Search Results (168)

HIV-1 proviral landscapes were investigated using near-full-length HIV single-genome sequencing on blood samples from five children with vertically acquired infection and on ART for ~7–9 years. Proviral structures were compared to published datasets in children prior to ART, children on short-term ART, and adults on ART. We found a strong selection for large internal proviral deletions in children, especially deletions of the env gene. Only 2.5% of the proviruses were sequence-intact, lower than in the comparative datasets from adults. Of the proviruses that retained the env gene, >80% contained two or more defects, most commonly stop codons and/or gag start mutations. Significantly fewer defects in the major splice donor site (MSD) and packaging signal were found in the children on short or long-term ART compared to the adults, and tat was more frequently defective in children. These results suggest that different selection pressures may shape the proviral landscape in children compared to adults and reveal potentially different genetic regions to target for measuring the intact HIV reservoir and for achieving HIV remission in children. Full article

Background/Objective: Variations in measles vaccine antibody response by age and HIV status have been reported. This study assessed measles pre-vaccination status and compared humoral response durability over the first five years of life among HIV-infected (HI) children on early treatment, HIV-exposed uninfected (HEU), and HIV-unexposed uninfected (HUU) children within the ANRS 12225—Pediacam III cohort in Cameroon. Methods: Measles vaccine (MCV) was administered at 6 and 9 months for HIV-exposed infants and at 9 months for HIV-unexposed infants, followed by a measles-mumps-rubella (MMR) dose at 15 months for all. Measles antibody titers were measured pre-vaccination, 1–6 months post-MCV doses, and annually until age 5 using ELISA (Enzygnost, Dade Behring). Results: A total of 496 children were included: 143 HI (median age at cART initiation: 4.2 months, (IQR: 3.2–5.6)), 180 HEU, and 173 HUU. Of these, 456 children were tested pre-vaccination (median age: 6.1 months, IQR: 5.6–6.8), with 6.1% (95% CI: 4.1–8.6) seropositive to measles antibodies, with differences across groups. At 18.4 months (IQR: 18.1–19.9), seropositivity rates were 96.7% (59/61) in HI, 96.8% (90/93) in HEU, and 100% (111/111) in HUU groups. For children following the 6 + 9 + 15-month or 9 + 15-month MCV schedules, seropositivity at 18, 36, 48, and 60 months was 96%, 89%, 87%, and 88%, respectively, with no significant differences between groups. Conclusions: Early cART initiation in HI children may result in a robust initial measles antibody response, with comparable persistence of antibody titers across all groups up to five years. Full article

The human immunodeficiency virus (HIV-1) infiltrates the central nervous system (CNS) early in infection, leading to HIV-associated neurocognitive impairments, particularly pronounced in children who exhibit neurodevelopmental delay. Viral proteins, including the transactivator of transcription protein (Tat) and viral protein R (Vpr) are pivotal in HIV-1 neuropathogenesis, with their amino acid sequence variation influencing disease progression. Due to the difficulty of collecting cerebrospinal fluid from children, few studies have examined whether key Tat and Vpr neuropathogenic signatures found in blood are also present in the cerebrospinal fluid (CSF) of children with HIV. We employed Sanger sequencing for Tat and Vpr sequence analysis using retrospectively collected CSF samples from a South African pediatric HIV-1 subtype C cohort (n = 4). We compared our CSF-derived sequences with pediatric blood-derived sequences (n = 43) from various geographical regions, sourced from the Los Alamos database. Neuropathogenic amino acid variants were identified in Tat and Vpr sequences derived from CSF samples of South African pediatric participants No significant differences were found between subtype C sequences from CSF and blood. Regional analysis highlighted unique amino acid signatures. Obtaining pediatric CSF for HIV-1 sequencing is highly challenging. Despite a small sample size, this study offers rare insights into Tat and Vpr sequences in children, improving understanding of the potential HIV-1 brain pathogenesis in pediatric populations. Full article

