Establishment, Implementation, Initial Outcomes, and Lessons Learned from Recent HIV Infection Surveillance Using a Rapid Test for Recent Infection Among Persons Newly Diagnosed With HIV in Thailand: Implementation Study.

Background: A recent infection testing algorithm (RITA) incorporating case surveillance (CS) with the rapid test for recent HIV infection (RTRI) was integrated into HIV testing services in Thailand as a small-scale pilot project in October 2020.

Objective: We aimed to describe the lessons learned and initial outcomes obtained after the establishment of the nationwide recent HIV infection surveillance project from April through August 2022.

Methods: We conducted desk reviews, developed a surveillance protocol and manual, selected sites, trained staff, implemented surveillance, and analyzed outcomes.

TargeTron inactivation of plasmid-regulated Chlamydia trachomatis CT084 results in a nonlytic phenotype.

Chlamydia trachomatis is an obligate intracellular bacterium that causes blinding trachoma and sexually transmitted disease. The chlamydial plasmid is a critical virulence factor in the pathogenesis of these diseases. Plasmid gene protein 4 (Pgp4) plays a major role in chlamydial virulence by regulating the expression of both chromosomal genes and Pgp3.

Should we initiate vasopressors earlier in patients with septic shock: A mini systemic review.

Septic shock treatment remains a major challenge for intensive care units, despite the recent prominent advances in both management and outcomes. Vasopressors serve as a cornerstone of septic shock therapy, but there is still controversy over the timing of administration. Specifically, it remains unclear whether vasopressors should be used early in the course of treatment.

TargeTron Inactivation of Chlamydia trachomatis Results in a Lipopolysaccharide 3-Deoxy-d-Manno-Oct-2-Ulosonic Acid-Deficient Strain That Is Cytotoxic for Cells.

All members of the family Chlamydiaceae have lipopolysaccharides (LPS) that possess a shared carbohydrate trisaccharide antigen, 3-deoxy-d-manno-oct-2-ulosonic acid (Kdo) that is functionally uncharacterized. A single gene, genus-specific epitope (), is responsible for attaching the tri-Kdo to lipid IVA. To investigate the function of Kdo in chlamydial host cell interactions, we made a -null strain (L2Δ) by using TargeTron mutagenesis.

The performance of using dried blood spot specimens for HIV-1 viral load testing: A systematic review and meta-analysis.

Background: Accurate routine HIV viral load testing is essential for assessing the efficacy of antiretroviral treatment (ART) regimens and the emergence of drug resistance. While the use of plasma specimens is the standard for viral load testing, its use is restricted by the limited ambient temperature stability of viral load biomarkers in whole blood and plasma during storage and transportation and the limited cold chain available between many health care facilities in resource-limited settings. Alternative specimen types and technologies, such as dried blood spots, may address these issues and increase access to viral load testing; however, their technical performance is unclear.

Diagnostic Accuracy of Dried Plasma Spot Specimens for HIV-1 Viral Load Testing: A Systematic Review and Meta-analysis.

Background: Dried plasma spot specimens may be a viable alternative to traditional liquid plasma in field settings, but the diagnostic accuracy is not well understood.

Methods: Standard databases (PubMed and Medline), conferences, and gray literature were searched until January 2019. The quality of evidence was evaluated using the Standards for Reporting Studies of Diagnostic Accuracy and Quality Assessment of Diagnostic Accuracy Studies-2 criteria.

The role of targeted regulation of by miR-10a-3p in the development and progression of paediatric mycoplasma pneumoniae pneumonia.

Background: MiR-10a-3p is associated with the pathogenesis of many immune inflammatory diseases including pneumonia (MPP), and cytochrome coxidase assembly homologue 11 (COX11) is one of its direct target proteins. This study investigates the function and mechanism of miR-10a-3p targeting with in the development and progression of paediatric MPP.

Methods: Ninty-seven paediatric MPP patients and 100 age- and sex-matched healthy children were enrolled.

Chlamydia evasion of neutrophil host defense results in NLRP3 dependent myeloid-mediated sterile inflammation through the purinergic P2X7 receptor.

Chlamydia trachomatis infection causes severe inflammatory disease resulting in blindness and infertility. The pathophysiology of these diseases remains elusive but myeloid cell-associated inflammation has been implicated. Here we show NLRP3 inflammasome activation is essential for driving a macrophage-associated endometritis resulting in infertility by using a female mouse genital tract chlamydial infection model.

