Drivers of Infectious Disease Outbreaks: How Climate, Environment and Disease Control Programs Influence Occurence of Infectious Disease Outbreaks

This research study described the factors driving infectious disease outbreaks using Foot-and-mouth disease (FMD) in Uganda and Lyme disease in North Dakota (ND), Minnesota (MN) and Wisconsin (WI) as case studies. Retrospective data on FMD vaccines and outbreaks in Uganda (2001 ? 2010) and Lyme disease in ND, MN and WI (1990 ? 2011) was used. The time (7.5 weeks) taken to respond to FMD outbreaks, limited serotyping/subtyping (9/121) of outbreaks and the low percentage of cattle vaccinated (2.1 ? 21.2%) portray ineffective control programs. Similarly, increase in fall temperature (P = 0.0189) and annual precipitation (P = 0.0250) were associated with increased human Lyme cases. Shrub land coverage and human population also increased in WI, MN and ND while forest coverage increased in ND. These favor tick and deer proliferation leading to increased human exposure to Lyme Borreliosis. Therefore ineffective disease control programs, climate and environment factors influence infectious disease occurrence

The sero-prevalence of brucellosis in cattle and their herders in Bahr el Ghazal region, South Sudan

<div><p>Background</p><p>Brucellosis is a worldwide recognized bacterial zoonotic disease. There is currently no information on bovine brucellosis sero-prevalence in South Sudan regardless of the economic, social and public health impact on populations. Therefore, for the first time in 33 years, we report the sero-prevalence of brucellosis in cattle and their herders. Furthermore, we characterize the drivers associated with the disease at the human-animal interface in Bahr el Ghazal region, South Sudan.</p><p>Methods</p><p>A total of 893 and 87 animal and human sera respectively were examined between December 2015 and May 2016. Rose Bengal Plate Test (RBPT) and Competitive Enzyme Linked Immuno Sorbent Assay (c-ELISA) were used in parallel to detect anti-<i>Brucella</i> antibodies. Questionnaires were administered to collect relevant metadata used for the association analysis in R version 3.2.3. Odds Ratio (OR) and Confidence Intervals (CI) were determined.</p><p>Results</p><p>Overall bovine brucellosis prevalence was 31% (95%CI = 28.0–34.2), with the highest 63% (95%CI = 53–70) and lowest 10% (95%CI = 4.5–20.1) prevalence estimates in Wau and Gogrial states respectively. The bovine sero-prevalence was approximately equally distributed among the male 30.4% (26.9–34.2) and the females 32.5% (26.8–38.7). Poor body condition (OR = 0.22; 95%CI = 0.07–0.54) and larger herd sizes (OR = 0.05; 95%CI = 0.008–0.173) were protective factors for brucellosis, while the opposite was true for the second (OR = 1.70; 95%CI = 1.08–2.67) and third (OR = 2.5; 95%CI = 1.46–4.47) lactation stage. The overall brucellosis sero-prevalence in herders was estimated at 33.3% (23.9–44.3).</p><p>Conclusion</p><p>We report a high prevalence of anti-<i>Brucella</i> antibodies in cattle and their herders in Bahr el Ghazal, indicating an enzootic status in the cattle population being an important source of infection for humans. This represents a genuine public health challenge. Therefore, there is need to raise awareness and build capacity and infrastructure in this fragile state to underwrite future public health strategies for brucellosis.</p></div

Awareness, Knowledge, and Perceptions Regarding Rabies Prevention Among Rural Communities in Masaka District, Central Uganda: A Qualitative Study.

Rabies is a zoonotic disease that is mainly transmitted to humans through dog bites. It remains a major public health threat in many Asian and African countries, including Uganda. The main objective of this study was to investigate awareness, knowledge, and perceptions of communities toward human and dog health related to rabies prevention, as well as dog management practices within Masaka district, central Uganda. Data collection involved nine key informant interviews (KIIs) and six focus group discussions (FGDs). Methods used during focus group discussions included qualitative interviews (using open-ended questions), simple ranking, and proportional piling. Data from KIIs and FGDs were analyzed using content analysis in NVivo (version 12.0). This study reveals that community members in the rural settings uses herbal concoctions in replacement or as an alternative to dog vaccination. Furthermore, the study reveals that dogs play the vital roles in the households like as they offer protection to people and household properties, despite being ranked second least among the household animals. The commonest livelihood activity was a small-scale mixed farming. Most of the households kept dogs, but they are ranked at second lowest in terms of economic value among all domestic animals. Free roaming and tethering were the common dog-keeping systems, and home-based feed (food leftovers, bones) was provided mainly to the tethered dogs. Rabies, also locally known as "Eddalu Lyembwa" (that can be translated as "madness of the dogs"), was ranked as the disease of most important among dogs, besides other common diseases such as skin diseases, venereal diseases, worm infestations, and tick infestations. Inadequate vaccination services for both humans and dogs were reported, and dog bite victims traveled a long distance to seek for post-exposure prophylaxis after dog bites. It can be concluded that there is a clear request for periodic mass vaccination campaigns against rabies among dogs, and access to vaccines within reasonable distances by humans after a rabies exposure, but also pre-emptive vaccination for those at high risk, such as veterinarians, needs to be improved

