Evaluation of nitrate reductase assay for early detection of multi and extensively drug resistance tuberculosis in our setup

Objective: To evaluate the performance of nitrate reductase assay on smear positive pulmonary specimens for detection of multi and extensively drug resistant tuberculosis simultaneously. Study Design: Cross-sectional analytical study. Place and Duration of Study: Microbiology Department, Armed Forces Institute of Pathology, Rawalpindi from June to December 2016

Methodology: Smear positive pulmonary samples were processed both by nitrate reductase method on Lowenstein Jenson medium and also inoculated on gold standard Bactec MGIT 960 TB system. All the specimens were first digested and decontaminated according to standard protocol before inoculation

Results: Out of total 76 samples, three did not give color and, therefore, were excluded from the final data analysis. Among the remaining 73 samples, mycobacterial index was: 28 specimens were having 1+ [1-9 bacilli/100 fields], 26 samples were 2+ [1-9 bacilli/ field], and 19 samples were having 3+ index [>9 bacilli/field]. The respective sensitivity and specificity were 84% and 100% for isoniazid [INH]; 82% and 100% for rifampin [RIF]; 67% and 100% for amikacin [AK]; and both 100% for ofloxacin [OFX]. Overall agreement in case of INH, RIF, AK, and OFX was 94.5%, 97.2%, 98.6% and100%, respectively. Overall average agreement was 97.5%

Conclusion: Nitrate reductase assay is a reliable, low cost and accurate method that can be used for early for diagnosis of multi and extensively drug resistant tuberculosis

Clinico-haematological features of paroxysmal nocturnal haemoglobinuria

The aim of this study was to determine the frequency of various clinico-haematological features in patients suffering from paroxysmal nocturnal haemoglobinuria [PNH]. It was an observational study carried out from October 2008 - January 2016. All the patients of PNH, diagnosed on the basis of clinical and laboratory findings and confirmed by CD55 and CD59 deficiency on red cells by means of flow cytometry, were included in the study. A total of 22 patients were diagnosed which included 18 [81.8%] males and 4 [18.1%] females. Median age was 27 years. Pallor, fever, fatigability and haemoglobinuria were the most common clinical features. Pancytopenia was seen in 13 [59.09%] and hypocellular marrow was found in 14 [63.6%] patients. One patient presented with Budd Chiari syndrome

Neuroendocrine carcinoma of gall bladder: a rare presentation with review of literature

Neuroendocrine tumors are the rarest tumors of gallbladder, The most aggressive variant is neuroendocrine carcinoma which presents in about 0.5% of all gallbladder carcinomas and 0.2% of all neuroendocrine tumors. It seems possible that survival rates can be improved by utilizing wide surgical resection combined with chemotherapy. We report a case of neuroendocrine carcinoma of gall bladder in a 20-year old female patient. In present case, the etiology was not known as patient did not have cholelithiasis or any symptoms related to chronic inflammation. Our extensive search of indexed literature shows that our patient was the youngest patient with this disease so far

Dual infection by burkholderia cepacia and pseudomonas putida in an infective endocarditis case

Infective endocarditis is rarely caused by Burkholderia cepacia

Pseudomonas putida has not been reported to cause infective endocarditis so far. This is the first case of infective endocarditis being reported, that is caused by Pseudomonas putida and Burkholderia cepacia in an immunocompetent host with no predisposing factors. Aortic valve replacement surgery was carried out and antibiotics were given, to which the patient responded well and recovered

Outcome of facility based management on severely malnourished children in district Ghotki and Larkana, Sindh

Background: A relatively effective method for the management of acute malnutrition in severely malnourished < 5 year children is their management according to WHO guidelines in stabilization centers where they are admitted with medical complications

Objectives: To improve the nutritional status of complicated malnourished children before their discharge from stabilization centers. Study design, settings and duration: Hospital based, exploratory study conducting in stabilization centers at Ghotki and Larkana. Sindh from September to November 2015

Subjects and Methods: By using universal sampling technique, all children who were enrolled and completed their treatment in October 2015 in the stabilization centers at Ghotki and Larkana, Sindh were included in the study. The parameters recorded included weight, length/height, mid upper arm circumference, heamoglobin level [both at the time of admission and discharge] while for nutritional rehabilitation, therapeutic milk F75 and F100 were given

Results: Total 78 children were enrolled for treatment in stabilization centers. Their average length of stay in stabilization center was 7.1 days. The average weight gain was found to be 9.028 [+/- 3.956]gm/kg/day which was statistically significant. The mean gain in the mid upper arm circumference, weight for height, body mass index and hemoglobin level at the time of discharge were also statistically significant [p < 0.000]. Height did not show any significant change

