen the knowledge about rabies and promote healthier practices towards FRD are recommended.

Does prior dengue virus exposure worsen clinical outcomes of Zika virus infection? A systematic review, pooled analysis and lessons learned

25 January 2019 - 10:00pm

by Jennifer Masel, Michael K. McCracken, Todd Gleeson, Brian Morrison, George Rutherford, Allison Imrie, Richard G. Jarman, Michael Koren, Simon Pollett

Zika virus (ZIKV) recently caused a pandemic complicated by Guillain-Barre syndrome (GBS) and birth defects. ZIKV is structurally similar to the dengue viruses (DENV) and in vitro studies suggest antibody dependent enhancement occurs in ZIKV infections preceded by DENV; however, the clinical significance of this remains unclear. We undertook a PRISMA-adherent systematic review of all current human and non-human primate (NHP) data to determine if prior infection with DENV, compared to DENV-naïve hosts, is associated with a greater risk of ZIKV clinical complications or greater ZIKV peak viremia in vivo. We identified 1146 studies in MEDLINE, EMBASE and the grey literature, of which five studies were eligible. One human study indicated no increase in the risk of GBS in ZIKV infections with prior DENV exposure. Two additional human studies showed a small increase in ZIKV viremia in those with prior DENV exposure; however, this was not statistically significant nor was it associated with an increase in clinical severity or adverse pregnancy outcomes. While no meta-analysis was possible using human data, a pooled analysis of the two NHP studies leveraging extended data provided only weak evidence of a 0.39 log10 GE/mL rise in ZIKV viremia in DENV experienced rhesus macaques compared to those with no DENV exposure (p = 0.22). Using a customized quality grading criteria, we further show that no existing published human studies have offered high quality measurement of both acute ZIKV and antecedent DENV infections. In conclusion, limited human and NHP studies indicate a small and non-statistically significant increase in ZIKV viremia in DENV-experienced versus DENV-naïve hosts; however, there is no evidence that even a possible small increase in ZIKV viremia would correlate with a change in ZIKV clinical phenotype. More data derived from larger sample sizes and improved sero-assays are needed to resolve this question, which has major relevance for clinical prognosis and vaccine design.

Discovery of <i>Leptospira</i> spp. seroreactive peptides using ORFeome phage display

24 January 2019 - 10:00pm

by Siti Roszilawati Ramli, Gustavo M. S. G. Moreira, Jonas Zantow, Marga G. A. Goris, Van Kinh Nguyen, Natalia Novoselova, Frank Pessler, Michael Hust

Background

Leptospirosis is the most common zoonotic disease worldwide. The diagnostic performance of a serological test for human leptospirosis is mainly influenced by the antigen used in the test assay. An ideal serological test should cover all serovars of pathogenic leptospires with high sensitivity and specificity and use reagents that are relatively inexpensive to produce and can be used in tropical climates. Peptide-based tests fulfil at least the latter two requirements, and ORFeome phage display has been successfully used to identify immunogenic peptides from other pathogens.

Methodology/Principal findings

Two ORFeome phage display libraries of the entire Leptospira spp. genomes from five local strains isolated in Malaysia or seven WHO reference strains were constructed. Subsequently, 18 unique Leptospira peptides were identified in a screen using a pool of sera from patients with acute leptospirosis. Five of these were validated by titration ELISA using different pools of patient or control sera. The diagnostic performance of these five peptides was then assessed against 16 individual sera from patients with acute leptospirosis and 16 healthy donors and was compared to that of two recombinant reference proteins from L. interrogans. This analysis revealed two peptides (SIR16-D1 and SIR16-H1) from the local isolates with good accuracy for the detection of acute leptospirosis (area under the ROC curve: 0.86 and 0.78, respectively; sensitivity: 0.88 and 0.94; specificity: 0.81 and 0.69), which was close to that of the reference proteins LipL32 and Loa22 (area under the ROC curve: 0.91 and 0.80; sensitivity: 0.94 and 0.81; specificity: 0.75 and 0.75).