Background: The MeMed BV^® BV score is a novel, promising host-protein score, differentiating bacterial from viral infections, that combines the expression levels of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), interferon gamma-induced protein-10 (IP-10), and C-reactive protein (CRP). The aim of our study was to determine its diagnostic accuracy in hospitalized febrile children. Methods: A prospective study was performed from December 2023 to April 2024 in two pediatric clinics at “Aghia Sophia” Children’s Hospital, Athens, Greece. Patients > 3 months old, presenting with fever, clinical suspicion of acute infection, and symptoms onset up to 7 days prior were considered eligible. Patients with cancer, Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), Tuberculosis (TB), and immunodeficiency were excluded. Two pediatricians reviewed the clinical, laboratory, microbiological, and radiological data and assigned the final diagnosis. The experts were blinded to the BV scores. Results: One hundred and thirty-five patients were enrolled. The predominant medical condition was respiratory tract infection (59.3% lower, 26.7% upper). Twenty-nine (21.5%) patients were diagnosed with bacterial infections. The BV score demonstrated a sensitivity of 96.2%, specificity of 88.7%, and negative predictive value (NPV) of 98.9% for bacterial infections. Equivocal BV scores were reported in 8.9% of cases and were excluded from calculations. The area under the curve was 0.96 (95% CI: 0.93–0.99). A ROC curve analysis was performed, and the optimal cut-off score was estimated at 60, providing a sensitivity of 93.1%, specificity of 88.7%, and NPV of 97.9%. Conclusions: In our study population, the BV score showed high sensitivity and NPV in bacterial infection diagnosis. Further studies are needed to assess the possibility of replacing the “equivocal” range with a narrower one or a specific cut-off value. Full article

Background: Human metapneumovirus (HMPV) is a significant cause of respiratory infections, particularly in children, the elderly, and immunocompromised individuals. However, data on HMPV infection in people living with HIV (PLWH) are limited, and cases of co-infection with influenza A virus in this population have not been previously described. Case Presentation: We reported the case of a 73-year-old HIV-positive man with multiple comorbidities, including insulin-dependent diabetes mellitus, who presented with fever, asthenia, and glycometabolic decompensation. Despite an initially unremarkable chest computed tomography (CT) scan, the patient developed progressive respiratory failure, requiring high-flow oxygen therapy. Molecular testing using the BIOFIRE^® FILMARRAY^® Pneumonia Panel Plus identified HMPV and influenza A virus as the causative pathogens. Bacterial cultures were negative, allowing for the discontinuation of empirical antibiotic therapy. The patient was successfully weaned off oxygen therapy and discharged after clinical improvement. Conclusions: This case highlights the potential severity of HMPV and influenza A co-infection in PLWH, emphasizing the importance of molecular diagnostics in distinguishing viral from bacterial infections. Rapid and accurate pathogen identification is essential for guiding appropriate antimicrobial stewardship and optimizing patient outcomes in community-acquired pneumonia. Full article

Background: HIV-related opportunistic infections like Pneumocystis jirovecii Pneumonia (PCP) remain a major contributor to child morbidity and mortality globally. PCP accounts for over 60% of AIDS in the first year of life and is responsible for a third of AIDS in children globally. Cotrimoxazole prophylaxis, which is an intervention directed towards tackling this burden, has not attained remarkable coverage despite advocacy towards scale-up. This work was therefore aimed at evaluating the efficacy of cotrimoxazole in the prevention of PCP among children exposed to and infected with HIV by carrying out a systematic review. Methods: Key scientific databases were searched for primary studies not older than 15 years old without language restrictions. Randomized Control Trials (RCTs) and Cohorts comparing the effectiveness of cotrimoxazole versus placebo in the prevention of PCP among children (<17 years) exposed to and infected with HIV were selected. Studies with a duration of follow-up not less than 3 months long were included. A meta-analysis was conducted on RevMan 5.3 statistical application software following data extraction, and the data quality and risk of bias were also assessed. Exactly Ten (10) studies were selected and analyzed. Findings: It was observed that cotrimoxazole had beneficial effects in terms of a reduction in mortality among HIV-exposed and infected children, as 72 fewer children in 1000 (based on an absolute 95% CI) will die as a result of cotrimoxazole compared to a placebo. Cotrimoxazole also significantly reduces hospital admissions (p-value of 0.008). The adverse events associated with cotrimoxazole are comparable to a placebo when co-administered with ARTS (p = 0.90), which did not impact adherence. Conclusion: The benefits of cotrimoxazole prophylaxis far outweigh its risks. Therefore, scaling up the intervention is recommended as a prophylactic for wider coverage, especially in resource-limited settings. Full article

