Cost of Acute and Sequelae Care for Japanese Encephalitis Patients, Bangladesh, 2011-2021.

Japanese encephalitis (JE) is associated with an immense social and economic burden. Published cost-of-illness data come primarily from decades-old studies. To determine the cost of care for patients with acute JE and initial and long-term sequelae from the societal perspective, we recruited patients with laboratory-confirmed JE from the past 10 years of JE surveillance in Bangladesh and categorized them as acute care, initial sequalae, and long-term sequelae patients. Among 157 patients, we categorized 55 as acute, 65 as initial sequelae (53 as both categories), and 90 as long-term sequelae. The average (median) societal cost of an acute JE episode was US $929 ($909), of initial sequelae US $75 ($33), and of long-term sequelae US $47 ($14). Most families perceived the effect of JE on their well-being to be extreme and had sustained debt for JE expenses. Our data about the high cost of JE can be used by decision makers in Bangladesh.

Risk-based Vaccines and the Need for Risk-based Subnational Vaccination Strategies for Introduction.

BACKGROUND: Most vaccines in the Expanded Program on Immunization are universal childhood vaccines (eg, measles and rotavirus vaccines). Other vaccines such as typhoid conjugate (TCV) and Japanese encephalitis vaccines are risk based and only used in countries where populations are at risk of these diseases. However, strategies to introduce risk-based vaccines are becoming complex due to increasing intracountry variability in disease incidence. There is a need to assess whether subnational vaccine strategies are appropriate. CRITERIA, CHALLENGES, AND BENEFITS: Subnational strategies consider intracountry heterogeneous risk and prioritize vaccination only in those areas that are at risk; there is no intent to introduce the vaccine nationally. The following variables should be considered to determine appropriateness of subnational strategies: disease burden, outbreak potential, treatment availability and costs, cost-effectiveness, and availability of other preventive interventions. We propose criteria for each variable and use a hypothetical country considering TCV introduction to show how criteria are applied to determine if a subnational strategy is appropriate. Challenges include granularity of disease-burden data, political challenges of vaccinating only a portion of a population, and potentially higher costs of introduction. Benefits include targeted reduction of disease burden, increased equity for marginalized populations, and progress on development goals. CONCLUSIONS: In the absence of perfect information at the national level, adopting a subnational vaccine strategy can provide country decision makers with an alternative to national vaccine introduction. Given the changing nature of communicable disease burden, subnational vaccination may be a tool to effectively avert mortality and morbidity while maximizing the use of available health and financial resources.

Japanese Encephalitis Virus as Cause of Acute Encephalitis, Bhutan.

In 2011, Bhutan's Royal Centre for Disease Control began Japanese encephalitis (JE) surveillance at 5 sentinel hospitals throughout Bhutan. During 2011-2018, a total of 20 JE cases were detected, indicating JE virus causes encephalitis in Bhutan. Maintaining JE surveillance will help improve understanding of JE epidemiology in this country.

Introduction of Typhoid Conjugate Vaccines in Africa and Asia.

Typhoid fever continues to be a major public health concern, particularly in many low- and middle-income countries. The current threats of increasing antimicrobial resistance, urbanization, and climate change elevate the urgency for better prevention and control efforts for typhoid fever. In 2017, the results of ground-breaking research on typhoid conjugate vaccines (TCVs), the World Health Organization prequalification of a TCV, and global policy and financing decisions have set the stage for the introduction of TCVs into routine immunization programs in endemic countries. Country-level decision-making and program planning are critical for local uptake and sustainability.

Forecasting Demand for the Typhoid Conjugate Vaccine in Low- and Middle-income Countries.

