Potential impact of introducing the pneumococcal conjugate vaccine into national immunization programmes : an economic-epidemiological analysis using data from India

Pneumococcal pneumonia causes an estimated 105,000 child deaths in India annually. The planned introduction of the serotype-based pneumococcal conjugate vaccine (PCV) is expected to avert child deaths, but the high cost of PCV relative to current vaccines provided under the Universal Immunization Programme has been a concern. Cost-effectiveness studies from high-income countries are not readily comparable because of differences in the distribution of prevalent serotypes, population, and health systems. We used IndiaSim, an agent-based simulation model representative of the Indian population and health system, to model the dynamics of Streptococcus pneumoniae. We estimate that PCV13 introduction would cost approximately $240 million and avert$48.7 million in out-of-pocket expenditures and 34,800 (95% confidence interval [CI] 29,600–40,800) deaths annually assuming coverage levels and distribution similar to DPT (diphtheria, pertussis, and tetanus) vaccination (~77%). Introducing the vaccine protects the population, especially the poorest wealth quintile, from potentially catastrophic expenditure. The net-present value of predicted money-metric value of insurance for 20 years of vaccination is $160,000 (95$151,000–$168,000) per 100,000 under-fives, and almost half of this protection is for the bottom wealth quintile ($78,000; 95% CI 70,800—84,400). Extending vaccination to 90% coverage averts additional lives and provides additional financial risk protection. Our estimates are sensitive to immunity parameters in our model; however, our assumptions are conservative, and if willingness to pay per years of life lost (YLL) averted is $228 or greater then introducing the vaccine is more cost-effective than our baseline (no vaccination) in more than 95% of simulations

Should New Anti-Malarial Drugs be Subsidized?

We use analytical and numerical models to explain and quantify the welfare effects of subsidies for artemisinin combination treatments (ACTs), a valuable new class of antimalarial drugs. There are two (second-best) efficiency rationales for such subsidies: by expanding drug use, they reduce infection transmission from one individual to another, and they slow the evolution of drug resistance by deterring use of substitute monotherapy drugs for which resistance emerges more rapidly than for ACTs. Our analysis merges epidemiological models of malaria transmission among individuals and mosquitoes, evolution of drug resistance, and economic models of the demand for alternative drugs; parameter values for the simulations are representative of malaria prevalence in sub-Saharan Africa. We find that large subsidies for ACT are welfare improving across many plausible scenarios for malaria transmission, drug-demand elasticities, and evolution of drug resistance; the benefits of the policy are often several times larger than the costs.antimalarial drugs, resistance externality, transmission externality, subsidies, welfare effects

Economic benefit of tuberculosis control

Tuberculosis is the most important infectious cause of adult deaths after HIV/AIDS in low- and middle-income countries. This paper evaluates the economic benefits of extending the World Health Organization's DOTS Strategy (a multi-component approach that includes directly observed treatment, short course chemotherapy and several other components) as proposed in the Global Plan to Stop TB, 2006-2015. The authors use a model-based approach that combines epidemiological projections of averted mortality and economic benefits measured using value of statistical life for the Sub-Saharan Africa region and the 22 high-burden, tuberculosis-endemic countries in the world. The analysis finds that the economic benefits between 2006 and 2015 of sustaining DOTS at current levels relative to having no DOTS coverage are significantly greater than the costs in the 22 high-burden, tuberculosis-endemic countries and the Africa region. The marginal benefits of implementing the Global Plan to Stop TB relative to a no-DOTS scenario exceed the marginal costs by a factor of 15 in the 22 high-burden endemic countries, a factor of 9 (95% CI, 8-9) in the Africa region, and a factor of 9 (95% CI, 9-10) in the nine high-burden African countries. Uncertainty analysis shows that benefit-cost ratios of the Global Plan strategy relative to sustained DOTS were unambiguously greater than one in all nine high-burden countries in Africa and in Afghanistan, Pakistan, and Russia. Although HIV curtails the effect of the tuberculosis programs by lowering the life expectancy of those receiving treatment, the benefits of the Global Plan are greatest in African countries with high levels of HIV.Health Monitoring&Evaluation,Disease Control&Prevention,Population Policies,Health Systems Development&Reform,Poverty and Health

