Hepatitis E seroprevalence and risk factors in humans and pig in Ghana.

BACKGROUND: Although Hepatitis E virus (HEV) infection has significant negative impact on the health and wellbeing of underprivileged populations, the burden of HEV in Ghana is still unclear, despite widespread water, sanitation, and hygiene (WASH) related conditions that predispose people to the risk of infection. METHODS: A cross-sectional study was conducted to explore rates of HEV seroprevalence and HEV prevalence, as well as risk factors in humans and domestic pigs in Ghana. These were determined using ELISAs manufactured by Wantai Beijing Biopharmaceuticals, China. The study involved 1365 community members, 105 pig farmers and 474 domestic pigs from four administrative regions of Ghana. RESULTS: Results showed overall seroprevalence and prevalence of 12.4% and 0.7% in community members and 15.2% and 2.9% in pig farmers respectively. There was no significant difference in the seroprevalence between the two groups (Z = 0.851; p = 0.3953). However, the prevalence in pig farmers was significantly higher than in community members (Z = 2.412; p = 0.016). Age (OR = 1.369, CI = 1.243 - 1.508; p = 0.0000), gender (OR = 1.419, CI = 1.101 - 1.991; p = 0.043), and the region of residence (OR = 1.569, CI = 1.348 - 1.827; p = 0.0000) were significant risk factors for HEV seroprevalence in a multivariate regression model. In pigs, overall seroprevalence and prevalence of 62.4% and 5.5% were recorded respectively. A significant difference in seroprevalence was found between confined (6.7%) and free-range pigs (88.3%), (Z = 7.492; p < 0.00001) in the Volta Region. Multivariate logistic regression showed a significant association between seroprevalence and husbandry (OR = 7.051, CI = 3.558- 13.972; p = 0.0000) and region (OR = 4.602, CI = 2.300 - 9.205; p = 0.0000) in pigs in the Volta and Greater Accra Region. CONCLUSION: From this study, HEV is endemic in Ghana with high seroprevalence in humans and pig populations. This underscores the need for awareness creation and action for prevention and control.

ZOONOTIC ENCOUNTERS AT THE SLAUGHTERHOUSE: PATHWAYS AND POSSIBILITIES FOR THE CONTROL OF CYSTIC ECHINOCOCCOSIS IN NORTHERN MOROCCO.

This study traces the biosocial dynamics of Echinococcus granulosus - a zoonotic tapeworm spread between dogs, livestock and people - at slaughterhouses in Morocco. One of the most important parasitic zoonoses worldwide, this neglected cestode is responsible for a debilitating, potentially life-threatening, human disease and significant livestock production losses. Transmission can be interrupted, among other ways, by restricting dogs from eating cyst-infected livestock viscera. Recent epidemiological studies in Sidi Kacem province, northern Morocco, found that government-operated slaughterhouses were 'hotspots' for hydatid cysts in livestock and infection in dogs. An ethnographic approach was used to compliment these studies, exploring 'how' and 'why' cysts were being openly discarded. All seven visited slaughterhouses had low levels of hygiene, oversight and infrastructure. This was described locally as perpetuating a sense of 'chaos' that normalized (un)hygienic practices and justified the ignoring of state rules and regulations. However deference to 'poor' infrastructure, both physically and symbolically, served to under-emphasize local institutional logics, which were mediated by prevailing risk perceptions, economic practices and local socio-political norms. These included inter-departmental government relationships, the motivation of veterinary technicians, the political lobbying of butchers and market-based mitigation strategies. The study shows the importance of understanding E. granulosus from a biosocial perspective, and the need for more long-term, participatory and integrated 'One Health' approaches for neglected zoonotic diseases.

Modelling the use of insecticide-treated cattle to control tsetse and Trypanosoma brucei rhodesiense in a multi-host population.

