Validation of Claims-Based Algorithm for Lyme Disease, Massachusetts, USA.

Compared with notifiable disease surveillance, claims-based algorithms estimate higher Lyme disease incidence, but their accuracy is unknown. We applied a previously developed Lyme disease algorithm (diagnosis code plus antimicrobial drug prescription dispensing within 30 days) to an administrative claims database in Massachusetts, USA, to identify a Lyme disease cohort during July 2000-June 2019. Clinicians reviewed and adjudicated medical charts from a cohort subset by using national surveillance case definitions. We calculated positive predictive values (PPVs). We identified 12,229 Lyme disease episodes in the claims database and reviewed and adjudicated 128 medical charts. The algorithm's PPV for confirmed, probable, or suspected cases was 93.8% (95% CI 88.1%-97.3%); the PPV was 66.4% (95% CI 57.5%-74.5%) for confirmed and probable cases only. In a high incidence setting, a claims-based algorithm identified cases with a high PPV, suggesting it can be used to assess Lyme disease burden and supplement traditional surveillance data.

Healthcare claims-based Lyme disease case-finding algorithms in the United States: A systematic literature review.

BACKGROUND AND OBJECTIVE: Lyme disease (LD) is the fifth most commonly reported notifiable infectious disease in the United States (US) with approximately 35,000 cases reported in 2019 via public health surveillance. However, healthcare claims-based studies estimate that the number of LD cases is >10 times larger than reported through surveillance. To assess the burden of LD using healthcare claims data and the effectiveness of interventions for LD prevention and treatment, it is important to use validated well-performing LD case-finding algorithms ("LD algorithms"). We conducted a systematic literature review to identify LD algorithms used with US healthcare claims data and their validation status. METHODS: We searched PubMed and Embase for articles published in English since January 1, 2000 (search date: February 20, 2021), using the following search terms: (1) "Lyme disease"; and (2) "claim*" or "administrative* data"; and (3) "United States" or "the US*". We then reviewed the titles, abstracts, full texts, and bibliographies of the articles to select eligible articles, i.e., those describing LD algorithms used with US healthcare claims data. RESULTS: We identified 15 eligible articles. Of these, seven studies used LD algorithms with LD diagnosis codes only, four studies used LD diagnosis codes and antibiotic dispensing records, and the remaining four studies used serologic test order codes in combination with LD diagnosis codes and antibiotics records. Only one of the studies that provided data on algorithm performance: sensitivity 50% and positive predictive value 5%, and this was based on Lyme disease diagnosis code only. CONCLUSIONS: US claims-based LD case-finding algorithms have used diverse strategies. Only one algorithm was validated, and its performance was poor. Further studies are warranted to assess performance for different algorithm designs and inform efforts to better assess the true burden of LD.

Hospital discharge diagnosis position: impact on adult pneumonia burden estimates.

OBJECTIVES: Pneumonia hospitalization studies using administrative claims rely on pneumonia coded in the first discharge diagnosis field over pneumonia in any coded field, and few have evaluated disposition following discharge. This study reports the total disease burden and discharge disposition among patients with pneumonia coded in any diagnosis field. STUDY DESIGN: Retrospective database review. METHODS: Data from the 2014 National Inpatient Sample of the Healthcare Cost and Utilization Project, a population-weighted, 20% sample of all US community hospitalizations, were analyzed for all pneumonia hospitalizations in adults aged 18 to 64 years and 65 years or older. Number of hospitalizations, hospital stay length, direct medical costs, in-hospital mortality, patient discharge disposition, illness severity, and likelihood of dying were evaluated based on the diagnosis field of pneumonia as a discharge diagnosis (eg, first, second, third, or further). RESULTS: In 2014, an estimated 2.4 million US adult hospitalizations were associated with pneumonia in any of the discharge diagnosis positions (33%-35% in first, 33%-36% in second, and 29%-34% in further positions). When estimates were based only on hospitalizations with pneumonia in the first diagnosis field, approximately 66% of hospitalizations, 78% of hospital days, 87% of in-hospital deaths, 76% and 73% of transfers to short-term hospitals and skilled nursing facilities, 68% of discharges with home health care services, and 82% of direct medical costs were excluded. CONCLUSIONS: Pneumonia hospitalizations were associated with substantial health care resource utilization and in-hospital mortality. Relying only on pneumonia in the first hospital diagnosis field may potentially underestimate the burden associated with pneumonia hospitalizations.