BACKGROUND: The World Health Organization (WHO) released a position paper in March 2018 calling for integration of a novel typhoid conjugate vaccine (TCV) into routine immunization along with catch-up campaigns for children up to age 15. Gavi, the Vaccine Alliance, has committed funding to help resource-constrained countries introduce this vaccine. In this article, the Typhoid Vaccine Acceleration Consortium forecasts demand if WHO recommendations are followed. METHODS: We built a model of global TCV introductions between 2020 and 2040 to estimate the demand of the vaccine for 133 countries. We estimated each country's year of introduction by examining its estimated incidence of typhoid fever, its history of introducing new vaccines, and any knowledge we have of its engagement with typhoid prevention, including intention to apply for Gavi funding. Our model predicted use in routine infant vaccination as well as campaigns targeting varying proportions of the unvaccinated population up to 15 years of age. RESULTS: Between 2020 and 2025, demand will predominantly come from African countries, many receiving Gavi support. After that, Asian countries generate most demand until 2030, when campaigns are estimated to end. Demand will then track the birth cohort of participating countries, suggesting an annual routine demand between 90 and 100 million doses. Peak demand is likely to occur between 2023 and 2026, approaching 300 million annual doses if campaign implementation is high. CONCLUSIONS: In our analysis, target population for catch-up campaigns is the main driver of uncertainty. At peak demand, there is some risk of exceeding presently estimated peak production capacity. Therefore, it will be important to carefully coordinate introductions, especially when accompanied by campaigns targeting large proportions of the eligible population.

Accelerating Typhoid Conjugate Vaccine Introduction: What Can Be Learned From Prior New Vaccine Introduction Initiatives?

The health consequences of typhoid, including increasing prevalence of drug-resistant strains, can stress healthcare systems. While vaccination is one of the most successful and cost-effective health interventions, vaccine introduction can take years and require considerable effort. The Typhoid Vaccine Acceleration Consortium (TyVAC) employs an integrated, proactive approach to accelerate the introduction of a new typhoid conjugate vaccine to reduce the burden of typhoid in countries eligible for support from Gavi, the Vaccine Alliance. TyVAC and its partners are executing a plan, informed by prior successful vaccine introductions, and tailored to the nuances of typhoid disease and the typhoid conjugate vaccine. The iterative process detailed herein summarizes the strategy and experience gained from the first 2 years of the project.

Diagnoses and ordering practices driving blood demand for treatment of anemia in Tanzania.

BACKGROUND: Resource-limited countries in Africa experience blood shortages. Understanding clinical drivers of blood demand can inform strategies to increase blood availability. STUDY DESIGN AND METHODS: From a national representative sample of 42 hospitals in Tanzania, patient records and requests for whole blood (WB) and red blood cells (RBCs) to treat anemia were analyzed using data collected prospectively from June through September 2013. Abstracted data included cause of anemia, number of requested units, clinical signs, and pretransfusion hemoglobin (Hb) levels. Weighted projections of nationwide drivers of blood demand for the year, 2013, were calculated. Mean posttransfusion Hb levels were estimated, and blood requests were assessed for clinical appropriateness. RESULTS: Malaria was the leading driver of blood demand for anemia among children, accounting for 67% (55,949 units; standard deviation [SD], 1911 units) of projected units requested for children in 2013. Maternal hemorrhage was the leading driver of blood demand for anemia among adults, accounting for 21% (31,321 units; SD, 963 units) of projected units requested. Seventeen percent (26,133 units; SD, 1013 units) of projected requested units were deemed inappropriate. Adults with severe anemia had a mean Hb level of 3.7 g/dL and a mean of 1.6 WB or RBC units per request, resulting in an estimated mean posttransfusion Hb level of 5.3 g/dL. CONCLUSIONS: Strategies to prevent and treat underlying causes of anemia and decrease inappropriate blood requests will likely increase blood availability. Restrictive blood ordering practices seen in adults with severe anemia suggests undertreatment of anemia and may result in an underestimation of the national blood demand.

Japanese Encephalitis Surveillance and Immunization - Asia and Western Pacific Regions, 2016.