A Chlamydial Plasmid-Dependent Secretion System for the Delivery of Virulence Factors to the Host Cytosol.

Chlamydia are obligate intracellular Gram-negative bacteria distinguished by a unique developmental biology confined within a parasitophorous vacuole termed an inclusion. The chlamydial plasmid is a central virulence factor in the pathogenesis of infection. Plasmid gene protein 4 (Pgp4) regulates the expression of plasmid gene protein 3 (Pgp3) and chromosomal glycogen synthase (GlgA), virulence factors secreted from the inclusion to the host cytosol by an unknown mechanism.

Leveraging gains from African Center for Integrated Laboratory Training to combat HIV epidemic in sub-Saharan Africa.

Background: In sub-Saharan Africa, there is dearth of trained laboratorians and strengthened laboratory systems to provide adequate and quality laboratory services for enhanced HIV control. In response to this challenge, in 2007, the African Centre for Integrated Laboratory Training (ACILT) was established in South Africa with a mission to train staffs from countries with high burdens of diseases in skills needed to strengthen sustainable laboratory systems. This study was undertaken to assess the transference of newly gained knowledge and skills to other laboratory staff, and to identify enabling and obstructive factors to their implementation.

High levels of HIV drug resistance among adults failing second-line antiretroviral therapy in Namibia.

To support optimal third-line antiretroviral therapy (ART) selection in Namibia, we investigated the prevalence of HIV drug resistance (HIVDR) at time of failure of second-line ART. A cross-sectional study was conducted between August 2016 and February 2017. HIV-infected people ≥15 years of age with confirmed virological failure while receiving ritonavir-boosted protease inhibitor (PI/r)-based second-line ART were identified at 15 high-volume ART clinics representing over >70% of the total population receiving second-line ART.

Chlamydia trachomatis Plasmid Gene Protein 3 Is Essential for the Establishment of Persistent Infection and Associated Immunopathology.

is an obligate intracellular bacterial pathogen that causes blinding trachoma and sexually transmitted disease afflicting hundreds of millions of people globally. A fundamental but poorly understood pathophysiological characteristic of chlamydial infection is the propensity to cause persistent infection that drives damaging inflammatory disease. The chlamydial plasmid is a virulence factor, but its role in the pathogenesis of persistent infection capable of driving immunopathology is unknown.

Low levels of HIV-1 drug resistance mutations in patients who achieved viral re-suppression without regimen switch: a retrospective study.

Background: We identified a HIV-positive cohort in virologic failure (VF) who re-suppressed without drug switch. We characterized their drug resistance mutations (DRM) and adherence profiles to learn how to better manage HIV drug resistance. A retrospective cohort study utilizing clinical data and stored samples.

Chlamydia trachomatis Lipopolysaccharide Evades the Canonical and Noncanonical Inflammatory Pathways To Subvert Innate Immunity.

is the most common bacterial cause of sexually transmitted infections. sexually transmitted infections are commonly asymptomatic, implying a pathogenic strategy for the evasion of innate inflammatory immune responses, a paradox as the outer membrane contains lipopolysaccharide (LPS), a known potent agonist of inflammatory innate immunity. Here, we studied the ability of chlamydial LPS to activate the proinflammatory canonical and noncanonical inflammasome pathways in mouse bone marrow-derived macrophages (BMDM).

PLCβ2 negatively regulates the inflammatory response to virus infection by inhibiting phosphoinositide-mediated activation of TAK1.

Excessive or uncontrolled release of proinflammatory cytokines caused by severe viral infections often results in host tissue injury or even death. Phospholipase C (PLC)s degrade phosphatidylinositol-4, 5-bisphosphate (PI(4,5)P2) lipids and regulate multiple cellular events. Here, we report that PLCβ2 inhibits the virus-induced expression of pro-inflammatory cytokines by interacting with and inhibiting transforming growth factor-β-activated kinase 1 (TAK1) activation.

High Levels of HIV-1 Drug Resistance in Children Who Acquired HIV Infection Through Mother to Child Transmission in the Era of Option B+, Haiti, 2013 to 2014.

Background: The main objective of this study was to determine the frequency and patterns of HIV drug resistance-associated mutations among children under 18 months of age born to HIV-1-positive mothers enrolled in the prevention of mother-to-child transmission services in Haiti.

