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by Colin J. Carlson, Eric R. Dougherty, Wayne GetzThe current outbreak of Zika virus poses a severe threat to human health. While the range of the virus has been cataloged growing slowly over the last 50 years, the recent explosive expansion in the Americas indicates that the full potential distribution of Zika remains uncertain. Moreover, many studies rely on its similarity to dengue fever, a phylogenetically closely related disease of unknown ecological comparability. Here we compile a comprehensive spatially-explicit occurrence dataset from Zika viral surveillance and serological surveys based in its native range, and construct ecological niche models to test basic hypotheses about its spread and potential establishment. The hypothesis that the outbreak of cases in Mexico and North America are anomalous and outside the native ecological niche of the disease, and may be linked to either genetic shifts between strains, or El Nino or similar climatic events, remains plausible at this time. Comparison of the Zika niche against the known distribution of dengue fever suggests that Zika is more constrained by the seasonality of precipitation and diurnal temperature fluctuations, likely confining autochthonous non-sexual transmission to the tropics without significant evolutionary change. Projecting the range of the diseases in conjunction with three major vector species (Aedes africanus, Ae. aegypti, and Ae. albopictus) that transmit the pathogens, under climate change, suggests that Zika has potential for northward expansion; but, based on current knowledge, our models indicate Zika is unlikely to fill the full range its vectors occupy, and public fear of a vector-borne Zika epidemic in the mainland United States is potentially informed by biased or limited scientific knowledge. With recent sexual transmission of the virus globally, we caution that our results only apply to the vector-borne transmission route of the pathogen, and while the threat of a mosquito-carried Zika pandemic may be overstated in the media, other transmission modes of the virus may emerge and facilitate naturalization worldwide.
Correction: Prevalence of Lymphatic Filariasis and Treatment Effectiveness of Albendazole/ Ivermectin in Individuals with HIV Co-infection in Southwest-Tanzania
by Inge Kroidl, Elmar Saathoff, Lucas Maganga, Petra Clowes, Leonard Maboko, Achim Hoerauf, Williams H. Makunde, Antelmo Haule, Prisca Mviombo, Bettina Pitter, Neema Mgeni, Joseph Mabuye, Dickens Kowuor, Upendo Mwingira, Mwelecele N. Malecela, Thomas Löscher, Michael Hoelscher
Clonal Evolution of <i>Enterocytozoon bieneusi</i> Populations in Swine and Genetic Differentiation in Subpopulations between Isolates from Swine and Humans
by Qiang Wan, Lihua Xiao, Xichen Zhang, Yijing Li, Yixin Lu, Mingxin Song, Wei LiEnterocytozoon bieneusi is a widespread parasite with high genetic diversity among hosts. Its natural reservoir remains elusive and data on population structure are available only in isolates from primates. Here we describe a population genetic study of 101 E. bieneusi isolates from pigs using sequence analysis of the ribosomal internal transcribed spacer (ITS) and four mini- and microsatellite markers. The presence of strong linkage disequilibrium (LD) and limited genetic recombination indicated a clonal structure for the population. Bayesian inference of phylogeny, structural analysis, and principal coordinates analysis separated the overall population into three subpopulations (SP3 to SP5) with genetic segregation of the isolates at some geographic level. Comparative analysis showed the differentiation of SP3 to SP5 from the two known E. bieneusi subpopulations (SP1 and SP2) from primates. The placement of a human E. bieneusi isolate in pig subpopulation SP4 supported the zoonotic potential of some E. bieneusi isolates. Network analysis showed directed evolution of SP5 to SP3/SP4 and SP1 to SP2. The high LD and low number of inferred recombination events are consistent with the possibility of host adaptation in SP2, SP3, and SP4. In contrast, the reduced LD and high genetic diversity in SP1 and SP5 might be results of broad host range and adaptation to new host environment. The data provide evidence of the potential occurrence of host adaptation in some of E. bieneusi isolates that belong to the zoonotic ITS Group 1.
