Case report: Rubella virus-associated cutaneous granuloma in an adult with TAP1 deficiency.

Rubella virus-associated granulomas commonly occur in immunocompromised individuals, exhibiting a diverse range of clinical presentations. These manifestations can vary from predominantly superficial cutaneous plaques or nonulcerative nodules to more severe deep ulcerative lesions, often accompanied by extensive necrosis and significant tissue destruction. TAP1 deficiency, an exceedingly rare primary immune-deficiency disorder, presents with severe chronic sino-pulmonary infection and cutaneous granulomas. This report highlights the occurrence of rubella virus-associated cutaneous granulomas in patients with TAP1 deficiency. Notably, the pathogenic mutation responsible for TAP1 deficiency stems from a novel genetic alteration that has not been previously reported. This novel observation holds potential significance for the field of diagnosis and investigative efforts in the context of immunodeficiency disorders.

Cutaneous granulomas associated with rubella virus: A clinical review.

Since the initial identification of vaccine-derived rubella virus (RuV) in the cutaneous granulomas of pediatric patients with inborn errors of immunity in 2014, more than 80 cases of RuV granulomas have been reported implicating both vaccine-derived and wild type RuV. Previously thought to arise exclusively in patients with significant immunocompromise, the identification of RuV granulomas in clinically immunocompetent patients adds nuance to our understanding of the interplay between host environment, immune dysregulation, and RuV granuloma formation. This review summarizes the literature on RuV granulomas including clinical and histopathologic features, proposed pathomechanisms supporting granuloma development, and potential therapeutic options. There is no standardized algorithm to guide the workup and diagnosis of suspected RuV granulomas. We highlight the importance of contributing RuV granuloma cases to ongoing Centers for Disease Control and Prevention surveillance efforts to monitor wild type and vaccine-derived RuV transmission. Studies advancing our understanding of RuV granulomas may provide insights into the role of viral infectious agents in granulomatous disease pathogenesis and guide the development of improved therapeutic options.

Differential diagnosis of fever and rash cases negative for measles and rubella to complement surveillance activities.

In the quest to eliminate measles virus (MV) and rubella virus (Ruv), every suspected case must be properly identified and diagnosed. Since 2017, in Milan (Italy), a total of 978 measles and rubella suspected cases (fever and rash) were investigated and 310 were not laboratory confirmed (discarded cases). To improve surveillance activities, we investigated the presence in discarded cases of 8 other viral pathogens commonly associated with rash: human herpesvirus 6 (HHV-6) and 7 (HHV-7), parvovirus B19 (B19V), enterovirus (EV), Epstein-Barr virus (EBV), human adenovirus (HAdV), cytomegalovirus (HCMV), and SARS-CoV-2. Differential diagnosis was carried out on 289 discarded cases by multiplex real-time PCR assays. At least one pathogen was detected in 188 cases (65.1%) with HHV-7 being the most frequently detected virus. No difference in the number of detected infections overtime was observed and infections were identified in all age groups. As expected, most HHV-6, EV, HAdV, and HCMV-positive cases were found in children aged 0-4 years and HHV-7 was most frequent in the 15-39 age group. In light of the World Health Organization measles elimination goal, the introduction of laboratory methods for differential diagnosis is required for the final classification of clinically compatible cases. The used screening panel allowed us to increase the percentage of virus-positive cases to 87.5%, allowing us to clarify viral involvement and epidemiology, improve diagnosis, and strengthen surveillance activities. As all investigated pathogens were detected, this diagnostic panel was a suitable tool to complement MV and RuV surveillance activities.

Phylogenetic analysis of congenital rubella virus from Indonesia: a case report.

BACKGROUND: Rubella is a common inherited infection resulting in congenital cataracts and a significant cause of permanent vision loss in developing countries. In 2016, Indonesia had the highest number of congenital rubella syndrome (CRS) cases globally. Here, we report the first genotype of the rubella virus extracted from the eye lens from a child with congenital cataracts due to CRS. CASE PRESENTATION: A female neonate was delivered by an elective caesarean delivery with normal birth weight at term from a 24-year-old mother in the rural setting. The baby presented with bilateral congenital cataracts, small-moderate secundum atrial septal defect, severe supravalvular pulmonary stenosis, and profound bilateral hearing loss. She also had microcephaly and splenomegaly. The patient's serology showed persistent positive IgG for rubella virus at the age of four years and four months. Following extraction during cataract surgery, viral detection of the lenses identified the presence of rubella. Phylogenetic analysis confirmed that the virus was grouped into genotype 1E. CONCLUSIONS: Our study reports the first phylogenetic analysis of the rubella virus extracted from the eye lens of a child with CRS in Indonesia. The detection of the rubella virus from eye lenses is remarkably promising. Our findings also emphasize the importance of molecular epidemiology in tracking the origin of rubella infection toward achieving virus eradication.