We present a mathematical model for the transmission of Trypanosoma brucei rhodesiense by tsetse vectors to a multi-host population. To control tsetse and T. b. rhodesiense, a proportion, ψ, of cattle (one of the hosts considered in the model) is taken to be kept on treatment with insecticides. Analytical expressions are obtained for the basic reproduction number, R0n in the absence, and R(0n)(T) in the presence of insecticide-treated cattle (ITC). Stability analysis of the disease-free equilibrium was carried out for the case when there is one vertebrate host untreated with insecticide. By considering three vertebrate hosts (cattle, humans and wildlife) the sensitivity analysis was carried out on the basic reproduction number (R(0n)(T)) in the absence and presence of ITC. The results show that R(03)(T) is more sensitive to changes in the tsetse mortality. The model is then used to study the control of tsetse and T. b. rhodesiense in humans through application insecticides to cattle either over the whole-body or to restricted areas of the body known to be favoured tsetse feeding sites. Numerical results show that while both ITC strategies result in decreases in tsetse density and in the incidence of T. b. rhodesiense in humans, the restricted application technique results in improved cost-effectiveness, providing a cheap, safe, environmentally friendly and farmer based strategy for the control of vectors and T. b. rhodesiense in humans.

An exploratory GIS-based method to identify and characterise landscapes with an elevated epidemiological risk of Rhodesian human African trypanosomiasis.

BACKGROUND: Specific land cover types and activities have been correlated with Trypanosoma brucei rhodesiense distributions, indicating the importance of landscape for epidemiological risk. However, methods proposed to identify specific areas with elevated epidemiological risk (i.e. where transmission is more likely to occur) tend to be costly and time consuming. This paper proposes an exploratory spatial analysis using geo-referenced human African trypanosomiasis (HAT) cases and matched controls from Serere hospital, Uganda (December 1998 to November 2002) to identify areas with an elevated epidemiological risk of HAT. METHODS: Buffers 3 km from each case and control were used to represent areas in which village inhabitants would carry out their daily activities. It was hypothesised that the selection of areas where several case village buffers overlapped would enable the identification of locations with increased risk of HAT transmission, as these areas were more likely to be frequented by HAT cases in several surrounding villages. The landscape within these overlap areas should more closely relate to the environment in which transmission occurs as opposed to using the full buffer areas. The analysis was carried out for each of four annual periods, for both cases and controls, using a series of threshold values (number of overlapping buffers), including a threshold of one, which represented the benchmark (e.g. use of the full buffer area as opposed to the overlap areas). RESULTS: A greater proportion of the overlap areas for cases consisted of seasonally flooding grassland and lake fringe swamp, than the control overlap areas, correlating well with the preferred habitat of the predominant tsetse species within the study area (Glossina fuscipes fuscipes). The use of overlap areas also resulted in a greater difference between case and control landscapes, when compared with the benchmark (using the full buffer area). CONCLUSIONS: These results indicate that the overlap analysis has enabled the selection of areas more likely to represent epidemiological risk zones than similar analyses using full buffer areas. The identification of potential epidemiological risk zones using this method requires fewer data than other proposed methods and further development may provide vital information for the targeting of control measures.

Healthcare Management of Human African Trypanosomiasis Cases in the Eastern, Muchinga and Lusaka Provinces of Zambia.

Human African trypanosomiasis (HAT) is a neglected tropical disease that has not received much attention in Zambia and most of the countries in which it occurs. In this study, we assessed the adequacy of the healthcare delivery system in diagnosis and management of rHAT cases, the environmental factors associated with transmission, the population at risk and the geographical location of rHAT cases. Structured questionnaires, focus group discussions and key informant interviews were conducted among the affected communities and health workers. The study identified 64 cases of rHAT, of which 26 were identified through active surveillance and 38 through passive surveillance. We identified a significant association between knowledge of the vector for rHAT and knowledge of rHAT transmission (p < 0.028). In all four districts, late or poor diagnosis occurred due to a lack of qualified laboratory technicians and diagnostic equipment. This study reveals that the current Zambian healthcare system is not able to adequately handle rHAT cases. Targeted policies to improve staff training in rHAT disease detection and management are needed to ensure that sustainable elimination of this public health problem is achieved in line with global targets.

Herd prevalence of bovine brucellosis and analysis of risk factors in cattle in urban and peri-urban areas of the Kampala economic zone, Uganda.

