Cervical cancer screening outcomes for HIV-positive women in the Lubombo and Manzini regions of Eswatini-Prevalence and predictors of a positive visual inspection with acetic acid (VIA) screen.

This study aimed to describe the prevalence and predictors of a positive VIA (visual inspection with acetic acid) cervical cancer screening test in women living with human immunodeficiency virus (HIV). We retrospectively analysed data from women aged ≥15 who accessed VIA screening from health facilities in the Lubombo and Manzini regions of Eswatini. Sociodemographic and clinical data from October 2020 to June 2023 were extracted from the client management information system (CMIS). VIA screening outcome was categorised into negative, positive, or suspicious. A logistic regression model estimated the adjusted odds ratio (AOR) of the predictors of a positive VIA screen at p<0.05 with 95% confidence intervals. Of 23,657 participants, 60.8% (n = 14,397) were from the Manzini region. The mean age was 33.3 years (standard deviation 7.0), and 33% (n = 7,714) were first-time screens. The prevalence of a positive VIA was 2.6% (95% CI: 2.2%, 3.0%): 2.8% (95% CI: 2.2%, 3.5%) in Lubombo and 2.4% (95% CI: 2.0%, 2.9%) in Manzini (p = 0.096). Screening at mission-owned (AOR 1.40; p = 0.001), NGO-owned (AOR 3.08; p<0.001) and industrial/workplace-owned health facilities (AOR 2.37; p = 0.044) were associated with increased odds of a positive VIA compared to government-owned health facilities. Compared to those aged 25-34, the odds of a positive VIA increased by 1.26 for those in the 35-44 age group (AOR 1.26; p = 0.017). Predictors with lower odds for a positive VIA test were: being on anti-retroviral therapy (ART) for 5-9 years (AOR 0.76; p = 0.004) and ≥10 years (AOR 0.66; p = 0.002) compared to <5 years; and having an undetectable viral load (AOR 0.39; p<0.001) compared to unsuppressed. Longer duration on ART and an undetectable viral load reduced the odds, while middle-aged women and screening at non-public health facilities increased the odds of a positive VIA screen.

Secondary syphilis presenting with alopecia and leukoderma in a stable HIV-positive patient in a resource-limited setting: a case report.

BACKGROUND: Syphilis is an infection caused by the bacteria Treponema pallidum. It is mainly transmitted through oral, vaginal and anal sex, in pregnancy and through blood transfusion. Syphilis develops in primary, secondary, latent and tertiary stages and presents with different clinical features at each stage. Infected patients can remain asymptomatic for several years and, without treatment, can, in extreme cases, manifest as damage in several organs and tissues, including the brain, nervous tissue, eyes, ear and soft tissues. In countries with a high human immunodeficiency virus (HIV) burden, syphilis increases the risk of HIV infections. We report the case of a young HIV-positive black woman who presented with alopecia and hypopigmentation as features of secondary syphilis. CASE PRESENTATION: A virologically suppressed 29-year-old woman on Anti-retroviral Therapy (ART) presented with a short history of generalized hair loss associated with a non-itchy maculopapular rash and skin depigmentation on the feet. Limited laboratory testing confirmed a diagnosis of secondary syphilis. She was treated with Benzathine Penicillin 2.4MU. After receiving three doses of the recommended treatment, the presenting features cleared, and the patient recovered fully. CONCLUSION: This case demonstrates the importance of a high index of clinical suspicion and testing for syphilis in patients presenting with atypical clinical features of secondary syphilis, such as hair loss and hypopigmentation. It also highlights the challenges in diagnosing and clinically managing syphilis in a resource-limited setting.

Corrigendum: Diabetes-Tuberculosis Care in Eswatini: A Qualitative Study of Opportunities and Recommendations for Effective Services Integration.

[This corrects the article DOI: 10.3389/ijph.2023.1605551.].

Tuberculosis services during the COVID-19 pandemic: A qualitative study on the impact of COVID-19 and practices for continued services delivery in Eswatini.

