Hydrogen sulphide-mediated alleviation and its interplay with other signalling molecules during temperature stress.

The sessile habit of plants does not provide choices to escape the environmental constraints, leading to negative impacts on their growth and development. This causes significant losses in the agriculture sector and raises serious issues on global food security. Extreme temperatures (high or low) influence several aspects of plant life and can cause reproduction malfunction. Therefore, a strategy for temperature amelioration is necessary for the management of agricultural productivity. Supplementation with various chemicals (e.g. phytohormones, gasotransmitters, osmolytes) is considered a good choice to manage plant stress. Gasotransmitters are well-recognized for stress mitigation in plants, among which hydrogen sulphide (H2 S) has proved promising to alleviate stress. Temperature (heat/cold) stress can stimulate the endogenous production of H2 S in plants, and many studies have reported the significance of H2 S for temperature stress amelioration. Here, H2 S led to positive changes in plant physiological, biochemical and molecular responses, which are usually compromised during stress. Further, H2 S also coordinate with other signalling components that act either upstream or downstream during stress mitigation. This review focuses on the significance of H2 S for mitigation of temperature stress, with a comprehensive discussion on cross-talk with other signalling components or supplements (e.g. NO, H2 O2 , salicylic acid, trehalose, proline). Finally, the review provides a rational assessment and holistic understanding of H2 S-mediated mitigation of extreme temperature stress and addresses the prospects for development of an effective strategy to manage temperature stress.

Colistin interacts synergistically with echinocandins against Candida auris.

Antifungal combination is an interesting approach for the treatment of several fungal infections but there is currently little evidence to support combined therapy in Candida auris infections. The antibacterial colistin has recently been shown to interact synergistically with antifungals against Candida spp., including azole-resistant isolates. The current study evaluated the in vitro interaction between colistin and either caspofungin or micafungin against 15 C. auris isolates by a checkerboard methodology based on the European Committee on Antimicrobial Susceptibility Testing (EUCAST) reference method. Results were analysed by two approaches: calculation of the fractional inhibitory concentration index (FICI) and response surface analysis based on the Bliss model. The minimum inhibitory concentration (MIC) range (geometric mean [Gmean]) of caspofungin and micafungin was 0.25 to 1 µg/mL (0.691 µg/mL) and 0.03 to 0.125 µg/mL (0.114 µg/mL), respectively. No activity was observed for colistin alone with MIC of >64 µg/mL for all the isolates. When colistin was combined with caspofungin, synergistic interactions were observed for all strains with FICI values of 0.08 to 0.14. In contrast, indifferent interactions were observed for the combination of colistin with micafungin with FICI values of 0.51 to 1.01. Synergy was also demonstrated using the Bliss model against all isolates for the colistin-caspofungin combination and in 60% of isolates for the colistin-micafungin combination. Antagonism was not observed for any combination.

Candida blankii: an emerging yeast in an outbreak of fungaemia in neonates in Delhi, India.

OBJECTIVE: Outbreaks of fungal sepsis due to emerging and rare multidrug-resistant Candida species are increasingly reported in health-care settings. We report an outbreak of fungaemia due to the rare multidrug-resistant yeast Candida blankii in an Indian neonatal unit. MATERIALS AND METHODS: Blood cultures grew C. blankii in nine neonates in the Neonatal Intensive Care Unit of a multispecialty hospital in Delhi during a period of 7 months. Isolates were identified by internal transcribed spacer and D1/D2 region sequencing. Antifungal susceptibility testing was performed by M27-A3 CLSI broth microdilution. To determine genetic relatedness among C. blankii isolates we undertook amplified fragment length polymorphism analysis and DNA sequencing using the Illumina NextSeq500 platform. RESULTS: Candida blankii fungaemia occurred at 2-3 postnatal days in nine low birthweight/very low birthweight neonates. All neonates were treated with fluconazole and four of the nine neonates died, resulting in a case fatality rate of 45%. Candida blankii was misidentified or not identified by automated identification systems. Fluconazole had higher geometric mean (GM) MICs (8 mg/L) than the other azoles. Also, anidulafungin (GM-MIC 2 mg/L) had high MICs. Genome sequencing confirmed transmission of genetically mostly indistinguishable strains. The C. blankii genome showed an altered 1,3-ß-d-glucan synthase protein and several larger deletions in the echinocandin target FKS1 gene, suggesting potential for development of antifungal resistance. CONCLUSIONS: The study emphasizes the emergence of a rare and uncommon yeast, C. blankii, with reduced susceptibility to one or more antifungal agents, in nosocomial fungaemia. Genomic insights of this rare yeast are reported using whole-genome sequence typing.

