Anti-Tuberculosis Potential of OJT008 against Active and Multi-Drug-Resistant Mycobacterium Tuberculosis: In Silico and In Vitro Inhibition of Methionine Aminopeptidase.

Despite the recent progress in the diagnosis of tuberculosis (TB), the chemotherapeutic management of TB continues to be challenging. Mycobacterium tuberculosis (Mtb), the etiological agent of TB, is classified as the 13th leading cause of death globally. In addition, 450,000 people were reported to develop multi-drug-resistant TB globally. The current project focuses on targeting methionine aminopeptidase (MetAP), an essential protein for the viability of Mtb. MetAP is a metalloprotease that catalyzes the excision of the N-terminal methionine (NME) during protein synthesis, allowing the enzyme to be an auspicious target for the development of novel therapeutic agents for the treatment of TB. Mtb possesses two MetAP1 isoforms, MtMetAP1a and MtMetAP1c, which are vital for Mtb viability and, hence, a promising chemotherapeutic target for Mtb therapy. In this study, we cloned and overexpressed recombinant MtMetAP1c. We investigated the in vitro inhibitory effect of the novel MetAP inhibitor, OJT008, on the cobalt ion- and nickel ion-activated MtMetAP1c, and the mechanism of action was elucidated through an in silico approach. The compound's potency against replicating and multi-drug-resistant (MDR) Mtb strains was also investigated. The induction of the overexpressed recombinant MtMetAP1c was optimized at 8 h with a final concentration of 1 mM Isopropyl ß-D-1-thiogalactopyranoside. The average yield from 1 L of Escherichia coli culture for MtMetAP1c was 4.65 mg. A preliminary MtMetAP1c metal dependency screen showed optimum activation with nickel and cobalt ions occurred at 100 µM. The half-maximal inhibitory concentration (IC50) values of OJT008 against MtMetAP1c activated with CoCl2 and NiCl2 were 11 µM and 40 µM, respectively. The in silico study showed OJT008 strongly binds to both metal-activated MtMetAP1c, as evidenced by strong molecular interactions and a higher binding score, thereby corroborating our result. This in silico study validated the pharmacophore's metal specificity. The potency of OJT008 against both active and MDR Mtb was <0.063 µg/mL. Our study reports OJT008 as an inhibitor of MtMetAP1c, which is potent at low micromolar concentrations against both active susceptible and MDR Mtb. These results suggest OJT008 is a potential lead compound for the development of novel small molecules for the therapeutic management of TB.

Inhibitory mechanism of clioquinol and its derivatives at the exopeptidase site of human angiotensin-converting enzyme-2 and receptor binding domain of SARS-CoV-2 viral spike.

The outbreak of SARS-CoV-2 infections around the world has prompted scientists to explore different approaches to develop therapeutics against COVID-19. This study focused on investigating the mechanism of inhibition of clioquinol (CLQ) and its derivatives (7-bromo-5-chloro-8-hydroxyquinoline (CLBQ), 5, 7-Dichloro-8-hydroxyquinoline (CLCQ)) against the viral glycoprotein, and human angiotensin-converting enzyme-2 (hACE-2) involved in SARS-CoV-2 entry. The drugs were docked at the exopeptidase site of hACE-2 and receptor binding domain (RBD) sites of SARS-CoV-2 Sgp to calculate the binding affinity of the drugs. To understand and establish the inhibitory characteristics of the drugs, molecular dynamic (MD) simulation of the best fit docking complex performed. Evaluation of the binding energies of the drugs to hACE-2 after 100 ns MD simulations revealed CLQ to have the highest binding energy value of -40.4 kcal/mol close to MLN-7640 (-45.4 kcal/mol), and higher than the exhibited values for its derivatives: CLBQ (-34.5 kcal/mol) and CLCQ (-24.8 kcal/mol). This suggests that CLQ and CLBQ bind more strongly at the exopeptidase site than CLCQ. Nevertheless, the evaluation of binding affinity of the drugs to SARS-CoV-2 Sgp showed the drugs are weakly bound at the RBD site, with CLBQ, CLCQ, CLQ exhibiting relatively low energy values of -16.8 kcal/mol, -16.34 kcal/mol, -12.5 kcal/mol, respectively compared to the reference drug, Bisoxatin (BSX), with a value of -25.8 kcal/mol. The structural analysis further suggests decrease in systems stability and explain the mechanism of inhibition of clioquinol against SARS-CoV-2 as reported in previous in vitro study.Communicated by Ramaswamy H. Sarma.