Use of a rapid digital microfluidics-powered immunoassay for assessing measles and rubella infection and immunity in outbreak settings in the Democratic Republic of the Congo.

The Democratic Republic of the Congo (DRC) has a high measles incidence despite elimination efforts and has yet to introduce rubella vaccine. We evaluated the performance of a prototype rapid digital microfluidics powered (DMF) enzyme-linked immunoassay (ELISA) assessing measles and rubella infection, by testing for immunoglobulin M (IgM), and immunity from natural infection or vaccine, by testing immunoglobulin G (IgG), in outbreak settings. Field evaluations were conducted during September 2017, in Kinshasa province, DRC. Blood specimens were collected during an outbreak investigation of suspected measles cases and tested for measles and rubella IgM and IgG using the DMF-ELISA in the field. Simultaneously, a household serosurvey for measles and rubella IgG was conducted in a recently confirmed measles outbreak area. DMF-ELISA results were compared with reference ELISA results tested at DRC's National Public Health Laboratory and the US Centers for Disease Control and Prevention. Of 157 suspected measles cases, rubella IgM was detected in 54% while measles IgM was detected in 13%. Measles IgG-positive cases were higher among vaccinated persons (87%) than unvaccinated persons (72%). In the recent measles outbreak area, measles IgG seroprevalence was 93% overall, while rubella seroprevalence was lower for children (77%) than women (98%). Compared with reference ELISA, DMF-ELISA sensitivity and specificity were 82% and 78% for measles IgG; 88% and 89% for measles IgM; 85% and 85% for rubella IgG; and 81% and 83% for rubella IgM, respectively. Rubella infection was detected in more than half of persons meeting the suspected measles case definition during a presumed measles outbreak, suggesting substantial unrecognized rubella incidence, and highlighting the need for rubella vaccine introduction into the national schedule. The performance of the DMF-ELISA suggested that this technology can be used to develop rapid diagnostic tests for measles and rubella.

Comparison of a chemiluminescence immunoassay and an enzyme immunoassay for detection of IgM antibodies against measles, mumps, rubella, cytomegalovirus (CMV), Epstein Barr virus (EBV), and human herpes virus (HHV) -1 and -2 infections.

PURPOSE: Outbreaks of vaccine-preventable viral diseases have been increasingly reported globally over the past few years. The burden of congenital viral infections, their impact on physical and mental development and the resulting economic loss to the family and the community are also well known. IgM antibody detection has been convenient in the diagnosis of acute viral infections, particularly in settings with limited resources where molecular tests are not feasible. METHODS: This is a comparative study between a chemiluminescence immunoassay (Liaison, DiaSorin, Saluggia, Italy) and an enzyme linked immunosorbent assay (ELISA) (Euroimmun, Lubeck, Germany) for the detection of IgM antibody against measles, mumps, rubella, CMV, EBV and HHV-1 and -2 viruses using a total of 345 samples. Results are expressed as agreement using kappa statistics. RESULTS: In this study, CLIA is perfectly comparable to ELISA for the detection of IgM antibodies against measles (0.86) and mumps (0.92) with a moderate agreement for rubella (0.52), CMV (0.57), EBV (0.50), and HHV-1 and -2 (0.47) assays. However, a PABAK (prevalence-adjusted bias-adjusted kappa) showed improved agreement for rubella (0.64), CMV (0.65), EBV (0.60), and HHV-1 and -2 (0.88) assays. CONCLUSIONS: IgM antibody assays (CLIA and ELISA) against measles and mumps virus can be comparably used depending on the laboratory setup, throughput and expertise.

Post Vaccine Rubella During a Measles Outbreak: Clinical Case.

