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.

Simulating the council-specific impact of anti-malaria interventions: A tool to support malaria strategic planning in Tanzania.

INTRODUCTION: The decision-making process for malaria control and elimination strategies has become more challenging. Interventions need to be targeted at council level to allow for changing malaria epidemiology and an increase in the number of possible interventions. Models of malaria dynamics can support this process by simulating potential impacts of multiple interventions in different settings and determining appropriate packages of interventions for meeting specific expected targets. METHODS: The OpenMalaria model of malaria dynamics was calibrated for all 184 councils in mainland Tanzania using data from malaria indicator surveys, school parasitaemia surveys, entomological surveillance, and vector control deployment data. The simulations were run for different transmission intensities per region and five interventions, currently or potentially included in the National Malaria Strategic Plan, individually and in combination. The simulated prevalences were fitted to council specific prevalences derived from geostatistical models to obtain council specific predictions of the prevalence and number of cases between 2017 and 2020. The predictions were used to evaluate in silico the feasibility of the national target of reaching a prevalence of below 1% by 2020, and to suggest alternative intervention stratifications for the country. RESULTS: The historical prevalence trend was fitted for each council with an agreement of 87% in 2016 (95%CI: 0.84-0.90) and an agreement of 90% for the historical trend (2003-2016) (95%CI: 0.87-0.93) The current national malaria strategy was expected to reduce the malaria prevalence between 2016 and 2020 on average by 23.8% (95% CI: 19.7%-27.9%) if current case management levels were maintained, and by 52.1% (95% CI: 48.8%-55.3%) if the case management were improved. Insecticide treated nets and case management were the most cost-effective interventions, expected to reduce the prevalence by 25.0% (95% CI: 19.7%-30.2) and to avert 37 million cases between 2017 and 2020. Mass drug administration was included in most councils in the stratification selected for meeting the national target at minimal costs, expected to reduce the prevalence by 77.5% (95%CI: 70.5%-84.5%) and to avert 102 million cases, with almost twice higher costs than those of the current national strategy. In summary, the model suggested that current interventions are not sufficient to reach the national aim of a prevalence of less than 1% by 2020 and a revised strategic plan needs to consider additional, more effective interventions, especially in high transmission areas and that the targets need to be revisited. CONCLUSION: The methodology reported here is based on intensive interactions with the NMCP and provides a helpful tool for assessing the feasibility of country specific targets and for determining which intervention stratifications at sub-national level will have most impact. This country-led application could support strategic planning of malaria control in many other malaria endemic countries.

Effectiveness and equity of the Tanzania National Voucher Scheme for mosquito nets over 10 years of implementation.

BACKGROUND: The Tanzania National Voucher Scheme (TNVS) was a public private partnership managed by the Ministry of Health that provided pregnant women and infants with highly subsidized (long-lasting) insecticide-treated nets between 2004 and 2014. It was implemented in the context of the National Insecticide Treated Nets (NATNETS) Programme and was the main keep up strategy for vulnerable populations. CASE DESCRIPTION: The programme design was adjusted considerably over time to incorporate new evidence, shifting public health policies, and changing donor priorities. Three TNVS models can be distinguished: (1) the fixed discount; (2) the fixed top-up; (3) the hybrid voucher model. The changes improved equity and effectiveness, but also had a profound effect on how the programme was managed and implemented. RESULTS: The TNVS reached the majority of beneficiaries with vouchers, and significantly increased household ownership and use of LLINs. While two mass distribution campaigns implemented between 2009 and 2011 achieved universal coverage and equity, the TNVS ensured continuous protection of the vulnerable populations before, during and after the campaigns. The TNVS stimulated and maintained a large national retail network which managed the LLIN supply chain. DISCUSSION AND LESSONS LEARNED: The effectiveness of the TNVS was a function of several interdependent factors, including the supply chain of vouchers through the public health system; the supply chain of nets in the commercial sector; the demand for nets from voucher recipients; management and risk mitigation measures; and the influence of global and donor objectives. CONCLUSION: The TNVS was a highly innovative and globally influential programme, which stimulated the thinking around effectively and equitably distributing ITNs, and contributed directly to the evolution of global policy. It was a fundamental component of the NATNETS programme which protected a malaria-vulnerable population for over a decade.

