Optimal Control of Shigellosis with Cost-Effective Strategies.

In this paper, we apply optimal control theory to the model for shigellosis. It is assumed that education campaign, sanitation, and treatment are the main controls for this disease. The aim is to minimize the number of infections resulting from contact with careers, infectious population, and contaminated environments while keeping the cost of associated controls minimum. We achieve this aim through the application of Pontryagin's Maximum Principle. Numerical simulations are carried out by using both forward and backward in time fourth-order Runge-Kutta schemes. We simulate the model under different strategies to investigate which option could yield the best results. The findings show that the strategy combining all three control efforts (treatment, sanitation, and education campaign) proves to be more beneficial in containing shigellosis than the rest. On the other hand, cost-effectiveness analysis is performed via incremental cost-effectiveness ratio (ICER). The findings from the ICER show that a strategy incorporating all three controls (treatment, sanitation, and education campaign) is the most cost-effective of all strategies considered in the study.

Investigation of a foodborne outbreak of Shigella sonnei in Ireland and Northern Ireland, December 2016: the benefits of cross-border collaboration and commercial sales data.

OBJECTIVES: To describe a cross-border foodborne outbreak of Shigella sonnei that occurred in Ireland and Northern Ireland (NI) in December 2016 whilst also highlighting the valuable roles of sales data and international collaboration in the investigation and control of this outbreak. STUDY DESIGN: A cross-border outbreak control team was established to investigate the outbreak. METHODS: Epidemiological, microbiological, and environmental investigations were undertaken. Traditional analytical epidemiological studies were not feasible in this investigation. The restaurant chain provided sales data, which allowed assessment of a possible increased risk of illness associated with exposure to a particular type of heated food product (product A). RESULTS: Confirmed cases demonstrated sole trimethoprim resistance: an atypical antibiogram for Shigella isolates in Ireland. Early communication and the sharing of information within the outbreak control team facilitated the early detection of the international dimension of this outbreak. A joint international alert using the European Centre for Disease Control's confidential Epidemic Intelligence Information System for Food- and Waterborne Diseases and Zoonoses (EPIS-FWD) did not reveal further cases outside of the island of Ireland. The outbreak investigation identified that nine of thirteen primary case individuals had consumed product A from one of multiple branches of a restaurant chain located throughout the island of Ireland. Product A was made specifically for this chain in a food production facility in NI. S. sonnei was not detected in food samples from the food production facility. Strong statistical associations were observed between visiting a branch of this restaurant chain between 5 and 9 December 2016 and eating product A and developing shigellosis. CONCLUSIONS: This outbreak investigation highlights the importance of international collaboration in the efficient identification of cross-border foodborne outbreaks and the value of using sales data as the analytical component of such studies.

Cost of Illness for Five Major Foodborne Illnesses and Sequelae in Sweden.

OBJECTIVES: The main objective of this study was to derive cost estimates of five major foodborne illnesses (campylobacteriosis, salmonellosis, enterohemorrhagic Escherichia coli (EHEC), yersiniosis and shigellosis) in Sweden. These estimates provide a necessary contribution to perform future cost-benefit analyses aimed at reducing the burden of foodborne disease. A secondary aim was to obtain estimates of the true number of cases that occur in the community, thus providing necessary ground for calculating costs. METHODS: The true number of cases for each foodborne illness was simulated by multiplying the reported number of cases by sequential multipliers, one for each potential source of information loss about a case. This assessment of the true number of cases was then used to estimate the number of cases of sequelae for each illness. An incidence-based analysis was then used to calculate direct medical and non-medical costs, as well as indirect costs. Data for estimating the true number of cases for each illness were primarily based on an expert panel, while the derivation of costs mainly utilized national registries, databases and published literature. RESULTS: The estimated number of cases was between 7- and 11-fold higher than the reported number of cases, indicating the importance of taking information loss into account when calculating costs. By far the most common pathogen of the five was campylobacter, with an estimated 101,719 (90% credibility interval [CI] 59,640-158,025) human cases occurring annually. For salmonella, 19,678 (90% CI 8394-40,456) cases were estimated to occur each year, while the other three pathogens were less common, with a yearly incidence of approximately 2500-5500 cases each. The total cost for the five pathogens (including sequelae) amounted to €142 million annually. Campylobacter was the most costly pathogen, representing 69% of the total costs. Salmonellosis and EHEC constituted 18 and 9% of these costs, respectively, while yersiniosis and shigellosis represented approximately 2% each. Costs for sequelae were significant and accounted for approximately 50% of the total costs. CONCLUSIONS: Our simulations indicated that campylobacter infection was more common and more costly than salmonella, EHEC, yersinia and shigella combined. Estimated costs for all illnesses were highly influenced by (1) considering potential information losses about cases in the population (which increased costs 7- to 11-fold), and (2) taking account of post-infection sequelae (which doubled the costs).