Objectives: To describe the impact of the COVID-19 pandemic on tuberculosis services and the different approaches healthcare workers adopted to ensure continued tuberculosis service delivery in Eswatini. Study design: This is a qualitative study with a cross-sectional design. Methods: Thirteen nurses and 9 doctors who provide tuberculosis care from 10 health facilities participated in an in-depth interview to describe how the COVID-19 pandemic affected tuberculosis services and the approaches adopted to ensure continued patient care. Twenty in-person and 2 telephone interviews were conducted. The participating facilities were selected based on a ranking criterion of the number of patients seen. Data were analyzed using thematic content analysis. NVivo 12 software was used for qualitative analysis, and the Consolidated Criteria guided the study for Reporting Qualitative research (COREQ). Results: Two major themes emerged: COVID-19 impacted services delivery and access; and best practices that ensured healthcare services delivery. Six sub-themes describe how COVID-19 impacted services: all attention focused on COVID-19; COVID worsened the health system challenges; COVID hindered patients from accessing care; patients defaulted due to the lockdown; COVID impacted the quality of care and increased the risk of infection among healthcare workers. Five sub-themes describe best practices that ensure continued service delivery: Home-based care, Patient support, Patient Education, Integrated Services, and Staff rotation. Conclusion: While various strategies were adopted globally to mitigate the impact of the COVID-19 pandemic, these strategies need contextualization to be effective and sustainably incorporated into routine care to ensure continuity of and access to TB and other healthcare services.

Implementation of the Automated Medication Dispensing System-Early Lessons From Eswatini.

Objectives: This article describes the implementation of an automated medication dispensing system (AMDS) in Eswatini to increase medication access and presents the early lessons from this implementation. Methods: The AMDS was installed at four health facilities across two regions through collaborative stakeholder engagement. Healthcare workers were trained, and clients who met the inclusion criteria accessed their medications from the system. Each step of the implementation was documented and summarised in this article. Results: Early lessons suggest that implementation of the AMDS is acceptable and feasible to clients and healthcare workers and that phased introduction of medication classes, commencing with antiretroviral therapy (ART) and incorporating other medications in later phases is feasible. Additionally, improved client-centred messaging and communication, consistent power supply and internet network connectivity, and scheduling medication pickup with other services increase AMDS system utilisation. Conclusion: Eswatini has many clients living with HIV and non-communicable diseases (NCDs). Easy, convenient, quick, non-stigmatising and client-centred access to ART and medication for NCDs is critical in addressing retention in care and achieving optimal treatment outcomes.

Diabetes-Tuberculosis Care in Eswatini: A Qualitative Study of Opportunities and Recommendations for Effective Services Integration.

Objective: This study describes the availability of basic services, equipment, and commodities for integrated DM-TB services, best practices by healthcare workers, and opportunities for better integration of DM-TB care in Eswatini. Methods: A qualitative design was used. Twenty-three healthcare workers participated in a survey and key informant interview. Results: Most respondents indicated DM and TB care are integrated and clients access blood pressure and fasting/random blood glucose assessment. Few respondents indicated they provide visual assessment, hearing assessment, and HbA1c testing. Respondents experienced stockouts of urinalysis strips, antihypertensive drugs, insulin, glucometer strips, and DM drugs in the previous 6 months before the interview. Four main themes emerged from the qualitative interviews-quality and current standards of care, best practices, opportunities, and recommendations to improve integrated services delivery. Conclusion: While DM care is provided for TB patients, the implementation of integrated DM-TB services is suboptimal as the quality and current standards of care vary across health facilities due to different patient-level and health system challenges. Some identified opportunities must be utilized for a successful DM-TB integration.

Systematic review and meta-analysis on the etiology of bacterial pneumonia in children in sub-Saharan Africa.

