Exploring the recent pioneering developments of small molecules in antimalarial drug armamentarium: A chemistry prospective appraisal.

Malaria is a very destructive and lethal parasitic disease that causes significant mortality worldwide, resulting in the loss of millions of lives annually. The uncontrolled intake of antimalarial drugs often employed in clinical settings has resulted in the emergence of numerous strains of plasmodium that are resistant to these drugs, including multidrug-resistant strains. Hence, there is an urgent need for developing unique classes of antimalarial drugs that function with distinct mechanisms of action. In this context, the design and development of hybrid compounds that combine pharmacophoric properties from different lead molecules into a single unit gives a unique perspective towards further development of malaria drugs in the next generation. In light of this, we have reviewed the progress of hybrid antimalarial agents from 2021 up to the present. This manuscript presents a comprehensive overview of the latest advancements in the medicinal chemistry pertaining to small molecules, with a specific focus on their potential as antimalarial agents. This review explores a variety of physiologically active compounds that have been described in the literature in order to lay a strong foundation for the logical design and eventual identification of antimalarial drugs based on lead frameworks.

A brief overview on recent advances in spiro[chromane-2,4'-piperidine]-4(3H)-one-functionalized compounds in medicinal chemistry research.

The spiro[chromane-2,4'-piperidine]-4(3H)-one is an important pharmacophore. It is a structural component in many drugs, drug candidates (or lead compounds) and various biochemical reagents. This review demonstrated an impressive progress in syntheses of spiro[chromane-2,4'-piperidine]-4(3H)-one-derived compoundsin the recent years and focuses on features of their biological relevance's. The prospects for the development of new biologically active substances containing a spiro[chromane-2,4'-piperidine]-4(3H)-one pharmacophore are analyzed and briefly discussed in terms of its structure, reaction, mechanism, scope and potential utility.

Neurosurgery and Neurology Practices during the Novel COVID-19 Pandemic: A Consensus Statement from India.

BACKGROUND: The COVID-19 infection outbreak has aroused increasing attention and affected thousands of people nationwide. The long incubation period, high infectious rate, varied manifestation, and absence of effective treatment make it difficult to manage the disease transmission. OBJECTIVE: The intended goals are to encourage efficient management of neurological and neurosurgical patients, resource utilization, and protecting the healthcare provider during the COVID-19 epidemic. Herein, we present a consensus statement from various centers in India. METHODOLOGY: In addition to the literature review, recommendations were included from neurologists and neurosurgeons from various centers in India. RESULTS: Every patient presenting for treatment should be treated as a potential asymptomatic infected case. Patients should be categorized based upon the priority as acute (require immediate treatment/surgery within 24 h), sub-acute (requiring treatment within a maximum of 7-10 days), or chronic (requiring treatment within a month). Non-essential elective surgeries and outpatient clinics should be avoided after informing the patient(s). There is a high risk of aerosol dispersion during intubation and certain neurosurgical procedures particularly those involving drills and endoscopes. These procedures should be performed wearing full personal protective equipment. The workflow of the operating rooms should also be modified significantly. Minor modifications in personal and professional lifestyles and routine training to use the PPE will ensure efficient management of resources. CONCLUSION: These recommendations could be used to mitigate the risks and reduce exposure to other patients, public, and healthcare staff.

Revised diagnostic criteria for neurocysticercosis.

BACKGROUND: A unified set of criteria for neurocysticercosis (NCC) has helped to standardize its diagnosis in different settings. METHODS: Cysticercosis experts were convened to update current diagnostic criteria for NCC according to two principles: neuroimaging studies are essential for diagnosis, and all other information provides indirect evidence favoring the diagnosis. Recent diagnostic advances were incorporated to this revised set. RESULTS: This revised set is structured in absolute, neuroimaging and clinical/exposure criteria. Absolute criteria include: histological confirmation of parasites, evidence of subretinal cysts, and demonstration of the scolex within a cyst. Neuroimaging criteria are categorized as major (cystic lesions without scolex, enhancing lesions, multilobulated cysts, and calcifications), confirmative (resolution of cysts after cysticidal drug therapy, spontaneous resolution of single enhancing lesions, and migrating ventricular cysts on sequential neuroimaging studies) and minor (hydrocephalus and leptomeningeal enhancement). Clinical/exposure criteria include: detection of anticysticercal antibodies or cysticercal antigens by well-standardized tests, systemic cysticercosis, evidence of a household Taenia carrier, suggestive clinical manifestations, and residency in endemic areas. Besides patients having absolute criteria, definitive diagnosis can be made in those having two major neuroimaging criteria (or one major plus one confirmative criteria) plus exposure. For patients presenting with one major and one minor neuroimaging criteria plus exposure, definitive diagnosis of NCC requires the exclusion of confounding pathologies. Probable diagnosis is reserved for individuals presenting with one neuroimaging criteria plus strong evidence of exposure. CONCLUSIONS: This revised set of diagnostic criteria provides simpler definitions and may facilitate its more uniform and widespread applicability in different scenarios.