Conclusions/Significance

This analysis lends further support for using ORFeome phage display to identify pathogen-associated immunogenic peptides, and it suggests that this technique holds promise for the development of peptide-based diagnostics for leptospirosis and, possibly, of vaccines against this pathogen.

3D images as a field grader training tool for trachomatous trichiasis: A diagnostic accuracy study in Ethiopia

24 January 2019 - 10:00pm

by Jeremy J. Hoffman, Esmael Habtamu, Hillary Rono, Zerihun Tadesse, Tariku Wondie, Temesgen Minas, Bizuayehu Gashaw, E. Kelly Callahan, David MacLeod, Matthew J. Burton

Background

Trachomatous trichiasis (TT) will continue to develop among those people who have had repeated infections after active trachoma is controlled. Detecting and treating affected individuals will remain necessary for years; a long “tail” of incident cases is anticipated. As the prevalence of TT declines, there will be fewer cases available for training trachoma graders (TG), necessitating alternative methods.

Methodology/Principal findings

Prospective, diagnostic accuracy study assessing sensitivity and specificity of 3D and 2D photography as a tool for training TG to detect TT. Individuals with TT in Ethiopia were examined, and 2D and 3D clinical images taken. Images were independently graded by four graders for presence or absence of trichiasis and compared to field grading. We recruited 153 participants. Clinical assessments and images were available for 306 eyes. Trichiasis was identified in 204 eyes by field grading. Image grading was performed on a selection of 262 eyes (131 with trichiasis). Most eyes with trichiasis had minor trichiasis (94/131). Pooled sensitivity was 88.3% (3D) and 98.0% (2D); pooled specificity was 59.8% (3D) and 26.8% (2D). 3D photo grading was 33.0% more specific than the 2D photo grading (p = 0.0002). The overall Kappa scores were 0.48 (3D) and 0.25 (2D). We trained 26 novice TG in Ethiopia using 3D images. They were tested on a 3D images set and had 71.4% agreement (kappa 0.46), relative to an expert. They were then tested examining 50 people, and had 86.8% agreement (kappa 0.75). We also tested 27 experienced TG on the same cases (86.4% agreement, kappa 0.75). There was no difference in performance between groups (p = 0.76). All participants preferred 3D over 2D images for training.

Conclusions/Significance

The slightly higher sensitivity of 2D photos comes at considerable cost in specificity. Training with 3D images enabled novice TG to identify cases as well as experienced TG. 3D were preferred to conventional 2D photos for training. Standardized 3D images of TT could be a useful tool for training TG, in settings where there are now few TT cases.

Estimating the association between being seropositive for cysticercosis and the prevalence of epilepsy and severe chronic headaches in 60 villages of rural Burkina Faso

24 January 2019 - 10:00pm

by Ida Sahlu, Hélène Carabin, Rasmané Ganaba, Pierre-Marie Preux, Assana Kone Cissé, Zekiba Tarnagda, Sarah Gabriël, Veronique Dermauw, Pierre Dorny, Cici Bauer, Athanase Millogo

Background

Individuals diagnosed with neurocysticercosis often present with epilepsy and sometimes with progressively worsening severe chronic headaches (WSCH). While cross-sectional associations between seropositivity to cysticercal antigens and epilepsy have been reported, few large scale studies have been conducted in West Africa and none have measured the association between seropositivity to cysticercal antigens and headaches. This study aimed at filling these knowledge gaps by estimating the strength of the cross-sectional association between seropositivity to cysticercal antigens and the prevalence of epilepsy and WSCH in 60 villages of Burkina Faso, West Africa.

Methodology/Principal findings

Baseline data from a cluster randomized controlled trial collected from January 2011 to February 2012 in 60 villages across three provinces in Burkina Faso were used. Between 78 and 80 individuals were screened for epilepsy and WSCH in each village, and those screened positive were confirmed by a physician. Seventy-five percent of all participants were asked to provide a blood sample to test for Taenia solium cysticercus circulating antigens. Hierarchical multivariable logistic models were used to measure the association between seropositivity to cysticercal antigens and epilepsy (lifetime and active) as well as WSCH. Among 3696 individuals who provided a blood sample, 145 were found to have epilepsy only, 140 WSCH only and 19 both. There were positive associations between seropositivity to cysticercal antigens and active epilepsy (prevalence odds ratio (POR): 2.40 (95%CI: 1.15–5.00)) and WSCH (POR: 2.59 (1.34–4.99)).

