Apophysomyces elegans was considered a rare but medically important zygomycete. We analyzed the clinical records of eight patients from a single center in whom zygomycosis due to A. elegans was diagnosed over a span of 25 months. We also attempted a DNA-based method for rapid identification of the fungi and looked for interstrain polymorphism using microsattelite primers. Three patients had cutaneous and subcutaneous infections, three had isolated renal involvement, one had rhino-orbital tissue infection, and the final patient had a disseminated infection involving the spleen and kidney. Underlying illnesses were found in two patients, one with diabetes mellitus and the other with chronic alcoholism. A history of traumatic implantation was available for three patients. All except two of the patients responded to surgical and/or medical therapy; the diagnosis for the two exceptions was made at the terminal stage of infection. Restriction enzyme (MboI, MspI, HinfI) digestion of the PCR-amplified internal transcribed spacer region helped with the rapid and specific identification of A. elegans. The strains could be divided into two groups according to their patterns, with clustering into one pattern obtained by using microsatellite [(GTG) 5 and (GAC) 5 ] PCR fingerprinting. The study highlights the epidemiology, clinical spectrum, and diagnosis of emerging A. elegans infections.Zygomycosis is a serious and often rapidly fatal infection especially in immunocompromised patients. It is caused by sparsely septate filamentous, saprophytic fungi belonging to the class Zygomycetes and the order Mucorales.

Nipah virus (NiV) encephalitis first reported in “Sungai Nipah” in Malaysia in 1999 has emerged as a global public health threat in the Southeast Asia region. From 1998 to 2018, more than 630 cases of NiV human infections were reported. NiV is transmitted by zoonotic (from bats to humans, or from bats to pigs, and then to humans) as well as human-to-human routes. Deforestation and urbanization of some areas have contributed to greater overlap between human and bat habitats resulting in NiV outbreaks. Common symptoms of NiV infection in humans are similar to that of influenza such as fever and muscle pain and in some cases, the inflammation of the brain occurs leading to encephalitis. The recent epidemic in May 2018 in Kerala for the first time has killed over 17 people in 7 days with high case fatality and highlighted the importance of One Health approach. The diagnosis is often not suspected at the time of presentation and creates challenges in outbreak detection, timely control measures, and outbreak response activities. Currently, there are no drugs or vaccines specific for NiV infection although this is a priority disease on the World Health Organization's agenda. Antivirals (Ribavirin, HR2-based fusion inhibitor), biologicals (convalescent plasma, monoclonal antibodies), immunomodulators, and intensive supportive care are the mainstay to treat severe respiratory and neurologic complications. There is a great need for strengthening animal health surveillance system, using a One Health approach, to detect new cases and provide early warning for veterinary and human public health authorities.

Rationale: Despite therapeutic progress in treating cystic fibrosis (CF) airway disease, airway inflammation with associated mucociliary dysfunction remains largely unaddressed. Inflammation reduces the activity of apically expressed large-conductance Ca 21 -activated and voltage-dependent K 1 (BK) channels, critical for mucociliary function in the absence of CFTR (CF transmembrane conductance regulator).Objectives: To test losartan as an antiinflammatory therapy in CF using CF human bronchial epithelial cells and an ovine model of CFlike airway disease.Methods: Losartan's antiinflammatory effectiveness to rescue BK activity and thus mucociliary function was tested in vitro using primary, fully redifferentiated human airway epithelial cells homozygous for F508del and in vivo using a previously validated, now expanded pharmacologic sheep model of CF-like, inflammation-associated mucociliary dysfunction.Measurements and Main Results: Nasal scrapings from patients with CF showed that neutrophilic inflammation correlated with reduced expression of LRRC26 (leucine rich repeat containing 26), the g subunit mandatory for BK function in the airways. TGF-b1 (transforming growth factor b1), downstream of neutrophil elastase, decreased mucociliary parameters in vitro. These were rescued by losartan at concentrations achieved by nebulization in the airway and oral application in the bloodstream: BK dysfunction recovered acutely and over time (the latter via an increase in LRRC26 expression), ciliary beat frequency and airway surface liquid volume improved, and mucus hyperconcentration and cellular inflammation decreased. These effects did not depend on angiotensin receptor blockade. Expanding on a validated and published nongenetic, CF-like sheep model, ewes inhaled CFTR inh 172 and neutrophil elastase for 3 days, which resulted in prolonged tracheal mucus velocity reduction, mucus hyperconcentration, and increased TGF-b1. Nebulized losartan rescued both mucus transport and mucus hyperconcentration and reduced TGF-b1.Conclusions: Losartan effectively reversed CF-and inflammationassociated mucociliary dysfunction, independent of its angiotensin receptor blockade.