In vitro antifungal combination of flucytosine with amphotericin B, voriconazole, or micafungin against Candida auris shows no antagonism.

Candida auris is an emerging, multidrug resistant pathogen, responsible for invasive hospital-acquired infections. Flucytosine is an effective anti-Candida drug, but which cannot be used as a monotherapy because of the risk of development of resistant mutants during treatment. It is therefore noteworthy to test possible combinations with flucytosine that may have a synergistic interaction. In this study, we determined the in vitro interaction between flucytosine and amphotericin B, micafungin, or voriconazole. These combinations have been tested against 15 C. auris isolates. The MIC range (Gmean) of flucytosine, amphotericin B, micafungin and voriconazole were 0.125 to 1 µg/mL (0.42 µg/ml), 0.25 to 1 µg/ml (0.66 µg/ml), 0.125 to 0.5 µg/ml (0.3 µg/ml) and 0.03 to 4 µg/ml (1.05 µg/ml), respectively. When tested in combination, indifferent interactions were mostly observed with fractional inhibitory concentration index values from 0.5 to 1, 0.31 to 1.01 and 0.5 to 1.06 for the combination of flucytosine with amphotericin B, micafungin and voriconazole, respectively. A synergy was observed for the strain CBS 10913 from Japan. No antagonism was observed for any combination. Combination of flucytosine with amphotericin B or micafungin may be relevant for the treatment of C. auris infections.

Allergic Bronchopulmonary Mycosis due to fungi other than Aspergillus.

Summary: Allergic bronchopulmonary mycosis (ABPM) is a clinical syndrome associated with immune sensitivity to various fungi that colonize the airways. Early diagnosis and treatment with systemic corticosteroids is the key in preventing the progression of the disease to irreversible lung fibrosis. Although Aspergillus has progressively gained recognition as a causative agent in past few decades, other fungi, that have been reported to cause ABPM, are not yet widely evaluated. We studied hundred and two patients with asthma for occurrence of ABPM. Patients were tested for cutaneous hypersensitivity and serum precipitin to 12 common fungal antigens. The positive cases were further evaluated for ABPM using standard criteria. Out of 102 asthma patients screened, 18 patients had either skin prick test (SPT) and/or serum precipitin positive. While 14 patients were SPT positive for one or more fungal antigen, two patients were serum precipitin positive for one or more fungi. Two patients had both serum precipitin positive as well as SPT positive. Six (5.8%) patients were diagnosed as ABPM as they fulfilled the criteria. Three of these were because of Aspergillus sp. Two were because of fungi other than Aspergillus namely Schizophyllum and Curvularia. One patient had ABPM because of both Aspergillus and Curvularia. In our study absolute eosinophil count (AEC), total IgE, serum precipitin and SPT had sensitivity of 100%, 100% 50% and 83.3% respectively for diagnosing ABPM. The specificity of these tests was 44.79%, 64.58% 98.96% and 88.54% respectively. Specfic IgE was positive in 50% of patients with either serum precipitin or SPT positivity. SPT or serum precipitin followed by specific IgE had sensitivity of 100% and specificity of 96.88% for diagnosing ABPM. SPT alone followed by Specific IgE had a sensitivity of 83.33% and specificity of 96.88% for diagnosing ABPM. We found that fungi other than Aspergillus such as schizophyllum, and curvularia, can be implicated in ABPM. Multiple fungal agents may be responsible for ABPM in an individual. There is a subset of patients of BA who have fungal sensitization but do not fulfil the criteria for ABPM. SPT was the single most sensitive and specific test, AEC >350 and total IgE more than 417IU were most sensitive tests and SPT followed by specific IgE was most effective strategy for diagnosing ABPM.

Candida auris: An emerging drug resistant yeast - A mini-review.