Introduction: Before the introduction of vaccination to protect children from pneumonia, Streptococcus pneumoniae and Haemophilus influenzae type B (HiB) were the most frequent aetiological agents causing bacterial pneumonia in children under five years old. However, the etiology of childhood pneumonia appears to be changing and nonvaccine- type S. pneumoniae, non-typeable H. influenzae, and Staphylococcus aureus are becoming more relevant. Objective: We conducted a systematic review aimed at identifying the common causes of bacterial pneumonia in children in sub-Saharan Africa. Methods: We searched PubMed, Web of Science and African Index Medicus and included primary studies conducted since January 2010 that reported on the bacterial causes of pneumonia in children under five from sub-Saharan Africa. We extracted data items (about the study setting, pneumonia diagnosis, sampling, microbiological methods, and etiological agents) as well as study quality indicators. Results: Streptococcus pneumoniae was the most common bacteria in blood cultures from children with pneumonia (8%, 95% CI: 4-14%), and H. influenzae was second (3%, 95% CI: 1-17%). Children's nasopharynx commonly contained S. pneumoniae (66%), Moraxella catarrhalis (62%), and H. influenzae (44%). Conclusion: S. pneumoniae and H. influenzae cause bacterial pneumonia in sub-Saharan African children. Our review also highlights the prevalence of potentially pathogenic bacteria in the nasopharynx of children under five and calls for more research into how nasopharyngeal colonization causes pneumonia.

Tuberculosis treatment and resulting abnormal blood glucose: a scoping review of studies from 1981 - 2021.

BACKGROUND: Hyperglycaemia is a risk factor for tuberculosis. Evidence of changes in blood glucose levels during and after tuberculosis treatment is unclear. OBJECTIVE: To compile evidence of changes in blood glucose during and after tuberculosis treatment and the effects of elevated blood glucose changes on treatment outcomes in previously normoglycaemic patients. METHODS: Original research studies (1980 to 2021) were identified in PubMed, Web of Science, CINAHL and Embase databases. RESULTS: Of the 1,277 articles extracted, 14 were included in the final review. All the studies were observational and 50% were prospective. Fasting blood sugar was the most common clinical test (64%), followed by the glycated haemoglobin test and the oral glucose tolerance test (each 50%). Most tests were conducted at baseline and in the third month of treatment. Twelve studies showed that the prevalence of hyperglycaemia in previously normoglycaemic patients decreased from baseline to follow-up and end of treatment. Three studies showed successful treatment outcomes of 64%, 75% and 95%. Patients with hyperglycaemia at baseline were more likely to develop cavitary lung lesions and poor treatment outcomes and had higher post-treatment mortality. There was no difference in outcomes by human immunodeficiency virus (HIV) status. CONCLUSION: Elevated blood glucose in normoglycaemic patients receiving treatment for tuberculosis decreased by the end of treatment. Positive HIV status did not affect glucose changes during treatment. Further research is needed to investigate post-treatment morbidity in patients with baseline hyperglycaemia and the effects of HIV on the association between blood glucose and tuberculosis.

GeneXpert rollout in three high-burden tuberculosis countries in Africa: A review of pulmonary tuberculosis diagnosis and outcomes from 2001 to 2019.

Background: The rollout of GeneXpert aimed at increasing early diagnosis of tuberculosis to improve treatment outcomes and global tuberculosis targets. Objective: This study evaluated trends in tuberculosis diagnosis and outcomes pre- and post-introduction of GeneXpert in three African countries - the Democratic Republic of the Congo (DRC), Nigeria and South Africa. Methods: Data from 2001 to 2019 were extracted from the World Health Organization's data repository. Descriptive analysis, paired t-tests and interrupted time series models were used. Results: Estimated tuberculosis incidence decreased from 327/100 000 to 324/100 000 in the DRC, and from 1220/100 000 to 988/100 000 in South Africa. Incidence remained at 219/100 000 in Nigeria. The tuberculosis case notification rate did not change significantly. Increases in the new case treatment success rates were statistically significant (DRC: p = 0.0201; Nigeria: p = 0.0001; South Africa: p = 0.0017); decreases in mortality were also statistically significant (DRC: p = 0.0264; Nigeria: p = 0.0001; South Africa: p < 0.0001). Time series models showed insignificant increases in new tuberculosis cases in DRC (n = 1856, p = 0.085) and Nigeria (n = 785, p = 0.555) from 2011 to 2019; and a statistically significant decrease in South Africa (n = 15 269, p = 0.006). Conclusion: Improvements in tuberculosis treatment outcomes were achieved, but little progress has been made in new case notification due to varied implementation and scale-up of GeneXpert across the three countries. Implementation barriers need to be addressed to achieve the required tuberculosis targets.

