Helena Greter

Global burden of human brucellosis : a systematic review of disease frequency

Background This report presents a systematic review of scientific literature published between 1990–2010 relating to the frequency of human brucellosis, commissioned by WHO. The objectives were to identify high quality disease incidence data to complement existing knowledge of the global disease burden and, ultimately, to contribute towards the calculation of a Disability-Adjusted Life Years (DALY) estimate for brucellosis. Methods/Principal Findings Thirty three databases were searched, identifying 2,385 articles relating to human brucellosis. Based on strict screening criteria, 60 studies were selected for quality assessment, of which only 29 were of sufficient quality for data analysis. Data were only available from 15 countries in the regions of Northern Africa and Middle East, Western Europe, Central and South America, Sub-Saharan Africa, and Central Asia. Half of the studies presented incidence data, six of which were longitudinal prospective studies, and half presented seroprevalence data which were converted to incidence rates. Brucellosis incidence varied widely between, and within, countries. Although study biases cannot be ruled out, demographic, occupational, and socioeconomic factors likely play a role. Aggregated data at national or regional levels do not capture these complexities of disease dynamics and, consequently, at-risk populations or areas may be overlooked. In many brucellosis-endemic countries, health systems are weak and passively-acquired official data underestimate the true disease burden. Conclusions High quality research is essential for an accurate assessment of disease burden, particularly in Eastern Europe, the Asia-Pacific, Central and South America and Africa where data are lacking. Providing formal epidemiological and statistical training to researchers is essential for improving study quality. An integrated approach to disease surveillance involving both human health and veterinary services would allow a better understanding of disease dynamics at the animal-human interface, as well as a more cost-effective utilisation of resources.

Clinical manifestations of human brucellosis: a systematic review and meta-analysis.

Background The objectives of this systematic review, commissioned by WHO, were to assess the frequency and severity of clinical manifestations of human brucellosis, in view of specifying a disability weight for a DALY calculation. Methods/Principal Findings Thirty three databases were searched, with 2,385 articles published between January 1990–June 2010 identified as relating to human brucellosis. Fifty-seven studies were of sufficient quality for data extraction. Pooled proportions of cases with specific clinical manifestations were stratified by age category and sex and analysed using generalized linear mixed models. Data relating to duration of illness and risk factors were also extracted. Severe complications of brucellosis infection were not rare, with 1 case of endocarditis and 4 neurological cases per 100 patients. One in 10 men suffered from epididymo-orchitis. Debilitating conditions such as arthralgia, myalgia and back pain affected around half of the patients (65%, 47% and 45%, respectively). Given that 78% patients had fever, brucellosis poses a diagnostic challenge in malaria-endemic areas. Significant delays in appropriate diagnosis and treatment were the result of health service inadequacies and socioeconomic factors. Based on disability weights from the 2004 Global Burden of Disease Study, a disability weight of 0.150 is proposed as the first informed estimate for chronic, localised brucellosis and 0.190 for acute brucellosis. Conclusions This systematic review adds to the understanding of the global burden of brucellosis, one of the most common zoonoses worldwide. The severe, debilitating, and chronic impact of brucellosis is highlighted. Well designed epidemiological studies from regions lacking in data would allow a more complete understanding of the clinical manifestations of disease and exposure risks, and provide further evidence for policy-makers. As this is the first informed estimate of a disability weight for brucellosis, there is a need for further debate amongst brucellosis experts and a consensus to be reached.

Prevalence of Fasciola gigantica infection in slaughtered animals in south-eastern Lake Chad area in relation to husbandry practices and seasonal water levels

