Malaria control in India has occupied high priority in health sector consuming major resources of the Central and State governments. Several new initiatives were launched from time to time supported by foreign aids but malaria situation has remained static and worsened in years of good rainfall. At times malaria relented temporarily but returned with vengeance at the local, regional and national level, becoming more resilient by acquiring resistance in the vectors and the parasites. National developments to improve the economy, without health impact assessment, have had adverse consequences by providing enormous breeding grounds for the vectors that have become refractory to interventions. As a result, malaria prospers and its control is in dilemma, as finding additional resources is becoming difficult with the ongoing financial crisis. Endemic countries must contribute to make up the needed resources, if malaria is to be contained. Malaria control requires long term planning, one that will reduce receptivity and vulnerability, and uninterrupted financial support for sustained interventions. While this seems to be a far cry, the environment is becoming more receptive for vectors, and epidemics visit the country diverting major resources in their containment, e.g. malaria, dengue and dengue haemorrhagic fevers, and Chikungunya virus infection. In the last six decades malaria has taken deep roots and diversified into various ecotypes, the control of these ecotypes requires local knowledge about the vectors and the parasites. In this review we outline the historical account of malaria and methods of control that have lifted the national economy in many countries. While battles against malaria should continue at the local level, there is a need for large scale environmental improvement. Global Fund for AIDS, Tuberculosis and Malaria has provided huge funds for malaria control worldwide touching US$ 2 billion in 2011. Unfortunately it is likely to decline to US$ 1.5 billion in the coming years against the annual requirement of US$ 5 billion. While appreciating the foreign assistance, we wish to highlight the fact that unless we have internal strength of resources and manpower, sustained battles against malaria may face serious problems in achieving the final goal of malaria elimination.

The introduction of drug eluting stents has resulted in dramatic reductions in the rates of restenosis and the need for repeat revascularization. In the last several years, concern has been raised regarding the long-term safety of this technology, particularly in the area of late restenosis and stent thrombosis. The development of newer anti-restenotic drug coatings, biodegradable polymers and even completely bioabsorbable stents offer the potential to address these limitations. Additional questions that have recently come to the forefront include the optimal duration of dual antiplatelet therapy, the use of platelet reactivity assays and genetic testing and drug eluting stent use in the treatment of acute myocardial infarction. This article will attempt to address these and other areas of controversy in the use and implementation of drug eluting stents.

Mycoplasma genitalium is a member of genital mycoplasmas, which is emerging as an important causative agent of sexually transmitted infections both in males and females. The advent of polymerase chain reaction and other molecular methods have made studies on M. genitalium more feasible, which is otherwise a difficult organism to isolate. Besides Chlamydia trachomatis, M. genitalium is now an important and established cause of non gonococcal urethritis (NGU) in men, more so in persistent and recurrent NGU. Multiple studies have also shown a positive association of M. genitalium with mucopurulent cervicitis and vaginal discharge in females as well. The evidences for M. genitalium pelvic inflammatory diseases and infertility are quite convincing and indicate that this organism has potential to cause ascending infection. Lack of clear association with M. genitalium has been reported for bacterial vaginosis and adverse pregnancy outcomes. Diagnosis of M. genitalium infections is performed exclusively using nucleic acid amplification tests (NAATs), owing to poor or slow growth of bacterium in culture. Although there are no guidelines available regarding treatment, macrolide group of antimicrobials appear to be more effective than tetracyclines. The present review provides an overview of the epidemiology, pathogenesis, clinical presentation and management of sexually transmitted infections due to M. genitalium.

Background & objectives : Monitoring of HIV-infected individuals on antiretroviral treatment (ART) ideally requires periodic viral load measurements to ascertain adequate response to treatment. While plasma viral load monitoring is widely available in high-income settings, it is rarely used in resource-limited regions because of high cost and need for sophisticated sample transport. Dried blood spot (DBS) as source specimens for viral load measurement has shown promise as an alternative to plasma specimens and is likely to be a useful tool for Indian settings. The present study was undertaken to investigate the performance of DBS in HIV-1 RNA quantification against the standard plasma viral load assay. Methods: Between April-June 2011, 130 samples were collected from HIV-1-infected (n=125) and non-infected (n=5) individuals in two district clinics in southern India. HIV-1 RNA quantification was performed from DBS and plasma using Abbott m2000rt system after manual RNA extraction. Statistical analysis included correlation, regression and Bland-Altman analysis. Results: The sensitivity of DBS viral load was 97 per cent with viral loads >3.0 log ₁₀ copies/ml. Measurable viral load (>3.0 log ₁₀ copies/ml) results obtained for the 74 paired plasma-DBS samples showed positive correlation between both the assays (r=0.96). For clinically acceptable viral load threshold values of >5,000 copies/ml, Bland-Altman plots showed acceptable limits of agreement (-0.21 to +0.8 log ₁₀ copies/ml). The mean difference was 0.29 log ₁₀ copies/ml. The cost of DBS was $2.67 lower compared to conventional plasma viral load measurement in the setting. Interpretation & conclusions : The significant positive correlation with standard plasma-based assay and lower cost of DBS viral load monitoring suggest that DBS sampling can be a feasible and economical means of viral load monitoring in HIV-infected individual in India and in other resource-limited settings globally.

