NAFAMOSTAT AS NASAL CHEMOPROPHYLAXIS FOR SARS-CoV-2 IN HAMSTERS

Background: Chemoprophylaxis is a critical tool for many infectious diseases, and in COVID-19 may have particular benefit for vulnerable patients that do not maximally benefit from vaccination. Nafamostat inhibits TMPRSS2, which catalyses a critical cell entry pathway for SARS-CoV-2. This study sought to assess efficacy of intranasal nafamostat against airborne transmission of SARSCoV-2 in Syrian Golden hamsters. Method(s): Male hamsters were intranasally administered water or 5 mg/kg nafamostat in water twice daily for 5 days (sentinels). One day after treatment initiation, sentinels were co-housed with an untreated hamster that was intranasally inoculated with 1 x 104 PFU of Wuhan SARS-CoV-2 (donor). Sentinels were separated from the donor by a perforated divider, allowing airflow between zones but not contact. Hamsters were weighed and throat-swabbed throughout. At day 4, all animals were culled, and lung and nasal turbinates were harvested. N-RNA was quantified relative to 18S-RNA by qPCR. A 2-way ANOVA with Bonferroni correction was applied to compare weight changes in the nafamostat group to those in controls. An unpaired t-test was used to compare viral RNA in lung and nasal turbinate between groups. Result(s): SARS-CoV-2 viral RNA was significantly lower in the nasal turbinates of nafamostat-treated hamsters compared to water-treated controls (P = 0.012;Figure 1). Within the lung, SARS-CoV-2 RNA was undetectable in the nafamostat-treated hamsters, but was detectable in the water-treated controls. Viral RNA was undetectable in the swabs of the nafamostat-treated hamsters at all timepoints, but was quantifiable in the water-treated control group from day 3. Body weight of the nafamostat-treated hamsters was significantly lower (P = < 0.001) than in the water-treated animals throughout. SARS-CoV-2 viral RNA was detectable in the donor hamsters lung, nasal turbinate and swab samples confirming validity of the experiment. Conclusion(s): This study demonstrated a protective effect of intranasal nafamostat against airborne SARS-CoV-2 transmission in Syrian golden hamsters. A phase IIa study of intravenously administered nafamostat yielded no evidence of clinical efficacy in hospitalised patients, but further investigation of intranasally administered nafamostat in a prophylactic setting may be warranted.

ADR profile among healthcare workers on hydroxychloroquine prophylaxis in a tertiary care teaching hospital in India

Background: WHO has declared Coronavirus 2019 (COVID-19) as pandemic on 11th March 2020. Hydroxychloroquine (HCQ) chemoprophylaxis has been approved by the Indian Council of Medical Research (ICMR) for asymptomatic healthcare workers treating suspected or confirmed COVID-19 cases and asymptomatic household contacts of confirmed patients. However, there is a scarcity of data regarding the efficacy and safety of HCQ for COVID-19 prophylaxis and treatment. Background: The present study was designed to evaluate the adverse drug reaction (ADR) profile of HCQ prophylaxis among healthcare workers in a tertiary care teaching hospital in India. Methods: A Descriptive cross-sectional study was conducted in Kalpana Chawla Medical College and Hospital, Karnal for duration of 3 months (April-June 2020). The study was performed on the reported ADRs due to HCQ prophylaxis by the healthcare workers to the ADR monitoring centre of the institute during this period. Results: Gastrointestinal disturbance such as loose stool (16.4%) and hyperacidity (14.9%) were the most commonly reported ADRs during the study period. The incident rate of adverse drug reactions was 23.7%. The number of ADRs was found to be significantly (p<0.01) more in female as compared to male. We have observed that most of the reactions were reported following the 1st day loading dose. Conclusions: Our results showed that gastrointestinal system was most commonly affected. Loose stool and hyperacidity were most frequently reported ADRs due to HCQ prophylaxis. Larger studies are required to ensure the safety of the use of HCQ as prophylaxis for COVID 19.

Return to Travel in the Coronavirus Disease 2019 Pandemic Recovery Period and Implications for Imported Malaria: Reinforcing Prevention, Early Diagnosis, and Appropriate Treatment of Malaria.

