An integrated study of human and animal infectious disease in the Lake Victoria crescent small-holder crop-livestock production system, Kenya

Background: The neglected zoonotic diseases (NZD) are an understudied group that are a major cause of illness throughout the developing world. In general, little is known about the prevalence and burden of NZDs in affected communities, particularly in relation to other infectious diseases with which they are often co-endemic. We describe the design and descriptive epidemiological outputs from an integrated study of human and animal zoonotic and non-zoonotic disease in a rural farming community in western Kenya. Methods: This cross-sectional survey involved 2113 people, their cattle (n = 983) and pigs (n = 91). People and animals were tested for infection or exposure to a wide range of zoonotic and non-zoonotic pathogens. Prevalence estimates, with adjustment for the complex study design, were derived. Evidence for spatial clustering in exposure or infection was identified using the spatial scan statistic. Results: There was a high prevalence of human parasitism in the community, particularly with hookworm (Ancylostoma duodenale or Necator americanus) (36.3% (95% CI 32.8–39.9)), Entamoeba histolytica/dispar (30.1% (95% CI 27.5–32.8)), and Plasmodium falciparum (29.4% (95% CI 26.8–32.0)). Human infection with Taenia spp. was also prevalent (19.7% (95% CI 16. 7–22.7)), while exposure to other zoonotic pathogens was comparatively rarer (Brucella spp., 0.6% (95% CI 0.2–0.9); Coxiella burnetii, 2.2% (95% CI 1.5–2.9); Rift Valley fever, 0.5% (95% CI 0.2–0.8)). A low prevalence of exposure to Brucella spp. was observed in cattle (0.26% (95% CI 0–0.56). This was higher for Rift Valley fever virus (1.4% (95% CI 0.5–2.22)) and C. burnetii (10.0% (95% CI 7.7–12.2)). The prevalence of Taenia spp. cysticercosis was 53.5% (95% CI 48.7–58.3) in cattle and 17.2% (95% CI 9.1–25.3) in pigs. Mycobacterium bovis infection was found in 2.2% of cattle (95% CI 1.3–3.2), while the prevalence of infection with Mycobacterium spp. was 8.2% (95% CI 6.8–9.6) in people. Conclusion: Zoonotic infections in people and animals occur in the context of a wide range of co-endemic pathogens in a rural community in western Kenya. The wide diversity of pathogens under study provides a unique opportunity to explore the distribution and determinants of infection in a multi-pathogen, multi-host system

Comparative assessment of onabotulinumtoxinA and mirabegron for overactive bladder: an indirect treatment comparison

CONTEXT: OnabotulinumtoxinA and mirabegron have recently gained marketing authorisation to treat symptoms of overactive bladder (OAB). OBJECTIVE: To evaluate the relative efficacy of mirabegron and onabotulinumtoxinA in patients with idiopathic OAB. DESIGN: Network meta-analysis. DATA SOURCES: A search of 9 electronic databases, review documents, guidelines and websites. METHODS: Randomised trials comparing any licensed dose of onabotulinumtoxinA or mirabegron with each other, anticholinergic drugs or placebo were eligible (19 randomised trials were identified). 1 reviewer extracted data from the studies and a second reviewer checked the data. Candidate trials were assessed for similarity and networks were developed for each outcome. Bayesian network meta-analysis was conducted using both fixed-effects and random-effects models. When there were differences in mean baseline values between mirabegron and onabotulinumtoxinA trials they were adjusted for using network meta-regression (NMR). RESULTS: No studies directly comparing onabotulinumtoxinA to mirabegron were identified. A network was created for each of the 7 outcomes, with 3-9 studies included in each individual network. The trials included in the networks were broadly similar. Patients in the onabotulinumtoxinA trials had more urinary incontinence and urgency episodes at baseline than patients in the mirabegron trials and these differences were adjusted for using NMR. Both onabotulinumtoxinA and mirabegron were more efficacious than placebo at reducing the frequency of urinary incontinence, urgency, urination and nocturia. OnabotulinumtoxinA was more efficacious than mirabegron (50 and 25 mg) in completely resolving daily episodes of urinary incontinence and urgency and in reducing the frequency of urinary incontinence, urgency and urination. NMR supported the results of the network meta-analysis. CONCLUSIONS: In the absence of head-to-head trials comparing onabotulinumtoxinA to mirabegron, this indirect comparison indicates that onabotulinumtoxinA may be superior to mirabegron in improving symptoms of urinary incontinence, urgency and urinary frequency in patients with idiopathic OAB