BackgroundFasciolosis has been described in sub-Saharan Africa in many accounts, but the latest reports from Chad are from the 1970s. Mobile pastoralists perceive liver parasites as a significant problem and think that proximity to Lake Chad can lead to infection. This study aimed to assess the importance of liver fluke infections in mobile pastoralists’ livestock in the south-eastern Lake Chad region.In 2011, all animals presented at three slaughter slabs near Gredaya in the south-eastern Lake Chad area were examined for infection with Fasciola spp. during routine meat inspections.ResultsThis study included 616 goats, 132 sheep and 130 cattle. The prevalence of adult Fasciola gigantica was 68% (CI 60-76%) in cattle, 12% (CI 10-16%) in goats and 23% (CI 16-30%) in sheep. From all infected animals (n = 200), 53% (n = 106) were classified as lightly infected with 1-10 parasites, 18% (n =36) as moderately infected with 11-100 parasites and 29% (n = 58) as heavily infected with more than 100 parasites per animal.Animals grazing close to the shores of Lake Chad had a much higher risk of infection (prevalence =38%; n = 329) than animals not feeding at the lake (n = 353), with only one goat being positive (prevalence = 0.28%).The ethnic group of the owner was a strong determinant for the risk of infection. Ethnic group likely served as a proxy for husbandry practices. Geospatial distribution showed that animals originating from areas close to the lake were more likely to be infected with F. gigantica than those from more distant areas.ConclusionsLivestock belonging to ethnic groups which traditionally stay near surface water, and which were reported to feed near Lake Chad, have a high risk of infection with F. gigantica. Pastoralist perception of fasciolosis as a priority health problem was confirmed.Regular preventive and post-exposure treatment is recommended for animals grazing near the lake. However, further economic analysis is needed.

Validation of a Point-of-Care Circulating Cathodic Antigen Urine Cassette Test for Schistosoma mansoni Diagnosis in the Sahel, and Potential Cross-Reaction in Pregnancy

On the shores of Lake Chad, schistosomiasis among mobile pastoralists was investigated in a field laboratory. Point-of-care circulating cathodic antigen (POC-CCA) cassette test, reagent strip, and filtration were conducted on urine samples. Fresh stool samples were subjected to the Kato-Katz technique, and fixed samples were examined with an ether-concentration method at a reference laboratory. POC-CCA urine cassette tests revealed a Schistosoma mansoni prevalence of 6.9%, compared with only 0.5% by stool microscopy. Three pregnant women with otherwise negative urine and stool testing had positive POC-CCA. This observation raises concern of cross-reactivity in pregnancy. Hence, two pregnant women in Switzerland with no history of schistosomiasis were subjected to POC-CCA and one tested positive. Our data suggest that POC-CCA can be performed under extreme Sahelian conditions (e.g., temperatures > 40°C), and it is more sensitive than stool microscopy for S. mansoni diagnosis. However, potential cross-reactivity in pregnancy needs further investigation.

Treatment of human and livestock helminth infections in a mobile pastoralist setting at Lake Chad: Attitudes to health and analysis of active pharmaceutical ingredients of locally available anthelminthic drugs.

Mobile pastoralists face challenges in accessing quality health care and medication for managing human and animal diseases. We determined livestock disease priorities, health seeking behaviour of people bearing helminthiases and - placing particular emphasis on trematode infections - treatment strategies and outcome satisfaction among mobile pastoralists of four ethnic groups in the Lake Chad area using focus group discussions. People suffering from schistosomiasis were interviewed about symptoms, health seeking behaviour and their satisfaction with respect to the provided treatment. Anthelminthic drugs for human and veterinary use obtained from various health care structures were analysed for active pharmaceutical ingredients (API) and quantity, using high pressure liquid chromatography-UV and liquid chromatography combined with tandem mass spectrometry. Most people suffering from schistosomiasis sought treatment at health care centres. Yet, they also consulted informal providers without medical training. Regarding animal health, self-mediated therapy was common to manage suspected livestock fascioliasis. Self-reported treatment satisfaction for human schistosomiasis and trematodiasis treatment outcome in livestock were low. Mobile pastoralists perceived the purchased drugs to be of low quality. Among 33 products locally sold as anthelminthic drugs for human or veterinary use, 27 contained albendazole or mebendazole, varying between 91% and 159% of the labelled amount. Six products were sold loosely with incomplete information and their API could not be identified. No counterfeit anthelminthic drugs were detected. None of the samples contained praziquantel or triclabendazole, the drugs of choice against schistosomiasis and fascioliasis, respectively. The perceived unsatisfactory treatment outcomes in humans and animals infected with trematodes are most likely due to empiric diagnosis and the resulting use of inadequate therapy for human schistosomiasis and the lack of efficacious drugs against livestock fascioliasis.

