Estimated impact of RTS,S/AS01 malaria vaccine allocation strategies in sub-Saharan Africa: A modelling study

BackgroundThe RTS,S/AS01 vaccine against Plasmodium falciparum malaria infection completed phase III trials in 2014 and demonstrated efficacy against clinical malaria of approximately 36% over 4 years for a 4-dose schedule in children aged 5–17 months. Pilot vaccine implementation has recently begun in 3 African countries. If the pilots demonstrate both a positive health impact and resolve remaining safety concerns, wider roll-out could be recommended from 2021 onwards. Vaccine demand may, however, outstrip initial supply. We sought to identify where vaccine introduction should be prioritised to maximise public health impact under a range of supply constraints using mathematical modelling.Methods and findingsUsing a mathematical model of P. falciparum malaria transmission and RTS,S vaccine impact, we estimated the clinical cases and deaths averted in children aged 0–5 years in sub-Saharan Africa under 2 scenarios for vaccine coverage (100% and realistic) and 2 scenarios for other interventions (current coverage and World Health Organization [WHO] Global Technical Strategy targets). We used a prioritisation algorithm to identify potential allocative efficiency gains from prioritising vaccine allocation among countries or administrative units to maximise cases or deaths averted. If malaria burden at introduction is similar to current levels—assuming realistic vaccine coverage and country-level prioritisation in areas with parasite prevalence >10%—we estimate that 4.3 million malaria cases (95% credible interval [CrI] 2.8–6.8 million) and 22,000 deaths (95% CrI 11,000–35,000) in children younger than 5 years could be averted annually at a dose constraint of 30 million. This decreases to 3.0 million cases (95% CrI 2.0–4.7 million) and 14,000 deaths (95% CrI 7,000–23,000) at a dose constraint of 20 million, and increases to 6.6 million cases (95% CrI 4.2–10.8 million) and 38,000 deaths (95% CrI 18,000–61,000) at a dose constraint of 60 million. At 100% vaccine coverage, these impact estimates increase to 5.2 million cases (95% CrI 3.5–8.2 million) and 27,000 deaths (95% CrI 14,000–43,000), 3.9 million cases (95% CrI 2.7–6.0 million) and 19,000 deaths (95% CrI 10,000–30,000), and 10.0 million cases (95% CrI 6.7–15.7 million) and 51,000 deaths (95% CrI 25,000–82,000), respectively. Under realistic vaccine coverage, if the vaccine is prioritised sub-nationally, 5.3 million cases (95% CrI 3.5–8.2 million) and 24,000 deaths (95% CrI 12,000–38,000) could be averted at a dose constraint of 30 million. Furthermore, sub-national prioritisation would allow introduction in almost double the number of countries compared to national prioritisation (21 versus 11). If vaccine introduction is prioritised in the 3 pilot countries (Ghana, Kenya, and Malawi), health impact would be reduced, but this effect becomes less substantial (change of <5%) if 50 million or more doses are available. We did not account for within-country variation in vaccine coverage, and the optimisation was based on a single outcome measure, therefore this study should be used to understand overall trends rather than guide country-specific allocation.ConclusionsThese results suggest that the impact of constraints in vaccine supply on the public health impact of the RTS,S malaria vaccine could be reduced by introducing the vaccine at the sub-national level and prioritising countries with the highest malaria incidence.

Alexandra Hogan and colleagues explore strategies to optimize vaccine allocation for maximum public health benefit in the face of potential supply constraints.     

Prevention and control of dengue and chikungunya in Colombia: A cost-effectiveness analysis

BackgroundChikungunya and dengue are emerging diseases that have caused large outbreaks in various regions of the world. Both are both spread by Aedes aegypti and Aedes albopictus mosquitos. We developed a dynamic transmission model of chikungunya and dengue, calibrated to data from Colombia (June 2014 –December 2017).Methodology/Principal findingsWe evaluated the health benefits and cost-effectiveness of residual insecticide treatment, long-lasting insecticide-treated nets, routine dengue vaccination for children aged 9, catchup vaccination for individuals aged 10–19 or 10–29, and portfolios of these interventions. Model calibration resulted in 300 realistic transmission parameters sets that produced close matches to disease-specific incidence and deaths. Insecticide was the preferred intervention and was cost-effective. Insecticide averted an estimated 95 chikungunya cases and 114 dengue cases per 100,000 people, 61 deaths, and 4,523 disability-adjusted life years (DALYs). In sensitivity analysis, strategies that included dengue vaccination were cost-effective only when the vaccine cost was 14% of the current price.Conclusions/SignificanceInsecticide to prevent chikungunya and dengue in Colombia could generate significant health benefits and be cost-effective. Because of limits on diagnostic accuracy and vaccine efficacy, the cost of dengue testing and vaccination must decrease dramatically for such vaccination to be cost-effective in Colombia. The vectors for chikungunya and dengue have recently spread to new regions, highlighting the importance of understanding the effectiveness and cost-effectiveness of policies aimed at preventing these diseases.     