Creating a Collaborative Trauma-Informed Interdisciplinary Citywide Victim Services Model Focused on Health Care for Survivors of Human Trafficking.

Although human trafficking is recognized as a public health issue, research on the health effects of human trafficking and best intervention practices is limited. We describe 2 citywide collaborative victim services models, the THRIVE (Trafficking, Healthcare, Resources, and Interdisciplinary Victim Services and Education) Clinic at the University of Miami and Jackson Health System in Miami, Florida, and the Greater Houston Area Pathways for Advocacy-based, Trauma-Informed Healthcare (PATH) Collaborative at Baylor College of Medicine, CommonSpirit Health, and San Jose Clinic in Houston, Texas, funded in part by the Office for Victims of Crime, which focus on trauma-informed health care delivery for victims of human trafficking. From June 2015 through September 2021, the THRIVE Clinic served 214 patients with an average age of 28.7 years at the time of their first visit. From October 2017 through September 2021, the PATH Collaborative received 560 suspected trafficking referrals, 400 of which screened positive for labor or sex trafficking. These models serve as a framework for replication of interdisciplinary practices to provide health care for this unique population and preliminary information about the strategies put in place to assist victims during their recovery. Key lessons include the importance of a citywide needs assessment, patient navigators, interdisciplinary care, and building community partnerships to ensure safe housing, transportation, identification, health insurance, vocation services, input from survivors, peer-to-peer mentorship, and medical-legal services. Further research is needed to understand the detrimental health effects of trafficking and the health care needs of victims. In addition, a need exists to develop optimal models of care for recovery and reintegration for this patient population and to address public health, legal, and medical policies to ensure access to and sustainability of comprehensive, trauma-informed, interdisciplinary victim services.

Epidemiology and Control of diabetes - tuberculosis comorbidity in Eswatini: protocol for the prospective study of tuberculosis patients on predictive factors, treatment outcomes and patient management practices.

INTRODUCTION: Previous studies indicate people with diabetes mellitus (DM) may have varying treatment outcomes when receiving treatment for tuberculosis (TB) and that TB infection or its treatment may predispose them to develop an abnormal blood glucose or type 2 DM. This has implications for Eswatini which is a high TB burden country and with increasing cases of non-communicable diseases including DM. This study will describe the epidemiology of DM-TB comorbidity in a prospective cohort of patients receiving TB treatment and identify best practices for integration of care for non-communicable diseases into TB services in Eswatini. METHODS AND ANALYSIS: This study will employ a mixed-methods approach. Data from a prospective cohort of newly enrolled patients with TB at 12 health facilities from 1 June 2022 to 30 September 2022, and followed up to 30 April 2023, will be used. For the qualitative, key informants who provide TB services at the health facilities will be interviewed. Quantitative data from patients will be analysed descriptively and by tests of association and multivariate modelling. Key informant interviews from healthcare workers will be analysed using content analysis. ETHICS AND DISSEMINATION: This research has been approved by the Eswatini Health and Human Research Review Board and participant confidentiality will be maintained. COVID-19 safety measures to reduce the risk of infection or transmission by researchers and participants have been instituted. Key programmatic findings and how they can impact healthcare delivery and access will be presented to the specific programme in the Eswatini Ministry of Health and other relevant stakeholders.

COVID-19-related research in Africa: a cross-sectional review of the International Clinical Trial Registration Platform (ICTRP).