Assessment on the burden of bacillary dysentery associated with floods during 2005-2009 in Zhengzhou City, China, using a time-series analysis.

BACKGROUND: We aimed to quantify the impact of few times floods on bacillary dysentery in Zhengzhou during 2005-2009. METHODS: The Spearman correlation test was applied first to examine the lagged effects of floods on monthly morbidity of bacillary dysentery during 2005-2009 in Zhengzhou. We further quantified the effects of 7 flood events on the morbidity of bacillary dysentery using the time-series Poisson regression controlling for climatic factors, seasonality, gender and age groups. We estimated years lived with disability (YLDs) to estimate the burden of bacillary dysentery attributed to floods among different population groups. RESULTS: A total of 15,841 cases of bacillary dysentery were reported in the study region over the study period. The relative risks of floods on the morbidity of bacillary dysentery and attributable YLDs among the whole study population, males, females, below 14 years old group, 15-64 years old group, and over 65 years old group were 2.80, 3.13, 2.53, 2.75, 3.03, 2.48, and 1.206, 1.513, 0.913, 3.593, 0.638, 0.880, respectively. CONCLUSIONS: Our findings contribute to developing local strategies to prevent and reduce health impact of floods.

Epidemiological study of shigellosis in an urban area of Argentina.

INTRODUCTION: Shigellosis represents one of the main causes of bloody diarrhoea in South America. This study aimed to establish the incidence of shigellosis in an urban zone of Buenos Aires, Argentina, by examining the type of Shigella and living conditions associated with this infection. METHODOLOGY: Between January 2009 and December 2010 we analyzed shigellosis in children admitted to the public health service with bloody diarrhoea from La Plata, the capital of Buenos Aires, Argentina. A total of 372 children under 15 years old with Shigella present in their stool samples were admitted to the study. Variables studied were patient age, type of Shigella, family economic status, and access to sewage services and safe drinking water. RESULTS: Shigella flexneri was found to be present in 66.8% of the cases. Incidence was 187 cases/year/100,000 children under 15 years old. Cases were mainly observed during the summer (38.5%) in the population of under 5 years old (69.1% of all cases). The risk of shigellosis increased 12 times in those children who lacked safe drinking water and this risk increased 1.5 times in the population without sewage services. Fewer cases of shigellosis were noted in downtown areas, while hot spots were identified in the suburbs. Treating one case of shigellosis has a local cost of US $976 while assuring safe drinking water and sewage services for one family costs US $634.  CONCLUSION: Incidence of shigellosis in urban areas is associated with quality of water and sewage services. Policies aimed at providing education and improving public utilities networks can help to reduce the incidence of shigellosis.

An ecological analysis of sociodemographic factors associated with the incidence of salmonellosis, shigellosis, and E. coli O157:H7 infections in US counties.

Identifying county-level sociodemographic and economic factors associated with the incidence of enteric disease may provide new insights concerning the dynamics of community transmission of these diseases as well as opportunities for prevention. We used data from the National Notifiable Diseases Surveillance System, the U.S. Census Bureau, and the Health Resources and Services Administration to conduct an ecological analysis of 26 sociodemographic and economic factors associated with the incidence of salmonellosis, shigellosis, and E. coli O157:H7 infections in US counties for the period 1993 to 2002. Our study indicates that race, ethnicity, place of residence, age, educational attainment, and poverty may affect the risk of acquiring one of these enteric bacterial diseases. The lack of specificity of information regarding salmonellae and shigellae serotypes may have led to less specific associations between community-level determinants and reported incidence of those diseases. Future ecological analyses should use serotype-specific data on incidence, which may be available from laboratory-based surveillance systems.

A cost function analysis of shigellosis in Thailand.