BackgroundAssessing the Plasmodium vivax burden in India is complicated by the potential threat of an emerging chloroquine (CQ) resistant parasite population from neighbouring countries in Southeast Asia. Chennai, the capital of Tamil Nadu and an urban setting for P. vivax in southern India, was selected as a sentinel site for investigating CQ efficacy and sensitivity in vivax malaria.MethodsCQ efficacy was evaluated with a 28-day in vivo therapeutic study, while CQ sensitivity was measured with an in vitro drug susceptibility assay. In both studies, isolates also underwent molecular genotyping to investigate correlations between parasite diversity and drug susceptibility to CQ. Molecular genotyping included sequencing a 604 base pair (bp) fragment of the P. vivax multidrug resistant gene-1 (Pvmdr1) for single nucleotide polymorphisms (SNPs) and also the amplification of eight microsatellite (MS) loci located across the genome on eight different chromosomes.ResultsIn the 28-day in vivo study (N=125), all subjects were aparasitaemic by Day 14. Passive case surveillance continuing beyond Day 28 in 22 subjects exposed 17 recurrent infections, which ranged from 44 to 148 days post-enrollment. Pvmdr1 sequencing of these recurrent infections revealed that 93.3% had identical mutant haplotypes (958M/Y976/1076L) to their baseline Day 0 infection. MS genotyping further revealed that nine infection pairs were related with ≥75% haplotype similarity (same allele at six or more loci). To test the impact of this mutation on CQ efficacy, an in vitro drug assay (N=68) was performed. No correlation between IC50 values and the percentage of ring-stage parasites prior to culture was observed (rsadj: -0.00063, p = 0.3307) and the distribution of alleles among the Pvmdr1 SNPs and MS haplotypes showed no significant associations with IC50 values.ConclusionsPlasmodium vivax was found to be susceptible to CQ drug treatment in both the in vivo therapeutic drug study and the in vitro drug assay. Though the mutant 1076L of Pvmdr1 was found in a majority of isolates tested, this single mutation did not associate with CQ resistance. MS haplotypes revealed strong heterogeneity in this population, indicating a low probability of reinfection with highly related haplotypes.

Pichia anomala is an emerging nosocomial pathogen and there is a need for methods that distinguish between different P. anomala strains. In the typing of several clinical as well as nonclinical P. anomala strains, the sequence variation of the internal transcribed spacer (ITS) was found to be inadequate for typing purposes. The intergenic spacer 1 (IGS1) region of the rDNA of several P. anomala strains was therefore investigated in detail. The IGS1 region (which varied from 1213 to 1231 bp in length) was interspersed with repeats and had more variation than the ITS regions. Comparative analysis in cases where analysis by the ITS was ambiguous clearly revealed the IGS1 region to be a more discriminatory tool in the typing of P. anomala strains.