Conclusion: The findings of this study indicate that management of severally malnourished children in accordance with the international standards resulted in significant improvement of nutritional status of children

Outcome of allogeneic haematopoietic stem cell transplantation in aplastic Anaemia

To analyze factors associated with survival, rejection and graft versus host disease in aplastic anaemia patients undergoing allogeneic haematopoietic stem cell transplantation [SCT] from HLA matched sibling donors. Analytical study. Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan from July 2001 to June 2010. Consecutive aplastic anaemia [AA] patients undergoing haematopoietic stem cell transplantation from HLA-matched sibling donors at this centre were included in this study. Potential factors affecting overall survival, rejection, disease-free survival and graft versus host disease were analyzed. Survival analysis was done by Kaplan-Meier method. Cox regression model was applied for multivariate analysis. Ninety male and thirty-five female patients with AA were included in the study. Median age was 18 years. Conditioning regimens used were cyclophosphamide [Cy] plus antilymphocyte globulin [ALG] or antithymocyte globulin [ATG], fludarabine [FLU] +Cy+ATG, Campath 1-H +Cy in 89, 30 and 6 cases respectively. GVHD prophylaxis used was ciclosporin [CSA] plus prednisolone and short methotrexate in 81 while 44 received CSA plus prednisolone. At a median follow-up of 1185 days OS and DFS were 84% and 78% respectively. Factors associated with better OS were male sex, Flu/Cy/ATG conditioning and use of bone marrow as stem cell source. Flu/Cy/ATG conditioning regimen, bone marrow as stem cell source and CSA, prednisolone and short methotrexate regimen were associated with better survival in AA

Hematopoietic stem cell transplantation in the eastern mediterranean region [EMRO] 2008-2009: report on behalf of the eastern mediterranean bone marrow transplantation [EMBMT] group

The Eastern Mediterranean Bone Marrow Transplantation [EMBMT] Group has accumulated over 25 years of data and experience in hematopoietic stem cell transplantation [HSCT], most particularly in he-moglobinopathies, severe aplastic anemia [SAA], and inherited metabolic and immune disorders, in addition to hematologic malignancies peculiar to the region and where recent updates in trends in activities are warranted. To study trends in HSCT activities in the World Health Organization-Eastern Mediterranean [EM] region surveyed by EMBMT between 2008 and 2009. STUDY DESIGN: Retrospective analysis of the survey data, mainly of the cumulative number of transplants, types of transplants [autologous vs. allogeneic], types of conditioning as myeloablative [MAC] vs. reduced intensity conditioning [RIC] and trends in leukemias, hemo-globinopathies, SAA, inherited bone marrow failure syndromes amongst others. Fourteen teams from ten Eastern Mediterranean Region Organization [EMRO] countries reported their data [100% return rate] to the EMBMT for the years 2008-2009 with a total of 2608 first HSCT [1286 in 2008; 1322 in 2009]. Allogeneic HSCT represented the majority [63%] in both years. The main indications for allogeneic HSCT were acute leukemias [732; 44%], bone marrow failure syndromes [331, 20%], hemoglobinopathies [255; 15%] and immune deficiencies [90; 5%]. There was a progressive increase in the proportions of chronic myeloid leukemia [CML] cases transplanted beyond the first chronic phase [3; 7% of all CML cases in 2008 vs 13; 29% in 2009]. The main indications for autologous transplants were plasma cell disorders [345; 36%] Hodgkin disease [256; 27%], non-Hodgkin lymphoma [207; 22%] and solid tumors [83; 9%]. RIC continued to show a progressive increase over the years [7% in 2007, 11% in 2008 and 13% in 2009], yet remained relatively low compared to contemporary practices in Europe published by EBMT. The vast majority [95%] of allo-HSCT sources were from sibling donors with a continued dominance of peripheral blood [PB] [1076; 63%], while cord blood transplant [CBT] increased to 83 [5% of allo-HSCT], matched unrelated donor [MUD] remained underutilized [1; 0%] and there were no haploidentical transplants reported. Large centers with >50 HSCT/year showed a plateau of the total number of allo-HSCT over the last 5 years that may be related to capacity issues and needs further study. There is an overall increased rate of HSCT in the EMRO region with a significant increase in utilization of CBT and allogeneic PB-HSCT as a valuable source. However, further research on outcome data and development of regional donor banks [CB and MUD] may help facilitate future planning to satisfy the regional needs and increase collaboration within the group and globally