Conclusions/Significance

Our study is the first to demonstrate a cross-sectional association between seropositivity to cysticercal antigens and WSCH in a large community-based study conducted in West Africa. The measured cross-sectional association had a strength similar to the ones previously observed between seropositivity to cysticercal antigens and lifetime or active epilepsy. As a result, preventing new cysticercosis cases in communities may reduce the prevalence of these two important neurological disorders.

Synthetic peptides as a novel approach for detecting antibodies against sand fly saliva

24 January 2019 - 10:00pm

by Michal Sima, Blanka Ferencova, Tapan Bhattacharyya, Michael A. Miles, Sergey V. Litvinov, Asrat Hailu, Gad Baneth, Petr Volf

Background

Hosts repeatedly bitten by sand flies develop antibodies against sand fly saliva and screening of these immunoglobulins can be employed to estimate the risk of Leishmania transmission, to indicate the feeding preferences of sand flies, or to evaluate the effectiveness of vector control campaigns. Previously, antibodies to sand fly saliva were detected using whole salivary gland homogenate (SGH) or recombinant proteins, both of which also have their disadvantages. This is the first study on sand flies where short peptides designed based on salivary antigens were successfully utilized for antibody screening.

Methodology/Principal findings

Specific IgG was studied in hosts naturally exposed to Phlebotomus orientalis, the main vector of Leishmania donovani in East Africa. Four peptides were designed by the commercial program EpiQuest-B, based on the sequences of the two most promising salivary antigens, yellow-related protein and ParSP25-like protein. Short amino acid peptides were synthesised and modified for ELISA experiments. Specific anti-P. orientalis IgG was detected in sera of dogs, goats, and sheep from Ethiopia. The peptide OR24 P2 was shown to be suitable for antibody screening; it correlated positively with SGH and its specificity and sensitivity were comparable or even better than that of previously published recombinant proteins.

Conclusions/Significance

OR24 P2, the peptide based on salivary antigen of P. orientalis, was shown to be a valuable tool for antibody screening of domestic animals naturally exposed to P. orientalis. We suggest the application of this promising methodology using species-specific short peptides to other sand fly-host combinations.

China’s shifting neglected parasitic infections in an era of economic reform, urbanization, disease control, and the Belt and Road Initiative

24 January 2019 - 10:00pm

by Lei Wang, Yang Zou, Xinping Zhu, Maria Elena Bottazzi, Peter J. Hotez, Bin Zhan

A <i>Biomphalaria glabrata</i> peptide that stimulates significant behaviour modifications in aquatic free-living <i>Schistosoma mansoni</i> miracidia

22 January 2019 - 10:00pm

by Tianfang Wang, Russell C. Wyeth, Di Liang, Utpal Bose, Guoying Ni, Donald P. McManus, Scott F. Cummins

The human disease schistosomiasis (or bilharzia) is caused by the helminth blood fluke parasite Schistosoma mansoni, which requires an intermediate host, the freshwater gastropod snail Biomphalaria glabrata (the most common intermediate host). The free-swimming parasite miracidia utilises an excellent chemosensory sense to detect and locate an appropriate host. This study investigated the biomolecules released by the snail that stimulate changes in the behaviour of the aquatic S. mansoni miracidia. To achieve this, we have performed an integrated analysis of the snail-conditioned water, through chromatography and bioassay-guided behaviour observations, followed by mass spectrometry. A single fraction containing multiple putative peptides could stimulate extreme swimming behaviour modifications (e.g. velocity, angular variation) similar to those observed in response to crude snail mucus. One peptide (P12;—R-DITSGLDPEVADD-KR—) could replicate the stimulation of miracidia behaviour changes. P12 is derived from a larger precursor protein with a signal peptide and multiple dibasic cleavage sites, which is synthesised in various tissues of the snail, including the central nervous system and foot. P12 consists of an alpha helix secondary structure as indicated by circular dichroism spectroscopy. This information will be helpful for the development of approaches to manipulate this parasites life cycle, and opens up new avenues for exploring other parasitic diseases which have an aquatic phase using methods detailed in this investigation.