Microbial uptake kinetics of dissolved organic carbon (DOC) compound groups from river water and sediments

Dissolved organic matter (DOM) represents a key component of carbon (C) cycling in freshwater ecosystems. While the behaviour of bulk dissolved organic carbon (DOC) in aquatic ecosystems is well studied, comparatively little is known about the turnover of specific DOC compounds. The aim of this study was to investigate the persistence of 14C-labelled low molecular weight (LMW) DOC at a wide range of concentrations (0.1 µM to 10 mM), in sediments and waters from oligotrophic and mesotrophic rivers within the same catchment. Overall, rates of DOC loss varied between compound groups (amino acids > sugars = organic acids > phenolics). Sediment-based microbial communities contributed to higher DOC loss from river waters, which was attributed, in part, to its greater microbial biomass. At higher DOC compound concentrations, DOC loss was greater in mesotrophic rivers in comparison to oligotrophic headwaters. A lag-phase in substrate use within sediments provided evidence of microbial growth and adaptation, ascribed here to the lack of inorganic nutrient limitation on microbial C processing in mesotrophic communities. We conclude that the higher microbial biomass and available inorganic nutrients in sediments enables the rapid processing of LMW DOC, particularly during high C enrichment events and in N and P-rich mesotrophic environments

One health research in Northern Tanzania – challenges and progress

East Africa has one of the world’s fastest growing human populations—many of whom are dependent on livestock—as well as some of the world’s largest wildlife populations. Humans, livestock, and wildlife often interact closely, intimately linking human, animal, and environmental health. The concept of One Health captures this interconnectedness, including the social structures and beliefs driving interactions between species and their environments. East African policymakers and researchers are recognising and encouraging One Health research, with both groups increasingly playing a leading role in this subject area. One Health research requires interaction between scientists from different disciplines, such as the biological and social sciences and human and veterinary medicine. Different disciplines draw on norms, methodologies, and terminologies that have evolved within their respective institutions and that may be distinct from or in conflict with one another. These differences impact interdisciplinary research, both around theoretical and methodological approaches and during project operationalisation. We present experiential knowledge gained from numerous ongoing projects in northern Tanzania, including those dealing with bacterial zoonoses associated with febrile illness, foodborne disease, and anthrax. We use the examples to illustrate differences between and within social and biological sciences and between industrialised and traditional societies, for example, with regard to consenting procedures or the ethical treatment of animals. We describe challenges encountered in ethical approval processes, consenting procedures, and field and laboratory logistics and offer suggestions for improvement. While considerable investment of time in sensitisation, communication, and collaboration is needed to overcome interdisciplinary challenges inherent in One Health research, this can yield great rewards in paving the way for successful implementation of One Health projects. Furthermore, continued investment in African institutions and scientists will strengthen the role of East Africa as a world leader in One Health research

A short-term mouse model that reproduces the immunopathological features of rhinovirus-induced exacerbation of COPD

© 2015 The Author(s). Viral exacerbations of chronic obstructive pulmonary disease (COPD), commonly caused by rhinovirus (RV) infections, are poorly controlled by current therapies. This is due to a lack of understanding of the underlying immunopathological mechanisms. Human studies have identified a number of key immune responses that are associated with RV-induced exacerbations including neutrophilic inflammation, expression of inflammatory cytokines and deficiencies in innate anti-viral interferon. Animal models of COPD exacerbation are required to determine the contribution of these responses to disease pathogenesis. We aimed to develop a short-term mouse model that reproduced the hallmark features of RV-induced exacerbation of COPD. Evaluation of complex protocols involving multiple dose elastase and lipopolysaccharide (LPS) administration combined with RV1B infection showed suppression rather than enhancement of inflammatory parameters compared with control mice infected with RV1B alone. Therefore, these approaches did not accurately model the enhanced inflammation associated with RV infection in patients with COPD compared with healthy subjects. In contrast, a single elastase treatment followed by RV infection led to heightened airway neutrophilic and lymphocytic inflammation, increased expression of tumour necrosis factor (TNF)-α, C-X-C motif chemokine 10 (CXCL10)/IP-10 (interferon γ-induced protein 10) and CCL5 [chemokine (C-C motif) ligand 5]/RANTES (regulated on activation, normal T-cell expressed and secreted), mucus hypersecretion and preliminary evidence for increased airway hyper-responsiveness compared with mice treated with elastase or RV infection alone. In summary, we have developed a new mouse model of RV-induced COPD exacerbation that mimics many of the inflammatory features of human disease. This model, in conjunction with human models of disease, will provide an essential tool for studying disease mechanisms and allow testing of novel therapies with potential to be translated into clinical practice