EPIICAL (Early treated Perinatally HIV-Infected individuals: Improving Children’s Actual Life) is a consortium of European and non-European research-driven organizations inter-connected with the aim of establishing a clinical and experimental platform for the early identification of novel therapeutic strategies for the pediatric Human Immunodeficiency Virus (HIV). Within the EPIICAL project, several pediatric clinical studies were conducted, requiring the collection and transfer of biological samples and associated data across boundaries within and outside Europe. To ensure compliance with the applicable rules on pediatric data and sample transfer and to support the efforts of academic partners, which may not always have the necessary expertise and resources in place for designing, managing and conducting multi-national studies, the consortium established a dedicated expert Working Group. This group has guided the consortium since the start of the project through the complexities of the ethical and regulatory aspects of international clinical studies. The group provided support in the design and preparation of the prospective and retrospective multi-center and multi-national pediatric studies with a focus on the clinical study protocols, informed consent and assent forms. In particular, well-structured informed consent and assent templates were developed, and data sharing and material transfer agreements were set up to regulate the transfer of samples among partners and sites. We considered that such support and the implementation of ad hoc agreements could provide effective practical solutions for addressing ethical and regulatory hurdles related to sharing data and transferring samples in international pediatric clinical research. Full article

Robust CD8⁺ T cell responses are critical for the control of HIV infection in both adults and children. Our understanding of the mechanisms driving these responses is based largely on studies of cells circulating in peripheral blood in adults, but the regulation of CD8⁺ T cell responses in tissue sites is poorly understood, particularly in pediatric infections. DNA methylation is an epigenetic modification that regulates gene transcription. Hypermethylated gene promoters are associated with transcriptional silencing and, conversely, hypomethylated promoters indicate gene activation. In this study, we evaluated DNA methylation signatures of CD8⁺ T cells isolated from several different anatomic compartments during pediatric AIDS-virus infection by utilizing the SIV_mac239/251 infected infant rhesus macaque model. We performed a stepwise methylation analysis starting with total cellular DNA, to immunomodulatory cytokine promoters, to specific CpG sites within the cytokine promoters in CD8⁺ T cells isolated from peripheral blood, lymph nodes, and intestinal tissue during the chronic phase of infection. Tissue-specific methylation patterns were determined for transcriptionally active promoters of key immunomodulatory cytokines: interferon gamma (IFNγ), interleukin-2 (IL-2), and tumor necrosis factor alpha (TNFα). In this study, we observed tissue-specific differences in CD8⁺ T cell modulation by DNA methylation in SIV-infected infant macaques, highlighting the importance of evaluating cells from both blood and tissues to obtain a complete picture of CD8⁺ T cell regulation during pediatric HIV infection. Full article

Background: There is limited evidence comparing hepatitis A seroprevalence among HIV-exposed uninfected (HEU), HIV-infected (HIV), and unexposed uninfected (HUU) children. This compromises rational vaccine decision-making. Methods: This study comprised a retrospective health facility-based population of children aged 1 month–12 years. Archival sera were tested for markers of acute (anti-HAV IgM) or past (total anti-HAV) HAV infection. Subgroup analysis was conducted based on perinatal HIV exposure or infection status. Results: Among 513 children, the median age was 10 (IQR: 4–25) months. The median maternal age was 29 (IQR: 25–34) years. An anti-HAV seropositivity of 95.1% (117/122 [95% CI 90.2–98.4]) was found among those ≤6 months of age, indicative of the rate of transplacental antibody transfer. Among 1–12-year-olds, hepatitis A seroprevalence was 19.3% (37/192 [95% CI 14.1–25.7]), while 1.1% (2/188 [95% CI 0.12–2.76]) had evidence of acute infection. Compared to HIV-exposed subgroups (HIV = 60%, 6/10 [95% CI 27.4–86.3] and HEU = 45%, 9/20 [95% CI 23.8–68]), hepatitis A seroprevalence among HUU children was low (29.2%, 47/161 [95% CI 22.4–37.0]). Conclusions: Natural immunity among HIV-exposed and unexposed children in South Africa is insufficient to protect against severe liver complications associated with HAV infection later in adulthood. Full article