OBJECTIVE: The declaration of the coronavirus disease (COVID-19), a pandemic in early 2020, has seen an upsurge in research globally to fill gaps in the epidemiology of the SARS-CoV-2 virus impact on health care and clinical management, as well as possible prevention and treatment modalities. Published literature on the different types of COVID-19 research conducted globally is varied and is particularly limited in Africa. This study sets out to describe the COVID-19-related research registered and conducted on the African continent. METHODS: This is a cross-sectional study of all COVID-19-related studies available in the WHO's International Clinical Trials Registry Platform (ICTRP) repository. We extracted studies registered from March 1, 2020, to July 15, 2021. A descriptive analysis of the extracted data was performed, and the findings were presented. RESULTS: At extraction, a total of 12,533 COVID-19-related studies were listed on the ICTRP portal. We included 9803 studies, after excluding 2060 duplicate records and 686 records without a site/country. While 9347 studies (96%) were conducted outside of Africa, only 456 studies (4%) were conducted in the African continent, of which 270 (59.2%) were interventional studies, and 184 (40.4%) were observational studies. About 80% of the studies were conducted in Egypt and South Africa, and most of these involved testing of drugs and biologicals. CONCLUSION: The African continent hosts considerably fewer COVID-19-related research compared to other parts of the world. This may have implications on scientific evidence available for implementing COVID-19 control efforts. There is, therefore, a need for local funding and ownership of research projects and north-south collaboration in research.

Trends in clinical trial registration in sub-Saharan Africa between 2010 and 2020: a cross-sectional review of three clinical trial registries.

OBJECTIVE: Prospective registration of clinical trials is an ethical, scientific, and legal requirement that serves several functions, including minimising research wastage and publication bias. Sub-Saharan Africa (SSA) is increasingly hosting clinical trials over the past few years, and there is limited literature on trends in clinical trial registration and reporting in SSA. Therefore, we set out to determine the trends in clinical trials registered in SSA countries between 2010 and July 2020. METHODS: A cross-sectional study design was used to describe the type of clinical trials that are conducted in SSA from 1 January 2010 to 31 July 2020. The registries searched were ClinicalTrials.gov (CTG), the Pan African Clinical Trials Register (PACTR), and the International Standard Randomized Controlled Trial Number (ISRCTN). Data were extracted into Excel and imported into STATA for descriptive analysis. RESULTS: CTG had the highest number of registered trials at 2622, followed by PACTR with 1501 and ISRCTN with 507 trials. Trials were observed to increase gradually from 2010 and peaked at 2018-2019. Randomised trials were the commonest type, accounting for at least 80% across the three registries. Phase three trials investigating drugs targeted at infections/infestations were the majority. Few completed trials had their results posted: 58% in ISRCTN and 16.5% in CTG, thus suggesting reporting bias. CONCLUSION: Despite the gradual increase in clinical trials registered during the period, recent trends suggest a drop in the number of trials registered across the region. Strengthening national and regional regulatory capacity will improve clinical trial registration and minimise reporting bias in completed clinical trials.

Considerations for Establishing Successful Coronavirus Disease Vaccination Programs in Africa.

The accelerated development of coronavirus disease (COVID-19) candidate vaccines is intended to achieve worldwide immunity. Ensuring COVID-19 vaccination is crucial to stemming the pandemic, reclaiming everyday life, and helping restore economies. However, challenges exist to deploying these vaccines, especially in resource-limited sub-Saharan Africa. In this article, we highlight lessons learned from previous efforts to scale up vaccine distribution and offer considerations for policymakers and key stakeholders to use for successful COVID-19 vaccination rollout in Africa. These considerations range from improving weak infrastructure for managing data and identifying adverse events after immunization to considering financing options for overcoming the logistical challenges of vaccination campaigns and generating demand for vaccine uptake. In addition, providing COVID-19 vaccination can be used to promote the adoption of universal healthcare, especially in sub-Saharan Africa countries.