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A patient with acute promyelocytic leukaemia developed invasive aspergillosis post chemotherapy during a pancytopenic episode, clinically involving the lungs and the gastrointestinal tract. Dichotomously branched septate fungal hyphae were demonstrated microscopically in stools and sputa. Cultures of the samples yielded Aspergillus flavus, which were identical by RFLP and random amplification of polymorphic DNA analyses and antifungal MICs, proving disseminated disease. To the best of the author's knowledge, this is the first time that boluses of fungal hyphae have been demonstrated microscopically in the stools of a patient with gastrointestinal aspergillosis. IntroductionInvasive fungal infections (IFIs) are an important cause of morbidity and mortality in patients with haematological malignancies. Invasive aspergillosis (IA) is particularly common during neutropenic episodes following anticancer chemotherapy (Wright et al., 2003). The most common site of involvement is the respiratory tract. However, autopsy studies conducted in immunocompromised patients with disseminated IA have shown the gastrointestinal tract (GIT) to be a frequent site of sub-clinical involvement (Hori et al., 2002). We describe a patient with acute promyelocytic leukaemia (APML) who developed IA post chemotherapy during a pancytopenic episode. This was diagnosed as disseminated IA by conventional methods of both microscopy and culture. Dissemination was proven in addition by DNA fingerprinting analysis of the Aspergillus flavus isolates from both sputum and stool. The highlight of this case report is the finding of fungal hyphae in the direct microscopic examination of stools, which although unusual, may be a significant finding in an immunocompromised patient. Microbiologists, mycologists and pathologists involved in patient care may thus be able to offer improved support to clinicians by becoming proficient in recognizing and interpreting such forms in clinical samples. Case reportAn 18-year-old male who received consolidation chemotherapy consisting of daunomycin and cytosine arabinoside for acute promyelocytic leukaemia developed febrile neutropenia on the 11th day. Other associated symptoms were throat pain, cough and nasal discharge. Physical examination, however, was normal. His total leukocyte count (TLC) and absolute neutrophil count (ANC) were 300 ml 21 and zero, respectively. Chest X-ray was normal. Sputum culture grew Klebsiella pneumoniae sensitive to aminoglycosides and third-generation cephalosporins. The patient had no indwelling catheter. Despite receiving intravenous ceftazidime, amikacin and fluconazole, along with other supportive measures, fever persisted and his condition worsened with the development of haemoptysis and epistaxis. Hence an aggressive IFI was suspected, for which fluconazole was substituted with amphotericin B at a dose of about 1 mg kg 21 per day (50 mg per day). Two days after a transient improvement in symptoms, the patient's condition deteriorated. He developed diarrhoea and respiratory distress...

Background and Objectives: The purpose of this study was to analyze trends in HIV prevalence and risk factors associated with HIV infection among pregnant women attending antenatal clinics in Odisha State, India. Methods: Data were from the HIV Sentinel Surveillance (HSS) among pregnant women, a descriptive cross-sectional study using consecutive sampling method and conducted in India. Data and samples were collected from pregnant women attending select antenatal clinics that act as designated sentinel sites in Odisha State, India, during the three months surveillance period and in three surveillance years: 2013, 2015, and 2017. All eligible pregnant women aged between 15 and 49 years, attending the sentinel sites for the first time during the surveillance period, were included. Information on their socio-demographic characteristics and blood samples were also collected. Results: In total, 38,384 eligible pregnant women were included in the survey. Of these, 107 women were HIV positive, with an overall prevalence of 0.28%. HIV prevalence indicated a stabilizing trend between 2013 and 2017. However, pregnant women whose spouses were non-agricultural laborers, truck drivers, or migrants were significantly at higher risk of being infected. Likewise, HIV prevalence significantly increased over the years among pregnant women whose spouses were in the service sector (government or private). District-wise fluctuations in HIV prevalence was observed, with the district of Cuttack recording the highest prevalence among the districts. Conclusion and Global Health Implications: Women who are spouses of non-agricultural laborers, truck drivers or migrants need focused interventions, such as creating awareness on HIV and its prevention. Migration, due to poverty and its impact on sexually transmitted diseases among migrants from low and middle-income countries, have been documented globally. Single male migrant specific interventions are recommended to halt the disease progression among pregnant women and general population in Odisha, India. Key words: • HIV sentinel surveillance • Pregnant women • HIV prevalence • Socio-demographic factor • Odisha • India   Copyright © 2020 Santhakumar et al. Published by Global Health and Education Projects, Inc. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0) which permits unre-stricted use, distribution, and reproduction in any medium, provided the original work, first published in this journal, is properly cited.