Host Th1/Th2 immune response to Taenia solium cyst antigens in relation to cyst burden of neurocysticercosis.

Neurocysticercosis (NCC), Taenia solium larval infection of the brain, is an important cause of acquired seizures in endemic countries, which relate to number, location and degenerating cysts in the brain. Multicyst infections are common in endemic countries although single-cyst infection prevails in India. Single-cyst infections in an endemic country suggest a role for host immunity limiting the infection. This study examined ex vivo CD4(+) T cells and in vitro Th1 and Th2 cytokine responses to T. solium cyst antigens of peripheral blood mononuclear cells of healthy subjects from endemic and nonendemic regions and of single- and multicyst-infected patients for association with cyst burden of NCC. T. solium cyst antigens elicited a Th1 cytokine response in healthy subjects of T. solium-endemic and T. solium-non-endemic regions and those with single-cyst infections and a Th2 cytokine response from subjects with multicyst neurocysticercosis. Multicyst neurocysticercosis subjects also exhibited low levels of effector memory CD4(+) T cells. Th1 cytokine response of T. solium exposure and low infectious loads may aid in limiting cyst number. Th2 cytokines and low effector T cells may enable multiple-cyst infections to establish and persist.

Electroanalysis of antitubercular drugs in pharmaceutical dosage forms and biological fluids: a review.

Tuberculosis remains a major global public health problem. Given the need for extensive analysis of antitubercular drugs, the development of sensitive, reliable and facile analytical methods to determine these compounds becomes necessary. Electrochemical techniques have inherent advantages over other well-established analytical methods, this review aiming to provide an updated overview of the latest trends (from 2006 till date) in the voltammetric determination of antitubercular drugs. Furthermore, the advantages and limitations of these methods are critically discussed. The review reveals that in spite of using a variety of chemically modified electrodes to determine antitubercular drugs, there is still a dearth of applicability of the voltammetric methods to quantify these compounds in human body fluids, especially in blood plasma.

Conservative antibiotic policy in patients undergoing non-trauma cranial surgery does not result in higher rates of postoperative meningitis: an audit of nine years of narrow-spectrum prophylaxis.

OBJECTIVE: To audit the efficacy of a conservative prophylactic antibiotic policy in patients undergoing non-trauma cranial surgery. MATERIALS AND METHODS: Prospectively collected infection data in consecutive patients who underwent non-trauma cranial surgeries in one neurosurgical unit between 1 January 2003 and 31 December 2011 were reviewed. Depending on the surgery performed, a one-day course of intravenous chloramphenicol or a single dose of ceftriaxone was used as the prophylactic antibiotic therapy. Patients with clinical and CSF features suggestive of meningitis were considered to have postoperative meningitis if the CSF culture was positive. RESULTS: Bacterial meningitis was diagnosed in 27 (0.8%) of 3401 patients included in the study. Multidrug-resistant (MDR, organisms that were resistant to two or more first line of antibiotics) organisms were grown from CSF in four patients with bacterial meningitis (0.1%). There were two deaths among the 27 patients with successful treatment of meningitis in the other 25 patients. CONCLUSION: In non-trauma neurosurgical patients undergoing elective cranial procedures, a conservative prophylactic antibiotic policy is effective in achieving low rates of bacterial meningitis with low rates of MDR infections. Therefore, our results make a compelling case for a conservative prophylactic antibiotic policy.