Cost-effectiveness of a reactive oral cholera immunization campaign using Shanchol™ in Malawi.

BACKGROUND: Oral cholera vaccines (OCV) have been recommended as additional measures for the prevention of cholera. However, little is known about the cost-effectiveness of OCV use in sub-Saharan Africa, particularly in reactive outbreak contexts. This study aimed to investigate the cost-effectiveness of the use of OCV Shanchol in response to a cholera outbreak in the Lake Chilwa area, Malawi. METHODS: The Excel-based Vaccine Introduction Cost-Effectiveness model was used to assess the cost-effectiveness ratios with and without indirect protection. Model input parameters were obtained from cost evaluations and epidemiological studies conducted in Malawi and published literature. One-way sensitivity and threshold analyses of cost-effectiveness ratios were performed. RESULTS: Compared with the reference scenario i.e. treatment of cholera cases, the immunization campaign would have prevented 636 and 1 020 cases of cholera without and with indirect protection, respectively. The cost-effectiveness ratios were US$19 212 per death, US$500 per case, and US$738 per DALY averted without indirect protection. They were US$10 165 per death, US$264 per case, and US$391 per DALY averted with indirect protection. The net cost per DALY averted was sensitive to four input parameters, including case fatality rate, duration of immunity (vaccine's protective duration), discount rate and cholera incidence. CONCLUSION: Relative to the Malawi gross domestic product per capita, the reactive OCV campaign represented a cost-effective intervention, particularly when considering indirect vaccine effects. Results will need to be assessed in other settings, e.g., during campaigns implemented directly by the Ministry of Health rather than by international partners.

Acute otitis media, antimicrobial prescriptions, and medical expenses among children in the United States during 2011-2016.

INTRODUCTION: We analyzed outpatient visits, incidence, antimicrobial prescriptions, and medical expenditures for acute otitis media (AOM) in the United States during 2011-2016. METHODS: Data sources included the National Disease and Therapeutic Index (NDTI™) projections by IQVIA (for AOM cases), The Medical Expenditure Panel Survey (for medical expenditures) and the US Census (for population estimates). Analyses focused on children aged ≤9 years between 2011 and 2016. We used the 2014 medical expenditure estimate per otitis media episode ($520) as proxy for all years. RESULTS: In 2011, there were an estimated 11.5 million AOM episodes in children aged 0-9 years in the US with AOM incidence rates (IR) of 476, 204, and 284 episodes per 1000 children aged 0-2, 3-9, and 0-9 years, respectively. All subsequent years had lower IRs, and by 2016, IR was 25.1% lower than in 2011 in children 0-9 years. In addition, there were estimates of 10.8 million and 9.2 million fewer cumulative AOM episodes and antimicrobial prescriptions for AOM nationwide between 2012 and 2016, compared to annual 2011 estimates, representing a ∼$5.6 billion decrease in direct medical expenditures. The average number of antibiotic prescriptions per AOM visit remained stable with 0.89 and 0.86 prescriptions per visit in 2011 and 2016, respectively. CONCLUSIONS: AOM incidence, antimicrobial prescriptions, and associated medical expenses decreased substantially between 2011 and 2016 in the United States. Antimicrobial prescribing practices remain unchanged. Additional studies are warranted to assess causality.

Epidemiology of Otitis Media With Otorrhea Among Bangladeshi Children: Baseline Study for Future Assessment of Pneumococcal Conjugate Vaccine Impact.

