Marie J. Ducrotoy

Brucellosis as an emerging threat in developing economies: lessons from Nigeria.

Nigeria is the most populous country in Africa, has a large proportion of the worlds poor livestock keepers, and is a hotspot for neglected zoonoses. A review of the 127 accessible publications on brucellosis in Nigeria reveals only scant and fragmented evidence on its spatial and temporal distribution in different epidemiological contexts. The few bacteriological studies conducted demonstrate the existence of Brucella abortus in cattle and sheep, but evidence for B. melitensis in small ruminants is dated and unclear. The bulk of the evidence consists of seroprevalence studies, but test standardization and validation are not always adequately described, and misinterpretations exist with regard to sensitivity and/or specificity and ability to identify the infecting Brucella species. Despite this, early studies suggest that although brucellosis was endemic in extensive nomadic systems, seroprevalence was low, and brucellosis was not perceived as a real burden; recent studies, however, may reflect a changing trend. Concerning human brucellosis, no studies have identified the Brucella species and most reports provide only serological evidence of contact with Brucella in the classical risk groups; some suggest brucellosis misdiagnoses as malaria or other febrile conditions. The investigation of a severe outbreak that occurred in the late 1970s describes the emergence of animal and human disease caused by the settling of previously nomadic populations during the Sahelian drought. There appears to be an increasing risk of re-emergence of brucellosis in sub-Saharan Africa, as a result of the co-existence of pastoralist movements and the increase of intensive management resulting from growing urbanization and food demand. Highly contagious zoonoses like brucellosis pose a threat with far-reaching social and political consequences.

The neglected zoonoses--the case for integrated control and advocacy.

The neglected zoonotic diseases (NZDs) have been all but eradicated in wealthier countries, but remain major causes of ill-health and mortality across Africa, Asia, and Latin America. This neglect is, in part, a consequence of under-reporting, resulting in an underestimation of their global burden that downgrades their relevance to policy-makers and funding agencies. Increasing awareness about the causes of NZDs and how they can be prevented could reduce the incidence of many endemic zoonoses. Addressing NZDs by targeting the animal reservoir can deliver a double benefit, as enhanced animal health means a reduced risk of infection for humans, as well as improved livelihoods through increased animal productivity. Advocacy for NZD control is increasing, but with it comes a growing awareness that NZD control demands activities both in the short term and over a long period of time. Moreover, despite the promise of cheap, effective vaccines or other control tools, these endemic diseases will not be sustainably controlled in the near future without long-term financial commitment, particularly as disease incidence decreases and other health priorities take hold. NZD intervention costs can seem high when compared with the public health benefits alone, but these costs are easily outweighed when a full cross-sector analysis is carried out and monetary/non-monetary benefits--particularly regarding the livestock sector--are taken into account. Public-private partnerships have recently provided advocacy for human disease control, and could prove equally effective in addressing endemic zoonoses through harnessing social impact investments. Evidence of the disease burdens imposed on communities by the NZDs and demonstration of the cost-effectiveness of integrated control can strengthen the case for a One Health approach to endemic zoonotic disease control.

Brucellosis in Sub-Saharan Africa: Current challenges for management, diagnosis and control

Brucellosis is a highly contagious zoonosis caused by bacteria of the genus Brucella and affecting domestic and wild mammals. In this paper, the bacteriological and serological evidence of brucellosis in Sub-Saharan Africa (SSA) and its epidemiological characteristics are discussed. The tools available for the diagnosis and treatment of human brucellosis and for the diagnosis and control of animal brucellosis and their applicability in the context of SSA are presented and gaps identified. These gaps concern mostly the need for simpler and more affordable antimicrobial treatments against human brucellosis, the development of a B. melitensis vaccine that could circumvent the drawbacks of the currently available Rev 1 vaccine, and the investigation of serological diagnostic tests for camel brucellosis and wildlife. Strategies for the implementation of animal vaccination are also discussed.

A review of the basis of the immunological diagnosis of ruminant brucellosis

Bacteria of the genus Brucella cause brucellosis, the most common bacterial zoonosis worldwide. The diagnosis of Brucella abortus and Brucella melitensis ruminant brucellosis is based on bacteriological and immunological tests, the latter being routinely used in control and eradication and surveillance programs. Infections by smooth and rough Brucella spp., the use of smooth and rough vaccines, and the false-positive serological reactions caused by Yersinia enterocolitica O:9 and other cross-reacting bacteria represent the immunological contexts in which those tests are used. This complex context explains the large number of brucellosis tests that have been developed, and that vary in antigen type, antigen presentation, antibody and conditions for the reaction, the response detected and the sample required. This wealth of information and an imperfect understanding of Brucella antigens and of the peculiarities of the immunoresponse to Brucella has created confusion and led to several misconceptions on the usefulness and limitations of the brucellosis diagnostic tests. In this review, Brucella antigens are examined focusing on cellular topology, supramolecular properties, epitopic structure and lipopolysaccharide and protein cross-reactivity in the various contexts of the immune response in ruminants. Then, the significance of these features in diagnostic tests that use whole bacteria is discussed with respect to the activities of ruminant immunoglobulins, and the effect of pH on unspecific agglutinations, non-agglutinating and blocking antibodies, pseudo-prozones and complement activation. Similarly, the bacterial surface lipopolysaccharides and cognate polysaccharides are discussed with regards to topological effects, epitope exposure, ionic strength and antibody avidity in immunoprecipitation, immunosorbent and fluorescence polarization assays. Finally, the search for immunodominant protein antigens and their use in immunological tests is reviewed. Critical review of the existing information is necessary both to select optimal tests according to the logistical means available and the epidemiological context, and to focus the development of new tests.