Japanese encephalitis (JE) virus is the most important vaccine-preventable cause of encephalitis in the Asia-Pacific region. The World Health Organization (WHO) recommends integration of JE vaccination into national immunization schedules in all areas where the disease is a public health priority (1). This report updates a previous summary of JE surveillance and immunization programs in Asia and the Western Pacific in 2012 (2). Since 2012, funding for JE immunization has become available through the GAVI Alliance, three JE vaccines have been WHO-prequalified,* and an updated WHO JE vaccine position paper providing guidance on JE vaccines and vaccination strategies has been published (1). Data for this report were obtained from a survey of JE surveillance and immunization practices administered to health officials in countries with JE virus transmission risk, the 2015 WHO/United Nations Children's Fund Joint Reporting Form on Immunization, notes and reports from JE meetings held during 2014-2016, published literature, and websites. In 2016, 22 (92%) of 24 countries with JE virus transmission risk conducted JE surveillance, an increase from 18 (75%) countries in 2012, and 12 (50%) countries had a JE immunization program, compared with 11 (46%) countries in 2012. Strengthened JE surveillance, continued commitment, and adequate resources for JE vaccination should help maintain progress toward prevention and control of JE.

Findings of Phlebotomy Practices in Kenya in 2010: Need for Action.

BACKGROUND: Phlebotomy, a commonly performed medical procedure in healthcare, is essential for disease diagnosis and patient management. However, poorly performed phlebotomy can compromise patient safety, healthcare worker (HCW) safety, and specimen quality. We carried out a study between June and July 2010 to assess knowledge, quality and safety of phlebotomy before implementation of a public-private partnership between Becton, Dickinson and Company and the US President's Emergency Plan for AIDS Relief. METHODS: This was a cross-sectional observational study in 8 healthcare facilities within 4 regions of Kenya. HCWs were observed conducting venous and capillary blood collections, and pre- and posttests were offered during HCW training. RESULTS: Of 283 blood samples obtained, 194 were venous draws conducted by 72 HCWs and 89 were capillary draws performed by 33 HCWs. Based on 12 preset quality-associated criteria, none of the 194 observed phlebotomies met the standard. In total, 91 HCWs were trained in phlebotomy. The mean knowledge increase between pre- and posttraining test was 41%, ranging from 39% to 45% (95% confidence interval, 29.3%-53.5%;P< .001). CONCLUSIONS: Inadequate knowledge and imperfect phlebotomy procedures were noted. This formed the basis for the safe phlebotomy partnership to address these deficiencies. To ensure sustainability, safe phlebotomy practices were integrated into preservice training.

Namibia's transition from whole blood-derived pooled platelets to single-donor apheresis platelet collections.

BACKGROUND: Few African countries separate blood donations into components; however, demand for platelets (PLTs) is increasing as regional capacity to treat causes of thrombocytopenia, including chemotherapy, increases. Namibia introduced single-donor apheresis PLT collections in 2007 to increase PLT availability while reducing exposure to multiple donors via pooling. This study describes the impact this transition had on PLT availability and safety in Namibia. STUDY DESIGN AND METHODS: Annual national blood collections and PLT units issued data were extracted from a database maintained by the Blood Transfusion Service of Namibia (NAMBTS). Production costs and unit prices were analyzed. RESULTS: In 2006, NAMBTS issued 771 single and pooled PLT doses from 3054 whole blood (WB) donations (drawn from 18,422 WB donations). In 2007, NAMBTS issued 486 single and pooled PLT doses from 1477 WB donations (drawn from 18,309 WB donations) and 131 single-donor PLT doses. By 2011, NAMBTS issued 837 single-donor PLT doses per year, 99.1% of all PLT units. Of 5761 WB donations from which PLTs were made in 2006 to 2011, a total of 20 (0.35%) were from donors with confirmed test results for human immunodeficiency virus or other transfusion-transmissible infections (TTIs). Of 2315 single-donor apheresis donations between 2007 and 2011, none of the 663 donors had a confirmed positive result for any pathogen. As apheresis replaced WB-derived PLTs, apheresis production costs dropped by a mean of 8.2% per year, while pooled PLT costs increased by an annual mean of 21.5%. Unit prices paid for apheresis- and WB-derived PLTs increased by 9 and 7.4% per year on average, respectively. CONCLUSION: Namibia's PLT transition shows that collections from repeat apheresis donors can reduce TTI risk and production costs.

Granulocyte transfusion therapy.