Changes in knowledge and practices related to taeniasis/cysticercosis after health education in a south Indian community.

A health education programme for taeniasis/cysticercosis was implemented and evaluated among schoolchildren and the general community in a rural block in southern India, an area that is endemic for cysticercosis. The baseline survey among 831 participants from three randomly selected villages showed poor knowledge regarding the spread of taeniasis and neurocysticercosis. There was also a lack of adequate hygiene and sanitation practices. Health education was given in these villages and in the schools located in these villages regarding the lifecycle of the pork tapeworm, spread of taeniasis and cysticercosis, and prevention of these conditions. The post-intervention test conducted 6 months later among 1060 participants revealed a 46% increase in the overall score of knowledge and practices. Awareness about the mode of spread of taeniasis and cysticercosis improved by almost 3 times and the reported practice of washing hands with soap and water before eating improved by 4.8 times and after using the toilet by 3.6 times. One person who reported the passage of tapeworm segments was confirmed to be a carrier of Taenia solium and was treated. The health education given on prevention of taeniasis and cysticercosis was useful in improving the knowledge and practices of the community and also in diagnosing taeniasis through self-reporting.

Relative seroprevalence of cysticercus antigens and antibodies and antibodies to Taenia ova in a population sample in south India suggests immunity against neurocysticercosis.

We evaluated the exposure of a community in Vellore district of south India to Taenia solium infection and its relationship to the prevalence of neurocysticercosis (NCC) causing active epilepsy. Seroprevalence of Taenia cysticercus antigens and antibodies were determined in 1064 randomly chosen asymptomatic individuals, antibodies to T. solium ova in 197 selected sera, and prevalence of taeniasis by a coproantigen test in 729 stool samples. The prevalence of NCC causing active epilepsy in Vellore district was determined in a population of 50 617. Coproantigens were detected in 0.8% (6 samples), Taenia cysticercus antigens in 4.5% (48 sera) and cysticercus IgG antibodies in 15.9% (169 sera) of the population. Cysticercus antibodies were directed against relatively low molecular weight cyst glycoprotein antigens in 14.9% (158 sera) of the population. IgG antibodies to Taenia ova were found in 81 (41.1%) of the selected samples. Prevalence of NCC causing active epilepsy was 1.3 per 1000 population. These results show high exposure of the population to the parasite and a relatively high prevalence of active infections (4.5% antigen positives) but a low prevalence of NCC causing active epilepsy (0.13%). These findings may indicate that the population is protected against developing neurocysticercosis. IgG antibodies directed against Taenia ova and low molecular weight cyst antigens may contribute to protection.

A diagnostic and therapeutic scheme for a solitary cysticercus granuloma.

BACKGROUND: Solitary cysticercus granuloma (SCG) is one of the most common forms of presentation of neurocysticercosis (NCC). The diagnostic workup and management approach to this condition remain uncertain and controversial. OBJECTIVE: To review evidence and develop a consensus approach to the diagnosis and treatment of SCG. METHODS: A multidisciplinary expert group meeting was convened in order to review and discuss various aspects of management of patients with SCG. Evidence reviewed was classified and a consensus was evolved according to standard protocols. RESULTS: SCG is commonly recognized on CT as an enhancing lesion measuring <20 mm. Further evaluation with MRI does not add much information. The use of antihelminthic agents (specifically, albendazole in combination with corticosteroids) and corticosteroids alone have been shown to improve radiologic resolution and seizure outcome in patients with SCG. However, the sizes of the effects are modest. By convention, all patients with SCG presenting with seizures are initiated on antiepileptic drugs (AEDs). Available evidence suggests that withdrawal of AEDs after complete resolution of the SCG is safe. There is a high risk of seizure relapse after AED withdrawal in patients with calcific residue following resolution of the SCG. The duration of AED prophylaxis in these individuals is unclear. CONCLUSIONS: It is desirable to have large, multicenter trials with sufficiently long follow-up, comparing outcomes with the use of antihelminthics with or without corticosteroids and corticosteroids alone in order to dissect out the benefits accrued due to each of these classes of drugs.

Long-term clinical evaluation of asymptomatic subjects positive for circulating Taenia solium antigens.

