Vaccine hesitancy and refusal among parents: An international ID-IRI survey.

INTRODUCTION: Although vaccines are the safest and most effective means to prevent and control infectious diseases, the increasing rate of vaccine hesitancy and refusal (VHR) has become a worldwide concern. We aimed to find opinions of parents on vaccinating their children and contribute to available literature in order to support the fight against vaccine refusal by investigating the reasons for VHR on a global scale. METHODOLOGY: In this international cross-sectional multicenter study conducted by the Infectious Diseases International Research Initiative (ID-IRI), a questionnaire consisting of 20 questions was used to determine parents' attitudes towards vaccination of their children. RESULTS: Four thousand and twenty-nine (4,029) parents were included in the study and 2,863 (78.1%) were females. The overall VHR rate of the parents was found to be 13.7%. Nineteen-point three percent (19.3%) of the parents did not fully comply with the vaccination programs. The VHR rate was higher in high-income (HI) countries. Our study has shown that parents with disabled children and immunocompromised children, with low education levels, and those who use social media networks as sources of information for childhood immunizations had higher VHR rates (p < 0.05 for all). CONCLUSIONS: Seemingly all factors leading to VHR are related to training of the community and the sources of training. Thus, it is necessary to develop strategies at a global level and provide reliable knowledge to combat VHR.

Clinical Profile, Treatment, and Outcome of Patients with Secondary Hemophagocytic Lymphohistiocytosis in Critically Ill Patients: A Prospective Observational Study.

Introduction: The objective of the study was to evaluate the clinical profile and outcome of patients with secondary hemophagocytic lymphohistiocytosis (HLH) in critically ill patients. Materials and methods: A prospective observational study was conducted where critically ill adult patients presenting with fever and bicytopenia were evaluated according to the HLH-2004 diagnostic criteria for the presence of secondary HLH. The underlying trigger, clinical profile, treatment, and outcome of patients with HLH were analyzed. Results: Of the 76 critically ill patients with fever and bicytopenia, 33 (43%) patients were diagnosed with HLH. The following triggers for HLH were identified: bacterial infections (23%), fungal infections (10%), viral infections (10%), parasitic infections (10%), autoimmune diseases (13%), and malignancy (8%). A total of 78% of the HLH cases received steroids, but the use of steroids was not associated with improvement in mortality. Conclusion: There is a high prevalence of HLH in patients presenting with fever and bicytopenia in critically ill adult patients. Infections were identified as the most common trigger of HLH. How to cite this article: Fazal F, Gupta N, Soneja M, Mitra DK, Satpathy G, Panda SK, et al. Clinical Profile, Treatment, and Outcome of Patients with Secondary Hemophagocytic Lymphohistiocytosis in Critically Ill Patients: A Prospective Observational Study. Indian J Crit Care Med 2022;26(5):564-567.

Nontuberculous mycobacteria: A report of eighteen cases from a tertiary care center in India.

CONTEXT: Nontuberculous mycobacteria (NTM) are ubiquitous mycobacteria present in environment and generally affect patients with either structural lung disease or immunosuppression and commonly involve lungs, lymph node, or skin. MATERIALS AND METHODS: Between July 2016 and February 2019, 18 cases of NTM were diagnosed and their relevant clinical, diagnostic, and treatment details were recorded after taking informed consent. RESULTS: We report 18 cases of NTM involving lungs (n = 11), skin and soft tissue (n = 3), joint (n = 2), genitourinary (n = 1), and central nervous system (n = 1). History of immunosuppression was present in two patients, whereas history of some form of intervention was seen in six patients. Mycobacterium fortuitum group (n = 5) was the most commonly isolated organism, followed by Mycobacterium avium complex (n = 4), Mycobacterium abscessus (n = 3), Mycobacterium kansasii (n = 2), and Mycobacterium chelonae (n = 1). In two patients, M. chelonae and M. abscessus were isolated in succession. Of these 18 patients, clinical response was present in 15 of the patients. Diagnosis and treatment of NTM in resource limited settings is extremely challenging. CONCLUSION: Most of the patients with NTM are misdiagnosed and are treated as tuberculosis in India, sometimes with a multidrug resistance regimen, which results in significant morbidity and mortality. We present these cases to shed some light on the epidemiology of NTM in this part of India.