Rubella is a vaccine preventable infection, and congenital rubella the most feared complication of this disease. Although young adult women are at greatest risk of post-vaccine rubella, this is also the group who potentially benefits the most from vaccine protection. Since post-vaccine disease has a mild and self-limited course, the benefit clearly exceeds the risk. During a measles outbreak in the north of Portugal, a 38-year-old woman presented with cervical posterior lymphadenopathies, fever and a maculo-papular rash one week after the administration of the measles, mumps and rubella vaccine. Measles was discarded and rubella viremia was demonstrated. Symptoms of rubella are non-specific and laboratory confirmation is essential. This is particularly relevant during a measles outbreak.

A rubéola é uma infeção prevenível por vacina, sendo a rubéola congénita a apresentação mais grave da doença. Apesar de serem o grupo que mais beneficia dela, as mulheres em idade fértil são também o grupo com maior risco de doença associada à vacina. Uma vez que as manifestações clínicas são ligeiras e transitórias, o benefício compensa largamente o risco. Durante o surto de sarampo que ocorreu no Porto em 2018, uma mulher de 38 anos recebeu a primeira dose da vacina contra o sarampo, rubéola e papeira. Uma semana depois, recorreu ao Serviço de Urgência por febre, exantema maculo-papular e adenopatias cervicais posteriores. Foi excluído sarampo e demonstrada viremia pelo vírus da rubéola. Os sintomas da rubéola são inespecíficos pelo que a confirmação laboratorial é essencial. Isto é ainda mais relevante em contexto de surto de sarampo.

Overview of a Provincial Prenatal Communicable Disease Screening Program: 2002-2016.

OBJECTIVE: This study sought to provide a 14-year overview of serological results from a provincial prenatal screening program. METHODS: Prenatal screening data from August 2002 to December 2016 were extracted from the Alberta Public Health Laboratory (ProvLab) Information system. Data were analyzed by year, communicable disease marker, test result, and maternal age category. The age-stratified proportion of seropositive results for hepatitis B virus, human immunodeficiency virus, and syphilis was determined, and the proportion of seronegative results was determined for rubella and varicella. The Mann Kendall Trend Test was performed to identify significant temporal trends in the results (Canadian Task Force Classification II-2). RESULTS: In total 821 910 prenatal specimens were examined. Overall, the proportion of prenatal specimens positive for hepatitis B virus showed a slight statistically significant upward trend from 0.50% in 2003 to 0.58% in 2016 (P = 0.03). The proportion of positive human immunodeficiency virus prenatal specimens showed no significant trend over the study period. The proportion of positive syphilis specimens increased from 2006 to 2008 (0.07% to 0.21%; P < 0.0001) and stayed relatively constant until a decrease began in 2015. The proportion of seronegative specimens for varicella and rubella showed a significant upward trend of 0.48% per year (P < 0.01) and 0.88% per year (P < 0.01), respectively. CONCLUSION: The Alberta Prenatal Screening Program for Selected Communicable Diseases presents a unique data set that allows us to look at screening results on a provincial level. Trends in results are reflective of communicable disease trends in the general population and should be monitored for effective infectious disease management of the maternal and newborn population.

TORCH screening used appropriately in China?─three years results from a teaching hospital in northwest China.

OBJECTIVES: TORCH infections caused by Toxoplasma gondii (TOX), rubella virus (RV), cytomegalovirus (CMV) and herpes simplex virus 1,2 (HSV-1,2) are associated with congenital anomalies. The study aimed to analyze the characteristics of TORCH screening in reproductive age women. METHODS: A total of 18,104 women (2015-2017) from a teaching hospital in Xi'an, China, were enrolled in the study. The characteristics of TORCH screening, i.e., the application of TORCH test, the seroprevalence, the impact of age, periods of gestation and woman with bad obstetric history (BOH) on the serological data were investigated. RESULTS: In the study, 319 women (1.76%) performed dynamic TORCH test. 51.66, 20.44 and 3.83% of the population did the test in the pre-gestation period, the first and third trimester, respectively. Quite a few pre-gestation women (29.74%) ignored screening of IgG antibodies. The overall IgG/IgM seropositvity of TOX, RV, CMV, HSV-1 and HSV-2 was 4.35%/0.35, 90%/0.63, 96.79%/0.97, 81.11%/0.14 and 6.1%/0.19%, respectively. The age-specific distributions and periods of gestation had no significant effect on the seroprevalence of TORCH agents, p>0.05. However, BOH was significantly associated with higher seropositvity of IgM (RV, CMV, HSV-1 and HSV-2) and IgG (CMV and HSV-1) antibodies, p < 0.05. CONCLUSION: In Xi'an region, more attentions should be paid to TOX, CMV, HSV-2 and the women with BOH for TORCH screening. Meanwhile, a greater emphasis needs to be placed on TORCH test used inappropriately in China.

