-
Journal of the International AIDS... Jun 2023Co-trimoxazole prophylaxis is recommended for children born to women with HIV to protect those who acquire HIV from opportunistic infections, severe bacterial infections... (Review)
Review
INTRODUCTION
Co-trimoxazole prophylaxis is recommended for children born to women with HIV to protect those who acquire HIV from opportunistic infections, severe bacterial infections and malaria. With scale-up of maternal antiretroviral therapy, most children remain HIV-exposed uninfected (HEU) and the benefits of universal co-trimoxazole are uncertain. We assessed the effect of co-trimoxazole on mortality and morbidity of children who are HEU.
METHODS
We performed a systematic review (PROSPERO number: CRD42021215059). We systematically searched MEDLINE, Embase, Cochrane CENTRAL, Global Health, CINAHL Plus, Africa-Wide Information, SciELO and WHO Global Index Medicus for peer-reviewed articles from inception to 4th January 2022 without limits. Ongoing randomized controlled trials (RCTs) were identified through registries. We included RCTs reporting mortality or morbidity in children who are HEU receiving co-trimoxazole versus no prophylaxis/placebo. The risk of bias was assessed using the Cochrane 2.0 tool. Data were summarized using narrative synthesis and findings were stratified by malaria endemicity.
RESULTS
We screened 1257 records and included seven reports from four RCTs. Two trials from Botswana and South Africa of 4067 children who are HEU found no difference in mortality or infectious morbidity in children randomized to co-trimoxazole prophylaxis started at 2-6 weeks of age compared to those randomized to placebo or no treatment, although event rates were low. Sub-studies found that antimicrobial resistance was higher in infants receiving co-trimoxazole. Two trials in Uganda investigating prolonged co-trimoxazole after breastfeeding cessation showed protection against malaria but no other morbidity or mortality differences. All trials had some concerns or a high risk of bias, which limited the certainty of evidence.
DISCUSSION
Studies show no clinical benefit of co-trimoxazole prophylaxis in children who are HEU, except to prevent malaria. Potential harms were identified for co-trimoxazole prophylaxis leading to antimicrobial resistance. The trials in non-malarial regions were conducted in populations with low mortality potentially reducing generalizability to other settings.
CONCLUSIONS
In low-mortality settings with few HIV transmissions and well-performing early infant diagnosis and treatment programmes, universal co-trimoxazole may not be required.
Topics: Infant; Female; Child; Humans; Trimethoprim, Sulfamethoxazole Drug Combination; HIV Infections; Malaria; Uganda; Anti-Infective Agents; World Health Organization; Randomized Controlled Trials as Topic
PubMed: 37292018
DOI: 10.1002/jia2.26079 -
SAGE Open Medicine 2023Visceral leishmaniasis remains a deadly parasitic disease with diagnostic complexities. Currently, point-of-care chest imaging is gaining momentum in the diagnosis of... (Review)
Review
OBJECTIVES
Visceral leishmaniasis remains a deadly parasitic disease with diagnostic complexities. Currently, point-of-care chest imaging is gaining momentum in the diagnosis of infectious diseases. Respiratory symptoms are common in visceral leishmaniasis. Here we aimed to systematically synthesize the evidence on the utility of chest imaging on the diagnosis and management of patients with visceral leishmaniasis.
METHODS
We searched PubMed, Scopus, Web of Science, ScienceDirect, and Google Scholar databases for studies reporting chest imaging findings in patients with visceral leishmaniasis, published in English from database inception to November 2022. We used the Joanna Briggs Institute checklists to evaluate the risk of bias. The protocol of this systematic review was registered with the Open Science Framework: https://doi.org/10.17605/OSF.IO/XP24W.
