Cholera Epidemic in Guinea-Bissau (2008): The Importance of “Place”

As resources are limited when responding to cholera outbreaks, knowledge about where to orient interventions is crucial. We describe the cholera epidemic affecting Guinea-Bissau in 2008 focusing on the geographical spread in order to guide prevention and control activities

Stage- and Gender-Specific Proteomic Analysis of Brugia malayi Excretory-Secretory Products

To succeed in infection, parasites must have ways to reach the host, penetrate its tissues and escape its defense systems. As they are not necessarily fatal, most helminth parasites remain viable within their host for many years, exerting a strong influence over the host immune function. Many of these functions are performed by products that are released from the parasite. We exploited the remarkable sensitivity of modern proteomics tools together with the availability of a sequenced genome to identify and compare the proteins released in vitro by adult males, adult females and the microfilariae of the filarial nematode Brugia malayi. This parasite is one of the etiological agents of lymphatic filariasis, a disease that poses continuing and significant threats to human health. The different forms of the parasite inhabit different compartments in the mammalian host. We found that the set of proteins released by each form is unique; they must reflect particular developmental processes and different strategies for evasion of host responses. The identification of these proteins will allow us to illuminate the biology of secretory processes in this organism and to establish a path for developing an understanding of how these parasite proteins function in immune evasion events

The Wolbachia endosymbiont as an anti-filarial nematode target

Human disease caused by parasitic filarial nematodes is a major cause of global morbidity. The parasites are transmitted by arthropod intermediate hosts and are responsible for lymphatic filariasis (elephantiasis) or onchocerciasis (river blindness). Within these filarial parasites are intracellular alpha-proteobacteria, Wolbachia, that were first observed almost 30 years ago. The obligate endosymbiont has been recognized as a target for anti-filarial nematode chemotherapy as evidenced by the loss of worm fertility and viability upon antibiotic treatment in an extensive series of human trials. While current treatments with doxycycline and rifampicin are not practical for widespread use due to the length of required treatments and contraindications, anti-Wolbachia targeting nevertheless appears a promising alternative for filariasis control in situations where current programmatic strategies fail or are unable to be delivered and it provides a superior efficacy for individual therapy. The mechanisms that underlie the symbiotic relationship between Wolbachia and its nematode hosts remain elusive. Comparative genomics, bioinfomatic and experimental analyses have identified a number of potential interactions, which may be drug targets. One candidate is de novo heme biosynthesis, due to its absence in the genome sequence of the host nematode, Brugia malayi, but presence in Wolbachia and its potential roles in worm biology. We describe this and several additional candidate targets, as well as our approaches for understanding the nature of the host-symbiont relationship

Indicators of river system hydromorphological character and dynamics: understanding current conditions and guiding sustainable river management

The work leading to this paper received funding from the EU’s FP7 programme under Grant Agreement No. 282656 (REFORM). The Indicators were developed within the context of REFORM deliverable D2.1, therefore all partners involved in this deliverable contributed to some extent to their discussion and development

Model-based geostatistical mapping of the prevalence of onchocerca volvulus in West Africa.

Background: The initial endemicity (pre-control prevalence) of onchocerciasis has been shown to be an important determinant of the feasibility of elimination by mass ivermectin distribution. We present the first geostatistical map of microfilarial prevalence in the former Onchocerciasis Control Programme in West Africa (OCP) before commencement of antivectorial and antiparasitic interventions. Methods and Findings: Pre-control microfilarial prevalence data from 737 villages across the 11 constituent countries in the OCP epidemiological database were used as ground-truth data. These 737 data points, plus a set of statistically selected environmental covariates, were used in a Bayesian model-based geostatistical (B-MBG) approach to generate a continuous surface (at pixel resolution of 5 km x 5km) of microfilarial prevalence in West Africa prior to the commencement of the OCP. Uncertainty in model predictions was measured using a suite of validation statistics, performed on bootstrap samples of held-out validation data. The mean Pearson’s correlation between observed and estimated prevalence at validation locations was 0.693; the mean prediction error (average difference between observed and estimated values) was 0.77%, and the mean absolute prediction error (average magnitude of difference between observed and estimated values) was 12.2%. Within OCP boundaries, 17.8 million people were deemed to have been at risk, 7.55 million to have been infected, and mean microfilarial prevalence to have been 45% (range: 2–90%) in 1975. Conclusions and Significance: This is the first map of initial onchocerciasis prevalence in West Africa using B-MBG. Important environmental predictors of infection prevalence were identified and used in a model out-performing those without spatial random effects or environmental covariates. Results may be compared with recent epidemiological mapping efforts to find areas of persisting transmission. These methods may be extended to areas where data are sparse, and may be used to help inform the feasibility of elimination with current and novel tools