Return to international travel in the COVID-19 pandemic recovery period is expected to increase the number of patients with imported malaria in the United States (US). Malaria prevention in travelers and preparedness for timely diagnosis and appropriate treatment are key to minimize imported malaria morbidity and mortality. Intravenous artesunate (IVAS) is now available from commercial distributors in the US for the treatment of severe malaria. Hospitals and pharmacists should have a plan for malaria treatment, including stocking artemether-lumefantrine for uncomplicated malaria, and stocking or planning for rapid procurement of IVAS for the treatment of severe malaria.

Successful design and execution of two gastric cancer chemoprevention trials in Central America and Puerto Rico

Gastric adenocarcinoma (GAC) is the third leading global cause of cancer mortality and leading infection-associated cancer. The high incidence regions are Latin America, East Asia, and Eastern Europe. In the U.S., GAC represents a major cancer disparity, double the incidence rates in all nonwhite populations, the opposite of Barrett's Esophagus and EAC. Immigrants from high incidence regions maintain the risk profile of their nations of origin. In a paradigm shift, recent guidelines now recommend surveillance endoscopy (eg, 3 years) for patients with high-risk gastric premalignant conditions (GPMCs). Clinical trials of chemoprevention agents for patients with GPMCs are lacking. We conducted two independent, NCI DCP funded, phase II placebo-controlled chemoprevention trials in patients with GPMCs (intestinal metaplasia, atrophic gastritis). The oral agents were curcumin and eflornithine (DFMO). A highly bioavailable preparation of curcumin was used. The RCTs were conducted in Puerto Rico and rural Honduras, with important characteristics: (1) representative of Caribbean and Mesoamerican populations and linked to large U.S. immigrant populations;(2) high prevalence of H. pylori infection and GPMCs;(3) absence of turmeric and curcuminoids in the local diets;(4) proven bidirectional collaboration with academic institutions in the U.S. In the curcumin trial (NCT02782949) H. pylori negative patients were randomized to study drug or placebo for 6 months. In the eflornithine study (NCT02794428), H. pylori positive and negative subjects were randomized to study drug or placebo for 18 months, with endoscopy at baseline, and 6. 18, and 24 months. The primary outcomes were based upon changes in histologic parameters at 6 months. Principal study challenges included: (1) International and bilingual regulatory environment;(2) Strengthening of the research infrastructure, particularly in Central America;(3) Participant recruitment, eg, in the curcumin RCT in Honduras wherein only 10-15% are H. pylori negative;(4) The Covid-19 pandemic;(5) Natural disasters (3 hurricanes). In Conclusion(s): Eflornithine and curcumin RCTs have been successfully completed, despite important challenges in implementation and execution. No losses to follow-up were encountered related to the pandemic or natural disasters. The south-south partnership may provide a model for chemoprevention and translational studies in Latino populations with prevalent cancers such as GAC..

A review of the role of infections in the aetiology of haemolysis in patients with sickle cell diseases: pathogenesis, management, and prevention

Background: Sickle cell disease (SCD) is associated with chronic haemolysis, immuno-suppression and susceptibility to infections, which may trigger infection-associated haemolysis (IAH). SCD patients are vulnerable to anaemic effect of IAH due to vicious interaction between pre-existing 'inherited' chronic haemolysis and 'acquired' IAH. IAH in SCD manifests as febrile haemolytic crisis with clinical and laboratory features of severe anaemia or pancytopenia. Clinico-pathological perspectives of IAH in SCD are fragmented. This review presents a comprehensive but concise overview of pathogenesis, management and prevention of IAH in SCD. Methodology and results: Online literature search using search terms such as 'sickle cell disease, viral, bacterial, parasitic, fungal, infections, hyperhaemolytic crisis, haemophagocytic syndrome, severe anaemia, pancytopenia' in various combinations was done on PubMed/Medline, Google, Google-Scholar and Bing. Overall, 112 relevant publications were retrieved, which included 109 peer reviewed journal articles, 2 World Health Organization (WHO) technical reports, and 1 edited text book. A range of bacterial (Bartonella spp, Mycoplasma spp., Mycobacterium avium complex), viral (Dengue, SARS-CoV-2, Parvovirus-B19, Cytomegalovirus, Epstein-Barr virus), parasitic (Plasmodium spp., Babesia spp.), and fungal (Histoplasma spp.) infections were associated with IAH in SCD. There are two broad types of IAH in patients with SCD;infection associated extra-medullary haemolysis (IAEMH) and infection associated intra-medullary haemolysis (IAIMH). While IAEMH is associated with severe anaemia due to intravascular haemolysis caused by red cell invasion, oxidative injury, auto-antibodies, and/or pathogen-haem interaction, IAIMH is associated with haemophagocytic tri-lineage destruction of haematopoietic precursors in the bone marrow. Conclusion(s): Various microbial pathogens have been associated with IAH in SCD. SCD patients with fever, severe anaemia or pancytopenia should be investigated for early diagnosis and prompt treatment of IAH, which is a life-threatening haematological emergency for which transfusion therapy alone may not suffice. Prompt and sustainable termination of IAH may require therapeutic combination of transfusion, anti-microbial chemotherapy, and immune modulation therapy. SCD patients should also receive counselling on hygiene, barrier protection against vectors, routine chemoprophylaxis for locally endemic diseases, and immunization for vaccine-preventable infections as a long-term preventive strategy against IAH. Copyright AJCEM 2022.

