Prevention of congenital toxoplasmosis in France using prenatal screening: A decision-analytic economic model.

BACKGROUND: Toxoplasma gondii is one of the world's most common parasites. Primary infection of the mother during pregnancy can lead to transmission to the fetus with risks of brain and eye lesions, which may cause lifelong disabilities. France instituted a national program based on monthly retesting of susceptible pregnant women to reduce the number of severe cases through prompt antenatal and postnatal treatment and follow-up. OBJECTIVE: To evaluate the ability of the French prenatal retesting program to reduce the lifetime costs of congenital toxoplasmosis. METHODS: We measured and then compared the costs and benefits of screening vs. not screening using decision-tree modelling. It included direct and indirect costs to society of treatment and care, and the lifetime lost earnings of children and caregivers. A probabilistic sensitivity analysis was carried out. FINDINGS: Total lifetime costs per live born child identified as congenitally infected were estimated to be €444 for those identified through prenatal screening vs €656 for those who were not screened. Estimates were robust to changes in all costs of diagnosis, treatment, and sequelae. INTERPRETATION: Screening for the prevention of the congenital T. gondii infection in France is cost saving at €212 per birth. Compared with no screening, screening every pregnant woman in France for toxoplasmosis in 2020 would have saved the country €148 million in addition to reducing or eliminating the devastating physical and emotional suffering caused by T. gondii. Our findings reinforce the conclusions of other decision-analytic modelling of prenatal toxoplasmosis screening.

Effectiveness of self-care interventions for integrated morbidity management of skin neglected tropical diseases in Anambra State, Nigeria.

BACKGROUND: Lymphatic filariasis (LF), Buruli ulcer (BU) and leprosy are neglected tropical diseases (NTDs) of the skin co-endemic in some communities in Nigeria. Not enough is known about the effectiveness of integrated morbidity management and disability prevention in people with these conditions. An integrated self-care intervention was carried out for people with these skin NTDs in two endemic communities of Anambra state, Nigeria. The objective of the study was to assess the effectiveness of self-care practices on costs of care, disability status and health-related quality of life. METHODS: This study utilised a quasi-experimental pre-test/post-test design to assess the effectiveness of the self-care interventions for people affected by NTDs to care for these impairments at home. Data were collected using questionnaires administered at the beginning and at the end of the intervention on monthly cost of morbidity care, and on participants' disability status and their quality of life (QoL). Focus group discussions (FGDs) were held with both the participants and healthcare workers at follow-up. RESULTS: Forty-eight participants were recruited. Thirty participants (62.5%) continued the self-care interventions until the end of the project. Of those, 25 (83%) demonstrated improvement from their baseline impairment status. The mean household costs of morbidity care per participant decreased by 66% after the intervention, falling from US$157.50 at baseline to US$53.24 after 6 months of self-care (p = 0.004). The mean disability score at baseline was 22.3; this decreased to 12.5 after 6 months of self-care (p < 0.001). Among the 30 participants who continued the interventions until the end of the project, 26 (86.7%) had severe disability score (i.e. a score of 10-46) at baseline, and the number with severe disability fell to 18 (60%) of the 30 after the intervention. The mean QoL score increased from 45.7 at baseline to 57.5 at the end of the intervention (p = 0.004). CONCLUSIONS: The 6-month self-care intervention for participants affected by BU, leprosy, or LF led to lower costs of care (including out-of-pocket costs and lost earnings due to morbidity), improved QoL scores, and reduced disability status. TRIAL REGISTRATION: ISRCTN Registry: ISRCTN20317241 ; 27/08/2021, Retrospectively registered.

Economic Costs and Benefits of Community-Based Lymphedema-Management Programs for Lymphatic Filariasis in India.