Serum Procalcitonin and Peripheral Venous Lactate for Predicting Dengue Shock and/or Organ Failure: A Prospective Observational Study
by Vipa Thanachartwet, Varunee Desakorn, Duangjai Sahassananda, Akanitt Jittmittraphap, Nittha Oer-areemitr, Sathaporn Osothsomboon, Manoon Surabotsophon, Anan WattanathumBackground
Currently, there are no biomarkers that can predict the incidence of dengue shock and/or organ failure, although the early identification of risk factors is important in determining appropriate management to reduce mortality. Therefore, we sought to determine the factors associated with dengue shock and/or organ failure and to evaluate the prognostic value of serum procalcitonin (PCT) and peripheral venous lactate (PVL) levels as biomarkers of dengue shock and/or organ failure.Methodology/Principal Findings
A prospective observational study was conducted among adults hospitalized for confirmed viral dengue infection at the Hospital for Tropical Diseases in Bangkok, Thailand between October 2013 and July 2015. Data, including baseline characteristics, clinical parameters, laboratory findings, serum PCT and PVL levels, management, and outcomes, were recorded on pre-defined case report forms. Of 160 patients with dengue, 128 (80.0%) patients had dengue without shock or organ failure, whereas 32 (20.0%) patients developed dengue with shock and/or organ failure. Using a stepwise multivariate logistic regression analysis, PCT ≥0.7 ng/mL (odds ratio [OR]: 4.80; 95% confidence interval [CI]: 1.60–14.45; p = 0.005) and PVL ≥2.5 mmol/L (OR: 27.99, 95% CI: 8.47–92.53; p <0.001) were independently associated with dengue shock and/or organ failure. A combination of PCT ≥0.7 ng/mL and PVL ≥2.5 mmol/L provided good prognostic value for predicting dengue shock and/or organ failure, with an area under the receiver operating characteristics curve of 0.83 (95% CI: 0.74–0.92), a sensitivity of 81.2% (95% CI: 63.6–92.8%), and a specificity of 84.4% (95% CI: 76.9–90.2%). Dengue shock patients with non-clearance of PCT and PVL expired during hospitalization.Conclusions/Significance
PCT ≥0.7 ng/mL and PVL ≥2.5 mmol/L were independently associated with dengue shock and/or organ failure. The combination of PCT and PVL levels could be used as prognostic biomarkers for the prediction of dengue shock and/or organ failure.
by Jin-ren Pan, Ju-ying Yan, Jia-yue Zhou, Xue-wen Tang, Han-qing He, Rong-hui Xie, Hai-yan Mao, Yan-jun Zhang, Shu-yun XieBackground
Sporadic Japanese encephalitis (JE) cases still have been reported in Zhejiang Province in recent years, and concerns about vaccine cross-protection and population-level immunity have been raised off and on within the public health sphere. Genotype I (GI) has replaced GIII as the dominant genotype in Asian countries during the past few decades, which caused considerable concerns about the potential change of epidemiology characteristics and the vaccine effectiveness. The aim of this study was to investigate the prevalence of JE neutralizing antibody and its waning antibody trend after live attenuated JE vaccine immunization. Additionally, this study analyzed the molecular characteristics of the E gene of Zhejiang Japanese encephalitis virus (JEV) strains, and established genetic relationships with other JEV strains.Methodology/Principal Findings
A total of 570 serum specimens were sampled from community population aged from 0 to 92 years old in Xianju county of Zhejiang Province in 2013–2014. Microseroneutralization test results were analyzed to estimate the population immunity and to observe antibody dynamics in vaccinated children. E genes of 28 JEV strains isolated in Zhejiang Province were sequenced for phylogenetic tree construction and molecular characteristics analysis with other selected strains. Positive JE neutralizing antibody rates were higher in residents ≥35 years old (81%~98%) and lower in residents <35 years old (0~57%). 7 or 8 years after the 2nd live attenuated vaccine dose, the antibodies against for 4 different strains with microseroneutralization test were decreased by 55%~73% on seropositive rates and by 25%~38% on GMTs respectively. JEV strains isolated in recent years were all grouped into GI, while those isolated in the 1980s belonged to GIII. On important amino acid sites related to antigenicity, there was no divergence between the Zhejiang JE virus strains and the vaccine strain (SA14-14-2).Conclusion/Significances
JE neutralizing antibody positive rates increase in age ≥10 years old population, likely reflecting natural infection or natural boosting of immunity through exposure to wild virus. JE seropositivity rates were quite low in <35 years old age groups in Zhejiang Province. Waning of neutralizing antibody after live attenuated vaccine immunization was observed, but the clinical significance should be further investigated. Both the peripheral antibody response and genetic characterization indicate that current live attenuated JE vaccine conferred equal neutralizing potency against GI or GIII of wild strains. GI has replaced GIII as the dominant genotype in Zhejiang in the past few decades. Although the chance of exposure to wild JE virus has reduced, the virus still circulates in nature; therefore, it is necessary to implement immunization program for children continually and to conduct surveillance activity periodically.
