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 need for further debate amongst brucellosis experts and a consensus to be reache

Exploring prospects of novel drugs for tuberculosis

Tuberculosis remains a disease with an enormous impact on public health worldwide. With the continuously increasing epidemic of drug-resistant tuberculosis, new drugs are desperately needed. However, even for the treatment of drug-sensitive tuberculosis, new drugs are required to shorten the treatment duration and thereby prevent development of drug resistance. Within the past ten years, major advances in tuberculosis drug research have been made, leading to a considerable number of antimycobacterial compounds which are now in the pipeline. Here we discuss a number of these novel promising tuberculosis drugs, as well as the discovery of two new potential drug targets for the development of novel effective drugs to curb the tuberculosis pandemic, ie, the coronin 1 and protein kinase G pathways. Protein kinase G is secreted by mycobacteria and is responsible for blocking lysosomal delivery within the macrophage. Coronin 1 is responsible for activating the phosphatase, calcineurin, and thereby preventing phagosome-lysosome fusion within the macrophage. Blocking these two pathways may lead to rapid killing of mycobacteri

Links between biodiversity and human infectious and non-communicable diseases: a review

INTRODUCTION: Biodiversity has intrinsic value and a fundamental role in human health. The relationship between them is complex, and the specific sustaining processes are still not well understood. In view of the rapidly evolving landscape, this literature review investigated scientific evidence for specific links between biodiversity and human infectious and non-communicable diseases to characterise identifiable relationships. METHODS: A search of the PubMed and Web of Science databases using keyword algorithms identified relevant manuscripts published between 1 January 2000 and 18 April 2019. Qualitative data were extracted from 155 studies investigating links between or mechanisms linking biodiversity and infectious disease, non-communicable disease, allergic/inflammatory disease and microbiomes. RESULTS: None of the reviewed studies documented causal evidence for a mechanism linking biodiversity and human health. The main mechanisms proposed to link biodiversity and transmission of infectious disease were dilution and amplification. The dilution hypothesis argues that an increase in species diversity leads to a decrease in pathogen prevalence. The amplification effect is the converse, that there is a positive correlation between species diversity and disease risk/infection prevalence. Several driving factors are postulated, including encounter reduction, interspecies competition and predation. In addition, it appears that scale, both spatial and temporal, highly impacts diversity-disease relationships. There is strong evidence that the early environment of a child, including maternally transferred prenatal signals, affects immune maturation, modifying later disease risk. Bi-directional axes communicate between the gut microbiome and the brain, as well as between the skin microbiome and the lung, leading to direct and indirect immune, humoral and neural mechanisms. The main challenges in assessing links between biodiversity and human health are the wide variation in definitions of health and biodiversity, and the heterogeneity in types of studies encountered, as well as the complexity of interactions in dynamic systems. CONCLUSIONS: Contextually adapted integrative approaches, which maintain dialogue across disciplines and amongst all stakeholders, are most likely to generate robust evidence. Because of the relevance of local scale, research engagement must occur across levels to generate legitimate practices and translate into sustainable, equitable policies. Recommendations for future action include: improve the knowledge base on contribution of biodiversity to health, increase awareness of health effects of natural and near-natural environments and biodiversity, and promote synergies by increasing policy coherence

Domestic dog demographic structure and dynamics relevant to rabies control planning in urban areas in Africa: the case of Iringa, Tanzania

<p>Background Mass vaccinations of domestic dogs have been shown to effectively control canine rabies and hence human exposure to rabies. Knowledge of dog population demography is essential for planning effective rabies vaccination programmes; however, such information is still rare for African domestic dog populations, particularly so in urban areas. This study describes the demographic structure and population dynamics of a domestic dog population in an urban sub-Saharan African setting. In July to November 2005, we conducted a full household-level census and a cross-sectional dog demography survey in four urban wards of Iringa Municipality, Tanzania. The achievable vaccination coverage was assessed by a two-stage vaccination campaign, and the proportion of feral dogs was estimated by a mark-recapture transect study.</p> <p>Results The estimated size of the domestic dog population in Iringa was six times larger than official town records assumed, however, the proportion of feral dogs was estimated to account for less than 1% of the whole population. An average of 13% of all households owned dogs which equalled a dog:human ratio of 1:14, or 0.31 dogs per household or 334 dogs km-2. Dog female:male ratio was 1:1.4. The average age of the population was 2.2 years, 52% of all individuals were less than one year old. But mortality within the first year was high (72%). Females became fertile at the age of 10 months and reportedly remained fertile up to the age of 11 years. The average number of litters whelped per fertile female per year was 0.6 with an average of 5.5 pups born per litter. The population growth was estimated at 10% y-1.</p> <p>Conclusions Such high birth and death rates result in a rapid replacement of anti-rabies immunised individuals with susceptible ones. This loss in herd immunity needs to be taken into account in the design of rabies control programmes. The very small proportion of truly feral dogs in the population implies that vaccination campaigns aimed at the owned dog population are sufficient to control rabies in urban Iringa, and the same may be valid in other, comparable urban settings.</p&gt