Bacterial and fungal infections continue to be a major cause of morbidity and mortality in severely neutropenic patients undergoing aggressive chemotherapy regimens or hematopoietic stem cell transplantation. Traditional granulocyte transfusion therapy, a logical approach in treating these infections, has been available for many years, and several controlled studies have shown this therapy to be useful. However, granulocyte transfusion therapy fell out of favor because the results were not clinically impressive, and adverse results were reported. These disappointing results were felt to be, in part, because of the low doses of granulocytes provided. More recent studies have attempted to increase the numbers of transfused cells by stimulating normal granulocyte donors with G-CSF (+/-corticosteroids). With these techniques, the number of granulocytes transfused can be increased 3-4 fold. The cells have been shown to circulate in recipients, and daily transfusions are capable of maintaining normal or near-normal blood neutrophil counts in previously severely neutropenic patients. The cells appear to function normally by a variety of in vitro and in vivo tests. Clinical benefit, as defined by survival or clearance of infection, has not been definitively determined. Results of an ongoing randomized controlled clinical trial should be available in the near future.

Progress toward prevention of transfusion-transmitted hepatitis B and hepatitis C infection--sub-Saharan Africa, 2000-2011.

Infections with hepatitis B virus (HBV) and hepatitis C virus (HCV) are major causes of morbidity and mortality globally, primarily because of sequelae of chronic liver disease including cirrhosis and hepatocellular carcinoma. The risks for HBV and HCV transmission via blood transfusions have been described previously and are believed to be higher in countries in sub-Saharan Africa. Reducing the risk for transfusion-transmitted human immunodeficiency virus (HIV), HBV, and HCV infection is a priority for international aid organizations, such as the U.S. President's Emergency Plan for AIDS Relief (PEPFAR), the Global Fund to Combat HIV/AIDS, Malaria, and Tuberculosis, and the World Health Organization (WHO). Over the last decade, PEPFAR and the Global Fund have supported blood safety programs in many sub-Saharan African countries with heavy burdens of HIV and acquired immunodeficiency syndrome (AIDS), hepatitis, malaria, and maternal mortality. This report summarizes HBV- and HCV-related surveillance data reported by the blood transfusion services of WHO member states to WHO's Global Database on Blood Safety (GDBS) (4). It also evaluates the performance of blood safety programs in screening for HBV and HCV in 38 sub-Saharan Africa countries. Selected GDBS indicators were compared for the years 2000 and 2004 (referred to as the 2000/2004 period) and 2010 and 2011 (referred to as the 2010/2011 period). From 2000/2004 to 2010/2011, the median of the annual number of units donated per country increased, the number of countries screening at least 95% of blood donations for HBV and HCV increased, and the median of the national prevalence of HBV and HCV marker-reactive blood donations decreased. These findings suggest that during the past decade, more blood has been donated and screened for HBV and HCV, resulting in a safer blood supply. Investments in blood safety should be continued to further increase the availability and safety of blood products in sub-Saharan Africa.

Estimating the cost of illness of acute Japanese encephalitis and sequelae care in Vietnam and Laos: A cross-sectional study.

BACKGROUND: Japanese encephalitis (JE) is a leading cause of acute encephalitis syndrome and resulting neurological disability in Asia and the Western Pacific. This study aims to estimate the cost of acute care, initial rehabilitation and sequelae care, in Vietnam and Laos. METHODOLOGY: We conducted a cross-sectional retrospective study using a micro-costing approach from the health system and household perspectives. Out-of-pocket direct medical and non-medical costs, indirect costs, and family impact were reported by patients and/or caregivers. Hospitalization costs were extracted from hospital charts. Acute costs covered expenditures from pre-hospital to follow-up visits while sequelae care costs were estimated from expenditures in the last 90 days. All costs are in 2021 US dollars. PRINCIPAL FINDINGS: 242 patients in two major sentinel sites in the North and South of Vietnam and 65 patients in a central hospital in Vientiane, Laos, with laboratory-confirmed JE were recruited regardless of age, sex, and ethnicity. In Vietnam, the mean total cost was $3,371 per acute JE episode (median $2,071, standard error [SE] $464) while annual costs were $404 for initial sequelae care (median $0, SE $220) and $320 for long-term sequelae care (median $0, SE $108). In Laos, the mean hospitalization costs in acute stage were $2,005 (median $1,698, SE $279) and the mean annual costs were $2,317 (median $0, SE $2,233) for initial sequelae care and $89 (median $0, SE $57) for long-term sequelae care. In both countries, most patients did not seek care for their sequelae. Families perceived extreme impact from JE and 20% to 30% of households still had sustained debts years after acute JE. CONCLUSIONS: JE patients and families in Vietnam and Laos suffer extreme medical, economic, and social hardship. This has policy implications for improving JE prevention in these two JE-endemic countries.