by Patrick C. Y. Woo, Susanna K. P. Lau, Candy C. Y. Lau, Edward T. K. Tung, Ken T. K. Chong, Fengjuan Yang, Hongmin Zhang, Raymond K. C. Lo, Jian-Pao Cai, Rex K. H. Au-Yeung, Wing-Fung Ng, Herman Tse, Samson S. Y. Wong, Simin Xu, Wai Hei Lam, Man-Kit Tse, Kong Hung Sze, Richard Y. Kao, Neil E. Reiner, Quan Hao, Kwok-Yung YuenBackground
Talaromyces marneffei is an opportunistic dimorphic fungus prevalent in Southeast Asia. We previously demonstrated that Mp1p is an immunogenic surface and secretory mannoprotein of T. marneffei. Since Mp1p is a surface protein that can generate protective immunity, we hypothesized that Mp1p and/or its homologs are virulence factors.Methodology/Principal Findings
We examined the pathogenic roles of Mp1p and its homologs in a mouse model. All mice died 21 and 30 days after challenge with wild-type T. marneffei PM1 and MP1 complemented mutant respectively. None of the mice died 60 days after challenge with MP1 knockout mutant (P<0.0001). Seventy percent of mice died 60 days after challenge with MP1 knockdown mutant (P<0.0001). All mice died after challenge with MPLP1 to MPLP13 knockdown mutants, suggesting that only Mp1p plays a significant role in virulence. The mean fungal loads of PM1 and MP1 complemented mutant in the liver, lung, kidney and spleen were significantly higher than those of the MP1 knockout mutant. Similarly, the mean load of PM1 in the liver, lung and spleen were significantly higher than that of the MP1 knockdown mutant. Histopathological studies showed an abundance of yeast in the kidney, spleen, liver and lung with more marked hepatic and splenic necrosis in mice challenged with PM1 compared to MP1 knockout and MP1 knockdown mutants. Likewise, a higher abundance of yeast was observed in the liver and spleen of mice challenged with MP1 complemented mutant compared to MP1 knockout mutant. PM1 and MP1 complemented mutant survived significantly better than MP1 knockout mutant in macrophages at 48 hours (P<0.01) post-infection. The mean fungal counts of Pichia pastoris GS115-MP1 in the liver (P<0.001) and spleen (P<0.05) of mice were significantly higher than those of GS115 at 24 hours post-challenge.Conclusions/Significance
Mp1p is a key virulence factor of T. marneffei. Mp1p mediates virulence by improving the survival of T. marneffei in macrophages.
by Zachary A. Klase, Svetlana Khakhina, Adriano De Bernardi Schneider, Michael V. Callahan, Jill Glasspool-Malone, Robert MaloneThe ongoing Zika virus epidemic in the Americas and the observed association with both fetal abnormalities (primary microcephaly) and adult autoimmune pathology (Guillain–Barré syndrome) has brought attention to this neglected pathogen. While initial case studies generated significant interest in the Zika virus outbreak, larger prospective epidemiology and basic virology studies examining the mechanisms of Zika viral infection and associated pathophysiology are only now starting to be published. In this review, we analyze Zika fetal neuropathogenesis from a comparative pathology perspective, using the historic metaphor of “TORCH” viral pathogenesis to provide context. By drawing parallels to other viral infections of the fetus, we identify common themes and mechanisms that may illuminate the observed pathology. The existing data on the susceptibility of various cells to both Zika and other flavivirus infections are summarized. Finally, we highlight relevant aspects of the known molecular mechanisms of flavivirus replication.
