Chikungunya virus (CHIKV) is an emerging arboviral infection with a global distribution and may cause fetal and neonatal infections after maternal CHIKV-infections during gestation. We performed a systematic review to evaluate the risk for: a) mother-to-child transmission (MTCT), b) antepartum fetal deaths (APFD), c) symptomatic neonatal disease, and d) neonatal deaths from maternal CHIKV-infections during gestation. We also recorded the neonatal clinical manifestations after such maternal infections (qualitative data synthesis). We searched PubMed (last search 3/2017) for articles, of any study design, with any of the above outcomes. We calculated the overall risk of MTCT, APFDs and risk of symptomatic neonatal disease by simple pooling. For endpoints with ≥5 events in more than one study, we also synthesized the data by random-effect-model (REM) meta-analysis. Among 563 identified articles, 13 articles from 8 cohorts were included in the quantitative data synthesis and 33 articles in the qualitative data synthesis. Most cohorts reported data only on symptomatic rather than on all neonatal infections. By extrapolation also of these data, the overall pooled-MTCT-risk across cohorts was at least 15.5% (206/1331), (12.6% by REMs). The pooled APFD-risk was 1.7% (20/1203); while the risk of CHIKV-confirmed-APFDs was 0.3% (3/1203). Overall, the pooled-risk of symptomatic neonatal disease was 15.3% (203/1331), (11.9% by REMs). The pooled risk of symptomatic disease was 50.0% (23/46) among intrapartum vs 0% (0/712) among antepartum/peripartum maternal infections. Infected newborns, from maternal infections during gestation were either asymptomatic or presented within their first week of life, but not at birth, with fever, irritability, hyperalgesia, diffuse limb edema, rashes and occasionally sepsis-like illness and meningoencephalitis. The pooled-risk of neonatal death was 0.6% (5/832) among maternal infections and 2.8% (5/182) among neonatal infections; long-term neurodevelopmental delays occurred in 50% of symptomatic neonatal infections. Published cohorts with data on the risk to the fetus and/or newborn from maternal CHIKV-infections during gestation were sparse compared to the number of recently reported CHIKV-infection outbreaks worldwide; however perinatal infections do occur, at high rates during intrapartum period, and can be related to neonatal death and long-term disabilities. Chikungunya virus (CHIKV) is an emerging arboviral infection with a global distribution and can cause infections of the fetus and newborn after maternal CHIKV-infections during gestation. In this systematic review, we evaluated the risk for mother-to-child transmission (MTCT), antepartum fetal deaths (APFD) and symptomatic neonatal disease from maternal CHIKV-infections during gestation. Whenever meaningful, we also synthesized the data by random-effect-model (REM) meta-analysis. We also recorded the list of clinical manifestations of neonatal infections after maternal infections during gestation. Overall, published cohorts with pertinent data to estimate the impact to the fetuses and newborns of maternal CHIKV-infections were sparse compared to the number of recently reported CHIKV-infection outbreaks worldwide. Most cohorts reported data only on symptomatic neonatal infections rather than on all (symptomatic and asymptomatic) neonatal infections. By extrapolation also of these data, the pooled MTCT-risk was at least 15.5% (206/1331), (12.6% by REMs). Symptomatic disease occurred almost exclusively with maternal infections around the time of delivery. Overall, the pooled risk of symptomatic disease was 15.3% (203/1331), (11.9% by REMs); however, the risk of symptomatic disease from intrapartum maternal infections was 50.0% (23/46) vs 0% (0/712) from antepartum/peripartum maternal infections. The pooled APFDs-risk was low (1.7%); however, APFDs occurred with maternal infections in all trimesters. Infected newborns were either asymptomatic or presented during their first week of life, but not at the time of birth, with manifestations such as fever, irritability, rashes, hyperalgesia syndrome, diffuse limb edema, bullous dermatitis and occasionally also meningoencephalitis. Long-term neurodevelopmental delays occurred in 50% of symptomatic neonatal infections.