A systematic review and meta-analysis of the prevalence of osteoarticular brucellosis

18 January 2019 - 10:00pm

by Shakirat A. Adetunji, Gilbert Ramirez, Margaret J. Foster, Angela A. M. Arenas-Gamboa

Background

Infection of bones and joints remains one of the most commonly described complications of brucellosis in humans and is predominantly reported in all ages and sexes in high-risk regions, such as the Middle East, Asia, South and Central America, and Africa. We aimed to systematically review the literature and perform a meta-analysis to estimate the global prevalence of osteoarticular brucellosis.

Methodology

Major bibliographic databases were searched using keywords and suitable combinations. All studies reporting the incidence and clinical manifestations of osteoarticular brucellosis in humans, and demonstrated by two or more diagnostic methods (bacteriological, molecular, serological, and/or radiographic) were included. Random effect model was used, and statistical significance was set at 0.5%

Principal findings

A total of 56 studies met the inclusion criteria and were included in the systematic review and meta-analysis. There was an evidence of geographical variation in the prevalence of osteoarticular disease with estimates ranging from 27% in low-risk regions to 36% in high-risk regions. However, the difference was not significant. Thus, brucellosis patients have at least 27% chance of developing osteoarticular disease.

Conclusions

The prevalence of OAB is not dependent on the endemicity of brucellosis in a particular region. Hence, further research should investigate the potential mechanisms of OAB, as well as the influence of age, gender, and other socioeconomic factor variations in its global prevalence, as this may provide insight into associated exposure risks and management of the disease.

Surface molecules of extracellular vesicles secreted by the helminth pathogen <i>Fasciola hepatica</i> direct their internalisation by host cells

18 January 2019 - 10:00pm

by Eduardo de la Torre-Escudero, Jared Q. Gerlach, Adam P. S. Bennett, Krystyna Cwiklinski, Heather L. Jewhurst, Kathryn M. Huson, Lokesh Joshi, Michelle Kilcoyne, Sandra O’Neill, John P. Dalton, Mark W. Robinson

Helminth parasites secrete extracellular vesicles (EVs) that can be internalised by host immune cells resulting in modulation of host immunity. While the molecular cargo of EVs have been characterised in many parasites, little is known about the surface-exposed molecules that participate in ligand-receptor interactions with the host cell surface to initiate vesicle docking and subsequent internalisation. Using a membrane-impermeable biotin reagent to capture proteins displayed on the outer membrane surface of two EV sub-populations (termed 15k and 120k EVs) released by adult F. hepatica, we describe 380 surface proteins including an array of virulence factors, membrane transport proteins and molecules involved in EV biogenesis/trafficking. Proteomics and immunohistochemical analysis show that the 120k EVs have an endosomal origin and may be released from the parasite via the protonephridial (excretory) system whilst the larger 15k EVs are released from the gastrodermal epithelial cells that line the fluke gut. A parallel lectin microarray strategy was used to profile the topology of major surface oligosaccharides of intact fluorogenically-labelled EVs as they would be displayed to the host. Lectin profiles corresponding to glycoconjugates exposed on the surface of the 15 K and 120K EV sub-populations are practically identical but are distinct from those of the parasite surface tegument, although all are predominated by high mannose sugars. We found that while the F. hepatica EVs were resistant to exo- and endo-glycosidases, the glyco-amidase PNGase F drastically remodelled the surface oligosaccharides and blocked the uptake of EVs by host macrophages. In contrast, pre-treatment with antibodies obtained from infected hosts, or purified antibodies raised against the extracellular domains of specific EV surface proteins (DM9-containing protein, CD63 receptor and myoferlin), significantly enhanced their cellular internalisation. This work highlights the diversity of EV biogenesis and trafficking pathways used by F. hepatica and sheds light on the molecular interaction between parasite EVs and host cells.