Improving thromboprophylaxis in children admitted to a quaternary care children's hospital with COVID-19

Background: The incidence of venous thrombo-embolism (VTE) in hospitalized children has increased by 70%-200% over the last 2-decades. Given this increase, many pediatric centers have initiated electronic clinical decision supports (ECDS) to prognosticate VTE risk and recommend appropriate prophylaxis. COVID-19 is a risk factor for VTE, however ECDS algorithms developed before the COVID-19 pandemic may not accurately prognosticate VTE risk in children with COVID-19. Aim(s): To identify areas for improvement of thromboprophylaxis recommendations for children admitted to hospital with COVID-19. Method(s): Inpatients with a positive COVID-19 PCR test on admission (or within 24 h) were identified at a quaternary-care pediatric center between March 1st 2020 and January 20th 2022. The results of the institution's automated thromboprophylaxis recommendations were compared to institutional best practice guidelines for COVID-19 thromboprophylaxis and to the thromboprophylaxis actually received by the patient. Using this data, a quality improvement (QI) initiative to improve adherence to COVID-19 thromboprophylaxis recommendations through ECDS optimization was implemented. This QI study was exempt from ethics approval. Result(s): Of the 375 inpatients with COVID-19 who underwent thromboprophylaxis screening, 43 were excluded as their COVID-19 was performed >24 h after admission and 5 were excluded for having incomplete data. Table 1 shows the characteristics of the final cohort. 179 (54.4%) patients had a D-dimer performed during their admission. The number of patients that met criteria for chemo-prophylaxis via each screening modality is shown in Figure 1. Five inpatients developed VTE;three had VTE symptoms at presentation, two were identified as high-risk for VTE by both the automated and best practice assessments but were not started on chemoprophylaxis due to family preference or a contraindication to anticoagulation. Conclusion(s): Automated thromboprophylaxis recommendations developed prior to the COVID-19 pandemic may not identify COVID-19 patients needing chemoprophylaxis. Existing ECDS tools need to be updated to reflect COVID-19 specific risk factors for VTEs.

Modification of Management Strategies During Sars COVID 2 Pandemic Improved the Quality, Criticality, and Outcomes of In-Patients