Estimating the impact of pneumococcal conjugate vaccines on childhood pneumonia in sub-Saharan Africa: A systematic review.

Background: This study aimed to summarise the evidence on the impact of routine administration of 10-valent and 13-valent pneumococcal conjugate vaccines on pneumonia in children under five years of age in sub-Saharan Africa. Methods: A systematic search of the literature was conducted including primary research reporting on the impact of 10- or 13-valent pneumococcal vaccines on childhood pneumonia in a sub-Saharan African country. Case-control, cohort, pre-post and time-series study designs were eligible for inclusion. Thematic narrative synthesis was carried out to summarise the findings. Results: Eight records were included in the final analysis, 6 records were pre-post or time-series studies, 1 was a case-control study and 1 report combined pre-post and case-control studies. Vaccine impact on clinical pneumonia measured as percentage reduction in risk (%RR) was mostly non-significant. The reduction in risk was more consistent in radiological and pneumococcal pneumonia. Conclusions: Evidence of the positive impact of routine infant pneumococcal vaccination on clinical pneumonia incidence in sub-Saharan Africa is inconclusive. Ongoing surveillance and further research is required to establish the long term trend in pneumonia epidemiology and aetiology after PCV introduction. PROSPERO registration: CRD42019142369 30/09/19.

Factors associated with COVID-19 infections and mortality in Africa: a cross-sectional study using publicly available data.

INTRODUCTION: The current COVID-19 pandemic is a global threat. This elicits questions on the level of preparedness and capacity of health systems to respond to emergencies relative to other parts of the world. METHODS: This cross-sectional study uses publicly available core health data for 53 African countries to determine risk factors for cumulative COVID-19 deaths and cases per million in all countries in the continent. Descriptive statistics were determined for the indicators, and a negative binomial regression was used for modelling the risk factors. RESULTS: In sub-Saharan Africa, an increase in the number of nursing and midwifery personnel decreased the risk of COVID-19 deaths (p=0.0178), while a unit increase in universal healthcare (UHC) index of service coverage and prevalence of insufficient physical activity among adults increased the risk of COVID-19 deaths (p=0.0432 and p=0.0127). An increase in the proportion of infants initiating breast feeding reduced the number of cases per million (p<0.0001), while an increase in higher healthy life expectancy at birth increased the number of cases per million (p=0.0340). CONCLUSION: Despite its limited resources, Africa's preparedness and response to the COVID-19 pandemic can be improved by identifying and addressing specific gaps in the funding of health services delivery. These gaps impact negatively on service delivery in Africa, which requires more nursing personnel and increased UHC coverage to mitigate the effects of COVID-19.

Cervical and anal human papillomavirus infection in adult women in American Samoa.

The prevalence of cervical and anal human papillomavirus (HPV) and risk factors associated with infections were evaluated in a cross-sectional study of 211 adult women in American Samoa. Overall, 53% of women reported ever having a Pap smear. Cervical and anal HPV was detected in 10% and 16% of women, respectively; 4% of women had concurrent cervical and anal HPV. The most common cervical genotypes were HPV 6, HPV 16, and HPV 53. Cutaneous HPV types were detected in 40% of anal infections. Cervical HPV infection was associated with anal HPV (age-adjusted odds ratio = 3.32, 1.10-10.00). After age adjustment, cervical HPV was associated with being unmarried, postsecondary education, hot running water at home, multiple sexual partners, nulliparity, condom use, and other contraceptive methods. In multivariate analyses, only age remained associated with cervical HPV and anal HPV. Cervical and anal HPV was more prevalent among younger women; only anal HPV was detected in older women.

Cancer in American Samoa.

This study, funded by the National Cancer Institute, assessed cancer awareness and service needs in American Samoa. Cancer is the second-leading cause of death in American Samoa, yet cancer specific resources are lacking. Assistance is needed to help: 1) increase cancer outreach and community awareness; 2) increase the cancer capacity of health professionals; 3) improve laboratory capacity for cancer screening and detection; and 4) establish a comprehensive and coordinated system of cancer services.