by Jacqueline Deen, Martin W. Weber, Thomas Jaenisch
by Priyanka Mehta, Peter J. Hotez
Correction: Integrated Analysis of Environment, Cattle and Human Serological Data: Risks and Mechanisms of Transmission of Rift Valley Fever in Madagascar
by Marie-Marie Olive, Véronique Chevalier, Vladimir Grosbois, Annelise Tran, Soa-Fy Andriamandimby, Benoit Durand, Jean-Pierre Ravalohery, Seta Andriamamonjy, Fanjasoa Rakotomanana, Christophe Rogier, Jean-Michel Heraud
by Reeta Subramaniam Mani
Expression of CD64 on Circulating Neutrophils Favoring Systemic Inflammatory Status in Erythema Nodosum Leprosum
by Veronica Schmitz, Rhana Berto da Silva Prata, Mayara Garcia de Mattos Barbosa, Mayara Abud Mendes, Sheila Santos Brandão, Thaís Porto Amadeu, Luciana Silva Rodrigues, Helen Ferreira, Fabrício da Mota Ramalho Costa, Jessica Brandão dos Santos, Fabiana dos Santos Pacheco, Alice de Miranda Machado, José Augusto da Costa Nery, Mariana de Andrea Hacker, Anna Maria Sales, Roberta Olmo Pinheiro, Euzenir Nunes SarnoErythema Nodosum Leprosum (ENL) is an immune reaction in leprosy that aggravates the patient´s clinical condition. ENL presents systemic symptoms of an acute infectious syndrome with high leukocytosis and intense malaise clinically similar to sepsis. The treatment of ENL patients requires immunosuppression and thus needs to be early and efficient to prevent both disabilities and permanent nerve damage. Some patients experience multiple episodes of ENL and prolonged use of immunosuppressive drugs may lead to serious adverse effects. Thalidomide treatment is extremely effective at ameliorating ENL symptoms. Several mechanisms have been proposed to explain the efficacy of thalidomide in ENL, including the inhibition of TNF production. Given its teratogenicity, thalidomide is prohibitive for women of childbearing age. A rational search for molecular targets during ENL episodes is essential to better understand the disease mechanisms involved, which may also lead to the discovery of new drugs and diagnostic tests. Previous studies have demonstrated that IFN-γ and GM-CSF, involved in the induction of CD64 expression, increase during ENL. The aim of the present study was to investigate CD64 expression during ENL and whether thalidomide treatment modulated its expression. Leprosy patients were allocated to one of five groups: (1) Lepromatous leprosy, (2) Borderline leprosy, (3) Reversal reaction, (4) ENL, and (5) ENL 7 days after thalidomide treatment. The present study demonstrated that CD64 mRNA and protein were expressed in ENL lesions and that thalidomide treatment reduced CD64 expression and neutrophil infiltrates—a hallmark of ENL. We also showed that ENL blood neutrophils exclusively expressed CD64 on the cell surface and that thalidomide diminished overall expression. Patient classification based on clinical symptoms found that severe ENL presented high levels of neutrophil CD64. Collectively, these data revealed that ENL neutrophils express CD64, presumably contributing to the immunopathogenesis of the disease.