The second wave of the pandemic exposed many hospitals to their unpreparedness to handle sudden surge patients due to lack of infrastructure to handle the relentless inflow of pts whilst also running short of beds, o2, ventilators, trained HCW's, PPE, medications, and other essentials. The aim of the study was to use judiciously the available resources, fine-tune the patient care, reduce the workload and burden of HCW s, optimize pts care, and improve the outcomes. This observation was done at a tertiary care hospital. The following fine-tuning was done: 1. Oxygen: Robust O2 systems that would support the pandemic, would take time to put in place, so conducting training programmers in a short period for HCW regarding optimal usage and avoid misusing or wastage of O2 was done in a relatively short time. We selected an HCW as O2 provider, the only job to check o2 delivery and SPO2 around the clock. 2. Foleys Catheters and Diapers: Patients on high O2 requirements when mobilized, O2 delivery to patients were discontinued along with disruption of prone positions and derecruitment of lungs and had severe hypoxia. So we started catheterizing the pts on high O2 need. 3. Family Visit: Family visits made pts comfortable, more compliant to the care. And it also reduced the significant burden of HCW's who had to otherwise communicate multiple times with their relatives via audio or video phone calls. This also brought transparency of the care. 4. Simple Protocols: We simplified the charts with only two sheets, one for the doctor one for the staff. These simple changes made work easy and more efficient and also help in collecting data. 5. DRUG Boy: Drugs indenting and on-time delivery were challenging. We selected a person only for drug delivery and later with drugs becoming precious and anticipating problems, drug boy used to deliver medications to the patient in presence of family. 6. Continuous Monitoring by a Leader: COVID is a dynamic process and requires continuous monitoring, timely interventions. Leaders have to take complete charge continuously from admission to discharge. Fragmented care by multiple people worsens the situations. 7. DVT Stockings: COVID is a prothrombotic state for the prevention of clots all moderate to severe pts were applied DVT stockings, along with chemoprophylaxis which prevented DVT significantly. 8. Anxiolytics, Restricted Mobilization, and Spirometry: Mild anxiolytics reduced the stress, work of breathing, and good compliance to the NIV. Strict restriction in mobilizing and adequate spirometry was supervised in moderate to severe COVID patients in the early stages to help in early recovery from COVID-19. 9. Prone Position in COVID: In moderate and severe ARDS in patients on O2 with face mask, O2 by BIPAP support and in invasively ventilated patients were subjected to prone positioning for 16-18 hours/day, which helped in improving lung recruitment oxygenation of patients and better outcomes while reducing the oxygen requirements. Conclusion: COVID pandemic is very challenging. Conservative management and fine-tuning of the resources available will have multiple benefits and also improve outcomes. With these innovations, quality will improved was costeffective and easily replicable in any hospital.

Hydroxychloroquine/Chloroquine Prophylaxis among Health-care Workers: Was it Really Preventive? - Evidence from a Multicentric Cross-sectional Study.

Background: Despite the low level of clinical evidence in hydroxychloroquine (HCQ) favor, it was prescribed for pre- and post-exposure prophylaxis in India and worldwide. In absence of a large randomized control trial, the evidence needs to be generated through observation study, hence the study was conducted to find the evidence for prophylaxis of HCQ. Materials and Methods: A multi-centric cross-sectional study involving government hospitals was chosen for serosurvey conducted from August 21, 2020, to November 20, 2020. Questionnaire was adopted from WHO. Data about chloroquine (CQ) use among health-care workers (HCWs) were added and the duration of CQ intake was also noted. Results: A total of 2,224 HCWs were recruited. The mean duration of time of taking HCQ was 7.1 weeks (standard deviation ± 6.1 weeks, median = 4 weeks with IQR, 3-10 weeks). Training on personal protective equipment (PPE), knowledge of handwashing, direct care to the patient, availability of alcohol hand rub, close contact with the patient, duration of contact, and usage of PPE were associated with HCQ intake. The antibody formation in group taking HCQ was 16.9% compared to 19.8% not taking it (P = 0.08). The Chi-square for linear trend for weeks of HCQ intake and antibody formation. However, the same was not statistically significant (Chi-square = 3.61, P = 0.06). Conclusion: Our study did not find a statistically significant association in the large multicentric study. The absolute difference of 2.9% in the two groups may not be sufficient to warrant its widespread use for prophylaxis.

Prophylactic use of hydroxychloroquine (HCQS) in COVID-19: A questionnaire-based study in health care professionals.

