Costs and cost-effectiveness of influenza illness and vaccination in low- and middle-income countries: A systematic review from 2012 to 2022.

BACKGROUND: Historically, lack of data on cost-effectiveness of influenza vaccination has been identified as a barrier to vaccine use in low- and middle-income countries. We conducted a systematic review of economic evaluations describing (1) costs of influenza illness; (2) costs of influenza vaccination programs; and (3) vaccination cost-effectiveness from low- and middle-income countries to assess if gaps persist that could hinder global implementation of influenza vaccination programs. METHODS AND FINDINGS: We performed a systematic search in Medline, Embase, Cochrane Library, CINAHL, and Scopus in January 2022 and October 2023 using a combination of the following key words: "influenza" AND "cost" OR "economic." The search included studies with publication years 2012 through 2022. Studies were eligible if they (1) presented original, peer-reviewed findings on cost of illness, cost of vaccination program, or cost-effectiveness of vaccination for seasonal influenza; and (2) included data for at least 1 low- or middle-income country. We abstracted general study characteristics and data specific to each of the 3 study types. Of 54 included studies, 26 presented data on cost-effectiveness, 24 on cost-of-illness, and 5 on program costs. Represented countries were classified as upper-middle income (UMIC; n = 12), lower-middle income (LMIC; n = 7), and low-income (LIC; n = 3). The most evaluated target groups were children (n = 26 studies), older adults (n = 17), and persons with chronic medical conditions (n = 12); fewer studies evaluated pregnant persons (n = 9), healthcare workers (n = 5), and persons in congregate living settings (n = 1). Costs-of-illness were generally higher in UMICs than in LMICs/LICs; however, the highest national economic burden, as a percent of gross domestic product and national health expenditure, was reported from an LIC. Among studies that evaluated the cost-effectiveness of influenza vaccine introduction, most (88%) interpreted at least 1 scenario per target group as either cost-effective or cost-saving, based on thresholds designated in the study. Key limitations of this work included (1) heterogeneity across included studies; (2) restrictiveness of the inclusion criteria used; and (3) potential for missed influenza burden from use of sentinel surveillance systems. CONCLUSIONS: The 54 studies identified in this review suggest an increased momentum to generate economic evidence about influenza illness and vaccination from low- and middle-income countries during 2012 to 2022. However, given that we observed substantial heterogeneity, continued evaluation of the economic burden of influenza illness and costs/cost-effectiveness of influenza vaccination, particularly in LICs and among underrepresented target groups (e.g., healthcare workers and pregnant persons), is needed. Use of standardized methodology could facilitate pooling across settings and knowledge sharing to strengthen global influenza vaccination programs.

WHO-led consensus statement on vaccine delivery costing: process, methods, and findings.

BACKGROUND: Differences in definitions and methodological approaches have hindered comparison and synthesis of economic evaluation results across multiple health domains, including immunization. At the request of the World Health Organization's (WHO) Immunization and Vaccines-related Implementation Research Advisory Committee (IVIR-AC), WHO convened an ad hoc Vaccine Delivery Costing Working Group, comprising experts from eight organizations working in immunization costing, to address a lack of standardization and gaps in definitions and methodological guidance. The aim of the Working Group was to develop a consensus statement harmonizing terminology and principles and to formulate recommendations for vaccine delivery costing for decision making. This paper discusses the process, findings of the review, and recommendations in the Consensus Statement. METHODS: The Working Group conducted several interviews, teleconferences, and one in-person meeting to identify groups working in vaccine delivery costing as well as existing guidance documents and costing tools, focusing on those for low- and middle-income country settings. They then reviewed the costing aims, perspectives, terms, methods, and principles in these documents. Consensus statement principles were drafted to align with the Global Health Cost Consortium costing guide as an agreed normative reference, and consensus definitions were drafted to reflect the predominant view across the documents reviewed. RESULTS: The Working Group identified four major workstreams on vaccine delivery costing as well as nine guidance documents and eleven costing tools for immunization costing. They found that some terms and principles were commonly defined while others were specific to individual workstreams. Based on these findings and extensive consultation, recommendations to harmonize differences in terminology and principles were made. CONCLUSIONS: Use of standardized principles and definitions outlined in the Consensus Statement within the immunization delivery costing community of practice can facilitate interpretation of economic evidence by global, regional, and national decision makers. Improving methodological alignment and clarity in program costing of health services such as immunization is important to support evidence-based policies and optimal resource allocation. On the other hand, this review and Consensus Statement development process revealed the limitations of our ability to harmonize given that study designs will vary depending upon the policy question that is being addressed and the country context.