Incidence and Risk Factors for Developing Dengue-Associated Hemophagocytic Lymphohistiocytosis in Puerto Rico, 2008 - 2013
by Esther M. Ellis, Tyler M. Sharp, Janice Pérez-Padilla, Liza González, B. Katherine Poole-Smith, Emmaculate Lebo, Charlotte Baker, Mark J. Delorey, Brenda Torres-Velasquez, Eduardo Ochoa, Brenda Rivera-Garcia, Hector Díaz-Pinto, Luis Clavell, Anabel Puig-Ramos, Gritta E. Janka, Kay M. TomashekBackground
Hemophagocytic lymphohistiocytosis (HLH) is a rare, potentially fatal disorder characterized by fever, pancytopenia, hepatosplenomegaly, and increased serum ferritin. HLH is being increasingly reported as a complication of dengue, a common tropical acute febrile illness.Methodology/Principal Findings
After a cluster of pediatric dengue-associated HLH patients was identified during the 2012–2013 dengue epidemic in Puerto Rico, active surveillance and a case-control investigation was conducted at four referral hospitals to determine the incidence of HLH in children and identify risk factors for HLH following dengue. Patients with dengue-associated HLH (cases) were matched by month of illness onset and admission hospital to dengue patients that did not develop HLH (controls). During 2008–2013, a total of 33 HLH patients were identified, of which 22 (67%) were associated with dengue and 1 died (dengue-associated HLH case-fatality rate: 4.5%). Two patients with dengue-associated HLH had illness onset in 2009, none had illness onset during the 2010 dengue epidemic, and 20 had illness onset during the 2012–2013 epidemic. Frequency of infection with either dengue virus (DENV)-1 or DENV-4 did not differ between cases and controls. Cases were younger than controls (median age: 1 vs. 13 years, p < 0.01), were hospitalized longer (18 vs. 5 days, p < 0.01), and were admitted more frequently to pediatric intensive care units (100% vs. 16%, p < 0.01). Cases had co-infection (18.2% vs. 4.5%, p = 0.04), recent influenza-like illness (54.5% vs. 25.0%, p = 0.01), and longer duration of fever (7 vs. 5 days; p < 0.01). Cases were more likely to have lymphadenopathy, hepatomegaly, splenomegaly, anemia, and elevated liver transaminases (p ≤ 0.02).Conclusions/Significance
During this cluster of dengue-associated HLH cases that was temporally associated with the 2012–2013 epidemic, most patients with dengue-associated HLH were infants and had higher morbidity than dengue inpatients. Physicians throughout the tropics should be aware of HLH as a potential complication of dengue, particularly in patients with anemia and severe liver injury.
Identification of RNA Binding Proteins Associated with Dengue Virus RNA in Infected Cells Reveals Temporally Distinct Host Factor Requirements
by Olga V. Viktorovskaya, Todd M. Greco, Ileana M. Cristea, Sunnie R. ThompsonBackground
There are currently no vaccines or antivirals available for dengue virus infection, which can cause dengue hemorrhagic fever and death. A better understanding of the host pathogen interaction is required to develop effective therapies to treat DENV. In particular, very little is known about how cellular RNA binding proteins interact with viral RNAs. RNAs within cells are not naked; rather they are coated with proteins that affect localization, stability, translation and (for viruses) replication.Methodology/Principal Findings
Seventy-nine novel RNA binding proteins for dengue virus (DENV) were identified by cross-linking proteins to dengue viral RNA during a live infection in human cells. These cellular proteins were specific and distinct from those previously identified for poliovirus, suggesting a specialized role for these factors in DENV amplification. Knockdown of these proteins demonstrated their function as viral host factors, with evidence for some factors acting early, while others late in infection. Their requirement by DENV for efficient amplification is likely specific, since protein knockdown did not impair the cell fitness for viral amplification of an unrelated virus. The protein abundances of these host factors were not significantly altered during DENV infection, suggesting their interaction with DENV RNA was due to specific recruitment mechanisms. However, at the global proteome level, DENV altered the abundances of proteins in particular classes, including transporter proteins, which were down regulated, and proteins in the ubiquitin proteasome pathway, which were up regulated.Conclusions/Significance
The method for identification of host factors described here is robust and broadly applicable to all RNA viruses, providing an avenue to determine the conserved or distinct mechanisms through which diverse viruses manage the viral RNA within cells. This study significantly increases the number of cellular factors known to interact with DENV and reveals how DENV modulates and usurps cellular proteins for efficient amplification.
