Spectrum of malabsorption syndrome among adults & factors differentiating celiac disease & tropical malabsorption.

Background & objectives: Aetiology of malabsorption syndrome (MAS) differs in tropical and temperate countries over time; clinical and laboratory parameters may differentiate between various causes. This study was undertaken to investigate the spectrum of MAS among Indian adults and to find out the features that may help to differentiate between TM and celiac disease. Methods: Causes of MAS, and factors differentiating tropical malabsorption (TM) from celiac disease (CD) were determined in 275 patients. Results: Using standard criteria, causes in 275 patients [age 37.5+13.2 yr, 170, (61.5%) male] were, TM 101 (37%), CD 53 (19%), small intestinal bacterial overgrowth 28 (10%), AIDS 15 (5.4%), giardiasis 13 (5%), hypogammaglobulinemia 12 (4%), intestinal tuberculosis 7 (2.5%), strongyloidiasis 6 (2%), immunoproliferative small intestinal disease 5 (2%), Crohn's disease 6 (2%), amyloidosis 4 (1.5%), intestinal lymphangiectasia 3 (1%) and unknown 22 (8%). On univariate analysis, patients with CD were younger than TM (30.6+12 vs. 39.3+12.6 yr, P<0.001), had lower body weight (41.3+11.8 vs. 49.9+11.2 kg, P<0.001), longer diarrhoea duration (median 36 inter-quartile range 17.8-120 vs. 24-months, 8-48, P<0.01), lower stool frequency (6/day, 5-8 vs. 8, 5-10, P<0.05), lower haemoglobin (9.4+3.2 vs. 10.4+2.7 g/dl, P<0.05), higher platelet count (2,58,000, range 1,35,500-3,23,500 vs. 1,60,000, 1,26,000-2,58,000/mm3, P<0.05), and more often had hepatomegaly (9/53, 17% vs. 4/101, 4%, P<0.01), and subtotal or partial villous atrophy (36/50, 72% vs. 28/87, 32%, P<0.001). Younger age (<35 yr), longer diarrhoea duration, higher platelet count and villous atrophy were significant on multivariate analysis. Interpretation & conclusions: TM and CD are common causes of MAS among Indian adults. Younger age (<35 yr), longer diarrhoea duration, higher platelet count and villous atrophy were found to be associated with CD.

A series on intestinal strongyloidiasis in immunocompetent and immunocompromised hosts.

Background: Strongyloidiasis, endemic in tropical areas, may be asymptomatic in immunocompetent subjects or may cause potentially fatal hyper-infection in immunocompromised patients. Methods: Of the 13,885 patients referred to the parasitology laboratory at our tertiary care referral center for stool microscopy, 15 were diagnosed as strongyloidiasis over a 6 year period. We assessed these patients retrospectively. Results: Most patients were young (median age 32 years, range 3-66) males (12, 80%). Seven patients (46.6%) were immunocompromised. All patients were symptomatic, and symptoms included chronic diarrhea (4, 26.7%), acute diarrhea (1, 6.7%), abdominal pain (6, 40%), weight loss (3, 20%), cough (2, 13.33%), vomiting (1, 6.7%), anemia (10, 66.7%) and eosinophilia (3, 20%). Thirteen patients (86.6%) were diagnosed on first stool microscopy. Duodenal biopsy showed normal histology in twelve (80%) and partial villous atrophy in one (6.7%) patient. Stool microscopy also revealed giardiasis and cryptosporidiosis in one patient each. Nine patients responded well to ivermectin and albendazole, one died and five were lost to followup. Conclusions: In endemic areas, even immunocompetent subjects may suffer from symptomatic strongyloidiasis and associated eosinophilia is uncommon.

Association between gastric mucosal glutathione-S-transferase activity, glutathione-S-transferase gene polymorphisms and Helicobacter pylori infection in gastric cancer.

Aim Helicobacter pylori infection, though common, leads to gastric cancer (GC) in less than 1% individuals, suggesting the role of host factors. We previously reported the role of glutathione–S–transferase (GST) polymorphisms, the gene encoding a carcinogen–detoxifying enzyme, in GC. This study was aimed to evaluate GST enzyme activity, GST polymorphism, glutathione (GSH) levels and H. pylori in patients with GC. Methods GST and GSH levels were estimated in gastric biopsies of 52 patients with GC, 37 functional dyspepsia (FD) and 39 peptic ulcer (PU), and correlated with H. pylori (ELISA) infection and GST polymorphisms. GST polymorphisms were separately analyzed in relationship to H. pylori in 82 GC, 72 FD, 53 PU and 89 healthy controls (HC). Results GST activity was lower in patients with GC in comparison to PU (p=0.03), but GSH levels were comparable. GSTT1 null genotype (GSTT1*0) and simultaneous deletion of both GSTT1 and GSTM1 genes was associated with lower enzyme activity (p=0.02 and 0.01, respectively). GST and GSH levels in H. pylori positive and negative patients with GC, FD and PU were comparable. Presence of H. pylori infection along with GSTT1*0 (p= 0.006) and GSTM1*0 (p=0.05) was associated with lower enzyme activity. GSTT1*0 was associated with higher odds ratio (OR) of GC in presence of H. pylori (GC vs. HC: p=0.02, OR 2.6 [95% CI=1–6] vs. p=0.7, 1.3 [0.4– 5.0]; GC vs. PU: p=0.04, OR 3 [95% CI=1–9] vs. not applicable (OR could not be computed as frequency of GSTT1*0 in H. pylori negative patients with PU was zero)]. Conclusions GC is associated with reduced GST activity. Odds ratio of GC associated with GSTT1*0 is enhanced in presence of H. pylori probably due to combined effect of both on enzyme activity.