TrkB Activation during a Critical Period Mimics the Protective Effects of Early Visual Experience on Perception and the Stability of Receptive Fields in Adult Superior Colliculus.

During a critical period in development, spontaneous and evoked retinal activity shape visual pathways in an adaptive fashion. Interestingly, spontaneous activity is sufficient for spatial refinement of visual receptive fields (RFs) in superior colliculus (SC) and visual cortex (V1), but early visual experience is necessary to maintain inhibitory synapses and stabilize RFs in adulthood (Carrasco et al., 2005, 2011; Carrasco and Pallas, 2006; Balmer and Pallas, 2015a). In V1, BDNF and its high-affinity receptor TrkB are important for development of visual acuity, inhibition, and regulation of the critical period for ocular dominance plasticity (Hanover et al., 1999; Huang et al., 1999; Gianfranceschi et al., 2003). To examine the generality of this signaling pathway for visual system plasticity, the present study examined the role of TrkB signaling during the critical period for RF refinement in SC. Activating TrkB receptors during the critical period (P33-P40) in dark reared subjects produced normally refined RFs, and blocking TrkB receptors in light-exposed animals resulted in enlarged adult RFs like those in dark reared animals. We also report here that deprivation- or TrkB blockade-induced RF enlargement in adulthood impaired fear responses to looming overhead stimuli and negatively impacted visual acuity. Thus, early TrkB activation is both necessary and sufficient to maintain visual RF refinement, robust looming responses, and visual acuity in adulthood. These findings suggest a common signaling pathway exists for the maturation of inhibition between V1 and SC.SIGNIFICANCE STATEMENT Receptive field refinement in superior colliculus differs from more commonly studied examples of critical period plasticity in visual pathways in that it does not require visual experience to occur; rather, spontaneous activity is sufficient. Maintenance of refinement beyond puberty requires a brief, early exposure to light to stabilize the lateral inhibition that shapes receptive fields. We find that TrkB activation during a critical period can substitute for visual experience in maintaining receptive field refinement into adulthood, and that this maintenance is beneficial to visual survival behaviors. Thus, as in some other types of plasticity, TrkB signaling plays a crucial role in receptive field refinement.

Methodological Considerations for Cost of Illness Studies of Enteric Fever.

This article presents a selection of practical issues, questions, and tradeoffs in methodological choices to consider when conducting a cost of illness (COI) study on enteric fever in low- to lower-middle-income countries. The experiences presented are based on 2 large-scale COI studies embedded within the Surveillance for Enteric Fever in Asia Project II (SEAP II), in Bangladesh, Nepal, and Pakistan; and the Severe Typhoid Fever Surveillance in Africa (SETA) Program in Burkina Faso, Ethiopia, Ghana, and Madagascar. Issues presented include study design choices such as controlling for background patient morbidity and healthcare costs, time points for follow-up, data collection methods for sensitive income and spending information, estimating enteric fever-specific health facility cost information, and analytic approaches in combining patient and health facility costs. The article highlights the potential tradeoffs in time, budget, and precision of results to assist those commissioning, conducting, and interpreting enteric fever COI studies.

Typhoid and Paratyphoid Cost of Illness in Bangladesh: Patient and Health Facility Costs From the Surveillance for Enteric Fever in Asia Project II.