Clinically immune hosts as a refuge for drug-sensitive malaria parasites

<p>Abstract</p> <p>Background</p> <p>Mutations in <it>Plasmodium falciparum </it>that confer resistance to first-line antimalarial drugs have spread throughout the world from a few independent foci, all located in areas that were likely characterized by low or unstable malaria transmission. One of the striking differences between areas of low or unstable malaria transmission and hyperendemic areas is the difference in the size of the population of immune individuals. However, epidemiological models of malaria transmission have generally ignored the role of immune individuals in transmission, assuming that they do not affect the fitness of the parasite. This model reconsiders the role of immunity in the dynamics of malaria transmission and its impact on the evolution of antimalarial drug resistance under the assumption that immune individuals are infectious.</p> <p>Methods</p> <p>The model is constructed as a two-stage susceptible-infected-susceptible (SIS) model of malaria transmission that assumes that individuals build up clinical immunity over a period of years. This immunity reduces the frequency and severity of clinical symptoms, and thus their use of drugs. It also reduces an individual's level of infectiousness, but does not impact the likelihood of becoming infected.</p> <p>Results</p> <p>Simulations found that with the introduction of resistance into a population, clinical immunity can significantly alter the fitness of the resistant parasite, and thereby impact the ability of the resistant parasite to spread from an initial host by reducing the effective reproductive number of the resistant parasite as transmission intensity increases. At high transmission levels, despite a higher basic reproductive number, <it>R</it>₀, the effective reproductive number of the resistant parasite may fall below the reproductive number of the sensitive parasite.</p> <p>Conclusion</p> <p>These results suggest that high-levels of clinical immunity create a natural ecological refuge for drug-sensitive parasites. This provides an epidemiological rationale for historical patterns of resistance emergence and suggests that future outbreaks of resistance are more likely to occur in low- or unstable-transmission settings. This finding has implications for the design of drug policies and the formulation of malaria control strategies, especially those that lower malaria transmission intensity.</p

Trends in antibiotic resistance in coagulase-negative staphylococci in the United States, 1999 to 2012

Coagulase-negative staphylococci (CoNS) are important bloodstream pathogens that are typically resistant to multiple antibiotics. Despite the concern about increasing resistance, there have been no recent studies describing the national prevalence of CoNS pathogens. We used national resistance data over a period of 13 years (1999 to 2012) from The Surveillance Network (TSN) to determine the prevalence of and assess the trends in resistance for Staphylococcus epidermidis, the most common CoNS pathogen, and all other CoNS pathogens. Over the course of the study period, S. epidermidis resistance to ciprofloxacin and clindamycin increased steadily from 58.3% to 68.4% and from 43.4% to 48.5%, respectively. Resistance to levofloxacin increased rapidly from 57.1% in 1999 to a high of 78.6% in 2005, followed by a decrease to 68.1% in 2012. Multidrug resistance for CoNS followed a similar pattern, and this rise and small decline in resistance were found to be strongly correlated with levofloxacin prescribing patterns. The resistance patterns were similar for the aggregate of CoNS pathogens. The results from our study demonstrate that the antibiotic resistance in CoNS pathogens has increased significantly over the past 13 years. These results are important, as CoNS can serve as sentinels for monitoring resistance, and they play a role as reservoirs of resistance genes that can be transmitted to other pathogens. The link between the levofloxacin prescription rate and resistance levels suggests a critical role for reducing the inappropriate use of fluoroquinolones and other broad-spectrum antibiotics in health care settings and in the community to help curb the reservoir of resistance in these colonizing pathogens

Influenza A H1N1 Pandemic Strain Evolution – Divergence and the Potential for Antigenic Drift Variants

The emergence of a novel A(H1N1) strain in 2009 was the first influenza pandemic of the genomic age, and unprecedented surveillance of the virus provides the opportunity to better understand the evolution of influenza. We examined changes in the nucleotide coding regions and the amino acid sequences of the hemagglutinin (HA), neuraminidase (NA), and nucleoprotein (NP) segments of the A(H1N1)pdm09 strain using publicly available data. We calculated the nucleotide and amino acid hamming distance from the vaccine strain A/California/07/2009 for each sequence. We also estimated Pepitope–a measure of antigenic diversity based on changes in the epitope regions–for each isolate. Finally, we compared our results to A(H3N2) strains collected over the same period. Our analysis found that the mean hamming distance for the HA protein of the A(H1N1)pdm09 strain increased from 3.6 (standard deviation [SD]: 1.3) in 2009 to 11.7 (SD: 1.0) in 2013, while the mean hamming distance in the coding region increased from 7.4 (SD: 2.2) in 2009 to 28.3 (SD: 2.1) in 2013. These trends are broadly similar to the rate of mutation in H3N2 over the same time period. However, in contrast to H3N2 strains, the rate of mutation accumulation has slowed in recent years. Our results are notable because, over the course of the study, mutation rates in H3N2 similar to that seen with A(H1N1)pdm09 led to the emergence of two antigenic drift variants. However, while there has been an H1N1 epidemic in North America this season, evidence to date indicates the vaccine is still effective, suggesting the epidemic is not due to the emergence of an antigenic drift variant. Our results suggest that more research is needed to understand how viral mutations are related to vaccine effectiveness so that future vaccine choices and development can be more predictive

The Effect of Medicaid Expansion on Utilization in Maryland Emergency Departments