Background & objectives : Estimation of parathyroid hormone (PTH) levels is important in the management of metabolic bone disorders. Here we describe a simple, sensitive and specific second generation immunoradiometric assay (IRMA) to detect intact PTH levels using different solid phase matrices. Different methods for immobilization of antibodies have also been evaluated. Methods: Experiments were carried out with physical adsorption of antibodies, covalent coupling using 2 per cent glutaraldehyde and N,N`carbonyldiimidazole. In all cases, antibodies raised against C-terminal were used as solid phase agent. Detector antibodies were N terminal antibodies that were radio-iodinated with ^[125] I followed by gel purification. Several of the antibodies coupled to various solid phase matrices were incubated with PTH standards and the detector antibody as well as the commercially available tracer from DiaSorin kit to identify a suitable match pair. Results: The best pair was polyclonal C-terminal PTH antibody along with the kit tracer from DiaSorin with regards to antibody coated to magnetic cellulose particles. Among the various antibodies and the solid phases evaluated, the best assay was obtained with the matched pair of antibodies (70×G67 and 70×G68) from Fitzgerald immobilized on polystyrene tubes. The polyclonal antibody against C-terminal PTH was chosen as the capture antibody and ^[125] I labelled polyclonal antibody against N-terminal PTH as the tracer. The sample values obtained in the antibody coated tubes were comparable to those obtained using a commercial kit. Interpretation & conclusions : The results indicated the feasibility of adopting this system for further development into a PTH IRMA for regular production as there is no indigenous kit available for intact PTH.

Background & objectives: Bio-manipulation technique is of primary importance during the development of transgenic mosquitoes. The study describes the variable factors that influence the viability of medically important mosquito vectors during microinjection. Methods: Three mosquito vectors belonging to the genus Aedes, Anopheles and Culex were microinjected at different developmental stages of their life cycle viz., egg, larvae, pupae and adult. Results: The improvisations revealed an increased survivability of biomanipulated mosquitoes during the embryonic and adult microinjection. The study of injecting larvae and pupae resulted in poor survivability. Interpretation & conclusions: The microinjection protocol was successfully tested on three important mosquito vectors. The critical period after biomanipulation which contributes heavily for the survivability factor was evaluated. The results provide a common protocol for biomanipulation of three mosquito vectors with enhanced survivability.

Background & objectives : Moxifloxacin (MFX) is reported to have promising antimycobacterial activity, and has a potential to shorten tuberculosis (TB) treatment. We undertook this study to examine the influence of rifampicin (RMP) and isoniazid (INH) on the steady state pharmacokinetics of MFX individually in healthy individuals. Methods: A baseline pharmacokinetic study of MFX (400 mg once daily) was conducted in 36 healthy adults and repeated after one week of daily MFX with either RMP (450/600 mg) (n = 18) or INH (300 mg) (n = 18). Plasma MFX concentrations were determined by a validated HPLC method. Results: Plasma peak concentration and exposure of MFX was significantly lower and plasma clearance significantly higher when combined with RMP (P<0.001). The C _max to MIC and AUC _0-12 to MIC ratios of MFX were significantly lower during concomitant RMP (P<0.001). INH had no significant effect on the pharmacokinetics of MFX. Interpretation & conclusions : Concomitant RMP administration caused a significant decrease in C _max and AUC _0-12 of MFX, the mean decreases being 26 and 29 per cent, respectively. It is uncertain whether this decrease would affect the treatment efficacy of MFX. Prospective studies in TB patients are needed to correlate MFX pharmacokinetics with treatment outcomes.

