Cytomorphological findings in drug defaulters of tuberculous lymphadenitis.

Objectives: Tuberculosis (TB) is an important health problem specially in the developing countries. Although effective chemotherapy is available, compliance of patient is a major challenge. The aim of this study was to describe cytomorphological features of drug defaulters on lymph node on fine-needle aspiration cytology (FNAC) and compare it with newly diagnosed cases. Material and Methods: A cross-sectional study was done for a period of 18 months, in which all patients having tuberculous lymphadenitis were included after taking detailed history regarding previous anti-TB drug intake. Cytomorphological findings in drug defaulters were evaluated and compared with newly diagnosed cases. Results: There were a total of 150 cases with 120 newly diagnosed and 30 drug defaulters. Splintered epithelioid cell granuloma was seen in 40% of drug defaulters, while it was absent in case of newly diagnosed cases (P < 0.0001). Well-formed epithelioid cell granuloma was most commonly seen in newly diagnosed cases (65.83%) followed by poorly formed granuloma (26.67%). Another significant finding was distribution of eosinophils which were significantly high in case of drug defaulters (56.67%) (P < 0.0001). Conclusion: Cytomorphological findings can help in identification of the drug defaulters on FNAC and thus plan further line of treatment.

Development of Two-Tube Loop-Mediated Isothermal Amplification Assay for Differential Diagnosis of Plasmodium falciparum and Plasmodium vivax and Its Comparison with Loopamp™ Malaria.

To strengthen malaria surveillance, field-appropriate diagnostics requiring limited technical resources are of critical significance. Loop-mediated isothermal amplification (LAMP) based malaria diagnostic assays are potential point-of-care tests with high sensitivity and specificity and have been used in low-resource settings. Plasmodium vivax-specific consensus repeat sequence (CRS)-based and Plasmodium falciparum-specific 18S rRNA primers were designed, and a two-tube LAMP assay was developed. The diagnostic performance of a closed-tube LAMP assay and Loopamp™ Malaria Detection (Pan/Pf, Pv) kit was investigated using nested PCR confirmed mono- and co-infections of P. vivax and P. falciparum positive (n = 149) and negative (n = 67) samples. The closed-tube Pv LAMP assay showed positive amplification in 40 min (limit of detection, LOD 0.7 parasites/µL) and Pf LAMP assay in 30 min (LOD 2 parasites/µL). Pv LAMP and Pf LAMP demonstrated a sensitivity and specificity of 100% (95% CI, 95.96-100% and 89.85-100%, respectively). The LoopampTM Pan/Pf Malaria Detection kit demonstrated a sensitivity and specificity of 100%, whereas LoopampTM Pv showed a sensitivity of 98.36% (95% CI, 91.28-99.71%) and specificity of 100% (95% CI, 87.54-100%). The developed two-tube LAMP assay is highly sensitive (LOD ≤ 2 parasite/µL), demonstrating comparable results with the commercial Loopamp™ Malaria Detection (Pf/pan) kit, and was superior in detecting the P. vivax co-infection that remained undetected by the Loopamp™ Pv kit. The developed indigenous two-tube Pf/Pv malaria detection can reliably be used for mass screening in resource-limited areas endemic for both P. falciparum and P. vivax malaria.

Lessons from implementation research on community management of Possible Serious Bacterial Infection (PSBI) in young infants (0-59 days), when the referral is not feasible in Palwal district of Haryana, India.