Lymphatic filariasis (LF) is endemic in 72 countries; 15 million persons live with chronic filarial lymphedema. It can be a disabling condition, frequently painful, leading to reduced mobility, social exclusion, and depression. The Global Program to Eliminate Lymphatic Filariasis aims to stop new infections and care for affected persons, but morbidity management has been initiated in only 38 countries. We examine economic costs and benefits of alleviating chronic lymphedema and its effects through simple limb care. We use economic and epidemiological data from 12 Indian states in which 99% of Indians with filariasis reside. Using census data, we calculate the age distribution of filarial lymphedema and predict the burden of morbidity of infected persons. We estimate lifetime medical costs and lost earnings due to lymphedema and acute dermatolymphangioadenitis (ADLA) with and without community-based limb-care programs. Programs of community-based limb care in all Indian endemic areas would reduce costs of disability by 52%, saving a per person average of US$2,721, equivalent to 703 workdays. Per-person savings are 185 times the program's per-person cost. Chronic lymphedema and ADLA impose a substantial physical and economic burden in filariasis-endemic areas. Low-cost programs for lymphedema management based on limb washing and topical medication are effective in reducing the number of ADLA episodes and stopping progression of disabling lymphedema. With reduced disability, people can work longer hours per day, more days per year, and in more strenuous, higher paying jobs, resulting in important economic benefits to themselves, their families, and their communities.

Economic benefits and costs of surgery for filarial hydrocele in Malawi.

BACKGROUND: Lymphatic filariasis (LF) is endemic in 72 countries of Africa, Asia, Oceania, and the Americas. An estimated 25 million men live with the disabling effects of filarial hydrocele. Hydrocele can be corrected with surgery with few complications. For most men, hydrocelectomy reduces or corrects filarial hydrocele and permits them to resume regular activities of daily living and gainful employment. METHODOLOGY AND PRINCIPAL FINDINGS: This study measures the economic loss due to filarial hydrocele and the benefits of hydrocelectomy and is based on pre- and post-operative surveys of patients in southern Malawi. We find the average number of days of work lost due to filarial hydrocele and daily earnings for men in rural Malawi. We calculate average annual lost earnings and find the present discounted value for all years from the time of surgery to the end of working life. We estimate the total costs of surgery. We compare the benefit of the work capacity restored to the costs of surgery to determine the benefit-cost ratio. For men younger than 65 years old, the average annual earnings loss attributed to hydrocele is US$126. The average discounted present value of lifetime earnings loss for those men is US$1684. The average budgetary cost of the hydrocelectomy is US$68. The ratio of the benefit of surgery to its costs is US$1684/US$68 or 24.8. Sensitivity analysis demonstrates that the results are robust to variations in cost of surgery and length of working life. CONCLUSION: The lifetime benefits of hydrocelectomy-to the man, his family, and his community-far exceed the costs of repairing the hydrocele. Scaling up subsidies to hydrocelectomy campaigns should be a priority for governments and international aid organizations to prevent and alleviate disability and lost earnings that aggravate poverty among the many millions of men with filarial hydrocele.

Congenital Chagas Disease in the United States: The Effect of Commercially Priced Benznidazole on Costs and Benefits of Maternal Screening.

Chagas disease, caused by Trypanosoma cruzi, is transmitted by insect vectors, and through transfusions, transplants, insect feces in food, and mother to child during gestation. An estimated 30% of infected persons will develop lifelong, potentially fatal cardiac or digestive complications. Treatment of infants with benznidazole is highly efficacious in eliminating infection. This work evaluates the costs of maternal screening and infant testing and treatment for Chagas disease in the United States, including the cost of commercially available benznidazole. We compare costs of testing and treatment for mothers and infants with the lifetime societal costs without testing and consequent morbidity and mortality due to lack of treatment or late treatment. We constructed a decision-analytic model, using one tree that shows the combined costs for every possible mother-child pairing. Savings per birth in a targeted screening program are $1,314, and with universal screening, $105 per birth. At current screening costs, universal screening results in $420 million in lifetime savings per birth-year cohort. We found that a congenital Chagas screening program in the United States is cost saving for all rates of congenital transmission greater than 0.001% and all levels of maternal prevalence greater than 0.06% compared with no screening program.

The cost-effectiveness of neonatal versus prenatal screening for congenital toxoplasmosis.