Methods: Between January 1, 2013 and December 31, 2014, HIV-positive remnant dried blood spots collected from children under 18 months of age for Early Infant Diagnosis at the National Public Health Laboratory were used for HIV-1 genotyping. HIV drug resistance mutations were analyzed using the Stanford Drug Resistance HIVdb program.

Human Immunodeficiency Virus-1 Drug Resistance Patterns Among Adult Patients Failing Second-Line Protease Inhibitor-Containing Regimens in Namibia, 2010-2015.

Three hundred sixty-six adult patients in Namibia with second-line virologic failures were evaluated for human immunodeficiency virus drug-resistant (HIVDR) mutations. Less than half (41.5%) harbored ≥1 HIVDR mutations to standardized second-line antiretroviral therapy (ART) regimen.

Low and Decreasing Prevalence and Rate of False Positive HIV Diagnosis - Chókwè District, Mozambique, 2014-2017.

In 2017, rapid human immunodeficiency virus (HIV) testing services enabled the HIV diagnosis and treatment of approximately 15.3 million persons with HIV infection in sub-Saharan Africa with life-saving antiretroviral therapy (ART) (1). Although suboptimal testing practices and misdiagnoses have been reported in sub-Saharan Africa and elsewhere, trends in population burden and rate of false positive HIV diagnosis (false diagnosis) have not been reported (2,3).

Compromise of Second-Line Antiretroviral Therapy Due to High Rates of Human Immunodeficiency Virus Drug Resistance in Mozambican Treatment-Experienced Children With Virologic Failure.

Background: Virologic failure (VF) is highly prevalent in sub-Saharan African children on antiretroviral therapy (ART) and is often associated with human immunodeficiency virus drug resistance (DR). Most children still lack access to routine viral load (VL) monitoring for early identification of treatment failure, with implications for the efficacy of second-line ART.

Methods: Children aged 1 to 14 years on ART for ≥12 months at 6 public facilities in Maputo, Mozambique were consecutively enrolled after informed consent.

Successes and challenges in optimizing the viral load cascade to improve antiretroviral therapy adherence and rationalize second-line switches in Swaziland.

Introduction: As antiretroviral therapy (ART) is scaled up, more patients become eligible for routine viral load (VL) monitoring, the most important tool for monitoring ART efficacy. For HIV programmes to become effective, leakages along the VL cascade need to be minimized and treatment switching needs to be optimized. However, many HIV programmes in resource-constrained settings report significant shortfalls.

Utilization of dried blood spot specimens can expedite nationwide surveillance of HIV drug resistance in resource-limited settings.

Introduction: Surveillance of HIV drug resistance (HIVDR) is crucial to ensuring the continued success of antiretroviral therapy (ART) programs. With the concern of reduced genotyping sensitivity of HIV on dried blood spots (DBS), DBS for HIVDR surveillance have been limited to ART-naïve populations. To investigate if DBS under certain conditions may also be a feasible sample type for HIVDR testing in ART patients, we piloted nationwide surveys for HIVDR among ART patients using DBS in two African countries with rapid scale-up of ART.

Pretreatment HIV drug resistance among adults initiating ART in Namibia.

Background: Continued use of standardized, first-line ART containing NNRTIs and NRTIs may contribute to ongoing emergence of HIV drug resistance (HIVDR) in Namibia.

Methods: A nationally representative cross-sectional survey was conducted during 2015-16 to estimate the prevalence of significant pretreatment HIV drug resistance (PDR) and viral load (VL) suppression rates 6-12 months after initiating standardized first-line ART. Consenting adult patients (≥18 years) initiating ART were interviewed about prior antiretroviral drug (ARV) exposure and underwent resistance testing using dried blood spot samples.

Circumcision status at HIV infection is not associated with plasma viral load in men: analysis of specimens from a randomized controlled trial.

Background: Male circumcision provides men with approximately 60% protection from acquiring HIV infection via heterosexual sex, and has become a key component of HIV prevention efforts in sub-Saharan Africa. Possible mechanisms for this protection include removal of the inflammatory anaerobic sub-preputial environment and the high concentration of Langerhans cells on the inside of the foreskin, both believed to promote local vulnerability to HIV infection. In people who do acquire HIV, viral load is partially determined by infecting partner viral load, potentially mediated by size of infecting inoculum.