Visceral leishmaniasis, or kala azar (KA): high incidence of refractoriness to antimony is contributed by anthroponotic transmission via post-KA dermal leishmaniasis

Individuals with visceral leishmaniasis, or kala azar (KA) and individuals with post-KA dermal leishmaniasis (PKDL) are considered to be reservoirs of transmission of Leishmania donovani in India. When intracellular amastigotes were used to assess the natural susceptibility that PKDL isolates and KA isolates have to sodium antimony gluconate (SAG), the mean ED(50) was found to be 12.0+/-2.49 and 11.0+/-1.38 microg/mL, respectively; and there was a significant correlation with the clinical response (r rank=0.99). All KA isolates, as well as a significant proportion (55%) of PKDL isolates from high-endemicity zones, were resistant to SAG. The median ED(50) for SAG-resistant PKDL isolates (20.0 microg/mL) was significantly higher (P<.05) than that for SAG-resistant KA isolates (15.7 microg/mL). SAG-resistant PKDL isolates may contribute to KA's increased refractoriness to SAG, via anthroponotic transmission of SAG-resistant strains.     

Sequential therapy versus standard triple-drug therapy for Helicobacter pylori eradication: A randomized study

Background

Antimicrobial resistance has decreased eradication rates for Helicobacter pylori infection worldwide. A sequential treatment schedule has been reported to be effective, but studies published to date were performed in Italy. We undertook this study to determine whether these results could be replicated in India.

Methods

A randomized, open-labeled, prospective controlled trial comparing sequential vs. standard triple-drug therapy was carried out at Lokmanya Tilak Municipal General Hospital, Mumbai. Two hundred and thirty-one patients with dyspepsia were randomized to a 10-day sequential regimen (40 mg of pantoprazole, 1 g of amoxicillin, each administered twice daily for the first 5 days, followed by 40 mg of pantoprazole, 500 mg of clarithromycin, and 500 mg of tinidazole, each administered twice daily for the remaining 5 days) or to standard 14-day therapy (40 mg of pantoprazole, 500 mg of clarithromycin, and 1 g of amoxicillin, each administered twice daily).

Results

The eradication rate achieved with the sequential regimen was significantly greater than that obtained with the triple therapy. Per-protocol eradication rate of sequential therapy was 92.4 % (95 % CI 85.8–96.1 %) vs. 81.8 % (95 % CI 73.9–87.8 %) (p?=?0.027) for standard drug therapy. Intention-to-treat eradication rates were 88.2 % (95 % CI 80.9–93.0 %) vs. 79.1 % (95 % CI 71.1–85.4 %), p?=?0.029, respectively. The incidence of major and minor side effects between therapy groups was not significantly different (14.6 % in the triple therapy group vs. 23.5 % in sequential group, p?=?0.12). Follow up was incomplete in 3.3 % and 4.7 % patients in standard and sequential therapy groups, respectively. Sequential therapy includes one additional antibiotic (tinidazole) that is not contained in standard therapy.

Conclusions

Sequential therapy was significantly better than standard therapy for eradicating H. pylori infection.     

Diagnosis of visceral leishmaniasis: developments over the last decade

Diagnostic parameters for visceral leishmaniasis (VL), a potentially fatal parasitic disease caused by Leishmania donovani, have been redefined in the last decade with the development of serological and molecular tests, though a definitive diagnosis still banks on the century-old parasitological methods in many areas. Recombinant antigens have improved performance of serodiagnostic methods. Serology-based tests, rk39 antigen dipstick, and direct agglutination test commonly employed in the field are highly sensitive methods, however, fail to distinguish past infections. Molecular approaches have become increasingly relevant due to remarkable sensitivity, specificity, and flexibility in choice of samples. Quantitative polymerase chain reaction is a highly sensitive and specific tool used in referral labs for detection/assessment of parasite load in VL patients and subsequently in monitoring treatment response to antileishmanial agents. The method displays potential to provide threshold for distinguishing asymptomatics in endemic areas. Currently, improvement in VL diagnostics is required for successful decentralized (point-of-care) testing in field conditions and to detect VL–HIV co-infection. Techniques such as loop-mediated isothermal amplification offer a reliable molecular diagnostic method for field application. The diagnosis based on bioanalytics/biosensors promise frontiers for point-of-care VL detection after adequate standardization. This review summarizes the recent developments in VL diagnostics, drawing attention towards the need for standardization of the diagnostics across the affected regions.     

Unilateral periventricular leukomalacia in association with pyruvate dehydrogenase deficiency

Pyruvate dehydrogenase (PDH) deficiency is a major cause of primary lactic acidosis and neurological dysfunction in infancy and early childhood. A deficiency of PDH E1 alpha, a subunit of the PDH complex, is a prominent cause of congenital lactic acidosis. We describe a female infant born at term and delivered by emergency Caesarean section because of fetal distress. There was no parental consanguinity. She presented at 5 months of age with failure to thrive, microcephaly, hypertonia, and developmental impairment. Her plasma and cerebrospinal fluid lactate were raised. She had raised plasma pyruvate with a normal lactate-pyruvate ratio. Magnetic resonance imaging of the brain showed a focal dilatation of the right lateral ventricle with unilateral periventricular leukomalacia (PVL) with subependymal cyst. Skin fibroblast culture assay revealed PDH deficiency, confirmed by mutation analysis of the E1 alpha subunit. At 18 months of age, she has hypertonia and global impairment and is making slow progress. Denver II assessment showed delay in gross motor, fine motor, adaptive, personal, social, and language categories. She has been treated with dichloroacetate and a ketogenic diet since the age of 10 and 13 months respectively, without any side effects. To our knowledge, unilateral PVL as a neuroradiological feature has not been described in children with PDH deficiency. PDH deficiency should be considered as a differential diagnosis if PVL is unilateral and if the perinatal history is not typical of PVL.     

Author affiliation addition: “Hepatitis B virus detected in paper currencies in a densely populated city of India: A plausible source of horizontal transmission?”

Addition of authors’ affiliation to "Hepatitis B virus detected in paper currencies in a densely populated city of India: A plausible source of horizontal transmission?" World J Hepatol 2020 Oct 27; 12(10): 775-791. In this article, one of the affiliations of two authors was not mentioned. Ruchi Supekar, a joint first author and Subhajit Biswas, the corresponding author are affiliated to Academy of Scientific and Innovative Research (AcSIR) Ghaziabad- 201002, India.