Mother-to-child Transmission Research Articles

PP-016 Congenital cytomegalovirus infection: a clinical study

PP-016 Congenital cytomegalovirus infection: a clinical study

Trends in preterm birth in women living with HIV in Switzerland over the last three decades: A multicentric, prospective, cohort study.

HIV infection and its management during pregnancy to reduce perinatal transmission has been associated with preterm birth (PTB). This management has drastically changed. We aimed to evaluate changes in rates of PTB over 34 years in women living with HIV (WLWH) in Switzerland, and to identify factors and interventions associated with these changes. We analysed data from 1238 singleton pregnancies, prospectively collected by the Swiss Mother and Child HIV Cohort Study (MoCHiV) and the Swiss HIV Cohort Study (SHCS) between 1986 and 2020. Rates of PTB in this cohort were compared with that of the general Swiss population for three time periods according to changing treatment strategies recommended at the time. We evaluated the association of PTB with sociodemographic, HIV infection and obstetric variables in uni- and multivariate logistic regression. Rate of PTB in WLWH was highest prior to 2010 (mean 20.4%), and progressively decreased since then (mean 11.3%), but always remained higher than in the general population (5%). Older maternal age, lower CD4 count and detectable viraemia at third trimester (T3), drug consumption and mode of delivery were all significantly associated with both PTB and period of study in univariate analysis. There was no association between PTB and type of antiretroviral regimen. No difference was found in the rate of spontaneous labor between PTB and term delivery groups. Only higher CD4 count at T3 and vaginal delivery were significantly associated with a decrease in PTB over time in multivariate analysis. Preterm birth in WLWH in Switzerland has drastically decreased over the last three decades, but remains twice the rate of that in the general population. Improved viral control and changes in mode of delivery (vaginal birth recommended if viral loads are low near birth) have led to this progress.

Candidiasis in Pregnancy: Relevant Aspects of the Pathology for the Mother and the Fetus and Therapeutic Strategies.

Vulvovaginal candidiasis (VVC) is a common condition that can lead to significant discomfort, affecting approximately 70-75% of women at least once in their lives. During pregnancy, the prevalence of VVC is estimated to be around 20%, peaking at about 30% in the third trimester, with a number of specific risk factors predisposing to yeast infection being identified and needing elucidation. This review aims to provide updated knowledge on candidiasis during pregnancy, addressing risk factors and maternal and neonatal outcomes, as well as discussing optimal therapeutic strategies to safeguard mothers and newborns. The bibliographic search involved two biomedical databases, PubMed and Embase, without imposing time limits. Among all Candida spp., Candida albicans remains the most frequent causative species. The hyperestrogenic environment of the vaginal mucosa and reduced immune defenses, physiological effects of pregnancy, create conditions favorable for Candida spp. vaginal colonization and hence VVC. Recent evidence shows an association between VVC and adverse obstetric outcomes, including premature membrane rupture (PROM), chorioamnionitis, preterm birth, and puerperal infections. Prompt and effective management of this condition is therefore crucial to prevent adverse obstetric outcomes, maternal-fetal transmission, and neonatal disease. Additional studies are required to confirm the benefits of systemic treatment for maternal candida infection or colonization in preventing premature birth or neonatal systemic candidiasis.

"Congenital cytomegalovirus in Sub-Saharan Africa-a narrative review with practice recommendations".

Cytomegalovirus (CMV) is the most common cause of congenital infection internationally, occurring in 0.67% of births, and increasingly recognised as a major public health burden due to the potential for long-term neurodevelopmental and hearing impairment. This burden includes estimates of 10% of childhood cerebral palsy and up to 25% of childhood deafness. In Sub-Saharan Africa, where CMV-seroprevalence is almost ubiquitous, prevalence of congenital CMV (cCMV) is higher than the global average, and yet there is a dearth of research and initiatives to improve recognition, diagnosis and treatment. This narrative review outlines the epidemiology and clinical presentation of cCMV, discusses issues of case identification and treatment in Sub-Saharan Africa, and recommends a framework of strategies to address these challenges. Considering the significant burden of cCMV disease in this setting, it is undoubtably time we embark upon improving diagnosis and care for these infants.

"Minimally symptomatic" congenital cytomegalovirus infection: latest data and emerging concepts.

