Integrating contact tracing and whole-genome sequencing to track the elimination of dog-mediated rabies: An observational and genomic study.

Background: Dog-mediated rabies is endemic across Africa causing thousands of human deaths annually. A One Health approach to rabies is advocated, comprising emergency post-exposure vaccination of bite victims and mass dog vaccination to break the transmission cycle. However, the impacts and cost-effectiveness of these components are difficult to disentangle. Methods: We combined contact tracing with whole-genome sequencing to track rabies transmission in the animal reservoir and spillover risk to humans from 2010 to 2020, investigating how the components of a One Health approach reduced the disease burden and eliminated rabies from Pemba Island, Tanzania. With the resulting high-resolution spatiotemporal and genomic data, we inferred transmission chains and estimated case detection. Using a decision tree model, we quantified the public health burden and evaluated the impact and cost-effectiveness of interventions over a 10-year time horizon. Results: We resolved five transmission chains co-circulating on Pemba from 2010 that were all eliminated by May 2014. During this period, rabid dogs, human rabies exposures and deaths all progressively declined following initiation and improved implementation of annual islandwide dog vaccination. We identified two introductions to Pemba in late 2016 that seeded re-emergence after dog vaccination had lapsed. The ensuing outbreak was eliminated in October 2018 through reinstated islandwide dog vaccination. While post-exposure vaccines were projected to be highly cost-effective ($256 per death averted), only dog vaccination interrupts transmission. A combined One Health approach of routine annual dog vaccination together with free post-exposure vaccines for bite victims, rapidly eliminates rabies, is highly cost-effective ($1657 per death averted) and by maintaining rabies freedom prevents over 30 families from suffering traumatic rabid dog bites annually on Pemba island. Conclusions: A One Health approach underpinned by dog vaccination is an efficient, cost-effective, equitable, and feasible approach to rabies elimination, but needs scaling up across connected populations to sustain the benefits of elimination, as seen on Pemba, and for similar progress to be achieved elsewhere. Funding: Wellcome [207569/Z/17/Z, 095787/Z/11/Z, 103270/Z/13/Z], the UBS Optimus Foundation, the Department of Health and Human Services of the National Institutes of Health [R01AI141712] and the DELTAS Africa Initiative [Afrique One-ASPIRE/DEL-15-008] comprising a donor consortium of the African Academy of Sciences (AAS), Alliance for Accelerating Excellence in Science in Africa (AESA), the New Partnership for Africa's Development Planning and Coordinating (NEPAD) Agency, Wellcome [107753/A/15/Z], Royal Society of Tropical Medicine and Hygiene Small Grant 2017 [GR000892] and the UK government. The rabies elimination demonstration project from 2010-2015 was supported by the Bill & Melinda Gates Foundation [OPP49679]. Whole-genome sequencing was partially supported from APHA by funding from the UK Department for Environment, Food and Rural Affairs (Defra), Scottish government and Welsh government under projects SEV3500 and SE0421.

Performance characteristics and costs of serological tests for brucellosis in a pastoralist community of northern Tanzania.

The control of brucellosis across sub-Saharan Africa is hampered by the lack of standardized testing and the use of tests with poor performance. This study evaluated the performance and costs of serological assays for human brucellosis in a pastoralist community in northern Tanzania. Serum collected from 218 febrile hospital patients was used to evaluate the performance of seven index tests, selected based on international recommendation or current use. We evaluated the Rose Bengal test (RBT) using two protocols, four commercial agglutination tests and a competitive enzyme-linked immunosorbent assay (cELISA). The sensitivity, specificity, positive predictive value, negative predictive value, Youden's index, diagnostic accuracy, and per-sample cost of each index test were estimated. The diagnostic accuracy estimates ranged from 95.9 to 97.7% for the RBT, 55.0 to 72.0% for the commercial plate tests, and 89.4% for the cELISA. The per-sample cost range was $0.69-$0.79 for the RBT, $1.03-$1.14 for the commercial plate tests, and $2.51 for the cELISA. The widely used commercial plate tests performed poorly and cost more than the RBT. These findings provide evidence for the public health value of discontinuing the use of commercial agglutination tests for human brucellosis in Tanzania.