Expression of lectin-like oxidized low-density lipoprotein receptors during ischemia-reperfusion and its role in determination of apoptosis and left ventricular dysfunction.

OBJECTIVES: The goal of this study was to determine the role of lectin-like oxidized low-density lipoprotein receptors (LOX-1), a recently identified oxidized low-density lipoprotein (ox-LDL) receptor, in ischemia-reperfusion injury to the heart. BACKGROUND: Reactive oxygen species (ROS) released during ischemia-reperfusion oxidize low-density lipoproteins; LOX-1 is upregulated by ox-LDL and ROS, and is involved in cell injury. METHODS: Anesthetized rats were subjected to left coronary artery ligation for 60 min (n = 10, ischemia group), or ischemia followed by 60 min of reperfusion (n = 30, ischemia-reperfusion group). Rats in the latter group were treated with saline, the LOX-1 blocking antibody JXT21 (10 mg/kg), or nonspecific anti-goat immunoglobulin G (IgG) (10 mg/kg). Ten other rats underwent thoracotomy without coronary ligation (sham control). RESULTS: Ischemia-reperfusion was associated with an increase in LOX-1 expression, lipid peroxidation and apoptosis, a large infarct area, and a decrease in left ventricular function (all, p < 0.01 vs. sham control and ischemia alone groups). Treatment of rats with LOX-1 antibody prevented ischemia-reperfusion-induced upregulation of LOX-1. Importantly, the LOX-1 antibody reduced apoptosis by 48%, lipid peroxidation by 39%, and myocardial infarct size by 45%, and improved left ventricular function (first derivative of pressure measured over time: -47% to -18%, p < 0.01). Nonspecific IgG had no effect. CONCLUSIONS: Lectin-like oxidized low-density lipoprotein receptors are upregulated during myocardial ischemia-reperfusion, and appear to be associated with apoptosis, necrosis, and left ventricular functional deterioration.

LOX-1 inhibition in myocardial ischemia-reperfusion injury: modulation of MMP-1 and inflammation.

A recently identified lectin-like oxidized low-density lipoprotein receptor (LOX-1) mediates endothelial cell injury and facilitates inflammatory cell adhesion. We studied the role of LOX-1 in myocardial ischemia-reperfusion (I/R) injury. Anesthetized Sprague-Dawley rats were subjected to 60 min of left coronary artery (LCA) ligation, followed by 60 min of reperfusion. Rats were treated with saline, LOX-1 blocking antibody JXT21 (10 mg/kg), or nonspecific anti-goat IgG (10 mg/kg) before I/R. Ten other rats underwent surgery without LCA ligation and served as a sham control group. LOX-1 expression was markedly increased during I/R (P < 0.01 vs. sham control group). Simultaneously, the expression of matrix metalloproteinase-1 (MMP-1) and adhesion molecules (P-selectin, VCAM-1, and ICAM-1) was also increased in the I/R area (P < 0.01 vs. sham control group). There was intense leukocyte accumulation in the I/R area in the saline-treated group. Treatment of rats with the LOX-1 antibody prevented I/R-induced upregulation of LOX-1 and reduced MMP-1 and adhesion molecule expression as well as leukocyte recruitment. LOX-1 antibody, but not nonspecific IgG, also reduced myocardial infarct size (P < 0.01 vs. saline-treated I/R group). To explore the link between LOX-1 and adhesion molecule expression, we measured expression of oxidative stress-sensitive p38 mitogen-activated protein kinase (p38 MAPK). The activity of p38 MAPK was increased during I/R (P < 0.01 vs. sham control), and use of LOX-1 antibody inhibited p38 MAPK activation (P < 0.01). These findings indicate that myocardial I/R upregulates LOX-1 expression, which through p38 MAPK activation increases the expression of MMP-1 and adhesion molecules. Inhibition of LOX-1 exerts an important protective effect against myocardial I/R injury.