BACKGROUND: Otitis media (OM) poses a high disease burden on Bangladeshi children, but little is known about its etiologies. We conducted a surveillance study in the largest pediatric hospital to characterize pathogens responsible for OM. METHODS: In the outpatient ear-nose-throat department of Dhaka Shishu Hospital, which serves 0 to 18-year-old children, we collected ear swabs from OM children with otorrhea from April 2014 to March 2015. We cultured all specimens for bacterial pathogens and assessed serotype and antimicrobial susceptibility of Streptococcus pneumoniae (Spn) and Haemophilus influenzae (Hi) isolates. RESULTS: We recorded 1111 OM episodes; 88% (981/1111) involved otorrhea, and we collected samples from 91% (891/981) of these children. Fifty-one percent (452/891) were culture positive (contaminants excluded), with Hi (21%, 187/891) and Spn (18%, 164/891) most commonly detected. Overall, 45 distinct single and mixed pathogens were revealed. Dominant pneumococcal serotypes were 19A, 19F, 3 and 14; 98% of Hi isolates were nontypeable. Pneumococcal conjugate vaccine (PCV)10 and PCV10 + 6A serotypes accounted for 8% and 9% of all OM and 46% and 49% of pneumococcus-positive cases, respectively, and were more likely to be nonsusceptible to at least 1 antibiotic (erythromycin and/or trimethoprim-sulfamethoxazole) than nonvaccine serotypes (91% vs. 77%). Staphylococcus aureus (9%, 83/891) and Pseudomonas aeruginosa (4%, 38/891) were also found. CONCLUSIONS: Nontypeable Hi (NTHi) and Spn are predominant causes of OM in Bangladesh. PCV10, introduced in March 2015, is likely to reduce pneumococcal and overall OM burden. Data collected post-PCV10 will provide comprehensive insight into the effects of this vaccine on these pathogens.

Innovative vaccine delivery strategies in response to a cholera outbreak in the challenging context of Lake Chilwa. A rapid qualitative assessment.

A reactive campaign using two doses of Shanchol Oral Cholera Vaccine (OCV) was implemented in 2016 in the Lake Chilwa Region (Malawi) targeting fish dependent communities. Three strategies for the second vaccine dose delivery (including delivery by a community leader and self-administration) were used to facilitate vaccine access. This assessment collected vaccine perceptions and opinions about the OCV campaign of 313 study participants, including: fishermen, fish traders, farmers, community leaders, and one health and one NGO officer. Socio-demographic surveys were conducted, In Depth Interviews and Focus Group Discussions were conducted before and during the campaign. Some fishermen perceived the traditional delivery strategy as reliable but less practical. Delivery by traditional leaders was acceptable for some participants while others worried about traditional leaders not being trained to deliver vaccines or beneficiaries taking doses on their own. A slight majority of beneficiaries considered the self-administration strategy practical while some beneficiaries worried about storing vials outside of the cold chain or losing vials. During the campaign, a majority of participants preferred receiving oral vaccines instead of injections given ease of intake and lack of pain. OCV was perceived as efficacious and safe. However, a lack of information on how sero-protection may be delayed and the degree of sero-protection led to loss of trust in vaccine potency among some participants who witnessed cholera cases among vaccinated individuals. OCV campaign implementation requires accompanying communication on protective levels, less than 100% vaccine efficacy, delays in onset of sero-protection, and out of cold chain storage.

A rapid qualitative assessment of oral cholera vaccine anticipated acceptability in a context of resistance towards cholera intervention in Nampula, Mozambique.