BACKGROUND: We conducted a cost of illness study to assess the economic burden of pediatric enteric fever (typhoid and paratyphoid) in Bangladesh. Results can inform public health policies to prevent enteric fever. METHODS: The study was conducted at 2 pediatric health facilities in Dhaka. For the patient and caregiver's perspective, we administered questionnaires on costs incurred from illness onset until the survey dates to caregivers of patients with blood culture positive cases at enrollment and 6 weeks later to estimate the direct medical, direct nonmedical, and indirect costs. From the perspective of the health care provider, we collected data on quantities and prices of resources used by the 2 hospitals to estimate the direct medical economic costs to treat a case of enteric fever. We collected costs in Bangladeshi takas and converted them into 2018 US dollars. We multiplied the unit cost per procedure by the frequency of procedures in the surveillance case cohort to calculate the average cost per case. RESULTS: Among the 1772 patients from whom we collected information, the median cost of illness per case of enteric fever from the patient and caregiver perspective was US $64.03 (IQR: US $33.90 -$173.48). Median direct medical and nonmedical costs per case were 3% of annual labor income across the sample. From the perspective of the healthcare provider, the average direct medical cost per case was US $58.64 (range: US $37.25 at Hospital B, US $73.27 at Hospital A). CONCLUSIONS: Our results show substantial economic burden of enteric fever in Bangladesh, with higher costs for patients receiving inpatient care. As antimicrobial resistance increases globally, the cost of illness could increase, due to more expensive and potent drugs required for treatment.

Typhoid and Paratyphoid Cost of Illness in Pakistan: Patient and Health Facility Costs From the Surveillance for Enteric Fever in Asia Project II.

BACKGROUND: The objective of this study was to estimate the cost of illness from enteric fever (typhoid and paratyphoid) at selected sites in Pakistan. METHODS: We implemented a cost-of-illness study in 4 hospitals as part of the Surveillance for Enteric Fever in Asia Project (SEAP) II in Pakistan. From the patient and caregiver perspective, we collected direct medical, nonmedical, and indirect costs per case of enteric fever incurred since illness onset by phone after enrollment and 6 weeks later. From the health care provider perspective, we collected data on quantities and prices of resources used at 3 of the hospitals, to estimate the direct medical economic costs to treat a case of enteric fever. We collected costs in Pakistani rupees and converted them into 2018 US dollars. We multiplied the unit cost per procedure by the frequency of procedures in the surveillance case cohort to calculate the average cost per case. RESULTS: We collected patient and caregiver information for 1029 patients with blood culture-confirmed enteric fever or with a nontraumatic terminal ileal perforation, with a median cost of illness per case of US $196.37 (IQR, US $72.89-496.40). The median direct medical and nonmedical costs represented 8.2% of the annual labor income. From the health care provider perspective, the estimated average direct medical cost per case was US $50.88 at Hospital A, US $52.24 at Hospital B, and US $11.73 at Hospital C. CONCLUSIONS: Enteric fever can impose a considerable economic burden in Pakistan. These new estimates of the cost of illness of enteric fever can improve evaluation and modeling of the costs and benefits of enteric fever prevention and control measures, including typhoid conjugate vaccines.

Typhoid and Paratyphoid Cost of Illness in Nepal: Patient and Health Facility Costs From the Surveillance for Enteric Fever in Asia Project II.

BACKGROUND: Enteric fever is endemic in Nepal and its economic burden is unknown. The objective of this study was to estimate the cost of illness due to enteric fever (typhoid and paratyphoid) at selected sites in Nepal. METHODS: We implemented a study at 2 hospitals in Nepal to estimate the cost per case of enteric fever from the perspectives of patients, caregivers, and healthcare providers. We collected direct medical, nonmedical, and indirect costs per blood culture-confirmed case incurred by patients and their caregivers from illness onset until after enrollment and 6 weeks later. We estimated healthcare provider direct medical economic costs based on quantities and prices of resources used to diagnose and treat enteric fever, and procedure frequencies received at these facilities by enrolled patients. We collected costs in Nepalese rupees and converted them into 2018 US dollars. RESULTS: We collected patient and caregiver cost of illness information for 395 patients, with a median cost of illness per case of $59.99 (IQR, $24.04-$151.23). Median direct medical and nonmedical costs per case represented ~3.5% of annual individual labor income. From the healthcare provider perspective, the average direct medical economic cost per case was $79.80 (range, $71.54 [hospital B], $93.43 [hospital A]). CONCLUSIONS: Enteric fever can impose a considerable economic burden on patients, caregivers, and health facilities in Nepal. These new estimates of enteric fever cost of illness can improve evaluation and modeling of the costs and benefits of enteric fever-prevention measures.