Determinants of the cost-effectiveness of intermittent preventive treatment for malaria in infants and children

Background

Trials of intermittent preventive treatment in infants (IPTi) and children (IPTc) have shown promising results in reducing malaria episodes but with varying efficacy and cost-effectiveness. The effects of different intervention and setting characteristics are not well known. We simulate the effects of the different target age groups and delivery channels, seasonal or year-round delivery, transmission intensity, seasonality, proportions of malaria fevers treated and drug characteristics.

Methods

We use a dynamic, individual-based simulation model of Plasmodium falciparum malaria epidemiology, antimalarial drug action and case management to simulate DALYs averted and the cost per DALY averted by IPTi and IPTc. IPT cost components were estimated from economic studies alongside trials.

Results

IPTi and IPTc were predicted to be cost-effective in most of the scenarios modelled. The cost-effectiveness is driven by the impact on DALYs, particularly for IPTc, and the low costs, particularly for IPTi which uses the existing delivery strategy, EPI. Cost-effectiveness was predicted to decrease with low transmission, badly timed seasonal delivery in a seasonal setting, short-acting and more expensive drugs, high frequencies of drug resistance and high levels of treatment of malaria fevers. Seasonal delivery was more cost-effective in seasonal settings, and year-round in constant transmission settings. The difference was more pronounced for IPTc than IPTi due to the different proportions of fixed costs and also different assumed drug spacing during the transmission season. The number of DALYs averted was predicted to decrease as a target five-year age-band for IPTc was shifted from children under 5 years into older ages, except at low transmission intensities.

Conclusions

Modelling can extend the information available by predicting impact and cost-effectiveness for scenarios, for outcomes and for multiple strategies where, for practical reasons, trials cannot be carried out. Both IPTi and IPTc are generally cost-effective but could be rendered cost-ineffective by characteristics of the setting, drug or implementation.     

Evaluation of COVID-19 vaccination strategies with a delayed second dose

Two of the Coronavirus Disease 2019 (COVID-19) vaccines currently approved in the United States require 2 doses, administered 3 to 4 weeks apart. Constraints in vaccine supply and distribution capacity, together with a deadly wave of COVID-19 from November 2020 to January 2021 and the emergence of highly contagious Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants, sparked a policy debate on whether to vaccinate more individuals with the first dose of available vaccines and delay the second dose or to continue with the recommended 2-dose series as tested in clinical trials. We developed an agent-based model of COVID-19 transmission to compare the impact of these 2 vaccination strategies, while varying the temporal waning of vaccine efficacy following the first dose and the level of preexisting immunity in the population. Our results show that for Moderna vaccines, a delay of at least 9 weeks could maximize vaccination program effectiveness and avert at least an additional 17.3 (95% credible interval [CrI]: 7.8–29.7) infections, 0.69 (95% CrI: 0.52–0.97) hospitalizations, and 0.34 (95% CrI: 0.25–0.44) deaths per 10,000 population compared to the recommended 4-week interval between the 2 doses. Pfizer-BioNTech vaccines also averted an additional 0.60 (95% CrI: 0.37–0.89) hospitalizations and 0.32 (95% CrI: 0.23–0.45) deaths per 10,000 population in a 9-week delayed second dose (DSD) strategy compared to the 3-week recommended schedule between doses. However, there was no clear advantage of delaying the second dose with Pfizer-BioNTech vaccines in reducing infections, unless the efficacy of the first dose did not wane over time. Our findings underscore the importance of quantifying the characteristics and durability of vaccine-induced protection after the first dose in order to determine the optimal time interval between the 2 doses.

There are two widely used COVID-19 vaccination strategies; administering the two doses three to four weeks apart or delaying the administration of the second dose. A modelling study calibrated to COVID-19 spread and vaccination in the US shows that delaying the second dose can maximize the benefits of vaccination programs under certain conditions.     

The potential impact of urine-LAM diagnostics on tuberculosis incidence and mortality: A modelling analysis

