Cost-effectiveness of prevention strategies against cervical cancer in women, Vientiane, Lao PDR

Introduction: En RDP Lao, le cancer du col de l’utérus est une des causes principales de morbidité et mortalité dues aux cancers. Le cancer du col peut être prévenu par des interventions de prévention primaire (vaccination) et secondaire (dépistage). Afin de réduire le fardeau de cette maladie, nous devrions considérer le coût et efficacité des diverses options de prévention pertinentes compte tenu des spécificités du contexte Lao. Objectives : l’objectif principal de ce travail est de simuler le coût-efficacité de stratégies préventives contre le cancer du col de l’utérus en RDP Lao. La thèse est basée sur trois études. La première étude a pour but de déterminer la sensibilité et la spécificité de la combinaison test à l’acide acétique (IVA) et frottis du col comme outil de dépistage. Ces paramètres ont été utilisés dans la troisième étude. La deuxième étude a pour but de déterminer le coût-efficacité de modalités de vaccination. La troisième étude a pour but de déterminer le coût-efficacité d'options de dépistage. Méthodologie : Une revue systématique et une méta-analyse ont été réalisées pour la première étude. Pour la deuxième et troisième étude, un modèle dynamique de la population a été établi pour refléter l’histoire naturelle du cancer du col de l’utérus. Le modèle a été calibré pour tenir compte de la structure d’âge de la population de la Capitale de Vientiane, ainsi que l'incidence du cancer du col de l’utérus et sa mortalité en RDP Lao. La principale issue d’intérêt était le coût incrémental des Années de vie ajustées pour l'incapacité (DALY), dans la perspective du système de santé publique. Le seuil utilisé pour définir si l'investissement requis devrait être considéré comme coût-efficace était celui proposé par l'OMS, soit un ratio coût-efficacité incrémental (ICER) de moins de un PNB per capita par DALY évité. Résultats : L’estimation moyenne de la sensibilité et de la spécificité de la combinaison des tests pour les cas de positivité (un de deux tests est positive) étaient de 0.87 (95% CI: 0.83-0.90) et 0.79 (95% CI: 0.63-0.89) respectivement. La deuxième étude a montré que la vaccination des jeunes filles âgées de 10 ans est très coût-efficace. Ajouter au programme de vaccination des jeunes filles un rattrapage vaccinal pour les femmes de 11 à 25 ans est plus coût-efficace qu'ajouter les garçons. Cependant, il faut augmenter l’âge maximal du rattrapage vaccinal à 75 si la couverture vaccinale est moins de 50% ou bien si la durée de protection du vaccin ou l’immunité naturelle ne dure pas plus que 10 ans ou si l’incidence de cancer du col de l’utérus est supérieure à 40% de l’estimation de Globocan, soit 17.5 cas pour 100 000 femmes. De plus, ajouter le dépistage à la vaccination des jeunes filles est une option plus coût-efficace que la vaccination seule. Parmi les stratégies de dépistage, l’IVA pour les femmes âgées de 30-65 ans tous les trois ans est l'option la plus coût-efficace. Elle est suivie par le test rapide de détection d’ADN-VPH tous les trois ans et la combinaison IVA-frottis conventionnel tous les cinq ans. La probabilité d'être coût-efficace pour ces stratégies est de 73%. Conclusion : Les décideurs devraient considérer d’étendre le programme de vaccination des jeunes filles actuellement mis en place à la capitale de Vientiane à l'ensemble du pays et de considérer l'ajout d’un composant de rattrapage vaccinal et un dépistage par IVA ou un test rapide de détection d’ADN-VPH.Introduction: In Lao PDR, cervical cancer is a leading cause of cancer morbidity and mortality. Cervical cancer can be prevented by primary (vaccination) and secondary (screening) interventions. To reduce the burden of this disease, we need to consider both the cost and effectiveness of the various prevention options that are relevant to the Lao context. Objectives: The main objective of this thesis is to simulate the cost-effectiveness of prevention strategies against cervical cancer in Lao PDR. The thesis is based on three studies. The first study aimed to determine the average sensitivity and specificity of combined Visual Inspection with Acetic Acid (VIA) and cytology testing. Theses parameters were used for the third study. The second study aimed to determine the cost-effectiveness of various vaccination modalities. The third study aimed to determine the cost-effectiveness of screening strategies. Methodology: A systematic review and a meta-analysis were conducted for the first study. For the second and third studies, a population-based compartment and dynamic model of the natural history of cervical cancer was built. The model was calibrated to the age structure of the Vientiane capital population, and the incidence and mortality rates of cervical cancer in Lao PDR. The main outcome of interest was the incremental cost per Disability-Adjusted Life Year (DALY) averted, under a public health care system perspective. The threshold for declaring an option very cost-effective was an Incremental cost-effectiveness ratio (ICER) lower than one GDP per capita per DALY averted, based on WHO recommendations. Results: The pooled estimates of the sensitivity and specificity of the combined VIA and cytology testing (with a positive result in at least one of them) were 0.87 (95% CI: 0.83-0.90) and 0.79 (95% CI: 0.63-0.89), respectively. The second study showed that a 10-year-old girl vaccination program is very cost-effective. Adding a catch-up vaccination element for 11-25 year old women to a girl vaccination program was more cost-effective than adding a boy vaccination component. However, the catch-up should be extended to a higher age if vaccination coverage is lower than 50% or if the duration of the natural immunity or the duration of vaccine protection is no longer than 10 years or if the incidence of cervical cancer is higher than 40% of the Globocan estimates, i.e 17.5 cases per 100 000 women. Additionally, adding a screening strategy to a girl vaccination program is more cost-effective than vaccination alone. Among the screening strategies, a three-yearly VIA screening program for 30-65 year-old women is the most cost-effective strategy, followed by the three-yearly rapid HPV DNA testing option and the five-yearly combined VIA and conventional cytology option, respectively. The probability of cost-effectiveness for these strategies is around 73%. Conclusion: Decision makers should consider expanding the girl vaccination program currently implemented in Vientiane capital nationwide and adding a catch-up vaccination element and a VIA or rapid HPV DNA testing program as appropriate