Haemophagocytic lymphohistiocytosis in human immunodeficiency virus: a systematic review of literature.

Diagnosis and management of hemophagocytic lymphohistiocytosis (HLH) in patients with human immunodeficiency virus (HIV) infection are scarcely described in the published literature. The aim of this systematic review was to delineate the triggers of HLH in patients with HIV and understand the role of steroids in the management. We conducted a comprehensive search of English medical literature via the Medline / PubMed database using different synonyms of "HIV" AND "HLH". The review was registered in PROSPERO (CRD42018099987). The titles and abstracts of the 185 articles between January 1986 and April 2018 were reviewed. The final analysis was done from 42 articles with 52 patients. HLH was associated with malignancy in 17 patients, while infection was found in 25 patients. No cause was identified in eight patients, out of which four had acute HIV infection. Death was reported in 21 patients. Presence of either malignancy (p = 0.051) or opportunistic infection (p = 0.69) was not associated with increased chances of death by univariate analysis. A total of 26 patients were treated with steroids, while etoposide was used in only four patients. Administration of steroids as a treatment of HLH was associated with more chances of death (p = 0.048). Malignancy and Opportunistic infections are important triggers for HLH in patients with HIV. Acute HIV by itself can act as a trigger for HLH. Evidence on the use of steroids as a treatment of HLH in patients with HIV is not convincing.

Impact of trainee-driven Antimicrobial Stewardship Program in a high burden resource-limited setting.

Antimicrobial Stewardship Program (ASP) is one of the most critical interventions required to halt the growing global antimicrobial resistance. The study aimed to evaluate the effect of trainee driven ASP implementation with limited available resources on outcome variables. An ASP team comprising of infectious diseases trainees and consultants was constituted to conduct stewardship activities in the Department of Medicine, All India Institute of Medical Sciences, a tertiary care apex institute in north India. Prospective audit and feedback were conducted by the team, and the following outcome variables were recorded and analyzed: the practice of sending cultures, appropriateness of prescribed empiric antibiotics, gross antimicrobial consumption and mortality. ASP intervention led to an increase in blood culture positivity rates by two folds (p<0.001). The trend of empiric prescription choices gradually shifted over time towards the use of more effective antibiotics according to the local antibiogram. Redundant usage of antibiotics substantially reduced over time. There was no impact of the antimicrobial stewardship program on the all-cause mortality rate. ASP had a significant effect on the practice of sending cultures and appropriateness of antibiotic usage. In resource-limited settings, trainee-driven antimicrobial stewardship program can succeed in inculcating rational practices among fellow residents and practicing physicians.

Evaluation of 16S rRNA broad range PCR assay for microbial detection in serum specimens in sepsis patients.

BACKGROUND: Early and accurate laboratory diagnosis and appropriate management of infection improves the survival rate in sepsis. In this study we evaluated broad range 16S rRNA and 16 S-23 S intergenic spacer region (ISR) PCR assays followed by nucleotide sequencing directly from patients' serum and automated blood culture for laboratory diagnosis in admitted sepsis patients. METHODS: A broad range 16S rRNA PCR and 16 S-23 S ISR PCR assay followed by nucleotide sequencing was used directly from patients' serum in hospital admitted patients in 62 sepsis and 16 suspected blood stream infection (sBSI) patients. Automated blood culture was also used in the same patients. Nucleotide sequences were analyzed against NCBI Genbank database and organisms were identified using CLSI MM18A guidelines. RESULTS: Bacterial culture were positive in 10/62 (16.12%) sepsis and 3/16 (18.75%) suspected BSI patients along with 3 detected fungi (2 in sepsis and 1 in suspected BSI group). PCR assay was positive in 36/62 (58.06%) sepsis and 6/16 (37.5%) suspected BSI patients respectively. All but 2 bacteria (both from culture negative patients) detected by PCR assay could be identified from nucleotide sequencing. Survival in sepsis patients was 77%. PCR assay could detect bacteria in 9/14 (64.28%) of sepsis patients with death. CONCLUSION: Broad range PCR assay was far superior for early diagnosis of infection. The bacteria which could not be detected by culture and were not commonly reported from this centre, were detected by the broad range PCR assays. Detection of these rare bacteria/fungi had significant clinical correlation with patient's underlying clinical conditions, immune status and prognosis. The tests could provide definitive diagnosis of infection in >58% of sepsis patients, which helped in patient management and better survival.