Background: Accumulating evidence suggests that toxoplasmosis in immunocompetent hosts can be severe and life-threatening. Methods: We performed a systematic review of severe toxoplasmosis cases in immunocompetent patients to gain insight into the epidemiology, clinical characteristics, radiological findings, and outcomes of these cases. We classified severe toxoplasmosis as cases with the symptomatic involvement of target organs (the lungs, central nervous system (CNS), and heart), disseminated disease, prolonged disease (>3 months), or a fatal outcome. Our primary analysis focused on cases published from 1985–2022 to avoid confounding with cases in AIDS patients. Results: We identified 82 pertinent articles (1985–2022) with a total of 117 eligible cases; the top five countries for these cases were French Guiana (20%), France (15%), Colombia (9%), India (9%), and Brazil (7%). Overall, 44% (51/117) of cases had pulmonary involvement, 39% (46/117) CNS, 31% (36/117) cardiac, 24% (28/117) disseminated disease, 2% (2/117) had prolonged disease, and 8% (9/117) of patients died. More than one organ was involved in 26% (31/117) of cases. Eighty-four percent (98/117) of cases occurred in the context of a recent acute primary Toxoplasma infection; for the remaining, the exact timing of infection was unclear. Genotyping data were very sparse. Among those reporting genotyping data, 96% (22/23) were caused by atypical non-type II strains; one case was caused by a type-II strain. Only half of the cases reported risk factors. The most common risk factors were eating raw/undercooked meat or eating game meat (47% (28/60)), drinking untreated water (37% (22/60)), or living in a toxoplasmosis high-prevalence area (38% (23/60)). For the 51 pulmonary cases, the main clinical presentation was pneumonia or pleural effusions in 94% (48/51) and respiratory failure in 47% (24/51). For the 46 CNS cases, the main clinical presentation was encephalitis in 54% (25/46), meningitis in 13% (6/46), focal neurologic findings in 24% (11/46), cranial nerve palsies in 17% (8/46), Guillain–Barre syndrome or Miller Fisher syndrome in 7% (3/46), and Brown–Sequard syndrome in 2% (1/46) of cases; more than one clinical manifestation could also be present. Among the 41 CNS cases reporting the CNS imaging findings, 68% (28/41) had focal supratentorial lesions and 7% (3/41) had focal infratentorial lesions. Brain abscess-like/mass-like lesions were seen in 51% (21/41) of cases. For the 36 cardiac cases, the main clinical presentation was myocarditis in 75% (27/36), pericarditis in 50% (18/36), heart failure and/or cardiogenic shock in 19% (7/36), and cardiac arrhythmias in 22% (8/36); more than one manifestation could also be present. Illness was critical in 49% (44/90) of cases intensive care unit care was needed in 54% (29/54) of cases among those reporting this information, and 9 patients died. Conclusion: The diagnosis of severe toxoplasmosis in immunocompetent hosts can be challenging. Toxoplasmosis should be considered in the differential diagnosis of immunocompetent patients presenting with severe illness of unclear etiology with pulmonary, cardiac, CNS, or multiorgan involvement/failure, or prolonged febrile illness, even in the absence of common exposure risk factors or common manifestations of toxoplasmosis (e.g., fever, mononucleosis-like illness, lymphadenopathy, and chorioretinitis). Fatal outcomes can also rarely occur in immunocompetent patients. Prompt initiation of anti-Toxoplasma treatment can be lifesaving.

Background A potential link between toxoplasmosis with schizophrenia (SCZ) has been extensively studied over the past 2 decades. Our study was aimed to determine whether, beyond an association, the...