Decision Making and Implementation of the First Public Sector Introduction of Typhoid Conjugate Vaccine-Navi Mumbai, India, 2018.

BACKGROUND: Typhoid fever prevention and control efforts are critical in an era of rising antimicrobial resistance among typhoid pathogens. India remains one of the highest typhoid disease burden countries, although a highly efficacious typhoid conjugate vaccine (TCV), prequalified by the World Health Organization in 2017, has been available since 2013. In 2018, the Navi Mumbai Municipal Corporation (NMMC) introduced TCV into its immunization program, targeting children aged 9 months to 14 years in 11 of 22 areas (Phase 1 campaign). We describe the decision making, implementation, and delivery costing to inform TCV use in other settings. METHODS: We collected information on the decision making and campaign implementation in addition to administrative coverage from NMMC and partners. We then used a microcosting approach from the local government (NMMC) perspective, using a new Microsoft Excel-based tool to estimate the financial and economic vaccination campaign costs. RESULTS: The planning and implementation of the campaign were led by NMMC with support from multiple partners. A fixed-post campaign was conducted during weekends and public holidays in July-August 2018 which achieved an administrative vaccination coverage of 71% (ranging from 46% in high-income to 92% in low-income areas). Not including vaccine and vaccination supplies, the average financial cost and economic cost per dose of TCV delivery were $0.45 and $1.42, respectively. CONCLUSION: The first public sector TCV campaign was successfully implemented by NMMC, with high administrative coverage in slums and low-income areas. Delivery cost estimates provide important inputs to evaluate the cost-effectiveness and affordability of TCV vaccination through public sector preventive campaigns.

Assessment of Economic Burden of Concurrent Measles and Rubella Outbreaks, Romania, 2011-2012.

We estimated the economic impact of concurrent measles and rubella outbreaks in Romania during 2011-2012. We collected costs from surveys of 428 case-patients and caretakers, government records, and health staff interviews. We then estimated financial and opportunity costs. During the study period, 12,427 measles cases and 24,627 rubella cases were recorded; 27 infants had congenital rubella syndrome (CRS). The cost of the outbreaks was US $9.9 million. Cost per case was US $439 for measles, US $132 for rubella, and US $44,051 for CRS. Up to 36% of households needed to borrow money to pay for illness treatment. Approximately 17% of patients continued to work while ill to pay their treatment expenses. Our key study findings were that households incurred a high economic burden compared with their incomes, the health sector bore most costs, and CRS costs were substantial and relevant to include in rubella outbreak cost studies.

Cost of a human papillomavirus vaccination project, Zimbabwe.

OBJECTIVE: To determine the cost of Zimbabwe's human papillomavirus (HPV) vaccination demonstration project. METHODS: The government of Zimbabwe conducted the project from 2014-2015, delivering two doses of HPV vaccine to 10-year-old girls in two districts. School delivery was the primary vaccination strategy, with health facilities and outreach as secondary strategies. A retrospective cost analysis was conducted from the provider perspective. Financial costs (government expenditure) and economic costs (financial plus the value of existing or donated resources including vaccines) were calculated by activity, per dose and per fully immunized girl. RESULTS: The project delivered 11 599 vaccine doses, resulting in 5724 fully immunized girls (5540 at schools, 168 at health facilities and 16 at outreach points). The financial cost for service delivery per fully immunized girl was United States dollars (US$) 5.34 in schools, US$ 34.90 at health facilities and US$ 288.63 at outreach; the economic costs were US$ 17.39, US$ 41.25 and US$ 635.84, respectively. The mean financial cost per dose was US$ 19.76 and per fully immunized girl was US$ 40.03 (economic costs were US$ 45.00 and US$ 91.19, respectively). The largest number of doses delivered (5788) occurred during the second vaccination round (the second group's first dose concurrently delivered with the first group's second dose), resulting in the lowest financial and economic service delivery costs per dose: US$ 1.97 and US$ 6.79, respectively. CONCLUSION: The mean service delivery cost was lower in schools (primary strategy) and when more girls were vaccinated in each round, demonstrating scale efficiency.