BackgroundLateral flow urine lipoarabinomannan (LAM) tests could offer important new opportunities for the early detection of tuberculosis (TB). The currently licensed LAM test, Alere Determine TB LAM Ag (‘LF-LAM’), performs best in the sickest people living with HIV (PLHIV). However, the technology continues to improve, with newer LAM tests, such as Fujifilm SILVAMP TB LAM (‘SILVAMP-LAM’) showing improved sensitivity, including amongst HIV-negative patients. It is important to anticipate the epidemiological impact that current and future LAM tests may have on TB incidence and mortality.Methods and findingsConcentrating on South Africa, we examined the impact that widening LAM test eligibility would have on TB incidence and mortality. We developed a mathematical model of TB transmission to project the impact of LAM tests, distinguishing ‘current’ tests (with sensitivity consistent with LF-LAM), from hypothetical ‘future’ tests (having sensitivity consistent with SILVAMP-LAM). We modelled the impact of both tests, assuming full adoption of the 2019 WHO guidelines for the use of these tests amongst those receiving HIV care. We also simulated the hypothetical deployment of future LAM tests for all people presenting to care with TB symptoms, not restricted to PLHIV. Our model projects that 2,700,000 (95% credible interval [CrI] 2,000,000–3,600,000) and 420,000 (95% CrI 350,000–520,000) cumulative TB incident cases and deaths, respectively, would occur between 2020 and 2035 if the status quo is maintained. Relative to this comparator, current and future LAM tests would respectively avert 54 (95% CrI 33–86) and 90 (95% CrI 55–145) TB deaths amongst inpatients between 2020 and 2035, i.e., reductions of 5% (95% CrI 4%–6%) and 9% (95% CrI 7%–11%) in inpatient TB mortality. This impact in absolute deaths averted doubles if testing is expanded to include outpatients, yet remains <1% of country-level TB deaths. Similar patterns apply to incidence results. However, deploying a future LAM test for all people presenting to care with TB symptoms would avert 470,000 (95% CrI 220,000–870,000) incident TB cases (18% reduction, 95% CrI 9%–29%) and 120,000 (95% CrI 69,000–210,000) deaths (30% reduction, 95% CrI 18%–44%) between 2020 and 2035. Notably, this increase in impact arises largely from diagnosis of TB amongst those with HIV who are not yet in HIV care, and who would thus be ineligible for a LAM test under current guidelines. Qualitatively similar results apply under an alternative comparator assuming expanded use of GeneXpert MTB/RIF (‘Xpert’) for TB diagnosis. Sensitivity analysis demonstrates qualitatively similar results in a setting like Kenya, which also has a generalised HIV epidemic, but a lower burden of HIV/TB coinfection. Amongst limitations of this analysis, we do not address the cost or cost-effectiveness of future tests. Our model neglects drug resistance and focuses on the country-level epidemic, thus ignoring subnational variations in HIV and TB burden.ConclusionsThese results suggest that LAM tests could have an important effect in averting TB deaths amongst PLHIV with advanced disease. However, achieving population-level impact on the TB epidemic, even in high-HIV-burden settings, will require future LAM tests to have sufficient performance to be deployed more broadly than in HIV care.

Saskia Ricks and colleagues model the impact of urine-LAM diagnostics for reducing tuberculosis incidence, across different implementation scenarios.     

Exploring the Potential Health Impact and Cost-Effectiveness of AIDS Vaccine within a Comprehensive HIV/AIDS Response in Low- and Middle-Income Countries

Background

The Investment Framework Enhanced (IFE) proposed in 2013 by the Joint United Nations Programme on HIV/AIDS (UNAIDS) explored how maximizing existing interventions and adding emerging prevention options, including a vaccine, could further reduce new HIV infections and AIDS-related deaths in low- and middle-income countries (LMICs). This article describes additional modeling which looks more closely at the potential health impact and cost-effectiveness of AIDS vaccination in LMICs as part of UNAIDS IFE.

Methods

An epidemiological model was used to explore the potential impact of AIDS vaccination in LMICs in combination with other interventions through 2070. Assumptions were based on perspectives from research, vaccination and public health experts, as well as observations from other HIV/AIDS interventions and vaccination programs. Sensitivity analyses varied vaccine efficacy, duration of protection, coverage, and cost.

Results

If UNAIDS IFE goals were fully achieved, new annual HIV infections in LMICs would decline from 2.0 million in 2014 to 550,000 in 2070. A 70% efficacious vaccine introduced in 2027 with three doses, strong uptake and five years of protection would reduce annual new infections by 44% over the first decade, by 65% the first 25 years and by 78% to 122,000 in 2070. Vaccine impact would be much greater if the assumptions in UNAIDS IFE were not fully achieved. An AIDS vaccine would be cost-effective within a wide range of scenarios.

Interpretation

Even a modestly effective vaccine could contribute strongly to a sustainable response to HIV/AIDS and be cost-effective, even with optimistic assumptions about other interventions. Higher efficacy would provide even greater impact and cost-effectiveness, and would support broader access. Vaccine efficacy and cost per regimen are critical in achieving cost-effectiveness, with cost per regimen being particularly critical in low-income countries and at lower efficacy levels.     

The Burden of Parasitic Zoonoses in Nepal: A Systematic Review

Background

Parasitic zoonoses (PZs) pose a significant but often neglected threat to public health, especially in developing countries. In order to obtain a better understanding of their health impact, summary measures of population health may be calculated, such as the Disability-Adjusted Life Year (DALY). However, the data required to calculate such measures are often not readily available for these diseases, which may lead to a vicious circle of under-recognition and under-funding.

Methodology

We examined the burden of PZs in Nepal through a systematic review of online and offline data sources. PZs were classified qualitatively according to endemicity, and where possible a quantitative burden assessment was conducted in terms of the annual number of incident cases, deaths and DALYs.

Principal Findings

Between 2000 and 2012, the highest annual burden was imposed by neurocysticercosis and congenital toxoplasmosis (14,268 DALYs [95% Credibility Interval (CrI): 5450–27,694] and 9255 DALYs [95% CrI: 6135–13,292], respectively), followed by cystic echinococcosis (251 DALYs [95% CrI: 105–458]). Nepal is probably endemic for trichinellosis, toxocarosis, diphyllobothriosis, foodborne trematodosis, taeniosis, and zoonotic intestinal helminthic and protozoal infections, but insufficient data were available to quantify their health impact. Sporadic cases of alveolar echinococcosis, angiostrongylosis, capillariosis, dirofilariosis, gnathostomosis, sparganosis and cutaneous leishmaniosis may occur.

