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Typhoid fever remains a significant health problem in sub-Saharan Africa, with incidence rates of >100 cases per 100,000 person-years of observation. Despite the prequalification of safe and effective typhoid conjugate vaccines (TCV), some uncertainties remain around future demand. Real-life effectiveness data, which inform public health programs on the impact of TCVs in reducing typhoid-related mortality and morbidity, from an African setting may help encourage the introduction of TCVs in high-burden settings. Here, we describe a cluster-randomized trial to investigate population-level protection of TYPBAR-TCV®, a Vi-polysaccharide conjugated to a tetanus-toxoid protein carrier (Vi-TT) against blood-culture-confirmed typhoid fever, and the synthesis of health economic evidence to inform policy decisions. A total of 80 geographically distinct clusters are delineated within the Agogo district of the Asante Akim region in Ghana. Clusters are randomized to the intervention arm receiving Vi-TT or a control arm receiving the meningococcal A conjugate vaccine. The primary study endpoint is the total protection of Vi-TT against blood-culture-confirmed typhoid fever. Total, direct, and indirect protection are measured as secondary outcomes. Blood-culture-based enhanced surveillance enables the estimation of incidence rates in the intervention and control clusters. Evaluation of the real-world impact of TCVs and evidence synthesis improve the uptake of prequalified/licensed safe and effective typhoid vaccines in public health programs of high burden settings. This trial is registered at the Pan African Clinical Trial Registry, accessible at Pan African Clinical Trials Registry (ID: PACTR202011804563392).

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.

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.

Background There is global consensus that Antimicrobial Resistance (AMR) poses an unprecedented challenge to modern medicine as we know it today; and the lack of new antibiotics in the pipeline is compounding the threat to contain emerging drug-resistant infections. In 2017, the World Health Organization (WHO) has articulated a priority pathogens list (PPL) to provide strategic direction to research and development of new anti-microbials. Anti-microbial resistance patterns of selected ‘drug-bug’ combinations based on the WHO-PPL in one tertiary health care facility in India are explored in this paper. Methods Culture reports of laboratory specimens, collected between 1st January 2014 and 31st October 2019 from paediatric patients in a tertiary care hospital in India, were retrospectively extracted. The antimicrobial susceptibility patterns for selected antimicrobials based on the WHO-PPL are analysed and reported. Results Of 12,256 culture specimens screened, 2,335 (19%) showed culture positivity; of which 1,556 were organisms from the WHO-PPL. E. coli was the most common organism isolated (37%) followed by Staphylococcus aureus (16%). Total 72% of E. coli were extended-spectrum beta-lactamases producers, 55% of Enterobacteriaceae were resistant to 3rd generation cephalosporins, and 53% of Staphylococcus aureus were Methicillin resistant. Time-trend analysis of the data showed continued high resistance to carbapenem in E coli, Klebsiella pneumoniae and Enterobacter cloacae. Conclusions The AMR trends and prevalence patterns are likely to be different, across various local settings, than as defined at the national level or the WHO-PPL. This difference needs to be recognised in decision and policy making. It is critical, that the evidence used at national and global levels, have reasonable geographical and population representation through standardised and more granular AMR surveillance, in order to improve the effectiveness of the overall national AMR response.

Vibrio cholera is a major contributor of diarrheal illness that causes significant morbidity and mortality globally. While there is literature on the health economics of diarrheal illnesses more generally, few studies have quantified the cost-of-illness and cost-effectiveness of cholera-specific prevention and control interventions. The present systematic review provides a comprehensive overview of the literature specific to cholera as it pertains to key health economic measures.A systematic review was performed with no date restrictions up through February 2017 in PubMed, Econlit, Embase, Web of Science, and Cochrane Review to identify relevant health economics of cholera literature. After removing duplicates, a total of 1993 studies were screened and coded independently by two reviewers, resulting in 22 relevant studies. Data on population, methods, and results (cost-of-illness and cost-effectiveness of vaccination) were compared by country/region. All costs were adjusted to 2017 USD for comparability.Costs per cholera case were found to be rather low:$100 per case in most settings, even when costs incurred by patients/families and lost productivity are considered. When wider socioeconomic costs are included, estimated costs are$1000/case. There is adequate evidence to support the economic value of vaccination for the prevention and control of cholera when vaccination is targeted at high-incidence populations and/or areas with high case fatality rates due to cholera. When herd immunity is considered, vaccination also becomes a cost-effective option for the general population and is comparable in cost-effectiveness to other routine immunizations.Cholera vaccination is a viable short-to-medium term option, especially as the upfront costs of building water, sanitation, and hygiene (WASH) infrastructure are considerably higher for countries that face a significant burden of cholera. While WASH may be the more cost-effective solution in the long-term when implemented properly, cholera vaccination can still be a feasible, cost-effective strategy.

A Typhoid Conjugate Vaccine (TCV) is expected to acquire WHO prequalification soon, which will pave the way for its use in many low- and middle-income countries where typhoid fever is endemic. Thus it is critical to forecast future vaccine demand to ensure supply meets demand, and to facilitate vaccine policy and introduction planning. We forecasted introduction dates for countries based on specific criteria and estimated vaccine demand by year for defined vaccination strategies in 2 scenarios: rapid vaccine introduction and slow vaccine introduction. In the rapid introduction scenario, we forecasted 17 countries and India introducing TCV in the first 5 y of the vaccine's availability while in the slow introduction scenario we forecasted 4 countries and India introducing TCV in the same time period. If the vaccine is targeting infants in high-risk populations as a routine single dose, the vaccine demand peaks around 40 million doses per year under the rapid introduction scenario. Similarly, if the vaccine is targeting infants in the general population as a routine single dose, the vaccine demand increases to 160 million doses per year under the rapid introduction scenario. The demand forecast projected here is an upper bound estimate of vaccine demand, where actual demand depends on various factors such as country priorities, actual vaccine introduction, vaccination strategies, Gavi financing, costs, and overall product profile. Considering the potential role of TCV in typhoid control globally; manufacturers, policymakers, donors and financing bodies should work together to ensure vaccine access through sufficient production capacity, early WHO prequalification of the vaccine, continued Gavi financing and supportive policy.

Typhoid vaccines have been available as a means of disease control and prevention since 1896; however, their use as a routine tool for disease prevention in endemic settings has been hampered because of: 1) insufficient data on disease burden particularly regarding the lack of health care access in the poorest communities affected by typhoid; 2) limitations of the typhoid vaccine, such as shorter duration of protection, moderate efficacy in young children, and no efficacy for infants; 3) inadequate evidence on potential economic benefits when used for a larger population; 4) neglect in favor of alternative interventions that require massive infrastructure; 5) no financial support or commitment regarding vaccine delivery cost; 6) ambivalence about whether to invest in water and sanitation hygiene versus the vaccine; and 7) clarity on global policy for country adoption. If current typhoid-protein conjugate vaccines live up to their promise of higher efficacy, longer duration of protection, and efficacy in young children, typhoid vaccine use will be a critical component of short- and medium-term disease control strategies. Typhoid control could be accelerated if the global framework includes plans for accelerated introduction of the conjugate typhoid vaccine in developing countries.