BACKGROUND: Congenital Toxoplasmosis (CT) can have severe consequences. France, Austria, and Slovenia have prenatal screening programs whereas some other countries are considering universal screening to reduce congenital transmission and severity of infection in children. The efficiency of such programs is debated increasingly as seroprevalence among pregnant women and incidence of congenital toxoplasmosis show a steady decrease. In addition, uncertainty remains regarding the effectiveness of pre- and postnatal treatments. METHOD: To identify cost-effective strategies, prenatal and neonatal screenings were compared using a decision-analytic model based on French guidelines and current knowledge of long-term evolution of the disease in treated children. Epidemiological data were extracted from the scientific literature and clinical data from the French Lyon cohort. Strategies were compared at one year of age, when infection can be definitively evaluated, and at 15 years of age, after which validated outcome data become scarce. The analysis was performed from the French Health Insurance System perspective and included direct medical costs for pregnant women and their children. RESULTS: The 1-year Incremental Cost-Effectiveness Ratio showed that prenatal screening would require investing €14,826 to avoid one adverse event (liveborn with CT, fetal loss, neonatal death or pregnancy termination) compared to neonatal screening. Extra investment increased up to €21,472 when considering the 15-year endpoint. CONCLUSIONS: Prenatal screening is cost-effective as compared to neonatal screening in moderate prevalence areas with predominant Type II strains. In addition, prenatal screening, by providing closer follow-up of women at risk increases the number of occasions for education avoiding toxoplasmosis.

Prevention and mitigation of congenital toxoplasmosis. Economic costs and benefits in diverse settings.

Congenital toxoplasmosis (CT), the result of a primary infection of pregnant women with Toxoplasma gondii which was transmitted to the fetus, may result in mild to deep injuries occurring in the newborn or later in its development or in adolescence. The visual and cognitive impairment that can result imposes substantial economic costs on the individual and society. Numerous observational studies favor the conclusion that, with preventive measures currently available, it is possible to reduce the incidence of infections in pregnant women, the incidence of fetal infection by preventing transplacental transmission, and the gravity of injury in infected newborns. Treatment of infected newborns can also reduce the severity of consequences and the frequency of their occurrence later in life. Prevention programs, however, are applied in only a few countries; in most countries implementation of a national prevention program has not been considered or has been thought to be too expensive. This article lists the methods of prevention of CT and describes existing national prevention programs in France and Austria. It analyzes the economic costs and benefits of maternal screening for CT prevention and mitigation for society and for health systems. The economic feasibility of implementing national screening in low-prevalence, high-cost countries is illustrated with the example of the United States. New diagnostic tools are discussed and the implication of lower costs is considered, for countries with well-established screening programs as well as those with inadequate prenatal care networks.

Congenital Chagas Disease in the United States: Cost Savings through Maternal Screening.

Chagas disease, caused by Trypanosoma cruzi, is transmitted by insect vectors through transfusions, transplants, insect feces in food, and from mother to child during gestation. Congenital infection could perpetuate Chagas disease indefinitely, even in countries without vector transmission. An estimated 30% of infected persons will develop lifelong, potentially fatal, cardiac or digestive complications. Treatment of infants with benznidazole is highly efficacious in eliminating infection. This work evaluates the costs of maternal screening and infant testing and treatment of Chagas disease in the United States. We constructed a decision-analytic model to find the lower cost option, comparing costs of testing and treatment, as needed, for mothers and infants with the lifetime societal costs without testing and the consequent morbidity and mortality due to lack of treatment or late treatment. We found that maternal screening, infant testing, and treatment of Chagas disease in the United States are cost saving for all rates of congenital transmission greater than 0.001% and all levels of maternal prevalence above 0.06% compared with no screening program. Newly approved diagnostics make universal screening cost saving with maternal prevalence as low as 0.008%. The present value of lifetime societal savings due to screening and treatment is about $634 million saved for every birth year cohort. The benefits of universal screening for T. cruzi as part of routine prenatal testing far outweigh the program costs for all U.S. births.

Congenital toxoplasmosis in Austria: Prenatal screening for prevention is cost-saving.

