Identification of genetic markers in Sodium Antimony Gluconate (SAG) sensitive and resistant Indian clinical isolates of Leishmania donovani through amplified fragment length polymorphism (AFLP)

Sodium Antimony Gluconate (SAG) is currently used worldwide as the first-line drugs for the treatment of visceral leishmaniasis (VL) and cutaneous leishmaniasis (CL) since 1940s. Unfortunately, the resistance of Leishmania parasite to this drug is increasing in several parts of the world. The mechanism of drug resistance in clinical isolates is still not very clear. Earlier, we have established a differentiation between six clinical isolates as sensitive and resistant on the basis of their sensitivity to SAG in vitro and in vivo as well as expression of proteophosphoglycan contents. In this preliminary study, we have further analyzed these isolates on the basis of their genetic diversity, molecular variance and phylogenetic structure using for the first time, a fingerprinting approach - amplified fragment length polymorphism (AFLP). Altogether 2338 informative AFLP bands were generated using 10 selective primer combinations. Percentage of polymorphism was 55.35%. A number of unique AFLP markers (217) were also identified in these strains. It was deduced that a higher rate of variations occurred among Leishmania clinical isolates which indicate the shifting of drug sensitive nature of parasite towards resistant condition.     

Self-harm and self-poisoning in southern India: choice of poisoning agents and treatment

Objective  To record cases of suicide and attempted suicide among a population of 108 000 people living in a primarily rural area of southern India, with the aim of guiding policies and strategies to restrict access to poisonous compounds at community level.
Method  Community-based surveillance over a period of 2 years.
Results and conclusion  The overall suicide rate was 71.4 per 100 000 population; the highest burden was among men. Most people died through hanging (81, 54%) and self-poisoning (46, 31%). Of the 46 who died from self-poisoning, 78.3% had taken pesticides and 19.7% had eaten poisonous plants. Eighty per cent of the self-poisoning cases obtained the poisonous substance in or in close proximity to the home, highlighting the importance of safe storage in the domestic environment. Of the 110 fatal and non-fatal self-poisoning cases, 87 (57.5%) were taken for treatment; 50 (57.4%) went to government hospitals and 37 (42.5%) to private facilities. This indicates the importance of including the private sector in the efforts to improve case management. Furthermore, the fact that 31 (67%) of the self-poisoning patients, who eventually died, were alive after 4 h provides an incentive to focus on improved case management and access to health services.     

Prevalence and risk factors for non-alcoholic fatty liver disease among adults in an urban Sri Lankan population

Background and Aims:  Non-alcoholic fatty liver disease (NAFLD) is an emerging problem in the Asia–Pacific region. However, its prevalence and risk factors in Asian (especially South Asian) communities is poorly studied. In this study, the aim was to determine the community prevalence and risk factors for NAFLD among adults in an urban Sri Lankan population.
Methods:  The study population consisted of 35–64-year-old adults, selected by stratified random sampling. NAFLD was diagnosed on established ultrasound criteria for fatty liver, safe alcohol consumption (< 14 units/week for men, < 7 units/week for females) and absence of hepatitis B and C markers. Blood pressure (BP) and anthropometric measurements were made, and fasting glucose, glycosylated hemoglobin, serum lipids, fasting serum insulin and serum alanine aminotransferase (ALT) were determined.
Results:  Of the 2985 study participants, 974 (32.6%) had NAFLD (605 [62.1%] women, mean age 52.8 years [standard deviation, 7.3]). On multivariate analysis, obesity, acanthosis nigricans, insulin resistance, elevated diastolic BP, fasting plasma glucose, plasma triglycerides, and ALT twice the upper limit of the reference range or more were independently associated with NAFLD.
Conclusion:  The prevalence of NAFLD among adults in this urban Sri Lankan community is high and is strongly associated with constituent features of the metabolic syndrome.     

A Novel Galacto-Glycerolipid from Oxalis corniculata Kills Entamoeba histolytica and Giardia lamblia