Lasting benefit of infant hepatitis B vaccination in adolescents in the Lao People’s Democratic Republic

Objectives Hepatitis B is endemic in Lao PDR with 8–10% of the adult population being chronically infected. We investigated the impact of hepatitis B vaccination on infection in adolescents born shortly before and after the introduction of the vaccine in 2001. Methods 779 students from Vientiane Capital and Bolikhamxay province were tested for HBV markers by ELISA. Socio-demographic information was collected with a standardized questionnaire. Predictors/risk factors for seroprotection or exposure to hepatitis B infection were assessed by bivariate and multivariable analyses. Results The prevalence of a serological vaccination profile increased significantly after the introduction of the vaccine (13.2%–21.9%, p < 0.05, in Vientiane; 3.0%–19.7%, p < 0.001, in Bolikhamxay), which translated into at least a 2-times lower prevalence of past infection. In logistic regression, older students in Bolikhamxay were less likely to be vaccinated and more likely to have been infected by HBV in the past. Conclusion Even though this study documented a sizable and lasting reduction in past hepatitis B infections in adolescents born after the introduction of infant hepatitis B vaccination, the overall levels of protective anti-HBs were low and warrant at least the introduction of a booster for adolescents. Furthermore, we suggest improving the coverage of the hepatitis B birth dose

Pertussis in Lao PDR: Seroprevalence and disease

Objectives Pertussis is a debilitating vaccine-preventable infection. The aim of this study was to determine susceptibility and exposure to pertussis in Lao PDR in different age groups and subpopulations. Methods A total 3072 serum samples were obtained from different cohorts: children with documented vaccination, pre-schoolers, schoolchildren, blood donors, healthcare workers (HCWs), and pregnant women and paired cord blood. Samples were tested for anti-pertussis toxin IgG antibodies. A history of Bordetella pertussis exposure was defined according to antibody titres. Four hundred and seventy-five throat swabs and nasopharyngeal aspirates were analysed by PCR for the presence of B. pertussis in symptomatic children at the Children's Hospital in Vientiane. Results Overall pertussis seroprevalence was 57.5%. The prevalence of titres indicating acute infection or recent vaccination or infection/vaccination within the last 12 months ranged from 7.4% (100/1356) in adults to 21.4% (25/117) in pre-schoolers (age 1–5 years). B. pertussis was detected in 1.05% (5/475) of children with respiratory symptoms in Vientiane Capital. Conclusions It is suggested that routine childhood vaccination, in particular outreach, as well as vaccination of HCWs should be strengthened. A childhood booster and vaccination of pregnant mothers should be considered. There is also a need to improve reporting and to introduce pertussis testing in at least one central facility

Potential lives saved in 73 countries by adopting multi-cohort vaccination of 9-14-year-old girls against human papillomavirus.