Stenotrophomonas maltophilia: More than Just a Colonizer!

Stenotrophomonas maltophilia is an emerging gram-negative pathogen that was previously labeled as a colonizer. Nowadays, with multiple antibiotic usage along with certain host factors, infections caused by this organism are getting attention. We hereby report two cases of ventilator-associated pneumonia in postoperative infants by Stenotrophomonas maltophilia in a cardiac intensive care unit (ICU). How to cite this article: Baidya A, Kodan P, Fazal F, Tsering S, Menon RP, Jorwal P, et al. Stenotrophomonas maltophilia: More than Just a Colonizer! Indian J Crit Care Med 2019;23(9):434-436.

Fatal familial hemophagocytic lymphohistiocytosis with perforin gene (PRF1) mutation and EBV-associated T-cell lymphoproliferative disorder of the thyroid

Familial hemophagocytic lymphohistiocytosis (FHL) is a rare fatal autosomal recessive disorder of immune dysregulation. The disease presents most commonly in the first year of life; however, symptomatic presentation throughout childhood and adulthood has also been identified. Biallelic mutation in the perforin gene is present in 20%­50% of all cases of FHL. Secondary hemophagocytic lymphohistiocytosis (HLH) in association with hematological malignancies is known; however, whether mutations in HLH-associated genes can be associated with FHL and hematolymphoid neoplasms is not well documented. Also, Epstein­Barr-virus- (EBV) positive systemic T-cell lymphoproliferative disease (SE-LPD) in the setting of FHL is not clearly understood. Here, we present the case of a young boy who presented with typical features of childhood FHL harboring the perforin gene (PRF1) mutation, and had SE-LPD diagnosed on autopsy, along with evidence of recent EBV infection. The patient expired due to progressive disease. Five siblings died in the second or third decade of life with undiagnosed disease. Genetic counseling was provided to the two surviving siblings and parents, but they could not afford genetic testing. One surviving sibling has intermittent fever and is on close follow-up for possible bone marrow transplantation.

Fatal familial hemophagocytic lymphohistiocytosis with perforin gene (PRF1) mutation and EBV-associated T-cell lymphoproliferative disorder of the thyroid.

Familial hemophagocytic lymphohistiocytosis (FHL) is a rare fatal autosomal recessive disorder of immune dysregulation. The disease presents most commonly in the first year of life; however, symptomatic presentation throughout childhood and adulthood has also been identified. Biallelic mutation in the perforin gene is present in 20%-50% of all cases of FHL. Secondary hemophagocytic lymphohistiocytosis (HLH) in association with hematological malignancies is known; however, whether mutations in HLH-associated genes can be associated with FHL and hematolymphoid neoplasms is not well documented. Also, Epstein-Barr-virus- (EBV) positive systemic T-cell lymphoproliferative disease (SE-LPD) in the setting of FHL is not clearly understood. Here, we present the case of a young boy who presented with typical features of childhood FHL harboring the perforin gene (PRF1) mutation, and had SE-LPD diagnosed on autopsy, along with evidence of recent EBV infection. The patient expired due to progressive disease. Five siblings died in the second or third decade of life with undiagnosed disease. Genetic counseling was provided to the two surviving siblings and parents, but they could not afford genetic testing. One surviving sibling has intermittent fever and is on close follow-up for possible bone marrow transplantation.

Haemophagocytic lymphohistiocytosis in patients with human immunodeficiency virus infection: to treat or not to treat.

