To estimate the global burden of congenital toxoplasmosis CT , which results from infection of pregnant women with Toxoplasma gondii. The authors systematically searched 9 major databases for published and unpublished sources and established direct contact with the authors of source materials. Searches were country-specific. To be included, studies had to report on the incidence of CT, on positivity to Toxoplasma -specific IgM in infants and pregnant women including seroconversion results or on positivity to Toxoplasma -specific IgG in the general population. Various modelling techniques were used, depending on the country-specific data available, to estimate the CT incidence and burden in each country.
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To estimate the global burden of congenital toxoplasmosis CT , which results from infection of pregnant women with Toxoplasma gondii. The authors systematically searched 9 major databases for published and unpublished sources and established direct contact with the authors of source materials. Searches were country-specific. To be included, studies had to report on the incidence of CT, on positivity to Toxoplasma -specific IgM in infants and pregnant women including seroconversion results or on positivity to Toxoplasma -specific IgG in the general population.
Various modelling techniques were used, depending on the country-specific data available, to estimate the CT incidence and burden in each country. These data were then synthesized into an estimate of the global incidence of CT and of the global burden of CT in disability-adjusted life years DALYs.
This was equivalent to a burden of 1. High burdens were seen in South America and in some Middle Eastern and low-income countries. Congenital toxoplasmosis poses a substantial burden of poor health globally. Toxoplasmosis should be included in future updates of the global burden of disease and the corresponding data should be used to support public health interventions to reduce disease burden.
Human infection can result from the ingestion or handling of undercooked or raw meat containing tissue cysts. Alternatively, it can result from direct contact with cats or from the consumption of water or food contaminated by oocysts excreted in the faeces of infected cats.
Congenital toxoplasmosis CT occurs in infants following maternal transmission. It can result in fetal death and abortion and in syndromes that include neurologic and neurocognitive deficits and chorioretinitis. In our systematic review we searched specifically for data on CT incidence in infants seropositivity to Toxoplasma -specific IgM or confirmed case series or on the rate of maternal transmission, from which to estimate the incidence of CT.
We also searched for country-specific data on seropositivity to Toxoplasma -specific IgM and IgG among women of reproductive age and in the general population, with and without age stratification. We used various models to estimate country-specific CT incidences from the data we obtained.
We sent the authors of retrieved publications an Excel Microsoft, Redmond, United States of America spreadsheet with data for them to check and amend as appropriate. We cross-checked any amendments suggested and incorporated them into our database where appropriate.
These search terms were also used in Russian, Spanish and Chinese in appropriate databases. Initially only publication dates between 1 January and 31 December with available abstract were used. Publications relating only to animal studies were excluded. If no data were available for a country, the search was repeated to include publications as early as The search was also widened in such cases by removing references to women of child-bearing age from the search terms.
Finally, during the preparation of the article, searches were repeated for countries with missing data for — We used an algorithm to select the best available evidence for each country Fig. From each source we extracted the following when available: incidence of CT, positivity to Toxoplasma -specific IgM in infants and in pregnant women, rate of seroconversion in pregnant women, and prevalence of CT in the general population, with and without age stratification; study period; study subjects; and sampling method where and how the subjects were selected.
No study was excluded on the basis of language. In countries where only one study was available, we used that study. When two or more publications with data of similar quality were available, we used the mean value given in the most recent publication and in the more valid studies and summed up the results of these, or we used the data in one publication to verify the estimates generated by the other s.
Where no data could be found, we extrapolated estimates from neighbouring countries from the same WHO region and in the same WHO mortality stratum. We entered all data extracted onto an Excel spreadsheet for further analysis. Because a variety of methods are used in toxoplasmosis surveillance globally, we used different methods depending on the type and quality of the data available.
In a few instances we were able to directly calculate the number of incident CT cases from reports of confirmed CT cases in a given country.
When the data pertained only to a sample of all possible cases, we used stochastic uncertainty analysis based on sample size as a proportion of the estimated number of births in the country. In the absence of recorded confirmed CT cases, it is possible to estimate the incidence of CT from serological surveys of infants at birth.
In the studies we analysed, blood was obtained by heel pricks or from the umbilical cord to measure Toxoplasma -specific IgM titres. Positive samples were usually confirmed with a second test because a single IgM test has poor positive predictive value. Data from such studies also needed to be adjusted for poor diagnostic sensitivity. Of these children, were diagnosed with CT during infancy but only were seropositive at birth, which shows that IgM testing at birth has a sensitivity of The presence of Toxoplasma -specific IgM in pregnant women indicates recent infection because IgM antibodies are relatively short-lived.
They can, however, remain detectable in blood for long after the pregnancy has ended. Using this approach, we estimated the probability that a pregnant woman who was IgM-positive had seroconverted during the pregnancy as being between Toxoplasma -specific IgG seroprevalence among women increases with age. Thus, the age-specific incidence of seroconversion in women can be estimated by using a logistic modelling approach across the group aged 15 to 50 years.
Demographic and age-stratified fertility data for each country and territory are available from the United States Census Bureau. The base year for the data used was For some countries only non-age-stratified seroprevalence reports were available. To estimate the proportion of seroconverting pregnant women who transmit toxoplasmosis to their offspring in utero, we identified manuscripts from the systematic review that contained data on cohorts of women who seroconverted during pregnancy.