Up to 2016, low- and middle-income countries mostly introduced routine human papillomavirus (HPV) vaccination for just a single age-cohort of girls each year. However, high-income countries have reported large reductions in HPV prevalence following "catch-up" vaccination of multiple age-cohorts in the year of HPV vaccine introduction. We used the mathematical model PRIME to project the incremental impact of vaccinating 10- to 14-year-old girls compared to routine HPV vaccination only in the same year that routine vaccination is expected to be introduced for 9-year-old girls across 73 low- and lower-middle-income countries. Adding multiple age-cohort vaccination could increase the number of cervical cancer deaths averted by vaccine introductions in 2015-2030 by 30-40% or an additional 1.23-1.79 million over the lifetime of the vaccinated cohorts. The number of girls needed to vaccinate to prevent one death is 101 in the most pessimistic scenario, which is only slightly greater than that for routine vaccination of 9-year-old girls (87). These results hold even when assuming that girls who have sexually debuted do not benefit from vaccination. Results suggest that multiple age-cohort vaccination of 9- to 14-year-old girls could accelerate HPV vaccine impact and be cost-effective

Seroprotection at different levels of the healthcare system after routine vaccination with diphtheria-tetanus-pertussis whole cell--hepatitis B--haemophilus influenzae type B in Lao People’s Democratic Republic

Background The Lao People’s Democratic Republic continues to sustain a considerable burden of vaccine-preventable diseases because of incomplete vaccine coverage and weak vaccine responses. We have assessed seroconversion after routine vaccination with the pentavalent vaccine to capture weaknesses of vaccine management at the different levels of the healthcare system. Methods A total of 1151 children (aged 8–28 months) with 3 documented doses of the pentavalent vaccine delivered at central hospitals in Vientiane and the provincial hospital, 3 district hospitals, and 10 health centers in Bolikhamxay province were enrolled. Sociodemographic information was collected with a standardized questionnaire. Serum samples were analyzed for antibodies against vaccine components, and bivariate and multivariable analyses were performed to identify risk factors for low vaccine responses. Results Seroprotection rates at the provincial, district, and health center level were as high as in central hospitals, but seroprotection rates in areas covered by remote health centers were significantly lower. Protective levels also rapidly decreased with age at sampling. Seroprotection rates in Bolikhamxay against the different components reached 70%–77% and were up to 20% higher than in previous studies in the same region; 18.8% more children received the hepatitis B vaccine birth dose and the hepatitis B virus infection rate was 4 times lower. Conclusions Vaccine immunogenicity has dramatically improved in a central province, likely due to training and investment in the cold chain. Nevertheless, there remains a need to focus on the “last mile” in remote areas were most children are vaccinated through outreach activities

Modelling population dynamics and seasonal movement to assess and predict the burden of melioidosis.

BACKGROUND: Melioidosis is an infectious disease that is transmitted mainly through contact with contaminated soil or water, and exhibits marked seasonality in most settings, including Southeast Asia. In this study, we used mathematical modelling to examine the impacts of such demographic changes on melioidosis incidence, and to predict the disease burden in a developing country such as Thailand. METHODOLOGY/PRINCIPAL FINDINGS: A melioidosis infection model was constructed which included demographic data, diabetes mellitus (DM) prevalence, and melioidosis disease processes. The model was fitted to reported melioidosis incidence in Thailand by age, sex, and geographical area, between 2008 and 2015, using a Bayesian Markov Chain Monte Carlo (MCMC) approach. The model was then used to predict the disease burden and future trends of melioidosis incidence in Thailand. Our model predicted two-fold higher incidence rates of melioidosis compared with national surveillance data from 2015. The estimated incidence rates among males were two-fold greater than those in females. Furthermore, the melioidosis incidence rates in the Northeast region population, and among the transient population, were more than double compared to the non-Northeast region population. The highest incidence rates occurred in males aged 45-59 years old for all regions. The average incidence rate of melioidosis between 2005 and 2035 was predicted to be 11.42 to 12.78 per 100,000 population per year, with a slightly increasing trend. Overall, it was estimated that about half of all cases of melioidosis were symptomatic. In addition, the model suggested a greater susceptibility to melioidosis in diabetic compared with non-diabetic individuals. CONCLUSIONS/SIGNIFICANCE: The increasing trend of melioidosis incidence rates was significantly higher among working-age Northeast and transient populations, males aged ≥45 years old, and diabetic individuals. Targeted intervention strategies, such as health education and awareness raising initiatives, should be implemented on high-risk groups, such as those living in the Northeast region, and the seasonally transient population