BACKGROUND: Primary infection of Toxoplasma gondii during pregnancy can be transmitted to the unborn child and may have serious consequences, including retinochoroiditis, hydrocephaly, cerebral calcifications, encephalitis, splenomegaly, hearing loss, blindness, and death. Austria, a country with moderate seroprevalence, instituted mandatory prenatal screening for toxoplasma infection to minimize the effects of congenital transmission. This work compares the societal costs of congenital toxoplasmosis under the Austrian national prenatal screening program with the societal costs that would have occurred in a No-Screening scenario. METHODOLOGY/PRINCIPAL FINDINGS: We retrospectively investigated data from the Austrian Toxoplasmosis Register for birth cohorts from 1992 to 2008, including pediatric long-term follow-up until May 2013. We constructed a decision-analytic model to compare lifetime societal costs of prenatal screening with lifetime societal costs estimated in a No-Screening scenario. We included costs of treatment, lifetime care, accommodation of injuries, loss of life, and lost earnings that would have occurred in a No-Screening scenario and compared them with the actual costs of screening, treatment, lifetime care, accommodation, loss of life, and lost earnings. We replicated that analysis excluding loss of life and lost earnings to estimate the budgetary impact alone. Our model calculated total lifetime costs of €103 per birth under prenatal screening as carried out in Austria, saving €323 per birth compared with No-Screening. Without screening and treatment, lifetime societal costs for all affected children would have been €35 million per year; the implementation costs of the Austrian program are less than €2 million per year. Calculating only the budgetary impact, the national program was still cost-saving by more than €15 million per year and saved €258 million in 17 years. CONCLUSIONS/SIGNIFICANCE: Cost savings under a national program of prenatal screening for toxoplasma infection and treatment are outstanding. Our results are of relevance for health care providers by supplying economic data based on a unique national dataset including long-term follow-up of affected infants.

Point-of-care testing for Toxoplasma gondii IgG/IgM using Toxoplasma ICT IgG-IgM test with sera from the United States and implications for developing countries.

BACKGROUND: Congenital toxoplasmosis is a serious but preventable and treatable disease. Gestational screening facilitates early detection and treatment of primary acquisition. Thus, fetal infection can be promptly diagnosed and treated and outcomes can be improved. METHODS: We tested 180 sera with the Toxoplasma ICT IgG-IgM point-of-care (POC) test. Sera were from 116 chronically infected persons (48 serotype II; 14 serotype I-III; 25 serotype I-IIIa; 28 serotype Atypical, haplogroup 12; 1 not typed). These represent strains of parasites infecting mothers of congenitally infected children in the U.S. 51 seronegative samples and 13 samples from recently infected persons known to be IgG/IgM positive within the prior 2.7 months also were tested. Interpretation was confirmed by two blinded observers. A comparison of costs for POC vs. commercial laboratory testing methods was performed. RESULTS: We found that this new Toxoplasma ICT IgG-IgM POC test was highly sensitive (100%) and specific (100%) for distinguishing IgG/IgM-positive from negative sera. Use of such reliable POC tests can be cost-saving and benefit patients. CONCLUSIONS: Our work demonstrates that the Toxoplasma ICT IgG-IgM test can function reliably as a point-of-care test to diagnose Toxoplasma gondii infection in the U.S. This provides an opportunity to improve maternal-fetal care by using approaches, diagnostic tools, and medicines already available. This infection has serious, lifelong consequences for infected persons and their families. From the present study, it appears a simple, low-cost POC test is now available to help prevent morbidity/disability, decrease cost, and make gestational screening feasible. It also offers new options for improved prenatal care in low- and middle-income countries.

Economic Costs and Benefits of a Community-Based Lymphedema Management Program for Lymphatic Filariasis in Odisha State, India.

Lymphatic filariasis afflicts 68 million people in 73 countries, including 17 million persons living with chronic lymphedema. The Global Programme to Eliminate Lymphatic Filariasis aims to stop new infections and to provide care for persons already affected, but morbidity management programs have been initiated in only 24 endemic countries. We examine the economic costs and benefits of alleviating chronic lymphedema and its effects through a simple limb-care program. For Khurda District, Odisha State, India, we estimated lifetime medical costs and earnings losses due to chronic lymphedema and acute dermatolymphangioadenitis (ADLA) with and without a community-based limb-care program. The program would reduce economic costs of lymphedema and ADLA over 60 years by 55%. Savings of US$1,648 for each affected person in the workforce are equivalent to 1,258 days of labor. Per-person savings are more than 130 times the per-person cost of the program. Chronic lymphedema and ADLA impose a substantial physical and economic burden on the population in filariasis-endemic areas. Low-cost programs for lymphedema management based on limb washing and topical medication for infection are effective in reducing the number of ADLA episodes and stopping progression of disabling and disfiguring lymphedema. With reduced disability, people are able to work longer hours, more days per year, and in more strenuous, higher-paying jobs, resulting in an important economic benefit to themselves, their families, and their communities. Mitigating the severity of lymphedema and ADLA also reduces out-of-pocket medical expense.