The cost of conventional serological testing for toxoplasmosis discourages universal adoption of prenatal monthly screening programs to prevent congenital toxoplasmosis. Point-of-care (POC) technology may constitute a cost-effective approach. We evaluated the diagnostic accuracy of 3 Toxoplasma POC tests against gold-standard testing performed at Palo Alto Medical Foundation Toxoplasma Serology Laboratory (PAMF-TSL). The POC tests included the following: Toxo IgG/IgM Rapid Test (Biopanda) and the OnSite Toxo IgG/IgM Combo-Rapid-test that detect IgG and IgM separately, and the Toxoplasma ICT-IgG-IgM-bk (LDBIO) that detects either or both immunoglobulin IgG/IgM in combination. Samples were selected from PAMF-TSL biobank (n = 210) and Centers for Disease Control and Prevention Toxoplasma 1998 Human Serum Panel (n = 100). Based on PAMF-TSL testing, Toxoplasma-infection status was classified in 4 categories: acute infections (n = 85), chronic infections (n = 85), false-positive Toxoplasma IgM (n = 60), and seronegative (n = 80). The POC testing was performed in duplicate following manufacturer’s instructions by investigators blinded to PAMF-TSL results. Sensitivity and specificity were calculated. A total of 1860 POC tests were performed. For detection of Toxoplasma IgG, sensitivity was 100% (170 of 170; 95% confidence interval [CI], 97.8%–100%) for all 3 POC kits; specificity was also comparable at 96.3% (77 of 80; 95% CI, 89.5%–98.9%), 97.5% (78 of 80; 95% CI, 91.3%–99.6%), and 98.8% (79 of 80; 95% CI, 93.2%–99.9%). However, sensitivity for detection of Toxoplasma IgM varied significantly across POC tests: Biopanda, 62.2% (51 of 82; 95% CI, 51.4%–71.9%); OnSite, 28% (23 of 82; 95% CI, 19.5%–38.6%); and LDBIO combined IgG/IgM, 100% (82 of 82; 95% CI, 95.5%–100%). Diagnostic accuracy was significantly higher for the LDBIO POC kit. The POC kits did not exhibit cross-reactivity for false-positive Toxoplasma-IgM sera. The 3 evaluated POC kits revealed optimal sensitivity for Toxoplasma-IgG antibodies. The LDBIO-POC test exhibited 100% sensitivity for the combined detection of IgG/IgM in acute and chronic Toxoplasma infection. Biopanda and Onsite POC tests exhibited poor sensitivity for Toxoplasma-IgM detection.

BACKGROUND: An important step toward improvement of the conduct of pediatric clinical research is the standardization of the ages of children to be included in pediatric trials and the optimal age-subgroups to be analyzed. METHODS: We set out to evaluate empirically the age ranges of children, and age-subgroup analyses thereof, reported in recent pediatric randomized clinical trials (RCTs) and meta-analyses. First, we screened 24 RCTs published in Pediatrics during the first 6 months of 2011; second, we screened 188 pediatric RCTs published in 2007 in the Cochrane Central Register of Controlled Trials; third, we screened 48 pediatric meta-analyses published in the Cochrane Database of Systematic Reviews in 2011. We extracted information on age ranges and age-subgroups considered and age-subgroup differences reported. RESULTS: The age range of children in RCTs published in Pediatrics varied from 0.1 to 17.5 years (median age: 5; interquartile range: 1.8–10.2) and only 25% of those presented age-subgroup analyses. Large variability was also detected for age ranges in 188 RCTs from the Cochrane Central Register of Controlled Trials, and only 28 of those analyzed age-subgroups. Moreover, only 11 of 48 meta-analyses had age-subgroup analyses, and in 6 of those, only different studies were included. Furthermore, most of these observed differences were not beyond chance. CONCLUSIONS: We observed large variability in the age ranges and age-subgroups of children included in recent pediatric trials and meta-analyses. Despite the limited available data, some age-subgroup differences were noted. The rationale for the selection of particular age-subgroups deserves further study.

OBJECTIVE: Compare the risk of harm from pharmacologic interventions in pediatric versus adult randomized controlled trials (RCTs). METHODS: We used systematic reviews from the Cochrane Database of Systematic Reviews. We considered separately 7 categories of harms/harm-related end points: severe harms, withdrawals due to harms, any harm, organ system–level harms, specific harms, withdrawals for any reason, and mortality. Systematic reviews with quantitative synthesis from at least 1 adult and 1 pediatric RCT for any of those end points were eligible. We calculated the summary odds ratio (experimental versus control intervention) in adult and pediatric trials/meta-analysis; the relative odds ratio (ROR) in adults versus children per meta-analysis; and the summary ROR (sROR) across all meta-analyses for each end point. ROR <1 means that the experimental intervention fared worse in children than adults. RESULTS: We identified 176 meta-analyses for 52 types of harms/harm-related end points with 669 adult and 184 pediatric RCTs. Of those, 165 had sufficient data for ROR estimation. sRORs showed statistically significant discrepancy between adults and children only for headache (sROR 0.82; 95% confidence interval 0.70–0.96). Nominally significant discrepancies for specific harms were identified in 12 of 165 meta-analyses (RORs 1 in 5). In 36% of meta-analyses, the ROR estimates suggested twofold or greater differences between children and adults, and the 95% confidence intervals could exclude twofold differences only in 18% of meta-analyses. CONCLUSIONS: Available evidence on harms/harm-related end points from pharmacologic interventions has large uncertainty. Extrapolation of evidence from adults to children may be tenuous. Some clinically important discrepancies were identified.