Although presence of cysticercal antigens in serum is presumed to indicate active cysticercosis not all positive persons are symptomatic. The significance of a positive antigen test in asymptomatic individuals, in predicting development of symptomatic cysticercosis on long-term follow up, is unknown. Forty two of 48 persons from Vellore district, India who were positive for circulating serum cysticercal antigens were followed up for four to five years. None of them developed clinical evidence of neurocysticercosis or subcutaneous cysts. We conclude that asymptomatic individuals with circulating cysticercal antigens have a low risk of developing symptomatic cysticercosis within four to five years.

Detecting spatial clusters of Taenia solium infections in a rural block in South India.

Neurocysticercosis (NCC) is a major cause of seizures/epilepsy in countries endemic for the disease. The objectives of this study were to spatially map the burden of active epilepsy (AE), NCC, taeniasis, seroprevalence for cysticercal antibodies and positivity to circulating cysticercal antigens in Kaniyambadi block (approximately 100 villages comprising 100 000 population) of Vellore district and to detect spatial clusters of AE, NCC, taeniasis and seroprevalence. Using geographic information system (GIS) techniques, all 21 study villages with over 8000 houses (population of 38 105) were mapped. Clustering of different indices of Taenia solium infection was determined using a spatial scan statistic (SaTScan). There was a primary spatial cluster of AE with a log likelihood ratio (LLR) of 10.8 and relative risk (RR) of 22.4; however, no significant clustering for NCC was detected. Five significant spatial clusters of seropositivity for cysticercal antibodies, two clusters of seropositivity for cysticercal antigens and one for taeniasis were detected (LLR of 8.35 and RR of 36.67). Our study has demonstrated the use of GIS methods in mapping and identifying 'hot spots' of various indices of T. solium infection in humans. This spatial analysis has identified pockets with high transmission rates so that preventive measures could be focused on an intensive scale.

Analysis of causes for late presentation of Indian patients with vestibular schwannoma.

OBJECTIVE: To determine the causes of delay in diagnosis and treatment of Indian patients with vestibular schwannomas. METHODS: In a prospective study from 2003 to 2005, 50 patients with a confirmed diagnosis of vestibular schwannoma were interviewed to determine the causes for (1) the delay between the patient noting the initial symptom and the definitive diagnosis, and (2) the reasons for delayed diagnosis. RESULTS: In 90 per cent of patients, the initial symptom was either hearing loss (62 per cent), vertigo (24 per cent) or tinnitus (4 per cent). However, most patients had been diagnosed and had presented for surgery only after neurological symptoms had became apparent. The delay between the initial medical consultation and the final diagnosis ranged from one month to 204 months (mean +/- standard deviation, 32.2 +/- 38.9 months). After the patient had noted symptoms, the diagnosis of vestibular schwannoma was delayed due to doctor-related causes in 80 per cent of cases, and due to patient-related causes in 20 per cent. Delay following diagnosis was minimal. CONCLUSIONS: Delay in the diagnosis of vestibular schwannoma in Indian patients is due to both doctor- and patient-related factors.

Seroprevalence of Taenia solium antibodies in Vellore district, south India.

Although Taenia solium neurocysticercosis is the cause of almost one-third of epilepsy in Vellore district, south India, the level of exposure to T. solium in the district is not known. This study determined the seroprevalence of cysticercus antibodies in seizure-free, study subjects aged 2-60 years from urban and rural areas of Vellore district. Cysticercus antibodies, as determined by immunoblots, were noted in 15.9% of 1063 people and were significantly higher in the rural population (17.7%) compared with the urban population (6.0%). Twenty-four percent of the rural population and 12% of the urban population ate pork. One-third of all households in the district had one or more members seropositive for cysticercus antibodies. The high index of exposure to T. solium in south India calls for improved animal husbandry and sanitation.

Oral triiodothyronine in the perioperative management of central hypothyroidism.

Oral triiodothyronine (T3) has never been described in literature as a major form of perioperative therapy. This series highlights the role of oral triiodothyronine in the perioperative management of patients with overt hypothyroidism for semi-urgent surgeries. We describe 12 patients with central hypothyroidism occurring secondary to pituitary tumours manifesting with severe neurological symptoms that required early surgical intervention. These patients were managed without any significant complications by administering perioperative oral triiodothyronine.