Universal and targeted screening of newborns for congenital cytomegalovirus (CMV) infection is increasing globally. Questions remain concerning the management of infants who have been identified with congenital CMV infection, especially those with "minimally symptomatic" or clinically inapparent infection. Our objective is to discuss current management of CMV-infected neonates with a focus on less affected infants with or without sensorineural hearing loss (SNHL). Valganciclovir is being prescribed increasingly in neonates with congenital CMV infection for improvement in hearing outcomes through 2 years of age. Treatment initiated in the first month of age is recommended for clinically apparent disease. A recent study showed hearing improvement at 18-22 months of age when therapy was initiated at age 1-3 months in infants with clinically inapparent CMV infection and isolated SNHL. Antiviral therapy with either ganciclovir or valganciclovir has shown moderate benefit in prevention of hearing deterioration among infants with clinically apparent CMV infection or isolated SNHL. Sustainability of benefit beyond 2 years of age remains unknown. At present, infants with clinically inapparent CMV infection (normal complete evaluation including hearing) should not receive antiviral therapy. All CMV-infected infants require close audiological and neurodevelopmental follow-up.

From diagnosis to management: current perspectives on congenital cytomegalovirus infection.

Congenital CMV (cCMV) infection is the most common infection of newborns and a leading cause of hearing loss and other neurologic disabilities in children. This review focuses on the diagnosis, presentation and management of cCMV infection. Cytomegalovirus is one of the leading causes of sensorineural hearing loss in children. It also leads to neurodevelopmental disabilities and learning problems throughout childhood in both symptomatic and asymptomatic newborns. Urine and saliva PCR testing are the preferred methods of testing newborn infants for cCMV. In recent years, newborn-targeted and universal screening programs have been implemented in several states and major medical centers with the goal of identifying infected infants at risk for hearing loss. Treatment for infants diagnosed with cCMV infection should be limited to those who are moderately to severely symptomatic at birth with cCMV infection, though treatment may be beneficial for children who are asymptomatic with isolated sensorineural hearing loss. As more children with cCMV are being identified through newborn screening, understanding the clinical presentation and sequelae is important for appropriate management of children with cCMV.

Universal and Expanded Screening Strategy for Congenital Cytomegalovirus Infection: Is Pool Testing by a Rapid Molecular Test in Saliva a New Choice in Developing Countries?

Background: Several screening strategies for identifying congenital CMV (cCMV) have been proposed; however, the optimal solution has yet to be determined. We aimed to determine the prevalence of cCMV by universal screening with saliva pool testing and to identify the clinical variables associated with a higher risk of cCMV to optimize an expanded screening strategy. Methods: We carried out a prospective universal cCMV screening (September/2022 to August/2023) of 2186 newborns, analyzing saliva samples in pools of five (Alethia-LAMP-CMV®) and then performed confirmatory urine CMV RT-PCR. Infants with risk factors (small for gestational age, failed hearing screening, HIV-exposed, born to immunosuppressed mothers, or <1000 g birth weight) underwent expanded screening. Multivariate analyses were used to assess the association with maternal/neonatal variables. Results: We identified 10 infants with cCMV (prevalence: 0.46%, 95% CI 0.22–0.84), with significantly higher rates (2.1%, 95% CI 0.58–5.3) in the high-risk group (p = 0.04). False positives occurred in 0.09% of cases. No significant differences in maternal/neonatal characteristics were observed, except for a higher prevalence among infants born to non-Chilean mothers (p = 0.034), notably those born to Haitian mothers (1.5%, 95% CI 0.31–4.34), who had higher odds of cCMV (OR 6.82, 95% CI 1.23–37.9, p = 0.04). Incorporating maternal nationality improved predictive accuracy (AUC: 0.65 to 0.83). Conclusions: For low-prevalence diseases such as cCMV, universal screening with pool testing in saliva represents an optimal and cost-effective approach to enhance diagnosis in asymptomatic patients. An expanded screening strategy considering maternal nationality could be beneficial in resource-limited settings.

Association of HBeAg decline rate from mid-pregnancy to delivery with HBeAg seroconversion after delivery in hepatitis B virus-infected mothers.