Conclusions/Significance

In settings with limited surveillance capacity, it is possible to quantify the health impact of PZs and other neglected diseases, thereby interrupting the vicious circle of neglect. In Nepal, we found that several PZs are endemic and are imposing a significant burden to public health, higher than that of malaria, and comparable to that of HIV/AIDS. However, several critical data gaps remain. Enhanced surveillance for the endemic PZs identified in this study would enable additional burden estimates, and a more complete picture of the impact of these diseases.     

Health and economic benefits of achieving hepatitis C virus elimination in Pakistan: A modelling study and economic analysis

BackgroundModelling suggests that achieving the WHO incidence target for hepatitis C virus (HCV) elimination in Pakistan could cost US$3.87 billion over 2018 to 2030. However, the economic benefits from integrating services or improving productivity were not included.Methods and findingsWe adapt a HCV transmission model for Pakistan to estimate the impact, costs, and cost-effectiveness of achieving HCV elimination (reducing annual HCV incidence by 80% by 2030) with stand-alone service delivery, or partially integrating one-third of initial HCV testing into existing healthcare services. We estimate the net economic benefits by comparing the required investment in screening, treatment, and healthcare management to the economic productivity gains from reduced HCV-attributable absenteeism, presenteeism, and premature deaths. We also calculate the incremental cost-effectiveness ratio (ICER) per disability-adjusted life year (DALY) averted for HCV elimination versus maintaining current levels of HCV treatment. This is compared to an opportunity cost-based willingness-to-pay threshold for Pakistan (US$148 to US$198/DALY).Compared to existing levels of treatment, scaling up screening and treatment to achieve HCV elimination in Pakistan averts 5.57 (95% uncertainty interval (UI) 3.80 to 8.22) million DALYs and 333,000 (219,000 to 509,000) HCV-related deaths over 2018 to 2030. If HCV testing is partially integrated, this scale-up requires an investment of US$1.45 (1.32 to 1.60) billion but will result in US$1.30 (0.94 to 1.72) billion in improved economic productivity over 2018 to 2030. This elimination strategy is highly cost-effective (ICER = US$29 per DALY averted) by 2030, with it becoming cost-saving by 2031 and having a net economic benefit of US$9.10 (95% UI 6.54 to 11.99) billion by 2050. Limitations include uncertainty around what level of integration is possible within existing primary healthcare services as well as a lack of Pakistan-specific data on disease-related healthcare management costs or productivity losses due to HCV.ConclusionsInvestment in HCV elimination can bring about substantial societal health and economic benefits for Pakistan.

Aaron G Lim and colleagues model the health and economic benefits of eliminating hepatitis C in Pakistan.     

Antenatal Syphilis Screening Using Point-Of-Care Testing in Low- and Middle-Income Countries in Asia and Latin America: A Cost-Effectiveness Analysis

BackgroundUntreated syphilis in pregnancy is associated with adverse clinical outcomes to the infant. In low- and middle-income countries in Asia and Latin America, 20%-30% of women are not tested for syphilis during pregnancy. We evaluated the cost-effectiveness of increasing the coverage for antenatal syphilis screening in 11 Asian and 20 Latin American countries, using a point-of-care immunochromatographic strip (ICS) test.MethodsThe decision analytical cost-effectiveness models reported incremental costs per disability-adjusted life years (DALYs) averted from the perspectives of the national health care payer. Clinical outcomes were stillbirths, neonatal deaths, and congenital syphilis. DALYs were computed using WHO disability weights. Costs included the ICS test, three injections of benzathine penicillin, and nurse wages. Country-specific inputs included the antenatal prevalence of syphilis and the proportion of women in the antenatal care setting that are screened for syphilis infection as reported in the 2014 WHO baseline report on global sexually transmitted infection surveillance. Country-specific data on the annual number of live births, proportion of women with at least one antenatal care visit, and per capita gross national income were also included in the model.ResultsThe incremental cost/DALY averted of syphilis screening is US$53 (range: US$10-US$332; Prob<1*per capita GDP=99.71%) in Asia and US$60 (range: US$5-US$225; Prob<1*per capita GDP=99.77%) in Latin America. Universal screening may reduce the annual number of stillbirths by 20,344 and 4,270, neonatal deaths by 8,201 and 1,721, cases of congenital syphilis by 10,952 and 2,298, and avert 925,039 and 197,454 DALYs in the aggregate Asian and Latin American panel, respectively.ConclusionAntenatal syphilis screening is highly cost-effective in all the 11 Asian and 20 Latin American countries assessed. Our findings support the decision to expand syphilis screening in countries with currently low screening rates or continue national syphilis screening programs in countries with high rates.     

Economic impact of dengue illness and the cost-effectiveness of future vaccination programs in Singapore

Background

Dengue illness causes 50–100 million infections worldwide and threatens 2.5 billion people in the tropical and subtropical regions. Little is known about the disease burden and economic impact of dengue in higher resourced countries or the cost-effectiveness of potential dengue vaccines in such settings.