A computational evaluation of structural stability of omicron and delta mutations of SARS-CoV-2 spike proteins and human ACE-2 interactions.

Several more infectious SARS-CoV-2 variants have emerged globally since SARS-CoV-2 pandemic and the discovery of the first D614G variant of SARS-CoV-2 spike proteins in 2020. Delta (B.1.617.2) and Omicron (B.1.1.529) variants have proven to be of major concern out of all the reported variants, considering their influence on the virus' transmissibility and severity. This study aimed at evaluating the impact of mutations on these two variants on stability and molecular interactions between the viral Spike protein and human angiotensin converting enzyme-2 (hACE-2). The spike proteins receptor binding domain (RBD) was docked with the hACE-2 using HADDOCK servers. To understand and establish the effects of the mutations on the structural stability and flexibility of the RBD-hACE-2 complex, molecular dynamic (MD) simulation of the docked complex was performed and evaluated. The findings from both molecular docking analysis and binding free energy showed that the Omicron (OM) variant has high receptiveness towards hACE-2 versus Delta variant (DT), thereby, responsible for its increase in transmission. The structural stability and flexibility evaluation of variants' systems showed that mutations on DT and OM variants disturbed the stability of either the spike protein or the RBD-hACE-2 complex, with DT variant having greater instability impact. This study, therefore, assumed this obvious instability observed in DT variant might be associated or responsible for the reported severity in DT variant disease over the OM variant disease. This study provides molecular insight into the effects of OM and DT variants on stability and interactions between SARS-CoV-2 protein and hACE-2.

HRSA-Funded MCH Pipeline Training Program: Advancing the MCH Pipeline and Workforce Through Research Collaborations.

PURPOSE: Presently, there are six undergraduate HRSA-funded MCH pipeline training programs (MCHPTP) in the nation and they have gained significant momentum since inception by recruiting, training and mentoring undergraduate students in a comprehensive MCH-focused approach. This article describes the outcomes from the 6 training programs; and primarily Baylor College of Medicine-Texas Southern University (BCM-TSU's) collaborative strategy focusing on the MCH research training and outcomes, which align with HRSA's MCH bureau's missions. DESCRIPTION: Each MCHPTP offers trainees interdisciplinary MCH research experiences through intra/inter-institutional collaborations and partnerships, but BCM-TSU's MCHPTP was the only one with the primary focus to be research. As a case study, the BCM-TSU Program developed an innovative research curriculum integrated with MCH Foundations Course that comprised 2 hour weekly meetings. Students were split into collaborative research groups of 4-5 students, with multidisciplinary peer-mentors, clinical fellows and MCH research faculty from institutions at the world-renowned Texas Medical Center. ASSESSMENT: Since the inception of the MCH mentorship programs, all six MCHPTPs have enrolled up to 1890 trainees and/or interns. BCM-TSU Program trainees are defined as undergraduate students in their 1st or 2nd year of college while research interns are upper classmen in their 3rd or 4th year of college. The case study showed that BCM-TSU Program trainees demonstrated outstanding accomplishments in the area of research through primary and co-authorships of 13 peer-reviewed journal publications by 78 trainees, over a period of 3 years, in addition to dozens of presentations at local, regional and national conferences. CONCLUSIONS: The research productivity of students in the six MCHPTPs is strongly indicative of the success of integrating MCH research mentoring into MCH didactic training. The development of a diverse and robust MCH mentorship program promotes and strengthens research activities in areas of high priority such as addressing health disparities in MCH morbidity and mortality in the U.S.

Success of Maternal and Child Health Pipeline Training Programs: Alumni Survey Results.