Background: Coronavirus disease-2019 (COVID-19) pandemic has engulfed the whole world with millions getting infected and losing their lives. Health care professionals (HCPs) who are in the front line of fighting with COVID-19 are particularly vulnerable and it is crucial to protect them from COVID-19. In this regard, the Indian Council of Medical Research (ICMR) has recommended hydroxychloroquine (HCQS) chemoprophylaxis in HCPs. However, considering the lack of sufficient evidence the HCP are in a dilemma about this aspect. Moreover, there is a paucity of data on use of HCQS as a chemoprophylaxis among Indian HCP. Hence, this study was carried out to study the extent of use and also the perception of Indian HCP toward use of HCQS as a chemoprophylaxis for COVID-19. Materials and Methods: This was a cross-sectional study done on 205 HCPs working across India. The responses were collected electronically using a prevalidated semi-structured questionnaire. Results: 62.9% (129/205) respondents reported having taken HCQS chemo-prophylaxis for COVID-19 while 34.7% (76/205) did not take it. Among HCP, who did not take the prophylaxis, the main reasons cited were concern about adverse effects (61.5%) and lack of robust evidence (24%). Only 14% of respondents felt that there was sufficient evidence to justify use of HCQS for prophylaxis while an overwhelming majority (86%) felt otherwise or were uncertain. Conclusion: The majority of participants felt that despite a lack of proven efficacy, ICMR guidelines on HCQS prophylaxis in COVID-19 are justified considering the pandemic situation. Our study also found that HCQS is well tolerated by participants and there was no reported serious adverse effect and cardiac-related side effects among them.

RésuméContexte: La pandémie de maladie à coronavirus-2019 (COVID-19) a englouti le monde entier avec des millions de personnes infectées et perdant leur des vies. Les professionnels de la santé (HCP) qui sont en première ligne dans la lutte contre le COVID-19 sont particulièrement vulnérables et il est essentiel de les protéger du COVID-19. À cet égard, le Conseil indien de la recherche médicale (ICMR) a recommandé l'hydroxychloroquine (HCQS) chimioprophylaxie chez les professionnels de la santé. Cependant, compte tenu du manque de preuves suffisantes, le professionnel de la santé est confronté à un dilemme à propos de cet aspect. En outre, il y a peu de données sur l'utilisation du HCQS comme chimioprophylaxie parmi les professionnels de la santé indiens. Par conséquent, cette étude a été menée pour étudier l'étendue de l'utilisation et aussi la perception des professionnels de la santé indiens à l'égard de l'utilisation du HCQS comme chimioprophylaxie pour le COVID-19. Matériel et Méthodes: c'était un étude transversale réalisée sur 205 professionnels de la santé travaillant en Inde. Les réponses ont été recueillies par voie électronique à l'aide d'un système semi-structuré prévalidé questionnaire. Résultats: 62,9% (129/205) des répondants ont déclaré avoir suivi une chimioprophylaxie HCQS pour le COVID-19, tandis que 34,7% (76/205) ne l'a pas pris. Parmi les professionnels de la santé qui n'ont pas pris de prophylaxie, les principales raisons invoquées étaient la préoccupation concernant les effets indésirables (61,5%) et le manque de preuves solides (24%). Seulement 14% des répondants estimaient qu'il y avait des preuves suffisantes pour justifier l'utilisation du HCQS à des fins prophylactiques alors qu'un une écrasante majorité (86%) pensait le contraire ou était incertaine. Conclusion: La majorité des participants ont estimé que malgré un manque de efficacité, les lignes directrices de l'ICMR sur la prophylaxie du HCQS dans le COVID-19 sont justifiées compte tenu de la situation pandémique. Notre étude a également révélé que Le HCQS est bien toléré par les participants et aucun effet indésirable grave ni effet secondaire cardiaque n'a été signalé parmi eux. Mots-clés: Chimioprophylaxie, COVID-19, hydroxychloroquine, Conseil indien de la recherche médicale.

A Double Whammy Pneumonia: The First Reported Case of Concurrent Neisseria meningitidis and SARS-CoV-2 Pneumonia.

Meningococcal pneumonia (MP) is a rare manifestation of meningococcal disease. The MP was first described in 1907 when Neisseria meningitidis (NM) isolates were identified in sputum samples obtained from soldiers with pneumonia. Preceding and concurrent viral infections constitute a major risk for MP. During the 1918-1919 influenza pandemic, a significant increase in MP cases were reported in patients with preceding influenza infection. Despite the end of the last H1N1 influenza pandemic in 2010, seasonal influenza infections still pose a risk for simultaneous MP. History appears to be repeating itself with concomitant bacterial and viral coinfection amid the current SARS-CoV-2 pandemic. Herein presented is a unique case of an elderly woman who presented with, to the best of our knowledge, the first reported case of possible concurrent SARS-CoV-2 and MP infections.