Narrative overview of animal and human brucellosis in Morocco: intensification of livestock production as a driver for emergence?

Brucellosis is one of the most widespread zoonoses in the world caused by several species of the genus Brucella. The disease, eradicated in many developed countries, is a re-emerging neglected zoonosis endemic in several zones especially in the Mediterranean region, impacting on human health and livestock production. A One Health approach could address brucellosis control in Morocco but scarcity of reliable epidemiological data, as well as underreporting, hinders the implementation of sustainable control strategies. Surveillance and control policies implemented by the Moroccan government in domestic animals (cattle and small ruminants) in the last few decades are assessed for disease impact. This study considers the origins of animal brucellosis in Morocco and the potential for emergence of brucellosis during a shift from extensive to intensive livestock production.

Phenotypic and genotypic characterization of Brucella strains isolated from autochthonous livestock reveals the dominance of B. abortus biovar 3a in Nigeria

Brucellosis is a worldwide widespread zoonosis caused by bacteria of the genus Brucella. Control of this disease in a given area requires an understanding of the Brucella species circulating in livestock and humans. However, because of the difficulties intrinsic to Brucella isolation and typing, such data are scarce for resource-poor areas. The paucity of bacteriological data and the consequent imperfect epidemiological picture are particularly critical for Sahelian and Sub-Sahara African countries. Here, we report on the characterization of 34 isolates collected between 1976 and 2012 from cattle, sheep and horses in Nigeria. All isolates were identified as Brucella abortus by Bruce-ladder PCR and assigned to biovar 3 by conventional typing. Further analysis by enhanced AMOS-ERY PCR showed that all of them belonged to the 3a sub-biovar, and MLVA analysis grouped them in a cluster clearly distinct from that formed by European B. abortus biovar 3b strains. Nevertheless, MLVA detected heterogeneity within the Nigerian biovar 3a strains. The close genetic profiles of the isolates from cattle, sheep and horses, suggest that, at least in some parts of Nigeria, biovar 3a circulates among animal species that are not the preferential hosts of B. abortus. Consistent with previous genetic analyses of 7 strains from Ivory Cost, Gambia and Togo, the analysis of these 34 Nigerian strains supports the hypothesis that the B. abortus biovar 3a lineage is dominant in West African countries.

Fulani cattle productivity and management in the Kachia Grazing Reserve, Nigeria

Kachia Grazing Reserve (KGR) in northern Nigeria was home to some 10,000 Fulani pastoralists and their 40,000 cattle in June 2011. This study examines productivity and management of cattle belonging to livestock keepers within the reserve before and after a mass immigration event when 3,000 refugees moved into the reserve with their cattle to escape inter-community violence during May 2011. Data, on livestock management strategies (transhumance) and production parameters (herd size, composition, fertility, dynamics), were collected in March, June and October 2011.Cattle productivity in KGR is geared to supporting Fulani households while maintaining herd wealth. High offtake of young animals, especially the selling of heifers, was an unusual finding and may indicate that KGR pastoralists have been restricting their herd size voluntarily as well as limiting milk production to household requirements. This is probably due to the absence of a commercial milk market and a higher reliance on the sale of young stock to meet cash needs.Despite the widespread perception that grazing reserves are promoting sedentarisation of Fulani pastoralists and curbing transhumance, the inhabitants of the KGR were observed to practise wide-ranging transhumance both during wet and dry seasons driven by the limited availability of grazing. Some households selected a sub-sample of animals for transhumance rather than sending their whole herd, and some maintained cattle on alternative land-holdings outside the reserve. KGR households described modifying their usual transhumance practices in response to the mass immigration event and insecurity.Nevertheless, the herd demography results from this study are broadly similar to data obtained from other studies over the past 40 years, indicating that productivity and management practices have remained relatively unchanged.

