The cost of typhoid illness in low- and middle-income countries, a scoping review of the literature.

Typhoid fever is responsible for a substantial health burden in low- and middle-income countries (LMICs). New means of prevention became available with the prequalification of typhoid conjugate vaccines (TCV) by the World Health Organization (WHO) in 2018. Policymakers require evidence to inform decisions about TCV. The economic burden related to typhoid fever can be considerable, both for healthcare providers and households, and should be accounted for in the decision-making process. We aimed to understand the breadth of the evidence on the cost of typhoid fever by undertaking a scoping review of the published literature. We searched scientific databases with terms referring to typhoid fever cost of illness to identify published studies for the period January 1st 2000 to May 24th 2024. We also conferred with stakeholders engaged in typhoid research to identify studies pending completion or publication. We identified 13 published studies reporting empirical data for 11 countries, most of them located in Asia. The total cost of a typhoid episode ranged from $23 in India to $884 in Indonesia (current 2022 United States Dollar [USD]). Household expenditures related to typhoid fever were characterized as catastrophic in 9 studies. We identified 5 studies pending completion or publication, which will provide evidence for 9 countries, most of them located in Africa. Alignment in study characteristics and methods would increase the usefulness of the evidence generated and facilitate cross-country and regional comparison. The gap in evidence across regions should be mitigated when studies undertaken in African countries are published. There remains a lack of evidence on the cost to treat typhoid in the context of increasing antimicrobial resistance. Decision-makers should consider the available evidence on the economic burden of typhoid, particularly as risk factors related to antimicrobial resistance and climate change increase typhoid risk. Additional studies should address typhoid illness costs, using standardized methods and accounting for the costs of antimicrobial resistance.

Linking epidemiological and genomic data in cases of enteric fever in England to inform clinical management and public health action.

OBJECTIVES: To explore the feasibility of linking data from enhanced surveillance patient questionnaires from each enteric fever case in England with genome sequencing data, including antimicrobial resistance (AMR) profiles, from the corresponding isolate of typhoidal salmonellae. METHODS: After linking data we interrogated the merged dataset and assessed the utility of passive surveillance data to match and monitor antimicrobial treatment regimens in enteric fever patients with the AMR profiles of the infectious agent. RESULTS: A high proportion of cases were given antibiotics (n = 1230/1415; 86.9%); half of the cases stated the class of antibiotic they were given (n = 630/1239) and half were prescribed cephalosporins (n = 316/630). Reported treatment with a combination of antibiotics increased with symptom severity. Nearly half of isolates (n = 644/1415; 45.5%) had mutations conferring resistance to ciprofloxacin. Based on genome-derived AMR profiles, typhoidal salmonellae isolates inferred to be susceptible to the recommended first-line antimicrobials were twice as likely to be isolated from individuals residing in the least deprived areas compared with the most deprived (n = 26/169; 15.4% versus n = 32/442; 7.2%). CONCLUSIONS: Due to the high proportion of missing data obtained from patient interviews, we recommend a more transparent and systematic approach to recording the antibiotic prescription details by healthcare professionals in primary and secondary care. A more robust approach to data capture at this point in the care pathway would enable us to audit inconsistencies in the prescribing algorithms across England and ensure equitable treatment across all sections of society. Integrating prescribing data with the genome-derived AMR profiles of the causative agent at the individual patient level provides an opportunity to monitor the impact of treatment on clinical outcomes, and to promote best practice in real time.

The increasing healthcare burden of enteric fever in a low-incidence setting.

OBJECTIVES: Enteric fever carries appreciable morbidity in non-endemic settings, particularly in returned travelers. This study aimed to characterize the healthcare burden of enteric fever in a low-incidence setting and to identify risk factors and opportunities for preventative interventions. METHODS: Analysis of a retrospective case series from a tertiary pediatric center (2015-2019), augmented by public health notification and microbiological laboratory data (2018-2019), from Western Sydney, Australia, a region with frequent travel links to South Asia. RESULTS: Eighty-nine (89) patients were diagnosed with enteric fever, including 43 children with complete demographic and travel data. Enteric fever cases increased over time (by 4.9 % per year) and incidence was three times higher in the pediatric population (<15 years old) compared to adults. Travel to India and visiting friends and relatives (VFR) travel were risk factors. Few children received enteric fever vaccination prior to travel, as pre-travel advice most commonly was not sought. CONCLUSIONS: Children visiting relatives in high-incidence countries are increasingly at risk for enteric fever, particularly when travelling to South Asia. Targeted health advice to travelers visiting friends and relatives is warranted to mitigate the healthcare burden of enteric fever in low-incidence settings.