There is still controversy about whether to continue antiviral therapy (AVT) after delivery, especially for pregnant women in the immune tolerance (IT) phase. In this study, a retrospective cohort study was conducted to explore the relationship between hepatitis B e antigen (HBeAg) decline rate (%) from mid-pregnancy to delivery and HBeAg seroconversion postpartum among patients using nucleos(t)ide analogs (NAs) to prevent mother-to-child transmission (MTCT), with the goal of identifying the ideal candidates for postpartum AVT continuation. This retrospective cohort study included 151 postpartum women. Univariate and multivariable logistic regression analyses were conducted to assess the association between the HBeAg decline rate (%) from mid-pregnancy to delivery and HBeAg seroconversion postpartum. Receiver operating characteristic (ROC) analysis was utilized to evaluate the predictive capacity of the HBeAg decline rate (%) and determine the optimal cut-off point. The univariate analysis revealed a significant association between the HBeAg decline rate (%) and HBeAg seroconversion postpartum (OR 1.068, 95% CI: 1.034-1.103, p < .001). In the multivariate regression analysis, adjusting for age, hepatitis B surface antigen (HBsAg) titre (log10 IU/mL) at mid-pregnancy, HBeAg titre (log10 S/CO) at mid-pregnancy, and hepatitis B virus (HBV) DNA load decline rate (%) from mid-pregnancy to delivery, the HBeAg decline rate(%) remained significantly associated with HBeAg seroconversion postpartum (OR 1.050, 95% CI: 1.015-1.093, p = .009). Then HBeAg decline rate (%) was treated as a categorical variable (tertiles) for sensitivity analysis. In the three distinct models, taking Tertile1 as a reference, women in Tertile3 still had a 4.201-fold (OR 4.201, 95% CI: 1.382-12.773, p = .011) higher risk of developing HBeAg seroconversion (p for trend <.05) after adjusting above covariates. The area under the curve (AUC) was 0.723 (95% CI: 0.627-0.819). The optimal cut-off value was 5.43%, with a sensitivity of 0.561, specificity of 0.791, and Youden's index of 0.352.A higher HBeAg decline rate (%) from mid-pregnancy to delivery independently correlated with an increased risk of HBeAg seroconversion postpartum. This decline rate can serve as a valuable clinical indicator for predicting HBeAg seroconversion.

Preexisting maternal immunity to AAV but not Cas9 impairs in utero gene editing in mice.

In utero gene editing (IUGE) is a potential treatment for inherited diseases that cause pathology before or soon after birth. Preexisting immunity to adeno-associated virus (AAV) vectors and Cas9 endonuclease may limit postnatal gene editing. The tolerogenic fetal immune system minimizes a fetal immune barrier to IUGE. However, the ability of maternal immunity to limit fetal gene editing remains a question. We investigated whether preexisting maternal immunity to AAV or Cas9 impairs IUGE. Using a combination of fluorescent reporter mice and a murine model of a metabolic liver disease, we demonstrated that maternal anti-AAV IgG antibodies were efficiently transferred from dam to fetus and impaired IUGE in a maternal titer-dependent fashion. By contrast, maternal cellular immunity was inefficiently transferred to the fetus, and neither maternal cellular nor humoral immunity to Cas9 impaired IUGE. Using human umbilical cord and maternal blood samples collected from mid- to late-gestation pregnancies, we demonstrated that maternal-fetal transmission of anti-AAV IgG was inefficient in midgestation compared with term, suggesting that the maternal immune barrier to clinical IUGE would be less relevant at midgestation. These findings support immunologic advantages for IUGE and inform maternal preprocedural testing protocols and exclusion criteria for future clinical trials.

Strengthening laboratory systems for ensuring accurate diagnoses in mother-to-child transmission (MTCT) prevention programs in Uganda: a narrative review.

Mother-to-child transmission (MTCT) of HIV remains a significant public health challenge in Uganda, necessitating a focused examination of the state of laboratory systems to ensure accurate diagnoses and effective prevention. The aim of this narrative review is to assess the current state of laboratory systems supporting MTCT prevention programs in Uganda, identify challenges hindering accurate diagnoses, and propose strategies for strengthening these systems to enhance the effectiveness of MTCT prevention efforts. This narrative review explores the current landscape of laboratory infrastructure in Uganda, addressing challenges unique to the country and proposing strategies for improvement. The discussion encompasses the integration of molecular testing, the role of point-of-care diagnostics, the implementation of quality assurance programs, and capacity-building initiatives for laboratory personnel. Additionally, technological innovations and their applicability in the Ugandan context are explored alongside the crucial aspect of integrating laboratory services into antenatal care. Drawing on global lessons, the review provides tailored recommendations for Uganda, spanning policy considerations, funding mechanisms, infrastructure enhancements, and workforce development. Looking towards the future, the review outlines potential collaborations, technological advancements, and strategic investments that can further fortify laboratory systems, ultimately contributing to the elimination of MTCT in Uganda.