BACKGROUND: Human brucellosis has been found to be prevalent in the urban areas of Kampala, the capital city of Uganda. A cross-sectional study was designed to generate precise information on the prevalence of brucellosis in cattle and risk factors for the disease in its urban and peri-urban dairy farming systems. RESULTS: The adjusted herd prevalence of brucellosis was 6.5% (11/177, 95% CI: 3.6%-10.0%) and the adjusted individual animal prevalence was 5.0% (21/423, 95% CI: 2.7%-9.3%) based on diagnosis using commercial kits of the competitive enzyme-linked immunosorbent assay (CELISA) for Brucella abortus antibodies. Mean within-herd prevalence was found to be 25.9% (95% CI: 9.7%-53.1%) and brucellosis prevalence in an infected herd ranged from 9.1% to 50%. A risk factor could not be identified at the animal level but two risk factors were identified at the herd level: large herd size and history of abortion. The mean number of milking cows in a free-grazing herd (5.0) was significantly larger than a herd with a movement restricted (1.7, p < 0.001). CONCLUSIONS: Vaccination should be targeted at commercial large-scale farms with free-grazing farming to control brucellosis in cattle in and around Kampala city.

Spatial epidemiology of hospital-diagnosed brucellosis in Kampala, Uganda.

BACKGROUND: A retrospective case-control study was undertaken to examine the spatial risk factors for human brucellosis in Kampala, Uganda. METHODS: Information on age, sex and month of diagnosis was derived from records from plate agglutination tests undertaken at Mulago Hospital, Kampala. Information on Parishes (LC2s) where patients reside was sourced from the outpatient registration book. In-patient fracture cases were selected for use as controls using 1:1 matching based on the age, sex and month of diagnosis. The locations of cases and controls were obtained by calculating Cartesian coordinates of the centroids of Parish level (LC2) polygons and a spatial scan statistic was applied to test for disease clustering. Parishes were classified according to the level of urbanization as urban, peri-urban or rural. RESULTS: Significantly more females than males were found to show sero-positivity for brucellosis when compared with the sex ratio of total outpatients, in addition female brucellosis patients were found to be significantly older than the male patients. Spatial clustering of brucellosis cases was observed including around Mulago Hospital (radius = 6.8 km, p = 0.001). The influence of proximity to the hospital that was observed for brucellosis cases was not significantly different from that observed in the controls. The disease cluster was confounded by the different catchment areas between cases and controls. The level of urbanization was not associated with the incidence of brucellosis but living in a slum area was a significant risk factor among urban dwellers (odds ratio 1.97, 95% CI: 1.10-3.61). CONCLUSIONS: Being female was observed to be a risk factor for brucellosis sero-positvity and among urban dwellers, living in slum areas was also a risk factor although the overall risk was not different among urban, peri-urban and rural areas of the Kampala economic zone.

Leishmaniasis Beyond East Africa.

Climate change is having a substantial impact on our environment and ecosystems and has altered the way humans live, access, and utilize resources with increased risk of zoonotic infectious disease encounters. As global temperatures continue to increase, they impact on public health, migration, food security and land conflict, and as new environments become favorable, exposure to disease carrying vectors. Increased forests or natural habitat clearance for land repurposing, urbanization, road building, and water management are related to an increase in emerging vector borne parasitic diseases. The East African region remains one of the most impacted regions globally for leishmaniasis, a vector borne disease that impacts significantly on the health, wellbeing and livelihoods of affected communities and for which a lack of reporting and control interventions hinder progress toward elimination of this neglected tropical disease. As our world continues to transform, both politically and climatically, it is essential that measures are put in place to improve surveillance and disease management with implementation of control measures, including vector control, especially in low- and middle-income countries that are expected to be most impacted by changes in climate. Only through effective management, now, can we be sufficiently resilient to preventing the inevitable spread of vectors into suitable habitat and expansion of the geographical range of leishmaniasis. This review offers a current perspective on Leishmaniasis as an endemic disease in East Africa and examines the potential of the recent emergence of Leishmania infection in hitherto unaffected regions to become a public health concern if no disease management is achieved.

Hepatitis E in Sub Saharan Africa - A significant emerging disease.