INTRODUCTION: While planning an immunization campaign in settings where public health interventions are subject to politically motivated resistance, designing context-based social mobilization strategies is critical to ensure community acceptability. In preparation for an Oral Cholera Vaccine campaign implemented in Nampula, Mozambique, in November 2016, we assessed potential barriers and levers for vaccine acceptability. METHODS: Questionnaires, in-depth interviews, and focus group discussions, as well as observations, were conducted before the campaign. The participants included central and district level government informants (national immunization program, logistics officers, public health directors, and others), community leaders and representatives, and community members. RESULTS: During previous well chlorination interventions, some government representatives and health agents were attacked, because they were believed to be responsible for spreading cholera instead of purifying the wells. Politically motivated resistance to cholera interventions resurfaced when an OCV campaign was considered. Respondents also reported vaccine hesitancy related to experiences of problems during school-based vaccine introduction, rumors related to vaccine safety, and negative experiences following routine childhood immunization. Despite major suspicions associated with the OCV campaign, respondents' perceived vulnerability to cholera and its perceived severity seem to override potential anticipated OCV vaccine hesitancy. DISCUSSION: Potential hesitancy towards the OCV campaign is grounded in global insecurity, social disequilibrium, and perceived institutional negligence, which reinforces a representation of estrangement from the central government, triggering suspicions on its intentions in implementing the OCV campaign. Recommendations include a strong involvement of community leaders, which is important for successful social mobilization; representatives of different political parties should be equally involved in social mobilization efforts, before and during campaigns; and public health officials should promote other planned interventions to mitigate the lack of trust associated with perceived institutional negligence. Successful past initiatives include public intake of purified water or newly introduced medication by social mobilizers, teachers or credible leaders.

Estimating the full public health value of vaccination.

There is an enhanced focus on considering the full public health value (FPHV) of vaccination when setting priorities, making regulatory decisions and establishing implementation policy for public health activities. Historically, a therapeutic paradigm has been applied to the evaluation of prophylactic vaccines and focuses on an individual benefit-risk assessment in prospective and individually-randomized phase III trials to assess safety and efficacy against etiologically-confirmed clinical outcomes. By contrast, a public health paradigm considers the population impact and encompasses measures of community benefits against a range of outcomes. For example, measurement of the FPHV of vaccination may incorporate health inequity, social and political disruption, disruption of household integrity, school absenteeism and work loss, health care utilization, long-term/on-going disability, the development of antibiotic resistance, and a range of non-etiologically and etiologically defined clinical outcomes. Following an initial conference at the Fondation Mérieux in mid-2015, a second conference (December 2016) was held to further describe the efficacy of using the FPHV of vaccination on a variety of prophylactic vaccines. The wider scope of vaccine benefits, improvement in risk assessment, and the need for partnership and coalition building across interventions has also been discussed during the 2014 and 2016 Global Vaccine and Immunization Research Forums and the 2016 Geneva Health Forum, as well as in numerous publications including a special issue of Health Affairs in February 2016. The December 2016 expert panel concluded that while progress has been made, additional efforts will be necessary to have a more fully formulated assessment of the FPHV of vaccines included into the evidence-base for the value proposition and analysis of unmet medical need to prioritize vaccine development, vaccine licensure, implementation policies and financing decisions. The desired outcomes of these efforts to establish an alternative framework for vaccine evaluation are a more robust vaccine pipeline, improved appreciation of vaccine value and hence of its relative affordability, and greater public access and acceptance of vaccines.

Cost-of-illness of cholera to households and health facilities in rural Malawi.

Cholera remains an important public health problem in many low- and middle-income countries. Vaccination has been recommended as a possible intervention for the prevention and control of cholera. Evidence, especially data on disease burden, cost-of-illness, delivery costs and cost-effectiveness to support a wider use of vaccine is still weak. This study aims at estimating the cost-of-illness of cholera to households and health facilities in Machinga and Zomba Districts, Malawi. A cross-sectional study using retrospectively collected cost data was undertaken in this investigation. One hundred patients were purposefully selected for the assessment of the household cost-of-illness and four cholera treatment centres and one health facility were selected for the assessment conducted in health facilities. Data collected for the assessment in households included direct and indirect costs borne by cholera patients and their families while only direct costs were considered for the assessment conducted in health facilities. Whenever possible, descriptive and regression analysis were used to assess difference in mean costs between groups of patients. The average costs to patients' households and health facilities for treating an episode of cholera amounted to US$65.6 and US$59.7 in 2016 for households and health facilities, respectively equivalent to international dollars (I$) 249.9 and 227.5 the same year. Costs incurred in treating a cholera episode were proportional to duration of hospital stay. Moreover, 52% of households used coping strategies to compensate for direct and indirect costs imposed by the disease. Both households and health facilities could avert significant treatment expenditures through a broader use of pre-emptive cholera vaccination. These findings have direct policy implications regarding priority investments for the prevention and control of cholera.