Background & objectives : Optic neuritis (ON) is characterized by sudden and rapid impairment of vision. Bartonella henselae is a known aetiological agent of cat scratch disease (CSD), which is a common cause of neuroretinitis, the least common type of optic neuritis. The present study was carried out to determine the microbiological aetiology of optic neuritis in patients attending a tertiary care eye hospital in north India, which was later confirmed with molecular characterization. Methods: Of the 50 patients suffering from optic neuritis reported to the Ophthalmology OPD of a tertiary care eye hospital in New Delhi, India, 29 were included in the study. Blood culture from these patients were processed for aerobic and anerobic cultures to rule out infective aetiology. Subsequently, PCR was done on archive, glycerol-stocked cultures. Results: Gram-negative pleomorphic coccobacilli grew in four of 29 patients tested. Characterization of these revealed Bartonella like organism as tested by the API 20E, API Staph, API Strept and RapID ANA systems. Electron microscopy revealed presence of polar flagella and bleb like projection all over the bacterial surface. PCR performed on preserved culture confirmed these as Bartonella sp. Interpretation & conclusions: Infections with Bartonella like organisms have not been demonstrated from India in cases of optic neuritis or in any of the other clinical syndromes in the past. The present study shows the isolation and characterization of Bartonella like organisms from optic neuritis patients. From clinical point of view it will be important to look for these organisms as aetiological agents in ON cases in order to treat with appropriate antibiotics.

Background & objectives : Ureaplasmas have been implicated in a variety of clinical conditions. However, only certain serovars of ureaplasmas are disease associated. Only a few classes of antimicrobial agents are available for the treatment of mycoplasmal infections in humans. Increase of resistance of genital mycoplasmas to antimicrobials has been reported worldwide. The aim of the present study was to determine the occurrence of Ureaplasma serovars in patients with infertility and genital tract infections with polymerase chain reaction (PCR)-based serotyping. The antimicrobial susceptibilities of Ureaplasma spp. and Mycoplasma hominis were also assessed to determine the most suitable treatment strategy. Methods: Sexually active adults (n=147) with symptoms of genital tract infections and 115 infertile women were enrolled. Endocervical swabs from women and urethral swabs from men were subjected to culture and multiplex PCR for detection of genital mycoplasmas. Serotyping of Ureaplasma was done by PCR and antimicrobial susceptibility to doxycycline, azithromycin, josamycin and ofloxacin was done by microbroth dilution method. Results: Ureaplasma was detected in 25.8 per cent patients with genital tract infections and 20.8 per cent in infertile women. Serovar 3/14 was the most frequent isolate followed by serovar 1 and serovar 6. The majority of Ureaplasma isolates were susceptible to doxycycline (91%) and josamycin (86%) followed by ofloxacin (77%) and azithromycin (71%). All the isolates of M. hominis were uniformly susceptible to doxycycline, josamycin and ofloxacin. Interpretation & conclusions : The predominance of Ureaplasma serovar 3/14 suggests their possible pathogenic role in genital tract infections and infertility. For empirical treatment, doxycycline could be the drug of choice for genital mycoplasmas.

Background & objectives : During recent decades, there has been a change in the epidemiology of Candida infections, characterized by a progressive shift from a predominance of Candida albicans to non-albicans Candida species. This study was undertaken to analyze the change in the epidemiology of candidaemia and antifungal use at tertiary care hospital in New Delhi, India, over a period of 10 years. Methods: A retrospective review of candidaemia between 1999 and 2008 and antifungal use from 2000 to 2008 was performed at Sir Ganga Ram Hosptial, New Delhi. Initially (1999-2005), isolates were differentiated as C. albicans and non- albicans Candida species. Between 2006-2008, these were identified to the species level and antifungal susceptibility was performed. Results: The occurrence of candidaemia and total antifungal use increased significantly. Candidaemia due to non-albicans species increased and this was correlated with an increasing use of fluconazole. There was emergence and increased isolation of a novel species C. haemulonii with decreased susceptibility to both amphotericin B and azoles. Overall, sensitivities of 89.6, 90.9, 88.6, 68.8 and 54.3 per cent to amphotericin B, 5 flucytosine, voriconazole, fluconazole and itraconazole, respectively were observed. Cross-resistance or reduced susceptibility to both fluconazole (MIC >16 μg/ml) and voriconazole was observed in 11.3 per cent isolates. Interpretation & conclusions : The study demonstrates a shift to non-albicans Candida species causing fungaemia and the emergence of amphotericin B and azole resistant novel species, C. haemulonii. Decreased susceptibility to fluconazole, as well as the threat of emergence of cross-resistance to voriconazole in the background of high azole consumption may limit the use of these agents as a presumptive therapy for Candida blood stream infections (BSI).