Laboratory practices and incidence of non-O157 shiga toxin-producing Escherichia coli infections.

We surveyed laboratories in Washington State, USA, and found that increased use of Shiga toxin assays correlated with increased reported incidence of non-O157 Shiga toxin-producing Escherichia coli (STEC) infections during 2005-2010. Despite increased assay use, only half of processed stool specimens underwent Shiga toxin testing during 2010, suggesting substantial underdetection of non-O157 STEC infections.

Antibody persistence and immune memory response following primary vaccination and boosting with live attenuated SA 14-14-2 Japanese encephalitis vaccine (CD-JEV) in Bangladesh: A phase 4 open-label clinical trial.

INTRODUCTION: Japanese encephalitis (JE) virus is one of the leading causes of viral encephalitis across temperate and tropical zones of Asia. The live attenuated SA 14-14-2 JE vaccine (CD-JEV) is one of three vaccines prequalified by the World Health Organization (WHO) to prevent JE. WHO currently recommends a single CD-JEV dose for infants in endemic settings. However, in the absence of long-term immunogenicity data, WHO has indicated a need for long-term immunogenicity studies to inform optimal dosing schedules and determine the need for booster doses. METHODS: This Phase 4, open-label clinical study measured neutralizing antibody (NAb) titers in Bangladeshi children three and four years after primary CD-JEV vaccination and 7 and 28 days after a booster CD-JEV vaccination given four years after primary vaccination. The study also assessed the tolerability and safety of the booster dose. A NAb titer of ≥1:10 was considered seroprotective. RESULTS: Of 560 children vaccinated between 10 and 12 months of age with CD-JEV three years earlier and enrolled in this study from 30 July 2015 through 03 January 2016, 52 (9.3%; 95% CI: 7.2-12.0) had a seroprotective titer at enrollment. One year later, of 533 children, 66 (12.4%; 95% CI: 9.9-15.5) had a seroprotective titer before receiving a booster dose. Of 524 children who received a booster CD-JEV dose, 479 (91.4%; 95% CI: 88.7-93.5) and 514 (98.1%; 95% CI: 96.5-99.0) were seroprotected 7 and 28 days later, respectively. The geometric mean titer (GMT) was 6 (95% CI: 6-6) at baseline, 105 (95% CI: 93-119) 7 days post-booster, and 167 (95% CI: 152-183) 28 days post-booster. No vaccine-associated neurologic adverse events or other serious adverse events were noted following the booster dose. CONCLUSIONS: Although most children did not have measurable antibody titers three and four years after a single primary CD-JEV dose, more than 90% of seronegative children had a strong anamnestic response within one week of a booster dose. This suggests that these children were immune despite the absence of measurable NAb prior to their booster.ClinicalTrials.gov Identifier: NCT02514746.

Effects of hand hygiene campaigns on incidence of laboratory-confirmed influenza and absenteeism in schoolchildren, Cairo, Egypt.

To evaluate the effectiveness of an intensive hand hygiene campaign on reducing absenteeism caused by influenza-like illness (ILI), diarrhea, conjunctivitis, and laboratory-confirmed influenza, we conducted a randomized control trial in 60 elementary schools in Cairo, Egypt. Children in the intervention schools were required to wash hands twice each day, and health messages were provided through entertainment activities. Data were collected on student absenteeism and reasons for illness. School nurses collected nasal swabs from students with ILI, which were tested by using a qualitative diagnostic test for influenza A and B. Compared with results for the control group, in the intervention group, overall absences caused by ILI, diarrhea, conjunctivitis, and laboratory-confirmed influenza were reduced by 40%, 30%, 67%, and 50%, respectively (p<0.0001 for each illness). An intensive hand hygiene campaign was effective in reducing absenteeism caused by these illnesses.