Epidemiology of cholera outbreaks and socio-economic characteristics of the communities in the fishing villages of Uganda: 2011-2015.

BACKGROUND: The communities in fishing villages in the Great Lakes Region of Africa and particularly in Uganda experience recurrent cholera outbreaks that lead to considerable mortality and morbidity. We evaluated cholera epidemiology and population characteristics in the fishing villages of Uganda to better target prevention and control interventions of cholera and contribute to its elimination from those communities. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a prospective study between 2011-15 in fishing villages in Uganda. We collected, reviewed and documented epidemiological and socioeconomic data for 10 cholera outbreaks that occurred in fishing communities located along the African Great Lakes and River Nile in Uganda. These outbreaks caused 1,827 suspected cholera cases and 43 deaths, with a Case-Fatality Ratio (CFR) of 2.4%. Though the communities in the fishing villages make up only 5-10% of the Ugandan population, they bear the biggest burden of cholera contributing 58% and 55% of all reported cases and deaths in Uganda during the study period. The CFR was significantly higher among males than females (3.2% vs. 1.3%, p = 0.02). The outbreaks were seasonal with most cases occurring during the months of April-May. Male children under age of 5 years, and 5-9 years had increased risk. Cholera was endemic in some villages with well-defined "hotspots". Practices predisposing communities to cholera outbreaks included: the use of contaminated lake water, poor sanitation and hygiene. Additional factors were: ignorance, illiteracy, and poverty. CONCLUSIONS/SIGNIFICANCE: Cholera outbreaks were a major cause of morbidity and mortality among the fishing communities in Uganda. In addition to improvements in water, sanitation, and hygiene, oral cholera vaccines could play an important role in the prevention and control of these outbreaks, particularly when targeted to high-risk areas and populations. Promotion and facilitation of access to social services including education and reduction in poverty should contribute to cholera prevention, control and elimination in these communities.

Cost of management of severe pneumonia in young children: systematic analysis.

BACKGROUND: Childhood pneumonia is a major cause of childhood illness and the second leading cause of child death globally. Understanding the costs associated with the management of childhood pneumonia is essential for resource allocation and priority setting for child health. METHODS: We conducted a systematic review to identify studies reporting data on the cost of management of pneumonia in children younger than 5 years old. We collected unpublished cost data on non-severe, severe and very severe pneumonia through collaboration with an international working group. We extracted data on cost per episode, duration of hospital stay and unit cost of interventions for the management of pneumonia. The mean (95% confidence interval, CI) and median (interquartile range, IQR) treatment costs were estimated and reported where appropriate. RESULTS: We identified 24 published studies eligible for inclusion and supplemented these with data from 10 unpublished studies. The 34 studies included in the cost analysis contained data on more than 95 000 children with pneumonia from both low- and-middle income countries (LMIC) and high-income countries (HIC) covering all 6 WHO regions. The total cost (per episode) for management of severe pneumonia was US$ 4.3 (95% CI 1.5-8.7), US$ 51.7 (95% CI 17.4-91.0) and US$ 242.7 (95% CI 153.6-341.4)-559.4 (95% CI 268.9-886.3) in community, out-patient facilities and different levels of hospital in-patient settings in LMIC. Direct medical cost for severe pneumonia in hospital inpatient settings was estimated to be 26.6%-115.8% of patients' monthly household income in LMIC. The mean direct non-medical cost and indirect cost for severe pneumonia management accounted for 0.5-31% of weekly household income. The mean length of stay (LOS) in hospital for children with severe pneumonia was 5.8 (IQR 5.3-6.4) and 7.7 (IQR 5.5-9.9) days in LMIC and HIC respectively for these children. CONCLUSION: This is the most comprehensive review to date of cost data from studies on the management of childhood pneumonia and these data should be helpful for health services planning and priority setting by national programmes and international agencies.