Background Invasive salmonellosis is a common community-acquired bacteremia in persons residing in sub-Saharan Africa. However, there is a paucity of data on severe typhoid fever and its associated acute and chronic host immune response and carriage. The Severe Typhoid Fever in Africa (SETA) program, a multicountry surveillance study, aimed to address these research gaps and contribute to the control and prevention of invasive salmonellosis. Methods A prospective healthcare facility–based surveillance with active screening of enteric fever and clinically suspected severe typhoid fever with complications was performed using a standardized protocol across the study sites in Burkina Faso, the Democratic Republic of Congo (DRC), Ethiopia, Ghana, Madagascar, and Nigeria. Defined inclusion criteria were used for screening of eligible patients for enrollment into the study. Enrolled patients with confirmed invasive salmonellosis by blood culture or patients with clinically suspected severe typhoid fever with perforation were eligible for clinical follow-up. Asymptomatic neighborhood controls and immediate household contacts of each case were enrolled as a comparison group to assess the level of Salmonella-specific antibodies and shedding patterns. Healthcare utilization surveys were performed to permit adjustment of incidence estimations. Postmortem questionnaires were conducted in medically underserved areas to assess death attributed to invasive Salmonella infections in selected sites. Results Research data generated through SETA aimed to address scientific knowledge gaps concerning the severe typhoid fever and mortality, long-term host immune responses, and bacterial shedding and carriage associated with natural infection by invasive salmonellae. Conclusions SETA supports public health policy on typhoid immunization strategy in Africa.

Background There are limited data on typhoid fever cost of illness (COI) and economic impact from Africa. Health economic data are essential for measuring the cost-effectiveness of vaccination or other disease control interventions. Here, we describe the protocol and methods for conducting the health economic studies under the Severe Typhoid Fever in Africa (SETA) program. Methods The SETA health economic studies will rely on the platform for SETA typhoid surveillance in 4 African countries—Burkina Faso, Ethiopia, Ghana, and Madagascar. A COI and long-term socioeconomic study (LT-SES) will be its components. The COI will be assessed among blood culture–positive typhoid fever cases, blood culture–negative clinically suspected cases (clinical cases), and typhoid fever cases with pathognomonic gastrointestinal perforations (special cases). Repeated surveys using pretested questionnaires will be used to measure out-of-pocket expenses, quality of life, and the long-term socioeconomic impact. The cost of resources consumed for diagnosis and treatment will be collected at health facilities. Results Results from these studies will be published in peer-reviewed journals and presented at scientific conferences to make the data available to the wider health economics and public health research communities. Conclusions The health economic data will be analyzed to estimate the average cost per case, the quality of life at different stages of illness, financial stress due to illness, and the burden on the family due to caregiving during illness. The data generated are expected to be used in economic analysis and policy making on typhoid control interventions in sub-Saharan Africa.

In many low income developing countries, socioeconomic, environmental and demographic factors have been linked to around half of the disease related deaths that occur each year. The aim of this study is to investigate the sociodemographic factors, mother and child health status, water, sanitation, and hygienic conditions of a Nepalese community residing in a hilly rural village, and to identify factors associated with mother and child health status and the occurrence of diarrheal and febrile disease. A community-based cross-sectional survey was carried out and 315 households from the village of Narjamandap were included in this study. Factors associated with diarrhea, febrile disease, and full maternal and under-five immunizations were assessed using logistic regression. Results showed that higher education level (middle school versus primary education, Odds Ratio (OR): 0.55, p = 0.04, high school versus primary education, OR 0.21, p = 0.001) and having a toilet facility at home were significantly associated with a lower risk of developing diarrhea and febrile disease (OR 0.49, p = 0.01), while, interestingly, the use of improved water supply was associated with higher risk (OR 3.07, p = 0.005). In terms of maternal immunization, the odds of receiving a tetanus toxoid vaccination were higher in women who had regular antenatal checkups (OR 12.9, p &lt, 0.001), and in those who developed complications during pregnancy (OR 4.54, p = 0.04), for under-five immunization, the odds of receiving full vaccination were higher among children from households that reported diarrhea (OR 2.76, p &lt, 0.001). The findings of this study indicated that gaps still exist in the mother and child healthcare being provided, in terms of receiving antenatal checkups and basic immunizations, as evidenced by irregular antenatal checkups, incomplete and zero vaccination cases, and higher under-five deaths. Specific public health interventions to promote maternal health and the health of under-five children are suggested.

Typhoid fever is an acute systemic infectious disease responsible for an estimated 12-20 million illnesses and over 150 000 deaths annually. In March, 2018, a new recommendation was issued by WHO for the programmatic use of typhoid conjugate vaccines in endemic countries. Health economic analyses of typhoid vaccines have informed funding decisions and national policies regarding vaccine rollout. However, by focusing only on averted typhoid cases and their associated costs, traditional cost-effectiveness analyses might underestimate crucial benefits of typhoid vaccination programmes, because the potential effect of typhoid vaccines on the treatment of patients with nonspecific acute febrile illnesses is not considered. For every true case of typhoid fever, three to 25 patients without typhoid disease are treated with antimicrobials unnecessarily, conservatively amounting to more than 50 million prescriptions per year. Antimicrobials for suspected typhoid might therefore be an important selective pressure for the emergence and spread of antimicrobial resistance globally. We propose that large-scale, more aggressive typhoid vaccination programmes-including catch-up campaigns in children up to 15 years of age, and vaccination in lower incidence settings-have the potential to reduce the overuse of antimicrobials and thereby reduce antimicrobial resistance in many bacterial pathogens. Funding bodies and national governments must therefore consider the potential for broad reductions in antimicrobial use and resistance in decisions related to the rollout of typhoid conjugate vaccines.

Cholera remains a public health threat among the least privileged populations and regions affected by conflicts and natural disasters. Together with Water, Sanitation and Hygiene practices, use of oral cholera vaccines (OCVs) is a key tool to prevent cholera. Bivalent whole-cell killed OCVs have been extensively used worldwide and found effective in protecting populations against cholera in endemic and outbreak settings. No cholera vaccine had been available for United States (US) travelers at risk for decades until 2016 when CVD 103-HgR (Vaxchora™), an oral live attenuated vaccine, was licensed by the US FDA. A single dose of Vaxchora™ protected US volunteers against experimental challenge 10 days and 3 months after vaccination. However, use of Vaxchora™ poses several challenges in resource poor settings as it requires reconstitution, is age-restricted to 18 to 64 years, has no data in populations endemic for cholera, and faces challenges related to cold chain and cost.