INTRODUCTION: The Maternal and Child Health (MCH) Pipeline Training Program, promotes development of a diverse health workforce by training undergraduate students from underrepresented minorities. We aimed to evaluate the success of this program based on three domains: (1) demographic characteristics, (2) academic and career development, and (3) attitudes towards the field of MCH and the training programs among graduates. METHODS: Three domains of success were determined through a collaborative effort between current program directors and the funding agency project officers. The survey with questions related to the three domains was distributed via an online platform to graduates from seven sites (one former site and six current sites). Data were analyzed and presented utilizing descriptive statistics. RESULTS: The survey was distributed to 550 graduates, 162 responded (37% response rate). Demographically, 78% were female, 54% were Black/African American, 22% were Latinx and 83% did not report any disability. Eighty percent of respondents applied to graduate/professional schools, 67% received admission. Graduates often continued to work in MCH fields (70%). Majority felt confident and knowledgeable in the field (89%) and agreed the faculty were supportive at their training sites (90%). CONCLUSION: The study highlights successes in recruiting from underrepresented minorities, particularly Black/African Americans and first-time college goers in the family into the MCH Pipeline Training Programs. Programs were successful in furthering academic and career development for most trainees. Attitudes towards MCH and the training programs were overwhelmingly positive. Continued support of these programs is critical in addressing health disparities and achieving health equity.

Inhibitory mechanism of Ambroxol and Bromhexine Hydrochlorides as potent blockers of molecular interaction between SARS-CoV-2 spike protein and human angiotensin-converting Enzyme-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects the host cells through interaction of its spike protein with human angiotensin-converting enzyme 2 (hACE-2). High binding affinity between the viral spike protein and host cells hACE-2 receptor has been reported to enhance the viral infection. Thus, the disruption of this molecular interaction will lead to reduction in viral infectivity. This study, therefore, aimed to analyze the inhibitory potentials of two mucolytic drugs; Ambroxol hydrochlorides (AMB) and Bromhexine hydrochlorides (BHH), to serve as potent blockers of these molecular interactions and alters the binding affinity/efficiency between the proteins employing computational techniques. The study examined the effects of binding of each drug at the receptor binding domain (RBD) of the spike protein and the exopeptidase site of hACE-2 on the binding affinity (ΔGbind) and molecular interactions between the two proteins. Binding affinity revealed that the binding of the two drugs at the RBD-ACE-2 site does not alter the binding affinity and molecular interaction between the proteins. However, the binding of AMB (-56.931 kcal/mol) and BHH (-46.354 kcal/mol) at the exopeptidase site of hACE-2, significantly reduced the binding affinities between the proteins compared to the unbound, ACE-2-RBD complex (-64.856 kcal/mol). The result further showed the two compounds have good affinity at the hACE-2 site, inferring they might be potent inhibitors of hACE-2. Residue interaction networks analysis further revealed the binding of the two drugs at the exopeptidase site of hACE-2 reduced the number of interacting amino residues, subsequently leading to loss of interactions between the two proteins, with BHH showing better reduction in the molecular interaction and binding affinity than AMB. The result of the structural analyses additionally, revealed that the binding of the drugs considerably influences the dynamic of the complexes when compared to the unbound complex. The findings from this study suggest the binding of the two drugs at the exopeptidase site reduces the binding effectiveness of the proteins than their binding at the RBD site, and consequently might inhibit viral attachment and entry.

Success of Maternal and Child Health Pipeline Training Programs: Alumni Survey Results.

INTRODUCTION: The Maternal and Child Health (MCH) Pipeline Training Program, promotes development of a diverse health workforce by training undergraduate students from underrepresented minorities. We aimed to evaluate the success of this program based on three domains: (1) demographic characteristics, (2) academic and career development, and (3) attitudes towards the field of MCH and the training programs among graduates. METHODS: Three domains of success were determined through a collaborative effort between current program directors and the funding agency project officers. The survey with questions related to the three domains was distributed via an online platform to graduates from seven sites (one former site and six current sites). Data were analyzed and presented utilizing descriptive statistics. RESULTS: The survey was distributed to 550 graduates, 162 responded (37% response rate). Demographically, 78% were female, 54% were Black/African American, 22% were Latinx and 83% did not report any disability. Eighty percent of respondents applied to graduate/professional schools, 67% received admission. Graduates often continued to work in MCH fields (70%). Majority felt confident and knowledgeable in the field (89%) and agreed the faculty were supportive at their training sites (90%). CONCLUSION: The study highlights successes in recruiting from underrepresented minorities, particularly Black/African Americans and first-time college goers in the family into the MCH Pipeline Training Programs. Programs were successful in furthering academic and career development for most trainees. Attitudes towards MCH and the training programs were overwhelmingly positive. Continued support of these programs is critical in addressing health disparities and achieving health equity.