Resource Needs for the Trivalent Oral Polio to Bivalent Oral Polio Vaccine Switch in Indonesia.

Background: We present an empirical economic cost analysis of the April 2016 switch from trivalent (tOPV) to bivalent (bOPV) oral polio vaccine at the national-level and 3 provinces (Bali, West Sumatera and Nusa Tenggara) for Indonesia's Expanded Program on Immunization. Methods: Data on the quantity and prices of resources used in the 4 World Health Organization guideline phases of the switch were collected at the national-level and in each of the sampled provinces, cities/districts, and health facilities. Costs were calculated as the sum of the value of resources reportedly used in each sampled unit by switch phase. Results: Estimated national-level costs were $46 791. Costs by health system level varied from $9062 to $34 256 at the province-level, from $4576 to $11 936 at the district-level , and from $3488 to $29 175 at the city-level. Estimated national costs ranged from $4 076 446 (Bali, minimum cost scenario) to $28 120 700 (West Sumatera, maximum cost scenario). Conclusions: Our findings suggest that the majority of tPOV to bOPV switch costs were borne at the subnational level. Considerable variation in reported costs among health system levels surveyed indicates a need for flexibility in budgeting for globally synchronized public health activities.

Refinement but not maintenance of visual receptive fields is independent of visual experience.

Visual deprivation is reported to prevent or delay the development of mature receptive field (RF) properties in primary visual cortex (V1) in several species. In contrast, visual deprivation neither prevents nor delays refinement of RF size in the superior colliculus (SC) of Syrian hamsters, although vision is required for RF maintenance in the SC. Here, we report that, contrary to expectation, visual cortical RF refinement occurs normally in dark-reared animals. As in the SC, a brief period of visual experience is required to maintain V1 RF refinement in adulthood. Whereas in the SC, 3 days of visual experience within a sensitive period (P37-40) was sufficient to protect RFs from deprivation-induced enlargement in adulthood, 7 days (P33-40) were required for RF size maintenance in V1. Thus, spontaneous activity is sufficient for RF refinement at these 2 levels of the visual pathway, and visual input is necessary only to prevent deprivation-induced RF enlargement in adulthood. These studies show that sensory experience during a late juvenile sensitive period protects the visual pathway against sensory deprivation in adulthood, and suggest that more importance may have been placed on the role of early visual experience in visual RF development than is warranted.

Visual experience prevents dysregulation of GABAB receptor-dependent short-term depression in adult superior colliculus.

Progressive loss of plasticity during development prevents refined circuits from regressing to an immature state and is thought to depend on maturation of GABAergic inhibition. For example, a gradual reduction in size of visual receptive fields (RFs) occurs in the superior colliculus (SC) during development. Maintenance of the refined state throughout adulthood requires early light exposure. Here we investigate the potential role of changes in long- or short-term plasticity in experience-dependent maintenance of refined RFs. Using an acute SC slice preparation, we found that long-term plasticity was not affected by visual deprivation, indicating that it does not underlie deprivation-induced RF enlargement. In contrast, visual deprivation altered short-term plasticity in an unexpected way. Specifically, GABAB receptor (GABABR)-mediated paired pulse depression was increased in slices from dark-reared animals. This increase was mimicked by GABAAR blockade in slices from normally reared animals, suggesting that experience-dependent maintenance of GABAAR function prevents an increase in probability of neurotransmitter release. GABABR-mediated short-term depression in response to strong stimulation (such as occurs during vision) was reduced in slices from dark-reared animals. This change was mimicked in slices from normal animals by reducing GABA release. These results are consistent with the hypothesis that early visual experience maintains GABAergic inhibition and prevents later deprivation-induced alterations of short-term depression in SC. Identifying how plasticity is restricted in mature circuits could guide therapies to enhance recovery of function in adults.

Responses to donor proliferation in Ghana's health sector: a qualitative case study.