TOXOPLASMOSIS: SEROPREVALENCE IN WOMEN OF REPRODUCTIVE AGE AND APPROACH IN PREGNANCY

Objective: Toxoplasmosis is a parasitosis that is mostly asymptomatic or with mild symptoms. It can lead to severe clinical conditions in immunosuppressed patients who had infections that mostly develop through reactivation, or in congenital infections that develop in fetuses infected as a result of vertical transmission. Since it is possible to prevent congenital toxoplasmosis with appropriate follow-up and treatment, our study aimed to determine the susceptible population and seroprevalence of our region and to evaluate the course of infections in this group. Material and Method: Patients of childbearing age who were evaluated in the last five years in our tertiary hospital were included in our study, and Anti Toxoplasma gondii IgM and IgG results in these patients were evaluated. The course of pregnant women who were thought to have primary infection, the follow-up of these patients and the treatments applied were evaluated. In addition, the follow-up of non-pregnant patients examined were also evaluated. Results: The seropositivity rate was found to be 30.7% (n=1703) in 5545 women included in the study, and the seropositivity rate was 31% (n=1399) in 4503 pregnant women. After detailed evaluations, of 16 pregnant women who were thought to have primary infection during pregnancy and were followed up in our hospital; one underwent medical abortion at the request of the family, and only four used the recommended treatment until the end of pregnancy, and congenital toxoplasmosis was not detected in any newborn. Since the many of pregnant women with possible primary infection (n=28) were not referred to the infectious diseases outpatient clinic, this group was not evaluated in detail and could not be monitored. Of the patients included in the study, 26 (0.4%) were examined to investigate the etiology of fever, 37 (0.6%) were examined to investigate the etiology of lymphadenopathy (LAP), and 29 (0.5%) were examined to investigate the cause of elevated liver function tests. Among the patients monitored with LAP, four (10.8%) were diagnosed with acute toxoplasmosis. Conclusion: As a result, it is very important to determine the seroprevalence of toxoplasmosis, to detect possible primary infections, especially in pregnant women, and to prevent congenital toxoplasmosis by clinicians to guide patients correctly so that the follow-up and treatment of this group of patients is not interrupted.

Homozygous mutation of OCLN gene in Pseudo-TORCH Syndrome Type I : A Case Report

Clinical similarities of TORCH syndrome but serological negative findings for an infectious agent named it Pseudo-TORCH syndrome, which follows autosomal recessive inheritance but it has genetic heterogeneity. Here we reported a case of 11 month old girl of consanguineous parent with psychomotor retardation, microcephaly and intracranial calcifications but she was serologically negative for TORCH infection and positive for homozygous mutation in the gene encoding occluding (OCLN) on chromosome 5. BANGLADESH J CHILD HEALTH 2022; VOL 46 (2) : 95-97

Management of PCOS Infertility then implementation of Garbhini Parichaya till Full Term by Ayurveda - Case Study

Primary Infertility associated with recurrent pregnancy loss because of Viral infections like TORCH and Polycystic Ovarian Syndrome (PCOS) is a worrisome issue nowadays. In modern medicine, antiviral drugs are the main treatment for TORCH, causing various side effects. Ayurveda being preventive and curative medicinal branch, has good positive outcome in the treatment of TORCH induced BOH and infertility. The Garbhini Paricharya refers to the care given to pregnant lady. It has to be started as soon as the signs and symptoms of pregnancy are seen. The rate of abortions can be prevented by following proper antenatal care detailed in Ayurveda. Presenting a case report of 32-year-old female came to Govt. Ayurvedic college and hospital, Varanasi with 11 years of married life and history of two consecutive spontaneous abortions and wasn’t able to conceive since then. She was detected with PCOS and Positive TORCH infection. Her last USG findings dated 17/01/2023 was right ovarian- PCOS morphology &amp; left ovarian- hemorrhagic cyst 54x60mm + subserosal uterine fibroid 20x27mm in fundal region with complaints of inability to conceive with complaints of delayed menses at interval of 2-6 months with prolonged bleeding with clots for 10-15 days for 7 years (after last abortion). Treatment protocol was based upon Samprapti Vighatan &amp; focused on Prakriti of patient, Dosha Pradhanya Lakshana &amp; Dosha Dushya Sammurchana. She was treated with Jalkumbhi Kshar with Varunadi Kwath for her fibroid and Pushpadhanva Rasa, Kanchanar Guggulu, Ashokarishta etc along with Nasya, Matra Basti and Uttar Basti. After 4 months of treatment, patient was treated successfully with Ayurvedic intervention and Garbhini paricharya with conception and delivery of a full-term healthy baby boy.