Differential Gel Electrophoresis (DIGE) Evaluation of Naphthoimidazoles Mode of Action: A Study in <i>Trypanosoma cruzi</i> Bloodstream Trypomastigotes
by Giselle Villa Flor Brunoro, Vitor Marcel Faça, Marcelle Almeida Caminha, André Teixeira da Silva Ferreira, Monique Trugilho, Kelly Cristina Gallan de Moura, Jonas Perales, Richard Hemmi Valente, Rubem Figueiredo Sadok Menna-BarretoBackground
The obligate intracellular protozoan Trypanosoma cruzi is the causative agent of Chagas disease, a neglected illness affecting millions of people in Latin America that recently entered non-endemic countries through immigration, as a consequence of globalization. The chemotherapy for this disease is based mainly on benznidazole and nifurtimox, which are very efficient nitroderivatives against the acute stage but present limited efficacy during the chronic phase. Our group has been studying the trypanocidal effects of naturally occurring quinones and their derivatives, and naphthoimidazoles derived from β-lapachone N1, N2 and N3 were the most active. To assess the molecular mechanisms of action of these compounds, we applied proteomic techniques to analyze treated bloodstream trypomastigotes, which are the clinically relevant stage of the parasite.Methodology/Principal Findings
The approach consisted of quantification by 2D-DIGE followed by MALDI-TOF/TOF protein identification. A total of 61 differentially abundant protein spots were detected when comparing the control with each N1, N2 or N3 treatment, for 34 identified spots. Among the differentially abundant proteins were activated protein kinase C receptor, tubulin isoforms, asparagine synthetase, arginine kinase, elongation factor 2, enolase, guanine deaminase, heat shock proteins, hypothetical proteins, paraflagellar rod components, RAB GDP dissociation inhibitor, succinyl-CoA ligase, ATP synthase subunit B and methionine sulfoxide reductase.Conclusion/Significance
Our results point to different modes of action for N1, N2 and N3, which indicate a great variety of metabolic pathways involved and allow for novel perspectives on the development of trypanocidal agents.
Prevalence of Active and Latent Yaws in the Solomon Islands 18 Months after Azithromycin Mass Drug Administration for Trachoma
by Michael Marks, Oliver Sokana, Eli Nachamkin, Elliot Puiahi, Georgina Kilua, Allan Pillay, Christian Bottomley, Anthony W. Solomon, David C. MabeyIntroduction
Both yaws and trachoma are endemic in the Pacific. Mass treatment with azithromycin is the mainstay of the WHO strategy for both the eradication of yaws and the elimination of trachoma as a public health problem, but the dose recommended for trachoma is lower than that for yaws. In countries where both diseases are endemic, there is a potential for synergy between yaws and trachoma control programs if mass treatment with the lower dose of azithromycin was shown to be effective for the treatment of yaws. In an earlier study, we demonstrated a profound reduction in the clinical and serological prevalence of yaws following a single round of mass treatment with azithromycin 20 mg/kg undertaken for the purposes of trachoma elimination.Methods
This survey was conducted 18 months following a single round of azithromycin mass treatment in the same communities in which we had conducted our previous six-month follow-up survey. We examined children aged 1–14 years and took blood and lesion samples for yaws diagnosis using the Treponema pallidum particle agglutination assay (TPPA) and the non-treponemal Rapid Plasma Reagin (RPR) test.Results
A total of 1,284 children were enrolled in the study. Amongst children aged 5–14 years, 223 had a positive TPPA (27.5%, 95% CI 13.6–47.7%). The TPPA seroprevalence amongst this age group did not differ significantly from either our pre-mass treatment survey or our initial follow-up survey. Thirty-five children had positive TPPA and positive RPR (4.3%, 95% CI 2.1–8.7%), and this did not differ significantly from our initial post-mass drug administration (MDA) follow-up survey (4.3% versus 3.5%, p = 0.43) but remained significantly lower than our initial pre-MDA survey (4.3% vs 21.7%, p <0.0001). Village-level MDA coverage was strongly associated with dual-seropositivity (p = 0.005). Amongst children aged 1–4 years, 16 had a positive TPPA (3.5%, 95% CI 1.6–7.1%). This did not differ significantly from the seroprevalence in this age group that had been predicted based on our previous surveys (3.5% vs 5%, p = 0.11). Fourteen children (1.1%) were considered to have a skin lesion clinically consistent with yaws, but none of these individuals was seropositive for yaws. Of nine cases where a swab could be collected for PCR, all were negative for Treponema pallidum subsp. pertenue DNA.Discussion
In this study we have shown that the benefit of a single round of mass treatment with azithromycin 20mg/kg appears to extend to 18 months without any further intervention. The lack of a significant change in seroprevalence from 6 to 18 months after mass treatment might suggest that interventions could be spaced at yearly intervals without a significant loss of impact, and that this might facilitate integration of yaws eradication with other neglected tropical disease (NTD) control programmes. MDA coverage above 90% was associated with significantly better outcomes than coverages lower than this threshold, and strategies to improve coverage at all stages of yaws eradication efforts should be investigated.