OBJECTIVE: The purpose of this study was to develop a cost function model to estimate the public treatment cost of shigellosis patients in Thailand. METHODS: This study is an incidence-based cost-of-illness analysis from a provider's perspective. The sample cases in this study were shigellosis patients residing in Kaengkhoi District, Saraburi Province, Thailand. All diarrhea patients who came to the health-care centers in Kaengkhoi District, Kaengkhoi District Hospital and Saraburi Regional Hospital during the period covering May 2002 to April 2003 were tested for Shigella spp. The sample for our study included all patients with culture that confirmed the presence of shigellosis. Public treatment cost was defined as the costs incurred by the health-care service facilities arising from individual cases. The cost was calculated based on the number of services that were utilized (clinic visits, hospitalization, pharmaceuticals, and laboratory investigations), as well as the unit cost of the services (material, labor and capital costs). The data were summarized using descriptive statistics. Furthermore, the stepwise multiple regressions were employed to create a cost function, and the uncertainty was tested by a one-way sensitivity analysis of varying discount rate, cost category, and drug prices. RESULTS: Cost estimates were based from 137 episodes of 130 patients. Ninety-four percent of them received treatment as outpatients. One-fifth of the episodes were children aged less than 5 years old. The average public treatment cost was US$8.65 per episode based on 2006 prices (95% CI, 4.79, and 12.51) (approximately US$1 = 38.084 Thai baht). The majority of the treatment cost (59.3%) was consumed by the hospitalized patients, though they only accounted for 5.8% of all episodes. The sensitivity analysis on the component of costs and drug prices showed a variation in the public treatment cost ranging from US$8.29 to US$9.38 (-4.20% and 8.43% of the base-case, respectively). The public treatment cost model has an adjusted R(2) of 0.788. The positive predictor variables were types of services (inpatient and outpatient), types of health-care facilities (health center, district hospital, regional hospital), and insurance schemes (civil servants medical benefit scheme, social security scheme and universal health coverage scheme). Treatment cost was estimated for various scenarios based on the fitted cost model. CONCLUSION: The average public treatment cost of shigellosis in Thailand was estimated in this study. Service types, health-care facilities, and insurance schemes were the predictors used to predict nearly 80% of the cost. The estimated cost based on the fitted model can be employed for hospital management and health-care planning.

Comparison of cost-of-illness with willingness-to-pay estimates to avoid shigellosis: evidence from China.

Previous studies have shown that cost of illness (COI) measures are lower than the conceptually correct willingness-to-pay (WTP) measure of the economic benefits of disease prevention. We compare COI with stated preference estimates of WTP associated with shigellosis in a rural area of China. COI data were collected through face-to-face interviews at 7 and 14 days after culture-confirmed diagnosis. WTP to avoid an episode similar to the one the respondent just experienced was elicited using a sliding-scale payment card. In contrast to previous studies' findings, average COI estimates (2002 PPP adjusted US dollars 28.2) approximate an upper bound estimate of WTP, rather than a lower bound. One explanation for the similarity between COI and WTP is that preventive expenditures and disutility due to pain and suffering are low for shigellosis. WTP to avoid additional cases in children aged 0-5 years is higher than in adults. Also, average COI (2002 PPP adjusted US dollars 28.4) for children is similar to a lower bound estimate of WTP (2002 PPP adjusted US dollars 16.4) and lies within the WTP range. Because the monetary loss associated with another episode in children is small, caregivers' higher WTP may be attributable to the disutility of illness due to the children's pain and suffering. These findings suggest that for some diseases, COI may approximate more comprehensive measures of economic benefits.

A multicentre study of Shigella diarrhoea in six Asian countries: disease burden, clinical manifestations, and microbiology.

BACKGROUND: The burden of shigellosis is greatest in resource-poor countries. Although this diarrheal disease has been thought to cause considerable morbidity and mortality in excess of 1,000,000 deaths globally per year, little recent data are available to guide intervention strategies in Asia. We conducted a prospective, population-based study in six Asian countries to gain a better understanding of the current disease burden, clinical manifestations, and microbiology of shigellosis in Asia. METHODS AND FINDINGS: Over 600,000 persons of all ages residing in Bangladesh, China, Pakistan, Indonesia, Vietnam, and Thailand were included in the surveillance. Shigella was isolated from 2,927 (5%) of 56,958 diarrhoea episodes detected between 2000 and 2004. The overall incidence of treated shigellosis was 2.1 episodes per 1,000 residents per year in all ages and 13.2/1,000/y in children under 60 months old. Shigellosis incidence increased after age 40 years. S. flexneri was the most frequently isolated Shigella species (1,976/2,927 [68%]) in all sites except in Thailand, where S. sonnei was most frequently detected (124/146 [85%]). S. flexneri serotypes were highly heterogeneous in their distribution from site to site, and even from year to year. PCR detected ipaH, the gene encoding invasion plasmid antigen H in 33% of a sample of culture-negative stool specimens. The majority of S. flexneri isolates in each site were resistant to amoxicillin and cotrimoxazole. Ciprofloxacin-resistant S. flexneri isolates were identified in China (18/305 [6%]), Pakistan (8/242 [3%]), and Vietnam (5/282 [2%]). CONCLUSIONS: Shigella appears to be more ubiquitous in Asian impoverished populations than previously thought, and antibiotic-resistant strains of different species and serotypes have emerged. Focusing on prevention of shigellosis could exert an immediate benefit first by substantially reducing the overall diarrhoea burden in the region and second by preventing the spread of panresistant Shigella strains. The heterogeneous distribution of Shigella species and serotypes suggest that multivalent or cross-protective Shigella vaccines will be needed to prevent shigellosis in Asia.