BACKGROUND: Neonatal sepsis is a major cause of death in India, which needs hospital management but many families cannot access hospitals. The World Health Organization and the Government of India developed a guideline to manage possible serious bacterial infection (PSBI) when a referral is not feasible. We implemented this guideline to achieve high coverage of treatment of PSBI with low mortality. METHODOLOGY: The implementation research study was conducted in over 50 villages of Palwal district, Haryana during August 2017-March 2019 and covered a population of 199143. Policy dialogue with central, state and district health authorities was held before initiation of the study. A baseline assessment of the barriers in the implementation of the PSBI intervention was conducted. The intervention was implemented in the program setting. The research team collected data throughout and also co-participated in the implementation of the intervention for the first six months to identify bottlenecks in the health system and at the community level. RE-AIM framework was utilized to document implementation strategies of PSBI management guideline. Implementation strategies by the district technical support unit (TSU) included: (i) empower mothers and families through social mobilization to improve care-seeking of sick young infants 0-59 days of age, (ii) build capacity through training and build confidence through technical support of health staff at primary health centers (PHC), community health centers (CHC) and sub-centers to manage young infants with PSBI signs and (iii) improve performance of accredited social health activists (ASHAs). FINDINGS: A total of 370 young infants with signs of PSBI were identified and managed in 5270 live births. Treatment coverage was 70% assuming that 10% of live births would have PSBI within the first two months of life. Mothers identified 87.6% (324/370) of PSBI cases. PHCs and CHCs became functional and managed 150 (40%) sick young infants with PSBI. Twenty four young infants (7-59days) who had only fast breathing were treated with oral amoxicillin without a referral. Referral to a hospital was refused by 126 (84%); 119 had clinical severe infection (CSI), one 0-6 days old had fast breathing and six had critical illness (CI). Of 119 CSI cases managed on outpatient injection gentamicin and oral amoxicillin, 116 (96.7%) recovered, 55 (45.8%) received all seven gentamicin injections and only one died. All 7-59 day old infants with fast breathing recovered, 23 on outpatient oral amoxicillin treatment; and 19 (79%) received all doses. Of 65 infants managed at either district or tertiary hospital, two (3.1%) died, rest recovered. Private providers managed 155 (41.9%) PSBI cases, all except one recovered, but sub-classification and treatment were unknown. Sub-centers could not be activated to manage PSBI. CONCLUSION: The study demonstrated resolution of implementation bottlenecks with existing resources, activated PHCs and CHCs to manage CSI and fast breathers (7-59 day old) on an outpatient basis with low mortality when a referral was not feasible. TSU was instrumental in these achievements. We established the effectiveness of oral amoxicillin alone in 7-59 days old fast breathers and recommend a review of the current national policy.

Real-Time Fluorimetry Loop-Mediated Isothermal Amplification for Diagnosis of Leishmaniasis and as a Tool for Assessment of Cure for Post-Kala-Azar Dermal Leishmaniasis.

Despite the dwindling number of visceral leishmaniasis (VL) cases in India, there is an urgent need for early and unequivocal diagnostics for controlling and preventing the reemergence of VL. Post-kala-azar dermal leishmaniasis (PKDL), a dermal sequela of VL, serves as a reservoir of the parasite. Diagnosis of PKDL, especially the macular variant, is challenging and poses impediment toward attainment of VL elimination. In this study, a real-time fluorimetry loop-mediated isothermal amplification (RealAmp) assay has been established for the detection of different clinical manifestations of leishmaniasis. The study included 150 leishmaniasis patients (25 VL, 25 cutaneous leishmaniasis [CL], and 100-PKDL) along with 120 controls. The assay demonstrated sensitivity of 100% (95% CI: 86.68-100) for diagnosis of VL and PKDL (95% CI: 79.61-100) and 96% (95% CI: 86.68-100) for CL with 100% specificity. Moreover, considering the cardinal role of PKDL, diagnosis using minimally invasive slit aspirate was explored, which demonstrated remarkable sensitivity of 96% (95% CI: 87.64-98.47). As a test of cure for PKDL, RealAmp successfully detected parasite in two of posttreatment cases who later reported relapse on follow-up. Also, direct sample lysis using slit aspirate was attempted in a small group that yielded sensitivity of 89% (95% CI: 67.20-96.90). RealAmp depicted excellent diagnostic accuracy in the diagnosis of leishmaniasis in concordance with the established SYBR Green I-based (Molecular Probes, Eugene, OR) visual loop-mediated isothermal amplification (LAMP) and the reference comparator real-time PCR. The study endorsed the employment of LAMP either as visual-LAMP or RealAmp for an accurate and expeditious diagnosis of PKDL and as a tool for assessment of cure.