<i>Naja annulifera</i> Snake: New insights into the venom components and pathogenesis of envenomation

18 January 2019 - 10:00pm

by Felipe Silva-de-França, Isadora Maria Villas-Boas, Solange Maria de Toledo Serrano, Bruno Cogliati, Sonia Aparecida de Andrade Chudzinski, Priscila Hess Lopes, Eduardo Shigueo Kitano, Cinthya Kimori Okamoto, Denise V. Tambourgi

Background

Naja annulifera is a medically important venomous snake occurring in some of the countries in Sub-Saharan Africa. Accidental bites result in severe coagulation disturbances, systemic inflammation and heart damage, as reported in dogs, and death, by respiratory arrest, in humans. Despite the medical importance of N. annulifera, little is known about its venom composition and the pathogenesis of envenomation. In this paper, the toxic, inflammatory and immunogenic properties of N. annulifera venom were analyzed.

Methodology/Principal findings

Venom proteomic analysis identified 79 different proteins, including Three Finger Toxins, Cysteine Rich Secretory Proteins, Metalloproteinases, Phospholipases A2 (PLA2), Hyaluronidase, L-amino-acid oxidase, Cobra Venom Factor and Serine Proteinase. The presence of PLA2, hyaluronidase, fibrinogenolytic and anticoagulant activities was detected using functional assays. The venom was cytotoxic to human keratinocytes. In an experimental murine model of envenomation, it was found that the venom induced local changes, such as swelling, which was controlled by anti-inflammatory drugs. Moreover, the venom caused death, which was preceded by systemic inflammation and pulmonary hemorrhage. The venom was shown to be immunogenic, inducing a strong humoral immune response, with the production of antibodies able to recognize venom components with high molecular weight and to neutralize its lethal activity.

Conclusions/Significance

The results obtained in this study demonstrate that N. annulifera venom contains toxins able to induce local and systemic inflammation, which can contribute to lung damage and death. Moreover, the venom is immunogenic, an important feature that must be considered during the production of a therapeutic anti-N. annulifera antivenom.

The impact of imperfect screening tools on measuring the prevalence of epilepsy and headaches in Burkina Faso

17 January 2019 - 10:00pm

by Ida Sahlu, Cici Bauer, Rasmané Ganaba, Pierre-Marie Preux, Linda D. Cowan, Pierre Dorny, Athanase Millogo, Hélène Carabin

Background

Epilepsy and progressively worsening severe chronic headaches (WSCH) are the two most common clinical manifestations of neurocysticercosis, a form of cysticercosis. Most community-based studies in sub-Saharan Africa (SSA) use a two-step approach (questionnaire and confirmation) to estimate the prevalence of these neurological disorders and neurocysticercosis. Few validate the questionnaire in the field or account for the imperfect nature of the screening questionnaire and the fact that only those who screen positive have the opportunity to be confirmed. This study aims to obtain community-based validity estimates of a screening questionnaire, and to assess the impact of verification bias and misclassification error on prevalence estimates of epilepsy and WSCH.

Methodology/Principal findings

Baseline screening questionnaire followed by neurological examination data from a cluster randomized controlled trial collected between February 2011 and January 2012 were used. Bayesian latent-class models were applied to obtain verification bias adjusted validity estimates for the screening questionnaire. These models were also used to compare the adjusted prevalence estimates of epilepsy and WSCH to those directly obtained from the data (i.e. unadjusted prevalence estimates). Different priors were used and their corresponding posterior inference was compared for both WSCH and epilepsy. Screening data were available for 4768 individuals. For epilepsy, posterior estimates for the sensitivity varied with the priors used but remained robust for the specificity, with the highest estimates at 66.1% (95%BCI: 56.4%;75.3%) for sensitivity and 88.9% (88.0%;89.8%) for specificity. For WSCH, the sensitivity and specificity estimates remained robust, with the highest at 59.6% (49.7%;69.1%) and 88.6% (87.6%;89.6%), respectively. The unadjusted prevalence estimates were consistently lower than the adjusted prevalence estimates for both epilepsy and WSCH.