Diagnostic algorithm for the confirmation of cases of measles and rubella in Mexico

Due to the successful implementation of measles and rubella elimination strategies, Mexico announced the interruption of endemic transmission of measles in 1996 and that of rubella in 2008. After a verification process, the region of the Americas was declared free of rubella and congenital rubella syndrome in 2015 and of measles in 2016. In order to maintain the elimination status in Mexico, it is essential to continue laboratory surveillance within the framework of the Global Measles and Rubella Laboratory Network. The Institute of Epidemiological Diagnosis and Reference, through the National Network of Public Health Laboratories, guarantees timely and reliable results in view of the possible reintroduction of these and other emerging pathogens.

Predictive Factors of Intraocular Pressure Level Evolution Over Time and Glaucoma Severity in Fuchs' Heterochromic Iridocyclitis.

Purpose: To investigate the clinical and virologic-associated and predictive factors of intraocular pressure (IOP) evolution over time and its severity in Fuchs' heterochromic iridocyclitis (FHC). Methods: Consecutive patients with both clinical FHC and intraocular synthesis of rubella virus (RV)-specific antibodies were included in this study. Specific ocular production of RV antibodies was confirmed using the quotient of serum/aqueous humor ratio of RV IgGs (Crv) and control antiviral IgGs (Cctl), using quantitative serology methods. Epidemiologic, clinical, biological, and virologic data at referral were collected and correlated with IOP values over time, occurrence, and severity of glaucoma. Results: Sixty-eight eyes of 68 patients were included. Mean age at diagnosis was 40.7 ± 11.1 years. Mean follow-up was 4.3 ± 4.3 years. Mean baseline Crv and Cctl values were 12.34 ± 14.67 and 216.70 ± 98.4, respectively. Mean baseline IOP was 17.2 ± 7.2 mm Hg (range, 9-40) and 15.6 ± 5.6 (range, 3-30) 5 years after referral. The predictive factors for pejorative IOP evolution over time and glaucoma severity were male sex (P = 0.03) and decreased Crv (P = 0.04) and presence of iris nodules (P < 0.001) and decreased Cctl (P = 0.02), respectively. Diagnostic delay was associated with increased likelihood of undergoing glaucoma surgery (P = 0.02). Conclusions: Time to diagnosis, male sex, presence of iris nodules at baseline, and decreased Crv and Cctl ratios were associated with increased likelihood of pejorative IOP evolution over time. Given the aggressiveness of glaucoma in FHC, these results provide interesting insight into what category of patients should need the closest screening.

A case of adult rubella in Japan.

We report the case of a 32-year-old Japanese female who presented with a mild sore throat, rash and posterior cervical and posterior auricular lymphadenopathy. She was diagnosed with rubella. Japan has experienced multiple outbreaks of rubella in recent times. Travelers to Japan should consider getting vaccinated for rubella.

Congenital B-cell Acute Lymphoblastic Leukemia with Congenital Rubella Infection.

BACKGROUND: Congenital B-cell Acute lymphoblastic leukemia (ALL) is a rare malignancy. CHARACTERISTICS: A newborn infant presented with purpuric spots and ecchymotic patches, blueberry muffin rash, depressed neonatal reflexes, respiratory distress and hepatosplenomegaly. Peripheral smear revealed atypical blast cells. Serum ELISA was positive for Rubella IgM and IgG antibodies. Flow cytometry suggested congenital B-cell ALL. OUTCOME: The baby died after 3 days due to suspected intracranial hemorrhage. MESSAGE: Congenital leukemia may be rarely associated with congenital rubella infection.

Evaluation of the Abbott ARCHITECT™ cytomegalovirus IgM/IgG, rubella IgM/IgG, and syphilis treponemal antibodies enzyme immunoassays in a mother and child health center population.