Background: Group A Streptococcus (Strep A) causes a broad spectrum of disease manifestations, ranging from benign symptoms including throat or skin infections, to fatal illness such as rheumatic heart disease, or chronic renal failure. Currently, there is no vaccine available against Strep A infections. Despite the high burden of Strep A-associated infections worldwide, little attention has been paid to the research of these diseases, including standardized surveillance programs, resulting in a lack of economic evaluations for prevention efforts. This study aims at identifying existing cost-effectiveness analyses (CEA) on any Strep A infections. Methods: A systematic literature review was conducted by searching the PubMed electronic database. Results: Of a total of 321, 44 articles met the criteria for inclusion. Overall, CEA studies on Strep A remain limited in number. In particular, a number of available CEA studies on Strep A are disproportionately lower in low-income countries than in high-income countries. Decision-analytic models were the most popular choice for CEA on Strep A. A majority of the models considered pharyngitis and acute rheumatic fever, but it was rare to observe a model which covered a wide range of disease manifestations. Conclusions: Future research is needed to address missing clinical outcomes, imbalance on study locations by income group, and the transmission dynamic of selected diseases.

Background Impact evaluation of vaccination programs is necessary for making decisions to introduce oral cholera vaccines (OCVs) in cholera-endemic countries. Methods We analyzed data to forecast the future global burden of cholera. We developed a mathematical model of cholera transmission in three countries as examples: Nigeria, Uganda, and Indonesia. After fitting the model, we evaluated the impact of OCVs delivered in four vaccination strategies varying by target age group and frequency of vaccination over the period of 2015–2030. Results Data suggest that the global annual incidence of cholera will increase from 3 046 238 in 2015 to 3 787 385 in 2030 with the highest burden in Asia and Africa where overall population size is large and the proportion of population with access to improved sanitation facilities is low. We estimate that OCV will reduce the cumulative incidence of cholera by half in Indonesia and >80% in Nigeria and Uganda when delivered to 1+ year olds every three years at a coverage rate of 50%, although cholera may persist through higher coverage rates (i.e., >90%). The proportion of person-to-person transmission compared to water-to-person transmission is positively correlated with higher vaccination impact in all three countries. Conclusions Periodic OCV vaccination every three or five years can significantly reduce the global burden of cholera although cholera may persist even with high OCV coverage. Vaccination impact will likely vary depending on local epidemiological conditions including age distribution of cases and relative contribution of different transmission routes.

Introduction Although the current pandemic of cholera originated in Asia, reports of cholera cases and outbreaks in the region are sparse. To provide a sub-regional assessment of cholera in South and Southeast Asia, we collated published and unpublished data from existing surveillance systems from Bangladesh, Cambodia, India, Malaysia, Nepal, Pakistan, Philippines, Thailand and Vietnam. Methods Data from existing country surveillance systems on diarrhea, acute watery diarrhea, suspected cholera and/or confirmed cholera in nine selected Asian countries (Bangladesh, Cambodia, India, Malaysia, Nepal, Pakistan, Philippines, Thailand and Vietnam) from 2011 to 2015 (or 2016, when available) were collated. We reviewed annual cholera reports from WHO and searched PubMed and/or ProMED to complement data, where information is not completely available. Results From 2011 to 2016, confirmed cholera cases were identified in at least one year of the 5- or 6-year period in the countries included. Surveillance for cholera exists in most countries, but cases are not always reported. India reported the most number of confirmed cases with a mean of 5964 cases annually. The mean number of cases per year in the Philippines, Pakistan, Bangladesh, Malaysia, Nepal and Thailand were 760, 592, 285, 264, 148 and 88, respectively. Cambodia and Vietnam reported 51 and 3 confirmed cholera cases in 2011, with no subsequent reported cases. Discussion and conclusion We present consolidated results of available surveillance in nine Asian countries and supplemented these with publication searches. There is paucity of readily accessible data on cholera in these countries. We highlight the continuing existence of the disease even in areas with improved sanitation and access to safe drinking water. Continued vigilance and improved surveillance in countries should be strongly encouraged.

Cholera, a diarrheal disease primarily affecting vulnerable populations in developing countries, is estimated to cause disease in more than 2.5 million people and kill almost 100,000 annually. An oral cholera vaccine (OCV) has been available globally since 2001; the demand for this vaccine from affected countries has however been very low, due to various factors including vaccine price and mode of administration. The low demand for the vaccine and limited commercial incentives to invest in research and development of vaccines for developing country markets has kept the global supply of OCVs down. Since 1999, the International Vaccine Institute has been committed to make safe, effective and affordable OCVs accessible. Through a variety of partnerships with collaborators in Sweden, Vietnam, India and South Korea, and with public and private funding, IVI facilitated development and production of two affordable and WHO-prequalified OCVs and together with other stakeholders accelerated the introduction of these vaccines for the global public-sector market.

Cholera is an endemic and epidemic disease in Bangladesh. On 3 March 2013, a meeting on cholera and cholera vaccination in Bangladesh was convened by the Foundation Merieux jointly with the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR, B). The purpose of the meeting was to discuss the investment case for cholera vaccination as a complimentary control and prevention strategy. The performance of a new low cost oral cholera vaccine, Shanchol™, used in recent trials in Bangladesh, was also reviewed in the context of a potential large-scale public-sector vaccination program. Findings showed the oral vaccine to be highly cost-effective when targeting ages 1–14y, and cost-effective when targeting ages 1+y, in high-burden/high-risk districts. Other vaccination strategies targeting urban slums and rural areas without improved water were found to be cost-effective. Regardless of cost-effectiveness (value), the budget impact (affordability) will be an important determinant of which target population and vaccination strategy is selected. Most importantly, adequate vaccine supply for the proposed vaccination programs must be addressed in the context of global efforts to establish a cholera vaccine stockpile and supply other control and prevention efforts.

Summary Background No access to safe water is an important risk factor for typhoid fever, yet risk-level heterogeneity is unaccounted for in previous global burden estimates. Since WHO has recommended risk-based use of typhoid polysaccharide vaccine, we revisited the burden of typhoid fever in low-income and middle-income countries (LMICs) after adjusting for water-related risk. Methods We estimated the typhoid disease burden from studies done in LMICs based on blood-culture-confirmed incidence rates applied to the 2010 population, after correcting for operational issues related to surveillance, limitations of diagnostic tests, and water-related risk. We derived incidence estimates, correction factors, and mortality estimates from systematic literature reviews. We did scenario analyses for risk factors, diagnostic sensitivity, and case fatality rates, accounting for the uncertainty in these estimates and we compared them with previous disease burden estimates. Findings The estimated number of typhoid fever cases in LMICs in 2010 after adjusting for water-related risk was 11·9 million (95% CI 9·9–14·7) cases with 129 000 (75 000–208 000) deaths. By comparison, the estimated risk-unadjusted burden was 20·6 million (17·5–24·2) cases and 223 000 (131 000–344 000) deaths. Scenario analyses indicated that the risk-factor adjustment and updated diagnostic test correction factor derived from systematic literature reviews were the drivers of differences between the current estimate and past estimates. Interpretation The risk-adjusted typhoid fever burden estimate was more conservative than previous estimates. However, by distinguishing the risk differences, it will allow assessment of the effect at the population level and will facilitate cost-effectiveness calculations for risk-based vaccination strategies for future typhoid conjugate vaccine. Funding Bill and Melinda Gates Foundation.

