Epi Notes

The South Carolina Department of Health and Environmental Control, Bureau of Disease Control publishes Epi Notes, with articles on epidemiology of reportable conditions; surveillance and reporting of diseases/conditions, outbreaks, and events of public health significance; prevention and treatment of disease; and other topics of interest to DHEC’s disease reporting partners.

Epi Notes

The South Carolina Department of Health and Environmental Control, Bureau of Disease Control publishes Epi Notes, with articles on epidemiology of reportable conditions; surveillance and reporting of diseases/conditions, outbreaks, and events of public health significance; prevention and treatment of disease; and other topics of interest to DHEC’s disease reporting partners.

Epi Notes

The South Carolina Department of Health and Environmental Control, Bureau of Disease Control publishes Epi Notes, with articles on epidemiology of reportable conditions; surveillance and reporting of diseases/conditions, outbreaks, and events of public health significance; prevention and treatment of disease; and other topics of interest to DHEC’s disease reporting partners.

Epi Notes

The South Carolina Department of Health and Environmental Control, Bureau of Disease Control publishes Epi Notes, with articles on epidemiology of reportable conditions; surveillance and reporting of diseases/conditions, outbreaks, and events of public health significance; prevention and treatment of disease; and other topics of interest to DHEC’s disease reporting partners.

Epi Notes

The South Carolina Department of Health and Environmental Control, Bureau of Disease Control publishes Epi Notes, with articles on epidemiology of reportable conditions; surveillance and reporting of diseases/conditions, outbreaks, and events of public health significance; prevention and treatment of disease; and other topics of interest to DHEC’s disease reporting partners.

Epi Notes

The South Carolina Department of Health and Environmental Control, Bureau of Disease Control publishes Epi Notes, with articles on epidemiology of reportable conditions; surveillance and reporting of diseases/conditions, outbreaks, and events of public health significance; prevention and treatment of disease; and other topics of interest to DHEC’s disease reporting partners.

Epi Notes

The South Carolina Department of Health and Environmental Control, Bureau of Disease Control publishes Epi Notes, with articles on epidemiology of reportable conditions; surveillance and reporting of diseases/conditions, outbreaks, and events of public health significance; prevention and treatment of disease; and other topics of interest to DHEC’s disease reporting partners.

Epi Notes

The South Carolina Department of Health and Environmental Control, Bureau of Disease Control publishes Epi Notes, with articles on epidemiology of reportable conditions; surveillance and reporting of diseases/conditions, outbreaks, and events of public health significance; prevention and treatment of disease; and other topics of interest to DHEC’s disease reporting partners.

Epi Notes

The South Carolina Department of Health and Environmental Control, Bureau of Disease Control publishes Epi Notes, with articles on epidemiology of reportable conditions; surveillance and reporting of diseases/conditions, outbreaks, and events of public health significance; prevention and treatment of disease; and other topics of interest to DHEC’s disease reporting partners.

Epi Notes

The South Carolina Department of Health and Environmental Control, Bureau of Disease Control publishes Epi Notes, with articles on epidemiology of reportable conditions; surveillance and reporting of diseases/conditions, outbreaks, and events of public health significance; prevention and treatment of disease; and other topics of interest to DHEC’s disease reporting partners.

Epi Notes

The South Carolina Department of Health and Environmental Control, Bureau of Disease Control publishes Epi Notes, with articles on epidemiology of reportable conditions; surveillance and reporting of diseases/conditions, outbreaks, and events of public health significance; prevention and treatment of disease; and other topics of interest to DHEC’s disease reporting partners.

Epi Notes

The South Carolina Department of Health and Environmental Control, Bureau of Disease Control publishes Epi Notes, with articles on epidemiology of reportable conditions; surveillance and reporting of diseases/conditions, outbreaks, and events of public health significance; prevention and treatment of disease; and other topics of interest to DHEC’s disease reporting partners.

2016 Dengue Fever Virus Cases

Dengue fever is the most common cause of fever in travelers returning from the Caribbean, Central America, and South Central Asia.* Dengue infections are commonly reported from most tropical countries of the South Pacific, Asia, the Caribbean, the Americas, and Africa. This disease is caused by four similar viruses (DENV-1, -2, -3, and -4) and is spread through the bites of infected mosquitoes. For information on current outbreaks, consult CDC’s Travelers’ Health website (http://www.cdc.gov/travel). Dengue fever is a severe, flu-like illness that affects infants, young children and adults, but seldom causes death. Dengue should be suspected when a high fever (40°C/104°F) is accompanied by two of the following symptoms: severe headache, pain behind the eyes, muscle and joint pains, nausea, vomiting, swollen glands or rash. Symptoms usually last for 2–7 days, after an incubation period of 4–10 days following the bite from an infected mosquito.