Oxalis corniculata is a naturally occurring weed that has been used in traditional medicine for the cure of dysentery and diarrhea in India. One of the common causes of dysentery is due to infection by the protist pathogen Entamoeba histolytica. Bioactivity profiling of extracts from O. corniculata identified several compounds that showed antiamoebic activity in axenic cultures of E. histolytica. These were characterized by nuclear magnetic resonance, infrared, and mass spectrometry as (i) Oc-1, a mixture of saturated fatty acids C₂₄ to C₂₈; (ii) Oc-2, a mixture of long-chain alcohols C₁₈ to C₂₈; and (iii) Oc-3, a single compound that was a galacto-glycerolipid (GGL). Of the different compounds that were obtained, the strongest antiamoebic activity was found in GGL. The addition of GGL to E. histolytica xenic cultures containing other microbial flora from the large intestine did not affect its antiamoebic activity. Amoebicidal concentrations of GGL had no effect on intestinal microbial flora or on the mammalian cell line HEK-293. GGL was also found to be equally effective in killing another protist pathogen, Giardia lamblia, that causes diarrhea in humans. The importance of this study is based on the identification of novel natural products and the possibility of developing these compounds as active agents to treat at least two pathogenic parasitic intestinal infections endemic to tropical regions.Infection with Entamoeba histolytica is one of the most common types of intestinal infection in tropical areas of the developing world. Epidemiological data on the prevalence of this infection indicate that about 500 million people worldwide are infected, 90% of which are asymptomatic carriers, whereas the remaining 10% show serious intestinal and extraintestinal diseases such as colitis, dysentery, and amoebic liver abscess. Currently, metronidazole is the drug of choice for the treatment of amoebiasis and other gastrointestinal pathogens such as Giardia and Trichomonas spp. and Helicobacter pylori. Resistance to metronidazole is acquired easily by many intestinal bacteria and protists such as Giardia intestinalis and Trichomonas vaginalis (2) and is therefore a matter of serious concern. In addition, metronidazole is mutagenic in bacteria and carcinogenic in experimental mammalian models at high doses over long periods (13, 14). Prolonged use of metronidazole leads to unpleasant side effects, such as headache, vertigo, nausea, and metallic taste and sometimes to toxicity in the central nervous system and pancreatitis (12). Therefore, there is an urgent need to develop alternative drugs that do not have these undesirable side effects.Several natural products with antiamoebic properties have been identified. These include emetine (9), tubulosine, cryptopleurine, berberine (19), and allicine (diallylsulfinate) (4, 5). However, either inefficacy in curing amoebiasis or the toxicity of these compounds has precluded their use as an alternative to metronidazole. The weed Oxalis corniculata is used in traditional medicine in India to cure dysentery, diarrhea, and skin diseases (11). In an effort to characterize active compounds from this plant, we used bioactivity profiling of its extracts and discovered a novel galacto-glycerolipid (GGL), in addition to two other compounds. We describe here the antiamoebic and antigiardial effect of the novel GGL and other compounds purified from O. corniculata.     

Foveal neovascularisation in diabetic retinopathy: case report and review of literature

To report a rare case of unilateral foveal neovascularisation in an asymptomatic patient with 15-year history of insulin-dependent diabetes mellitus and bilateral proliferative diabetic retinopathy and diabetic macular edema. Fundus fluorescein angiography and optical coherence tomography scan confirmed the presence of foveal neovascularisation. There was complete regression of the foveal neovascularisation after pan retinal laser photocoagulation. We review the literature on foveal neovascularisation in diabetic retinopathy and propose a possible pathogenic mechanism for development of foveal neovascularisation in diabetic retinopathy and the reason for the response to pan retinal laser photocoagulation.     

High-dose chemotherapy and autologous stem cell rescue for atypical teratoid/rhabdoid tumor of the central nervous system

Atypical Teratoid/Rhabdoid tumors (AT/RT) of the central nervous system are rare but aggressive tumors of childhood. Median survival with surgery and standard chemotherapy is less than 12 months. In an attempt to improve outcome, patients were treated with aggressive surgical resection and multi-agent chemotherapy, followed by high dose chemotherapy with autologous stem cell rescue. Nine consecutive children (median age 21 months) were diagnosed with AT/RT at the University of California San Francisco Childrens Hospital from 1997 to 2007 and treated with this aggressive approach. Diagnosis was confirmed using molecular markers. There are two long-term survivors (78 and 98 months from diagnosis). One additional patient is alive with disease. Three patients died of disease during therapy. Three patients died of disease after therapy was complete. There were no toxic deaths. Two of nine patients treated for AT/RT at our institution with high dose chemotherapy and autologous bone marrow transplant are long-term survivors, suggesting that a subset of patients can be cured with this approach.     

The first cases of Candida auris candidaemia in Oman

Candida auris has been recognised as a problematic healthcare‐associated emerging yeast which is often misidentified as Candida haemulonii by commercial systems. Correct early identification of C. auris is important for appropriate antifungal treatment and implementing effective infection control measures. Here we report emergence of the first C. auris cases in Oman, initially misidentified as C. haemulonii.     

FungiScope™—Global Emerging Fungal Infection Registry

Rare invasive fungal diseases (IFD) are challenging for the treating physicians because of their unspecific clinical presentation, as well as the lack of standardised diagnostic and effective treatment strategies. Late onset of treatment and inappropriate medication is associated with high mortality, thus, urging the need for a better understanding of these diseases. The purpose of FungiScope^? is to continuously collect clinical information and specimens to improve the knowledge on epidemiology and eventually improve patient management of these orphan diseases. FungiScope^? was founded in 2003, and today, collaborators from 66 countries support the registry. So far, clinical data of 794 cases have been entered using a web‐based approach. Within the growing network of experts, new collaborations developed, leading to several publications of comprehensive analyses of patient subgroups identified from the registry. Data extracted from FungiScope^? have also been used as the sole control group for the approval of a new antifungal drug. Due to the rarity of these diseases, a global registry is an appropriate method of pooling the scarce and scattered information. Joining efforts across medical specialities and geographical borders is key for researching rare IFD. Here, we describe the structure and management of the FungiScope^? registry.