Hepatitis E is an emerging endemic disease found across the African continent, but there are clear differences in epidemiology between North Africa and countries south of the Sahara. In this systematic review, Google scholar and PubMed databases were searched for peer-reviewed articles on HEV epidemiology. Publications meeting our inclusion criteria were critically reviewed to extract consistent findings and identify knowledge gaps. Hepatitis E has been reported in 25 of the 49 countries in Sub Saharan Africa. Mortality rates of 1-2% in the general population and ~ 20% in pregnant women. Outbreaks were closely linked to refugees and Internally Displaced Persons in camps which accounted for 50% of reported outbreaks. There was very little research and concrete evidence for sources of contamination and transmission routes. There are indications of zoonotic transmission of Hepatitis E Virus infection but further research in these fields is required.

Serosurvey of Avian Influenza Viruses (H5, H7, and H9) and Associated Risk Factors in Backyard Poultry Flocks of Lahore District, Pakistan.

Rural poultry constitutes 56% of the total poultry population in Pakistan; however, epidemiological information about avian influenza viruses (AIVs) in backyard poultry flocks is lacking. A cross-sectional survey of villages of Lahore district was conducted from July 2009 to August 2009 using two-stage cluster sampling and probability proportional to size (PPS) sampling to estimate seroprevalence and its associated risk factors. A random selection of 35 clusters from 308 villages of Lahore were considered, and from each cluster, six chickens aged >2 months were selected. A total of 210 serum samples were collected and examined by the hemagglutination inhibition (HI) test for specific antibodies against AIV subtypes H5, H7, and H9. Overall weighted seroprevalence for AIVs was 65.2% (95% CI: 55.6-74.8%), and for subtype H5, H7 & H9 was 6.9% (95% CI: 10.8-23.0%), 0% (95% CI: 0-1.7%), and 62.0% (95% CI: 52.2-71.8%) respectively. However, none of the samples were positive for H7. The average flock size was 17.3 birds, and the main purpose of keeping poultry was for eggs/meat (70.6%, 95% CI: 59.7-81.4). A majority of them were reared in a semi-caged system (83%, 95% CI: 74.5-91.3). Backyard birds were received from different sources, that is, purchased from the market or received as a gift from friends or any NGO, and were 5.7 times more likely to become avian influenza (AI) seropositive than those that were not exposed to these sources (CI 95%: 2.0-716.0). Backyard birds which were received from different sources, that is, purchased from the market or received from friends or any NGO, were 5.7 times more likely to become AI seropositive compared to those that were not (CI 95%: 2.5-18.7). To reduce the risk of AIV in Pakistan, continuous surveillance of backyard poultry would be needed.

Controlling Tsetse Flies and Ticks Using Insecticide Treatment of Cattle in Tororo District Uganda: Cost Benefit Analysis.

Background: The endemic vector-borne diseases transmitted by tsetse and ticks impose heavy burdens on the livestock keepers in Africa. Applying deltamethrin to the belly, legs, and ears of cattle offers a possibility of mitigating these losses at a cost affordable to livestock keepers. Although studies have quantified the impacts of individual diseases on livestock productivity, little is known about the dual economic benefits of controlling both tsetse and ticks, nor about the number of cattle that need to be treated to confer these benefits. Alongside an epidemiological study in south-east Uganda, a farm level assessment was done to investigate the benefits and costs of spraying different proportions of the village cattle population using this restricted application protocol. Methods: A study comprising 1,902 semi-structured interviews was undertaken over a period of 18 months. Financial data on household income and expenditure on cattle was collected, and cost-benefit analysis was done pre- and post-intervention and for different spraying regimes. The total cost of the intervention was obtained from the implementation costs of the epidemiological study and from expenses incurred by participating farmers enabling examination of benefit-cost ratios and incremental benefit-cost ratios for each treatment regime. Results: The benefit-cost analysis of spraying 25%, 50%, and 75% of the cattle population yielded average benefit-cost ratios of 3.85, 4.51, and 4.46. The incremental benefit-cost ratios from spraying each additional 25% of the cattle population were 11.38, 3.89, and 0.79, showing a very high return on investment for spraying 50% of the population, with returns reducing thereafter. Conclusion: Comparing the gross margins per bovine, the study found that increasing the proportion of cattle sprayed yielded increasing benefits to the farmers, but that these benefits were subject to diminishing returns. From a practical viewpoint, this study recommends spraying only draft cattle to control trypanosomiasis and tick-borne diseases in this area as they make 38.62% of the cattle population, approaching the 50% threshold. In areas with a lower proportion of draft males, farmers could be advised to also include cows.