RESULTS
Of 1792 studies initially retrieved, 17 studies with 59 participants were included. Of the 59 patients, 51% (30) had respiratory symptoms and 20% (12) were human immunodeficiency virus co-infected. Chest X-ray, high-resolution computed tomography, and chest ultrasound findings were available for 95% (56), 93% (55), and 2% (1) of the patients, respectively. The most common findings were pleural effusion (20%; 12), reticular opacities (14%; 8), ground-glass opacities (12%; 7), and mediastinal lymphadenopathies (10%; 6). High-resolution computed tomography was more sensitive than chest X-ray and detected lesions that were lost on chest X-ray, 62% (37) versus 29% (17). In almost all cases, regression of the lesions was observed with treatment. Microscopy of pleural or lung biopsy detected amastigotes. Polymerase chain reaction yield was better in pleural and bronchoalveolar lavage fluids. A parasitological diagnosis from pleural and pericardial fluid was possible in AIDS patients. Overall, the risk of bias was low.
CONCLUSIONS
Visceral leishmaniasis patients frequently had abnormal findings on high-resolution computed tomography. Chest ultrasound is a useful alternative in resource-limited settings to aid in diagnosis and subsequent treatment follow-up, especially when routine tests yield negative results despite clinical suspicion.
PubMed: 37284569
DOI: 10.1177/20503121231177812 -
Journal of Personalized Medicine May 2023Approximately 1 in 10 children with hearing loss is affected by auditory neuropathy spectrum disorder (ANSD). People who have ANSD usually have great difficulty...
Approximately 1 in 10 children with hearing loss is affected by auditory neuropathy spectrum disorder (ANSD). People who have ANSD usually have great difficulty understanding speech or communicating. However, it is possible for these patients to have audiograms that may indicate profound hearing loss up to normal hearing. This disorder is prognosed with positive, intact or present otoacoustic emissions (OAE) and/or cochlear microphonics (CM) as well as abnormal or absent auditory brainstem responses (ABR). Treatment methods include conventional hearing aids as well as cochlear implants. Cochlear implants (CI) usually promise better speech understanding for ANSD patients. We performed a systematic literature review aiming to show what improvements can effectively be achieved with cochlear implants in children with ANSD and compare this with our experience with two cases of ANSD implanted at our clinic. The retrospective review of two young CI patients diagnosed with ANSD during infancy demonstrated improvements over time in speech development communicated by their parents.
PubMed: 37241018
DOI: 10.3390/jpm13050848 -
The Lancet. HIV May 2023Point-of-care (POC) nucleic acid testing for diagnosis of HIV in infants facilitates earlier initiation of antiretroviral therapy (ART) than with centralised...
BACKGROUND
Point-of-care (POC) nucleic acid testing for diagnosis of HIV in infants facilitates earlier initiation of antiretroviral therapy (ART) than with centralised (standard-of-care, SOC) testing, but can be more expensive. We evaluated cost-effectiveness data from mathematical models comparing POC with SOC to provide global policy guidance.
METHODS
In this systematic review of modelling studies, we searched PubMed, MEDLINE, Embase, the National Health Service Economic Evaluation Database, Econlit, and conference abstracts, combining terms for "HIV" + "infant"/"early infant diagnosis" + "point-of-care" + "cost-effectiveness" + "mathematical models", without restrictions from database inception to July 15, 2022. We selected reports of mathematical cost-effectiveness models comparing POC with SOC for HIV diagnosis in infants younger than 18 months. Titles and abstracts were independently reviewed, with full-text review for qualifying articles. We extracted data on health and economic outcomes and incremental cost-effectiveness ratios (ICERs) for narrative synthesis. The primary outcomes of interest were ICERs (comparing POC with SOC) for ART initiation and survival of children living with HIV.
FINDINGS
Our search identified 75 records through database search. 13 duplicates were excluded, leaving 62 non-duplicate articles. 57 records were excluded and five were reviewed in full text. One article was excluded as it was not a modelling study, and four qualifying studies were included in the review. These four reports were from two mathematical models from two independent modelling groups. Two reports used the Johns Hopkins model to compare POC with SOC for repeat early infant diagnosis testing in the first 6 months in sub-Saharan Africa (first report, simulation of 25 000 children) and Zambia (second report, simulation of 7500 children). In the base scenario, POC versus SOC increased probability of ART initiation within 60 days of testing from 19% to 82% (ICER per additional ART initiation range US$430-1097; 9-month cost horizon) in the first report; and from 28% to 81% in the second ($23-1609, 5-year cost horizon). Two reports compared POC with SOC for testing at 6 weeks in Zimbabwe using the Cost-Effectiveness of Preventing AIDS Complications-Paediatric model (simulation of 30 million children; lifetime horizon). POC increased life expectancy and was considered cost-effective compared with SOC (ICER $711-850 per year of life saved in HIV-exposed children). Results were robust throughout sensitivity and scenario analyses. In most scenarios, platform cost-sharing (co-use with other programmes) resulted in POC being cost-saving compared with SOC.