OBJECTIVE: To investigate how donors and government agencies responded to a proliferation of donors providing aid to Ghana's health sector between 1995 and 2012. METHODS: We interviewed 39 key informants from donor agencies, central government and nongovernmental organizations in Accra. These respondents were purposively selected to provide local and international views from the three types of institutions. Data collected from the respondents were compared with relevant documentary materials - e.g. reports and media articles - collected during interviews and through online research. FINDINGS: Ghana's response to donor proliferation included creation of a sector-wide approach, a shift to sector budget support, the institutionalization of a Health Sector Working Group and anticipation of donor withdrawal following the country's change from low-income to lower-middle income status. Key themes included the importance of leadership and political support, the internalization of norms for harmonization, alignment and ownership, tension between the different methods used to improve aid effectiveness, and a shift to a unidirectional accountability paradigm for health-sector performance. CONCLUSION: In 1995-2012, the country's central government and donors responded to donor proliferation in health-sector aid by promoting harmonization and alignment. This response was motivated by Ghana's need for foreign aid, constraints on the capacity of governmental human resources and inefficiencies created by donor proliferation. Although this decreased the government's transaction costs, it also increased the donors' coordination costs and reduced the government's negotiation options. Harmonization and alignment measures may have prompted donors to return to stand-alone projects to increase accountability and identification with beneficial impacts of projects.

How Connecticut health directors deal with public health budget cuts at the local level.

OBJECTIVES: We investigated the perspectives of local health jurisdiction (LHJ) directors on coping mechanisms used to respond to budget reductions and constraints on their decision-making. METHODS: We conducted in-depth interviews with 17 LHJ directors. Interviews were audio recorded, transcribed, and analyzed using the constant comparative method. RESULTS: LHJ directors use a range of coping mechanisms, including identifying alternative revenue sources, adjusting services, amending staffing arrangements, appealing to local political leaders, and forming strategic partnerships. LHJs also face constraints on their decision-making because of state and local statutory requirements, political priorities, pressures from other LHJs, and LHJ structure. CONCLUSIONS: LHJs respond creatively to budget cuts to maintain important public health services. Some LHJ adjustments to administrative resources may obscure the long-term costs of public health budget cuts in such areas as staff morale and turnover. Not all coping strategies are available to each LHJ because of the contextual constraints of its locality, pointing to important policy questions on identifying optimum jurisdiction size and improving efficiency.

A global comprehensive vaccine-preventable disease surveillance strategy for the immunization Agenda 2030.

As part of the Immunization Agenda 2030, a global strategy for comprehensive vaccine-preventable disease (VPD) surveillance was developed. The strategy provides guidance on the establishment of high-quality surveillance systems that are 1) comprehensive, encompassing all VPD threats faced by a country, in all geographic areas and populations, using all laboratory and other methodologies required for timely and reliable disease detection; 2) integrated, wherever possible, taking advantage of shared infrastructure for specific components of surveillance such as data management and laboratory systems; 3) inclusive of all relevant data needed to guide immunization program management actions. Such surveillance systems should generate data useful to strengthen national immunization programs, inform vaccine introduction decision-making, and reinforce timely and effective detection and response. All stakeholders in countries and globally should work to achieve this vision.

Compromise of auditory cortical tuning and topography after cross-modal invasion by visual inputs.

Brain damage resulting in loss of sensory stimulation can induce reorganization of sensory maps in cerebral cortex. Previous research on recovery from brain damage has focused primarily on adaptive plasticity within the affected modality. Less attention has been paid to maladaptive plasticity that may arise as a result of ectopic innervation from other modalities. Using ferrets in which neonatal midbrain damage results in diversion of retinal projections to the auditory thalamus, we investigated how auditory cortical function is impacted by the resulting ectopic visual activation. We found that, although auditory neurons in cross-modal auditory cortex (XMAC) retained sound frequency tuning, their thresholds were increased, their tuning was broader, and tonotopic order in their frequency maps was disturbed. Multisensory neurons in XMAC also exhibited frequency tuning, but they had longer latencies than normal auditory neurons, suggesting they arise from multisynaptic, non-geniculocortical sources. In a control group of animals with neonatal deafferentation of auditory thalamus but without redirection of retinal axons, tonotopic order and sharp tuning curves were seen, indicating that this aspect of auditory function had developed normally. This result shows that the compromised auditory function in XMAC results from invasion by ectopic visual inputs and not from deafferentation. These findings suggest that the cross-modal plasticity that commonly occurs after loss of sensory input can significantly interfere with recovery from brain damage and that mitigation of maladaptive effects is critical to maximizing the potential for recovery.