The actual and potential costs of meningitis surveillance in the African meningitis belt: Results from Chad and Niger.

BACKGROUND: The introduction of serogroup A meningococcal conjugate vaccine in the African meningitis belt required strengthened surveillance to assess long-term vaccine impact. The costs of implementing this strengthening had not been assessed. METHODOLOGY: The ingredients approach was used to retrospectively determine bacterial meningitis surveillance costs in Chad and Niger in 2012. Resource use and unit cost data were collected through interviews with staff at health facilities, laboratories, government offices and international partners, and by reviewing financial reports. Sample costs were extrapolated to national level and costs of upgrading to desired standards were estimated. RESULTS: Case-based surveillance had been implemented in all 12 surveyed hospitals and 29 of 33 surveyed clinics in Niger, compared to six out of 21 clinics surveyed in Chad. Lumbar punctures were performed in 100% of hospitals and clinics in Niger, compared to 52% of the clinics in Chad. The total costs of meningitis surveillance were US$ 1,951,562 in Niger and US$ 338,056 in Chad, with costs per capita of US$ 0.12 and US$ 0.03, respectively. Laboratory investigation was the largest cost component per surveillance functions, comprising 51% of the total costs in Niger and 40% in Chad. Personnel resources comprised the biggest expense type: 37% of total costs in Niger and 26% in Chad. The estimated annual, incremental costs of upgrading current systems to desired standards were US$ 183,299 in Niger and US$ 605,912 in Chad, which are 9% and 143% of present costs, respectively. CONCLUSIONS: Niger's more robust meningitis surveillance system costs four times more per capita than the system in Chad. Since Chad spends less per capita, fewer activities are performed, which weakens detection and analysis of cases. Countries in the meningitis belt are diverse, and can use these results to assess local costs for adapting surveillance systems to monitor vaccine impact.

The Need for an Information Communication and Advocacy Strategy to Guide a Research Agenda to Address Burden of Invasive Nontyphoidal Salmonella Infections in Africa.

Invasive nontyphoidal salmonellosis (iNTS) is often not recognized clinically, and prevention of iNTS is largely ignored by policy planners and decision makers. During 2010, an estimated 3.4 million cases and 681,316 deaths occurred worldwide due to iNTS, with the largest estimated disease burden in resource-limited areas of sub-Saharan Africa. These figures likely underestimate global burden for several reasons, further complicating efforts to raise awareness of iNTS. To increase disease recognition and facilitate development of interventions, a communication and advocacy plan should be developed and implemented by actors in different sectors of global health, including researchers and scientists, funders, vaccine manufacturers, civil society organizations, and government officials from highly affected countries.

Acceptability and Feasibility of Delivering Pentavalent Vaccines in a Compact, Prefilled, Autodisable Device in Vietnam and Senegal.