Diabetes in pregnancy and risk of near-miss, maternal mortality and foetal outcomes in the USA: a retrospective cross-sectional analysis.

BACKGROUND: The prevalence of diabetes in pregnant women has increased in the USA over recent decades. The primary aim of this study was to assess the association between diabetes in pregnancy and maternal near-miss incident, maternal mortality and selected adverse foetal outcomes. METHODS: We conducted a retrospective, cross-sectional analysis among pregnancy-related hospitalizations in USA between 2002 and 2014. We examined the association between DM and GDM as exposures and maternal in-hospital mortality, maternal cardiac arrest, early onset of delivery, poor foetal growth and stillbirth as the outcome variables. RESULTS: Among the 57.3 million pregnant women in the study population, the prevalence of GDM and DM was 5.4 and 1.3%, respectively. We found that pregnant women with DM were three times more likely to experience cardiac arrest (OR = 3.21; 95% CI = 2.57-4.01) and in-hospital maternal death (OR = 3.05; 95% CI = 2.45-3.79), as compared to those without DM. Among pregnant women with GDM and DM, the risk for early onset of delivery was higher, compared to women without GDM or DM. CONCLUSION: A diagnosis of diabetes prior to pregnancy contributes significantly to the risk of maternal cardiac arrest, maternal mortality and adverse foetal outcomes.

Trends and Risk Factors for Leishmaniasis among Reproductive Aged Women in the United States.

BACKGROUND AND OBJECTIVE: Leishmaniasis, a neglected tropical disease, is endemic in several regions globally, but commonly regarded as a disease of travelers in the United States (US). The literature on leishmaniasis among hospitalized women in the US is very limited. The aim of this study was to explore trends and risk factors for leishmaniasis among hospitalized women of reproductive age within the US. METHODS: We analyzed hospital admissions data from the 2002-2017 Nationwide Inpatient Sample among women aged 15-49 years. We conducted descriptive statistics and bivariate analyses for factors associated with leishmaniasis. Utilizing logistic regression, we assessed the association between sociodemographic and hospital characteristics with leishmaniasis disease among hospitalized women of reproductive age in the US. Joinpoint regression was used to examine trends over time. RESULTS: We analyzed 131,529,239 hospitalizations; among these, 207 cases of leishmaniasis hospitalizations were identified, equivalent to an overall prevalence of 1.57 cases per million during the study period. The prevalence of leishmaniasis was greatest among older women of reproductive age (35-49 years), Hispanics, those with Medicare, and inpatient stay in large teaching hospitals in the Northeast of the US. Hispanic women experienced a statistically significant increased odds of leishmaniasis diagnosis (OR, 1.80; 95% CI, 1.19-4.06), compared to Non-Hispanic (NH) White women. Medicaid and Private Insurance appeared to serve as a protective factor in both unadjusted and adjusted models. We did not observe a statistically significant change in leishmaniasis rates over the study period. CONCLUSION AND GLOBAL HEALTH IMPLICATIONS: Although the prevalence of leishmaniasis among women of reproductive age appears to be low in the US, some risk remains. Thus, appropriate educational, public health and policy initiatives are needed to increase clinical awareness and timely diagnosis/treatment of the disease.

A Framework for Protecting Pregnant Women in the Era of COVID-19 Pandemic.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent for the coronavirus disease 2019 (COVID-19) pandemic, highlighted and compounded problems while posing new challenges for the pregnant population. Although individual organizations have provided disparate information, guidance, and updates on managing the pregnant population during the current COVID-19 pandemic, it is important to develop a collective model that highlights all the best practices needed to protect the pregnant population during the pandemic. To establish a standard for ensuring safety during the pandemic, we present a framework that describes best practices for the management of the pregnant population during the ongoing COVID-19 pandemic.