Validation of SYBR green I based closed tube loop mediated isothermal amplification (LAMP) assay and simplified direct-blood-lysis (DBL)-LAMP assay for diagnosis of visceral leishmaniasis (VL).

BACKGROUND: The World Health Organization has targeted elimination of visceral leishmaniasis (VL) in the Indian subcontinent (ISC) by 2020. Despite distinctive decline seen in the number of VL cases in ISC, there is still a quest for development of a diagnostic test which has the utility for detection of active infection and relapse cases and as a test of cure. The present study validated the sensitivity and specificity of SYBR Green I based closed tube LAMP assay reported by us for diagnosis of VL. METHODOLOGY: The validation study was carried out at two endemic sites in India, located at Rajendra Memorial Research Institute of Medical Sciences (RMRIMS), Patna and Institute of Medical Sciences (IMS), Banaras Hindu University (BHU), Varanasi. Standard operating protocols were provided at the two sites for applying LAMP assay on confirmed VL cases. The diagnostic accuracy of LAMP assay was evaluated by Receiver operator curve (ROC) analysis. Furthermore, a simplified LAMP assay based on direct blood lysis, DBL-LAMP, was developed and verified for its diagnostic accuracy. PRINCIPAL FINDINGS: A total of 267 eligible participants were included in the study which comprised of 179 VL cases and 88 controls. Sensitivity and specificity of the LAMP assay were 98.32% (95% C.I- 95.2-99.7%) and 96.59% (95% C.I.-90.4-99.3%), respectively. ROC curve analysis depicted no significant difference between area under curve (AUCROC) for LAMP assay and rK39 RDT, indicative of LAMP as an excellent diagnostic test. DBL-LAMP assay, performed on 67 VL and 100 control samples, yielded a sensitivity of 93.05% (95% C.I- 84.75-97%) and specificity of 100% (95% C.I.- 96.30-100%). CONCLUSIONS/SIGNIFICANCE: The validated closed tube LAMP for diagnosis of VL will provide impetus to the ongoing VL elimination programme in ISC. The assay based on direct blood lysis promotes its scope for application in field settings by further reducing time and cost.

Seasonal Variation and Dengue Burden in Paediatric Patients in New Delhi.

OBJECTIVE: We conducted a study to find a relationship between main weather parameters with admission of positive dengue cases in a tertiary hospital. METHODS: Retrospective analysis was undertaken to identify epidemiological trend of dengue in 2016 from paediatric wards of a tertiary hospital in New Delhi. Data were collected on patient particulars and daily weather from January to December 2016. RESULTS: A total of 266 confirmed cases of dengue were considered. Relative humidity (RH) was associated with burden of positive dengue cases. On week-wise analysis, each surge of dengue admission was preceded by heavy rain 4-6 weeks earlier. Monthly averaged daily temperature range and RH were noted to have strong correlations with dengue burden, keeping an interval of 2 months in between. CONCLUSIONS: Weather parameters seem to influence magnitude of dengue epidemic, particularly in dengue season. There is need to have an in-depth study about developing a prediction model for dengue epidemic.

Profile of Children Hospitalized with Acute Poisoning in New Delhi.

195 cases of acute poisoning among children (age<12 y) in a tertiary hospital were identified over a period of one year. Two-thirds (63%) of them were males and 75% were below five years of age. Poisoning by medicines was most common (17%) followed by ingestion of corrosives/detergents (16%) and kerosene (14%).

Causes of Death among Children Aged >5 Years in a Public Hospital in New Delhi.

Retrospective analysis was done for 3817 children aged 5-12 years admitted in a tertiary-care, public hospital in New Delhi between January to December, 2015. Mortality rate was 5.8%. About 47.1% deaths were due to central nervous system involvement; viral meningoencephalitis being the predominant cause. Overall, infectious diseases caused >80% of deaths. Public health interventions to reduce child mortality need to review such data for effective measures.

Mortality in newborns referred to tertiary hospital: An introspection.