Candida auris is an emerging fungal pathogen responsible for nosocomial invasive infection outbreaks on five continents. Large healthcare-related outbreaks of C. auris infection and colonization have been reported from different countries. Whole genome sequence analysis identified strong phylogeographic C. auris clades specific to particular geographical areas suggesting transmission of particular clades within countries. However, the mode of transmission within the healthcare environment is not clear and is likely to be multifactorial. The emergence of C. auris is alarming because this organism can harbor or develop multidrug resistance. This explains why C. auris infections are difficult to treat. In addition, difficulties in its identification in the routine diagnostic laboratory have a significant impact on outbreak detection and management. This mini-review highlights the available literature on C. auris, with particular insight into its epidemiology and the problems caused by its antifungal resistance.

In search of effective H1N1 neuraminidase inhibitor by molecular docking, antiviral evaluation and membrane interaction studies using NMR.

Considering the need for discovery of new antiviral drugs, in view to combat the issue of resistance particularly to anti-influenza drugs, a series of 2'-amino, 3'-amino and 2', 4'-dihydroxy chalcone derivatives were designed. Structure-based drug design was used to design inhibitors of influenza virus - H1N1 neuraminidase enzyme. These were further optimized by a combination of iterative medicinal chemistry principles and molecular docking. Based on the best docking scores, some chalcone derivatives were synthesized and characterized by infrared spectroscopy (IR) and proton nuclear magnetic resonance (NMR). The molecules were evaluated for their anti-influenza action against influenza A/Pune isolate/2009 (H1N1) virus by in vitro enzyme-based assay (neuraminidase inhibition assay). We have then selected few of them for multinuclear NMR studies, 31P NMR, in order to probe the molecular mechanism of their antiviral action. Reasonably good correlation between docking scores; anti-influenza activity; and 31P NMR results were observed. The computational predictions were in consensus with the experimental results. It was observed that among tested compounds, derivative 1A, viz. 2', 4'-dihydroxy-4-methoxy chalcone, showed highest activity (IC50 = 2.23 µmol/l) against the virus under study. This derivative 1A can be explored further to provide a future therapeutic option for the treatment and prophylaxis of H1N1 viral infections.

Posaconazole MIC Distributions for Aspergillus fumigatus Species Complex by Four Methods: Impact of cyp51A Mutations on Estimation of Epidemiological Cutoff Values.

Estimating epidemiological cutoff endpoints (ECVs/ECOFFS) may be hindered by the overlap of MICs for mutant and nonmutant strains (strains harboring or not harboring mutations, respectively). Posaconazole MIC distributions for the Aspergillus fumigatus species complex were collected from 26 laboratories (in Australia, Canada, Europe, India, South and North America, and Taiwan) and published studies. Distributions that fulfilled CLSI criteria were pooled and ECVs were estimated. The sensitivity of three ECV analytical techniques (the ECOFFinder, normalized resistance interpretation [NRI], derivatization methods) to the inclusion of MICs for mutants was examined for three susceptibility testing methods (the CLSI, EUCAST, and Etest methods). The totals of posaconazole MICs for nonmutant isolates (isolates with no known cyp51A mutations) and mutant A. fumigatus isolates were as follows: by the CLSI method, 2,223 and 274, respectively; by the EUCAST method, 556 and 52, respectively; and by Etest, 1,365 and 29, respectively. MICs for 381 isolates with unknown mutational status were also evaluated with the Sensititre YeastOne system (SYO). We observed an overlap in posaconazole MICs among nonmutants and cyp51A mutants. At the commonly chosen percentage of the modeled wild-type population (97.5%), almost all ECVs remained the same when the MICs for nonmutant and mutant distributions were merged: ECOFFinder ECVs, 0.5 µg/ml for the CLSI method and 0.25 µg/ml for the EUCAST method and Etest; NRI ECVs, 0.5 µg/ml for all three methods. However, the ECOFFinder ECV for 95% of the nonmutant population by the CLSI method was 0.25 µg/ml. The tentative ECOFFinder ECV with SYO was 0.06 µg/ml (data from 3/8 laboratories). Derivatization ECVs with or without mutant inclusion were either 0.25 µg/ml (CLSI, EUCAST, Etest) or 0.06 µg/ml (SYO). It appears that ECV analytical techniques may not be vulnerable to overlap between presumptive wild-type isolates and cyp51A mutants when up to 11.6% of the estimated wild-type population includes mutants.