Estimated global incidence of Japanese encephalitis: a systematic review.

OBJECTIVE: To update the estimated global incidence of Japanese encephalitis (JE) using recent data for the purpose of guiding prevention and control efforts. METHODS: Thirty-two areas endemic for JE in 24 Asian and Western Pacific countries were sorted into 10 incidence groups on the basis of published data and expert opinion. Population-based surveillance studies using laboratory-confirmed cases were sought for each incidence group by a computerized search of the scientific literature. When no eligible studies existed for a particular incidence group, incidence data were extrapolated from related groups. FINDINGS: A total of 12 eligible studies representing 7 of 10 incidence groups in 24 JE-endemic countries were identified. Approximately 67,900 JE cases typically occur annually (overall incidence: 1.8 per 100,000), of which only about 10% are reported to the World Health Organization. Approximately 33,900 (50%) of these cases occur in China (excluding Taiwan) and approximately 51,000 (75%) occur in children aged 0-14 years (incidence: 5.4 per 100,000). Approximately 55,000 (81%) cases occur in areas with well established or developing JE vaccination programmes, while approximately 12,900 (19%) occur in areas with minimal or no JE vaccination programmes. CONCLUSION: Recent data allowed us to refine the estimate of the global incidence of JE, which remains substantial despite improvements in vaccination coverage. More and better incidence studies in selected countries, particularly China and India, are needed to further refine these estimates.

Age as an independent risk factor for intensive care unit admission or death due to 2009 pandemic influenza A (H1N1) virus infection.

OBJECTIVE: This study evaluated risk factors for intensive care unit (ICU) admission or death among people hospitalized with 2009 pandemic influenza A (pH1N1) virus infection. METHODS: We based analyses on data collected in Washington State from April 27 to September 18, 2009, on deceased or hospitalized people with laboratory-confirmed pH1N1 infection reported by health-care providers and hospitals as part of enhanced public health surveillance. We used bivariate analyses and multivariable logistic regression to identify risk factors associated with ICU admission or death due to pH1N1. RESULTS: We identified 123 patients admitted to the hospital but not an ICU and 61 patients who were admitted to an ICU or died. Independent of high-risk medical conditions, both older age and delayed time to hospital admission were identified as risk factors for ICU admission or death due to pH1N1. Specifically, the odds of ICU admission or death were 4.44 times greater among adults aged 18-49 years (95% confidence interval [CI] 1.97, 10.02) and 5.93 times greater among adults aged 50-64 years (95% CI 2.24, 15.65) compared with pediatric patients < 18 years of age. Likewise, hospitalized cases admitted more than two days after illness onset had 2.17 times higher odds of ICU admission or death than those admitted within two days of illness onset (95% CI 1.10, 4.25). CONCLUSION: Although certain medical conditions clearly influence the need for hospitalization among people infected with pH1N1 virus, older age and delayed time to admission each played an independent role in the progression to ICU admission or death among hospitalized patients.

Vaccines to Prevent Meningitis: Historical Perspectives and Future Directions.

Despite advances in the development and introduction of vaccines against the major bacterial causes of meningitis, the disease and its long-term after-effects remain a problem globally. The Global Roadmap to Defeat Meningitis by 2030 aims to accelerate progress through visionary and strategic goals that place a major emphasis on preventing meningitis via vaccination. Global vaccination against Haemophilus influenzae type B (Hib) is the most advanced, such that successful and low-cost combination vaccines incorporating Hib are broadly available. More affordable pneumococcal conjugate vaccines are becoming increasingly available, although countries ineligible for donor support still face access challenges and global serotype coverage is incomplete with existing licensed vaccines. Meningococcal disease control in Africa has progressed with the successful deployment of a low-cost serogroup A conjugate vaccine, but other serogroups still cause outbreaks in regions of the world where broadly protective and affordable vaccines have not been introduced into routine immunization programs. Progress has lagged for prevention of neonatal meningitis and although maternal vaccination against the leading cause, group B streptococcus (GBS), has progressed into clinical trials, no GBS vaccine has thus far reached Phase 3 evaluation. This article examines current and future efforts to control meningitis through vaccination.