The effects of hibernation on the contractile and biochemical properties of skeletal muscles in the thirteen-lined ground squirrel, Ictidomys tridecemlineatus

Hibernation is a crucial strategy of winter survival used by many mammals. During hibernation, thirteen-lined ground squirrels, Ictidomys tridecemlineatus, cycle through a series of torpor bouts, each lasting more than a week, during which the animals are largely immobile. Previous hibernation studies have demonstrated that such natural models of skeletal muscle disuse cause limited or no change in either skeletal muscle size or contractile performance. However, work loop analysis of skeletal muscle, which provides a realistic assessment of in vivo power output, has not previously been undertaken in mammals that undergo prolonged torpor during hibernation. In the present study, our aim was to assess the effects of 3 months of hibernation on contractile performance (using the work loop technique) and several biochemical properties that may affect performance. There was no significant difference in soleus muscle power output-cycle frequency curves between winter (torpid) and summer (active) animals. Total antioxidant capacity of gastrocnemius muscle was 156% higher in torpid than in summer animals, suggesting one potential mechanism for maintenance of acute muscle performance. Soleus muscle fatigue resistance was significantly lower in torpid than in summer animals. Gastrocnemius muscle glycogen content was unchanged. However, state 3 and state 4 mitochondrial respiration rates were significantly suppressed, by 59% and 44%, respectively, in mixed hindlimb skeletal muscle from torpid animals compared with summer controls. These findings in hindlimb skeletal muscles suggest that, although maximal contractile power output is maintained in torpor, there is both suppression of ATP production capacity and reduced fatigue resistance

Antimicrobial resistance among farming communities in Wakiso District, Central Uganda: A knowledge, awareness and practice study

Background Antibiotics are increasingly becoming ineffective as antimicrobial resistance (AMR) continues to develop and spread globally—leading to more difficult to treat infections. Countries such as Uganda are still challenged with implementation of AMR related strategies due to data paucity. This includes a lack of data on the prevailing knowledge and awareness of antimicrobial resistance and antibiotic use among farming communities, both commercial and subsistence, which are instrumental in the implementation of targeted interventions. The aim of our study was to assess the knowledge, attitudes and practices on AMR among subsistence and commercial farmers in Wakiso district, central Uganda. Methods A cross-sectional study was conducted using a semi-structured questionnaire in Wakiso district, Central Uganda in between June and September 2021. Polytomous latent class analyses were performed to group participants based on their responses. Multivariable regression and conditional inference trees were used to determine the association between demographic factors and knowledge on antibiotics and AMR. Results A total of 652 respondents participated in the study among whom 84% were able to correctly describe what antibiotics are. Subsistence farmers (OR = 6.89, 95% CI [3.20; 14.83]), and to a lesser extent, farming community members which obtained their main income by another business (OR = 2.25, 95% CI [1.345; 3.75]) were more likely to be able to describe antibiotics correctly than individuals involved in commercial farming. Based on the latent class analysis, three latent classes indicating different levels of knowledge on AMR, were found. Subsistence farming, higher educational level and younger age were found to be associated with belonging to a class of better knowledge. Conclusion The majority of participants were able to correctly describe antibiotics and aware of AMR, however there was some degree of misunderstanding of several AMR concepts. Targeted AMR interventions should improve awareness and also ensure that not only subsistence farmers, but commercial farmers, are included