Persistence of brucellosis in pastoral systems

Regarded as a highly contagious, zoonotic disease with worldwide distribution, brucellosis is endemic in many countries and settings and is responsible for a considerable economic and health-related burden. Limited information is available on the persistence and prevalence of brucellosis in pastoral communities, due to the difficulty in gathering information and to their mobility. However, since these communities are economically and culturally dependent on livestock, it is important to further determine the cause of persistent disease and develop possible methods for its management. The two main objectives of this paper are to review the literature, identifying various epidemiological and social factors that affect the persistence of brucellosis in pastoral ecosystems, and determine prevalence estimates within these communities. The general trend of the summarised studies indicates low-level, relatively stable transmission of brucellosis in pastoral areas, when compared to transmission in intensive and semi-intensive peri-urban production systems. A formal mathematical analysis can be undertaken using matrix models or coupled differential equations. This allows an examination of the various conditions under which the number of diseased, infected or exposed animals remains stable. The authors examined an existing mathematical differential equation model for brucellosis in Mongolia for its equilibrium conditions and found it reasonably robust, though clearly more data are needed to estimate threshold densities for brucellosis transmission in other regions of the world. However, the results indicate the importance of livestock demographic determinants for brucellosis persistence. The paper concludes that brucellosis remains largely persistent in pastoral areas of the world, despite (varying) control efforts. Plans to control brucellosis in pastoral settings should include ecological considerations, such as sustaining ecosystem services in pastoral areas. This approach would include placing limitations on livestock stocking density, land reform, improved governance and integrated social and economic development

Molecular characterization of two common Chadian cattle breeds

In previous studies, significant differences in Mycobacterium bovis infection prevalence was reported between two Chadian cattle breeds. Those findings and the established differentiation due to phenotypic characteristics suggest that the two breeds (Arab and Mbororo) are genetically different. To evaluate the genetic structure and the differences between these breeds, the genetic diversity within and between breeds was evaluated based on a total of 205 multilocus genotypes (21 microsatellite loci). All of the loci under investigation were polymorphic and the number of alleles ranged from 4 to14 within the two populations. The analysis of population fixation resulted in a FST value of 0.006. Further the population assignment of the individual genotypes and the exact test of population differentiation did not support the hypothesis that the samples drawn from the two populations are genetically different. Population admixture and sample collection are discussed as possible reasons for the rejection of the hypothesis. Finally, recommendations for sample collection in extensive systems are give

Parasitic Infections, Anemia and Malnutrition Among Rural Settled and Mobile Pastoralist Mothers and Their Children in Chad

Malnutrition, resulting from various etiologies, is common in rural Chadian women and children. This cross-sectional study assessed the spectrum of parasitic infection and level of anemia and their effect on nutritional status in settled and mobile pastoral mothers and children near Lake Chad. Intestinal parasites were evaluated using direct fecal smears and the Kato-Katz technique. Malaria status was determined using Paracheck-Pf® rapid diagnostic test, and anemia was assessed with the Hemocue photometer. Nutritional status was evaluated using anthropometric parameters. At the end of the 2008 wet season, the prevalence of malnutrition was 36% [confidence interval (CI) 30-42] among women and 15% (CI 11-18) among children. The prevalence of intestinal parasitic infection was 75% (CI 68-83) among women and 60% (CI 53-66) among children. The predominant helminth species was Ascaris lumbricoides while Entamoeba histolytica/dispar was the most common protozoan. The hookworm prevalence was 14% (CI 8-20) in women and 18% (CI 13-23) in children. Malaria prevalence was low among women (1%, CI 0.5-2) and children (3% CI 2-5). No significant difference was observed in the prevalence of parasitic infection between the mobile pastoralist and rural sedentary populations. Thirty-four percent (CI 27-40) of nonpregnant women, 53% (CI 34-72) of pregnant women, and 27% (CI 23-32) of children were anemic. In subjects infected with Plasmodium, all women and 54% (CI 22-85) of children were anemic. Malnutrition was significantly associated with anemia in mothers and with selected intestinal parasites, anemia and age in their childre