Rush to judgment: the STI-treatment trials and HIV in sub-Saharan Africa.

INTRODUCTION: The extraordinarily high incidence of HIV in sub-Saharan Africa led to the search for cofactor infections that could explain the high rates of transmission in the region. Genital inflammation and lesions caused by sexually transmitted infections (STIs) were a probable mechanism, and numerous observational studies indicated several STI cofactors. Nine out of the ten randomized controlled trials (RCTs), however, failed to demonstrate that treating STIs could lower HIV incidence. We evaluate all 10 trials to determine if their design permits the conclusion, widely believed, that STI treatment is ineffective in reducing HIV incidence. DISCUSSION: Examination of the trials reveals critical methodological problems sufficient to account for statistically insignificant outcomes in nine of the ten trials. Shortcomings of the trials include weak exposure contrast, confounding, non-differential misclassification, contamination and effect modification, all of which consistently bias the results toward the null. In any future STI-HIV trial, ethical considerations will again require weak exposure contrast. The complexity posed by HIV transmission in the genital microbial environment means that any future STI-HIV trial will face confounding, non-differential misclassification and effect modification. As a result, it is unlikely that additional trials would be able to answer the question of whether STI control reduces HIV incidence. CONCLUSIONS: Shortcomings in published RCTs render invalid the conclusion that treating STIs and other cofactor infections is ineffective in HIV prevention. Meta-analyses of observational studies conclude that STIs can raise HIV transmission efficiency two- to fourfold. Health policy is always implemented under uncertainty. Given the known benefits of STI control, the irreparable harm from not treating STIs and the likely decline in HIV incidence resulting from STI control, it is appropriate to expand STI control programmes and to use funds earmarked for HIV prevention to finance those programmes.

Living with uncertainty.

The persistence of highly endemic parasitic, bacterial and viral diseases makes individuals and populations vulnerable to emerging and re-emerging diseases. Evaluating the role of multiple component, often interacting, causes of disease may be impossible with research tools designed to isolate single causes. Similarly, it may not be possible to identify statistically significant treatment effects, even for interventions known to be effective, when multiple morbidities are present. Evidence continues to accumulate that nutritional deficiencies, bacterial, viral and parasitic coinfections accelerate HIV transmission. Inclusion of antiparasitics and other beneficial interventions in HIV-prevention protocols is impeded by reliance on inappropriate methodologies. Lack of full scientific certainty is not a reason for postponing safe, cost-effective measures to prevent irreversible damage.

Maternal serologic screening to prevent congenital toxoplasmosis: a decision-analytic economic model.

OBJECTIVE: To determine a cost-minimizing option for congenital toxoplasmosis in the United States. METHODOLOGY/PRINCIPAL FINDINGS: A decision-analytic and cost-minimization model was constructed to compare monthly maternal serological screening, prenatal treatment, and post-natal follow-up and treatment according to the current French (Paris) protocol, versus no systematic screening or perinatal treatment. Costs are based on published estimates of lifetime societal costs of developmental disabilities and current diagnostic and treatment costs. Probabilities are based on published results and clinical practice in the United States and France. One- and two-way sensitivity analyses are used to evaluate robustness of results. Universal monthly maternal screening for congenital toxoplasmosis with follow-up and treatment, following the French protocol, is found to be cost-saving, with savings of $620 per child screened. Results are robust to changes in test costs, value of statistical life, seroprevalence in women of childbearing age, fetal loss due to amniocentesis, and to bivariate analysis of test costs and incidence of primary T. gondii infection in pregnancy. Given the parameters in this model and a maternal screening test cost of $12, screening is cost-saving for rates of congenital infection above 1 per 10,000 live births. If universal testing generates economies of scale in diagnostic tools-lowering test costs to about $2 per test-universal screening is cost-saving at rates of congenital infection well below the lowest reported rates in the United States of 1 per 10,000 live births. CONCLUSION/SIGNIFICANCE: Universal screening according to the French protocol is cost saving for the US population within broad parameters for costs and probabilities.

HIV and concurrent sexual partnerships: modelling the role of coital dilution.