Conclusions/Significance

This study demonstrates that in some settings, the prevalence of epilepsy and WSCH can be considerably underestimated when using the two-step approach. We provide an analytic solution to obtain more valid prevalence estimates of these neurological disorders, although more community-based validity studies are needed to reduce the uncertainty of the estimates. Valid estimates of these two neurological disorders are essential to obtain accurate burden values for neglected tropical diseases such as neurocysticercosis that manifest as epilepsy or WSCH.

Trial registration

ClinicalTrials.gov NCT03095339.

Development of a preliminary <i>in vitro</i> drug screening assay based on a newly established culturing system for pre-adult fifth-stage <i>Onchocerca volvulus</i> worms

17 January 2019 - 10:00pm

by Denis Voronin, Nancy Tricoche, Shabnam Jawahar, Michael Shlossman, Christina A. Bulman, Chelsea Fischer, Michael T. Suderman, Judy A. Sakanari, Sara Lustigman

Background

The human filarial parasite Onchocerca volvulus is the causative agent of onchocerciasis (river blindness). It causes blindness in 270,000 individuals with an additional 6.5 million suffering from severe skin pathologies. Current international control programs focus on the reduction of microfilaridermia by annually administering ivermectin for more than 20 years with the ultimate goal of blocking of transmission. The adult worms of O. volvulus can live within nodules for over 15 years and actively release microfilariae for the majority of their lifespan. Therefore, protracted treatment courses of ivermectin are required to block transmission and eventually eliminate the disease. To shorten the time to elimination of this disease, drugs that successfully target macrofilariae (adult parasites) are needed. Unfortunately, there is no small animal model for the infection that could be used for discovery and screening of drugs against adult O. volvulus parasites. Here, we present an in vitro culturing system that supports the growth and development of O. volvulus young adult worms from the third-stage (L3) infective stage.

Methodology/Principal findings

In this study we optimized the culturing system by testing several monolayer cell lines to support worm growth and development. We have shown that the optimized culturing system allows for the growth of the L3 worms to L5 and that the L5 mature into young adult worms. Moreover, these young O. volvulus worms were used in preliminary assays to test putative macrofilaricidal drugs and FDA-approved repurposed drugs.

Conclusion

The culture system we have established for O. volvulus young adult worms offers a promising new platform to advance drug discovery against the human filarial parasite, O. volvulus and thus supports the continuous pursuit for effective macrofilaricidal drugs. However, this in vitro culturing system will have to be further validated for reproducibility before it can be rolled out as a drug screen for decision making in macrofilaricide drug development programs.

High-accuracy detection of malaria vector larval habitats using drone-based multispectral imagery

17 January 2019 - 10:00pm

by Gabriel Carrasco-Escobar, Edgar Manrique, Jorge Ruiz-Cabrejos, Marlon Saavedra, Freddy Alava, Sara Bickersmith, Catharine Prussing, Joseph M. Vinetz, Jan E. Conn, Marta Moreno, Dionicia Gamboa

Interest in larval source management (LSM) as an adjunct intervention to control and eliminate malaria transmission has recently increased mainly because long-lasting insecticidal nets (LLINs) and indoor residual spray (IRS) are ineffective against exophagic and exophilic mosquitoes. In Amazonian Peru, the identification of the most productive, positive water bodies would increase the impact of targeted mosquito control on aquatic life stages. The present study explores the use of unmanned aerial vehicles (drones) for identifying Nyssorhynchus darlingi (formerly Anopheles darlingi) breeding sites with high-resolution imagery (~0.02m/pixel) and their multispectral profile in Amazonian Peru. Our results show that high-resolution multispectral imagery can discriminate a profile of water bodies where Ny. darlingi is most likely to breed (overall accuracy 86.73%- 96.98%) with a moderate differentiation of spectral bands. This work provides proof-of-concept of the use of high-resolution images to detect malaria vector breeding sites in Amazonian Peru and such innovative methodology could be crucial for LSM malaria integrated interventions.

