Livestock, pathogens, vectors, and their environment: a causal inference-based approach to estimating the pathway-specific effect of livestock on human African trypanosomiasis risk

Livestock are important reservoirs for many diseases, and investigation of such zoonoses has long been the focus of One Health research. However, the effects of livestock on human and environmental health extend well beyond direct disease transmission. In this retrospective ecological cohort study we use pre-existing data and methods derived from causal inference and spatial epidemiology to estimate three hypothesized mechanisms by which livestock can come to bear on human African trypanosomiasis (HAT) risk: the reservoir effect, by which infected cattle and pigs are a source of infection to humans; the zooprophylactic effect, by which preference for livestock hosts exhibited by the tsetse fly vector of HAT means that their presence protects humans from infection; and the environmental change effect, by which livestock keeping activities modify the environment in such a way that habitat suitability for tsetse flies, and in turn human infection risk, is reduced. We conducted this study in four high burden countries: at the point level in Uganda, Malawi, and Democratic Republic of Congo (DRC), and at the county-level in South Sudan. Our results indicate cattle and pigs play an important reservoir role for the rhodesiense form (rHAT) in Uganda, however zooprophylaxis outweighs this effect for rHAT in Malawi. For the gambiense form (gHAT) we found evidence that pigs may be a competent reservoir, however dominance of the reservoir versus zooprophylactic pathway for cattle varied across countries. We did not find compelling evidence of an environmental change effect.

Does a One Health Approach to Human African Trypanosomiasis Control Hasten Elimination? A Stochastic Compartmental Modeling Approach

Background: In response to large strides in the control of human African trypanosomiasis (HAT), in the early 2000s the WHO set targets for elimination of both the gambiense (gHAT) and rhodesiense (rHAT) forms as a public health (EPHP) problem by 2020, and elimination of gHAT transmisson (EOT) by 2030. While global EPHP targets have been met, and EOT appears within reach, there is ample evidence that current control strategies will not achieve gHAT EOT in the presence of animal reservoirs, the role of which is currently uncertain. Furthermore, rHAT is not targeted for EOT due to the known importance of animal reservoirs for this form. Methods: To evaluate the utility of a One Health approach to gHAT and rHAT EOT, we built and parameterized a compartmental stochastic model, using the Institute for Disease Modeling's Compartmental Modeling Software, to six HAT epidemics: the national rHAT epidemics in Uganda and Malawi, the national gHAT epidemics in Uganda and South Sudan, and two separate gHAT epidemics in Democratic Republic of Congo distinguished by dominant vector species. In rHAT foci the reservoir animal sub-model was stratified on four species groups, while in gHAT foci domestic swine were assumed to be the only competent reservoir. The modeled time horizon was 2005-2045, with calibration performed using HAT surveillance data from 2000-2004 and Optuna. Interventions included insecticide and trypanocide treatment of domestic animal reservoirs at varying coverage levels. Results: Validation against HAT surveillance data indicates favorable performance overall, with the possible exception of DRC. EOT was not observed in any modeled scenarios for rHAT, however insecticide treatment consistently performed better than trypanocide treatment in terms of rHAT control. EOT was not observed for gHAT at 0% coverage of domestic reservoirs with trypanocides or insecticides, but was observed by 2030 in all test scenarios; again, insecticides demonstrated superior performance to trypanocides. Conclusions: EOT cannot be achieved for rHAT without control of wildlife reservoirs, however insecticide treatment of domestic animals holds promise for improved control. In the presence of domestic animal reservoirs, gHAT EOT will not be achieved under current control strategies.

Policy and Linkages in the Application of a One Health System for Reporting and Controlling African Trypanosomiasis and Other Zoonotic Diseases in Zambia

The capacity to detect, control and manage emerging and re-emerging zoonotic diseases in Africa has been limited by a lack of utilisation of available reporting structures and policies to support programmes at national and local levels. This study explored the impact of the Zambian government policies on animal and human disease reporting and management and on One Health opportunities. An in-depth review and analysis of strengths, weaknesses, opportunities, and threats in the existing policies and reporting structures in the departments responsible for Veterinary Services, Health, and Wildlife, was conducted. According to our findings, sub-optimal implementation of existing policies related to the control of zoonotic diseases was impacting disease reporting, and reporting structures play an important role in effective and sustainable reporting of zoonotic diseases. Further, the study explored capacities and strategies in trypanosomiasis control as a case study that could prompt effective adoption of a One Health approach, and as such, the study suggests measures that could help to assess the performance of a One Health system in the control of African trypanosomiasis and other zoonotic diseases.