Methods and Findings

We estimate the direct and indirect costs of dengue from hospitalized and ambulatory cases in Singapore. We consider inter alia the impacts of dengue on the economy using the human-capital and the friction cost methods. Disease burden was estimated using disability-adjusted life years (DALYs) and the cost-effectiveness of a potential vaccine program was evaluated. The average economic impact of dengue illness in Singapore from 2000 to 2009 in constant 2010 US$ ranged between $0.85 billion and $1.15 billion, of which control costs constitute 42%–59%. Using empirically derived disability weights, we estimated an annual average disease burden of 9–14 DALYs per 100 000 habitants, making it comparable to diseases such as hepatitis B or syphilis. The proportion of symptomatic dengue cases detected by the national surveillance system was estimated to be low, and to decrease with age. Under population projections by the United Nations, the price per dose threshold for which vaccines stop being more cost-effective than the current vector control program ranged from $50 for mass vaccination requiring 3 doses and only conferring 10 years of immunity to $300 for vaccination requiring 2 doses and conferring lifetime immunity. The thresholds for these vaccine programs to not be cost-effective for Singapore were $100 and $500 per dose respectively.

Conclusions

Dengue illness presents a serious economic and disease burden in Singapore. Dengue vaccines are expected to be cost-effective if reasonably low prices are adopted and will help to reduce the economic and disease burden of dengue in Singapore substantially.     

The Impact and Cost-Effectiveness of a Four-Month Regimen for First-Line Treatment of Active Tuberculosis in South Africa

Background

A 4-month first-line treatment regimen for tuberculosis disease (TB) is expected to have a direct impact on patient outcomes and societal costs, as well as an indirect impact on Mycobacterium tuberculosis transmission. We aimed to estimate this combined impact in a high TB-burden country: South Africa.

Method

An individual based M. tb transmission model was fitted to the TB burden of South Africa using a standard TB natural history framework. We measured the impact on TB burden from 2015–2035 of introduction of a non-inferior 4-month regimen replacing the standard 6-month regimen as first-line therapy. Impact was measured with respect to three separate baselines (Guidelines, Policy and Current), reflecting differences in adherence to TB and HIV treatment guidelines. Further scenario analyses considered the variation in treatment-related parameters and resistance levels. Impact was measured in terms of differences in TB burden and Disability Adjusted Life Years (DALYs) averted. We also examined the highest cost at which the new regimen would be cost-effective for several willingness-to-pay thresholds.

Results

It was estimated that a 4-month regimen would avert less than 1% of the predicted 6 million person years with TB disease in South Africa between 2015 and 2035. A similarly small impact was seen on deaths and DALYs averted. Despite this small impact, with the health systems and patient cost savings from regimen shortening, the 4-month regimen could be cost-effective at $436 [NA, 5983] (mean [range]) per month at a willingness-to-pay threshold of one GDP per capita ($6,618).

Conclusion

The introduction of a non-inferior 4-month first-line TB regimen into South Africa would have little impact on the TB burden. However, under several scenarios, it is likely that the averted societal costs would make such a regimen cost-effective in South Africa.     

Potential Cost-Effectiveness of Prenatal Distribution of Misoprostol for Prevention of Postpartum Hemorrhage in Uganda

Background

In settings where home birth rates are high, prenatal distribution of misoprostol has been advocated as a strategy to increase access to uterotonics during the third stage of labor to prevent postpartum hemorrhage (PPH). Our objective was to project the potential cost-effectiveness of this strategy in Uganda from both governmental (the relevant payer) and modified societal perspectives.

Methods and Findings

To compare prenatal misoprostol distribution to status quo (no misoprostol distribution), we developed a decision analytic model that tracked the delivery pathways of a cohort of pregnant women from the prenatal period, labor to delivery without complications or delivery with PPH, and successful treatment or death. Delivery pathway parameters were derived from the Uganda Demographic and Health Survey. Incidence of PPH, treatment efficacy, adverse event and case fatality rates, access to misoprostol, and health resource use and cost data were obtained from published literature and supplemented with expert opinion where necessary. We computed the expected incidence of PPH, mortality, disability adjusted life years (DALYs), costs and incremental cost effectiveness ratios (ICERs). We conducted univariate and probabilistic sensitivity analyses to examine robustness of our results. In the base-case analysis, misoprostol distribution lowered the expected incidence of PPH by 1.0% (95% credibility interval (CrI): 0.55%, 1.95%), mortality by 0.08% (95% CrI: 0.04%, 0.13%) and DALYs by 0.02 (95% CrI: 0.01, 0.03). Mean costs were higher with prenatal misoprostol distribution from governmental by US$3.3 (95% CrI: 2.1, 4.2) and modified societal (by US$1.3; 95% CrI: -1.6, 2.8) perspectives. ICERs were US$191 (95% CrI: 82, 443) per DALY averted from a governmental perspective, and US$73 (95% CI: -86, 256) per DALY averted from a modified societal perspective.