Multicenter, International Study of MIC/MEC Distributions for Definition of Epidemiological Cutoff Values for Sporothrix Species Identified by Molecular Methods.

Clinical and Laboratory Standards Institute (CLSI) conditions for testing the susceptibilities of pathogenic Sporothrix species to antifungal agents are based on a collaborative study that evaluated five clinically relevant isolates of Sporothrixschenckii sensu lato and some antifungal agents. With the advent of molecular identification, there are two basic needs: to confirm the suitability of these testing conditions for all agents and Sporothrix species and to establish species-specific epidemiologic cutoff values (ECVs) or breakpoints (BPs) for the species. We collected available CLSI MICs/minimal effective concentrations (MECs) of amphotericin B, five triazoles, terbinafine, flucytosine, and caspofungin for 301 Sporothrix schenckii sensu stricto, 486 S. brasiliensis, 75 S. globosa, and 13 S. mexicana molecularly identified isolates. Data were obtained in 17 independent laboratories (Australia, Europe, India, South Africa, and South and North America) using conidial inoculum suspensions and 48 to 72 h of incubation at 35°C. Sufficient and suitable data (modal MICs within 2-fold concentrations) allowed the proposal of the following ECVs for S. schenckii and S. brasiliensis, respectively: amphotericin B, 4 and 4 µg/ml; itraconazole, 2 and 2 µg/ml; posaconazole, 2 and 2 µg/ml; and voriconazole, 64 and 32 µg/ml. Ketoconazole and terbinafine ECVs for S. brasiliensis were 2 and 0.12 µg/ml, respectively. Insufficient or unsuitable data precluded the calculation of ketoconazole and terbinafine (or any other antifungal agent) ECVs for S. schenckii, as well as ECVs for S. globosa and S. mexicana These ECVs could aid the clinician in identifying potentially resistant isolates (non-wild type) less likely to respond to therapy.

A prospective international Aspergillus terreus survey: an EFISG, ISHAM and ECMM joint study.

OBJECTIVES: A prospective international multicentre surveillance study was conducted to investigate the prevalence and amphotericin B susceptibility of Aspergillus terreus species complex infections. METHODS: A total of 370 cases from 21 countries were evaluated. RESULTS: The overall prevalence of A. terreus species complex among the investigated patients with mould-positive cultures was 5.2% (370/7116). Amphotericin B MICs ranged from 0.125 to 32 mg/L, (median 8 mg/L). CONCLUSIONS: Aspergillus terreus species complex infections cause a wide spectrum of aspergillosis and the majority of cryptic species display high amphotericin B MICs.

Intussusception of Small Intestine as a Result of Inflammatory Fibroid Polyp Causing Small Bowel Obstruction in an Adult Patient.

Intussusception is the telescoping of one segment of bowel into the adjacent segment. It is more commonly seen in children,however rarely encountered in adult patients. Proximal segment of bowel is called intussusceptum which is intussuscepted into the lumen of the adjacent distal segment known as intussuscipiens. There is always a lead point causing this disorder especially in adults. We presented a case of a 45 year old man who presented in emergency department of our institute with history and clinical features of acute intestinal obstruction since 10 days. Patient was resuscitated, investigated and taken for exploratory laparotomy under General anaesthesia. Segment of involved small gut was resected and well circumscribed polypoidal mass was found in intussuscepted bowel. Histopathological examination of the specimen revealed the features of inflammatory fibroid polyp.

Whole genome sequencing of emerging multidrug resistant Candida auris isolates in India demonstrates low genetic variation.

Candida auris is an emerging multidrug resistant yeast that causes nosocomial fungaemia and deep-seated infections. Notably, the emergence of this yeast is alarming as it exhibits resistance to azoles, amphotericin B and caspofungin, which may lead to clinical failure in patients. The multigene phylogeny and amplified fragment length polymorphism typing methods report the C. auris population as clonal. Here, using whole genome sequencing analysis, we decipher for the first time that C. auris strains from four Indian hospitals were highly related, suggesting clonal transmission. Further, all C. auris isolates originated from cases of fungaemia and were resistant to fluconazole (MIC >64 mg/L).

Multidrug-resistant Candida auris: 'new kid on the block' in hospital-associated infections?