Correction: The Economic Impact of Malignant Catarrhal Fever on Pastoralist Livelihoods.

[This corrects the article DOI: 10.1371/journal.pone.0116059.].

Assessment of GeneXpert GxAlert platform for multi-drug resistant tuberculosis diagnosis and patients' linkage to care in Tanzania.

OBJECTIVE: The gap between patients diagnosed with multi-drug resistant tuberculosis (MDR-TB) and enrolment in treatment is one of the major challenges in tuberculosis control programmes. A 4-year (2013-2016) retrospective review of patients' clinical data and subsequent in-depth interviews with health providers were conducted to assess the effectiveness of the GeneXpert GxAlert platform for MDR-TB diagnosis and its impact on linkage of patients to care in Tanzania. RESULTS: A total of 782 new rifampicin resistant cases were notified, but only 242 (32.3%) were placed in an MDR-TB regimens. The remaining 540 (67.07%) patients were not on treatment, of which 103 patients had complete records on the GxAlert database. Of the 103 patients: 39 were judged as untraceable; 27 died before treatment; 12 were treated with first-line anti-TBs; 9 repeat tests did not show rifampicin resistance; 15 were not on treatment due to communication breakdown, and 1 patient was transferred outside the country. In-depth interviews with health providers suggested that the pre-treatment loss for the MDR-TB patients was primarily attributed to health system and patients themselves. We recommend strengthening the health system by developing and implementing well-defined interventions to ensure all diagnosed MDR-TB patients are accurately reported and timely linked to treatment.

Assessment of sputum smear-positive but culture-negative results among newly diagnosed pulmonary tuberculosis patients in Tanzania.

Diagnosis of pulmonary tuberculosis (TB) in technology-limited countries is widely achieved by smear microscopy, which has limited sensitivity and specificity. The frequency and clinical implication of smear-positive but culture-negative among presumptive TB patients remains unclear. A cross-sectional substudy was conducted which aimed to identify the proportion of nontuberculous mycobacteria (NTM) infections among 94 "smear-positive culture-negative" patients diagnosed between January 2013 and June 2016 in selected health facilities in Tanzania. Out of 94 sputa, 25 (26.60%) were GeneXpert® mycobacteria TB positive and 11/94 (11.70%) repeat-culture positive; 5 were Capilia TB-Neo positive and confirmed by GenoType MTBC to be Mycobacterium tuberculosis/Mycobacterium canettii. The remaining 6 Capilia TB-Neo negative samples were genotyped by GenoType® CM/AS, identifying 3 (3.19%) NTM, 2 Gram positive bacteria, and 1 isolate testing negative, together, making a total of 6/94 (6.38%) confirmed false smear-positives. Twenty-eight (29.79%) were confirmed TB cases, while 60 (63.83%) remained unconfirmed cases. Out of 6 (6.38%) patients who were HIV positive, 2 patients were possibly coinfected with mycobacteria. The isolation of NTM and other bacteria among smear-positive culture-negative samples and the presence of over two third of unconfirmed TB cases emphasize the need of both advanced differential TB diagnostic techniques and good clinical laboratory practices to avoid unnecessary administration of anti-TB drugs.

The economic impact of malignant catarrhal fever on pastoralist livelihoods.

