Nicola A. Wardrop

Bayesian geostatistical analysis and prediction of Rhodesian human African trypanosomiasis.

Background The persistent spread of Rhodesian human African trypanosomiasis (HAT) in Uganda in recent years has increased concerns of a potential overlap with the Gambian form of the disease. Recent research has aimed to increase the evidence base for targeting control measures by focusing on the environmental and climatic factors that control the spatial distribution of the disease. Objectives One recent study used simple logistic regression methods to explore the relationship between prevalence of Rhodesian HAT and several social, environmental and climatic variables in two of the most recently affected districts of Uganda, and suggested the disease had spread into the study area due to the movement of infected, untreated livestock. Here we extend this study to account for spatial autocorrelation, incorporate uncertainty in input data and model parameters and undertake predictive mapping for risk of high HAT prevalence in future. Materials and Methods Using a spatial analysis in which a generalised linear geostatistical model is used in a Bayesian framework to account explicitly for spatial autocorrelation and incorporate uncertainty in input data and model parameters we are able to demonstrate a more rigorous analytical approach, potentially resulting in more accurate parameter and significance estimates and increased predictive accuracy, thereby allowing an assessment of the validity of the livestock movement hypothesis given more robust parameter estimation and appropriate assessment of covariate effects. Results Analysis strongly supports the theory that Rhodesian HAT was imported to the study area via the movement of untreated, infected livestock from endemic areas. The confounding effect of health care accessibility on the spatial distribution of Rhodesian HAT and the linkages between the diseases distribution and minimum land surface temperature have also been confirmed via the application of these methods. Conclusions Predictive mapping indicates an increased risk of high HAT prevalence in the future in areas surrounding livestock markets, demonstrating the importance of livestock trading for continuing disease spread. Adherence to government policy to treat livestock at the point of sale is essential to prevent the spread of sleeping sickness in Uganda.

Global epidemiology of avian influenza A H5N1 virus infection in humans, 1997-2015: A systematic review of individual case data

SUMMARY Avian influenza viruses A(H5N1) have caused a large number of typically severe human infections since the first human case was reported in 1997. However, there is a lack of comprehensive epidemiological analysis of global human cases of H5N1 from 1997-2015. Moreover, few studies have examined in detail the changing epidemiology of human H5N1 cases in Egypt, especially given the most recent outbreaks since November 2014 which have the highest number of cases ever reported globally over a similar period. Data on individual cases were collated from different sources using a systematic approach to describe the global epidemiology of 907 human H5N1 cases between May 1997 and April 2015. The number of affected countries rose between 2003 and 2008, with expansion from East and Southeast Asia, then to West Asia and Africa. Most cases (67.2%) occurred from December to March, and the overall case fatality risk was 53.5% (483/903) which varied across geographical regions. Although the incidence in Egypt has increased dramatically since November 2014, compared to the cases beforehand there were no significant differences in the fatality risk , history of exposure to poultry, history of human case contact, and time from onset to hospitalization in the recent cases.

Modelling environmental factors correlated with podoconiosis: a geospatial study of non-filarial elephantiasis