Livestock Network Analysis for Rhodesiense Human African Trypanosomiasis Control in Uganda.

Background: Infected cattle sourced from districts with established foci for Trypanosoma brucei rhodesiense human African trypanosomiasis (rHAT) migrating to previously unaffected districts, have resulted in a significant expansion of the disease in Uganda. This study explores livestock movement data to describe cattle trade network topology and assess the effects of disease control interventions on the transmission of rHAT infectiousness. Methods: Network analysis was used to generate a cattle trade network with livestock data which was collected from cattle traders (n = 197) and validated using random graph methods. Additionally, the cattle trade network was combined with a susceptible, infected, recovered (SIR) compartmental model to simulate spread of rHAT (R o 1.287), hence regarded as "slow" pathogen, and evaluate the effects of disease interventions. Results: The cattle trade network exhibited a low clustering coefficient (0.5) with most cattle markets being weakly connected and a few being highly connected. Also, analysis of the cattle movement data revealed a core group comprising of cattle markets from both eastern (rHAT endemic) and northwest regions (rHAT unaffected area). Presence of a core group may result in rHAT spread to unaffected districts and occurrence of super spreader cattle market or markets in case of an outbreak. The key cattle markets that may be targeted for routine rHAT surveillance and control included Namutumba, Soroti, and Molo, all of which were in southeast Uganda. Using effective trypanosomiasis such as integrated cattle injection with trypanocides and spraying can sufficiently slow the spread of rHAT in the network. Conclusion: Cattle trade network analysis indicated a pathway along which T. b. rhodesiense could spread northward from eastern Uganda. Targeted T. b. rhodesiense surveillance and control in eastern Uganda, through enhanced public-private partnerships, would serve to limit its spread.

Critical Linkages Between Livestock Production, Livestock Trade and Potential Spread of Human African Trypanosomiasis in Uganda: Bioeconomic Herd Modeling and Livestock Trade Analysis.

Background: Tsetse-transmitted human African trypanosomiasis (HAT) remains endemic in Uganda. The chronic form caused by Trypanosoma brucei gambiense (gHAT) is found in north-western Uganda, whereas the acute zoonotic form of the disease, caused by T. b. brucei rhodesiense (rHAT), occurs in the eastern region. Cattle is the major reservoir of rHAT in Uganda. These two forms of HAT are likely to converge resulting in a public health disaster. This study examines the intricate and intrinsic links between cattle herd dynamics, livestock trade and potential risk of spread of rHAT northwards. Methods: A bio-economic cattle herd model was developed to simulate herd dynamics at the farm level. Semi-structured interviews (n = 310), focus group discussions (n = 9) and key informant interviews (n = 9) were used to evaluate livestock markets (n = 9) as part of the cattle supply chain analysis. The cattle market data was used for stochastic risk analysis. Results: Cattle trade in eastern and northern Uganda is dominated by sale of draft and adult male cattle as well as exportation of young male cattle. The study found that the need to import draft cattle at the farm level was to cover deficits because of the herd structure, which is mostly geared towards animal traction. The importation and exportation of draft cattle and disposal of old adult male cattle formed the major basis of livestock movement and could result in the spread of rHAT northwards. The risk of rHAT infected cattle being introduced to northern Uganda from the eastern region via cattle trade was found to be high (i.e. probability of 1). Conclusion: Through deterministic and stochastic modelling of cattle herd and cattle trade dynamics, this study identifies critical links between livestock production and trade as well as potential risk of rHAT spread in eastern and northern Uganda. The findings highlight the need for targeted and routine surveillance and control of zoonotic diseases such as rHAT.

Secondary Bacterial Infections in Patients With Viral Pneumonia.