INTERPRETATION
Four reports from two different models suggest that POC is a cost-effective and potentially cost-saving strategy for upscaling of early infant testing compared with SOC.
FUNDING
Bill & Melinda Gates Foundation, Unitaid, National Institute of Allergy and Infectious Diseases, National Institute of Child Health and Human Development, WHO, and Massachusetts General Hospital Research Scholars.
Topics: Child; Humans; State Medicine; HIV Infections; Point-of-Care Systems; Point-of-Care Testing; Early Diagnosis; Cost-Benefit Analysis; Acquired Immunodeficiency Syndrome
PubMed: 37149292
DOI: 10.1016/S2352-3018(23)00029-2 -
Cureus Mar 2023Human immunodeficiency virus (HIV) is a viral infection which progressively leads to acquired immunodeficiency syndrome (AIDS) in the absence of treatment. This happens... (Review)
Review
Human immunodeficiency virus (HIV) is a viral infection which progressively leads to acquired immunodeficiency syndrome (AIDS) in the absence of treatment. This happens through the destruction of crucial cells in the immune system, such as the helper T cells, dendritic cells, and macrophages. Since the first case was isolated in the 20th century, the disease has spread rapidly among humans, with significant renal, cardiovascular, respiratory, and neurological complications. It is predominantly sexually transmitted but non-sexual transmission. A relationship between HIV and renal diseases has been suggested for a long time, but only a few systematic studies have centered on this association. This systematic review aims to analyze the possible association between HIV and renal diseases as well as the range and pathogenesis of these renal diseases. HIV remains a critical infectious disease globally, inciting substantial morbidity and mortality. Studies have shown that people living with HIV (PLWH) are at increased risk of acute and chronic kidney disease. This review is based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Google Scholar, and Cochrane databases were searched exhaustively using the inclusion criteria of free full-text English papers that have exclusively studied humans in the last 20 years. Sixteen articles were selected including a systematic review, observational studies, and comprehensive narrative reviews on the role of HIV in the etiology of renal diseases, and were systemically reviewed and analyzed to elicit the wide range of possible renal complications resulting from HIV infection.
PubMed: 37123789
DOI: 10.7759/cureus.36755 -
Pathogens (Basel, Switzerland) Mar 2023Accumulating evidence suggests that toxoplasmosis in immunocompetent hosts can be severe and life-threatening. (Review)
Review
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 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- treatment can be lifesaving.
PubMed: 37111429
DOI: 10.3390/pathogens12040543 -
Clinical and Experimental Medicine Nov 2023The aim of this review is to provide a comprehensive overview about the link between viruses and celiac disease. A systematic search on PubMed, Embase, and Scopus was... (Review)
Review
The aim of this review is to provide a comprehensive overview about the link between viruses and celiac disease. A systematic search on PubMed, Embase, and Scopus was conducted on March 07, 2023. The reviewers independently selected the articles and chose which articles to include. The review is a textual systemic review, and all relevant articles were included based on title and abstract. If there was a disagreement between the reviewers, they came to a consensus during deliberation sessions. A total of 178 articles were selected for the review and read in full; only part of them was retained. We found studies between celiac disease and 12 different viruses. Some of the studies were done only on small groups. Most studies were on pediatric population. Evidence for an association was found with several viruses (trigger or protective). It seems that only a part of the viruses could induce the disease. Several points are important to keep in mind: firstly, simple mimicry or that the virus induces a high level of TGA is not sufficient to promote the disease. Secondly, inflammatory background is necessary to induce CD with virus. Thirdly, IFN type 1 seems to have an important role. Some of the viruses are potential or known triggers like enteroviruses, rotaviruses, reoviruses, and influenza. Further studies are needed to better understand the role of viruses in celiac disease to better treat and prevent the disease.