Toxoplasmosis is a disease caused by the intracellular protozoan Toxoplasma gondii, which has infected a third of the global population. Immunocompromised individuals and children with congenital disorders are most likely to be impacted by toxoplasmosis, and accurate diagnosis is essential. Toxoplasmosis is associated with HIV, schizophrenia, and diabetes. However, few studies have analyzed the association with other microorganisms. The purpose of this study was to determine the prevalence of coinfection of Toxoplasma gondii with other pathogens. From November 1997 to June 2024, PubMed, Science Direct, LAT index, Web of Science, Google Scholar, and Research Gate were searched. The keywords used were “Toxoplasma and microorganism coinfection”, “Toxoplasma coinfection and parasites”, “Toxoplasma coinfection and Protozoans or Bacteria or Helminths or Nematodes or Trematodes or Mycobacterium”, “Toxoplasma gondii in coinfection with virus”, and “Human Toxoplasmosis and coinfection”. Next, OpenMeta Analyst Software version 12.11 was used for meta-analysis, creating forest plots, and determining heterogeneity I². A total of 17,535 patients in 48 articles, of whom 5848 were seropositive to T. gondii, were included in this review. Population studies showed that the prevalence of virus infection was most frequent (32%), followed by parasites (18.4%), bacteria (29.7%), and fungi (5.8%). The pooled prevalence of coinfection was found to be 29.1%, with a lower bound of 0.232, an upper bound of 0.350, a standard error of 0.030, and p < 0.001. Heterogeneity (I²) was 99.12%, p < 0.001, with a global variance tau2 = 0.042. Toxoplasma gondii is an opportunist that mainly affects immunocompromised populations. The main coinfections were found to be viral infections, with HIV ranking first, followed by cytomegalovirus, hepatitis B and C, rubella, herpes simplex 1 and 2, SARS-CoV-2, and coxsackie virus. Full article

Schistosomiasis, which affects a large number of people worldwide, is among the most overlooked parasitic diseases. The disease is mainly prevalent in sub-Saharan Africa, southeast Asian countries, and South America due to the lack of adequate sanitation. The disease is mainly associated with poor hygiene, sanitation, and contaminated water, so it is also known as a disease of poverty. Three Schistosoma species (S. mansoni, S. japonicum, and S. haematobium) cause significant human infections. Co-infections with Schistosoma and other parasites are widely common. All these parasites may cause intestinal or urogenital schistosomiasis, where the disease may be categorized into the acute, sensitized, and chronic phases. The disease is more prevalent among school children, which may cause anemia and reduce development. Chronic infections frequently cause significant liver, intestinal, and bladder damage. Women exposed to contaminated water while performing normal duties like washing clothes might acquire urogenital schistosomiasis (UGS), which can cause tissue damage and raise the risk of blood-borne disease transmission, including human immunodeficiency virus (HIV) transmission. Praziquantel (PZQ) is the World Health Organization (WHO)-prescribed treatment for individuals who are known to be infected, but it does not prevent further re-infections with larval worms. Vaccine development and new molecular-based diagnosis techniques have promised to be a reliable approach to the diagnosis and prevention of schistosomiasis. The current review emphasizes the recent advancement in the diagnosis of schistosomiasis by molecular techniques and the treatment of schistosomiasis by combined and alternative regimes of drugs. Moreover, this review has also focused on the recent outbreak of schistosomiasis, the development of vaccines, and their clinical trials. Full article

Malignant lymphoma is an unusual form of gallbladder neoplasm. Almost all these tumors are diffuse large B-cell lymphomas or mucosa-associated lymphoid tissue-type lymphomas. Herein, we present a literature review of gallbladder Burkitt’s lymphoma (BL) cases that includes also an unpublished case in an HIV-infected child, observed by our center. The patient (a five-year-old black female child) attended the Federal Hospital of Lagoa, Rio de Janeiro, Brazil, underwent cholecystectomy, and the postoperative pathological analysis of the gallbladder revealed a diagnosis of BL (EBV-positive). Also, HIV serology was performed and returned positive. She was transferred to the Martagão Gesteira Institute of Pediatrics and Childcare for oncological treatment, dying from sepsis and disease progression about 18 months later. The patient did not undergo ART/cART. Previous cases of gallbladder BL were herein described and analyzed to characterize the clinicopathological features and possible similarities. BL can occur in the gallbladder both in the context of HIV infection and in the pediatric population. A biopsy is mandatory in cases with suggestive findings of lymphoma, and an early diagnosis can change the course of the disease. Furthermore, the case highlights the importance of an early initiation of ART/cART in people living with HIV (PLWH), especially in children. Full article