Pulmonary diseases of viral origin are often followed by the manifestation of secondary infections, leading to further clinical complications and negative disease outcomes. Thus, research on secondary infections is essential. Here, we review clinical data of secondary bacterial infections developed after the onset of pulmonary viral infections. We review the most recent clinical data and current knowledge of secondary bacterial infections and their treatment in SARS-CoV-2 positive patients; case reports from SARS-CoV, MERS-CoV, SARS-CoV2 and the best-studied respiratory virus, influenza, are described. We outline treatments used or prophylactic measures employed for secondary bacterial infections. This evaluation includes recent clinical reports of pulmonary viral infections, including those by COVID-19, that reference secondary infections. Where data was provided for COVID-19 patients, a mortality rate of 15.2% due to secondary bacterial infections was observed for patients with pneumonia (41 of 268). Most clinicians treated patients with SARS-CoV-2 infections with prophylactic antibiotics (63.7%, n = 1,901), compared to 73.5% (n = 3,072) in all clinical reports of viral pneumonia included in this review. For all cases of viral pneumonia, a mortality rate of 10.9% due to secondary infections was observed (53 of 482). Most commonly, quinolones, cephalosporins and macrolides were administered, but also the glycopeptide vancomycin. Several bacterial pathogens appear to be prevalent as causative agents of secondary infections, including antibiotic-resistant strains of Staphylococcus aureus and Klebsiella pneumoniae.

Secondary Bacterial Infections During Pulmonary Viral Disease: Phage Therapeutics as Alternatives to Antibiotics?

Secondary bacterial infections manifest during or after a viral infection(s) and can lead to negative outcomes and sometimes fatal clinical complications. Research and development of clinical interventions is largely focused on the primary pathogen, with research on any secondary infection(s) being neglected. Here we highlight the impact of secondary bacterial infections and in particular those caused by antibiotic-resistant strains, on disease outcomes. We describe possible non-antibiotic treatment options, when small molecule drugs have no effect on the bacterial pathogen and explore the potential of phage therapy and phage-derived therapeutic proteins and strategies in treating secondary bacterial infections, including their application in combination with chemical antibiotics.

The prevalence of methicillin-resistant Staphylococcus aureus among diabetic patients: a meta-analysis.

AIMS: Diabetic patients have multiple risk factors for colonisation with methicillin-resistant Staphylococcus aureus (MRSA), a nosocomial pathogen associated with significant morbidity and mortality. This meta-analysis was conducted to estimate the prevalence of MRSA among diabetic patients. METHODS: The MEDLINE, Embase, BIOSIS, and Web of Science databases were searched for studies published up to May 2018 that reported primary data on the prevalence of MRSA in 10 or more diabetic patients. Two authors independently assessed study eligibility and extracted the data. The main outcomes were the pooled prevalence rates of MRSA colonisation and infection among diabetic populations. RESULTS: Eligible data sets were divided into three groups containing data about the prevalence of MRSA colonisation or in diabetic foot or other infections. From 23 data sets, the prevalence of MRSA colonisation among 11577 diabetics was 9.20% (95% CI, 6.26-12.63%). Comparison of data from 14 studies that examined diabetic and non-diabetic patients found that diabetics had a 4.75% greater colonisation rate (P < 0.0001). From 41 data sets, the prevalence of MRSA in 10994 diabetic foot infection patients was 16.78% (95% CI, 13.21-20.68%). Among 2147 non-foot skin and soft-tissue infections, the MRSA prevalence rate was 18.03% (95% CI, 6.64-33.41). CONCLUSIONS: The prevalence of MRSA colonisation among diabetic patients is often higher than among non-diabetics; this may make targeted screening attractive. In the UK, many diabetic patients may already be covered by the current screening policies. The prevalence and impact of MRSA among diabetic healthcare workers requires further research. The high prevalence of MRSA among diabetic foot infections may have implications for antimicrobial resistance, and should encourage strategies aimed at infection prevention or alternative therapies.

Analysis of risk factors for T. brucei rhodesiense sleeping sickness within villages in south-east Uganda.