Study objective A proposed benefit of expanding Medicaid eligibility under the Patient Protection and Affordable Care Act (ACA) was a reduction in emergency department (ED) utilization for primary care needs. Pre-ACA studies found that new Medicaid enrollees increased their ED utilization rates, but the effect on system-level ED visits was less clear. Our objective was to estimate the effect of Medicaid expansion on aggregate and individual-based ED utilization patterns within Maryland. Methods We performed a retrospective cross-sectional study of ED utilization patterns across Maryland, using data from Maryland’s Health Services Cost Review Commission. We also analyzed utilization differences between pre-ACA (July 2012 to December 2013) uninsuredpatients who returned post-ACA (July 2014 to December 2015). Results The total number of ED visits in Maryland decreased by 36,531 (–1.2%) between the 6 quarters pre-ACA and the 6 quarters post-ACA. Medicaid-covered ED visits increased from 23.3% to 28.9% (159,004 additional visits), whereas uninsured patient visits decreased from 16.3% to 10.4% (181,607 fewer visits). Coverage by other insurance types remained largely stable between periods. We found no significant relationship between Medicaid expansion and changes in ED volume by hospital. For patients uninsured pre-ACA who returned post-ACA, the adjusted visits per person during 6 quarters was 2.38 (95% confidence interval 2.35 to 2.40) for those newly enrolled in Medicaid post-ACA compared with 1.66 (95% confidence interval 1.64 to 1.68) for those remaining uninsured. Conclusion There was a substantial increase in patients covered by Medicaid in the post-ACA period, but this did not significantly affect total ED volume. Returning patients newly enrolled in Medicaid visited the ED more than their uninsured counterparts; however, this cohort accounted for only a small percentage of total ED visits in Maryland

Water, sanitation and hygiene interventions to reduce healthcare-associated infections among mothers and neonates in low- and middle-income countries

Background: Despite global improvements in water, sanitation and hygiene (WASH), many healthcare facilities in low- and middle-income countries still lack access to basic WASH services, which threatens patient safety by reducing the capacity to effectively conduct infection prevention and control (IPC) leading to the spread of healthcare-associated infections (HAIs). This is particularly important for pregnant women and neonates, who are especially vulnerable to infection. Though the percentage of institutional births has been increasing in LMICs, gaps remain in understanding the impact and cost-effectiveness of WASH interventions on HAI morbidity and mortality among mothers and neonates in LMICs. Methods: We developed a representative model of the Indian healthcare system, and estimated the impact, cost, and cost-effectiveness of improving WASH in healthcare facilities in India. We analyzed five scenarios: (1) increased access to water in facilities below standard; (2) improved sanitation in facilities below standard; (3) increased IPC due to increased water; (4) increased IPC through non-water-based efforts; and (5) limited increase in hand-hygiene IPC only. Effectiveness was measured as the change in HAI cases and deaths, as a result of interventions. HAIs in the analysis were restricted to bacterial infections not directly caused by unclean water. Cost-effectiveness was measured as the cost per death averted over a 5-year-period. Results: There are an estimated 6,000 deaths in pregnant mothers and nearly 50,000 neonatal deaths in India due to HAIs annually. Investments in improving water access and sanitation (scenarios 1 & 2) had only a limited impact on HAI mortality (Figure 1). However, increases in water-based IPC significantly reduced HAI deaths across all facilities and settings, though the impact was greater in rural areas where water is currently less available and IPC compliance is typically lower. Non-water based IPC was also effective in reducing the impact of HAIs, however was generally less cost-effective (Figure 2). Conclusions: We found that improvements in water quality and accessibility can aid in reducing mortality caused by HAIs, governments and healthcare facilities. However, the effectiveness and cost-effectiveness of these improvements to reduce HAIs are limited unless paired with improvements in IPC. While non-water based IPC activities were effective, improving access to clean water would have additional impacts through reductions in direct infections making them likely to be far more cost-effective. As LMICs continue to grow economically, prioritizing these types of infrastructure projects can have large benefits both directly through reductions in diarrheal disease and indirectly through reductions in HAIs

The Frequency of Influenza and Bacterial Co-infection: A Systematic Review and Meta-Analysis.

AIM: Co-infecting bacterial pathogens are a major cause of morbidity and mortality in influenza. However, there remains a paucity of literature on the magnitude of co-infection in influenza patients. METHOD: A systematic search of MeSH, Cochrane Library, Web of Science, SCOPUS, EMBASE, and PubMed was performed. Studies of humans in which all individuals had laboratory confirmed influenza, and all individuals were tested for an array of common bacterial species, met inclusion criteria. RESULTS: Twenty-seven studies including 3,215 participants met all inclusion criteria. Common etiologies were defined from a subset of eight articles. There was high heterogeneity in the results (I(2) = 95%), with reported co-infection rates ranging from 2% to 65%. Though only a subset of papers were responsible for observed heterogeneity, subanalyses and meta-regression analysis found no study characteristic that was significantly associated with co-infection. The most common co-infecting species were Streptococcus pneumoniae and Staphylococcus aureus, which accounted for 35% (95% CI, 14%-56%) and 28% (95% CI, 16%-40%) of infections, respectively; a wide range of other pathogens caused the remaining infections. An assessment of bias suggested that lack of small-study publications may have biased the results. CONCLUSIONS: The frequency of co-infection in the published studies included in this review suggests that though providers should consider possible bacterial co-infection in all patients hospitalized with influenza, they should not assume all patients are co-infected and be sure to properly treat underlying viral processes. Further, high heterogeneity suggests additional large-scale studies are needed to better understand the etiology of influenza bacterial co-infection. This article is protected by copyright. All rights reserved