The epidemiology of zoonotic brucellosis in Bahr el Ghazal region of South Sudan

Background - In this study, we focused on three zoonotic brucellosis risk groups; abattoir workers, febrile cases at Wau hospital and cattle herders, in Bahr el Ghazal region, South Sudan. Competitive c-ELISA was used to detect anti-Brucella antibodies in 725 individuals between December 2015 and May 2016. In addition, questionnaire metadata, focus group discussions and key informant interviews were used to characterize the epidemiology of zoonotic brucellosis in this region. Results - Overall, we estimate 27.2 % (95% CI = 23.9–30.6) brucellosis sero-prevalence; 32.1% (95% CI = 26.2–38.4), 23.0% (95% CI = 19.1–27.4) and 34.6% (95% CI = 24.4–46.3) among abattoir workers, febrile cases, and herders, respectively. Marital status (Single, OR = 0.58, 95%CI: 0.36–0.91, P = 0.02) and ethnicity (Kerash OR = 6.01, 95%CI: 1.97–21.10, P = 0.003 and Balanda, OR = 3.78, 95%CI: 1.42–12.02, P = 0.01) were associated with brucellosis. While gender and ethnicity were important factors for general awareness of zoonotic diseases. Highly ranked occupations at risk included veterinarian, butchers and milk handlers. We also identified covariate patterns for clinical diagnostics and public health interventions. Conclusion - We report the highest sero-prevalence of zoonotic brucellosis in three risk groups in the East African region. All this is not only occurring in a population with limited awareness that brucellosis is a zoonotic disease but also where one in nine health workers tested was sero-positive. We identified social demographic associations with brucellosis, however, the qualitative analysis suggests these are more complex and nuanced. Therefore, future studies could benefit from the use of the mixed methods approach to add extensiveness and depth to our understanding of zoonotic disease drivers, in order to implement mitigating measures such as cattle vaccination

Leishmania amazonensis Arginase Compartmentalization in the Glycosome Is Important for Parasite Infectivity

In Leishmania, de novo polyamine synthesis is initiated by the cleavage of L-arginine to urea and L-ornithine by the action of arginase (ARG, E.C. 3.5.3.1). Previous studies in L. major and L. mexicana showed that ARG is essential for in vitro growth in the absence of polyamines and needed for full infectivity in animal infections. The ARG protein is normally found within the parasite glycosome, and here we examined whether this localization is required for survival and infectivity. First, the localization of L. amazonensis ARG in the glycosome was confirmed in both the promastigote and amastigote stages. As in other species, arg− L. amazonensis required putrescine for growth and presented an attenuated infectivity. Restoration of a wild type ARG to the arg− mutant restored ARG expression, growth and infectivity. In contrast, restoration of a cytosol-targeted ARG lacking the glycosomal SKL targeting sequence (argΔSKL) restored growth but failed to restore infectivity. Further study showed that the ARGΔSKL protein was found in the cytosol as expected, but at very low levels. Our results indicate that the proper compartmentalization of L. amazonensis arginase in the glycosome is important for enzyme activity and optimal infectivity. Our conjecture is that parasite arginase participates in a complex equilibrium that defines the fate of L-arginine and that its proper subcellular location may be essential for this physiological orchestration

Progressive Visceral Leishmaniasis Is Driven by Dominant Parasite-induced STAT6 Activation and STAT6-dependent Host Arginase 1 Expression

The clinicopathological features of the hamster model of visceral leishmaniasis (VL) closely mimic active human disease. Studies in humans and hamsters indicate that the inability to control parasite replication in VL could be related to ineffective classical macrophage activation. Therefore, we hypothesized that the pathogenesis of VL might be driven by a program of alternative macrophage activation. Indeed, the infected hamster spleen showed low NOS2 but high arg1 enzyme activity and protein and mRNA expression (p<0.001) and increased polyamine synthesis (p<0.05). Increased arginase activity was also evident in macrophages isolated from the spleens of infected hamsters (p<0.05), and arg1 expression was induced by L. donovani in primary hamster peritoneal macrophages (p<0.001) and fibroblasts (p<0.01), and in a hamster fibroblast cell line (p<0.05), without synthesis of endogenous IL-4 or IL-13 or exposure to exogenous cytokines. miRNAi-mediated selective knockdown of hamster arginase 1 (arg1) in BHK cells led to increased generation of nitric oxide and reduced parasite burden (p<0.005). Since many of the genes involved in alternative macrophage activation are regulated by Signal Transducer and Activator of Transcription-6 (STAT6), and because the parasite-induced expression of arg1 occurred in the absence of exogenous IL-4, we considered the possibility that L. donovani was directly activating STAT6. Indeed, exposure of hamster fibroblasts or macrophages to L. donovani resulted in dose-dependent STAT6 activation, even without the addition of exogenous cytokines. Knockdown of hamster STAT6 in BHK cells with miRNAi resulted in reduced arg1 mRNA expression and enhanced control of parasite replication (p<0.0001). Collectively these data indicate that L. donovani infection induces macrophage STAT6 activation and STAT6-dependent arg1 expression, which do not require but are amplified by type 2 cytokines, and which contribute to impaired control of infection