A secreted schistosome cathepsin B1 cysteine protease and acute schistosome infection induce a transient T helper 17 response

17 January 2019 - 10:00pm

by Kateryna Soloviova, Ellen C. Fox, John P. Dalton, Conor R. Caffrey, Stephen J. Davies

The natural history of schistosome infection in the mammalian host is determined by CD4+ T helper responses mounted against different parasite life cycle stages. A T helper 2 (TH2) response to schistosome eggs is required for host survival and establishment of chronic infection. However, a TH2 cell-derived cytokine also contributes to an immune milieu that is conducive to schistosome growth and development. Thus, the same responses that allow for host survival have been co-opted by schistosomes to facilitate parasite development and transmission, underscoring the significance of CD4+ T cell responses to both worms and eggs in the natural history of schistosome infection. Here we show that a cathepsin B1 cysteine protease secreted by schistosome worms not only induces TH2 responses, but also TH1 and TH17 responses, by a mechanism that is dependent on the proteolytic activity of the enzyme. Further investigation revealed that, in addition to the expected TH1 and TH2 responses, acute schistosome infection also induces a transient TH17 response that is rapidly down-regulated at the onset of oviposition. TH17 responses are implicated in the development of severe egg-induced pathology. The regulation of worm-induced TH17 responses during acute infection could therefore influence the expression of high and low pathology states as infection progresses.

Epidemiology of <i>Strongyloides stercoralis</i> infection in Bolivian patients at high risk of complications

17 January 2019 - 10:00pm

by Laurent Gétaz, Rosario Castro, Pablo Zamora, Marcelo Kramer, Nestor Gareca, Maria del Carmen Torrico-Espinoza, José Macias, Susana Lisarazu-Velásquez, Gloria Rodriguez, Carola Valencia-Rivero, Thomas Perneger, François Chappuis

Background

Strongyloidiasis can be fatal in immunocompromised patients, but few epidemiological studies investigated the burden of this neglected tropical disease among these populations, particularly in low- and middle-income countries such as Bolivia. This study aimed to fill in this gap by estimating prevalence rate and risk factors associated with strongyloidiasis among patients at high risk of complications

Methods

A cross-sectional study was carried out in Santa Cruz (elevation 400 meters, tropical climate) and Cochabamba (elevation 2,500 meters, temperate climate), among patients with cancer, HIV infection and rheumatic or hematologic disease, using four coproparasitological techniques and one serological (ELISA) test.

Results

In total, 1,151 patients participated in this study, including individuals who were HIV-positive (30%) or with rheumatic (29%), oncologic (32%) or hematologic (9%) diseases. The serological and coproparasitological prevalence was 23.0% (95% confidence interval [CI], 20.7–25.5; n = 265/1151) and 7.6% (95% CI, 6.2–9.3; n = 88/1151), respectively, with an estimated actual prevalence of 20.2% (95% CI, 17.9–22.5). Positive serology and positive coproparasitology were associated with younger age and lower education levels. There was no significant difference in prevalence between Cochabamba and Santa Cruz as defined by coproparasitology (6.4% vs. 8.9%; p = 0.11) or serology (24.0% vs. 22.0%; p = 0.4). Among 64 patients in Cochabamba who had never travelled to the tropical lowlands, 5 (7.8%) had a positive coproparasitology.

Conclusions

Strongyloidiasis is widely prevalent in Bolivia among vulnerable patients at increased risk of life-threatening complications. Transmission of the parasite occurs both in tropical lowlands and temperate elevation (≥ 2,500 m). Control strategies to prevent transmission and complications of this serious parasitic disease should be urgently reinforced.

Ghana: Accelerating neglected tropical disease control in a setting of economic development

17 January 2019 - 10:00pm

by Peter J. Hotez, Nana-Kwadwo Biritwum, Alan Fenwick, David H. Molyneux, Jeffrey D. Sachs

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