Conclusions

Prenatal distribution of misoprostol is potentially cost-effective in Uganda and should be considered for national-level scale up for prevention of PPH.     

Cost-effectiveness of the national dog rabies prevention and control program in Mexico, 1990–2015

BackgroundRabies is a viral zoonosis that imposes a substantial disease and economic burden in many developing countries. Dogs are the primary source of rabies transmission; eliminating dog rabies reduces the risk of exposure in humans significantly. Through mass annual dog rabies vaccination campaigns, the national program of rabies control in Mexico progressively reduced rabies cases in dogs and humans since 1990. In 2019, the World Health Organization validated Mexico for eliminating rabies as a public health problem. Using a governmental perspective, we retrospectively assessed the economic costs, effectiveness, and cost-effectiveness of the national program of rabies control in Mexico, 1990–2015.MethodologyCombining various data sources, including administrative records, national statistics, and scientific literature, we retrospectively compared the current scenario of annual dog vaccination campaigns and post-exposure prophylaxis (PEP) with a counterfactual scenario without an annual dog vaccination campaign but including PEP. The counterfactual scenario was estimated using a mathematical model of dog rabies transmission (RabiesEcon). We performed a thorough sensitivity analysis of the main results.Principal findingsResults suggest that in 1990 through 2015, the national dog rabies vaccination program in Mexico prevented about 13,000 human rabies deaths, at an incremental cost (MXN 2015) of $4,700 million (USD 300 million). We estimated an average cost of $360,000 (USD 23,000) per human rabies death averted, $6,500 (USD 410) per additional year-of-life, and $3,000 (USD 190) per dog rabies death averted. Results were robust to several counterfactual scenarios, including high and low rabies transmission scenarios and various assumptions about potential costs without mass dog rabies vaccination campaigns.ConclusionsAnnual dog rabies vaccination campaigns have eliminated the transmission of dog-to-dog rabies and dog-mediated human rabies deaths in Mexico. According to World Health Organization standards, our results show that the national program of rabies control in Mexico has been highly cost-effective.     

A Cost Effectiveness and Capacity Analysis for the Introduction of Universal Rotavirus Vaccination in Kenya: Comparison between Rotarix and RotaTeq Vaccines

Background

Diarrhoea is an important cause of death in the developing world, and rotavirus is the single most important cause of diarrhoea associated mortality. Two vaccines (Rotarix and RotaTeq) are available to prevent rotavirus disease. This analysis was undertaken to aid the decision in Kenya as to which vaccine to choose when introducing rotavirus vaccination.

Methods

Cost-effectiveness modelling, using national and sentinel surveillance data, and an impact assessment on the cold chain.

Results

The median estimated incidence of rotavirus disease in Kenya was 3015 outpatient visits, 279 hospitalisations and 65 deaths per 100,000 children under five years of age per year. Cumulated over the first five years of life vaccination was predicted to prevent 34% of the outpatient visits, 31% of the hospitalizations and 42% of the deaths. The estimated prevented costs accumulated over five years totalled US$1,782,761 (direct and indirect costs) with an associated 48,585 DALYs. From a societal perspective Rotarix had a cost-effectiveness ratio of US$142 per DALY (US$5 for the full course of two doses) and RotaTeq US$288 per DALY ($10.5 for the full course of three doses). RotaTeq will have a bigger impact on the cold chain compared to Rotarix.

Conclusion

Vaccination against rotavirus disease is cost-effective for Kenya irrespective of the vaccine. Of the two vaccines Rotarix was the preferred choice due to a better cost-effectiveness ratio, the presence of a vaccine vial monitor, the requirement of fewer doses and less storage space, and proven thermo-stability.     

The Cost and Cost-Effectiveness of Scaling up Screening and Treatment of Syphilis in Pregnancy: A Model

Background

Syphilis in pregnancy imposes a significant global health and economic burden. More than half of cases result in serious adverse events, including infant mortality and infection. The annual global burden from mother-to-child transmission (MTCT) of syphilis is estimated at 3.6 million disability-adjusted life years (DALYs) and $309 million in medical costs. Syphilis screening and treatment is simple, effective, and affordable, yet, worldwide, most pregnant women do not receive these services. We assessed cost-effectiveness of scaling-up syphilis screening and treatment in existing antenatal care (ANC) programs in various programmatic, epidemiologic, and economic contexts.

Methods and Findings

We modeled the cost, health impact, and cost-effectiveness of expanded syphilis screening and treatment in ANC, compared to current services, for 1,000,000 pregnancies per year over four years. We defined eight generic country scenarios by systematically varying three factors: current maternal syphilis testing and treatment coverage, syphilis prevalence in pregnant women, and the cost of healthcare. We calculated program and net costs, DALYs averted, and net costs per DALY averted over four years in each scenario. Program costs are estimated at $4,142,287 – $8,235,796 per million pregnant women (2010 USD). Net costs, adjusted for averted medical care and current services, range from net savings of $12,261,250 to net costs of $1,736,807. The program averts an estimated 5,754 – 93,484 DALYs, yielding net savings in four scenarios, and a cost per DALY averted of $24 – $111 in the four scenarios with net costs. Results were robust in sensitivity analyses.