This resulted in congenitally-infected infants, or a mean transmission rate of We used this mean transmission rate for both the IgM-positive pregnant women and for those who seroconverted during pregnancy, estimated from the formula relating increasing IgG seropositivity with increasing age. In one study from the United Kingdom of Great Britain and Northern Ireland, 9 the authors employed a systematic review of the published literature from the United Kingdom to estimate the national incidence of toxoplasmosis and used various data sources.
From this toxoplasmosis incidence we estimated the number of incident CT cases using the transmission rate described above. Some countries had no reported data for CT or any seroprevalence data. We had to model their data using data from neighbouring countries.
Other countries had sparse data that may not have been nationally representative. This was assessed by examining the target population reported, to check for non-random or biased sampling that included only certain populations.
In cases in which the data were sparse or of poor quality and in which alternative data were not available, we assumed a much greater uncertainty surrounding CT incidence and prevalence estimates. Wherever possible, we adjusted observed prevalences in accordance with the reported performance of the diagnostic test employed. We obtained the sensitivity and specificity of the diagnostic tests from either the original study, from the test manufacturer or from other reports in which the same test had been used.
In many studies in which the diagnostic test had poor positive predictive value, false positives were largely eliminated by using a secondary confirmatory test and follow-up. Thus, when we used data from such studies we only had to adjust for the sensitivity of the test. YLL is the number of years lost on account of death, and YLD is the number of years lived with a disability, weighted by a factor between 0 and 1 for the severity of the disability.
The duration of all sequelae of CT was considered to be lifelong, with the exception of a fraction of the cases of chorioretinitis, in which the onset of clinical signs can occur at a mean age of approximately 10 years, according to the evidence. The incidence of sequelae for all regions except the Region of the Americas was calculated as suggested in a previous study. There is considerable parasite polymorphism in South America.
We used the same disease model as reported in a previous paper. Only the most severe disability weight was given to any one case. Thus, an infant with both chorioretinits and severe central nervous system abnormalities was only given the weight for the latter.
This adjustment was important, for example, for South American cases, since most CT patients there appear to have chorioretinitis.
Data were obtained from Kortbeek et al. In the most recent GBD study the disability weight for impaired vision ranged from 0. This covers the range of vision deficits reported in the GBD study. Similarly, the DWs we used for neurological disorders seem consistent with the range of values suggested in that study.
We also looked for potentially biased data by examining the targeted populations reported in each study and checking for non-representative sampling such as sampling in an unrepresentative geographic region of a given country. For data with a score of 1 we modelled uncertainty on the sample size of the data. Data with higher bias scores were given progressively wider uncertainty limits.
Appropriate PERT distributions were used for parameters not bound between 0 and 1. For countries without data, we used uniform distributions, with the highest and lowest estimates representing the extremes of estimates for neighbouring countries.
Our search generated unique citations, including those found in the reference lists of papers found through the systematic review and additional materials supplied by the authors who were contacted.
Of this total, we retrieved publications and we used data from of these publications to estimate the incidence of CT in countries Fig. This included 41 publications — 30 published before and 11 after — that were identified when the search criteria were extended for specific countries with no data. All the citations we used are listed in the appendices. We were unable to retrieve data for 87 countries. Flowchart showing study selection for the review of the evidence surrounding congenital toxoplasmosis CT.
This amounted to an incidence rate of approximately 1. From the annual incidence, the global burden of CT was calculated to be 1. We have used all available evidence and various techniques to generate our data.
Hence, we believe that our estimates of the global burden of CT are robust. Most commonly we obtained CT incidence estimates from age-stratified seroprevalence data, which were the most widely available.
Although this approach has been used before, 8 , 22 — 25 it has at least two major disadvantages. First, infection pressure, or probability of exposure to T. In particular, children and adults can have different rates of seroconversion. Second, the evidence suggests that seroprevalence has decreased over the last few decades in high-income countries. However, we ameliorated this potential bias, since there was substantially more data from other sources in high-income countries, such as birth surveillance data.
In lower-income countries, on the other hand, there is less certain evidence of decreases in seroprevalence over time. Indeed, in Malaysia and the Russian Federation, seroprevalence appears to be increasing in the general population. Furthermore, in countries undergoing rapid industrialization, such as China, demand for meat has increased enormously, and this might increase the risk of exposure to T.
We adjusted the data in accordance with the known performance of the diagnostic tests used in the studies, while taking into account any secondary or confirmatory tests used.
Congenital toxoplasmosis is caused by transplacental acquisition of Toxoplasma gondii. Manifestations, if present, are prematurity, intrauterine growth restriction, jaundice, hepatosplenomegaly, myocarditis, pneumonitis, rash, chorioretinitis, hydrocephalus, intracranial calcifications, microcephaly, and seizures. Diagnosis is by serologic testing or PCR. Treatment is with pyrimethamine , sulfadiazine , and leucovorin. See also Toxoplasmosis in adults and Overview of Neonatal Infections.
The global burden of congenital toxoplasmosis: a systematic review
Congenital toxoplasmosis: Serology, PCR, parasite isolation and molecular characterization of Toxoplasma gondii. Venturini 2. Congenital toxoplasmosis diagnosis in the newborn is a very important issue due to the need for early treatment to prevent future sequels. In this study we have evaluated the different diagnostic tests used in 67 congenital exposed newborns, including serological tests, PCR, parasite isolation and molecular characterization.