Modeling household dynamics on Respiratory Syncytial Virus (RSV).

Respiratory Syncytial Virus (RSV) is the most common cause of respiratory tract infection in infants and children and shows increasing trend among elderly people worldwide. In many developing country settings, population and household structures have gone through some significant changes in the past decades, namely fewer births, more elderly population, and smaller household size but more RSV high-risk individuals. These dynamics have been captured in a mathematical model with RSV transmission dynamics to predict the disease burden on the detailed population for future targeted interventions. The population and disease dynamics model was constructed and tested against the hospitalization data for Acute Lower Respiratory Tract Infection due to RSV in rural Thai settings between 2005 and 2011. The proportion of extended families is predicted to increase by about 10% from 2005 to 2020, especially for those with elderly population, while the classic nuclear family type (with adults and children) will decline by about 10%. For RSV, infections from extended family type (approximately 60% of all household types) have majorly contributed to the force of infection (FOI). While the model predicted the increase of FOI from the extended family by 15% from 2005 to 2020, the FOI contributed by other household types would be either stable or decrease in the same time period. RSV incidence rate is predominantly high among babies (92.2%) and has been predicted to decrease slightly over time (from 940 to 864 cases per 100,000 population by 2020), while the incidence rates among children and elderly people may remain steadily low over the same period. However, the estimated incidence rates among elderly people were twice than those in children. The model predicts that approximately 60% of FOI for RSV will come from members of the extended family type. The incidence rate of RSV among children and elderly in extended families was about 20 times lower than that in infants and the trend is steady. Targeted intervention strategies, such as health education in some specific groups and targeted vaccination, may be considered, with the focus on extended family type. Target interventions on babies can lessen the transmission to children and elderly especially when transmission within households of extended family type is high

A Population Dynamic Model to Assess the Diabetes Screening and Reporting Programs and Project the Burden of Undiagnosed Diabetes in Thailand.

Diabetes mellitus (DM) is rising worldwide, exacerbated by aging populations. We estimated and predicted the diabetes burden and mortality due to undiagnosed diabetes together with screening program efficacy and reporting completeness in Thailand, in the context of demographic changes. An age and sex structured dynamic model including demographic and diagnostic processes was constructed. The model was validated using a Bayesian Markov Chain Monte Carlo (MCMC) approach. The prevalence of DM was predicted to increase from 6.5% (95% credible interval: 6.3-6.7%) in 2015 to 10.69% (10.4-11.0%) in 2035, with the largest increase (72%) among 60 years or older. Out of the total DM cases in 2015, the percentage of undiagnosed DM cases was 18.2% (17.4-18.9%), with males higher than females (p-value < 0.01). The highest group with undiagnosed DM was those aged less than 39 years old, 74.2% (73.7-74.7%). The mortality of undiagnosed DM was ten-fold greater than the mortality of those with diagnosed DM. The estimated coverage of diabetes positive screening programs was ten-fold greater for elderly compared to young. The positive screening rate among females was estimated to be significantly higher than those in males. Of the diagnoses, 87.4% (87.0-87.8%) were reported. Targeting screening programs and good reporting systems will be essential to reduce the burden of disease

Potential health and economic impacts of dexamethasone treatment for patients with COVID-19

Acknowledgements We thank all members of the COVID-19 International Modelling Consortium and their collaborative partners. This work was supported by the COVID-19 Research Response Fund, managed by the Medical Sciences Division, University of Oxford. L.J.W. is supported by the Li Ka Shing Foundation. R.A. acknowledges funding from the Bill and Melinda Gates Foundation (OPP1193472).Peer reviewedPublisher PD