Human and livestock trematode infections in a mobile pastoralist setting at Lake Chad : added value of a One Health approach beyond zoonotic diseases research

Background At Lake Chad in Central Africa, mobile pastoralists face economic losses due to livestock trematodiases. Fasciola gigantica and Schistosoma bovis-trematodes that affect livestock-share transmission ecology traits with Schistosoma haematobium and S. mansoni that cause human schistosomiasis. This project aimed at assessing treatment strategies and elucidating the predictive potential of human and livestock trematode infections. Methods Schistosomiasis and fascioliasis were investigated concurrently in humans and cattle by repeated cross-sectional surveys. Urine and stool samples from humans and faecal samples from cattle were examined for trematode eggs. Treatment strategies were assessed by means of focus group discussions and in-depth interviews. Results Mobile pastoralists of four ethnic groups participated. Prevalence of human schistosomiasis and livestock trematodiases showed considerable heterogeneity from one ethnic group to another, but correlated within ethnic groups. Effective trematocidal drugs were not available in the study area. Conclusions Mutual predictive potential of human schistosomiasis and livestock fascioliasis relates to distinct livestock husbandry practices. Introducing efficacious strategic treatment against human schistosomiasis and livestock fascioliasis might improve human and animal health and well-being. Our research provides evidence for the benefits of a One Health approach targeting diseases that share specific ecological traits.

Re-infection with Fasciola gigantica 6-month post-treatment with triclabendazole in cattle from mobile pastoralist husbandry systems at Lake Chad

At Lake Chad in central Africa, livestock fascioliasis caused by Fasciola gigantica represents a major veterinary health problem, particularly in cattle reared in mobile pastoralist husbandry systems. We assessed re-infection after a single dose of triclabendazole with fascioliasis in cattle in a mobile pastoralist setting towards the end of the dry season. Within the cattle herds of 14 groups of mobile pastoralists, 375 cattle were randomly selected. A faecal sample was obtained from each animal to determine the prevalence of F. gigantica. Animals were administered a single oral dose of triclabendazole (12mg/kg). A second faecal sample was obtained 6-month post-treatment after cattle had returned from the annual migration cycle. Faecal samples were fixed in sodium acetate-acetic acid-formalin (SAF), and examined for F. gigantica using the sedimentation technique. From the 375 cattle enrolled at baseline, 198 animals (53%) in 12 groups of mobile pastoralists were re-sampled at the 6-month follow-up. Baseline prevalence did not differ noteworthy between animals lost to follow-up and those re-examined. At baseline, bovine fascioliasis prevalence in cattle with follow-up data was 41.9% (95% confidence interval (CI) 35.2-48.9%). At the 6-month post-treatment follow-up, the prevalence was 46.0% (95% CI 39.2-52.9%), ranging between 0% and 75% at the herd level. The mean faecal egg counts at the unit of the herd were higher at follow-up compared to baseline. The observed persistent high prevalence of F. gigantica infection in cattle shows that a single pre-rainy season treatment does not prevent rapid re-infection despite the partial migration away from the high-risk areas at Lake Chad into drier areas. A locally adapted strategic control package for fascioliasis in cattle in the Lake Chad area ought to integrate targeted triclabendazole treatment and seasonal transhumance practices.

Human and animal health surveys among pastoralists.

Valid human and livestock health surveys, including longitudinal follow-up, are feasible among mobile pastoralists and provide fundamental information to agencies for interventions that are responsive to realities and effective in addressing the needs of pastoralists. However, pastoralists are often excluded from studies, surveillance systems and health programmes. The occurrence of preventable and treatable diseases such as perinatal tetanus, measles and tuberculosis are indicative of limited access to health providers and information. It is difficult for health services to include effective outreach with their available financial and human resources. One consequence is that maternal mortality rates among pastoralists are unacceptably high. Environmental determinants such as the quality of water and the pasture ecosystems further influence the morbidity of pastoralists. In the Sahel, the nutritional status of pastoralist children is seasonally better than that of settled children; but pastoralist women tend to have higher acute malnutrition rates. Pastoralist women are more vulnerable than men to exclusion from health services for different context-specific reasons. Evidence-based control measures can be assessed in cluster surveys with simultaneous assessments of health among people and livestock, where data on costs of disease and interventions are also collected. These provide important arguments for governmental and non-governmental agencies for intervention development. New, integrated One Health surveillance systems making use of mobile technology and taking into account local concepts and the experiences and priorities of pastoralist communities, combined with sound field data, are essential to develop and provide adapted human and animal health services that are inclusive for mobile pastoralist communities and allow them to maintain their mobile way of life.