Cost-effectiveness and public health impact of typhoid conjugate vaccine introduction strategies in Bangladesh.

PURPOSE: Typhoid fever causes substantial morbidity and mortality in Bangladesh. The government of Bangladesh plans to introduce typhoid conjugate vaccines (TCV) in its expanded program on immunization (EPI) schedule. However, the optimal introduction strategy in addition to the costs and benefits of such a program are unclear. METHODS: We extended an existing mathematical model of typhoid transmission to integrate cost data, clinical incidence data, and recently conducted serosurveys in urban, semi-urban, and rural areas. In our primary analysis, we evaluated the status quo (i.e., no vaccination) and eight vaccine introduction strategies including routine and 1-time campaign strategies, which differed by age groups targeted and geographic focus. Model outcomes included clinical incidence, seroincidence, deaths, costs, disability-adjusted life years (DALYs), and incremental cost-effectiveness ratios (ICERs) for each strategy. We adopted a societal perspective, 10-year model time horizon, and 3 % annual discount rate. We performed probabilistic, one-way, and scenario sensitivity analyses including adopting a healthcare perspective and alternate model time horizons. RESULTS: We projected that all TCV strategies would be cost saving compared to the status quo. The preferred strategy was a nationwide introduction of TCV at 9-12 months of age with a single catch-up campaign for children ages 1-15, which was cost saving compared to all other strategies and the status quo. In the 10 years following implementation, we projected this strategy would avert 3.77 million cases (95 % CrI: 2.60 - 5.18), 11.31 thousand deaths (95 % CrI: 3.77 - 23.60), and save $172.35 million (95 % CrI: -14.29 - 460.59) compared to the status quo. Our findings were broadly robust to changes in parameter values and willingness-to-pay thresholds. CONCLUSIONS: We projected that nationwide TCV introduction with a catch-up campaign would substantially reduce typhoid incidence and very likely be cost saving in Bangladesh.

Salmonella Typhi: A Review of Antibiogram Journey in Developing Countries.

BACKGROUND: Typhoid fever poses a significant health challenge in low- and middleincome countries (LMiCs), impacting millions of individuals across various age groups. Its prevalence is particularly pronounced in South Asia. Factors contributing to its transmission in South Asia include rapid unplanned urbanization, urban-rural disparities, provision of poor water and sanitation facilities, and open defecation. The mortality rate of typhoid fever is up to 1%, and those who survive have a protracted period of poor health and carry an enormous financial burden. The treatment is further complicated by the emerging antibiotic resistance leaving few treatment options in hands. This issue has become more urgent due to the further emergence of extended drug-resistant (XDR) and multidrug-resistant (MDR) typhoid strains, as well as their subsequent global spread. Fluoroquinolone-resistant Salmonella spp. is currently classified by the World Health Organization (WHO) as a high (Priority 2) pathogen. As a result, establishing minimum inhibitory concentrations (MIC) according to the latest guidelines may prove effective in treating typhoid fever and minimizing the rising threat of drug resistance.

Typhoid Fever and Non-typhoidal Salmonella Outbreaks: A Portrait of Regional Socioeconomic Inequalities in Brazil.

Typhoid fever occurs in an endemic form in Brazil and is a serious public health problem in some regions. In this scenario, further research is urgently needed to identify the associations between socioeconomic factors and typhoid fever, contributing to guiding policy decisions in the country. We aimed to investigate the influence of socioeconomic disparities on the prevalence of typhoid fever and non-typhoidal Salmonella (NTS) in Brazil. A search for data from 2010 to 2019 was carried out with the national health and human development agencies. As milk and derivatives are the fourth food incriminated in food outbreaks in Brazil, analyses for detecting Salmonella spp. in commercial dairy products allowed us to assess whether the outbreaks associated with these foods are due to inadequacies in sanitary control in dairy establishments or whether they are mainly home-based outbreaks. Predictive models validated by the bootstrapping method demonstrate an association of NTS prevalence reduction with improvements in the Sanitation Service Index (Rv ≥ -8 0.686; p ≤ 0.01) and Municipal Human Development Index - MHDI - (Rv = -0.789; p ≤ 0.02). In the North, typhoid fever prevalence had seasonal variability with the rainfall, while sanitation services (Rv ≥-0.684; p ≤ 0.04) and MHDI (Rv ≥-0.949; p ≤ 0.003) directly influenced Northeast and South Brazil. Thus, the unequal distribution of investments in the sanitation sector contributed to disparities in typhoid fever prevalence among Brazilian regions. The absence of Salmonella spp. in commercial samples ratified the collected data that the outbreaks of Salmonella spp. in the Brazilian population occur mainly at residences. These findings show that implementing public health education and increasing investments in sanitation in regions with poor service can control outbreaks of Salmonella spp. in Brazilian endemic areas.