Discovery of Clioquinol and analogues as novel inhibitors of Severe Acute Respiratory Syndrome Coronavirus 2 infection, ACE2 and ACE2 - Spike protein interaction in vitro.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the etiological agent for coronavirus disease 2019 (COVID-19), has resulted in an ongoing pandemic. Presently, there are no clinically approved drugs for COVID-19. Hence, there is an urgent need to accelerate the development of effective antivirals. Herein, we discovered Clioquinol (5-chloro-7-iodo-8-quinolinol (CLQ)), a Food and Drug Administration (FDA) approved drug, and two of its analogues (7-bromo-5-chloro-8-hydroxyquinoline (CLBQ14); and 5, 7-Dichloro-8-hydroxyquinoline (CLCQ)) as potent inhibitors of SARS-CoV-2 infection-induced cytopathic effect in vitro. In addition, all three compounds showed potent anti-exopeptidase activity against recombinant human angiotensin-converting enzyme 2 (rhACE2) and inhibited the binding of rhACE2 with SARS-CoV-2 Spike (RBD) protein. CLQ displayed the highest potency in the low micromolar range, with its antiviral activity showing a strong correlation with inhibition of rhACE2 and rhACE2-RBD interaction. Altogether, our findings provide a new mode of action and molecular target for CLQ and validates this pharmacophore as a promising lead series for the clinical development of potential therapeutics for COVID-19.

Racial/Ethnic Disparities in the Burden of HIV/Cervical Cancer Comorbidity and Related In-hospital Mortality in the USA.

OBJECTIVE: The purpose of this study was to determine whether cervical cancer is a risk factor for early mortality among women with HIV and whether racial/ethnic disparity predicted in-hospital death among women living with HIV and diagnosed with cervical cancer. METHODS: We conducted a population-based study using the National Inpatient Sample (NIS) database comprising hospitalized HIV-positive women with or without cervical cancer diagnosis, from 2003 through 2015. We compared trends in the rates of cervical cancer, in-hospital death, and years of potential life lost (YPLL) by race/ethnicity. RESULTS: We identified 2,613,696 women with HIV, and among them, 5398 had cervical cancer. The prevalence of cervical cancer (per 10,000) was 9.3 for NH-Whites, 30.9 among NH-Blacks, and 30.2 for Hispanics. Rates of cervical cancer over time diminished significantly only among NH-Whites (average annual percent change (AAPC), - 5.8 (- 9.7, - 1.8)), and YPLL in women with cervical cancer decreased significantly only in NH-Whites (AAPC, - 6.2 (- 10.1, - 2.0)). Cervical cancer was associated with increased odds of in-hospital death overall (OR 2.24 (1.59-3.15)) and among NH-Blacks (OR 2.03 (1.30-3.18)) only. CONCLUSIONS: NH-Blacks and Hispanics with HIV remain at increased risk for concurrent diagnosis of cervical cancer compared with NH-Whites. Moreover, NH-Black women with HIV and cervical cancer are at greatest risk for in-hospital death. The findings emphasize the need for a more robust prevention strategy among minority women to reduce the high burden of HIV/cervical cancer and related mortality.

Trends and Racial/Ethnic Disparities in the Rates of Pre-eclampsia by HIV Status in the US.

BACKGROUND: Preeclampsia and HIV account for a significant proportion of the global burden of disease and pose severe maternal-fetal risks. There is a dearth of literature regarding racial/ethnic disparities in preeclampsia associated with HIV/AIDS in the US. METHODS: We retrospectively analyzed data from the National Inpatient Sample (NIS) database from 2002 to 2015 on a cohort of hospitalized pregnant women with or without preeclampsia and HIV. Joinpoint regression models were used to identify trends in the rates of preeclampsia among pregnant women living with or without HIV, stratified by race/ethnicity over the study period. We also assessed the association between preeclampsia and various socio-demographic factors. RESULTS: We analyzed over 60 million pregnancy-related hospitalizations, of which 3665 had diagnoses of preeclampsia and HIV, corresponding to a rate of 0.61 per 10,000. There was an increasing trend in the diagnosis of preeclampsia among hospitalized, pregnant women without HIV across each racial/ethnic category. The highest prevalence of preeclampsia was among non-Hispanic (NH) Blacks, regardless of HIV status. CONCLUSION: The increase in rates of pre-eclampsia between 2002 and 2015 was mostly noted among pregnant women without HIV. Regardless of HIV status, NH-Blacks experienced the highest discharge prevalence of preeclampsia.