BACKGROUND: Prefilled syringes are the standard in developed countries but logistic and financial barriers prevent their widespread use in developing countries. The current study evaluated use of a compact, prefilled, autodisable device (CPAD) to deliver pentavalent vaccine by field actors in Senegal and Vietnam. METHODS: We conducted a logistic, programmatic, and anthropological study that included a) interviews of immunization staff at different health system levels and parents attending immunization sessions; b) observation of immunization sessions including CPAD use on oranges; and c) document review. RESULTS: Respondents perceived that the CPAD would improve safety by being non-reusable and preventing needle and vaccine exposure during preparation. Preparation was considered simple and may reduce immunization time for staff and caretakers. CPAD impact on cold storage requirements depended on the current pentavalent vaccine being used; in both countries, CPAD would reduce the weight and volume of materials and safety boxes thereby potentially improving outreach strategies and waste disposal. CPAD also would reduce stock outages by bundling vaccine and syringes and reduce wastage by using a non-breakable plastic presentation. Respondents also cited potential challenges including ability to distinguish between CPAD and other pharmaceuticals delivered via a similar mechanism (such as contraceptives), safety, and concerns related to design and ease of administration (such as activation, ease of delivery, and needle diameter and length). CONCLUSIONS: Compared to current pentavalent vaccine presentations in Vietnam and Senegal, CPAD technology will address some of the main barriers to vaccination, such as supply chain issues and safety concerns among health workers and families. Most of the challenges we identified can be addressed with health worker training, minor design modifications, and health messaging targeting parents and communities. Potentially the largest remaining barrier is the marginal increase in pentavalent cost--if any--from CPAD use, which we did not assess in our study.

Costs of routine immunization and the introduction of new and underutilized vaccines in Ghana.

BACKGROUND: Limited knowledge exists on the full cost of routine immunization in Africa. Ghana was the first African country to simultaneously introduce rotavirus, pneumococcal and measles second-dose vaccines. Given their high price, it would be beneficial to Ghanaian health authorities to know the true cost of their introduction. METHODS: The economic costs of routine immunization for 2011 and the incremental costs of new vaccines were assessed as part of a multi-country study on costing and financing of routine immunization known as the Expanded Program on Immunization Costing (EPIC). Immunization delivery costs were evaluated at the local facility, district, regional, and central levels. Stratified random sampling was used for district and facility selection. We calculated the allocation of nationwide costs to the four health-system levels. RESULTS: The total aggregated national costs for routine immunization - including vaccine costs - equaled US$ 53.5 million during 2011 (including central, regional, and district costs); this equated to US$ 60.3 per fully immunized child (FIC) when counting vaccine costs, or US$ 48.1 without. National immunization program delivery costs were allocated as follows: local facility level, 85% of total national cost; district, 11%; central, 2% and regional, 2%. Salaried labor represented 61% of total costs, and vaccines represented 17%. For new vaccine introduction, programmatic start-up costs amounted to US$ 3.9 million, primarily due to salaried labor (66%). The mean facility-level cost per vaccine dose administered in a routine immunization program was US$ 5.1 (with a range of US$ 2.4-7.8 depending on facility characteristics) and US$ 3.7 for delivery costs. DISCUSSION: We identified a high cost per fully immunized child, mostly due to non-vaccine costs at the facility level, which indicates that immunization program financing - whether national or donor-driven - must take a broad viewpoint. This substantial variation in overall costs emphasizes the additional effort associated with reaching children in various settings.

Determinants of routine immunization costing in Benin and Ghana in 2011.

BACKGROUND: Existing tools to evaluate costs do not always capture the heterogeneity of costs at the facility level. This study seeks to address this issue through an analysis of determinants of health facility immunization costs. METHODS: A statistical analysis on facility routine delivery and vaccine costs was conducted using ordinary least squares regression. Explanatory variables included the number of doses administered; proportion of time spent by facility staff on immunization; average staff wage; whether the health facility had enough staff; presence of cold chain equipment; distance to a vaccine collection point; and, facility ownership. Data were drawn from representative samples of primary care facilities in Benin and Ghana (46 and 50 facilities, respectively) collected as part of the EPIC studies. RESULTS: Weighted average RI immunization facility cost was US$ 16,459 in Ghana and US$ 14,994 in Benin. The regression found total doses administered to be positively and significantly associated with facility cost in both countries. A 10% increase in doses resulted in a 4% increase in cost in Ghana, and a 7.5% increase in Benin. In Ghana, the proportion of immunization time, presence of cold chain, and sufficiency of staff were positively and significantly associated with total cost. In Benin, facility cost was negatively and significantly related to distance to the vaccine collection point. In the pooled sample, facilities in capital cities were associated with significantly higher costs. CONCLUSIONS: This study provides evidence on the importance of the level of scale in determining facility immunization cost, as well as the role of availability of health workers and time they spend on immunization in Ghana and Benin. This type of analysis can provide insights into the costs of scaling up immunization services, and can assist with development of more efficient immunization strategies.