A systematic review of current immunological tests for the diagnosis of cattle brucellosis

Brucellosis is a worldwide extended zoonosis with a heavy economic and public health impact. Cattle, sheep and goats are infected by smooth Brucella abortus and Brucella melitensis, and represent a common source of the human disease. Brucellosis diagnosis in these animals is largely based on detection of a specific immunoresponse. We review here the immunological tests used for the diagnosis of cattle brucellosis. First, we discuss how the diagnostic sensitivity (DSe) and specificity (DSp), balance should be adjusted for brucellosis diagnosis, and the difficulties that brucellosis tests specifically present for the estimation of DSe/DSp in frequentistic (gold standard) and Bayesian analyses. Then, we present a systematic review (PubMed, GoogleScholar and CABdirect) of works (154 out of 991; years 1960-August 2017) identified (by title and Abstract content) as DSe and DSp studies of smooth lipopolysaccharide, O-polysaccharide-core, native hapten and protein diagnostic tests. We summarize data of gold standard studies (n = 23) complying with strict inclusion and exclusion criteria with regards to test methodology and definition of the animals studied (infected and S19 or RB51 vaccinated cattle, and Brucella-free cattle affected or not by false positive serological reactions). We also discuss some studies (smooth lipopolysaccharide tests, protein antibody and delayed type hypersensitivity [skin] tests) that do not meet the criteria and yet fill some of the gaps in information. We review Bayesian studies (n = 5) and report that in most cases priors and assumptions on conditional dependence/independence are not coherent with the variable serological picture of the disease in different epidemiological scenarios and the bases (antigen, isotype and immunoglobulin properties involved) of brucellosis tests, practical experience and the results of gold standard studies. We conclude that very useful lipopolysaccharide (buffered plate antigen and indirect ELISA) and native hapten polysaccharide and soluble protein tests exist, provided they are applied taking into account the means available and the epidemiological contexts of this disease: i) mass vaccination; ii) elimination based on vaccination combined with test-and-slaughter; and iii) surveillance and existence of false positive serological reactions. We also conclude that the insistence in recent literature on the lack of usefulness of all smooth lipopolysaccharide or native hapten polysaccharide tests in areas where S19 vaccination is implemented is a misinterpretation that overlooks scientific and practical evidence.

Wealth, household heterogeneity and livelihood diversification of Fulani pastoralists in the Kachia Grazing Reserve, northern Nigeria, during a period of social transition

Background A mixed methods study was undertaken in the Kachia Grazing Reserve of northern Nigeria. Surveys in March, June and October 2011 included focus group discussions, key informant and in-depth household interviews, concerning livelihood practices, animal health, ownership, and productivity. In May 2011, 249 Fulani families fleeing post-election violence entered the reserve with their livestock, increasing the number of households by one third. Results Despite being settled within a grazing reserve, over half of households sent all their cattle away on seasonal transhumance and another third sent some away. Cattle accounted for 96% of total tropical livestock units (TLU), of which 26% were cattle kept permanently outside the reserve. While all households cited livestock as their main source of income, 90% grew crops and 55% derived income from off-farm activities. A multiple correspondence analysis showed that for each extra member of a household its TLU value increased by 2.0 [95% CI, 1.4–2.7], while for each additional marriage its TLU increased by 15.7 [95% CI, 7.1–24.3]. A strong association was also observed between small herds, small households with only one wife, alongside marked geographical wealth differences within the reserve. New immigrant families had larger household sizes (33) and livestock holdings (122 TLU) than old settlers (22 people and 67 TLU). Prior to the mass immigration, the distribution of TLU per person was unimodal: 41% of households were classified as ‘poor’ and 27% as ‘medium’, whereas post-immigration it was bi-modal, with 26% classified as ‘very poor’ and 28% as ‘medium’. Conclusions While cattle remain the principal source of Fulani income and wealth, the inhabitants of Kachia Grazing Reserve have diversified their livelihood strategies to respond to changing circumstances and stress, especially the limited availability of grazing within the reserve and political insecurity outside, resulting in continued transhumance, the maintenance of smaller livestock holdings and pushing households into poverty.

How do you get the Rose Bengal Test at the point-of-care to diagnose brucellosis in Africa? The importance of a systems approach.

Brucellosis is a major neglected zoonotic disease, whose burden both in animals and humans is severely under-reported. Diagnosis in humans identifies cases in order to treat the disease at the individual level. In animals diagnosis is implemented at the population level in the context of appropriate control or eradication strategies. Molecular and bacteriological diagnosis are rarely undertaken in sub-Saharan Africa, at least outside research projects, due to cost, skills and laboratory infrastructure issues. The brucellosis toolbox contains a wide range of serological tests, but the perfect test for use in animals and humans respectively does not exist. Drug and diagnostic discovery for the neglected zoonoses are notoriously poor, and there is limited investment interest in developing new tools for brucellosis diagnosis. But are current tools being used to their full capacity? The rose Bengal test (RBT) stands out as an efficient, practical and very cheap test adapted for use in the resource-poor context. In this paper, we argue that a social science or systems approach to explore the practicality of improving diagnostic capacity at the point-of care in high-risk brucellosis areas of rural Africa may be a step towards solving the issue of under-diagnosis, but this must go hand-in-hand with implementation of control measures at source in the animal reservoir and capacity to treat human cases.