Chronic diarrhea and malabsorption due to hypogammaglobulinemia: a report on twelve patients.

Hypogammaglobulinemic sprue (HGS), which may predispose to infection, is uncommon. Twelve patients (all men; median age 29 years, 15–50) with HGS (4%) of 296 with chronic small bowel diarrhea and malabsorption syndrome (MAS) during a 10-year period were analyzed. Treatment of HGS was delayed due to misdiagnosis as intestinal tuberculosis (n=7) and diarrhea-predominant irritable bowel syndrome (n=1). All had diarrhea and weight loss (median loss 12 Kg). Associated conditions were clubbing, bronchiectasis, and seizure (2 patients each), and hypothyroidism (n=1). Laboratory parameters were urinary D-xylose median 0.46 g/5 g/5 h (range 0.2–1.6; normal ≥1), fecal fat 11.9 g/day (3.8–16.7; normal ≤7 g), serum IgA, IgG, and IgM: 23.5 mg/dL (17–114; normal 90–450), 584 mg/dL (145–1051; normal 800–1800), and 23 (0–40.3; normal 60–280). IgA, IgG, and IgM were low in 10, 10, and 11, respectively. Duodenal biopsy was normal in 6 patients and showed partial villous atrophy in 6 and nodular lymphoid hyperplasia in two. Associated infections were giardiasis (n=1), disseminated strongyloidiasis (1), small intestinal bacterial overgrowth (3), septicemia (2), and septic arthritis (1). Two patients died of sepsis, five are well on immunoglobulin and specific antiinfective treatment, and five are lost to follow up. Approximately 4% patients with MAS have hypogammaglobulinemia, which is often associated with infection and is diagnosed late.

Extended spectrum β--lactamases in Escherichia coli & Klebsiella pneumoniae & associated risk factors.

Background & objectives: Extended spectrum β-lactamases (ESBLs) have emerged as a major threat worldwide with limited treatment options. The genotypes of ESBL producing strains largely remain unknown in India; hence the present study was aimed to determine the occurrence of ESBLs in Escherichia coli and Klebsiella pneumoniae, their molecular types and associated risk factors in a tertiary care hospital. Methods: Total 200 consecutive clinical isolates of E. coli (n=143) and K. pneumoniae (n=57) collected between February and July 2006 at Sanjay Gandhi Postgraduate Institute of Medical Sciences, a tertiary care hospital in north India, were examined phenotypically for ESBL production. ESBL strains were further typed for the blaTEM/SHV/CTX-M genes by PCR using specifi c primers. The blaCTX-M cluster was identifi ed by restriction analysis and genotype by sequencing of PCR product. Resistance to other antimicrobial agents was also studied. Various risk factors associated with ESBL infections were analyzed by logistic regressions. Results: ESBLs were found in 63.6 per cent E. coli and 66.7 per cent K. pneumoniae isolates. Majority of the typeable isolates harboured two or more ESBL genes (57.3%). Overall blaCTX-M was the commonest genotype (85.4%) followed by blaTEM (54.9%) and blaSHV (32.9%) either alone or in combination. All CTX-M enzymes in E. coli and 87.5 per cent in K. pneumoniae belonged to the CTX-M-1 cluster. Sequencing was done for randomly selected 20 blaCTX-M PCR products and all were identifi ed as CTXM- 3. Resistance of ESBL isolates to other antibiotics was amikacin 14.7 per cent, gentamicin 66.7 per cent, trimethoprim/sulphamethoxazole 79.1 per cent and ciprofl oxacin 93.8 per cent. Prior antibiotic exposure, use of intravenous device and urinary catheter, renal insuffi ciency and ICU admission were associated with ESBL infection on univariate analysis. On multivariate, antibiotic exposure (P=0.001) and use of urinary catheter (P<0.001) were identififi ed as risk for ESBL infection. Interpretation & conclusions: Our study showed high ESBL occurrence with CTX-M as the emerging type in our hospital and CTX-M-3 being reported for the fi rst time in India. High co-resistance to other non-β-lactam antibiotics is a major challenge for management of ESBL infections.