Haemophagocytic lymphohistiocytosis (HLH) in Human Immunodeficiency Virus (HIV) infected individuals can either be due to the disease itself or due to associated infections/malignancies. The treatment for HLH requires immunosuppressive therapy but administering immunosuppressive therapy to an already immunosuppressed patient (HIV infection) is complex. We present two such cases of HLH in patients infected with HIV. In the first case, no alternate cause for HLH was found even after extensive investigations and it was attributed to the uncontrolled HIV replication. Patient was started on dexamethasone for the same but succumbed to hospital acquired pneumonia. The second patient was diagnosed with Hodgkin's lymphoma but he succumbed to his illness before initiating immunosuppressive therapy for HLH. We report these cases to highlight the dilemma and a need for further research in this direction.

Management of ventilator-associated pneumonia (VAP) caused by resistant gram-negative bacteria: which is the best strategy to treat?

Introduction: Treatment of ventilator-associated pneumonia (VAP) is a major challenge. The increase in multi-drug resistant bacteria has not been accompanied by the validation of new drugs, or by any new antimicrobial strategies to exploit the available agents. VAP due to Gram-negative bacteria has increased mortality, both due to the resistant pathogens themselves and due to inappropriate treatment. Local epidemiology, patients' characteristics and clinical responses provide the most important information for therapeutic decision-making. Moreover, data on VAP therapy due to resistant bacteria are lacking, and the choice of treatment is often based on clinical practice and individual experience. Areas covered: This review summarizes the strategies available for treating the three most prevalent resistant Gram-negative organisms causing VAP: Pseudomonas aeruginosa, Acinetobacter baumannii and Enterobacteriaceae. The review covers the results of a Pubmed search, clinical practice guidelines and reviews, and the authors' experience. Expert opinion: The existing evidence focuses on bloodstream infections or other sites rather than pneumonia and there are no recommendations for the treatment of VAP by multi-drug resistant Gram-negative bacteria, especially for combination regimens. The approval of new drugs is needed to provide effective and safe alternatives for treating carbapenemase-producing strains. Precision medicine and personalized approach are also fundamental in future research.

Toxic shock syndrome: the great masquerader.

Toxic shock syndrome is a rare but potentially lethal toxin-mediated illness that can be caused by streptococcal and staphylococcal species. It initially presents as a febrile illness that rapidly progresses to multiorgan dysfunction, hence a high index of suspicion coupled with rapid verification of the diagnosis and aggressive treatment is required to improve the outcome of the disease. A 23-year-old man presented with high-grade fever associated with headache, retro-orbital pain, gastroenteritis and gum bleeds. Treatment was initiated keeping in mind the possibility of dengue haemorrhagic fever. However, further clinical deterioration led us to re-examine our patient, revealing an old neglected wound. Microbiological confirmation of methicillin-resistant Staphylococcus aureus from the wound swab and prompt institution of appropriate treatment led to a favourable outcome in a case known to be associated with serious morbidity and mortality.

Is there a need for shifting patients on long term nevirapine based regimens to efavirenz based regimens: a cross-sectional study?

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are the backbone of effective anti-retroviral therapy in the developing world. Efavirenz is the current NNRTI of choice due to reports of higher incidence of serious adverse events with nevirapine. Majority of patients with Human immunodeficiency virus (HIV) infection in India are still on nevirapine based therapy. The aim of the study was to evaluate the need of shifting these patients to efavirenz based therapy. A cross-sectional study was conducted on adult patients, who were on NNRTI based regimen for more than one year with good adherence. The patients were divided into efavirenz or nevirapine groups based on the treatments they were receiving at the time of study. The different arms were compared based on their clinical and laboratory profile, adverse events and immunological response. A total of 244 patients were recruited. A total of 125 patients were receiving nevirapine based regimen while 119 patients were receiving efavirenz based regimen. There was no significant difference in the frequency of hematological and biochemical derangements between the two groups. There was no difference in the median highest CD4 count achieved during therapy between the two groups. Clinically observed side effects were more common in the efavirenz group. These results suggest that there isn't enough evidence to shift patients tolerating long term nevirapine based therapy to efavirenz based therapy.