Mortality, Morbidity and Health-Seeking Behaviour during the Ebola Epidemic 2014–2015 in Monrovia Results from a Mobile Phone Survey
by Anna Kuehne, Emily Lynch, Esaie Marshall, Amanda Tiffany, Ian Alley, Luke Bawo, Moses Massaquoi, Claudia Lodesani, Philippe Le Vaillant, Klaudia Porten, Etienne GignouxBetween March 2014 and July 2015 at least 10,500 Ebola cases including more than 4,800 deaths occurred in Liberia, the majority in Monrovia. However, official numbers may have underestimated the size of the outbreak. Closure of health facilities and mistrust in existing structures may have additionally impacted on all-cause morbidity and mortality. To quantify mortality and morbidity and describe health-seeking behaviour in Monrovia, Médecins sans Frontières (MSF) conducted a mobile phone survey from December 2014 to March 2015. We drew a random sample of households in Monrovia and conducted structured mobile phone interviews, covering morbidity, mortality and health-seeking behaviour from 14 May 2014 until the day of the survey. We defined an Ebola-related death as any death meeting the Liberian Ebola case definition. We calculated all-cause and Ebola-specific mortality rates. The sample consisted of 6,813 household members in 905 households. We estimated a crude mortality rate (CMR) of 0.33/10,000 persons/day (95%CI:0.25–0.43) and an Ebola-specific mortality rate of 0.06/10,000 persons/day (95%-CI:0.03–0.11). During the recall period, 17 Ebola cases were reported including those who died. In the 30 days prior to the survey 277 household members were reported sick; malaria accounted for 54% (150/277). Of the sick household members, 43% (122/276) did not visit any health care facility. The mobile phone-based survey was found to be a feasible and acceptable alternative method when data collection in the community is impossible. CMR was estimated well below the emergency threshold of 1/10,000 persons/day. Non-Ebola-related mortality in Monrovia was not higher than previous national estimates of mortality for Liberia. However, excess mortality directly resulting from Ebola did occur in the population. Importantly, the small proportion of sick household members presenting to official health facilities when sick might pose a challenge for future outbreak detection and mitigation. Substantial reported health-seeking behaviour outside of health facilities may also suggest the need for adapted health messaging and improved access to health care.
