Mobilizing resources with an investment case to mitigate cross-border malaria transmission and achieve malaria elimination in South Africa.

South Africa's effort to eliminate malaria is significantly challenged by a large number of imported malaria cases, especially from neighbouring Mozambique. The country has a funding gap to achieve its malaria elimination goals (prior to 2019) and is ineligible to receive a national allocation from the Global Fund. The findings of an IC were utilised to successfully mobilise resources for malaria elimination in South Africa in 2018. A five-step resource mobilisation strategy was implemented to highlight financing challenges and leverage the economic evidence from an IC for malaria elimination in South Africa. South Africa's malaria programme implements control and elimination activities in three malaria-endemic provinces (KwaZulu Natal, Limpopo, and Mpumalanga). Driven by the IC findings, the South African government took an unprecedented step and increased total domestic malaria financing by approximately 36%, from the 2018/19 to the 2019/20 financial years through the creation of a new conditional grant for malaria. The IC findings predicted that malaria control in southern Mozambique is a prerequisite to eliminate malaria in South Africa. Based on this, the South African government also allocated funding towards a co-financing mechanism to support malaria control efforts in southern Mozambique. The IC findings assisted the South African National Department of Health to make a convincing case to key government decision-makers to invest in national malaria elimination and maximise economic returns in the long run. The South African government is the first in Southern Africa to mobilise a significant increase in domestic malaria financing to address the financial sustainability of both national and regional malaria elimination efforts. Continued surveillance activities will be required to prevent the re-establishment of malaria transmission even after malaria elimination is achieved in South Africa. Information sharing and close collaboration with provincial and national government officials were key to the successful outcome.

Clinical Effects of the 'Crisis Toolbox' (CTB): A Brief, Skills Based, Intervention Delivered in a Crisis Resolution and Home Treatment Team.

Access to psychological interventions for people under Crisis Resolution and Home Treatment Teams (CRHTTs) is limited. The Crisis Toolbox (CTB) is a skills-based intervention designed to increase access using flexible methods of delivery. This study aimed to evaluate the clinical effects of the CTB. A retrospective service evaluation of 399 participants who accessed the CTB between November 2020 and February 2021 was employed. Sessional measures comprising the Patient Health Questionnaire (PHQ-9) and Generalised Anxiety Scale (GAD-7) were recorded across three time points. Overall, there were significantly decreasing trends in PHQ-9 (ß = - 1.6, p < 0.001) and GAD-7 scores (ß = - 1.5, p < 0.001) in participants who accessed the CTB. The magnitude and direction of specific trends differed according to age, diagnosis, and neurodiversity. The CTB could help reduce depression and anxiety in people experiencing crisis. Randomised controlled trials are now required to test its acceptability, feasibility, and effectiveness.

Investment case for malaria elimination in South Africa: a financing model for resource mobilization to accelerate regional malaria elimination.

BACKGROUND: Malaria continues to be a public health problem in South Africa. While the disease is mainly confined to three of the nine provinces, most local transmissions occur because of importation of cases from neighbouring countries. The government of South Africa has reiterated its commitment to eliminate malaria within its borders. To support the achievement of this goal, this study presents a cost-benefit analysis of malaria elimination in South Africa through simulating different scenarios aimed at achieving malaria elimination within a 10-year period. METHODS: A dynamic mathematical transmission model was developed to estimate the costs and benefits of malaria elimination in South Africa between 2018 and 2030. The model simulated a range of malaria interventions and estimated their impact on the transmission of Plasmodium falciparum malaria between 2018 and 2030 in the three endemic provinces of Limpopo, Mpumalanga and KwaZulu-Natal. Local financial, economic, and epidemiological data were used to calibrate the transmission model. RESULTS: Based on the three primary simulated scenarios: Business as Usual, Accelerate and Source Reduction, the total economic burden was estimated as follows: for the Business as Usual scenario, the total economic burden of malaria in South Africa was R 3.69 billion (USD 223.3 million) over an 11-year period (2018-2029). The economic burden of malaria was estimated at R4.88 billion (USD 295.5 million) and R6.34 billion (~ USD 384 million) for the Accelerate and Source Reduction scenarios, respectively. Costs and benefits are presented in midyear 2020 values. Malaria elimination was predicted to occur in all three provinces if the Source Reduction strategy was adopted to help reduce malaria rates in southern Mozambique. This could be achieved by limiting annual local incidence in South Africa to less than 1 indigenous case with a prediction of this goal being achieved by the year 2026. CONCLUSIONS: Malaria elimination in South Africa is feasible and economically worthwhile with a guaranteed positive return on investment (ROI). Findings of this study show that through securing funding for the proposed malaria interventions in the endemic areas of South Africa and neighbouring Mozambique, national elimination could be within reach in an 8-year period.

Malaria elimination transmission and costing in the Asia-Pacific: Developing an investment case.