Two cases of Osteoarticular Mucor menace: A diagnostic and management conundrum.

Mucormycosis is an uncommon aggressive fungal infection usually seen in immunocompromised hosts or patients with burns and trauma. The common presentations include rhino-orbital-cerebral and pulmonary involvement. Osteoarticular involvement is a rare presentation of this disease. We present two cases of osteoarticular mucormycosis of pelvis and long bones of the lower limb, one in a patient with burn injury and other one in a patient with chronic granulomatous disease, hitherto a rarely reported association. Delayed diagnosis in a setting where tuberculosis is a common cause of chronic osteomyelitis, challenges in medical and surgical management of these patients are discussed in this report.

The phytochemistry, traditional uses and pharmacology of Piper Betel. linn (Betel Leaf): A pan-asiatic medicinal plant.

Since antiquity, Piper betel. Linn, commonly known as betel vine, has been used as a religious, recreational and medicinal plant in Southeast Asia. The leaves, which are the most commonly used plant part, are pungent with aromatic flavor and are widely consumed as a mouth freshener. It is carminative, stimulant, astringent and is effective against parasitic worms. Experimental studies have shown that it possess diverse biological and pharmacological effects, which includes antibacterial, antifungal, larvicidal, antiprotozal, anticaries, gastroprotective effects, free radical scavenging, antioxidant, anti-inflammatory hepatoprotective, immunomodulatory, antiulcer and chemopreventive activities. The active principles hydroxychavicol, allylpyrocatechol and eugenol with their plethora of pharmacological properties may also have the potential to develop as bioactive lead molecule. In this review, an attempt is made to summarize the religious, traditional uses, phytochemical composition and experimentally validated pharmacological properties of Piper betel. Emphasis is also placed on aspects warranting detail studies for it to be of pharmaceutical/clinical use to humans.

Anti-diabetic effects of the Indian indigenous fruit Emblica officinalis Gaertn: active constituents and modes of action.

Dietary constituents are shown to play an important role in the development of diabetes. Studies have shown that the fruits of Emblica officinalis Gaertn or Phyllanthus emblica Linn, colloquially known as Indian gooseberry or amla and/or some of its important constituents (including gallic acid, gallotanin, ellagic acid and corilagin), possess anti-diabetic effects through their antioxidant and free radical scavenging properties. Amla has also been reported to prevent/reduce hyperglycemia, cardiac complications, diabetic nephropathy, neuropathy, cataractogenesis and protein wasting. However, clinical trial data with human subjects are limited and preliminary. For the first time this review summarizes the anti-diabetic affects of amla and also addresses the mechanisms mediating these properties.

Safety considerations in pharmacotherapy of bipolar disorder.

Bipolar disorder is a chronic, frequently relapsing illness with a prevalence of 1.2% to 3.4% in the general population. It is associated with high disability, higher comorbidity due to medical illnesses, and significant social and economical consequences for patients, their families, and society. The episodic nature of this disease warrants rational use of medications and proper monitoring for adverse events. Various drug classes, such as mood stabilizers, antipsychotics, benzodiazepines, and antidepressants, are used for the acute and maintenance treatment of bipolar disorder. Each group of drugs is associated with wide array of adverse events and drug interactions, which are the main hurdles in treatment outcome and compliance. Common side effects seen with several agents, particularly antipsychotics, are somnolence, weight gain, extrapyramidal symptoms, dyslipidemia, type-2 diabetes, and hyperprolactinemia. Major drug interactions are seen with drugs such as carbamazepine, due to hepatic enzyme induction. Adverse effects such as somnolence are tolerability concerns and can be managed easily; others, such as diabetes mellitus, are safety concerns. It is prudent to have precise knowledge of the individual drug's side-effect profile, pharmacokinetics, and pharmacodynamics, to plan a treatment regimen. More research is needed to understand potential risks of various drugs and to devise and incorporate monitoring protocols in the treatment regimen.