Epidemics of Crimean-Congo hemorrhagic fever (CCHF) in Sudan between 2010 and 2020

Crimean-Congo hemorrhagic fever (CCHF) is a zoonotic arboviral disease that poses a great threat to global health in the Old World, and it is endemic in Europe, Asia, and Africa, including Sudan. In this retrospective study, we reviewed previous epidemiological reports about the major epidemics of CCHF throughout Sudan between 2010 and 2020. During these epidemics, the infection of humans with Crimean-Congo hemorrhagic fever virus (CCHFV), the causative agent of CCHF, was diagnosed using qRT-PCR. We have identified 88 cases of CCHF, including 13 fatalities reported during five epidemics that occurred in 2010, 2011, 2015, 2019, and 2020. The two epidemics in 2010 and 2011 were by far the largest, with 51 and 27 cases reported, respectively. The majority of cases (78%) were reported in the endemic region of Kordofan. Here, we document that the first emergence of CCHFV in the Darfur region, West Sudan, occurred in 2010. We were not able to investigate outbreak dynamics through phylogenetic analysis due to the limited diagnostic capacity and the lack of sequencing services in the country. These findings call for establishing a genomic-based integrated One Health surveillance and response system for the early preparedness, prevention, and control of CCHF in the country

Productivity loss and cost of bovine tuberculosis for the dairy livestock sector in Ethiopia

Bovine tuberculosis (BTB) is endemic in Ethiopia. Although upgraded dairy cattle account for only 1% of the total cattle population, they are the backbone of the marketed milk production in the country. Supported by research data outputs from three years, we report in this paper an estimate of the productivity loss and cost of BTB to the Ethiopian dairy sector in two dairy settings, the urban production system in Central Ethiopia (model 1) and the national upgraded dairy production (model 2). Primary data sources were used (e.g. market survey; three-year longitudinal productivity survey; abattoir survey) as well as secondary data sources. A matrix population model, composed of a population vector representing the herd composition that is repeatedly multiplied with a projection matrix, was developed to simulate the livestock dairy population. The initial herd structure was simulated over 30 years to obtain an equilibrium herd-structure representing an Eigenvector of the projection matrix. We performed an incremental cost of disease analysis by comparing livestock production with and without BTB during a period of 10 years. We assumed a BTB prevalence of 40%. In year ten, the Net present value (NPV) of livestock production in terms of milk, meat and hides was estimated at 154.5 million USD for model 1 and 1.7 billion USD for model 2. Loss of NPV over 10 years was estimated at 12 million USD for model 1 and 131.7 million USD for model 2, representing roughly 7.3% loss in NPV or 219 USD per animal. This is a benchmark against which a national TB control program could be developed in the future to calculate its benefit/cost ratio

First serodetection and molecular phylogenetic documentation of; Coxiella burnetii; isolates from female camels in Wasit governorate, Iraq

This study aims to detect Coxiellaburnetiiin one-humped female camels (Camelus dromedarius) using ELISA andconfirmation of infection by PCR with the phylogenetic analysis of local isolates. The 91 adult female camels were selected for clinical examination and blood sampling fromdifferent areas in Badra and Al-Numaniyah districts in Wasitgovernorate, Iraq, from February to April 2019. The prevalence of Coxiella(C.) burnetiiwas 19.8% and 4.4% by ELISA and PCR, respectively. Targeting 16S rRNA genes from three positive samples were documented in the Genbank-NCBI under accession numbers of MN900579.1, MN900580.1, and MN900581.1. Clinical evaluation revealed insignificant variation in temperature, pulse, respiratory rates, and lymph node enlargement among the positive and negative animals. The findings also showed that camels of the Badra regions have positive signs. burnetiicompared to other regions, and the infection was increased significantly in April and March. In conclusion, our findings confirmed the prevalence ofC. burnethamong Iraqi female camels, suggesting that these animals might be a source of the pathogenfor humans and other animal species. Therefore, further studies are necessary to provide more detailed data about the prevalence of C. burnetiito to improve effective control measures