Frequency of ocular manifestations of chronic graft versus host disease

With the advancement of techniques for haematopoietic cell transplantation, the number of transplant survivors is increasing rapidly and so are the chances of chronic graft versus host disease [cGVHD]. The ocular manifestations of this disease have not been explored in our local population. This study was conducted to determine the frequency of ocular complications in cases of cGVHD following successful bone marrow transplantation. Twelve diagnosed cases of cGVHD were evaluated from June 2008 to March 2009 and there ocular manifestations were noted especially the ocular surface disorders, using double staining method with fluorescein and rose-bengal. Nine patients [75%] were having dry eyes, 7 [58.3%] with mebomian glands dysfunction, 4 [33%] with acute conjunctivitis, 2 [16.7%] with bilateral lacrimal canalicular occlusion, and 1 [8.3%] each of bilateral posterior subcapsular cataract, unilateral sterile corneal epithelial defect, anterior uveitis, retinal haemorrhages and disc oedema. The higher frequency of dry eyes along with other ocular manifestations in patients of cGVHD suggests the need of close ophthalmic monitoring in all such cases

Vancomycin resistant enterococcal sepsis in an acute myeloid leu kemic patient

Neutropenic fever is an important cause of morbidity and mortality during therapy of acute myeloid leukemia. Patients with acute myeloid leukemia are at increased risk of acquiring vancomycin resistant enterococcal infection and its treatment remains problematic. Vancomycin therapy for more than 7 days is usually associated with inducible vancomycin-resistant enterococcal infections. We report a case of vancomycin resistant enterococcal sepsis in a patient of acute myeloid leukemia

Relapsed diffuse large B-cell lymphoma treated by reduced-intensity allogeneic stem cell transplantation with donor lymphocyte infusion

A 42 years old male with relapsed diffuse large B-cell lymphoma was given second-line chemotherapy followed by reduced intensity allogeneic stem cell transplantation from HLA matched brother. Twelve weeks posttransplant, his disease relapsed evidenced by the appearance of lymphoma cells in the peripheral blood and declining donor chimerism. Donor lymphocyte infusion was given that induced complete lymphoma remission. The patient is well 3 years posttransplant with his disease in complete remission

Pulmonary cryptosporidiosis in a bone marrow transplant recepient

Cryptosporidium, a protozoan parasite of Phylum Apicomplexa, causes acute short term intestinal infection in immunocompetent individuals. However, in immunocompromised patients, it causes prolonged and life threatening watery diarrhea, rarely with extra-intestinal involvement. We present a case of Cryptosporidium parvum with pulmonary involvement who was managed with azithromycin and co-trimoxazole combination. This is the second reported case in the world in HIV negative patient undergoing bone marrow transplantation

Bilateral lacrimal bicanalicular obstruction in chronic graft versus host disease

Bone Marrow transplantation has been increasingly used for the treatments of various blood cancers for last two decades. As a complication, a variable number of patients develop Chronic Graft Verses Host Disease [cGVHD] six to eight months later. Ocular involvement occurs in 60 to 80% of patients with cGVHD. Though dry eye sensation is the most common ocular symptom of cGVHD we report here a case of excessive watering due to bilateral lacrimal bicanalicular obstruction secondary to ocular involvement in cGVHD along with onset of dry eye features

Post-transplant outcome in chronic myeloid leukaemia

To determine post-transplant survival in chronic myeloid leukaemia patients undergoing allogeneic stem cell transplant. Longitudinal, descriptive study. Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan, between April 2002 and August 2007. All patients of chronic myeloid leukaemia in chronic phase having HLA identical donor and age under 55 years, normal hepatic, renal and cardiac functions with good performance status were selected. Patients in accelerated phase or blast crisis, poor performance status, impaired hepatic, renal, cardiac functions or pregnancy were excluded. Survival was calculated from the date of transplant to death or last follow-up according to Kaplan-Meier and Cox [proportional hazard] regression analysis methods. Thirty seven patients with chronic myeloid leukaemia underwent allogeneic stem cell transplant from HLA identical sibling donors. Thirty two patients were male and five were females. Median age of patients was 28 years. All patients and donors were CMV positive. Post-transplant complications encountered were acute GvHD [Grade II-IV] [n=13, 35.1%], chronic GvHD in 18.9% [n=7], Veno Occlusive Disease [VOD] in 5.4% [n=2], acute renal failure in 2.7% [n=1], haemorrhagic cystitis in 2.7% [n=1], bacterial infections in 40.5% [n=15], fungal infections in 16.2% [n=6], CMV infection in 5.4% [n=2], tuberculosis in 5.4% [n=2], Herpes zoster infection 2.7% [n=1] and relapse in 2.7% [n=1]. Mortality was observed in 27% [n=10]. Major causes of mortality were GvHD, VOD, septicemia, CMV infection and disseminated Aspergillosis. Overall Disease Free Survival [DPS] was 73% with a median duration of follow-up of 47.4 +/- 12 months. DPS was 81% in standard risk and 54.5% in high-risk group. Results of allogeneic stem cell transplant in standard risk group CML patients were good and comparable with other international centres, however, results in high-risk CML patients need further improvement, although, number of patients in this group is small