Background: The Asia-Pacific region has made significant progress against malaria, reducing cases and deaths by over 50% between 2010 and 2015. These gains have been facilitated in part, by strong political and financial commitment of governments and donors. However, funding gaps and persistent health system challenges threaten further progress. Achieving the regional goal of malaria elimination by 2030 will require an intensification of efforts and a plan for sustainable financing. This article presents an investment case for malaria elimination to facilitate these efforts. Methods: A transmission model was developed to project rates of decline of Plasmodium falciparum and Plasmodium vivax malaria and the output was used to determine the cost of the interventions that would be needed for elimination by 2030. In total, 80 scenarios were modelled under various assumptions of resistance and intervention coverage. The mortality and morbidity averted were estimated and health benefits were monetized by calculating the averted cost to the health system, individual households, and society. The full-income approach was used to estimate the economic impact of lost productivity due to premature death and illness, and a return on investment was computed. Results: The study estimated that malaria elimination in the region by 2030 could be achieved at a cost of USD 29.02 billion (range: USD 23.65-36.23 billion) between 2017 and 2030. Elimination would save over 400,000 lives and avert 123 million malaria cases, translating to almost USD 90 billion in economic benefits. Discontinuing vector control interventions and reducing treatment coverage rates to 50% will result in an additional 845 million cases, 3.5 million deaths, and excess costs of USD 7 billion. Malaria elimination provides a 6:1 return on investment. Conclusion: This investment case provides compelling evidence for the benefits of continued prioritization of funding for malaria and can be used to develop an advocacy strategy.

An Investment Case to Prevent the Reintroduction of Malaria in Sri Lanka.

Sri Lanka has made remarkable gains in reducing the burden of malaria, recording no locally transmitted malaria cases since November 2012 and zero deaths since 2007. The country was recently certified as malaria free by World Health Organization in September 2016. Sri Lanka, however, continues to face a risk of resurgence due to persistent receptivity and vulnerability to malaria transmission. Maintaining the gains will require continued financing to the malaria program to maintain the activities aimed at preventing reintroduction. This article presents an investment case for malaria in Sri Lanka by estimating the costs and benefits of sustaining investments to prevent the reintroduction of the disease. An ingredient-based approach was used to estimate the cost of the existing program. The cost of potential resurgence was estimated using a hypothetical scenario in which resurgence assumed to occur, if all prevention of reintroduction activities were halted. These estimates were used to compute a benefit-cost ratio and a return on investment. The total economic cost of the malaria program in 2014 was estimated at U.S. dollars (USD) 0.57 per capita per year with a financial cost of USD0.37 per capita. The cost of potential malaria resurgence was, however, much higher estimated at 13 times the cost of maintaining existing activities or 21 times based on financial costs alone. This evidence suggests a substantial return on investment providing a compelling argument for advocacy for continued prioritization of funding for the prevention of reintroduction of malaria in Sri Lanka.

Kuru prions and sporadic Creutzfeldt-Jakob disease prions have equivalent transmission properties in transgenic and wild-type mice.

Kuru provides our principal experience of an epidemic human prion disease and primarily affected the Fore linguistic group of the Eastern Highlands of Papua New Guinea. Kuru was transmitted by the practice of consuming dead relatives as a mark of respect and mourning (transumption). To date, detailed information of the prion strain type propagated in kuru has been lacking. Here, we directly compare the transmission properties of kuru prions with sporadic, iatrogenic, and variant Creutzfeldt-Jakob disease (CJD) prions in Prnp-null transgenic mice expressing human prion protein and in wild-type mice. Molecular and neuropathological data from these transmissions show that kuru prions are distinct from variant CJD and have transmission properties equivalent to those of classical (sporadic) CJD prions. These findings are consistent with the hypothesis that kuru originated from chance consumption of an individual with sporadic CJD.

Dissociation of pathological and molecular phenotype of variant Creutzfeldt-Jakob disease in transgenic human prion protein 129 heterozygous mice.

All neuropathologically confirmed cases of variant Creutzfeldt-Jakob disease (vCJD), characterized by abundant florid plaques and type 4 disease-related prion protein (PrP(Sc)) in the brain, have been homozygous for methionine at polymorphic residue 129 of PRNP. The distinctive neuropathological and molecular phenotype of vCJD can be faithfully recapitulated in Prnp-null transgenic mice homozygous for human PrP M129 but not V129, where a distinct prion strain is propagated. Here we model susceptibility of 129MV heterozygotes, the most common PRNP genotype, in transgenic mice and show that, remarkably, propagation of type 4 PrP(Sc) was not associated with characteristic vCJD neuropathology. Depending on the source of the inoculum these mice can develop four distinct disease phenotypes after challenge with bovine spongiform encephalopathy (BSE) prions or vCJD (human-passaged BSE) prions. vCJD-challenged mice had higher attack rates of prion infection than BSE-challenged recipients. These data argue that human PRNP 129 heterozygotes will be more susceptible to infection with vCJD prions than to cattle BSE prions and may present with a neuropathological phenotype distinct from vCJD.