This study evaluated the concordance of Architect™ chemiluminescent microparticle immunoassays with Captia™ ELISA for cytomegalovirus (CMV) IgM and IgG, with Enzygnost™ and Captia™ ELISA for rubella IgM and IgG and with Trep-Sure™ ELISA for syphilis treponemal antibodies in a mixed pediatric and obstetrical population. Total agreement between assays and Kappa statistic value were 82.5% (95% CI: 75.6-87.7) and 0.65 (95% CI: 0.54-0.77) for CMV IgM, 82.8% (95% CI: 76.7-87.6) and 0.65 (95% CI: 0.55-0.75) for CMV IgG, 89.2% (95% CI: 82.9-93.4) and 0.56 (95% CI: 0.36-0.75) for rubella IgM, 88.6% (95% CI: 82.9-92.6) and 0.74 (95% CI: 0.63-0.84) for rubella IgG, and 97.9% (95% CI: 94.5-99.4) and 0.89 (95% CI: 0.79-1.00) for syphilis treponemal antibodies. This study demonstrates that the Architect™ chemiluminescent microparticle immunoassays correlate well with other FDA-approved ELISA assays in this specific population.

Demystifying viral anterior uveitis: A review.

A viral aetiology should be suspected when anterior uveitis is accompanied by ocular hypertension, diffuse stellate keratic precipitates or the presence of iris atrophy. The most common viruses associated with anterior uveitis include herpes simplex virus, varicella-zoster virus, cytomegalovirus and rubella virus. They may present as the following: Firstly, granulomatous cluster of small and medium-sized keratic precipitates in Arlt's triangle, with or without corneal scars, suggestive of herpes simplex or varicella-zoster virus infection. Secondly, Posner-Schlossman syndrome with few medium-sized keratic precipitates, minimal anterior chamber cells and extremely high intraocular pressure; this is mainly associated with cytomegalovirus. Thirdly, Fuchs uveitis syndrome, with fine stellate keratic precipitates diffusely distributed over the corneal endothelium, with diffuse iris stromal atrophy but without posterior synechiae, is associated mainly with rubella or cytomegalovirus infection. In rubella, the onset is in the second to third decade. It presents with posterior subcapsular cataract, may have iris heterochromia and often develops vitritis without macular oedema. Cytomegalovirus affects predominantly Asian males in the fifth to seventh decade, the keratic precipitates may be pigmented or appear in coin-like pattern or develop nodular endothelial lesions, but rarely vitritis. Eyes with cytomegalovirus tend to have lower endothelial cell counts than the fellow eye. As their ocular manifestations are variable and may overlap considerably, viral AU can pose a diagnostic dilemma. Thus, quantitative polymerase chain reaction or Goldmann-Witmer coefficient assay from aqueous humour samples are preferred to confirm the aetiology and determine the disease severity as this impacts the treatment.

Clinical value of enzyme immunoassay that detects rubella-specific immunoglobulin M immediately after disease onset.

A total of 300 patients with nucleic acid test-confirmed rubella, mostly adults, were investigated to determine the clinical value of a rubella-specific IgM test using an EIA kit. IgM titers increased after rash onset, the median IgM titer being significantly higher 3 days post-onset than on previous days (P < 0.0001). Similarly, the IgM-positive rate at 3 days post-onset (61.5%) was significantly higher than on previous days (P < 0.0001). This IgM test against rubella at 3 days or more post-disease onset provides the clinically relevant information.

Rubella Seropositivity in Pregnant Women After Vaccination Campaign in Brazil's Federal District.

Rubella is an acute viral disease that usually does not generate sequels; however, in pregnant women the infection can cause serious abnormalities to fetuses, which are collectively called congenital rubella syndrome. In Brazil, population immunization was started in 1992, but few epidemiological studies have been conducted to assess vaccination coverage and seroconversion since then. The aim of this work is to evaluate the seropositivity of pregnant women to rubella virus after vaccination campaign was carried out in 2008. Serological tests for rubella diagnosis were performed in 87 pregnant women who attended the University of Brasilia Hospital, Federal District, Brazil. Antirubella IgG antibodies were detected in 83 out of 87 pregnant women (95.4%), with an age-independent seroprevalence. Only one woman was positive in IgM serological tests. Our data suggest high levels of vaccination coverage and antirubella immunization in the Brazil Federal District population.