T-Cell Immune Responses in Newborns and Long-Term Sequelae in Congenital Cytomegalovirus Infection (CYTRIC Study)

The objective of this study was to assess the role of T-lymphocyte immune responses in newborns with congenital cytomegalovirus (CMV) infection (cCMV) and their potential association with the development of long-term sequelae. A multicenter, prospective study from 2017 to 2022 was conducted across 8 hospitals in Spain. Blood samples were collected within the first month of life from neonates diagnosed with cCMV. Intracellular cytokine staining was employed to evaluate the presence of CMV-specific interferon-gamma (IFN-γ)-producing CD8+ and CD4+ T lymphocytes (CMV-IFN-γ-CD8+/CD4+) using flow cytometry. The development of sequelae, including hearing loss and neurologic impairment, was assessed during follow-up. In total, 64 newborns were included; 42 infants (65.6%) had symptomatic cCMV. The median age at the last follow-up visit was 25.3months (IQR 20.1-34.4). Eighteen infants had long-term sequelae (28.1%), predominantly hearing loss (20.3%) and neurologic disorders (15.6%). No relationship was observed between total count or percentage of CMV-specific IFN-γ-CD8+ or CD4+ lymphocytes and long-term sequelae. Multivariable analysis demonstrated an association between lower total lymphocyte count and long-term sequelae (aOR 0.549, 95% CI: 0.323-0.833), which requires further study. CMV-specific IFN-γ-CD4+ and CD8+ T-lymphocyte responses in neonates with cCMV were not predictive of long-term sequelae.

An assessment of turnaround times of infant Deoxyribonucleic acid-Polymerase Chain Reaction testing and the associated factors in Western Kenya: A mixed methods study.

The HIV/AIDS continues being a significant global public health priority in the 21st century with social and economic consequences Mother-to-child transmission (MTCT) occurs when an HIV-infected woman passes the virus to her infant and about 90% of these MTCT infections occurs in Africa where children and infants are still dying of HIV. Early definitive diagnosis using Deoxyribonucleic acid reaction of HIV infection in infants is critical to ensuring that HIV-infected infants receive appropriate and timely care and treatment to reduce HIV related morbidity and mortality. To assess the Infant Deoxyribonucleic acid-Polymerase Chain Reaction (DNA-PCR) Turnaround Time (TAT) of dry blood spots and associated factors in Vihiga, Bungoma, Kakamega and Busia counties, in Kenya. A mixed methods study using a) retrospectively collected data from Ministry of Health Laboratory registers, Early Infant Diagnosis (EID) database from 28 health facilities and b) 9 key informant interviews with laboratory in-charges were conducted. A total of 2,879 HIV exposed babies' data were abstracted from January 2012 to June 2013. The mean TAT from specimen collection and results received back at the facilities was 46.90 days, Vihiga county having the shortest mean duration at 33.7days and Kakamega county having the longest duration at 51.7days (p = 0.001). In addition, the mean transport time from specimen collection and receipt at Alupe Kenya Medical Research Institute (KEMRI) reference Laboratory was 16.50 days. Vihiga County had the shortest transport time at 13.01 days while Busia had the longest at 18.99 days (p = 0.001). Longer TAT was due to the batching of specimens at the peripheral health facilities and hubbing to the nearest referral hospitals. The TAT for DNA-PCR specimen was 46.90 days with Vihiga County having the shortest TAT due to lack of specimen batching and hubbing. Discourage specimen batching/hubbing and support point-of-care early infant diagnosis (EID) tests.

Pediatric immunotherapy and HIV control.