Conclusions

Eliminating MTCT of syphilis through expanded screening and treatment in ANC is likely to be highly cost-effective by WHO-defined thresholds in a wide range of settings. Countries with high prevalence, low current service coverage, and high healthcare cost would benefit most. Future analyses can be tailored to countries using local epidemiologic and programmatic data.     

Projections of the Current and Future Disease Burden of Hepatitis C Virus Infection in Malaysia

Background

The prevalence of hepatitis C virus (HCV) infection in Malaysia has been estimated at 2.5% of the adult population. Our objective, satisfying one of the directives of the WHO Framework for Global Action on Viral Hepatitis, was to forecast the HCV disease burden in Malaysia using modelling methods.

Methods

An age-structured multi-state Markov model was developed to simulate the natural history of HCV infection. We tested three historical incidence scenarios that would give rise to the estimated prevalence in 2009, and calculated the incidence of cirrhosis, end-stage liver disease, and death, and disability-adjusted life-years (DALYs) under each scenario, to the year 2039. In the baseline scenario, current antiviral treatment levels were extended from 2014 to the end of the simulation period. To estimate the disease burden averted under current sustained virological response rates and treatment levels, the baseline scenario was compared to a counterfactual scenario in which no past or future treatment is assumed.

Results

In the baseline scenario, the projected disease burden for the year 2039 is 94,900 DALYs/year (95% credible interval (CrI): 77,100 to 124,500), with 2,002 (95% CrI: 1340 to 3040) and 540 (95% CrI: 251 to 1,030) individuals predicted to develop decompensated cirrhosis and hepatocellular carcinoma, respectively, in that year. Although current treatment practice is estimated to avert a cumulative total of 2,200 deaths from DC or HCC, a cumulative total of 63,900 HCV-related deaths is projected by 2039.

Conclusions

The HCV-related disease burden is already high and is forecast to rise steeply over the coming decades under current levels of antiviral treatment. Increased governmental resources to improve HCV screening and treatment rates and to reduce transmission are essential to address the high projected HCV disease burden in Malaysia.     

Costs and Cost-Effectiveness of 9-Valent Human Papillomavirus (HPV) Vaccination in Two East African Countries

Background

Current prophylactic vaccines against human papillomavirus (HPV) target two of the most oncogenic types, HPV-16 and -18, which contribute to roughly 70% of cervical cancers worldwide. Second-generation HPV vaccines include a 9-valent vaccine, which targets five additional oncogenic HPV types (i.e., 31, 33, 45, 52, and 58) that contribute to another 15–30% of cervical cancer cases. The objective of this study was to determine a range of vaccine costs for which the 9-valent vaccine would be cost-effective in comparison to the current vaccines in two less developed countries (i.e., Kenya and Uganda).

Methods and Findings

The analysis was performed using a natural history disease simulation model of HPV and cervical cancer. The mathematical model simulates individual women from an early age and tracks health events and resource use as they transition through clinically-relevant health states over their lifetime. Epidemiological data on HPV prevalence and cancer incidence were used to adapt the model to Kenya and Uganda. Health benefit, or effectiveness, from HPV vaccination was measured in terms of life expectancy, and costs were measured in international dollars (I$). The incremental cost of the 9-valent vaccine included the added cost of the vaccine counterbalanced by costs averted from additional cancer cases prevented. All future costs and health benefits were discounted at an annual rate of 3% in the base case analysis. We conducted sensitivity analyses to investigate how infection with multiple HPV types, unidentifiable HPV types in cancer cases, and cross-protection against non-vaccine types could affect the potential cost range of the 9-valent vaccine. In the base case analysis in Kenya, we found that vaccination with the 9-valent vaccine was very cost-effective (i.e., had an incremental cost-effectiveness ratio below per-capita GDP), compared to the current vaccines provided the added cost of the 9-valent vaccine did not exceed I$9.7 per vaccinated girl. To be considered very cost-effective, the added cost per vaccinated girl could go up to I$5.2 and I$16.2 in the worst-case and best-case scenarios, respectively. At a willingness-to-pay threshold of three times per-capita GDP where the 9-valent vaccine would be considered cost-effective, the thresholds of added costs associated with the 9-valent vaccine were I$27.3, I$14.5 and I$45.3 per vaccinated girl for the base case, worst-case and best-case scenarios, respectively. In Uganda, vaccination with the 9-valent vaccine was very cost-effective when the added cost of the 9-valent vaccine did not exceed I$8.3 per vaccinated girl. To be considered very cost-effective, the added cost per vaccinated girl could go up to I$4.5 and I$13.7 in the worst-case and best-case scenarios, respectively. At a willingness-to-pay threshold of three times per-capita GDP, the thresholds of added costs associated with the 9-valent vaccine were I$23.4, I$12.6 and I$38.4 per vaccinated girl for the base case, worst-case and best-case scenarios, respectively.