This study is the first to partially quantify the potential economic benefits that a vaccine, effective at protecting cattle against malignant catarrhal fever (MCF), could accrue to pastoralists living in East Africa. The benefits would result from the removal of household resource and management costs that are traditionally incurred avoiding the disease. MCF, a fatal disease of cattle caused by a virus transmitted from wildebeest calves, has plagued Maasai communities in East Africa for generations. The threat of the disease forces the Maasai to move cattle to less productive grazing areas to avoid wildebeest during calving season when forage quality is critical. To assess the management and resource costs associated with moving, we used household survey data. To estimate the costs associated with changes in livestock body condition that result from being herded away from wildebeest calving grounds, we exploited an ongoing MCF vaccine field trial and we used a hedonic price regression, a statistical model that allows estimation of the marginal contribution of a good's attributes to its market price. We found that 90 percent of households move, on average, 82 percent of all cattle away from home to avoid MCF. In doing so, a herd's productive contributions to the household was reduced, with 64 percent of milk being unavailable for sale or consumption by the family members remaining at the boma (the children, women, and the elderly). In contrast cattle that remained on the wildebeest calving grounds during the calving season (and survived MCF) remained fully productive to the family and gained body condition compared to cattle that moved away. This gain was, however, short-lived. We estimated the market value of these condition gains and losses using hedonic regression. The value of a vaccine for MCF is the removal of the costs incurred in avoiding the disease.

The global one health paradigm: challenges and opportunities for tackling infectious diseases at the human, animal, and environment interface in low-resource settings.

Zoonotic infectious diseases have been an important concern to humankind for more than 10,000 years. Today, approximately 75% of newly emerging infectious diseases (EIDs) are zoonoses that result from various anthropogenic, genetic, ecologic, socioeconomic, and climatic factors. These interrelated driving forces make it difficult to predict and to prevent zoonotic EIDs. Although significant improvements in environmental and medical surveillance, clinical diagnostic methods, and medical practices have been achieved in the recent years, zoonotic EIDs remain a major global concern, and such threats are expanding, especially in less developed regions. The current Ebola epidemic in West Africa is an extreme stark reminder of the role animal reservoirs play in public health and reinforces the urgent need for globally operationalizing a One Health approach. The complex nature of zoonotic diseases and the limited resources in developing countries are a reminder that the need for implementation of Global One Health in low-resource settings is crucial. The Veterinary Public Health and Biotechnology (VPH-Biotec) Global Consortium launched the International Congress on Pathogens at the Human-Animal Interface (ICOPHAI) in order to address important challenges and needs for capacity building. The inaugural ICOPHAI (Addis Ababa, Ethiopia, 2011) and the second congress (Porto de Galinhas, Brazil, 2013) were unique opportunities to share and discuss issues related to zoonotic infectious diseases worldwide. In addition to strong scientific reports in eight thematic areas that necessitate One Health implementation, the congress identified four key capacity-building needs: (1) development of adequate science-based risk management policies, (2) skilled-personnel capacity building, (3) accredited veterinary and public health diagnostic laboratories with a shared database, and (4) improved use of existing natural resources and implementation. The aim of this review is to highlight advances in key zoonotic disease areas and the One Health capacity needs.

The feasibility of canine rabies elimination in Africa: dispelling doubts with data.

BACKGROUND: Canine rabies causes many thousands of human deaths every year in Africa, and continues to increase throughout much of the continent. METHODOLOGY/PRINCIPAL FINDINGS: This paper identifies four common reasons given for the lack of effective canine rabies control in Africa: (a) a low priority given for disease control as a result of lack of awareness of the rabies burden; (b) epidemiological constraints such as uncertainties about the required levels of vaccination coverage and the possibility of sustained cycles of infection in wildlife; (c) operational constraints including accessibility of dogs for vaccination and insufficient knowledge of dog population sizes for planning of vaccination campaigns; and (d) limited resources for implementation of rabies surveillance and control. We address each of these issues in turn, presenting data from field studies and modelling approaches used in Tanzania, including burden of disease evaluations, detailed epidemiological studies, operational data from vaccination campaigns in different demographic and ecological settings, and economic analyses of the cost-effectiveness of dog vaccination for human rabies prevention. CONCLUSIONS/SIGNIFICANCE: We conclude that there are no insurmountable problems to canine rabies control in most of Africa; that elimination of canine rabies is epidemiologically and practically feasible through mass vaccination of domestic dogs; and that domestic dog vaccination provides a cost-effective approach to the prevention and elimination of human rabies deaths.