Emerging vancomycin resistance in enterococci in India.

Infection caused by vancomycin resistant enterococci (VRE) leads to adverse outcome and is a real challenge. Despite increasing reports of VRE in different countries, there is scanty data on this issue from India. A total of 685 enterococci were isolated from various clinical samples from January to December 2004. Antimicrobial susceptibility was performed as prescribed by National Committee for Clinical Laboratory Standards (NCCLS). Vancomycin resistance was confirmed by minimum inhibitory concentration (MIC). Resistant phenotype was determined by Polymerase chain reaction (PCR). Of 685, 456 (67%) were E. faecalis and 229 (33%) were E. faecium. Resistance to various antibiotics in E. faecalis and E. faecium was as follows: ampicillin 33% and 54%, erythromycin 91% and 86%, ciprofloxacin 69% and 81%, tetracycline 50% and 54% and high level gentamicin resistance in 62% and 77% respectively. Vancomycin resistance was confirmed in 10 (1.4%) cases by MIC and all had Van A phenotype by PCR. Emergence of vancomycin resistant enterococci is of great concern because of its epidemic potential and scanty therapeutic options. Prompt diagnosis and efficient infection control measures can restrict its spread.

Strongyloides stercoralis infestation in a patient with severe ulcerative colitis.

Asymptomatic infestation with Strongyloides stercoralis, common in the tropics, may result in potentially fatal hyperinfection during treatment with immunosuppressive drugs used to treat patients with severe ulcerative colitis (UC). Hence, importance of early recognition and treatment of this nematode in patients with UC before starting immunosuppressive drugs can not be overemphasized. We report a 23-yrs old man with UC who presented with acute severe attack. Since his UC did not respond to intravenous hydrocortisone over 6 days, oral cyclosporine was started on 7th day after repeating stool microscopy, which revealed larvae of Strongyloides stercoralis. Duodenal aspirate also confirmed presence of multiple larvae. He responded to treatment for Strongyloides stercoralis , continuation of hydrocortisone and cyclosporine. Importance of early diagnosis of infestation with Strongyloides stercoralis while on treatment with immunosuppressive drugs for severe UC is emphasized. Difficulties in diagnosis and management of Strongyloides stercoralis infestation in patients with UC are discussed.

Utility of hydrogen breath tests in diagnosis of small intestinal bacterial overgrowth in malabsorption syndrome and its relationship with oro-cecal transit time.

BACKGROUND: Small intestinal bacterial overgrowth (SIBO), which may result from intestinal stasis, is common in malabsorption syndrome (MAS). Quantitative culture of upper gut aspirate is used as a gold standard for the diagnosis of SIBO. Studies on diagnosis of SIBO using non-invasive hydrogen breath tests are contradictory. METHODS: 83 patients (age 35 [14-70] y; 50 men) with MAS due to various causes were investigated for SIBO using quantitative culture of upper gut aspirate obtained using a special endoscopic catheter and glucose and lactulose hydrogen breath tests (GHBT, LHBT). Sustained elevation in breath hydrogen of 12 ppm above basal and two separate peaks (one due to SIBO and the other from colon) were diagnostic of SIBO in GHBT and LHBT, respectively. Oro-cecal transit time (OCTT) was estimated using LHBT in 71 patients. RESULTS: Thirty two of 81 (39.5%) patients with MAS had SIBO on culture (>or= 10(5) CFU/mL). Using aspirate culture as the gold standard, sensitivity, specificity, positive and negative predictive values and diagnostic accuracy of GHBT to diagnose SIBO were 44%, 80%, 62%, 67% and 65%, respectively; the corresponding values for LHBT were 31%, 86%, 62%, 54% and 55%, respectively. OCTT in patients with SIBO diagnosed on GHBT and/or aspirate culture (n=58) was longer than in those without (170 [60-250] vs. 120 [50-290] min, p=0.02); of others, 7 were hydrogen non-producers and in 6 OCTT could not be assessed due to sustained early peak because of SIBO. CONCLUSIONS: GHBT and LHBT are highly specific but insensitive for diagnosis of SIBO in MAS; OCTT is longer in patients with MAS and SIBO than in those without.

Helicobacter pylori-induced apoptosis in pathogenesis of gastric carcinoma.