Since being first reported in an ear swab in 2009, and in blood cultures in 2011, invasive infections with Candida auris have been reported in many countries across several continents. We review current knowledge of the epidemiology of this emerging multidrug-resistant pathogen. The importance of species identification and the inadequacies of many widely used identification systems are considered. We recommend that hospitals develop their own policies for the prevention and control of infections with this pathogen. Elements of such policies and the limitations of the existing knowledge base are discussed.

Phenotyping at hot spots and tagging of QTLs conferring spot blotch resistance in bread wheat.

Spot blotch is a major foliar disease of wheat caused by Bipolaris sorokiniana in warm and humid environments of the world including South Asian countries. In India, it has a larger impact in Indo-Gangetic plains of the country. Therefore, the present study was undertaken to phenotype a mapping population at different hot spots of India and to detect quantitative trait loci (QTL) for resistance to spot blotch in wheat. For this study, 209 single seed descent (SSD) derived F8, F9, F10 recombinant inbred lines (RILs) of the cross 'Sonalika' (an Indian susceptible cultivar)/'BH 1146' (a Brazilian resistant cultivar) were assessed for spot blotch resistance at two hot spot locations (Coochbehar and Kalyani) for three years and for two years under controlled conditions in the polyhouse (Karnal). The population showed large variation in spot blotch reaction for disease severity in all the environments indicating polygenic nature of the disease. Microsatellite markers were used to create the linkage maps. Joint and/or individual year analysis by composite interval mapping (CIM) and likelihood of odds ratio (LOD) >2.1, detected two consistent QTLs mapped on chromosome 7BL and 7DL and these explained phenotypic variation of 11.4 percent and 9.5 percent over the years and locations, respectively. The resistance at these loci was contributed by the parent 'BH 1146' and shown to be independent of plant height and earliness. Besides, association of some agro-morphological traits has also been observed with percent disease severity. These identified genomic regions may be used in future wheat breeding programs through marker assisted selection for developing spot blotch resistant cultivars.

Seroepidemiological survey of health care workers in Maharashtra.

CONTEXT: HCWs all over the world carry occupational risk of getting infected with major blood borne infections through needle stick injuries (NSIs). As health care industry has been expanding, risk of nosocomial infections is increasing proportionately. Measures to prevent it and put in place a mechanism to control these injuries are needed urgently, especially in India where there is not only increase in domestic demand but impetus in health tourism. AIM: To determine HBs Ag, HBc IgM level and to assess anti-HBs level prevalence in HCWs, in a tertiary care hospital and to study the influence of factors like age and sex in the vaccinated HCWs and formulate mechanism to increase awareness to create a safe working environment in the hospitals. SETTINGS AND DESIGN: 437 HCWs, working in Laboratories, Surgical, Medical or Dental departments in 11 Civil Hospitals and Sub-district Hospitals covering 8 circles of the State. METHODS AND MATERIAL: Qualitative and Quantitative estimation of HBs Ag and Anti-HBs by sandwich ELISA technique and qualitative HBc IgM level by antibody-capture, non-competitive test. Liver profile (SGPT, SGOT and Alkaline Phosphatase) by IFCC method done. STATISTICAL ANALYSIS USED: Tabulation and Pie Circle Result: 193 of the total 229 vaccinated HCWs tested positive for core antibody, meaning that they were infected prior to HBs Ag vaccination, leaving a total of 36 'truly' vaccinated HCWs. 11 HBs Ag positive HCWs were tested for Liver Profile and all had ALAT, ASAT and ALP within normal range. Out of total number of 141 HCWs having 10 and below IU/L anti HBs, 5 HCWs were positive for HBS Ag, showing a positivity of 3.5%. CONCLUSION: Need of vaccination and for post-vaccination serological testing of all HCWs considering the high rates of non-responders and low responders (anti-HBs-34.2%). Importance of educating the HCWs of safety precautions while handling body fluids, and the management of ' sharps ' injuries.

Molecular characterization of nucleoprotein gene of rabies virus from Maharashtra, India.