Background & objectives : Ocular infection with Chlamydia trachomatis is a major public health problem in densely populated countries like India. The true prevalence of such infections is uncertain due to insufficient data available from India. The aim of this study was to do a retrospective analysis of C. trachomatis eye infections in patients attending the outpatient department of Dr Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, over a period of 12 years. Methods: From 1997 to 2008, the Chlamydia laboratory received conjunctival swabs from 1281 consecutive patients for C. trachomatis detection after thorough clinical examination. Specimens were subjected to direct fluorescent antigen detection assay using monoclonal antibody based commercial kit to detect the presence of C. trachomatis antigen. Results: Antigen positivity varied between 22-28 per cent. Children below 11 yr and people above the age of 60 yr showed comparatively higher antigen positivity (25.7 and 27.8%, respectively). As compared to males significantly (P<0.05) higher number of females in the age group of 31-60 yr were positive for C. trachomatis antigen. Patients with the clinical diagnosis of follicular/allergic conjunctivitis and trachoma showed higher rate of antigen positivity. Interpretation & conclusions : Northern India having dry and arid climatic conditions in most parts of the year was considered in the past as one of the trachoma hyper-endemic foci. The study indicated that laboratory proven C. trachomatis eye infection still persisted in this part of the country throughout the study period of 12 years.

Background & objectives : Prevention of parent-to-child transmission (PPTCT) services are an integral part of National AIDS Control Programme and their critical appraisal is necessary for improving quality care. The present study was conducted to evaluate the performance of PPTCT services in West Bengal during April, 2008 - March 2009 and April 2009 - March 2010 and identify gaps in service delivery for making suitable recommendations. Methods: Data were collected from the Computerized Management Information System and validated by cross-checking records at each district. Focus group discussions (FGDs) were conducted among programme managers, counsellors and antenatal women attending the Integrated Counselling and Testing Centres. Performance indicators and outcomes of FGDs were analyzed. Results: The proportion of antenatal women tested declined in 2009-2010 from 2008-2009 (64.3 to 63.8%). Proportions of counseled cases also declined (72.5 vs. 68.4%). HIV positivity rates among those tested were 0.13 and 0.14 per cent, respectively in two years. Proportion of mother-baby pairs receiving nevirapine prophylaxis was increased by 5 per cent. Medical colleges, and category A districts having high HIV prevalence provided better services. Follow up services of HIV-exposed birth cohorts were grossly unsatisfactory. Interpretation & conclusions : Gaps were identified at each step of service delivery for which capacity building, improvement of infrastructure including laboratory services and ensuring emergency labour room testing up to the sub-district level were imperative. Outsourcing follow up services to other community based organizations may also be considered.

Background & objectives : Scrub typhus is one of the differential diagnoses of haemorrhagic fevers especially if associated with jaundice and/or renal failure. Goa State in the western region of India has been witnessing increased incidence of such fevers, therefore, the present study was undertaken to identify whether scrub typhus is the aetiological agent. Methods: Adult patients presenting with undiagnosed febrile illness between June 2009 to October 2010, were evaluated. Testing was done using a commercial ELISA kit for specific IgM antibodies against Orientia tsutsugamushi. Results: Of the 44 patients included in the study, 15 (34%) were found to be positive for IGM antibodies against O. tsutsugamushi. The cases were seen mainly in the months between July to November. The common symptoms noted were fever, myalgias, gastrointestinal complaints, followed by breathlessness, rash and jaundice. The pathognomonic features such as eschar and lymphadenopathy were seen only in two patients. Nearly two third of the patients had leukocytosis (67%) and low serum albumin (60%). The most common complication noticed was hepatitis (80%) followed by acute respiratory distress syndrome (ARDS) (60%), thrombocytopenia (40%) and acute renal failure (33%). Five patients died in the course of illness. Interpretation & conclusions : Our results showed that scrub typhus should be considered in the differential diagnosis of acute febrile illness associated with gastrointestinal symptoms, rash, myalgia , including those with organ dysfunctions such as hepatorenal syndrome, coagulopathy or ARDS. Empirical treatment with doxycycline or macrolides may be given in cases with strong suspicion of scrub typhus.