Rapid depletion of dissolved organic sulphur (DOS) in freshwaters

Sulphur (S) is a key macronutrient for all organisms, with similar cellular requirements to that of phosphorus (P). Studies of S cycling have often focused on the inorganic fraction, however, there is strong evidence to suggest that freshwater microorganisms may also access dissolved organic S (DOS) compounds (e.g. S-containing amino acids). The aim of this study was to compare the relative concentration and depletion rates of organic 35S-labelled amino acids (cysteine, methionine) with inorganic S (Na235SO4) in oligotrophic versus mesotrophic river waters draining from low nutrient input and moderate nutrient input land uses respectively. Our results showed that inorganic SO42− was present in the water column at much higher concentrations than free amino acids. In contrast to SO42−, however, cysteine and methionine were both rapidly depleted from the mesotrophic and oligotrophic waters with a halving time < 1 h. Only a small proportion of the DOS removed from solution was mineralized and excreted as SO42− (< 16% of the total taken up) suggesting that the DOS could be satisfying a demand for carbon (C) and S. In conclusion, even though inorganic S was abundant in freshwater, it appears that the aquatic communities retained the capacity to take up and assimilate DOS

Environmental predictors of bovine Eimeria infection in western Kenya

Eimeriosis is caused by a protozoan infection affecting most domestic animal species. Outbreaks in cattle are associated with various environmental factors in temperate climates but limited work has been done in tropical settings. The objective of this work was to determine the prevalence and environmental factors associated with bovine Eimeria spp. infection in a mixed farming area of western Kenya. A total of 983 cattle were sampled from 226 cattle-keeping households. Faecal samples were collected directly from the rectum via digital extraction and analysed for the presence of Eimeria spp. infection using the MacMaster technique. Individual and household level predictors of infection were explored using mixed effects logistic regression. The prevalence of individual animal Eimeria infection was 32.8% (95% CI 29.9–35.9). A positive linear relationship was found between risk of Eimeria infection and increasing temperature (OR = 1.4, 95% CI 1.06–1.86) and distance to areas at risk of flooding (OR = 1.49, 95% CI 1.17–1.91). There was weak evidence of non-linear relationship between Eimeria infection and the proportion of the area around a household that was classified as swamp (OR = 1.12, 95% CI 0.87–1.44; OR (quadratic term) = 0.85, 95% CI 0.73–1.00), and the sand content of the soil (OR = 1.18, 95% CI 0.91–1.53; OR (quadratic term) = 1.1, 95% CI 0.99–1.23). The risk of animal Eimeria spp. infection is influenced by a number of climatic and soil-associated conditions.</p

General contextual effects on neglected tropical disease risk in rural Kenya

The neglected tropical diseases (NTDs) are characterized by their tendency to cluster within groups of people, typically the poorest and most marginalized. Despite this, measures of clustering, such as within-group correlation or between-group heterogeneity, are rarely reported from community-based studies of NTD risk. We describe a general contextual analysis that uses multi-level models to partition and quantify variation in individual NTD risk at multiple grouping levels in rural Kenya. The importance of general contextual effects (GCE) in structuring variation in individual infection with Schistosoma mansoni, the soil-transmitted helminths, Taenia species, and Entamoeba histolytica/dispar was examined at the household-, sublocation- and constituency-levels using variance partition/intra-class correlation co-efficients and median odds ratios. These were compared with GCE for HIV, Plasmodium falciparum and Mycobacterium tuberculosis. The role of place of residence in shaping infection risk was further assessed using the spatial scan statistic. Individuals from the same household showed correlation in infection for all pathogens, and this was consistently highest for the gastrointestinal helminths. The lowest levels of household clustering were observed for E. histolytica/dispar, P. falciparum and M. tuberculosis. Substantial heterogeneity in individual infection risk was observed between sublocations for S. mansoni and Taenia solium cysticercosis and between constituencies for infection with S. mansoni, Trichuris trichiura and Ascaris lumbricoides. Large overlapping spatial clusters were detected for S. mansoni, T. trichiura, A. lumbricoides, and Taenia spp., which overlapped a large cluster of elevated HIV risk. Important place-based heterogeneities in infection risk exist in this community, and these GCEs are greater for the NTDs and HIV than for TB and malaria. Our findings suggest that broad-scale contextual drivers shape infectious disease risk in this population, but these effects operate at different grouping-levels for different pathogens. A general contextual analysis can provide a foundation for understanding the complex ecology of NTDs and contribute to the targeting of interventions