Situation analysis of parasitological and entomological indices of onchocerciasis transmission in three drainage basins of the rain forest of South West Cameroon after a decade of ivermectin treatment

BACKGROUND: Community-Directed Treatment with Ivermectin (CDTI) is the main strategy adopted by the African Programme for Onchocerciasis control (APOC). Recent reports from onchocerciasis endemic areas of savannah zones have demonstrated the feasibility of disease elimination through CDTI. Such information is lacking in rain forest zones. In this study, we investigated the parasitological and entomological indices of onchocerciasis transmission in three drainage basins in the rain forest area of Cameroon [after over a decade of CDTI]. River basins differed in terms of river number and their flow rates; and were characterized by high pre-control prevalence rates (60-98%). METHODS: Nodule palpation and skin snipping were carried out in the study communities to determine the nodule rates, microfilarial prevalences and intensity. Simulium flies were caught at capture points and dissected to determine the biting, parous, infection and infective rates and the transmission potential. RESULTS: The highest mean microfilaria (mf) prevalence was recorded in the Meme (52.7%), followed by Mungo (41.0%) and Manyu drainage basin (33.0%). The same trend was seen with nodule prevalence between the drainage basins. Twenty-three (23/39) communities (among which 13 in the Meme) still had mf prevalence above 40%. All the communities surveyed had community microfilarial loads (CMFL) below 10 mf/skin snip (ss). The infection was more intense in the Mungo and Meme. The intensity of infection was still high in younger individuals and children less than 10 years of age. Transmission potentials as high as 1211.7 infective larvae/person/month were found in some of the study communities. Entomological indices followed the same trend as the parasitological indices in the three river basins with the Meme having the highest values. CONCLUSION: When compared with pre-control data, results of the present study show that after over a decade of CDTI, the burden of onchocerciasis has reduced. However, transmission is still going on in this study site where loiasis and onchocerciasis are co-endemic and where ecological factors strongly favour the onchocerciasis transmission. The possible reasons for this persistent and differential transmission despite over a decade of control efforts using ivermectin are discussed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13071-015-0817-2) contains supplementary material, which is available to authorized users

Electrodiagnostic subtyping in Guillain–Barr\ue9 syndrome patients in the International Guillain–Barr\ue9 Outcome Study

\ua9 2024 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.Background and purpose: Various electrodiagnostic criteria have been developed in Guillain–Barr\ue9 syndrome (GBS). Their performance in a broad representation of GBS patients has not been evaluated. Motor conduction data from the International GBS Outcome Study (IGOS) cohort were used to compare two widely used criterion sets and relate these to diagnostic amyotrophic lateral sclerosis criteria. Methods: From the first 1500 patients in IGOS, nerve conduction studies from 1137 (75.8%) were available for the current study. These patients were classified according to nerve conduction studies criteria proposed by Hadden and Rajabally. Results: Of the 1137 studies, 68.3% (N = 777) were classified identically according to criteria by Hadden and Rajabally: 111 (9.8%) axonal, 366 (32.2%) demyelinating, 195 (17.2%) equivocal, 35 (3.1%) inexcitable and 70 (6.2%) normal. Thus, 360 studies (31.7%) were classified differently. The areas of differences were as follows: 155 studies (13.6%) classified as demyelinating by Hadden and axonal by Rajabally; 122 studies (10.7%) classified as demyelinating by Hadden and equivocal by Rajabally; and 75 studies (6.6%) classified as equivocal by Hadden and axonal by Rajabally. Due to more strictly defined cutoffs fewer patients fulfilled demyelinating criteria by Rajabally than by Hadden, making more patients eligible for axonal or equivocal classification by Rajabally. In 234 (68.6%) axonal studies by Rajabally the revised El Escorial (amyotrophic lateral sclerosis) criteria were fulfilled; in axonal cases by Hadden this was 1.8%. Conclusions and discussion: This study shows that electrodiagnosis in GBS is dependent on the criterion set utilized, both of which are based on expert opinion. Reappraisal of electrodiagnostic subtyping in GBS is warranted

