Dataset Information

The Immunoglobulin M-Shed Acute Phase Antigen (SAPA)-test for the Early Diagnosis of Congenital Chagas Disease in the Time of the Elimination Goal of Mother-to-Child Transmission.

ABSTRACT:

Background

Diagnosis of congenital Chagas disease (CChD) in most endemic areas is based on low-sensitive microscopy at birth and 9-month immunoglobulin G (IgG), which has poor adherence. We aim to evaluate the accuracy of the Immunoglobulin M (IgM)-Shed Acute Phase Antigen (SAPA) test in the diagnosis of CChD at birth.

Methods

Two cohort studies (training and validation cohorts) were conducted in 3 hospitals in the department of Santa Cruz, Bolivia. Pregnant women were screened for Chagas disease, and all infants born to seropositive mothers were followed for up to 9 months to diagnose CChD. A composite reference standard was used to determine congenital infection and was based on the parallel use of microscopy, quantitative polymerase chain reaction (qPCR), and IgM-trypomastigote excreted-secreted antigen (TESA) blot at birth and/or 1 month, and/or the detection of anti-Trypanosoma cruzi IgG at 6 or 9 months. The diagnostic accuracy of the IgM-SAPA test was calculated at birth against the composite reference standard.

Results

Adherence to the 6- or 9-month follow-up ranged from 25.3% to 59.7%. Most cases of CChD (training and validation cohort: 76.5% and 83.7%, respectively) were detected during the first month of life using the combination of microscopy, qPCR, and/or IgM-TESA blot. Results from the validation cohort showed that when only 1 infant sample obtained at birth was evaluated, the qPCR and the IgM-SAPA test have similar accuracy (sensitivity: range, 79.1%-97.1% and 76.7%-94.3%, respectively, and specificity: 99.5% and 92.6%, respectively).

Conclusions

The IgM-SAPA test has the potential to be implemented as an early diagnostic tool in areas that currently rely only on microscopy.

SUBMITTER: Castro-Sesquen YE

PROVIDER: S-EPMC8282310 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundDetection of congenital T. cruzi transmission is considered one of the pillars of control programs of Chagas disease. Congenital transmission accounts for 25% of new infections with an estimated 15,000 infected infants per year. Current programs to detect congenital Chagas disease in Latin America utilize microscopy early in life and serology after 6 months. These programs suffer from low sensitivity by microscopy and high loss to follow-up later in infancy. We developed a Chagas urine nanoparticle test (Chunap) to concentrate, preserve and detect T. cruzi antigens in urine for early, non-invasive diagnosis of congenital Chagas disease.Methodology/principal findingsThis is a proof-of-concept study of Chunap for the early diagnosis of congenital Chagas disease. Poly N-isopropylacrylamide nano-particles functionalized with trypan blue were synthesized by precipitation polymerization and characterized with photon correlation spectroscopy. We evaluated the ability of the nanoparticles to capture, concentrate and preserve T. cruzi antigens. Urine samples from congenitally infected and uninfected infants were then concentrated using these nanoparticles. The antigens were eluted and detected by Western Blot using a monoclonal antibody against T. cruzi lipophosphoglycan. The nanoparticles concentrate T. cruzi antigens by 100 fold (western blot detection limit decreased from 50 ng/ml to 0.5 ng/ml). The sensitivity of Chunap in a single specimen at one month of age was 91.3% (21/23, 95% CI: 71.92%-98.68%), comparable to PCR in two specimens at 0 and 1 month (91.3%) and significantly higher than microscopy in two specimens (34.8%, 95% CI: 16.42%-57.26%). Chunap specificity was 96.5% (71/74 endemic, 12/12 non-endemic specimens). Particle-sequestered T. cruzi antigens were protected from trypsin digestion.Conclusion/significanceChunap has the potential to be developed into a simple and sensitive test for the early diagnosis of congenital Chagas disease.

Project description:BackgroundRetention along the elimination of Mother to Child Transmission (eMTCT) cascade in Uganda remains poor as only 62.7%-69.5% are followed up to 18months. The objective of this study was to determine the rates of retention of mother-baby pairs at two levels of the eMTCT cascade (12 and 18 months) and associated factors.MethodsThis was a longitudinal analysis of 368 mother-baby pairs who were enrolled into the eMTCT program in Kaberamaido district from January 2013 to December 2018. Data was extracted from early infant diagnosis (EID) and mothers' ART registers, entered into Microsoft Excel and then exported to Stata statistical software package version 14.0 for management and analysis. Descriptive statistics such as mean and frequencies were computed at univariate level. At the bivariate level, Cox proportional hazard regression was performed to assess the level of association between the primary outcome and each independent variable, while Cox proportional hazard regression model was built at multivariate level to determine the factors independently associated with retention of mother-baby pairs in the eMTCT program.ResultsOf the 368 mothers enrolled into the study, their average age was 29.7years (SD = 6.6). Nearly two-thirds of the mothers were married/cohabiting, (n = 232, 63.0%). The 368 mother baby pairs were observed for a total time of 6340 person months, with majority, 349 (94.8%, 95%CI = 92.0-96.7) still active in eMTCT care, while 19(5.2%, 95%CI = 3.3-8.0) were lost to follow up at 12months. At 18 months, 323 (87.8%, 95%CI = 84.0-90.8) were active in eMTCT program while 45(12.2%, 95 CI = 9.2-16.0) were lost to follow up. At bivariate level, marital status, health facility level of enrolment, mothers' ART treatment supporter, and mothers' ART enrolment time were significantly associated with survival/lost to follow up (LTFU) of mother-baby pairs along the eMTCT cascade. At multivariable level, the mothers' time of ART initiation was significantly associated with survival/lost to follow up (LTFU) of mother-baby pairs at along the eMTCT cascade, with mothers-baby pairs who were initiated during the antenatal/post-natal periods having higher hazards of LTFU compared to those who initiated ART before Antenatal period (before pregnancy), aHR = 4.37(95%CI, 1.62-11.76, P = 0.003). Mother-baby pairs who were enrolled into the eMTCT program after the implementation of HIV test and treat policy (year 2017 and 2018) had higher hazards of LTFU as compared to those enrolled before the implementation of test and treat policy in Uganda (year 2013-2016), aHR = 2.22(95% CI, 1.15-4.30, P = 0.017). All the other factors had no significant association with lost to follow up and cascade completion at multivariate level.ConclusionThere was high level of retention of mother-baby pairs in the eMTCT program in Kaberamaido at 12 months, but it was suboptimal at 18months. ART initiation during the antenatal and/or post-natal period was significantly associated with suboptimal retention of mother-baby pairs along the eMTCT cascade.