BACKGROUND: Sleeping sickness (HAT) caused by T.b. rhodesiense is a major veterinary and human public health problem in Uganda. Previous studies have investigated spatial risk factors for T.b. rhodesiense at large geographic scales, but none have properly investigated such risk factors at small scales, i.e. within affected villages. In the present work, we use a case-control methodology to analyse both behavioural and spatial risk factors for HAT in an endemic area. METHODS: The present study investigates behavioural and occupational risk factors for infection with HAT within villages using a questionnaire-based case-control study conducted in 17 villages endemic for HAT in SE Uganda, and spatial risk factors in 4 high risk villages. For the spatial analysis, the location of homesteads with one or more cases of HAT up to three years prior to the beginning of the study was compared to all non-case homesteads. Analysing spatial associations with respect to irregularly shaped geographical objects required the development of a new approach to geographical analysis in combination with a logistic regression model. RESULTS: The study was able to identify, among other behavioural risk factors, having a family member with a history of HAT (p = 0.001) as well as proximity of a homestead to a nearby wetland area (p < 0.001) as strong risk factors for infection. The novel method of analysing complex spatial interactions used in the study can be applied to a range of other diseases. CONCLUSION: Spatial risk factors for HAT are maintained across geographical scales; this consistency is useful in the design of decision support tools for intervention and prevention of the disease. Familial aggregation of cases was confirmed for T. b. rhodesiense HAT in the study and probably results from shared behavioural and spatial risk factors amongmembers of a household.

Estimating the burden of rhodesiense sleeping sickness during an outbreak in Serere, eastern Uganda.

BACKGROUND: Zoonotic sleeping sickness, or HAT (Human African Trypanosomiasis), caused by infection with Trypanosoma brucei rhodesiense, is an under-reported and neglected tropical disease. Previous assessments of the disease burden expressed as Disability-Adjusted Life Years (DALYs) for this infection have not distinguished T.b. rhodesiense from infection with the related, but clinically distinct Trypanosoma brucei gambiense form. T.b. rhodesiense occurs focally, and it is important to assess the burden at the scale at which resource-allocation decisions are made. METHODS: The burden of T.b. rhodesiense was estimated during an outbreak of HAT in Serere, Uganda. We identified the unique characteristics affecting the burden of rhodesiense HAT such as age, severity, level of under-reporting and duration of hospitalisation, and use field data and empirical estimates of these to model the burden imposed by this and other important diseases in this study population. While we modelled DALYs using standard methods, we also modelled uncertainty of our parameter estimates through a simulation approach. We distinguish between early and late stage HAT morbidity, and used disability weightings appropriate for the T.b. rhodesiense form of HAT. We also use a model of under-reporting of HAT to estimate the contribution of un-reported mortality to the overall disease burden in this community, and estimate the cost-effectiveness of hospital-based HAT control. RESULTS: Under-reporting accounts for 93% of the DALY estimate of rhodesiense HAT. The ratio of reported malaria cases to reported HAT cases in the same health unit was 133:1, however, the ratio of DALYs was 3:1. The age productive function curve had a close correspondence with the HAT case distribution, and HAT cases occupied more patient admission time in Serere during 1999 than all other infectious diseases other than malaria. The DALY estimate for HAT in Serere shows that the burden is much greater than might be expected from its relative incidence. Hospital based control in this setting appears to be highly cost-effective, highlighting the value of increasing coverage of therapy and reducing under-reporting. CONCLUSION: We show the utility of calculating DALYs for neglected diseases at the local decision making level, and emphasise the importance of improved reporting systems for acquiring a better understanding of the burden of neglected zoonotic diseases.

The Long Wait for a New Drug for Human African Trypanosomiasis.

Human African trypanosomiasis (HAT) is responsible for around 3000 reported cases each year. Treatments for HAT are expensive and problematic to administer, and available drugs are old and less than ideal, some with high levels of toxicity that result in debilitating and, in some cases, fatal side effects. Treatment options are limited, with only one drug, eflornithine, introduced in the last 28 years. Here we examine the limitations of current chemotherapeutic approaches to manage HAT, the constraints to new drug development exploring drug failures and new drugs on the horizon, and consider the epidemiological, political, social, and economic factors influencing drug development.