Treatment of Breast Disease During the Coronavirus Pandemic

INTRODUCTION: The COVID-19 pandemic peaked in New York City in Spring 2020. From March 20-May 4, all elective operations were suspended due to the number of hospitalized Covid-19 patients. In this study, we sought to describe patterns of care for surgical patients during this time. METHODS: An IRB approved retrospective review was performed of patients who presented to our hospital system from March-May 2020, diagnosed with breast cancer or atypia. RESULTS: We identified 75 patients with breast cancer and 19 patients with atypia. According to standard of care, 55/75 (73%) cancer patients would have undergone upfront surgery. 2/55 (4%) instead were treated with neoadjuvant chemotherapy (NCT), 34/55 (62%) with neoadjuvant endocrine therapy (NET), and 19/55 (34%) had no immediate treatment. 12/19 (63%) with no immediate treatment had DCIS only. 7 had invasive disease, and mean days from diagnosis to surgery was 63 days (range 47-79). One patient had a positive node. A total of 20/75 (27%) patients needed NCT based on advanced stage or molecular profile and had no delay in starting treatment. Of the 34 NET patients, 5 (14.7%) were treated for approximately 6 months and 24 (70.6%) were treated for approximately 6 weeks as a bridge to surgery only. Of the 34 patients who received NET, 5 (14.7%) had an apparent decrease in T stage: 3 patients with clinical T1 disease had no residual disease. 2 had clinical T2 and ultimately had pathological T1 disease. Of the 19 patients with atypia, 6 (31.6%) started chemoprevention preoperatively and 1 patient was already receiving it for a previous LCIS diagnosis. All underwent subsequent surgery and 1/19 (5.3%) patients was upstaged to DCIS. CONCLUSIONS: During the peak of Covid-19, with delay of surgery, we observed an increased utilization of NET when compared to usual treatment patterns, with no apparent adverse effects. While further studies are needed to validate our results, we may see more wide spread use of NET in the future to temporize patients as needed.

Treatment of COVID-19 Pneumonia and Acute Respiratory Distress with Ramatroban, a Thromboxane A2 and Prostaglandin D2 Receptor Antagonist: A 4-Patient Case Series Report

Lungs in COVID-19 patients produce lipid mediators measured in bronchoalveolar lavage fluid (BALF), notably thromboxane B2 (TxB2) >> prostaglandin E2 > prostaglandin D2 (PGD2).1 High levels of TxA2 metabolites in BALF from COVID-19 associated ARDS,1 and systemically in non- ICU COVID-19 patients2,3 led us to propose a critical role for TxA2 prostanoid receptors (TPr) in COVID-19 respiratory distress. We hypothesized that TxA2/TPr signaling in airways, pulmonary microvasculature, and veins contributes to pulmonary edema and hypoxemia in COVID-19 pneumonia. TPr signaling contracts intrapulmonary veins with 10-fold higher potency than arteries.4 High concentrations of TxA2 impede pulmonary venous blood flow, increase microvascular pressure, and force fluid into alveoli.4 TPr signaling also activates platelets and triggers tissue factor expression on monocytes, which may contribute to thrombosis in COVID-19. A TPr antagonist was previously reported to decrease pulmonary capillary pressure by selectively reducing post-capillary resistance in patients with acute lung injury.5 PGD2 stimulation of Dprostanoid receptor 2 (DPr2, aka CRTH2) suppresses interferon lambda (IFN-λ) transcription in the upper respiratory tract in response to respiratory viruses. PGD2/DPr2 antagonism boosts local IFN- λ antiviral responses and limits viral replication.6 Antagonism of TxA2/TPr and PGD2/DPr2 signaling has been proposed for antiviral, antithrombotic and immunomodulatory action in COVID- 19.7 Ramatroban is an oral, dual receptor antagonist of TxA2/TPr and PGD2/DPr2 and a potential candidate for chemoprophylaxis and treatment of COVID-19.1,7 With well-established safety, ramatroban has been used since 2000 in Japan for the treatment of allergic rhinitis.8 We report here a small case series of four consecutive outpatients with COVID-19 with new onset or worsening respiratory distress and hypoxemia who were treated with oral ramatroban (Baynas®, Bayer Yakuhin, Japan). Summarized below, ramatroban afforded rapid improvement in respiratory distress and hypoxemia, followed by complete recovery, successfully avoiding hospitalization. Conclusion: Four consecutive outpatients with COVID-19 were treated with ramatroban. Improvement within hours was followed by gradual complete recovery, thereby avoiding hospitalization. As a safe, oral drug, ramatroban merits clinical trials for both outpatients and hospitalized patients with SARS-CoV-2 infection and COVID-19.