Topics: Child; Humans; Celiac Disease; Viruses
PubMed: 37103650
DOI: 10.1007/s10238-023-01070-9 -
PloS One 2023Undernutrition (Body Mass Index < 18.5 kg/m2) is a common problem and a major cause of hospital admission for patients living with HIV. Though sub-Saharan Africa is the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Undernutrition (Body Mass Index < 18.5 kg/m2) is a common problem and a major cause of hospital admission for patients living with HIV. Though sub-Saharan Africa is the most commonly affected region with HIV and malnutrition, a meta-analysis study that estimates the prevalence and correlates of undernutrition among adults living with HIV has not yet been conducted. The objective of this study was to determine the pooled prevalence of undernutrition and associated factors among adults living with HIV/AIDS in sub-Saharan Africa.
METHODS
Studies published in English were searched systematically from databases such as PubMed, Google Scholar, and gray literature, as well as manually from references in published articles. Observational studies published from 2009 to November 2021 were included. The data extraction checklist was prepared using Microsoft Excel and includes author names, study area, publication year, sample size, prevalence/odds ratio, and confidence intervals. The results were presented and summarized in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) standard. Heterogeneity was investigated using the Q test, I2, τ2, τ and predictive interval. STATA version 17 was used to analyze the data. A meta-analysis using a random-effects model was used to determine the overall prevalence and adjusted odds ratio. The study has been registered in PROSPERO with a protocol number of CRD42021268603.
RESULTS
In this study, a total of 44 studies and 22,316 participants were included. The pooled prevalence of undernutrition among adult people living with HIV (PLWHIV) was 23.72% (95% CI: 20.69-26.85). The factors associated with undernutrition were participants' age (AOR = 0.5, 95% CI: 0.29-0.88), gender (AOR = 2.08, 95% CI: 0.22-20.00), World Health Organization (WHO) clinical stage (AOR = 3.25, 95% CI: 2.57-3.93), Cluster of Differentiation 4 (CD4 count) (AOR = 1.94, 95% CI: 1.53-2.28), and duration of ART (AOR = 2.32, 95% CI: 1.6-3.02).
CONCLUSION
The pooled prevalence of undernutrition among adult PLWHIV in sub-Saharan Africa remained high. WHO clinical stage, CD4 count, duration of ART treatment, age, and sex were found to be the factors associated with undernutrition. Reinforcing nutrition counseling, care, and support for adults living with HIV is recommended. Priority nutritional screening and interventions should be provided for patients with advanced WHO clinical stages, low CD4 counts, the male gender, younger age groups, and ART beginners.
Topics: Humans; Adult; Male; Nutrition Assessment; Prevalence; Nutritional Status; HIV Infections; Malnutrition; Africa South of the Sahara
PubMed: 36961844
DOI: 10.1371/journal.pone.0283502 -
Journal of the International AIDS... Mar 2023Human immunodeficiency virus (HIV) continues to rise in young people among low- and middle-income countries (LMIC). The US National Institutes of Health (NIH) supports... (Review)
Review
INTRODUCTION
Human immunodeficiency virus (HIV) continues to rise in young people among low- and middle-income countries (LMIC). The US National Institutes of Health (NIH) supports the largest public investment in HIV research globally. Despite advancements in the last decade, adolescents and young adults (AYA) remain underrepresented in research to improve HIV prevention and care. We undertook a programme analysis of NIH grants and conducted a targeted review of linked publications on international AYA research across the HIV prevention and care continuum (HPCC) to inform new initiatives to address the needs of AYA in these settings.
METHODS
NIH-funded grants from 2012 to 2017, pertaining to AYA in LMIC, and evaluating areas of HIV prevention, care and/or treatment were identified. A systematic review of publications limited to funded grants was performed in two waves: 2012-2017 and 2018-2021. The review included a landscape assessment and an evaluation of NIH-defined clinical trials, respectively. Data on outcomes across the HPCC were abstracted and analysed.