Highlighting opportunities/potential for immunotherapy by understanding dynamics of HIV control during pediatric HIV infection with and without antiretroviral therapy (ART), as modeled in Simian immunodeficiency virus (SIV) and Simian-human immunodeficiency virus (SHIV)-infected rhesus macaques and observed in clinical trials. This review outlines mode of transmission, pathogenesis of pediatric HIV, unique aspects of the infant immune system, infant macaque models and immunotherapies. During the earliest stages of perinatal HIV infection, the infant immune system is characterized by a unique environment defined by immune tolerance and lack of HIV-specific T cell responses which contribute to disease progression. Moreover, primary lymphoid organs such as the thymus appear to play a distinct role in HIV pathogenesis in children living with HIV (CLWH). Key components of the immune system determine the degree of viral control, targets for strategies to induce viral control, and the response to immunotherapy. The pursuit of highly potent broadly neutralizing antibodies (bNAbs) and T cell vaccines has revolutionized the approach to HIV cure. Administration of HIV-1-specific bNAbs, targeting the highly variable envelope improves humoral immunity, and T cell vaccines induce or improve T cell responses such as the cytotoxic effects of HIV-1-specific CD8+ T cells, both of which are promising options towards virologic control and ART-free remission as evidenced by completed and ongoing clinical trials. Understanding early events during HIV infection and disease progression in CLWH serves as a foundation for predicting or targeting later outcomes by harnessing the immune system's natural responses. The developing pediatric immune system offers multiple opportunities for specific long-term immunotherapies capable of improving quality of life during adolescence and adulthood.

Assessments at week 2 and 3 in Term Newborns Diagnoses with Prolonged Jaundice

Introduction: Jaundice is one of the most common problems at neonatal period and seen in 60-70% of all newborns at first days of life. Prolonged jaundice is defined as hyperbilirubinemia persisting at the end of week 2 in term newborns. In this study, we reviewed term newborns diagnosed with prolonged jaundice. It was aimed to demonstrate delaying laboratory evaluations for a week in infants with favorable clinical presentation can prevent unnecessary tests in majority of newborns. Materials and methods: The study included full-term newborns who presented after day 14 of life and diagnosed with prolonged jaundice at neonatology outpatient clinic of Health Sciences University, Keçiören Teaching and Research Hospital in 2016. Overall, 336 infants with prolonged jaundice were screened. The infants with congenital anomaly, those with findings of sepsis or severe infection, those with history of intrauterine infection, those with history of acholic stool and those with no available data were excluded. In 180 patients included, clinical evaluations, bilirubin levels and advanced test results were assessed at baseline and weekly follow-up. Findings: Of the infants included, 51.7% were boys while 48.3% were girls. The most common blood type was A Rh (+). There was ABO incompatibility alone in 24 infants (14.2%), Rh incompatibility alone in 6 infants (3.5%) and ABO plus Rh incompatibility in 3 infants (1.2%). In 130 infants, total bilirubin was studied on both week 2 and 3. At week 3, total bilirubin value was ≥10 mg/dl in only 36 infants (27.7%) while it was decreased below 10 mg/dL in 94 infants (72.3%). Urinary tract infection (UTI) was detected in 7 of 38 infants with available tests at week 2. Two of 6 infants with UTI had other clinical signs of UTI. Mean total bilirubin value was 17.9 mg/dL in 5 infants. A significant correlation was found between UTI and vomiting, breastfeeding and feeding pattern (p

Effect of Dolutegravir-Based First-Line Antiretroviral Therapy on Mother-to-Child Transmission of HIV Among HIV-Exposed Infants in Ethiopia: a Before-and-After Study.

Currently, Dolutegravir (DTG)-based regimens are administered to women on Option B plus to prevent mother-to-child transmission (MTCT) of the virus. However, its effect on reducing MTCT of human immunodeficiency virus (HIV) among HIV-exposed infants over the previously used Efavirenz (EFV)-based regimen is unknown. This study aimed to compare the effects of DTG-based and EFV-based regimens on the MTCT of HIV among HIV-exposed infants in Ethiopia. An uncontrolled before-and-after study design was conducted among 958 mother-infant pairs (479 on EFV-based and 479 on DTG-based regimens) enrolled in the prevention of mother-to-child transmission (PMTCT) care from September 2015 to February 2023. The outcome variable was the HIV infection status among the exposed infants. A log-binomial model was employed, and the proportion was computed to compare the incidence of MTCT of HIV in both groups. The risk ratio (RR) with a 95% confidence interval (CI) was calculated to assess the predictor variables. Mothers on DTG-based regimens were approximately 44% (adjusted risk ratio (aRR): 0.56; 95% CI: 0.44, 0.70) less likely to transmit HIV to their infants than those on EFV-based regimens. In addition, poor or fair adherence to antiretroviral therapy (ART) (aRR: 5.82; 95% CI: 3.41, 9.93), home delivery (aRR: 3.61; 95% CI: 2.32, 5.62), mixed feeding practice (aRR: 1.83; 95% CI: 1.45, 2.3) and not receiving antiretroviral prophylaxis (aRR: 3.26; 95% CI: 1.6, 6.64) were found to increase the risk of MTCT of HIV infection, whereas older maternal age (aRR: 0.93; 95% CI: 0.9, 0.96) was a protective factor. Mother-to-child transmission of HIV was less frequently observed in mother-infant pairs exposed to the DTG-based regimens as compared to those exposed to the EFV-based regimens. Thus, DTG-based first-line ART regimens supplementation should be sustained to achieve global and national targets for zero new infections in HIV-exposed infants.

