Background: Recent advances in mosquito eradication and antimalarial treatments have reduced the malaria burden only modestly. An effective malaria vaccine remains a high priority, but its development has several challenges. Among many potential candidates, the RTS,S/AS01 vaccine (Mosquirix^TM) remains the leading candidate. Objective and Method: This review aims to understand the advances in the RTS,S/AS01 vaccine, and future comments regarding the vaccine’s effectiveness in malaria eradication. Literature review for the past five decades was performed searching PubMed, EMBASE Ovid, and Cochrane Library, with using the following search items: (“malaria” OR “WHO’s malaria” OR “Plasmodium falciparum” OR “RTS,S” OR “RTS,S/AS01” OR “RTS,S/AS02” OR “pre-erythrocytic malaria” OR “circumsporozoite” OR “Mosquirix”) AND (“vaccine” OR “vaccination”). Results: RTS,S/AS01, a recombinant pre-erythrocytic vaccine containing Plasmodium falciparum surface-protein (circumsporozoite) antigen, is safe, well-tolerated, and immunogenic in children. Three doses, along with a booster, have a modest efficacy of about 36% in children (age 5– 17 months) and about 26% in infants (age 6– 12 weeks) against clinical malaria during a 48-month follow-up. However, the efficacy varies among population subgroups and with the parasite strain, it reduces without a booster and offers protection for a limited duration. Because of its potential cost-effectiveness and positive public health effect, the vaccine is being investigated in a pilot program for mortality benefits and broader deployment. Conclusion: The RTS,S/AS01 vaccine prevents malaria; however, it should be considered another addition to the malaria-control program and not as an eradication tool because of its relatively low to modest efficacy.

Background: A folic-acid antagonist, methotrexate, is one of the most commonly prescribed drugs with its expanding use in clinical practice. The drug requires regular monitoring given its wide range of adverse effects including bone marrow suppression, hepatic or renal dysfunction, gastrointestinal distress, mucocutaneous damage, and neurotoxicity. The toxicity usually occurs rapidly and leads to severe neutropenia, sepsis, and advanced renal failure that are difficult to manage. Methods: This review is an update for the clinicians to understand the pharmacology, clinical features, laboratory evaluation, and treatment of patients with methotrexate overdose. High-quality literature of the past six decades was collected and reviewed in this article. Several landmark articles were reviewed using PubMed, EMBASE Ovid, and the Cochrane Library, that have important implications in current clinical practice. Results: Methotrexate overdose has complex toxicokinetic and produces myriad clinical features mimicking conditions of lesser severity. Organ dysfunction related to bone marrow, kidney or central nervous system is lifethreatening. The management should focus on high-quality supportive care, antidotal therapy (folinic acid and carboxypeptidase- G2) and plasma alkalization. Conclusion: In accordance with the dictum “prevention is better than cure”, the author emphasizes on the role of patient education, regular clinical observation, and laboratory monitoring for prompt recognition and diagnosis of methotrexate overdosing at the earliest stage.

Ayurvedic formulations are widely used and perceived as safer medicine and subjected to be self-prescribed. However, recent reports have demonstrated adulterating these drugs with toxic quantities of heavy metals. To study the magnitude of the problem in Indian-manufactured Ayurvedic medications, we randomly collected common over-the-counter Ayurvedic preparations from the licensed Ayurvedic shops in the local markets of Chandigarh in 2017. The samples were analyzed to identify and quantify eight metal ions, including mercury, arsenic, lead, cadmium, zinc, iron, copper, and chromium, using inductively coupled plasma mass spectrometry in Postgraduate Institute of Medical Education and Research, Chandigarh. The permissible limit set by the Food and Agriculture Organization/World Health Organization (FAO/WHO) for herbal medicines was followed to define the high metal concentrations. Out of 43 Ayurvedic preparations, 42 were analyzed. Heavy metals were detected in all formulations. The median (range) concentrations (in μg/g or mg/kg) of the metals were quantified as follows- mercury, 13.52 (0.00–61 095.99); arsenic, 0.00 (0.00–1038.83); lead, 1.40 (0.00–57.09); zinc, 84.2200 (26.48–22 519.03); iron, 1356.21 (128.24–136 835.25); copper, 17.1450 (0.00–12 756.86) and chromium, 20.9050 (0.00–2717.58). The metal contents above the FAO/WHO-mandated limit for zinc, mercury, arsenic, and lead were detected in 35, 29, 6, and 2 formulations, respectively. All medications contained detectable quantities of zinc and iron. Copper was detected in all except one. Cadmium was not found in any sample. Ayurvedic medications have a high prevalence of heavy metals. An evaluation of the sources of contamination and the necessary drug safety regulations are required.

The aetiology of pyrexia of unknown origin (PUO) varies dramatically according to epidemiology. We studied the cause and spectrum of PUO in Indian adults. A total of 152 patients (112 prospectively and 40 retrospectively) met Petersdorf and Beeson's criteria. The diagnostic evaluation was guided by potentially diagnostic clues, based on a ‘step-wise’ approach. The five main categories, i.e. infectious, neoplastic, non-infectious inflammatory, miscellaneous and undiagnosed comprised 43.4%, 21.5%, 19.7%, 2.0% and 12.5%, respectively. The top three causes were tuberculosis (n = 43, 28.3%), lymphoma (n = 19, 12.5%) and adult-onset Still's disease (n = 12, 7.9%). Tuberculosis predominated in all age groups, and about 70% of cases had the extrapulmonary form, the most common being gastrointestinal. Hodgkin and non-Hodgkin lymphomas were equally distributed, but solid malignancies were uncommon. Adult-onset Still's disease was the second commonest cause in adults aged ≤ 40 years. Fever resolved spontaneously in 12/19 cases of undiagnosed cause. Extrapulmonary tuberculosis remains the most prevalent PUO in India.

Several studies have demonstrated a shift in the spectrum of infective endocarditis (IE) in the developed world. We aimed to investigate whether demographic and microbiologic characteristics of IE have changed in India. A retrospective analysis of patients with in north India between 2010 and 2020. The clinical and laboratory profiles of 199 IE admitted to an academic hospital patients who met the modified Duke criteria for definite IE were analysed. The mean age was 34 years, and 84% were males. The main predisposing conditions were injection drug use (IDU) (n = 71, 35.7%), congenital heart disease (n = 46, 21.6%), rheumatic heart disease (n = 25, 12.5%), and prosthetic device (n = 19, 9.5%). 17.1% of patients developed IE without identified predispositions. Among 64.3% culture-positive cases, the most prevalent causative pathogens were Staphylococcus aureus (46.1%), viridans streptococci (7.0%), enterococci (6.0%), coagulase-negative staphylococci (5.5%), gram negative bacilli (5.5%), polymicrobial (5.5%), and Candida (1.0%). The tricuspid (30.3%), mitral (25.6%), and aortic (21.6%) valves were the most common sites of infection, and 60.3% had large vegetations (>10 mm). Systemic embolization occurred in 55.3% of patients at presentation. Cardiac surgery was required for 13.1%. In-hospital mortality was 17.1% and was associated with prosthetic devices (p-value, 0.001), baseline leucocytosis (p-value, 0.036) or acute kidney injury (p-value, 0.001), and a microbial etiology of gram negative bacilli or enterococci (p-value, 0.005). IDU is now the most important predisposition for IE in India, and S. aureus has become the leading cause of native valve endocarditis with or without IDU.

J Fam Med Primary Care, Official publication of Academy of Family Physicians of India,India