Background Use of the oral cholera vaccine (OCV) is a vital short-term strategy to control cholera in endemic areas with poor water and sanitation infrastructure. Identifying, estimating, and categorizing the delivery costs of OCV campaigns are useful in analyzing cost-effectiveness, understanding vaccine affordability, and in planning and decision making by program managers and policy makers. Objectives To review and re-estimate oral cholera vaccination program costs and propose a new standardized categorization that can help in collation, analysis, and comparison of delivery costs across countries. Data sources Peer reviewed publications listed in PubMed database, Google Scholar and World Health Organization (WHO) websites and unpublished data from organizations involved in oral cholera vaccination. Study eligibility criteria The publications and reports containing oral cholera vaccination delivery costs, conducted in low- and middle-income countries based on World Bank Classification. Limits are humans and publication date before December 31st, 2014. Participants No participants are involved, only costs are collected. Intervention Oral cholera vaccination and cost estimation. Study appraisal and synthesis method A systematic review was conducted using pre-defined inclusion and exclusion criteria. Cost items were categorized into four main cost groups: vaccination program preparation, vaccine administration, adverse events following immunization and vaccine procurement; the first three groups constituting the vaccine delivery costs. The costs were re-estimated in 2014 US dollars (US$) and in international dollar (I$). Results Ten studies were identified and included in the analysis. The vaccine delivery costs ranged from US$0.36 to US$ 6.32 (in US$2014) which was equivalent to I$ 0.99 to I$ 16.81 (in I$2014). The vaccine procurement costs ranged from US$ 0.29 to US$ 29.70 (in US$2014), which was equivalent to I$ 0.72 to I$ 78.96 (in I$2014). The delivery costs in routine immunization systems were lowest from US$ 0.36 (in US$2014) equivalent to I$ 0.99 (in I$2014). Limitations The reported cost categories are not standardized at collection point and may lead to misclassification. Costs for some OCV campaigns are not available and analysis does not include direct and indirect costs to vaccine recipients. Conclusions and implications of key findings Vaccine delivery cost estimation is needed for budgeting and economic analysis of vaccination programs. The cost categorization methodology presented in this study is helpful in collecting OCV delivery costs in a standardized manner, comparing delivery costs, planning vaccination campaigns and informing decision-making., Author Summary We reviewed and re-estimated oral cholera vaccine delivery costs in low and middle income countries standardizing cost categories. The cost categorization proposed here can help in collation, analysis, comparison and economic analysis of OCV delivery costs across countries.

Background While the global burden of typhoid fever has been often brought up for attention, the detailed surveillance information has only been available for the limited number of countries. As more efficacious vaccines will be available in the near future, it is essential to understand the geographically diverse patterns of typhoid risk levels and to prioritize the right populations for vaccination to effectively control the disease. Methods A composite index called the typhoid risk factor (TRF) index was created based on data with the Global Positioning System (GPS). Demographic and Health Surveys (DHS) and National Geographical Data Center (NGDC) satellite lights data were used for this analysis. A count model was adopted to validate the TRF index against the existing surveillance burden data. The TRF index was then re-estimated for 66 countries using the most recent data and mapped out for two geographical levels (sub-national boundary and grid-cell levels). Results The TRF index which consists of drinking water sources, toilet facility types, and population density appeared to be statistically significant to explain variation in the disease burden data. The mapping analysis showed that typhoid risk levels vary not only by country but also by sub-national region. The grid-cell level analysis highlighted that the distribution of typhoid risk factors is uneven within the sub-national boundary level. Typhoid risk levels are geographically heterogeneous. Conclusions Given the insufficient number of surveillance studies, the TRF index serves as a useful tool by capturing multiple risk factors of the disease into a single indicator. This will help decision makers identify high risk areas for typhoid as well as other waterborne diseases. Further, the study outcome can guide researchers to find relevant places for future surveillance studies. Electronic supplementary material The online version of this article (doi:10.1186/s12879-016-2074-1) contains supplementary material, which is available to authorized users.