Understanding the interplay between infections and severe acute malnutrition is critical in attaining good clinical outcomes when managing malnourished children. However, review studies describing the profile of the associated pathogens in the malnourished African paediatric population are sparse in the literature. We aimed to identify the spectrum of pathogens from studies reporting infections in severely malnourished African children, as well as the antibiotic resistance pattern and clinical outcomes. A systematic literature review of the PubMed database was conducted following PRISMA guidelines from January 2001 to June 2024. The search algorithm was ((marasmus) OR (kwashiorkor) OR (severe acute malnutrition) OR (protein energy malnutrition)) AND (Africa). For a more comprehensive retrieval, an additional search algorithm was deployed: ((HIV) OR (tuberculosis)) AND (severe acute malnutrition). We included 60 studies conducted between 2001 and 2024. Most of the studies were from East Africa (n = 45, 75%) and Southern Africa (n = 5, 8.3%). A total of 5845 pathogens were identified comprising 2007 viruses, 2275 bacteria, 1444 parasites, and 119 fungal pathogens. The predominant pathogens were HIV, Mycobacterium tuberculosis, and malaria parasites accounting for 33.8%, 30%, and 24.2% of pathogens identified. Antibiotic susceptibility testing was documented in only three studies. Fatality rates were reported in 45 studies and ranged from 2% to 56% regardless of the category of pathogen. This review affirms the deleterious effect of infections in malnourished patients and suggests a gross underdiagnosis as studies were found from only 17 (31.5%) African countries. Moreover, data on fungal infections in severely malnourished African children were nearly absent despite this population being at risk. Thus, there is an urgent need to prioritize research investigating African children with severe acute malnutrition for fungal infections besides other pathogens and improve the availability of diagnostic tools and the optimized usage of antibiotics through the implementation of antimicrobial stewardship programmes. Full article

Background: Over the past two decades, intervention strategies to improve the use of the elimination of mother-to-child transmission (EMTCT) services have been implemented for several reasons. The reasons include elimination of HIV infections during pregnancy, delivery, breastfeeding, prevention of HIV, prevention of unintended pregnancies, and safer conception. Poor utilization of EMTCT services has been proven to put the child at risk of acquiring HIV, which could have been avoided. Objective: This study aims to explore and describe interventions to promote the elimination of mother-to-child transmission services among pregnant and nursing mothers in Africa. Method: A scoping literature review technique was undertaken on research papers published in English that focused on EMTCT, barriers, interventions, and methods to address challenges to EMTCT utilization. These were screened independently and coded. Results: The analysis comprised 14 out of approximately 9029 literature sources. Intervention strategies to improve EMTCT service utilization, according to the findings, include accessibility and affordability, healthcare worker training, integrating the elimination of mother-to-child transmission into maternal and child health services, community-based interventions, family-centred approaches, and the use of technology. Conclusions: Interventions that increase women’s use of EMTCT services will contribute to the aim of HIV-free generation by reducing new HIV infections in children and saving lives. Full article

Human Immunodeficiency Virus (HIV) infection during pregnancy poses significant risks to both maternal and child health, with potential adverse effects on perinatal outcomes. This study aimed to compare perinatal outcomes, including birth weight, length, Apgar scores, and prematurity rates, between HIV-exposed, uninfected (HEU) children and HIV-unexposed, uninfected (HUU) children. A total of 204 neonates were included in the study, comprising 102 born to HIV-positive mothers and 102 born to uninfected mothers. Our findings revealed significant differences in birth weight (p < 0.001), length (p < 0.001), and Apgar scores at both 1 min (p = 0.003) and 5 min (p < 0.001) between HIV-exposed and -unexposed children. The HIV-exposed group exhibited lower birth weights and lengths, along with lower Apgar scores, indicating potential neonatal health challenges. No significant disparities were observed in the prematurity risk between the two groups (OR = 2.58, p = 0.126), but the risk of being born small for gestational age (SGA) in the case of HEU newborns was significantly high (OR = 17.41, p < 0.001). The significant differences in birth weight, length, and Apgar scores underscore the need for tailored healthcare interventions and support for neonates born to HIV-positive mothers. These findings contribute to our understanding of the complex interplay between maternal HIV infection and perinatal outcomes, guiding healthcare professionals in delivering targeted care for this vulnerable population. Full article