RESULTS
Among grant applications, 14% were funded and linked to 103 publications for the analytic database, 76 and 27 from the first and second waves, respectively. Fifteen (15%) wave 1 and 27 (26%) wave 2 publications included an NIH-defined clinical trial. Among these, 36 (86%) did not target a key population (men who have sex with men, drug users and sex workers) and 37 (88%) were exclusively focused on sub-Saharan Africa. Thirty (71%) publications addressed at least one HPCC milestone. Specific focus was on milestones in HIV prevention, care or both, for 12 (29%), 13 (31%) and five (12%) of publications, respectively. However, few addressed access to and retention in HIV care (4 [14%]) and none included microbicides or treatment as prevention. More focus is needed in crucial early steps of the HIV care continuum and on biomedical HIV prevention interventions.
DISCUSSION AND CONCLUSIONS
Research gaps remain in this portfolio across the AYA HPCC. To address these, NIH launched an initiative entitled Prevention and Treatment through a Comprehensive Care Continuum for HIV-affected Adolescents in Resource Constrained Settings (PATC H) to generate needed scientific innovation for effective public health interventions for AYA affected by HIV in LMIC.
Topics: Male; Humans; Young Adult; Adolescent; HIV Infections; HIV; Homosexuality, Male; Sexual and Gender Minorities; Continuity of Patient Care
PubMed: 36951058
DOI: 10.1002/jia2.26065 -
Journal of the International AIDS... Feb 2023Tenofovir alafenamide (TAF) is approved for paediatric use in fixed-dose combination tablets, but efficacy and safety data in children are limited. We conducted a... (Review)
Review
INTRODUCTION
Tenofovir alafenamide (TAF) is approved for paediatric use in fixed-dose combination tablets, but efficacy and safety data in children are limited. We conducted a systematic review on the efficacy/effectiveness and safety of TAF in infants, children and adolescents living with HIV.
METHODS
We searched MEDLINE, Embase, the Cochrane Library, clinical trial registries, reference lists and relevant conferences to identify literature published January 2009-March 2021. We included clinical trials and observational studies assessing the efficacy/effectiveness or safety of TAF through ≥6 months of treatment in participants aged 0-19 years.
RESULTS AND DISCUSSION
Overall 3626 abstracts and 371 full papers were screened. Four single-arm, innovator-funded trials (341 participants) and a pooled analysis of those trials were identified. All four trials included treatment-experienced and virally suppressed children or adolescents. One trial also included treatment-naïve adolescents with baseline viral load >1000 copies/ml. The risk of bias was rated as low in one study and unclear in the other three owing to missing data on study design (all conference presentations). At 48 weeks, 92% (46/50) of treatment-naïve participants were virally suppressed (one trial). Among treatment-experienced participants with viral load at 48 weeks, 214 of 224 participants were virally suppressed. Across the studies, one grade 3/4 adverse event was considered drug-related (intermediate uveitis). There were three discontinuations for adverse events (grade 2 anxiety and insomnia, grade 1 iridocyclitis [drug-related] and grade 1 pulmonary tuberculosis [unrelated to treatment]). One accidental death occurred across the four studies. In the pooled analysis of 223 participants, the median change in bone mineral density z-score (height- and age-adjusted) from baseline to 48 weeks was -0.12 (interquartile range [IQR] -0.46, 0.17) to 0.05 (IQR not reported) for spine, and -0.09 (IQR -0.33, 0.07) to 0.09 (IQR not reported) for total body less head. Weight-for-age z-scores increased by 0.25 from baseline to 48 weeks.
CONCLUSIONS
Four single-arm trials were identified in this systematic review, with initial evidence suggesting good viral suppression and no obvious safety concerns in children and adolescents on TAF-containing regimens over 24-48 weeks. However, further comparative and longer-term safety data are needed in children and adolescents, including on weight and metabolic changes.
Topics: Infant; Humans; Child; Adolescent; Tenofovir; HIV Infections; Anti-HIV Agents; HIV-1; Adenine; Emtricitabine
PubMed: 36823283
DOI: 10.1002/jia2.26037