The epidemiology of foot-and-mouth disease at the wildlife-livestock interface in northern Tanzania

Foot-and-mouth disease (FMD), a disease of cloven hooved animals caused by FMD virus (FMDV), is one of the most economically devastating diseases of livestock worldwide. The global burden of disease is borne largely by livestock-keepers in areas of Africa and Asia where the disease is endemic and where many people rely on livestock for their livelihoods and food-security. Yet, there are many gaps in our knowledge of the drivers of FMDV circulation in these settings. In East Africa, FMD epidemiology is complicated by the circulation of multiple FMDV serotypes (distinct antigenic variants) and by the presence of large populations of susceptible wildlife and domestic livestock. The African buffalo (Syncerus caffer) is the only wildlife species with consistent evidence of high levels of FMDV infection, and East Africa contains the largest population of this species globally. To inform FMD control in this region, key questions relate to heterogeneities in FMD prevalence and impacts in different livestock management systems and to the role of wildlife as a potential source of FMDV for livestock. To develop FMD control strategies and make best use of vaccine control options, serotype-specific patterns of circulation need to be characterised. In this study, the impacts and epidemiology of FMD were investigated across a range of traditional livestock-keeping systems in northern Tanzania, including pastoralist, agro-pastoralist and rural smallholder systems. Data were generated through field studies and laboratory analyses between 2010 and 2015. The study involved analysis of existing household survey data and generated serological data from cross-sectional livestock and buffalo samples and longitudinal cattle samples. Serological analyses included non-structural protein ELISAs, serotype-specific solid-phase competitive ELISAs, with optimisation to detect East African FMDV variants, and virus neutralisation testing. Risk factors for FMDV infection and outbreaks were investigated through analysis of cross-sectional serological data in conjunction with a case-control outbreak analysis. A novel Bayesian modeling approach was developed to infer serotype-specific infection history from serological data, and combined with virus isolation data from FMD outbreaks to characterise temporal and spatial patterns of serotype-specific infection. A high seroprevalence of FMD was detected in both northern Tanzanian livestock (69%, [66.5 - 71.4%] in cattle and 48.5%, [45.7-51.3%] in small ruminants) and in buffalo (80.9%, [74.7-86.1%]). Four different serotypes of FMDV (A, O, SAT1 and SAT2) were isolated from livestock. Up to three outbreaks per year were reported by households and active surveillance highlighted up to four serial outbreaks in the same herds within three years. Agro-pastoral and pastoral livestock keepers reported more frequent FMD outbreaks compared to smallholders. Households in all three management systems reported that FMD outbreaks caused significant impacts on milk production and sales, and on animals’ draught power, hence on crop production, with implications for food security and livelihoods. Risk factor analyses showed that older livestock were more likely to be seropositive for FMD (Odds Ratio [OR] 1.4 [1.4-1.5] per extra year) and that cattle (OR 3.3 [2.7-4.0]) were more likely than sheep and goats to be seropositive. Livestock managed by agro-pastoralists (OR 8.1 [2.8-23.6]) or pastoralists (OR 7.1 [2.9-17.6]) were more likely to be seropositive compared to those managed by smallholders. Larger herds (OR: 1.02 [1.01-1.03] per extra bovine) and those that recently acquired new livestock (OR: 5.57 [1.01 – 30.91]) had increased odds of suffering an FMD outbreak. Measures of potential contact with buffalo or with other FMD susceptible wildlife did not increase the likelihood of FMD in livestock in either the cross-sectional serological analysis or case-control outbreak analysis. The Bayesian model was validated to correctly infer from ELISA data the most recent serotype to infect cattle. Consistent with the lack of risk factors related to wildlife contact, temporal and spatial patterns of exposure to specific FMDV serotypes were not tightly linked in cattle and buffalo. In cattle, four serial waves of different FMDV serotypes that swept through southern Kenyan and northern Tanzanian livestock populations over a four-year period dominated infection patterns. In contrast, only two serotypes (SAT1 and SAT2) dominated in buffalo populations. Key conclusions are that FMD has a substantial impact in traditional livestock systems in East Africa. Wildlife does not currently appear to act as an important source of FMDV for East African livestock, and control efforts in the region should initially focus on livestock management and vaccination strategies. A novel modeling approach greatly facilitated the interpretation of serological data and may be a potent epidemiological tool in the African setting. There was a clear temporal pattern of FMDV antigenic dominance across northern Tanzania and southern Kenya. Longer-term research to investigate whether serotype-specific FMDV sweeps are truly predictable, and to shed light on FMD post-infection immunity in animals exposed to serial FMD infections is warranted.