BACKGROUND: India is one of the largest contributors in the pool of neonatal death in the world. However, there are inadequate data on newborns referred to tertiary care centers. The present study aimed to find out predictors of mortality among newborns delivered elsewhere and admitted in a tertiary hospital in New Delhi between February and September 2014. MATERIALS AND METHODS: Hospital data for were retrieved and analyzed for determining predictors for mortality of the newborns. Time of admission, referral and presenting clinical features were considered. RESULTS: Out of 1496 newborns included in the study, there were 300 deaths. About 43% deaths took place in first 24 hours of life. Asphyxia and low birth weight were the main causes of death in early neonatal period, whereas sepsis had maximum contribution in deaths during late neonatal period. Severe hypothermia, severe respiratory distress, admission within first 24 hours of life, absence of health personnel during transport and referral from any hospital had significant correlation with mortality. CONCLUSIONS: There is need for ensure thermoregulation, respiratory sufficiency and presence of health personnel during transport.

Successful aortic valve replacement surgery in a patient with severe haemophilia a with low titre inhibitor.

In spite of the modern day innovations, managing severe Haemophilia patients with inhibitors continues to be a challenge. The management of patients with severe haemophilia with inhibitors who are undergoing major surgeries like open heart surgery is technically demanding, fraught with peri-operative complications and needs a multidisciplinary approach. We describe a young man with severe haemophilia with low titre inhibitors who underwent a successful open heart surgery and aortic valve replacement, supported only with bolus doses of Factor VIII and tranexamic acid without any complications.

Atypical presentation of posterior reversible encephalopathy: in a child with bilateral grade IV vesicoureteric reflux.

Posterior reversible encephalopathy, better known as potential reversible encephalopathy syndrome (PRES), is a clinicoradiological entity mostly described in adult populations manifesting predominantly as bilateral symmetrical diffuse white matter vasogenic oedema in parieto-occipital regions. Rarely it may also present as patchy reversible areas of involvement in the basal ganglia, brainstem and deep white matter. It is reported scarcely in childhood populations. Frequent association with acute hypertension (67-80%) is reported in many studies. Involvement of the brainstem and cervical cord (apart from the typical parieto-occipital lesions) is an extremely rare imaging manifestation of PRES and its recognition is important to avoid misdiagnosis as myelitis or acute disseminated encephalomyelitis by proper clinical correlation. We hereby report a case of PRES in a 7-year-old child showing an uncommon pattern on imaging study involving the brain as well as the brainstem and cervical spinal cord.

Hypokalemic periodic paralysis and distal renal tubular acidosis associated with renal morphological changes.

We report an unusual case of 5-yrs-old girl presenting with recurrent episodic weakness with documented hypokalemia, polyuria and failure to thrive. The child was finally diagnosed as having distal renal tubular acidosis. Imaging studies revealed associated hypoechoic spaces in renal medulla. Long term treatment with alkali and maintenance of normokalemia lead to regression of these morphological changes.

Atypical subacute sclerosing panencephalitis with short onset latency.

An 11-month-old boy presented with focal seizures, myoclonic jerks and altered sensorium of one month duration, with a history of measles at eight months of age. A diagnosis of Subacute sclerosing panencephalitis (SSPE) was made on the basis of typical EEG changes and presence of anti-measles antibody in cerebrospinal fluid. A differential diagnosis of SSPE should be considered in all forms of acute encephalopathy in infants for early diagnosis and management.

Stress induced hyperglycemia in a term baby mimicking diabetic ketoacidosis with stroke.

Stress/sepsis induced transient hyperglycemia in the newborn may present with extremely high blood sugar values and may mimic neonatal diabetes mellitus. We present a case of neonatal septicemia with stress induced hyperglycemia mimicking neonatal diabetes mellitus. Extremely high blood sugar values upto 1529 mg/dl with metabolic acidosis were noted in a term good weight baby causing a diagnostic dilemma. It can be seen even in term babies, contrary to the belief that it occurs in preterm and small for gestation babies. Considering the prognostic implications it may cause it is important that hyperglycemia is promptly treated by insulin infusion.