Improving water and sanitation is the preferred choice for cholera control in the long-term. Nevertheless, vaccination is an available tool that has been shown to be a cost-effective option for cholera prevention in endemic countries or during outbreaks. In 2011 the first low-cost oral cholera vaccine for international use was given prequalification by the World Health Organization (WHO). To increase and prioritize use of the vaccine, WHO created a global stockpile in 2013 from which countries may request oral cholera vaccine for reactive campaigns. WHO has issued specific guidelines for applying for the vaccine, which was previously in short supply (despite prequalification for a second oral vaccine in 2015). The addition of a third WHO-prequalified oral cholera vaccine in 2016 is expected to increase the global stockpile considerably and alleviate supply issues. However, prioritization and best use of the vaccine (e.g. how, when and where to use) will remain challenges. We describe 12 past oral cholera vaccine campaigns, conducted in settings with varying burdens of cholera. These case studies illustrate three key challenges faced in the use of the oral cholera vaccines: regulatory hurdles, cold chain logistics and vaccine coverage and uptake. To pave the way for the introduction of current and future oral cholera vaccines, we discuss operational challenges and make recommendations for future research with respect to each of these challenges.Améliorer l'accès à l'eau et à l'assainissement est le meilleur moyen de lutter contre le choléra à long terme. Néanmoins, la vaccination s'avère être un outil accessible et rentable pour la prévention du choléra dans les pays où cette maladie est endémique ou pendant des épidémies. En 2011, l'Organisation mondiale de la Santé (OMS) a présélectionné le premier vaccin anticholérique oral à faible coût destiné à un usage international. Afin de favoriser et de hiérarchiser l'usage de ce vaccin, l'OMS a créé en 2013 une réserve mondiale auprès de laquelle les pays peuvent demander des vaccins anticholériques oraux et mettre en œuvre des campagnes réactives. L'OMS a publié des directives spécifiques pour demander ce vaccin, qui n'était auparavant disponible qu'en quantité limitée (malgré la présélection d'un second vaccin oral en 2015). L'ajout, en 2016, d'un troisième vaccin anticholérique oral présélectionné par l'OMS devrait permettre d'augmenter sensiblement les réserves mondiales et d'atténuer les problèmes d'approvisionnement. Il restera cependant à traiter les questions de la hiérarchisation et du meilleur usage du vaccin (par ex., comment, à quel moment et à quel endroit l’utiliser). Nous décrivons ici 12 campagnes de vaccination orale contre le choléra qui ont été menées dans des régions diversement touchées par cette maladie. Ces études de cas illustrent trois grands défis qui se posent lors de l'utilisation de vaccins anticholériques oraux: les obstacles règlementaires, la logistique de la chaîne du froid et la couverture ainsi que le taux de vaccination. Afin de préparer l'introduction de vaccins anticholériques oraux, existants et futurs, nous examinons les difficultés opérationnelles et formulons des recommandations concernant de futurs travaux de recherche sur chacune de ces difficultés.La mejora del agua y el saneamiento es la opción preferida para el control del cólera a largo plazo. Sin embargo, la vacunación es una herramienta disponible que ha demostrado ser una alternativa rentable para la prevención del cólera en países endémicos o durante brotes. En 2011, la Organización Mundial de la Salud (OMS) precalificó la primera vacuna anticolérica oral de bajo coste para uso internacional. Para aumentar y priorizar el uso de la vacuna, en 2013 la OMS creó una reserva global de la cual los países podían solicitar vacunas anticoléricas orales para campañas reactivas. La OMS ha publicado directrices específicas para la aplicación de la vacuna, cuyo suministro era escaso anteriormente (a pesar de la precalificación para una segunda vacuna oral en 2015). Está previsto que el hecho de añadir una tercera vacuna anticolérica oral precalificada por la OMS en 2016 aumente las reservas globales de forma considerable y reduzca los problemas de suministro. No obstante, la priorización y el buen uso de la vacuna (por ejemplo, cómo, cuándo y dónde utilizarla) seguirán siendo asuntos importantes. Se describen 12 campañas anteriores de vacunación oral contra el cólera, realizadas en entornos con distintos niveles de cólera. Estos estudios de casos ilustran los tres problemas principales que surgen al utilizar vacunas anticoléricas orales: obstáculos reglamentarios, logística de la gestión de la cadena de frío y cobertura y aceptación de la vacuna. Para allanar el terreno en la introducción de vacunas anticoléricas orales en el presente y en el futuro, se analizan las dificultades operativas y se presentan recomendaciones para futuras investigaciones con respecto a estos problemas.يُعد تحسين الماء والصرف الصحي الخيار المفضل للسيطرة على الكوليرا على المدى البعيد. وبالرغم من ذلك، تُعد خدمات التحصين أداة متاحة أثبتت جدارتها كخيار فعال من حيث التكلفة للوقاية من الكوليرا في الدول التي يستوطن بها هذا المرض أو أثناء حوادث تفشي الأمراض. تم منح أول لقاح فموي منخفض التكلفة ضد الكوليرا اعتمادًا مبدئيًا للاستخدام الدولي من قبل منظمة الصحة العالمية وذلك في عام 2011. لزيادة استخدام اللقاح ومنحه الأولوية، أنشأت منظمة الأمم المتحدة مخزونًا عالميًا في عام 2013 يمكن للدول أن تطلب منه اللقاح الفموي ضد الكوليرا من أجل حملات الاستجابة للمرض. أصدرت منظمة الصحة العالمية مبادئ توجيهية محددة لاستخدام اللقاح الذي كان به نقصًا (على الرغم من الاعتماد المبدئي لقاح فموي ثانٍ في عام 2015). ومن المتوقع أن تؤدي إضافة اللقاح الفموي الثالث – الحاصل على اعتماد مبدئي من جانب منظمة الصحة العالمية ضد الكوليرا في عام 2016 – إلى زيادة المخزون العالمي بشكل كبير وتخفيف مشاكل المخزون. ومع ذلك، فإن تحديد أولوية اللقاح والاستخدام الأمثل له ستظل تحديًا قائمًا (على سبيل المثال، كيف ومتى وأين يتم استخدامه). ونوضح 12 حملة سابقة لتطعيم اللقاح الفموي ضد الكوليرا أجريت في مواقع يختلف بها عبء الكوليرا. وتوضح دراسات الحالة هذه ثلاثة تحديات رئيسية تم مواجهتها عند استخدام اللقاح الفموي ضد الكوليرا، وهي المتمثلة في: العقبات التنظيمية، والخدمات اللوجستية للنقل في حاويات مبرّدة، وتغطية خدمات التحصين واستيعابها. ومن أجل تمهيد الطريق لتقديم اللقاحات الفموية الحالية والمستقبلية ضد الكوليرا، فقد ناقشنا التحديات العملية وقدمنا توصيات للبحوث المستقبلية فيما يتعلق بكلٍ من هذه التحديات.从长远看，改善水质及卫生设施是控制霍乱的优选。 不过，疫苗接种也是一种可行的方法，并且已经证实对于疾病流行国家或疾病爆发期间霍乱的预防，是一种性价比高的选择。 2011 年首批供国际使用的低成本口服霍乱疫苗通过了世界卫生组织 (WHO) 的资格预审。 为增加并优化疫苗的使用，世界卫生组织在 2013 年创建了一个全球储存处，各国可从中申请口服霍乱疫苗以开展各项响应活动。 世界卫生组织发布了申请该疫苗的具体指南，该疫苗之前一直处于短缺状态（尽管第二种口服疫苗在 2015 年通过了资格预审） 于 2016 年推出的第三种通过世界卫生组织资格预审的口服霍乱疫苗有望大量增加全球存储并缓解供应问题。 然而，疫苗的优化及最佳使用（如，如何使用、何时使用以及在哪里使用）仍将面临挑战。 我们描述了过去在遭受不同程度霍乱影响的地区开展的 12 项口服霍乱疫苗活动。 这些案例研究表明口服霍乱疫苗的应用主要面临三大挑战： 监管障碍、冷链物流及疫苗覆盖率及接种率。 为扫清当前及未来引进口服霍乱疫苗所面临的障碍，我们讨论了实际操作方面的挑战并为有关各项挑战的未来研究提出了推荐意见。.Усовершенствование водоснабжения и санитарии является предпочтительной мерой для борьбы с холерой в долгосрочной перспективе. Тем не менее вакцинация является доступным инструментом, который, как было продемонстрировано, является экономически эффективным вариантом для профилактики холеры в эндемичных странах или во время вспышек этого заболевания. В 2011 году первая недорогая пероральная вакцина против холеры для международного использования получила преквалификацию Всемирной организации здравоохранения (ВОЗ). Для увеличения объемов использования, а также определения приоритетного использования вакцины в 2013 году ВОЗ создала ее глобальные запасы, из которых страны могут запросить пероральную вакцину против холеры для кампаний по противодействию этому заболеванию. ВОЗ опубликовала конкретные рекомендации по применению вакцины, которая ранее была в дефиците (несмотря на преквалификацию второй пероральной вакцины в 2015 году). Ожидается, что добавление третьей пероральной вакцины против холеры, преквалифицированной ВОЗ в 2016 году, значительно пополнит мировые запасы и облегчит проблемы поставок. Тем не менее остается сложной задачей определение приоритетного и наиболее эффективного использования вакцины (например, как, когда и где использовать). Мы описали 12 прошлых кампаний с применением пероральной противохолерной вакцины, проводимых в условиях с различной микробной нагрузкой. Эти клинические наблюдения иллюстрируют три основные проблемы, с которыми сталкиваются при использовании пероральных противохолерных вакцин: нормативные препятствия, проблемы с материально-техническим обеспечением холодовой цепи и проблемы охвата вакцинацией. Чтобы подготовить почву для внедрения текущих и будущих пероральных противохолерных вакцин, мы рассматриваем эксплуатационные проблемы и разрабатываем рекомендации для будущих исследований в отношении каждой из этих проблем.