IntroductionThe precise trigger of podoconiosis — endemic non-filarial elephantiasis of the lower legs — is unknown. Epidemiological and ecological studies have linked the disease with barefoot exposure to red clay soils of volcanic origin. Histopathology investigations have demonstrated that silicon, aluminium, magnesium and iron are present in the lower limb lymph node macrophages of both patients and non-patients living barefoot on these clays. We studied the spatial variation (variations across an area) in podoconiosis prevalence and the associated environmental factors with a goal to better understanding the pathogenesis of podoconiosis.MethodsFieldwork was conducted from June 2011 to February 2013 in 12 kebeles (administrative units) in northern Ethiopia. Geo-located prevalence data and soil samples were collected and analysed along with secondary geological, topographic, meteorological and elevation data. Soil data were analysed for chemical composition, mineralogy and particle size, and were interpolated to provide spatially continuous information. Exploratory, spatial, univariate and multivariate regression analyses of podoconiosis prevalence were conducted in relation to primary (soil) and secondary (elevation, precipitation, and geology) covariates.ResultsPodoconiosis distribution showed spatial correlation with variation in elevation and precipitation. Exploratory analysis identified that phyllosilicate minerals, particularly clay (smectite and kaolinite) and mica groups, quartz (crystalline silica), iron oxide, and zirconium were associated with podoconiosis prevalence. The final multivariate model showed that the quantities of smectite (RR = 2.76, 95% CI: 1.35, 5.73; p = 0.007), quartz (RR = 1.16, 95% CI: 1.06, 1.26; p = 0.001) and mica (RR = 1.09, 95% CI: 1.05, 1.13; p < 0.001) in the soil had positive associations with podoconiosis prevalence.ConclusionsMore quantities of smectite, mica and quartz within the soil were associated with podoconiosis prevalence. Together with previous work indicating that these minerals may influence water absorption, potentiate infection and be toxic to human cells, the present findings suggest that these particles may play a role in the pathogenesis of podoconiosis and acute adenolymphangitis, a common cause of morbidity in podoconiosis patients.

Changing epidemiology of human brucellosis, China, 1955–2014

Brucellosis, a zoonotic disease, was made statutorily notifiable in China in 1955. We analyzed the incidence and spatial–temporal distribution of human brucellosis during 1955–2014 in China using notifiable surveillance data: aggregated data for 1955–2003 and individual case data for 2004–2014. A total of 513,034 brucellosis cases were recorded, of which 99.3% were reported in northern China during 1955–2014, and 69.1% (258, 462/374, 141) occurred during February–July in 1990–2014. Incidence remained high during 1955–1978 (interquartile range 0.42–1.0 cases/100,000 residents), then decreased dramatically in 1979–1994. However, brucellosis has reemerged since 1995 (interquartile range 0.11–0.23 in 1995–2003 and 1.48–2.89 in 2004–2014); the historical high occurred in 2014, and the affected area expanded from northern pastureland provinces to the adjacent grassland and agricultural areas, then to southern coastal and southwestern areas. Control strategies in China should be adjusted to account for these changes by adopting a One Health approach.

Taenia solium in Europe: Still endemic?

The pork tapeworm, Taenia solium, causes an important economic and health burden, mainly in rural or marginalized communities of sub-Saharan Africa, Asia, and Latin-America. Although improved pig rearing conditions seem to have eliminated the parasite in most Western European countries, little is known about the true endemicity status of T. solium throughout Europe. Three recent reviews indicate that autochthonous human T. solium taeniasis/cysticercosis may be possible in Europe, but that current peer-reviewed literature is biased towards Western Europe. Officially reported data on porcine cysticercosis are highly insufficient. Favourable conditions for local T. solium transmission still exist in eastern parts of Europe, although the ongoing integration of the European Union is speeding up modernisation and intensification of the pig sector. Further evidence is urgently needed to fill the gaps on the European T. solium endemicity map. We urge to make human cysticercosis notifiable and to improve the reporting of porcine cysticercosis.

Individual correlates of Podoconiosis in areas of varying endemicity : a case-control study