Community health workers in low- and middle-income countries: what do we know about scaling up and sustainability?

OBJECTIVES: We sought to provide a systematic review of the determinants of success in scaling up and sustaining community health worker (CHW) programs in low- and middle-income countries (LMICs). METHODS: We searched 11 electronic databases for academic literature published through December 2010 (n = 603 articles). Two independent reviewers applied exclusion criteria to identify articles that provided empirical evidence about the scale-up or sustainability of CHW programs in LMICs, then extracted data from each article by using a standardized form. We analyzed the resulting data for determinants and themes through iterated categorization. RESULTS: The final sample of articles (n = 19) present data on CHW programs in 16 countries. We identified 23 enabling factors and 15 barriers to scale-up and sustainability, which were grouped into 3 thematic categories: program design and management, community fit, and integration with the broader environment. CONCLUSIONS: Scaling up and sustaining CHW programs in LMICs requires effective program design and management, including adequate training, supervision, motivation, and funding; acceptability of the program to the communities served; and securing support for the program from political leaders and other health care providers.

Scaling up depot medroxyprogesterone acetate (DMPA): a systematic literature review illustrating the AIDED model.

BACKGROUND: Use of depot medroxyprogesterone acetate (DMPA), often known by the brand name Depo-Provera, has increased globally, particularly in multiple low- and middle-income countries (LMICs). As a reproductive health technology that has scaled up in diverse contexts, DMPA is an exemplar product innovation with which to illustrate the utility of the AIDED model for scaling up family health innovations. METHODS: We conducted a systematic review of the enabling factors and barriers to scaling up DMPA use in LMICs. We searched 11 electronic databases for academic literature published through January 2013 (n = 284 articles), and grey literature from major health organizations. We applied exclusion criteria to identify relevant articles from peer-reviewed (n = 10) and grey literature (n = 9), extracting data on scale up of DMPA in 13 countries. We then mapped the resulting factors to the five AIDED model components: ASSESS, INNOVATE, DEVELOP, ENGAGE, and DEVOLVE. RESULTS: The final sample of sources included studies representing variation in geographies and methodologies. We identified 15 enabling factors and 10 barriers to dissemination, diffusion, scale up, and/or sustainability of DMPA use. The greatest number of factors were mapped to the ASSESS, DEVELOP, and ENGAGE components. CONCLUSIONS: Findings offer early empirical support for the AIDED model, and provide insights into scale up of DMPA that may be relevant for other family planning product innovations.

Cross-modal plasticity results in increased inhibition in primary auditory cortical areas.

Loss of sensory input from peripheral organ damage, sensory deprivation, or brain damage can result in adaptive or maladaptive changes in sensory cortex. In previous research, we found that auditory cortical tuning and tonotopy were impaired by cross-modal invasion of visual inputs. Sensory deprivation is typically associated with a loss of inhibition. To determine whether inhibitory plasticity is responsible for this process, we measured pre- and postsynaptic changes in inhibitory connectivity in ferret auditory cortex (AC) after cross-modal plasticity. We found that blocking GABAA receptors increased responsiveness and broadened sound frequency tuning in the cross-modal group more than in the normal group. Furthermore, expression levels of glutamic acid decarboxylase (GAD) protein were increased in the cross-modal group. We also found that blocking inhibition unmasked visual responses of some auditory neurons in cross-modal AC. Overall, our data suggest a role for increased inhibition in reducing the effectiveness of the abnormal visual inputs and argue that decreased inhibition is not responsible for compromised auditory cortical function after cross-modal invasion. Our findings imply that inhibitory plasticity may play a role in reorganizing sensory cortex after cross-modal invasion, suggesting clinical strategies for recovery after brain injury or sensory deprivation.