Central Nervous System Tuberculosis with SARS-CoV-2 Infection: A Short Case-series from Sri Lanka

Objective: To report a series of patients with clinical and imaging findings suggestive of central nervous system (CNS) Tuberculosis (TB) and active or recent SARS-CoV-2 infection presenting to a single tertiary care center within a two-month period. Background: A presumptive diagnosis of CNS TB is made in the setting of relevant clinical and epidemiologic factors together with typical radiographic findings. Immunosuppression is clearly associated with reactivation or re-infection of TB, although triggers leading to a reactivation are unclear. It is postulated that the SARS-CoV-2 infection suppresses the host innate and adaptive immunity. Design/Methods: NA Results: Three patients with suspected and one with confirmed CNS TB were identified. Patient one presented with a history of fever and altered sensorium for one-week. Concurrent SARS-CoV-2 infection was confirmed. CT-brain showed an obstructive hydrocephalus and an External Ventricular Drain was placed. Cerebrospinal fluid (CSF) nucleic acid amplification test (NAAT) for TB was positive. Patients 2-4 were diabetic and had SARS-CoV-2 infection identified concurrently or in the preceding two weeks. They presented with a history of headache & diplopia of two weeks duration. Examination revealed multiple cranial nerve palsies. The common MRI features were contrast enhancement & soft tissue thickening in the cavernous sinus wall. Patient two had multiple tuberculomas, patient three had orbital apex involvement and patient four had Meckel's cave thickening. CSF analysis revealed elevated proteins without cells and NAAT for TB was negative. All patients were started on anti-TB chemoprophylaxis with corticosteroids. Conclusions: Given the potential immunomodulatory role of SARS-CoV-2, we hypothesize that the viral infection acted as a trigger for the reactivation of TB in the CNS. In addition, three out of four of our patients had cavernous sinus wall involvement which is an unusual finding in CNS TB.

Development of New Strategies for Malaria Chemoprophylaxis: From Monoclonal Antibodies to Long-Acting Injectable Drugs.

Drug discovery for malaria has traditionally focused on orally available drugs that kill the abundant, parasitic blood stage. Recently, there has also been an interest in injectable medicines, in the form of monoclonal antibodies (mAbs) with long-lasting plasma half-lives or long-lasting depot formulations of small molecules. These could act as prophylactic drugs, targeting the sporozoites and other earlier parasitic stages in the liver, when the parasites are less numerous, or as another intervention strategy targeting the formation of infectious gametocytes. Generally speaking, the development of mAbs is less risky (costly) than small-molecule drugs, and they have an excellent safety profile with few or no off-target effects. Therefore, populations who are the most vulnerable to malaria, i.e., pregnant women and young children would have access to such new treatments much faster than is presently the case for new antimalarials. An analysis of mAbs that were successfully developed for oncology illustrates some of the feasibility aspects, and their potential as affordable drugs in low- and middle-income countries.

Managing a COVID 19 patient at different health care and field level settings. (Special Issue: The epidemiologist and the pandemic.)

This continuing medical education (CME) outlines current national strategies to combat the pandemic of Corona virus (COVID 19). During a pandemic it is an obligation for each and every health care worker to be well versed with current guidelines. Three types of COVID dedicated health facilities as separate areas for suspect and confirmed cases are designed. Management of cases depend on their clinical status and result of COVID-19 testing. All three COVID dedicated health facilities of facilities are linked to the Surveillance team (IDSP). Isolation and quarantine play a key role in slowing the spread of COVID 19 and protecting people. Strict infection prevention and control practices are crucial in COVID 19 management. Evolving advisory on mask management, Chemoprophylaxis for COVID 19, Telemedicine in COVID 19, AYUSH in COVID 19, COVID-19 screening tool and others are to be carefully practiced. Ultimately prevention at individual, family, workplace and community level is the backbone of all strategies against COVID 19.

Chemoprophylaxis against COVID-19 among health-care workers using Ivermectin in low- and middle-income countries: A systematic review and meta-analysis.