BACKGROUND: Despite a possible role of Helicobacter pylori in gastric carcinoma (GC), its pathogenesis is not clear. There is scanty data on apoptosis in GC in relation to H. pylori and CagA antibody. Therefore, we studied gastric epithelial apoptosis in GC and non-ulcer dyspepsia (NUD) with or without H. pylori infection, and the degree of apoptosis in relation to CagA antibody status. METHODS: 20 patients each with GC and NUD were investigated for H. pylori using rapid urease test (RUT), IgG anti-H. pylori and anti-CagA antibodies, histology of endoscopically normal-looking mucosa for H. pylori, intestinal metaplasia (IM), and apoptosis using TUNEL assay. Positivity to one tissue-based (RUT or histology) and one serology based (anti-H. pylori or CagA IgG) test was taken as diagnostic of active H. pylori infection, and negative result in both tissue-based tests suggested its absence. RESULTS: Patients with GC more often had anti-H. pylori IgG (16 of 20 vs. 8 of 20; p=0.02) and a trend towards higher apoptotic index (AI) (48.6 [19.2 to 71.7] vs. 41.4 [11.7 to 63.6]; p=0.06) than NUD. AI was higher in GC (66.7 [57.5 to 71.7] vs. 32.6 [19.2 to 39.8]; p<0.0001) and NUD (58.6 [50.7 to 63.6] vs. 24.4 [11.7 to 32.2]; p<0.0001) infected with H. pylori than in those without infection. AI was also higher in GC than in NUD with H. pylori infection (66.7 [57.5 to 71.7] vs. 58.6 [50.7 to 63.6]; p=0.01). Four of the 20 patients with GC and none with NUD had IM (p=ns). There was no difference in AI in relation to CagA antibody. AI positively correlated with patients' age in presence of H. pylori infection (correlation coefficient=0.5, p=0.03) but not in its absence. CONCLUSION: Exaggerated apoptosis may play a role in H. pylori-mediated gastric diseases including carcinogenesis. AI increases with aging in patients infected with H. pylori.

Frequency of leptospirosis in patients of acute febrile illness in Uttar Pradesh.

OBJECTIVE: This study was performed to asses the disease burden of leptospirosis in and around Lucknow among patients presenting with acute febrile illness and conforming to the case definition of leptospirosis. METHODS: A total of 346 serum samples (mostly paired) and an equal number of urine samples were collected from patients presenting with acute febrile illness and fulfilling the criteria of clinical diagnosis of leptospirosis from January 2001 to December 2001. Patients attending a tertiary care hospital as well as from various communities in and around Lucknow were included in this study. All sera and urine samples were tested for the presence of IgM antibody by Leptodipstick test and by dark-field microscopy (DFM) respectively. All positive and 10% negative sera were tested at national leptospirosis reference centre at Andaman and Nicobar Islands for microagglutination test (MAT). RESULTS: IgM antibody was detected in 25/346 (7%) patients ranging in age from 9-65 years. DFM was positive in only in one case. MAT was positive in 4/17 cases tested and the prevalent serogroups were L. grippotyphosa and L. pomona in two each. Common presenting features in these patients were fever (25/25) and jaundice (17/25). History of contact with animal or water contaminated with animal urine was present in 96% cases. CONCLUSION: Leptospirosis is not uncommon in Uttar Pradesh. However larger epidemiological studies are required to know the actual disease burden. Dark-field microscopy is an insensitive method for the diagnosis of leptospirosis and is not suitable for surveillance.

Serodiagnosis of smear and culture-negative neurotuberculosis with enzyme linked immunosorbent assay for anti A-60 immunoglobulins.

Early diagnosis of neurotuberculosis (NTB), useful in prevention of mortality and morbidity, remains a challenge despite availability of several tests. An ELISA test to detect IgG and IgM antibodies against Mycobacterial antigen A-60 (Anda Biologicals, France) was done in 677 specimens; group 1 (NTB): 373 sera and 167 cerebrospinal fluid (CSF), group 2: 100 sera from healthy subjects, group 3: 17 CSF from patients undergoing neurosurgical operations for non-tubercular diseases. Anti-A 60 IgA estimation was done in 99 sera from group 1 and all 100 from group 2. Working dilutions were 1:200 for serum and 1:10 for CSF. Serum IgM and IgG anti-A 60 antibodies were more often detected in group 1 than in 2 (50% Vs 10%, p<.001). Anti-IgG and IgM antibody were detected more often in group 1 than in group 3 (33% Vs 6%, p<.001). In serum and CSF both IgM positivity was more than IgG in 2 subgroups of NTB and these are tubercular meningitis, spinal tuberculosis whereas in tuberculoma IgG positivity was more as compared to other 2 groups. Sera were more often positive than CSF (50% Vs 33%, p<.001). Of 32 patients, in whom magnetic resonance imaging (MRI) was done, 15/18 (83%) patients with suggestive findings in MRI had a positive ELISA (IgG or IgM). AntiA-60 antibody is a useful aid in the diagnosis of NTB, especially in smear and culture negative NTB where one does not have much diagnostic opportunities to choose from.