Avaliação da completitude dos registros de febre tifóide notificados no Sinan pela Bahia / Assessment of completion of typhoid fever notification forms registered at Sinan by health services in the state of Bahia

Este estudo avaliou a completitude das fichas de investigação epidemiológica (FIE) de Febre Tifóide, na Bahia (2003-2006), e discutiu implicações para a vigilância e perfil epidemiológico da doença, tendo o Sistema de Informação de Agravos de Notificação (Sinan) e prontuários médicos como fontes de dados. O indicador empregado foi a proporção de cada campo preenchido, classificado como excelente (>90 por cento); regular (70 por cento-89 por cento) ou de baixa (<70 por cento) completitude. A maioria dos campos apresentou regular (70 por cento-89 por cento) ou baixa (<70 por cento) completitude. Somente nas variáveis de identificação verificou-se 100 por cento de completitude. Foram estatisticamente significantes as diferenças entre antes e após o encerramento de casos pendentes referentes ao número de casos confirmados (aumento anual médio de 15 por cento, em 2004-2006) e as proporções de FIE cujo campo “classificação final”encontrava-se preenchido (de 81,9 por cento em 2003 e 67,0 por cento em 2005, para 89,5 por cento e 77,6 por cento, nesses mesmos anos). O estudo evidenciou a necessidade de investimentos na melhoria do preenchimento das FIE da febre tifóide na Bahia e esclarecimento dos profissionais de saúde sobre a importância da informação.

This study assessed the filling out of typhoid fever epidemiological investigation forms (EIF) from 2003 to 2006 in the State of Bahia, Brazil and indicated its impact on surveillance and epidemiological profile of the disease. Data consisted of cases registered in the Information System for Notifiable Diseases (Sinan) and hospital medical records. The indicator used was each field completion rate which was classified as excellent (>90 percent), average (70 percent-89 percent) or low (<70 percent). Completion of variables ranged mostly from average (70 percent-89 percent) to low (< 70 percent) and only identification data were fulfilled 100 percent. Statistically significant differences were observed comparing data before and after resolving pending cases (with a 15 percent average annual increase of confirmed cases from 2004 to 2006). Also, the percentage of completion of the “final classification” field increased from 81.9 percent to 89.5 percent in 2003 and from 67.0 percent to 77.6 percent in 2005). Findings show the need to invest on data quality improvement related to the completion of all fields of typhoid fever investigation forms in Bahia and to instruct professionals on the importance of health information.

Efecto de una campaña de prevención de cólera en la diarrea aguda de lactantes / Effects of a cholera preventive campaign in infant acute diarrhea

Mientras la morbilidad detectada y la evolución nutricional de lactantes seleccionados por un predictor de riesgo de enfermar estaban siendo investigados mediante estudios de seguimiento, consecutivos, entre los años 1989 y 1992 en una población de bajos recursos socioeconómicos de Santiago metropolitano, en 1991 aparecieron casos de cólera en el país, lo que motivó una intensa campaña educativa, preventiva. Como una forma de evaluarla, se compararon los resultados, con respecto a enfermedad diarreica, antes (grupo 1, n:49) y después de su aplicación (grupo 2, n:44) entre los lactantes del seguimiento aludido. La incidencia mensual y duración de los episodios de diarrea disminuyó significativamente después de la campaña (p<0,001 y p<0,015, respectivamente). Las madres consultaron precozmente (p<0,023) y aumentó la automedicación (de 2,1 por ciento a 12,5 por ciento). No se observó aumento del uso de sales de rehidratación oral. Los enteropatógenos identificados durante los episodios no variaron y no se aisló V. cholerae antes ni después de la campaña. En conclusión, la campaña disminuyó la frecuencia y duración de la enfermedad diarreica en este grupo de mayor riesgo, incluso más que intervenciones previas especialmente diseñadas con este propósito