Modelling to infer the role of animals in gambiense human African trypanosomiasis transmission and elimination in DRC

Gambiense human African trypanosomiasis (gHAT) has been targeted for elimination of transmission (EoT) to humans by 2030. Whilst this ambitious goal is rapidly approaching, there remain fundamental questions about the presence of non-human animal transmission cycles and their potential role in slowing progress towards, or even preventing, EoT. In this study we focus on the country with the most gHAT disease burden, the Democratic Republic of Congo (DRC), and use mathematical modelling to assess whether animals may contribute to transmission in specific regions, and if so, how their presence could impact the likelihood and timing of EoT. By fitting two model variants – one with, and one without animal transmission – to the human case data from 2000–2016 we estimate model parameters for 158 endemic health zones of DRC. We evaluate the statistical support for each model variant in each health zone and infer the contribution of animals to overall transmission and how this could impact predicted time to EoT. We conclude that there are 24/158 health zones where there is moderate or high statistical support for some animal transmission. However, – even in these regions – we estimate that animals would be extremely unlikely to maintain transmission on their own. Animal transmission could hamper progress towards EoT in some settings, with projections under continuing interventions indicating that the number of health zones expected to achieve EoT by 2030 reduces from 68 to 61 if animals are included in the model. With supplementary vector control (at a modest 60% tsetse reduction) added to medical screening and treatment interventions, the predicted number of health zones meeting the goal increases to 147/158 for the model including animals. This is due to the impact of vector reduction on transmission to and from all hosts.

Economic evaluation of disease elimination: An extension to the net-benefit framework and application to human African trypanosomiasis

The global health community has earmarked a number of diseases for elimination or eradication, and these goals have often been praised on the premise of long-run cost savings. However, decision makers must contend with a multitude of demands on health budgets in the short or medium term, and costs per case often rise as the burden of a disease falls, rendering such efforts beyond the cost-effective use of scarce resources. In addition, these decisions must be made in the presence of substantial uncertainty regarding the feasibility and costs of elimination or eradication efforts. Therefore, analytical frameworks are necessary to consider the additional effort for reaching global goals, like elimination or eradication, that are beyond the cost-effective use of country resources. We propose a modification to the net-benefit framework to consider the implications of switching from an optimal strategy, in terms of cost-per-burden averted, to a strategy with a higher likelihood of meeting the global target of elimination or eradication. We illustrate the properties of our framework by considering the economic case of efforts to eliminate the transmission of gambiense human African trypanosomiasis (gHAT), a vector-borne, parasitic disease in West and Central Africa, by 2030.

Prevalence and outcomes of malaria as co-infection among patients with human African trypanosomiasis: a systematic review and meta-analysis

Human African trypanosomiasis (HAT) is endemic in Africa; hence, the possibility of co-infection with malaria among patients with HAT exists. The present study investigated co-infection with malaria among patients with HAT to provide current evidence and characteristics to support further studies. Potentially relevant studies that reported Plasmodium spp. infection in patients with HAT was searched in PubMed, Web of Science, and Scopus. The risk of bias among the included studies was assessed using the checklist for analytical cross-sectional studies developed by the Joanna Briggs Institute. The pooled prevalence of Plasmodium spp. infection in patients with HAT was quantitatively synthesized using a random-effects model. Subgroup analyses of study sites and stages of HAT were performed to identify heterogeneity regarding prevalence among the included studies. The heterogeneity of the outcome among the included studies was assessed using Cochran’s Q and I2 statistics for consistency. Publication bias was assessed if the number of included studies was 10 or more. For qualitative synthesis, a narrative synthesis of the impact of Plasmodium spp. infection on the clinical and outcome characteristics of HAT was performed when the included studies provided qualitative data. Among 327 studies identified from three databases, nine studies were included in the systematic review and meta-analysis. The prevalence of Plasmodium spp. co-infection (692 cases) among patients with HAT (1523 cases) was 50% (95% confidence interval [CI] = 28–72%, I2 = 98.1%, seven studies). Subgroup analysis by type of HAT (gambiense or rhodesiense HAT) revealed that among patients with gambiense HAT, the pooled prevalence of Plasmodium spp. infection was 46% (95% CI = 14–78%, I2 = 96.62%, four studies), whereas that among patients with rhodesiense HAT was 44% (95% CI = 40–49%, I2 = 98.3%, three studies). Qualitative syntheses demonstrated that Plasmodium spp. infection in individuals with HAT might influence the risk of encephalopathy syndrome, drug toxicity, and significantly longer corrected QT time. Moreover, longer hospital stays and higher treatment costs were recorded among co-infected individuals. Because of the high prevalence of malaria among patients with HAT, some patients were positive for malaria parasites despite being asymptomatic. Therefore, it is suggested to test every patient with HAT for malaria before HAT treatment. If malaria is present, then antimalarial treatment is recommended before HAT treatment. Antimalarial treatment in patients with HAT might decrease the probability of poor clinical outcomes and case fatality in HAT.