Background & objectives : Sleep restriction is a common feature of modern lifestyle and its effects can be extended to pregnancy. Several neurobehavioural consequences of sleep restriction during pregnancy have been reported, among which stand out perinatal depression and maternal fatigue, however, its effects over mother-infant relationship warrant further investigation. Thus, this study was aimed to evaluate the effects of sleep restriction during pregnancy over maternal behaviour and maternal aggression through animal models. Methods: Eighteen 90-day-old female Wistar rats were distributed in two groups: (i) Control - not submitted to any manipulation during pregnancy, and (ii) Sleep restriction - submitted to sleep restriction during the entire pregnancy (21 days) through the multiple platforms technique. In the postpartum day 5, resident-intruder paradigm and the latencies test were performed to assess both maternal behaviour and maternal aggression. Results: The sleep-restricted females displayed grooming in less frequency and duration, and with higher latency when compared to normal animals, while maternal aggression and maternal behaviour parameters remained equivalent between groups. Interpretation & conclusions : Considering the maintenance of maternal behavioural parameters, the inhibition of grooming seems to exert an adaptive mechanism, enabling sleep-restricted rats to display maternal behaviour properly.

Background & objectives : Decline in cognitive functions is a major challenge for professionals during sustained wakefulness. We used middle latency response (MLR), event related potentials P300-ERP and contingent negative variation (CNV) and Raven's Advanced Progressive Matrices (RAPM) - a standard neuropsychological test were used to evaluate cognitive impairment after total sleep deprivation (SD); and to study the impact of meditation as an intervention for this impairment. Methods: Healthy male volunteers (n=10) drawn randomly from the Indian Army participated in a 6-night study design executed before and after two months of meditation practice: night 1-adaptation, night 2-baseline, night 3-24 h SD, night 4-recovery sleep, night 5-24 h SD after 60 days meditation, night 6-recovery sleep after SD. A 36 h SD was obtained by keeping the subject awake for 12 h after 24 h SD. Results: The latency and amplitude of P300 increased after 36 h SD. Amplitudes and latencies of both early and late CNV increased after 24 and 36 h SD, indicating deficient orientation and impairment of attention and perception. Prolonged CNV reaction time after 36 h SD manifested deficient motor response following second (imperative) stimulus. Latency of MLR Na registered significant change following 36 h SD compared to baseline (P<0.01) and recovery (P<0.05). RAPM score showed significant decrease after 36 h of wakefulness indicating impaired analytical ability and difficulty in problem solving. None of these parameters showed any significant alteration after SD, following meditation practice. Interpretation & conclusions : The present results showed that SD impaired cognitive performance to graded extents significantly, but this deterioration could be improved to a significant extent using meditation.

Background & objectives : Pedestrians contribute to 30-40 per cent of all road traffic injuries in India. However, there is a paucity of literature on pedestrian head injury as compared to two wheeler trauma. The purpose of the present study was to study the pattern of pedestrian injuries and their outcome with a special focus on head injuries. Methods: The study was conducted in two parts in the Trauma Center at National Institute of Mental Health & Neuro Sciences, Bangalore. A retrospective study was conducted at the casualty services of the hospital in which 529 consecutive pedestrians who sustained injury in a road traffic accident were studied from June to September 2009. In the second part, records from the hospital mortuary were retrospectively analyzed from 2007 to 2009. An analysis of 326 patients who died as a pedestrian in road accidents during this period was performed. Results: Patients in both paediatric and elderly age groups constituted 47.6 per cent (252/529) of all casualty admissions. Majority of the pedestrian injuries (41.7%, 221/529) occurred between 1600 - 2100 h; 87.1 per cent of all patients received some primary care before admission. The most common offending vehicle was a two wheeler (49.1%, 260/529). At the time of admission, 55.2 per cent (292/529) patients had sustained a moderate or severe head injury (GCS 3-13), and 40.5 per cent (214/529) had an abnormal CT scan. In addition, 90.4 per cent (478/529) patients had also sustained associated injuries. Major thoracoabdominal trauma was seen in 4 per cent and spine injury in 2.3 per cent of the patients. The mortality rate was 6.6 per cent. In the postmortem group, pedestrian deaths constituted 26.2 per cent of all the postmortems conducted. Two wheelers were the offending vehicle in the majority of the fatal crashes (39.9%). Interpretation & conclusions : Pedestrian injuries form a major part of the workload of a neurotrauma emergency. Majority of them sustained moderate to severe head injury. More attention, infrastructure and strict implementation of rules may help reduce this burden.