Ambroxol Hydrochloride Inhibits the Interaction between Severe Acute Respiratory Syndrome Coronavirus 2 Spike Protein's Receptor Binding Domain and Recombinant Human ACE2.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), enters the host cells through two main pathways, both involving key interactions between viral envelope-anchored spike glycoprotein of the novel coronavirus and the host receptor, angiotensin-converting enzyme 2 (ACE2). To date, SARS-CoV-2 has infected up to 26 million people worldwide; yet, there is no clinically approved drug or vaccine available. Therefore, a rapid and coordinated effort to re-purpose clinically approved drugs that prevent or disrupt these critical entry pathways of SARS-CoV-2 spike glycoprotein interaction with human ACE2, could potentially accelerate the identification and clinical advancement of prophylactic and/or treatment options against COVID-19, thus providing possible countermeasures against viral entry, pathogenesis and survival. Herein, we discovered that Ambroxol hydrochloride (AMB), and its progenitor, Bromhexine hydrochloride (BHH), both clinically approved drugs are potent effective modulators of the key interaction between the receptor binding domain (RBD) of SARS-CoV-2 spike protein and human ACE2. We also found that both compounds inhibited SARS-CoV-2 infection-induced cytopathic effect at micromolar concentrations. Therefore, in addition to the known TMPRSS2 activity of BHH; we report for the first time that the BHH and AMB pharmacophore has the capacity to target and modulate yet another key protein-protein interaction essential for the two known SARS-CoV-2 entry pathways into host cells. Altogether, the potent efficacy, excellent safety and pharmacologic profile of both drugs along with their affordability and availability, makes them promising candidates for drug repurposing as possible prophylactic and/or treatment options against SARS-CoV-2 infection.

Role of Social Determinants of Health in Widening Maternal and Child Health Disparities in the Era of Covid-19 Pandemic.

We present a conceptual model that describes the social determinants of health (SDOH) pathways contributing to worse outcomes in minority maternal and child health (MCH) populations due to the current COVID-19 pandemic. We used International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10) codes in the categories Z55-Z65 to identify SDOH that potentially modulate MCH disparities. These SDOH pathways, coupled with pre-existing comorbidities, exert higher-than-expected burden of maternal-fetal morbidity and mortality in minority communities. There is an urgent need for an increased infusion of resources to mitigate the effects of these SDOH and avert permanent truncation in quality and quantity of life among minorities following the COVID-19 pandemic.

Discovery of Clioquinol and Analogues as Novel Inhibitors of Severe Acute Respiratory Syndrome Coronavirus 2 Infection, ACE2 and ACE2 - Spike Protein Interaction In Vitro.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the etiological agent for coronavirus disease 2019 (COVID-19), has emerged as an ongoing global pandemic. Presently, there are no clinically approved vaccines nor drugs for COVID-19. Hence, there is an urgent need to accelerate the development of effective antivirals. Here in, we discovered Clioquinol (5-chloro-7-iodo-8-quinolinol (CLQ)), a FDA approved drug and two of its analogues (7-bromo-5-chloro-8-hydroxyquinoline (CLBQ14); and 5, 7-Dichloro-8-hydroxyquinoline (CLCQ)) as potent inhibitors of SARS-CoV-2 infection induced cytopathic effect in vitro . In addition, all three compounds showed potent anti-exopeptidase activity against recombinant human angiotensin converting enzyme 2 (rhACE2) and inhibited the binding of rhACE2 with SARS-CoV-2 Spike (RBD) protein. CLQ displayed the highest potency in the low micromolar range, with its antiviral activity showing strong correlation with inhibition of rhACE2 and rhACE2-RBD interaction. Altogether, our findings provide a new mode of action and molecular target for CLQ and validates this pharmacophore as a promising lead series for clinical development of potential therapeutics for COVID-19.

Trends and associated characteristics for Chagas disease among women of reproductive age in the United States, 2002 to 2017.