[Study on the cost-effectiveness of therapeutic scheme of acute bacillary dysentery].

A prospective study on the casts of acute bacillary dysentery treatment with antibiotics of aminoglycoside and the 3rd generation of cephalosporin, along with drug sensitive test in vitro was carried out. The results showed that the clinical therapeutic effects and the sensitive rates to drug in vitro between the two kinds of antibiotics were not statistically different (P > 0.05), but the costs of treatment with these two methods were significantly different. The therapeutic costs were calculated in Ren Ming Bi per day per kilogram body weight. The average therapeutic cost with the 3rd generation of cephalosporin was 44.85 times as that with aminoglycoside. The highest cost by Fortum was 364 times Higher than by Gentamycin. Through cost analysis, conclusion was drawn that the 3rd generation of cephalosporin should not be taken as first choice to treat a acute bacillary dysentery.

[Experiences in an auxiliary hospital for children with dysentery]. / Erfahrungen in einem Hilfskrankenhaus für ruhrkranke Kinder.

An explosive epidemic caused by Sh. flexneri, mainly in babies and infants, has obliged to rigorous anti-epidemic measures. In the centre of all efforts started by "district-commission for combat against epidemics" there was the arrangement and the management of an auxiliary hospital placed in a so-called "Kinderkombination". The public antiepidemic document must be completely revised. The economic consequences were enormous.

Reduction of enteric infectious disease in rural China by providing deep-well tap water.

Enteric infectious disease (EID), defined here as bacillary dysentery, viral hepatitis A, El Tor cholera, or acute watery diarrhoea, is an important public health problem in most developing countries. This study assessed the impact on EID of providing deep-well tap water (DWTW) through household taps in rural China. For this purpose, we compared the incidence of EID in six study villages (population, 10,290) in Qidong County that had DWTW with that in six control villages (population 9397) that had only surface water. Both the bacterial counts and chemical properties of the DWTW met established hygiene standards for drinking water. The incidence of EID in the study region was 38.6% lower than in the control region; however, the introduction of DWTW supplies did not significantly affect the incidence of bacillary dysentery. These results indicate that the construction and use of DWTW systems with household taps is associated with decreased incidences of El Tor cholera, viral hepatitis A, and acute watery diarrhoea. Since high construction costs have led many authorities to question the value of DWTW, we carried out a cost-benefit analysis of the programme. The cost of constructing a DWTW system averaged US $36,000 at 1983 prices, or US $10.50 per capita. The combined capital and operating costs of a DWTW system were US $1.46 per capita per annum over its 20-year estimated life. The benefits derived from reductions in cost of illness and savings in time to fetch water were 2.2 times the costs at present values Capital outlays were recouped in a 3.6-year payback period and the provision of DWTW proved highly beneficial in both economic and social terms.

Health and economic impacts of antimicrobial resistance.

For comparison of the impacts of infections due to antimicrobial-resistant bacteria with those of infections due to antimicrobial-susceptible strains of the same bacteria, data were evaluated from 175 published and unpublished reports of investigations of nosocomial and community-acquired infections with selected bacteria. The evaluation of outcomes of hospital-acquired infections with resistant organisms was often confounded by risk factors also associated with poor outcomes. Nevertheless, for both nosocomial and community-acquired infections, the mortality, the likelihood of hospitalization, and the length of hospital stay were usually at least twice as great for patients infected with drug-resistant strains as for those infected with drug-susceptible strains of the same bacteria. Poor outcomes could be attributed both to the expected effects of ineffective antimicrobial therapy and to the unexpected occurrence of drug-resistant infections complicated by prior antimicrobial therapy for other medical problems. Although the adverse economic and health effects of drug-resistant bacterial infections can only be roughly quantified, it is concluded that antimicrobial resistance is an important health problem and an economic burden to society.

Interruption of shigellosis by hand washing.

High attack rates, increasing resistance to antibiotics and high mortality make shigellosis a serious problem. As Shigella is associated with poor hygiene we examined the effectiveness of a simple intervention, washing hands with soap and water, in checking the spread of the disease. The study population was comprised of confirmed cases of shigellosis. These and matched controls were followed up for 10 days. Several pieces of soap and earthenware pitchers for storing water were provided to the study families and they were advised to wash their hands with soap and water after defaecation and before meals. Compliance was monitored daily by observing the size of the soap and residual water. Rectal swabs of contacts of both the groups were obtained for culture. The secondary infection rate was 10.1% in the study group and 32.4% in the control group. The secondary case (symptomatic) rate was 2.2% in the study group and 14.2% in the control group. These results suggest that hand-washing has a positive interrupting effect, even in unsanitary environments.