The case for a typhoid vaccine probe study and overview of design elements.

Recent advances in typhoid vaccine, and consideration of support from Gavi, the Vaccine Alliance, raise the possibility that some endemic countries will introduce typhoid vaccine into public immunization programs. This decision, however, is limited by lack of definitive information on disease burden. We propose use of a vaccine probe study approach. This approach would more clearly assess the total burden of typhoid across different syndromic groups and account for lack of access to care, poor diagnostics, incomplete laboratory testing, lack of mortality and intestinal perforation surveillance, and increasing antibiotic resistance. We propose a cluster randomized trial design using a mass immunization campaign among all age groups, with monitoring over a 4-year period of a variety of outcomes. The primary outcome would be the vaccine preventable disease incidence of prolonged fever hospitalization. Sample size calculations suggest that such a study would be feasible over a reasonable set of assumptions.

Use of vaccines as probes to define disease burden.

Vaccine probe studies have emerged in the past 15 years as a useful way to characterise disease. By contrast, traditional studies of vaccines focus on defining the vaccine effectiveness or efficacy. The underlying basis for the vaccine probe approach is that the difference in disease burden between vaccinated and unvaccinated individuals can be ascribed to the vaccine-specific pathogen. Vaccine probe studies can increase understanding of a vaccine's public health value. For instance, even when a vaccine has a seemingly low efficacy, a high baseline disease incidence can lead to a large vaccine-preventable disease burden and thus that population-based vaccine introduction would be justified. So far, vaccines have been used as probes to characterise disease syndromes caused by Haemophilus influenzae type b, pneumococcus, rotavirus, and early infant influenza. However, vaccine probe studies have enormous potential and could be used more widely in epidemiology, for example, to define the vaccine-preventable burden of malaria, typhoid, paediatric influenza, and dengue, and to identify causal interactions between different pathogens.

Budget process bottlenecks for immunization financing in the Democratic Republic of the Congo (DRC).

BACKGROUND: In Democratic Republic of the Congo (DRC), the availability of domestic resources for the immunization program is limited and relies mostly on external donor support. DRC has introduced a series of reforms to move the country toward performance-based management and program budgets. METHODS: The objectives of the study were to: (i) describe the budget process norm, (ii) analyze the budget process in practice and associated bottlenecks at each of its phases, and (iii) collect suggestions made by the actors involved to improve the situation. Quantitative and qualitative data were collected through: a review of published and gray literature, and individual interviews. RESULTS: Bottlenecks in the budget process and disbursement of funds for immunization are one of the causes of limited domestic resources for the program. Critical bottlenecks include: excessive use of off-budget procedures; limited human resources and capacity; lack of motivation; interference from ministries with the standard budget process; dependency toward the development partner's disbursements schedule; and lack of budget implementation tracking. Results show that the health sector's mobilization rate was 59% in 2011. For the credit line specific to immunization program activities, the mobilization rate for the national Expanded Program for Immunization (EPI) was 26% in 2011 and 43% for vaccines (2010). The main bottleneck for the EPI budget line (2011) and vaccine budget line (2011) occurs at the authorization phase. DISCUSSION: Budget process bottlenecks identified in the analysis lead to a low mobilization rate for the immunization program. The bottlenecks identified show that a poor flow of funds causes an insufficient percentage of already allocated resources to reach various health system levels.