BACKGROUND: American trypanosomiasis, commonly referred to as Chagas disease, is caused by a single cell protozoan known as Trypanosoma cruzi (T. cruzi). Although those affected are mainly in Latin America, Chagas has been detected in the United States (US), Canada and in many European countries due to migration. Few studies have explored the epidemiology of Chagas within the US or changes in disease burden over the past decade. The objective of this study was to explore the trends and associated characteristics for Chagas disease among hospitalized women of reproductive age in the US. METHODS: We analyzed admissions data including socio-demographic and hospital characteristics for inpatient hospitalization for women of reproductive age (15-49 years) in the US from 2002 through 2017. We employed Joinpoint regression analysis to determine trends in the prevalence of Chagas disease over this period. RESULTS: A total of 487 hospitalizations of Chagas disease were identified, corresponding to 3.7 per million hospitalizations over the study period. The rate statistically increased from 1.6 per million in 2002 to 7.6 per million hospitalizations in 2017. Chagas was most prevalent among older women, Hispanics and those in the highest zip income bracket. The in-hospital mortality rate was about 10 times greater among women with Chagas compared to those without the condition (3.1% versus 0.3%), and the condition tended to be clustered in women treated at large, urban teaching hospitals in the Northeastern region of the US. CONCLUSION: Chagas disease diagnosis appears to be increasing among hospitalized women of reproductive age in the US with a 10-fold elevated risk of mortality.

A Surveillance System for the Maternal and Child Health (MCH) Population During the COVID-19 Pandemic.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent for coronavirus disease 2019 (COVID-19), and its ensuing mitigation measures have negatively affected the Maternal and Child Health (MCH) population. There is currently no surveillance system established to enhance our understanding of SARS-CoV-2 transmission to guide policy decision making to protect the MCH population in this pandemic. Based on reports of community and household spread of this novel infection, we present an approach to a robust family-centered surveillance system for the MCH population. The surveillance system encapsulates data at the individual and community levels to inform stakeholders, policy makers, health officials and the general public about SARS-CoV-2 transmission dynamics within the MCH population.

Opioid-Related Disorders Among Pregnant Women with Sickle Cell Disease and Adverse Pregnancy Outcomes.

OBJECTIVE: Opioid use during pregnancy has increased in recent years, parallel with the opioid epidemic in the general population. Opioids are commonly used as an analgesic for pain crisis, a hallmark symptom of sickle cell disease (SCD). With the amplified frequency and severity of SCD pain crisis during pregnancy, the use of opioids may increase concurrently. The aim of this study was to examine trends in opioid-related disorders (ORDs) among pregnant women with and without SCD, as well as assess the risk for preterm labor, maternal sepsis, and poor fetal growth among patients with SCD and ORD. METHODS: We conducted a retrospective analysis of inpatient pregnancy- and childbirth-related hospital discharge data from the 2002-2014 National (Nationwide) Inpatient Sample database. The primary outcome was the risk of ORD in pregnant women with SCD and its impact on threatened preterm labor, fetal growth, and maternal sepsis. RESULTS: Among the >57 million pregnancy-related hospitalizations examined, 9.6 per 10,000 had SCD. ORD in mothers with SCD was four times as prevalent as in those without SCD (2% vs 0.5%). A significant rise in ORD occurred throughout the study period and was associated with an increased risk of maternal sepsis, threatened preterm labor, and poor fetal growth. CONCLUSIONS: Pregnant women with SCD have a fourfold increased risk of ORD compared with their non-SCD counterparts. The current opioid epidemic continues to worsen in both groups, warranting a tailored and effective public health response to reduce the resulting adverse pregnancy outcomes.

Opioid Use Among HIV-Positive Pregnant Women and the Risk for Maternal-Fetal Complications.

OBJECTIVE: To assess patient- and hospital-level characteristics associated with opioid use in human immunodeficiency virus (HIV)-positive pregnant women and fetal health outcomes. METHODS: Using the 2002-2014 Nationwide Inpatient Sample database, we analyzed discharge records to describe the rates of opioid use among HIV-positive pregnant women. Logistic regression was used to quantify the magnitude of the association between exposure status and maternal-fetal outcomes. RESULTS: Opioid use was fourfold greater among HIV-positive pregnant women compared with their HIV-negative counterparts (odds ratio 4.0; 95% confidence interval 3.15-5.12). Relatively smaller but significant increases in the early onset of delivery, poor fetal growth, abortive pregnancy, and spontaneous abortion also were observed in association with HIV-positive status and opioid drug use during pregnancy. CONCLUSIONS: An increased risk of negative maternal-fetal complications persists among HIV-positive women who use opioids during pregnancy. Focusing on predisposing factors and monitoring opioid dispensing may mitigate overuse or abuse in this vulnerable population.