Conclusions

This study provides a threshold range of incremental costs associated with the 9-valent HPV vaccine that would make it a cost-effective intervention in comparison to currently available HPV vaccines in Kenya and Uganda. These prices represent a 71% and 61% increase over the price offered to the GAVI Alliance ($5 per dose) for the currently available 2- and 4-valent vaccines in Kenya and Uganda, respectively. Despite evidence of cost-effectiveness, critical challenges around affordability and feasibility of HPV vaccination and other competing needs in low-resource settings such as Kenya and Uganda remain.     

Cost-effectiveness of 2009 pandemic influenza A(H1N1) vaccination in the United States

Background

Pandemic influenza A(H1N1) (pH1N1) was first identified in North America in April 2009. Vaccination against pH1N1 commenced in the U.S. in October 2009 and continued through January 2010. The objective of this study was to evaluate the cost-effectiveness of pH1N1 vaccination.

Methodology

A computer simulation model was developed to predict costs and health outcomes for a pH1N1 vaccination program using inactivated vaccine compared to no vaccination. Probabilities, costs and quality-of-life weights were derived from emerging primary data on pH1N1 infections in the US, published and unpublished data for seasonal and pH1N1 illnesses, supplemented by expert opinion. The modeled target population included hypothetical cohorts of persons aged 6 months and older stratified by age and risk. The analysis used a one-year time horizon for most endpoints but also includes longer-term costs and consequences of long-term sequelae deaths. A societal perspective was used. Indirect effects (i.e., herd effects) were not included in the primary analysis. The main endpoint was the incremental cost-effectiveness ratio in dollars per quality-adjusted life year (QALY) gained. Sensitivity analyses were conducted.

Results

For vaccination initiated prior to the outbreak, pH1N1 vaccination was cost-saving for persons 6 months to 64 years under many assumptions. For those without high risk conditions, incremental cost-effectiveness ratios ranged from $8,000–$52,000/QALY depending on age and risk status. Results were sensitive to the number of vaccine doses needed, costs of vaccination, illness rates, and timing of vaccine delivery.

Conclusions

Vaccination for pH1N1 for children and working-age adults is cost-effective compared to other preventive health interventions under a wide range of scenarios. The economic evidence was consistent with target recommendations that were in place for pH1N1 vaccination. We also found that the delays in vaccine availability had a substantial impact on the cost-effectiveness of vaccination.     

Synergistic interventions to control COVID-19: Mass testing and isolation mitigates reliance on distancing

Stay-at-home orders and shutdowns of non-essential businesses are powerful, but socially costly, tools to control the pandemic spread of SARS-CoV-2. Mass testing strategies, which rely on widely administered frequent and rapid diagnostics to identify and isolate infected individuals, could be a potentially less disruptive management strategy, particularly where vaccine access is limited. In this paper, we assess the extent to which mass testing and isolation strategies can reduce reliance on socially costly non-pharmaceutical interventions, such as distancing and shutdowns. We develop a multi-compartmental model of SARS-CoV-2 transmission incorporating both preventative non-pharmaceutical interventions (NPIs) and testing and isolation to evaluate their combined effect on public health outcomes. Our model is designed to be a policy-guiding tool that captures important realities of the testing system, including constraints on test administration and non-random testing allocation. We show how strategic changes in the characteristics of the testing system, including test administration, test delays, and test sensitivity, can reduce reliance on preventative NPIs without compromising public health outcomes in the future. The lowest NPI levels are possible only when many tests are administered and test delays are short, given limited immunity in the population. Reducing reliance on NPIs is highly dependent on the ability of a testing program to identify and isolate unreported, asymptomatic infections. Changes in NPIs, including the intensity of lockdowns and stay at home orders, should be coordinated with increases in testing to ensure epidemic control; otherwise small additional lifting of these NPIs can lead to dramatic increases in infections, hospitalizations and deaths. Importantly, our results can be used to guide ramp-up of testing capacity in outbreak settings, allow for the flexible design of combined interventions based on social context, and inform future cost-benefit analyses to identify efficient pandemic management strategies.     

Climate influences on the cost-effectiveness of vector-based interventions against malaria in elimination scenarios

Despite the dependence of mosquito population dynamics on environmental conditions, the associated impact of climate and climate change on present and future malaria remains an area of ongoing debate and uncertainty. Here, we develop a novel integration of mosquito, transmission and economic modelling to assess whether the cost-effectiveness of indoor residual spraying (IRS) and long-lasting insecticidal nets (LLINs) against Plasmodium falciparum transmission by Anopheles gambiae s.s. mosquitoes depends on climatic conditions in low endemicity scenarios. We find that although temperature and rainfall affect the cost-effectiveness of IRS and/or LLIN scale-up, whether this is sufficient to influence policy depends on local endemicity, existing interventions, host immune response to infection and the emergence rate of insecticide resistance. For the scenarios considered, IRS is found to be more cost-effective than LLINs for the same level of scale-up, and both are more cost-effective at lower mean precipitation and higher variability in precipitation and temperature. We also find that the dependence of peak transmission on mean temperature translates into optimal temperatures for vector-based intervention cost-effectiveness. Further cost-effectiveness analysis that accounts for country-specific epidemiological and environmental heterogeneities is required to assess optimal intervention scale-up for elimination and better understand future transmission trends under climate change.