Drug discovery: Insights from the invertebrate Caenorhabditis elegans

Therapeutic drug development is a long, expensive, and complex process that usually takes 12–15 years. In the early phases of drug discovery, in particular, there is a growing need for animal models that ensure the reduction in both cost and time. Caenorhabditis elegans has been traditionally used to address fundamental aspects of key biological processes, such as apoptosis, aging, and gene expression regulation. During the last decade, with the advent of large-scale platforms for screenings, this invertebrate has also emerged as an essential tool in the pharmaceutical research industry to identify novel drugs and drug targets. In this review, we discuss the reasons why C. elegans has been positioned as an outstanding cost-effective option for drug discovery, highlighting both the advantages and drawbacks of this model. Particular attention is paid to the suitability of this nematode in large-scale genetic and pharmacological screenings. High-throughput screenings in C. elegans have indeed contributed to the breakthrough of a wide variety of candidate compounds involved in extensive fields including neurodegeneration, pathogen infections and metabolic disorders. The versatility of this nematode, which enables its instrumentation as a model of human diseases, is another attribute also herein underscored. As illustrative examples, we discuss the utility of C. elegans models of both human neurodegenerative diseases and parasitic nematodes in the drug discovery industry. Summing up, this review aims to demonstrate the impact of C. elegans models on the drug discovery pipeline.Fil: Giunti, Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Andersen, Natalia Denise. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Rayes, Diego Hernán. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: de Rosa, Maria Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentin

The global distribution of lymphatic filariasis, 2000–18: a geospatial analysis

Background Lymphatic filariasis is a neglected tropical disease that can cause permanent disability through disruption of the lymphatic system. This disease is caused by parasitic filarial worms that are transmitted by mosquitos. Mass drug administration (MDA) of antihelmintics is recommended by WHO to eliminate lymphatic filariasis as a public health problem. This study aims to produce the first geospatial estimates of the global prevalence of lymphatic filariasis infection over time, to quantify progress towards elimination, and to identify geographical variation in distribution of infection. Methods A global dataset of georeferenced surveyed locations was used to model annual 2000–18 lymphatic filariasis prevalence for 73 current or previously endemic countries. We applied Bayesian model-based geostatistics and time series methods to generate spatially continuous estimates of global all-age 2000–18 prevalence of lymphatic filariasis infection mapped at a resolution of 5 km2 and aggregated to estimate total number of individuals infected. Findings We used 14 927 datapoints to fit the geospatial models. An estimated 199 million total individuals (95% uncertainty interval 174–234 million) worldwide were infected with lymphatic filariasis in 2000, with totals for WHO regions ranging from 3·1 million (1·6–5·7 million) in the region of the Americas to 107 million (91–134 million) in the South-East Asia region. By 2018, an estimated 51 million individuals (43–63 million) were infected. Broad declines in prevalence are observed globally, but focal areas in Africa and southeast Asia remain less likely to have attained infection prevalence thresholds proposed to achieve local elimination. Interpretation Although the prevalence of lymphatic filariasis infection has declined since 2000, MDA is still necessary across large populations in Africa and Asia. Our mapped estimates can be used to identify areas where the probability of meeting infection thresholds is low, and when coupled with large uncertainty in the predictions, indicate additional data collection or intervention might be warranted before MDA programmes cease