Blood culture is often used in definitive diagnosis of typhoid fever while, bone marrow culture has a greater sensitivity and considered reference standard. The sensitivity of blood culture measured against bone marrow culture results in measurement bias because both tests are not fully sensitive. Here we propose a combination of the two cultures as a reference to define true positive S. Typhi cases. Based on a systematic literature review, we identified ten papers that had performed blood and bone marrow culture for S. Typhi in same subjects. We estimated the weighted mean of proportion of cases detected by culture measured against true S. Typhi positive cases using a random effects model. Of 529 true positive S. Typhi cases, 61 % (95 % CI 52-70 %) and 96 % (95 % CI 93-99 %) were detected by blood and bone marrow cultures respectively. Blood culture sensitivity was 66 % (95 % CI 56-75 %) when compared with bone marrow culture results. The use of blood culture sensitivity as a proxy measure to estimate the proportion of typhoid fever cases detected by blood culture is likely to be an underestimate. As blood culture sensitivity is used as a correction factor in estimating typhoid disease burden, epidemiologists and policy makers should account for the underestimation.

Background Documentation of the long-term impact of supportive supervision using a monitoring tool in STI intervention with sex workers, men who have sex with men and injection-drug users is limited. The authors report methods and results of continued quality monitoring in a large-scale STI services provided as a part of a broader HIV-prevention package in six Indian states under Avahan, the India AIDS Initiative. Methodology Guidelines and standards for STI services, and a supportive supervisory tool to monitor the quality were developed for providing technical support to STI component of large-scale HIV-prevention intervention through 372 project-supported STI clinics. The tool contained 80 questions to track the quality of STI services provided on a five-point scoring scale in five performance areas: coverage, quality of clinic and services, referral networks, community involvement and technical support. Results The tool was applied to different STI clinics during supportive supervision visits conducted once in every 3 months to assess quality, give immediate feedback and develop a quality score. A total of 292 clinics managed by seven lead implementing partners in six Indian states were covered in 15 quarters over 45 months. Overall quality indicators for the five performance areas showed a three- to sevenfold improvement over the period. Conclusion It was possible to improve quality over the long-term in STI interventions for sex workers, men who have sex with men and injection-drug users using an interactive and comprehensive supportive supervision tool which gives on-the-spot feedback. However, such an effort is time-consuming and resource-intensive, and needs a structured approach.

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Background The control of typhoid fever being an important public health concern in low and middle income countries, improving typhoid surveillance will help in planning and implementing typhoid control activities such as deployment of new generation Vi conjugate typhoid vaccines. Methods We conducted a systematic literature review of longitudinal population-based blood culture-confirmed typhoid fever studies from low and middle income countries published from 1st January 1990 to 31st December 2013. We quantitatively summarized typhoid fever incidence rates and qualitatively reviewed study methodology that could have influenced rate estimates. We used meta-analysis approach based on random effects model in summarizing the hospitalization rates. Results Twenty-two papers presented longitudinal population-based and blood culture-confirmed typhoid fever incidence estimates from 20 distinct sites in low and middle income countries. The reported incidence and hospitalizations rates were heterogeneous as well as the study methodology across the sites. We elucidated how the incidence rates were underestimated in published studies. We summarized six categories of under-estimation biases observed in these studies and presented potential solutions. Conclusions Published longitudinal typhoid fever studies in low and middle income countries are geographically clustered and the methodology employed has a potential for underestimation. Future studies should account for these limitations. Electronic supplementary material The online version of this article (doi:10.1186/s12879-016-1351-3) contains supplementary material, which is available to authorized users.

Background The rise in dengue fever cases and the absence of dengue vaccines will likely cause governments to consider various types of effective means for controlling the disease. Given strong public interests in potential dengue vaccines, it is essential to understand the private economic benefits of dengue vaccines for accelerated introduction of vaccines into the public sector program and private markets of high-risk countries. Methodology/Principal Findings A contingent valuation study for a hypothetical dengue vaccine was administered to 400 households in a multi-country setting: Vietnam, Thailand, and Colombia. All respondents received a description of the hypothetical dengue vaccine scenarios of 70% or 95% effectiveness for 10 or 30 years with a three dose series. Five price points were determined after pilot tests in order to reflect different local situations such as household income levels and general perceptions towards dengue fever. We adopted either Poisson or negative binomial regression models to calculate average willingness-to-pay (WTP), as well as median WTP. We found that there is a significant demand for dengue vaccines. The parametric median WTP is $26.4 ($8.8 per dose) in Vietnam, $70.3 ($23.4 per dose) in Thailand, and $23 ($7.7 per dose) in Colombia. Our study also suggests that respondents place more value on vaccinating young children than school age children and adults. Conclusions/Significance Knowing that dengue vaccines are not yet available, our study provides critical information to both public and private sectors. The study results can be used to ensure broad coverage with an affordable price and incorporated into cost benefit analyses, which can inform prioritization of alternative health interventions at the national level., Author Summary Dengue is complicated. There are four serotypes of the dengue virus, and dengue infection occurs in almost all age groups. Infection with one serotype provides life-long immunity to that specific serotype but does not protect against the other three serotypes. Unlike other diseases which already have preventable vaccines developed, currently there are no commercially available vaccines for dengue fever. Even if the first vaccine becomes available, it is expected that there will be a limited number of vaccine doses available in the first few years. Due to the increase in dengue fever cases, there is already huge public and private interest in potential dengue vaccines. This study reports the household willingness-to-pay for a hypothetical dengue vaccine in three dengue endemic countries. We found that household demand is strongly related to price and income. It was also observed that more than half of the study populations are willing to pay for vaccines when price is lower than the median estimates reported here. This study may contribute to a more effective decision on dengue vaccine introduction.