CONTEXT: Rabies poses a serious public health concern in developing countries such as India. AIMS: The study focuses on molecular diagnosis of street rabies virus (RABV) from human clinical specimens received from Maharashtra, India. MATERIALS AND METHODS: Nucleoprotein gene from eight (of total 20 suspected samples) rabies cases that tested positive for rabies antigen using reverse transcriptase-polymerase chain reaction (RT-PCR) were sequenced. RESULTS: Sequence analysis using basic local alignment search tool (BLAST) and multiple sequence alignment (MSA) and phylogenetic analysis showed similarity to previously reported sequences from India and those of Arctic lineages. CONCLUSIONS: The circulating RABV strains in Maharashtra, India show genetic relatedness to RABV strains reported from Indo-Arctic lineages and India-South and Japan.

Evidence of genotypic diversity among Candida auris isolates by multilocus sequence typing, matrix-assisted laser desorption ionization time-of-flight mass spectrometry and amplified fragment length polymorphism.

Candida auris is a multidrug-resistant nosocomial bloodstream pathogen that has been reported from Asian countries and South Africa. Herein, we studied the population structure and genetic relatedness among 104 global C. auris isolates from India, South Africa and Brazil using multilocus sequence typing (MLST), amplified fragment length polymorphism (AFLP) fingerprinting and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). RPB1, RPB2 and internal transcribed spacer (ITS) and D1/D2 regions of the ribosomal DNA were sequenced for MLST. Further, genetic variation and proteomic assessment was carried out using AFLP and MALDI-TOF MS, respectively. Both MLST and AFLP typing clearly demarcated two major clusters comprising Indian and Brazilian isolates. However, the South African isolates were randomly distributed, suggesting different genotypes. MALDI-TOF MS spectral profiling also revealed evidence of geographical clustering but did not correlate fully with the genotyping methods. Notably, overall the population structure of C. auris showed evidence of geographical clustering by all the three techniques analysed. Antifungal susceptibility testing by the CLSI microbroth dilution method revealed that fluconazole had limited activity against 87% of isolates (MIC90, 64 mg/L). Also, MIC90 of AMB was 4 mg/L. Candida auris is emerging as an important yeast pathogen globally and requires reproducible laboratory methods for identification and typing. Evaluation of MALDI-TOF MS as a typing method for this yeast is warranted.

Pathogenicity of Candida viswanathii for normal and cortisone-treated mice.

The pathogenicity of Candida viswanathii, PCI 501/1 (CBS 4024), originally isolated from CSF of a fatal case of meningitis in India, is reported. Also, included is a global overview of the occurrence of C. viswanathii in clinical and environmental sources. The investigation was done in normal and cortisone-treated albino mice challenged intravenously with variable doses of 1×10(6), 4×10(6) and 16×10(6) actively growing yeast cells of the fungus. The animals were kept under observation up to 3 weeks when they were sacrificed for a mycological and histopathologic study. As apparent from the data on morbidity and mortality, the species exhibited low virulence for normal mice, whereas it caused significantly higher mortality (P<0.0008) and morbidity (macroscopic lesions) (P<0.0004) in cortisone group. Likewise, there was overall higher recovery of C. viswanathii in culture from the cortisone-treated than in the normal group of mice. These observations are indicative of C. viswanathii being an opportunistic pathogen. It is recognized that a definitive identification of C. viswanathii requires mycological expertise for comprehensive phenotypic characterization or the application of expensive techniques such as Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOF MS) and molecular techniques, facilities for which are generally lacking in a vast majority of laboratory diagnostic centers especially in developing countries. Consequently, the prevalence of C. viswanathii in clinical and environmental samples is currently likely to be underestimated.

Exogenous interferon prolongs survival of rabies infected mice.

Rabies is an acute viral infection that causes encephalomyelitis in almost all warm blooded animals and is invariably fatal once the clinical signs appear. The present study was carried out to assess the effect of recombinant human interferon alpha (rhIFN α-2A) treatment on the survival of rabies infected mice and its correlation with cytokines expression. The gene expression of TNF-α and IL-6 was measured by SYBR Green Real Time PCR for two groups-"Pre-exposure" (mice were inoculated with rhIFN α-2A prior to rabies infection) and "Post-exposure" (mice were inoculated with rhIFN α-2A post rabies virus infection). Delayed mortality was observed in interferon treated infected groups. In addition, statistically significant decrease (P < 0.0001) in the expression of TNF-α and IL-6 was observed, both in the pre-exposure and post-exposure groups. These findings indicate that modulation of cytokine secretion using exogenous biologicals such as rhIFN may offer novel therapeutic approaches to treat diseases such as rabies.