School Distribution as Keep-Up Strategy to Maintain Universal Coverage of Long-Lasting Insecticidal Nets: Implementation and Results of a Program in Southern Tanzania.

Tanzania successfully scaled up coverage of long-lasting insecticidal nets (LLINs) through mass campaigns. To sustain these gains, a school-based approach was piloted in the country's Southern Zone starting in 2013, called the School Net Program 1 (SNP1). We report on the design, implementation, monitoring, and outputs of the second round (SNP2) undertaken in 2014. SNP2 was conducted in all schools in Lindi, Mtwara, and Ruvuma regions, targeting students in primary (Standards 1, 3, 5, and 7) and secondary (Forms 2 and 4) schools and all teachers. In Lindi region, 2 additional classes (Standards 2 and 4) were targeted. LLIN distribution data were managed using an Android software application called SchoolNet. SNP2 included 2,337 schools, 473,700 students, and 25,269 teachers. A total of 5,070 people were trained in LLIN distribution (487 trainers and 4,583 distributors), and 4,392 (434 ward and 3,958 village) community change agents undertook sensitization and mobilization. A total of 507,775 LLINs were distributed to schools, with 464,510 (97.9% of those registered) students and 24,206 (95.8% of those registered) school teachers receiving LLINs. LLIN ownership and use is expected to have increased, potentially further reducing the burden of malaria in the Southern Zone of Tanzania.

Evaluation of HIV antigen/antibody combination ELISAs for diagnosis of HIV infection in Dar Es Salaam, Tanzania.

INTRODUCTION: The aim of this study was to evaluate the performance of Enzygnost HIV Integral II antigen/antibody combination ELISAs in order to formulate HIV ELISA testing algorithms for the Ministry of Health and Social Welfare, Tanzania. METHODS: This was a laboratory-based evaluation of Enzygnost HIV Integral II Antibody/ Antigen, Murex HIV antigen/antibody and Vironostika HIV Uniform II antigen/antibody conducted between October 2011 and May 2012. RESULTS: A total of 600 blood samples were included in the evaluation. A total of 209/596 (35.1%) serum samples were confirmed HIV positive. Of these, the prevalence of HIV infection was 2.3% (3/130), 2.3% (3/127), 2.2% (3/139) and 100% (200/200) for VCT clients, ANC attendees, blood donors and CTC patients, respectively. Three hundred and eighty seven (64.9%) were HIV negative samples. Sensitivity was 100% (95% CI; 98.3-100%) for all the three HIV ELISAs. The specificity for the Enzygnost HIV Integral II and Murex was 100% (95% CI; 99.1-100%). The final specificity at repeat testing was 99.5% (95% CI; 98.2-99.9%) for Vironostika. Enzygnost HIV Integral II detected HIV infection seven days since first bleed. CONCLUSION: Initial testing using either Vironostika or Murex HIV antigen/antibody combination ELISA followed by testing of reactive samples on the Enzygnost HIV Integral II gave a sensitivity and specificity of 100% with reduced window period. Combination of two HIV antigen/antibody combination ELISAs can be used as an alternative confirmatory testing strategy for screening of donated blood at the National and Zonal blood transfusion centres and in lab diagnosis of HIV infection.

Prediction, assessment of the Rift Valley fever activity in East and Southern Africa 2006-2008 and possible vector control strategies.

Historical outbreaks of Rift Valley fever (RVF) since the early 1950s have been associated with cyclical patterns of the El Niño/Southern Oscillation (ENSO) phenomenon, which results in elevated and widespread rainfall over the RVF endemic areas of Africa. Using satellite measurements of global and regional elevated sea surface temperatures, elevated rainfall, and satellite derived-normalized difference vegetation index data, we predicted with lead times of 2-4 months areas where outbreaks of RVF in humans and animals were expected and occurred in the Horn of Africa, Sudan, and Southern Africa at different time periods from September 2006 to March 2008. Predictions were confirmed by entomological field investigations of virus activity and by reported cases of RVF in human and livestock populations. This represents the first series of prospective predictions of RVF outbreaks and provides a baseline for improved early warning, control, response planning, and mitigation into the future.