Coronavirus disease-2019 (COVID-19) is a novel viral infectious disease that the World Health Organization (WHO) has announced to be a pandemic. This meta-analysis was aimed at providing evidence for the use of ivermectin to prevent COVID-19 among hospital workers in low-resource countries. Medical databases including African Journals online, Google Scholar, PubMed, Cochrane library, EMBASE, COVID-19 research database (WHO), Clinicaltrials.gov, and SCOPUS were searched for studies on Ivermectin as a chemoprophylactic drug against COVID-19 among hospital personnel in settings with limited resources. Preprint servers such as bioRxiv and medRxiv as well as the gray literature were also searched. Studies adjudged to be eligible were identified using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses algorithm. Statistical analyses were done using Stata version 14.3. Seven studies were selected for the meta-analysis. The total sample size was 2652. There were two randomized controlled trials and five nonrandomized studies. Some studies dosed Ivermectin daily while some dosed it weekly. However, one of the studies dosed it monthly. The studies reported variable clinical benefits. I2 statistic was 92%, and random effect model was used. The pooled odd ratio was 0.11 (95% confidence interval 0.09-0.13). This implies that 89% of the participants benefited from taking Ivermectin as a form of preexposure chemoprophylaxis. Ivermectin has a significant clinical benefit as a preventive drug against COVID-19 for hospital personnel in settings with limited resources.

Treatment and prevention of community-acquired bacterial meningitis

Bacterial meningitis is a serious infection that requires immediate treatment. Recommended empiric antimicrobial therapy is based upon the most likely pathogen, according to a patient’s age and immune status. Antimicrobial therapy should be modified after identification of the causative microorganism and results of susceptibility tests. Preventive measures include the use of vaccines that target Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae, as well as the use of chemoprophylaxis in selected situations. Pharmacists are in a key position to recommend appropriate antimicrobial therapy for the treatment and prophylaxis of bacterial meningitis and to ensure that patients are receiving recommended vaccinations.

Prophylactic Role of Ivermectin in Severe Acute Respiratory Syndrome Coronavirus 2 Infection Among Healthcare Workers.

Introduction Healthcare workers (HCWs) are vulnerable to getting infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Preventing HCWs from getting infected is a priority to maintain healthcare services. The therapeutic and preventive role of ivermectin in coronavirus disease 2019 (COVID-19) is being investigated. Based on promising results of in vitro studies of oral ivermectin, this study was conducted with the aim to demonstrate the prophylactic role of oral ivermectin in preventing SARS-CoV-2 infection among HCWs at the All India Institute of Medical Sciences (AIIMS) Bhubaneswar. Methods A prospective cohort study was conducted at AIIMS Bhubaneswar, which has been providing both COVID and non-COVID care since March 2020. All employees and students of the institute who provided written informed consent participated in the study. The uptake of two doses of oral ivermectin (300 µg/kg/dose at a gap of 72 hours) was considered as exposure. The primary outcome of the study was COVID-19 infection in the following month of ivermectin consumption, diagnosed as per Government of India testing criteria (real-time reverse transcriptase polymerase chain reaction [RT-PCR]) guidelines. The log-binomial model was used to estimate adjusted relative risk (ARR), and the Kaplan-Meier failure plot was used to estimate the probability of COVID-19 infection with follow-up time. Results Of 3892 employees, 3532 (90.8%) participated in the study. The ivermectin uptake was 62.5% and 5.3% for two doses and single dose, respectively. Participants who took ivermectin prophylaxis had a lower risk of getting symptoms suggestive of SARS-CoV-2 infection (6% vs 15%). HCWs who had taken two doses of oral ivermectin had a significantly lower risk of contracting COVID-19 infection during the following month (ARR 0.17; 95% CI, 0.12-0.23). Females had a lower risk of contracting COVID-19 than males (ARR 0.70; 95% CI, 0.52-0.93). The absolute risk reduction of SARS-CoV-2 infection was 9.7%. Only 1.8% of the participants reported adverse events, which were mild and self-limiting. Conclusion Two doses of oral ivermectin (300 µg/kg/dose given 72 hours apart) as chemoprophylaxis among HCWs reduced the risk of COVID-19 infection by 83% in the following month. Safe, effective, and low-cost chemoprophylaxis has relevance in the containment of pandemic alongside vaccine.