by Zaida Herrador, Mar Siles-Lucas, Pilar Aparicio, Rogelio Lopez-Velez, Alin Gherasim, Teresa Garate, Agustín BenitoBackground
Cystic echinococcosis (CE) is a parasitic disease caused by the tapeworm Echinococcus granulosus. Although present throughout Europe, deficiencies in the official reporting of CE result in under-reporting and misreporting of this disease, which in turn is reflected in the wrong opinion that CE is not an important health problem. By using an alternative data source, this study aimed at describing the clinical and temporal-spatial characteristics of CE hospitalizations in Spain between 1997 and 2012.Methodology/Principal Findings
We performed a retrospective descriptive study using the Hospitalization Minimum Data Set (CMBD in Spanish). All CMBD’s hospital discharges with echinococcosis diagnosis placed in first diagnostic position were reviewed. Hospitalization rates were computed and clinical characteristics were described. Spatial and temporal distribution of hospital discharges was also assessed. Between 1997 and 2012, 14,010 hospitalizations with diagnosis of CE were recorded, 55% were men and 67% were aged over 45 years. Pediatric hospitalizations occurred during the whole study period. The 95.2% were discharged at home, and only 1.7% were exitus. The average cost was 8,439.11 €. The hospitalization rate per 100,000 per year showed a decreasing trend during the study period. All the autonomous communities registered discharges, even those considered as non-endemic. Maximum rates were reached by Extremadura, Castilla-Leon and Aragon. Comparison of the CMBD data and the official Compulsory Notifiable Diseases (CND) reports from 2005 to 2012 showed that official data were lower than registered hospitalization discharges.Conclusions
Hospitalizations distribution was uneven by year and autonomous region. Although CE hospitalization rates have decreased considerably due to the success of control programs, it remains a public health problem due to its severity and economic impact. Therefore, it would be desirable to improve its oversight and surveillance, since officially reported data are underestimating the real burden of CE in Spain.
by Elizabeth A. Dietrich, Stanley A. Langevin, Claire Y.-H. Huang, Payal D. Maharaj, Mark J. Delorey, Richard A. Bowen, Richard M. Kinney, Aaron C. BraultWest Nile virus (WNV) replicates in a wide variety of avian species, which serve as reservoir and amplification hosts. WNV strains isolated in North America, such as the prototype strain NY99, elicit a highly pathogenic response in certain avian species, notably American crows (AMCRs; Corvus brachyrhynchos). In contrast, a closely related strain, KN3829, isolated in Kenya, exhibits a low viremic response with limited mortality in AMCRs. Previous work has associated the difference in pathogenicity primarily with a single amino acid mutation at position 249 in the helicase domain of the NS3 protein. The NY99 strain encodes a proline residue at this position, while KN3829 encodes a threonine. Introduction of an NS3-T249P mutation in the KN3829 genetic background significantly increased virulence and mortality; however, peak viremia and mortality were lower than those of NY99. In order to elucidate the viral genetic basis for phenotype variations exclusive of the NS3-249 polymorphism, chimeric NY99/KN3829 viruses were created. We show herein that differences in the NS1-2B region contribute to avian pathogenicity in a manner that is independent of and additive with the NS3-249 mutation. Additionally, NS1-2B residues were found to alter temperature sensitivity when grown in avian cells.
Knowledge, Attitudes, and Practices regarding Diarrhea and Cholera following an Oral Cholera Vaccination Campaign in the Solomon Islands
by Eleanor Burnett, Tenneth Dalipanda, Divi Ogaoga, Jenny Gaiofa, Gregory Jilini, Alison Halpin, Vance Dietz, Kashmira Date, Eric Mintz, Terri Hyde, Kathleen Wannemuehler, Catherine YenBackground
In response to a 2011 cholera outbreak in Papua New Guinea, the Government of the Solomon Islands initiated a cholera prevention program which included cholera disease prevention and treatment messaging, community meetings, and a pre-emptive cholera vaccination campaign targeting 11,000 children aged 1–15 years in selected communities in Choiseul and Western Provinces.Methodology and Principal Findings
We conducted a post-vaccination campaign, household-level survey about knowledge, attitudes, and practices regarding diarrhea and cholera in areas targeted and not targeted for cholera vaccination. Respondents in vaccinated areas were more likely to have received cholera education in the previous 6 months (33% v. 9%; p = 0.04), to know signs and symptoms (64% vs. 22%; p = 0.02) and treatment (96% vs. 50%; p = 0.02) of cholera, and to be aware of cholera vaccine (48% vs. 14%; p = 0.02). There were no differences in water, sanitation, and hygiene practices.Conclusions
This pre-emptive OCV campaign in a cholera-naïve community provided a unique opportunity to assess household-level knowledge, attitudes, and practices regarding diarrhea, cholera, and water, sanitation, and hygiene (WASH). Our findings suggest that education provided during the vaccination campaign may have reinforced earlier mass messaging about cholera and diarrheal disease in vaccinated communities.