Background Podoconiosis is a non-filarial form of elephantiasis resulting in lymphedema of the lower legs. Previous studies have suggested that podoconiosis arises from the interplay of individual and environmental factors. Here, our aim was to understand the individual-level correlates of podoconiosis by comparing 460 podoconiosis-affected individuals and 707 unaffected controls. Methods/principal findings This was a case-control study carried out in six kebeles (the lowest governmental administrative unit) in northern Ethiopia. Each kebele was classified into one of three endemicity levels: ‘low’ (prevalence <1%), ‘medium’ (1–5%) and ‘high’ (>5%). A total of 142 (30.7%) households had two or more cases of podoconiosis. Compared to controls, the majority of the cases, especially women, were less educated (OR = 1.7, 95% CI = 1.3 to 2.2), were unmarried (OR = 3.4, 95% CI = 2.6–4.6) and had lower income (t = −4.4, p<0.0001). On average, cases started wearing shoes ten years later than controls. Among cases, age of first wearing shoes was positively correlated with age of onset of podoconiosis (r = 0.6, t = 12.5, p<0.0001). Among all study participants average duration of shoe wearing was less than 30 years. Between both cases and controls, people in ‘high’ and ‘medium’ endemicity kebeles were less likely than people in ‘low’ endemicity areas to ‘ever’ have owned shoes (OR = 0.5, 95% CI = 0.4–0.7). Conclusions Late use of shoes, usually after the onset of podoconiosis, and inequalities in education, income and marriage were found among cases, particularly among females. There were clustering of cases within households, thus interventions against podoconiosis will benefit from household-targeted case tracing. Most importantly, we identified a secular increase in shoe-wearing over recent years, which may give opportunities to promote shoe-wearing without increasing stigma among those at high risk of podoconiosis.

Latent Trypanosoma brucei gambiense foci in Uganda: a silent epidemic in children and adults?

Trypanosoma brucei gambiense sleeping sickness follows a long asymptomatic phase and persists in ancient foci from which epidemic clinical disease arises. A putative focus of T. b. gambiense infections has been identified, initially in mothers and young children, on the Lake Albert shoreline of Western Uganda leading to mass screening of 6207 individuals in September 2008. T. b. gambiense infections were identified by Card Agglutination Test for Trypanosomiasis (CATT) and sub-species-specific PCR although parasitological methods failed to confirm any patent trypanosome infections. In April 2009, CATT positives were re-visited; diagnosis of individuals by CATT and PCR was unstable over the two time points and parasites remained undetected, even using mini Anion Exchange Centrifugation Technique (mAECT). These observations suggest the possibility of a silent focus of disease, where all infected individuals are in a latent stage, and highlight our limited understanding of the local natural history and disease progression of T. b. gambiense in children and adults.

Tsetse Fly (G.f. fuscipes) distribution in the Lake Victoria Basin of Uganda

Tsetse flies transmit trypanosomes, the causative agent of human and animal African trypanosomiasis. The tsetse vector is extensively distributed across sub-Saharan Africa. Trypanosomiasis maintenance is determined by the interrelationship of three elements: vertebrate host, parasite and the vector responsible for transmission. Mapping the distribution and abundance of tsetse flies assists in predicting trypanosomiasis distributions and developing rational strategies for disease and vector control. Given scarce resources to carry out regular full scale field tsetse surveys to up-date existing tsetse maps, there is a need to devise inexpensive means for regularly obtaining dependable area-wide tsetse data to guide control activities. In this study we used spatial epidemiological modelling techniques (logistic regression) involving 5000 field-based tsetse-data (G. f. fuscipes) points over an area of 40,000 km2, with satellite-derived environmental surrogates composed of precipitation, temperature, land cover, normalised difference vegetation index (NDVI) and elevation at the sub-national level. We used these extensive tsetse data to analyse the relationships between presence of tsetse (G. f. fuscipes) and environmental variables. The strength of the results was enhanced through the application of a spatial autologistic regression model (SARM). Using the SARM we showed that the probability of tsetse presence increased with proportion of forest cover and riverine vegetation. The key outputs are a predictive tsetse distribution map for the Lake Victoria basin of Uganda and an improved understanding of the association between tsetse presence and environmental variables. The predicted spatial distribution of tsetse in the Lake Victoria basin of Uganda will provide significant new information to assist with the spatial targeting of tsetse and trypanosomiasis control.