BACKGROUND: The concurrency hypothesis asserts that high prevalence of overlapping sexual partnerships explains extraordinarily high HIV levels in sub-Saharan Africa. Earlier simulation models show that the network effect of concurrency can increase HIV incidence, but those models do not account for the coital dilution effect (non-primary partnerships have lower coital frequency than primary partnerships). METHODS: We modify the model of Eaton et al (AIDS and Behavior, September 2010) to incorporate coital dilution by assigning lower coital frequencies to non-primary partnerships. We parameterize coital dilution based on the empirical work of Morris et al (PLoS ONE, December 2010) and others. Following Eaton et al, we simulate the daily transmission of HIV over 250 years for 10 levels of concurrency. RESULTS: At every level of concurrency, our focal coital-dilution simulation produces epidemic extinction. Our sensitivity analysis shows that this result is quite robust; even modestly lower coital frequencies in non-primary partnerships lead to epidemic extinction. CONCLUSIONS: In order to contribute usefully to the investigation of HIV prevalence, simulation models of concurrent partnering and HIV epidemics must incorporate realistic degrees of coital dilution. Doing so dramatically reduces the role that concurrency can play in accelerating the spread of HIV and suggests that concurrency cannot be an important driver of HIV epidemics in sub-Saharan Africa. Alternative explanations for HIV epidemics in sub-Saharan Africa are needed.

Concurrent sexual partnerships do not explain the HIV epidemics in Africa: a systematic review of the evidence.

The notion that concurrent sexual partnerships are especially common in sub-Saharan Africa and explain the region's high HIV prevalence is accepted by many as conventional wisdom. In this paper, we evaluate the quantitative and qualitative evidence offered by the principal proponents of the concurrency hypothesis and analyze the mathematical model they use to establish the plausibility of the hypothesis.We find that research seeking to establish a statistical correlation between concurrency and HIV prevalence either finds no correlation or has important limitations. Furthermore, in order to simulate rapid spread of HIV, mathematical models require unrealistic assumptions about frequency of sexual contact, gender symmetry, levels of concurrency, and per-act transmission rates. Moreover, quantitative evidence cited by proponents of the concurrency hypothesis is unconvincing since they exclude Demographic and Health Surveys and other data showing that concurrency in Africa is low, make broad statements about non-African concurrency based on very few surveys, report data incorrectly, report data from studies that have no information about concurrency as though they supported the hypothesis, report incomparable data and cite unpublished or unavailable studies. Qualitative evidence offered by proponents of the hypothesis is irrelevant since, among other reasons, there is no comparison of Africa with other regions.Promoters of the concurrency hypothesis have failed to establish that concurrency is unusually prevalent in Africa or that the kinds of concurrent partnerships found in Africa produce more rapid spread of HIV than other forms of sexual behaviour. Policy makers should turn attention to drivers of African HIV epidemics that are policy sensitive and for which there is substantial epidemiological evidence.

Complexity, cofactors, and the failure of AIDS policy in Africa.

Global AIDS policy still treats HIV as an exceptional case, abstracting from the context in which infection occurs. Policy is based on a simplistic theory of HIV causation, and evaluated using outdated tools of health economics. Recent calls for a health systems strategy - preventing and treating HIV within a programme of comprehensive health care - have not yet influenced the silo approach of AIDS policy.Evidence continues to accumulate, showing that multiple factors, such as malnutrition, malaria and helminthes, increase the risk of sexual and vertical transmission of HIV. Moreover, complementary interventions that reduce viral load, improve immune response, and interrupt pathways of transmission could increase the effectiveness of antiretroviral drugs and other tools of AIDS policy.In health economics, the omission of estimates of increasing returns generated by disease or treatment synergies biases cost-effectiveness analysis against multiple, yet inexpensive, interventions. Current tools of cost-effectiveness analysis only identify local maxima in a complex landscape, and can play, at best, a marginal role in the epidemic, especially where it is already generalized.Cost-effectiveness analyses for HIV that are based on the wrong epidemiological model can generate Type III errors: we get precise answers to the wrong questions about how to intervene. To control the epidemic, AIDS policy needs to utilize an epidemiological model that reflects the interactions of biological as well as behavioural variables that determine the course of HIV epidemics around the world. Cost-effectiveness analysis can benefit from using economic concepts of externalities and increasing returns to incorporate disease interactions and beneficial treatment spillovers for coinfections in HIV-prevention policy.