Clinicoetiological profile of congenital cataracts in children: A single-center experience

Introduction: Congenital cataract is the most common treatable cause of blindness during infancy and is responsible for 5%–20% of blindness in children worldwide. Materials and Methods: It was a retrospective descriptive study analyzing the causes of congenital cataracts in infants referred to the pediatric neurology department of a tertiary care institution, in South India. Results: Thirty-two infants with congenital cataracts underwent evaluation. Thirteen (40.6%) were &lt;6 months and 19 (59.4%) beyond 6 months of age. White reflex in eyes was the primary complaint in 14 (43.8%), not looking at the caregiver in 10 (31.3%), squint in 5 (15.6%), and involuntary movement of eyeballs in 3 (9.4%) patients. Cataracts were bilateral in 26 (81.3%) and unilateral in 6 (18.7%) patients. The associated features were developmental delay in 25 (78.1%), microcephaly in 15 (46.9%), seizures in 6 (18.8%), cardiac disease in 6 (18.8%), focal deficit in 3 (9.4%), and deafness in 2 (6.3%). Neuroimaging revealed basal ganglia calcifications in 6 (18.7%), cerebral atrophy in 3 (9.4%), gliosis in parieto-occipital regions and hyperintensities in frontal regions in 2 (6.3%) children each, and hydrocephalus, Dandy–Walker malformation, thin corpus callosum, and hypomyelination in one (3.1%) each. The etiological causes were confirmed rubella syndrome in 7 (21.9%), probable rubella syndrome in 3 (9.4%), confirmed cytomegalovirus in 6 (18.8%), probable cytomegalovirus in 7 (21.9%), herpes virus infection in 1 (3.1%), combined infections in 2 (6.3%), Down syndrome in 3 (9.4%), Lowe syndrome in 1 (3.1%), and idiopathic in 2 (6.3%) patients. Conclusion: Intrauterine infections, especially cytomegaloviral and rubella infections, are the common causes for congenital cataracts in infants. Vaccination against rubella, knowledge about intrauterine infections, mode of spread, and prevention are the needs of the hour.

Dysregulation of fetal-derived cochlear resident tissue macrophage mediate CMV-associated sensorineural hearing loss

Abstract Cytomegalovirus (CMV) is the most common congenital viral infection in the developed world and leading cause of non-genetic sensorineural hearing loss (SNHL) in children. Here we investigated the role of fetal-derived resident tissue macrophages (RTMs) in normal cochlear development and their role in CMV-associated SNHL. Using genetic fate mapping, we uncovered dual sources of fetal-derived RTMs from yolk sac (YS) and fetal liver (FL) hematopoiesis. YS-derived RTMs naturally recede after cochlea maturity while FL-derived RTMs expand, revealing a temporal layering of RTMs. Additionally YS-derived and FL-derived RTMs demonstrate spatial specificity, seeding distinct cochlear tissues. Both anti-CSF1R depletion of fetal-RTMs and embryonic genetic deletion of YS-derived RTMs by CSF1R-flox lead to SNHL and impaired cochlear tissue development, revealing the requirement for fetal RTMs in normal cochlear development. During CMV infection, scRNAseq and fate-mapping analysis revealed an infiltration of bone marrow-derived macrophages at the expense of yolk-sac derived RTMs, indicating that CMV infection disrupted the normal temporal layering of fetal-derived RTMs in the cochlea. Fetal-derived RTMs also upregulated inflammation-associated pathways and downregulated pathways critical for inner ear development, such as FGF and TGFb signaling. Together these data reveal perturbation of developing RTMs that regulate normal cochlear development as a mechanism underlying CMV-mediated SNHL.