Project description:BACKGROUND:Women of reproductive age living with HIV (WRLHIV), HIV-positive pregnant women, adolescent girls and young women (AGYW) are key populations for eliminating mother-to-child of HIV (eMTCT) in South Africa. We describe the geographical distribution of WRLHIV, their pregnant counterparts and AGYW for risk-adjusted allocation of eMTCT interventions. METHODS:For the year 2018, we triangulated data from the Thembisa Model with five routine HIV-related and demographic data sources to determine the distribution of WRLHIV (15-49 years) and AGYW (15-24 years) nationally and by province. Data analysed included total population estimates, number of live-births, live-births to HIV-positive women, age-specific HIV prevalence rates, intrauterine (IU)-transmission rates and IU-case rates/100 000 live-births. IU-transmission rates and IU-case rates were calculated from de-duplicated routine HIV test-data for neonates (aged <7days). Data de-duplication was achieved by a patient-linking algorithm that uses probabilistic matching of demographics (name, surname, date of birth), supplemented by manual matching to account for spelling errors. RESULTS:There were 58 million people in South Africa in 2018. Females (all ages) constituted 51% of the population. Women of reproductive age constituted 27% and AGYW constituted 8% of the total population. WRLHIV, AGYW living with HIV and HIV-positive pregnant women accounted for 7%, 0.8% and 0.4% of the total population respectively. Gauteng was the most populous province followed by KwaZulu-Natal, with Western Cape and Eastern Cape in third and fourth positions. The distribution of WRLHIV and AGYW followed a similar trend. However, Mpumalanga and Limpopo provinces had higher proportions of WRLHIV and AGYW living with HIV ahead of Western Cape. KwaZulu-Natal had the highest number of live-births to HIV-positive women. The national IU-transmission rate of <1% translated into 241 cases/100 000. While provincial IU-case rates were fairly similar at 179-325, districts IU-case rates varied, ranging from 87-415 cases/100 000 live-births. CONCLUSION:Findings suggest that the need for eMTCT interventions is greatest in Gauteng, KwaZulu-Natal, Western Cape and Eastern Cape. Limpopo and Mpumalanga provinces may require more HIV prevention and family planning services because of high fertility rates, high number of WRLHIV and AGYW living with HIV. eMTCT will require robust viral load monitoring among WRLHIV, pregnant and breastfeeding women. The national laboratory database can provide this service near-real time.

Project description:IntroductionHigh maternal HIV incidence contributes substantially to mother-to-child HIV transmission (MTCT) in some settings. Since 2006, HIV retesting during the third trimester and breastfeeding has been recommended by the World Health Organization in higher prevalence (≥5%) settings to reduce MTCT. However, many countries lack clarity on when and how often to retest pregnant and postpartum women to optimize resources and service delivery. We reviewed and characterized national guidelines on maternal retesting based on timing and frequency.MethodsWe identified 52 countries to represent variations in HIV prevalence, geography, and MTCT priority and searched available national MTCT, HIV testing and HIV treatment policies published between 2007 and 2017 for recommendations on retesting during pregnancy, labour/delivery and postpartum. Recommended retesting frequency and timing was extracted. Country HIV prevalence was classified as: very low (<1%), low (1% to 5%), intermediate (>5 to <15%) and high (≥15%). Women with unknown HIV status at delivery/postpartum were included in retesting guidelines.Results and discussionOverall, policies from 49 countries were identified; 51% from 2015 or later and most (n = 25) were from Africa. Four countries were high HIV prevalence, seven intermediate, sixteen low and twenty-two very low. Most (n = 31) had guidance on universal voluntary opt-out HIV testing at the first antenatal care (ANC) visit. Beyond the first ANC visit, the majority (78%, n = 38) had guidance on retesting; 22 recommended retesting all women with unknown/negative status, five only if unknown HIV status, three in pregnancy based on risk and eight combining these approaches. Retesting was universally recommended during pregnancy, labour/delivery, and postpartum for all high prevalence settings and four of seven intermediate prevalence settings. Five UNAIDS priority countries for EMTCT with low/very low HIV prevalence, but high/intermediate MTCT, had no guidance on retesting.ConclusionsRetesting guidelines for pregnant and postpartum women were ubiquitous in high prevalence countries and defined in some intermediate prevalence countries, but absent in some low HIV prevalence countries with high MTCT. Countries may require additional guidance on how to optimize maternal HIV testing and whether to prioritize retesting efforts or discontinue universal retesting based on HIV incidence. Research is needed to assess country-level guideline implementation and impact.