The dispersal ecology of Rhodesian sleeping sickness following its introduction to a new area

Tsetse-transmitted human and animal trypanosomiasis are constraints to both human and animal health in sub-Saharan Africa, and although these diseases have been known for over a century, there is little recent evidence demonstrating how the parasites circulate in natural hosts and ecosystems. The spread of Rhodesian sleeping sickness (caused by Trypanosoma brucei rhodesiense) within Uganda over the past 15 years has been linked to the movement of infected, untreated livestock (the predominant reservoir) from endemic areas. However, despite an understanding of the environmental dependencies of sleeping sickness, little research has focused on the environmental factors controlling transmission establishment or the spatially heterogeneous dispersal of disease following a new introduction. In the current study, an annually stratified case-control study of Rhodesian sleeping sickness cases from Serere District, Uganda was used to allow the temporal assessment of correlations between the spatial distribution of sleeping sickness and landscape factors. Significant relationships were detected between Rhodesian sleeping sickness and selected factors, including elevation and the proportion of land which was “seasonally flooding grassland” or “woodlands and dense savannah.” Temporal trends in these relationships were detected, illustrating the dispersal of Rhodesian sleeping sickness into more ‘suitable’ areas over time, with diminishing dependence on the point of introduction in concurrence with an increasing dependence on environmental and landscape factors. These results provide a novel insight into the ecology of Rhodesian sleeping sickness dispersal and may contribute towards the implementation of evidence-based control measures to prevent its further spread.

The Influence of Socio-economic, Behavioural and Environmental Factors on Taenia spp. Transmission in Western Kenya: Evidence from a Cross-Sectional Survey in Humans and Pigs

Taenia spp. infections, particularly cysticercosis, cause considerable health impacts in endemic countries. Despite previous evidence of spatial clustering in cysticercosis and the role of environmental factors (e.g. temperature and humidity) in the survival of eggs, little research has explored these aspects of Taenia spp. epidemiology. In addition, there are significant gaps in our understanding of risk factors for infection in humans and pigs. This study aimed to assess the influence of socio-economic, behavioural and environmental variables on human and porcine cysticercosis. A cross-sectional survey for human taeniasis (T. solium and T. saginata), human cysticercosis (T. solium) and pig cysticercosis (T. solium) in 416 households in western Kenya was carried out. These data were linked to questionnaire responses and environmental datasets. Multi-level regression was used to examine the relationships between covariates and human and porcine cysticercosis. The HP10 Ag-ELISA sero-prevalence (suggestive of cysticercosis) was 6.6% for humans (95% CI 5.6%–7.7%), and 17.2% for pigs (95% CI 10.2%–26.4%). Human taeniasis prevalence, based on direct microscopic observation of Taenia spp. eggs (i.e. via microscopy results only) was 0.2% (95% CI 0.05%–0.5%). Presence of Taenia spp. antigen in both humans and pigs was significantly associated with a range of factors, including positive correlations with land cover. The presence of HP10 antigen in humans was correlated (non-linearly) with the proportion of land within a 1 km buffer that was flooding agricultural land and grassland (odds ratio [OR] = 1.09 and 0.998; p = 0.03 and 0.03 for the linear and quadratic terms respectively), gender (OR = 0.58 for males compared to females, p = 0.02), level of education (OR = 0.62 for primary level education versus no formal education, p = 0.09), use of well water for drinking (OR = 2.76 for those who use well water versus those who do not, p = 0.02) and precipitation (OR = 0.998, p = 0.02). Presence of Taenia spp. antigen in pigs was significantly correlated with gender and breeding status of the pig (OR = 10.35 for breeding sows compared to boars, p = 0.01), and the proportion of land within a 1 km buffer that was flooding agricultural land and grassland (OR = 1.04, p = 0.004). These results highlight the role of multiple socio-economic, behavioural and environmental factors in Taenia spp. transmission patterns. Environmental contamination with Taenia spp. eggs is a key issue, with landscape factors influencing presence of Taenia spp. antigens in both pigs and humans.