Background Service provider costs for vaccine delivery have been well documented; however, vaccine recipients’ costs have drawn less attention. This research explores the private household out-of-pocket and opportunity costs incurred to receive free oral cholera vaccine during a mass vaccination campaign in rural Odisha, India. Methods Following a government-driven oral cholera mass vaccination campaign targeting population over one year of age, a questionnaire-based cross-sectional survey was conducted to estimate private household costs among vaccine recipients. The questionnaire captured travel costs as well as time and wage loss for self and accompanying persons. The productivity loss was estimated using three methods: self-reported, government defined minimum daily wages and gross domestic product per capita in Odisha. Findings On average, families were located 282.7 (SD = 254.5) meters from the nearest vaccination booths. Most family members either walked or bicycled to the vaccination sites and spent on average 26.5 minutes on travel and 15.7 minutes on waiting. Depending upon the methodology, the estimated productivity loss due to potential foregone income ranged from $0.15 to $0.29 per dose of cholera vaccine received. The private household cost of receiving oral cholera vaccine constituted 24.6% to 38.0% of overall vaccine delivery costs. Interpretation The private household costs resulting from productivity loss for receiving a free oral cholera vaccine is a substantial proportion of overall vaccine delivery cost and may influence vaccine uptake. Policy makers and program managers need to recognize the importance of private costs and consider how to balance programmatic delivery costs with private household costs to receive vaccines., Author Summary The price of vaccine and the costs of its delivery are two important economic measures considered by governments and various international organizations in their decisions on the use of a new vaccine. However, the costs to the vaccine recipients resulting from their travel, time and wage loss are hardly considered and rarely documented. Even if the vaccine is provided for free, the costs borne by vaccine recipients could be sufficient enough to be a hurdle for taking vaccine. We elucidate this less explored angle of “vaccine recipient cost” in the context of oral cholera vaccine mass campaign in Odisha, India. Our research shows that the potential loss of income for individuals for receiving oral cholera vaccine ranged from 25% to 38% of overall vaccine delivery costs. We believe our findings have global implications on future decisions and policy making on vaccine introduction in balancing programmatic delivery costs with private household costs to receive vaccines.

Introduction The substantial morbidity and mortality associated with recent cholera outbreaks in Haiti and Zimbabwe, as well as with cholera endemicity in countries throughout Asia and Africa, make a compelling case for supplementary cholera control measures in addition to existing interventions. Clinical trials conducted in Kolkata, India, have led to World Health Organization (WHO)-prequalification of Shanchol, an oral cholera vaccine (OCV) with a demonstrated 65% efficacy at 5 years post-vaccination. However, before this vaccine is widely used in endemic areas or in areas at risk of outbreaks, as recommended by the WHO, policymakers will require empirical evidence on its implementation and delivery costs in public health programs. The objective of the present report is to describe the organization, vaccine coverage, and delivery costs of mass vaccination with a new, less expensive OCV (Shanchol) using existing public health infrastructure in Odisha, India, as a model. Methods All healthy, non-pregnant residents aged 1 year and above residing in selected villages of the Satyabadi block (Puri district, Odisha, India) were invited to participate in a mass vaccination campaign using two doses of OCV. Prior to the campaign, a de jure census, micro-planning for vaccination and social mobilization activities were implemented. Vaccine coverage for each dose was ascertained as a percentage of the censused population. The direct vaccine delivery costs were estimated by reviewing project expenditure records and by interviewing key personnel. Results The mass vaccination was conducted during May and June, 2011, in two phases. In each phase, two vaccine doses were given 14 days apart. Sixty-two vaccination booths, staffed by 395 health workers/volunteers, were established in the community. For the censused population, 31,552 persons (61% of the target population) received the first dose and 23,751 (46%) of these completed their second dose, with a drop-out rate of 25% between the two doses. Higher coverage was observed among females and among 6–17 year-olds. Vaccine cost at market price (about US$1.85/dose) was the costliest item. The vaccine delivery cost was $0.49 per dose or $1.13 per fully vaccinated person. Discussion This is the first undertaken project to collect empirical evidence on the use of Shanchol within a mass vaccination campaign using existing public health program resources. Our findings suggest that mass vaccination is feasible but requires detailed micro-planning. The vaccine and delivery cost is affordable for resource poor countries. Given that the vaccine is now WHO pre-qualified, evidence from this study should encourage oral cholera vaccine use in countries where cholera remains a public health problem., Author Summary Cholera – an acute life-threatening diarrheal illness – continues to disrupt public health in resource poor countries. The devastating outbreaks in Haiti and Zimbabwe – to name just two of many occurrences – calls for the use of available oral cholera vaccines as an additional tool in the arsenal of cholera control measures. An oral cholera vaccine (Shanchol) has been licensed in India since 2009; however, there has only been limited use of this vaccine in government public health programs. A vaccination campaign using 2 doses of Shanchol was conducted in Odisha, India, during May and June, 2011, where 31,552 persons (61% of the target population) received the first dose and 23,751 of them completed their second dose. The vaccine delivery cost was $0.49 per dose. Through our findings and experience, we discuss the organization of the cholera vaccination campaign in Odisha, the challenges met for conducting the campaign and the strategies designed to overcome those challenges, and the delivery costs incurred in the use of this vaccine, the first of its kind, in a public health setting. We believe that evidence from this study is of significant interest and use to policymakers from countries where cholera remains a public health problem.

Introduction In 2010, the World Health Organization released a new cholera vaccine position paper, which recommended the use of cholera vaccines in high-risk endemic areas. However, there is a paucity of data on the burden of cholera in endemic countries. This article reviewed available cholera surveillance data from Uganda and assessed the sufficiency of these data to inform country-specific strategies for cholera vaccination. Methods The Uganda Ministry of Health conducts cholera surveillance to guide cholera outbreak control activities. This includes reporting the number of cases based on a standardized clinical definition plus systematic laboratory testing of stool samples from suspected cases at the outset and conclusion of outbreaks. This retrospective study analyzes available data by district and by age to estimate incidence rates. Since surveillance activities focus on more severe hospitalized cases and deaths, a sensitivity analysis was conducted to estimate the number of non-severe cases and unrecognized deaths that may not have been captured. Results Cholera affected all ages, but the geographic distribution of the disease was very heterogeneous in Uganda. We estimated that an average of about 11,000 cholera cases occurred in Uganda each year, which led to approximately 61–182 deaths. The majority of these cases (81%) occurred in a relatively small number of districts comprising just 24% of Uganda's total population. These districts included rural areas bordering the Democratic Republic of Congo, South Sudan, and Kenya as well as the slums of Kampala city. When outbreaks occurred, the average duration was about 15 weeks with a range of 4–44 weeks. Discussion There is a clear subdivision between high-risk and low-risk districts in Uganda. Vaccination efforts should be focused on the high-risk population. However, enhanced or sentinel surveillance activities should be undertaken to better quantify the endemic disease burden and high-risk populations prior to introducing the vaccine., Author Summary Uganda has reported cholera cases to the World Health Organization every year since 1997. Thus, the country may consider the introduction of a WHO-prequalified oral cholera vaccine. This article reviews cholera surveillance data from 1997–2010 with a focus on the 2005–2010 time period to identify high risk populations that may be targeted for preventive vaccination campaigns. We estimated that an average of about 61–182 deaths occur each year. Most cases (81%) occurred in a relatively small number of districts comprising just 24% of Uganda's total population. While there is a clear distinction between low and high-risk districts, sentinel surveillance would help to better quantify the burden in endemic districts. An economic analysis should also be undertaken prior to making a decision to introduce a cholera vaccine.