New prophylactic and therapeutic treatments to combat pathogenic Enterohaemorrhagic Escherichia coli

Bacterial diarrhoeal diseases have significant influence on global human health, and are a leading cause of preventable death in the developing world. Enterohaemorrhagic Escherichia coli (EHEC), pathogenic strains of E. coli that carry potent toxins, have been associated with a high number of large-scale outbreaks caused by contaminated food and water sources. This pathotype produces diarrhoea and haemorrhagic colitis in infected humans, and in some patients leads to the development of haemolytic uremic syndrome (HUS), which can result in mortality and chronic kidney disease. A major obstacle to the treatment of EHEC infections is the increased risk of HUS development that is associated with antibiotic treatment, and rehydration and renal support are often the only options available. New treatments designed to prevent or clear E. coli infections and reduce symptoms of illness would therefore have large public health and economic impacts. The three main aims of this thesis were: to explore mouse models for pre-clinical evaluation in vivo of small compounds that inhibit a major EHEC colonisation factor, to assess the production and role of two proteins considered promising candidates for a broad-spectrum vaccine against pathogenic E. coli, and to investigate a novel compound that has recently been identified as a potential inhibitor of EHEC toxin production. As EHEC cannot be safely tested in humans due to the risk of HUS development, appropriate small animal models are required for in vivo testing of new drugs. A number of different mouse models have been developed to replicate different features of EHEC pathogenesis, several of which we investigated with a focus on colonisation mediated by the Type III Secretion System (T3SS), a needle-like structure that translocates bacterial proteins into host cells, resulting in a tight, intimate attachment between pathogen and host, aiding colonisation of the gastrointestinal tract. As E. coli models were found not to depend significantly on the T3SS for colonisation, the Citrobacter rodentium model, a natural mouse pathogen closely related to E. coli, was deemed the most suitable mouse model currently available for in vivo testing of T3SS-targeting compounds. Two bacterial proteins, EaeH (an outer membrane adhesin) and YghJ (a putative secreted lipoprotein), highly conserved surface-associated proteins recently identified as III protective antigens against E. coli infection of mice, were explored in order to determine their suitability as candidates for a human vaccine against pathogenic E. coli. We focused on the expression and function of these proteins in the EHEC O157:H7 EDL933 strain and the adherent-invasive E. coli (AIEC) LF82 strain. Although expression of EaeH by other E. coli pathotypes has recently been shown to be upregulated upon contact with host intestinal cells, no evidence of this upregulation could be demonstrated in our strains. Additionally, while YghJ was produced by the AIEC strain, it was not secreted by bacteria under conditions that other YghJ-expressing E. coli pathotypes do, despite the AIEC strain carrying all the genes required to encode the secretion system it is associated with. While our findings indicate that a vaccine that raises antibodies against EaeH and YghJ may have limited effect on the EHEC and AIEC strains we used, recent studies into these proteins in different E. coli pathogens have suggested they are still excellent candidates for a broadly effective vaccine against E. coli. Finally, we characterised a small lead compound, identified by high-throughput screening as a possible inhibitor of Shiga toxin expression. Shiga toxin production causes both the symptoms of illness and development of HUS, and thus reduction of toxin production, release, or binding to host receptors could therefore be an effective way to treat infections and decrease the risk of HUS. Inhibition of Shiga toxin production by this compound was confirmed, and was shown to be caused by an inhibitory effect on activation of the bacterial SOS response rather than on the Shiga toxin genes themselves. The bacterial target of this compound was identified as RecA, a major regulator of the SOS response, and we hypothesise that the compound binds covalently to its target, preventing oligomerisation of RecA into an activated filament. Altogether, the results presented here provide an improved understanding of these different approaches to combating EHEC infection, which will aid the development of safe and effective vaccines and anti-virulence treatments against EHEC.