To measure the prevalence of specific learning disabilities (SpLDs) such as dyslexia, dysgraphia and dyscalculia among primary school children in a South Indian city. A cross-sectional multi-staged stratified randomized cluster sampling study was conducted among children aged 8–11 years from third and fourth standard. A six level screening approach that commenced with identification of scholastic backwardness followed by stepwise exclusion of impaired vision and hearing, chronic medical conditions and subnormal intelligence was carried out among these children. In the final step, the remaining children were subjected to specific tests for reading, comprehension, writing and mathematical calculation. The prevalence of specific learning disabilities was 15.17% in sampled children, whereas 12.5%, 11.2% and 10.5% had dysgraphia, dyslexia and dyscalculia respectively. This study suggests that the prevalence of SpLDs is at the higher side of previous estimations in India. The study is unique due to its large geographically representative design and identification of the problem using simplified screening approach and tools, which minimizes the number and time of specialist requirement and spares the expensive investigation. This approach and tools are suitable for field situations and resource scarce settings. Based on the authors’ experience, they express the need for more prevalence studies, remedial education and policy interventions to manage SpLDs at main stream educational system to improve the school performance in Indian children.

Sir,We read with interest the original article by Mogasale et al. on“Prevalence of Specific Learning Disabilities among PrimarySchool Children in a South Indian City” [1]. We acknowledgethat the authors have addressed an important issue. Howeverwe have four objections about the methodology employed bythe authors to estimate the prevalence of specific learningdisabilities (SpLDs) in their study. Our objections are as under:Firstly, during screening levels 2 and 3, the authors haveexcluded all children with impaired vision and impairedhearing. Only children having ≥40 % non-correctable visualor auditory disability should have been excluded [2]. It iswell known that a child with SpLDs can have impairedvision and/or impaired hearing as a co-morbid condition.Secondly, during screening level 5, children’s intellec-tual functioning was determined using the Seguin FormBoard test. This is a simple screening test wherein thechild has to put ten differently shaped wooden blocksinto a large form board with recesses corresponding tothese shapes in a specified time limit. It is used to assessvisual discrimination and matching and eye-hand coordi-nation and is an inappropriate test for this study. In ouropinion the authors should have employed the standardintelligence test viz., Wechsler Intelligence Scale for Chil-dren test (Indian adaptation) to determine that the child’sintellectual functioning was normal [2].Thirdly, during screening level 6, the educational testingof the children was done by a Pediatric PostgraduateStudent. It is mandatory that a qualified Special Educator(M.Ed. in Special Education) does the educational testingfor diagnosing SpLDs [2,3].Lastly, there is no mention of any attempt done to screenfor or diagnose attention-deficit/hyperactivity disorder(ADHD) in the study. Many children with ADHD developpoor school performance due to their hyperactivity, impul-siveness and/or inattention. It is well known that up to 20 %of children with ADHD have co-morbid SpLDs [4].To conclude, we do not agree with the results of the studyand the authors’ naive claim that SpLDs can be diagnosedwithout using a standard psychological test or withoutemploying the services of a Special Educator.References1. MogasaleVV,PatilVD,PatilNM,MogasaleV.Prevalenceofspecificlearningdisabilitiesamongprimaryschoolchildrenin a South Indian city. Indian J Pediatr. 2012;79:342-7.2. Karande S, Kulkarni M. Specific learning disability: theinvisible handicap. Indian Pediatr. 2005;42:315-9.3. Karande S, Sholapurwala R, Kulkarni M. Managingspecific learning disability in schools in India. IndianPediatr. 2011;48:515-20.4. Karande S. Attention deficit hyperactivity disorder - areview for family physicians. Indian J Med Sci. 2005;59:546-55.Authors ReplySir,We carefully appraised the good points brought-up byKarande et al in the response letter. This has provided usan opportunity to reaffirm our views stated in the paper thatwe have used a realistic approach at the school level to

Background Cholera is endemic in several Asian and African countries and has gained increased attention in recent years after large outbreaks. Interest is growing about use of oral cholera vaccine to control cholera in endemic settings. We analysed the economics and epidemiology of oral cholera vaccines for this purpose. Methods We assessed the effect of repeated cholera vaccination campaigns to prevent outbreaks in high-risk endemic areas accounting for programme and disease costs. We used a demand forecast to predict the potential year of adoption for various cholera-endemic countries based on country characteristics. We used a dynamic disease transmission model to assess the population-level effect of cholera vaccination programmes on disease incidence and mortality. Findings Demand from 33 endemic countries in Africa and Asia is predicted to be 6–18 million doses in 2015 rising to 62–141 million doses per year by 2022, depending on the assumed programme option. Costs will range from US$18 million to $49 million in 2015 and increase to $140 million–319 million per year by 2022. Between 2015 and 2022, the vaccination programmes could prevent 2·3 million–4·9 million cases of cholera and 75 000–154 000 deaths. All programme options were very cost-effective compared with regional average gross domestic product, with the cost per disability-adjusted life-year averted ranging from $151 to $785. Interpretation A targeted programme of cholera vaccination using the oral killed whole-cell vaccine in 33 endemic countries would significantly reduce the cholera disease burden and risk of epidemics, and would be cost-effective. Funding Government of Kuwait, Government of Sweden, and Government of South Korea.

Background: Meningococcal disease is characterized by a arked variation in incidence and serogroup distribution by region nd over time. In several European countries, Canada andAustralia, mmunization programs, including universal vaccination of infants r toddlers, with catch-up campaigns in children and adolescents, imed at controlling disease caused bymeningococcal serogroup C, ave been successful in reducing disease incidence through direct nd indirect protection. More recently, meningococcal conjugate accines targeting disease caused by serogroups A, C, W135 and Y ave been licensed and are being used in adolescent programs in he USA and Canada. Also, a mass immunization campaign against erogroup A disease has been implemented in Africa. Methods: We gathered published information about meningooccal epidemiology and vaccination policy as well as deducing accination policy decisions from an observation of howmeningooccal vaccines are used in different situations. Results: The policy options available for control ofmeningococal infection are: routine age-specific recommendations; routine nfant strategy plus catch-up (eg UK, Spain, Iceland, Portugal); rouine toddler strategy plus catch-up (eg Australia, The Netherlands, elgium, France, most of Canada); adolescent-only strategy (USA ndManitoba). Outbreak control policies have been usedwith sucess in the Africanmeningitis belt countries, New Zealand, Norway nd Normandy. Policies to prevent travel-associated disease (eg ajj and Amrah) have also been adopted in various parts of the orld. The prevailing serogroup epidemiology determines the use f monovalent versus multivalent vaccines and decisions on the chedule can be affected by the potential for herd protection. Conclusion: Enhanced surveillance including the use of sensiive molecular techniques and capture/recapture, along with the vailability of existing and newmeningococcal vaccines, for examle against serogroup B, allow for both improved policy decisions nd more impactful reductions in the global burden of meningooccal infection.