Comparison of anthracycline-based combination chemotherapy with or without all-trans retinoic acid in acute promyelocytic leukemia

To compare survival in Acute Promyelocytic Leukemia [APL] patients treated with or without All-Trans Retinoic Acid [ATRA]. Longitudinal, comparative study. The Armed Forces Bone Marrow Transplant Centre [AFBMTC], Rawalpindi, Pakistan from May 2001 to April 2007. All consecutive newly diagnosed patients of acute promyelocytic leukemia, treated at Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan, between May 2001 and April 2007, were included and given chemotherapy according to availability of ATRA. Diagnosis was confirmed on morphology/ karyotyping/ molecular analysis. Eligibility criteria included confirmed morphologic diagnosis and/or by demonstration of t[15;17] and/or PML/RAR alpha re-arrangement, no prior chemotherapy, normal hepatic and renal function, Eastern Cooperative Oncology Group [ECOG] performance status of 0 - 2 and no contraindications to ATRA [history of sensitivity to Vit. A or other retinoids]. All patients having history of cardiac failure [LVEF < 50] and arrhythmias, ECOG performance status 3 and 4, relapse / refractory disease, ALT twice normal values, serum creatinine > 150 micro mol/L and pregnancy were excluded from this study. Survival was calculated from the date of chemotherapy to death or last follow-up according to Kaplan-Meier and Cox [Proportional hazard] regression analysis methods. During the 6 years study period, 31 newly diagnosed patients with acute promyelocytic leukemia received treatment at AFBMTC. Seventeen patients received anthracycline-based remission induction and consolidation chemotherapy, while 14 received ATRA-based remission induction, consolidation and by two years maintenance therapy. Overall Survival [OS], Disease Free Survival [DFS] and mortality were 29.4%, 29.4% and 70.6% respectively in 17 patients who received anthracycline based chemotherapy, whereas in patients who received ATRA-based chemotherapy OS, DFS and mortality was 71.4%, 64.2% and 28.6% respectively. Major causes of mortality were septicemia and chemotherapy related toxicity. Response to ATRA-based chemotherapy in patient cohort was better as compared with anthracycline based chemotherapy [71.4% vs. 29.4%] in terms of survival and mortality

Pneumocystis carinii and Trichosporon beigelii pneumonia following allogeneic haemopoeitic stem cell transplantation

Pneumocystis Carinii and Trichosporon beigelii are opportunistic infections in immunocompromised patients. We report a case of a young lady who underwent haemopoeitic stem cell transplantation for relapsed acute lymphoblastic leukemia. This 25 years old female developed fever, dry cough and rapidly progressive dyspnoea during post transplant neutropenia and was found to be suffering from Pneumocystis carinii pneumonia. She was successfully treated with Co-trimoxazole. The patient again presented with similar symptoms on day 55 post transplant. This time Trichosporon beigelii was isolated from bronchoalveolar lavage and she responded to prompt antifungal therapy. Other complications encountered during the subsequent course were extensive subcutaneous emphysema and spontaneous pneumothorax that required chest intubation and brief hospitalization. The patient is presently nine months post transplant and is asymptomatic

Clinicohaematological features of iron deficiency anaemia in children between 1-5 years of age

To study the clinicohaematological features of iron deficiency anaemia in children between 1-5 years of age. Children between 1-5 years of age suffering from iron deficiency anaemia were included in this study. Personal and family data was obtained for each child. Height and weight were recorded and degree of malnutrition determined as per modified Gomez classification. Samples for blood counts were taken in K[3]EDTA and complete blood counts were performed. Differential leucocyte count and RBC morphology was done by visual reviewing of slides. Ferritin was measured for each patient. Cut off value for defining anaemia was set at 11 g/dl as per WHO criteria. SPSS computer software was used for mean and SD calculations. Different clinical features were cross tabulated with measured Hb levels to evaluate their correlation. Chi-Square test was used to see the significant level. A total of 191 patients were studied with mean age of 1.9 [SD 0.89] years. Male to female ratio was 2:1. Overall, 121[63.3%] children had varying degrees of malnutrition. Mean Hb was 8.2 g/dl [SD 1.3]. Majority of the patients [62.3%] had Hb between 6.1-8 g/dl. Sixty patients had Hb>8 g/dl while 12 had Hb

Graft versus host disease in allogeneic stem cell transplantation - 3 l/2 years experience

To evaluate the frequency and outcome of graft versus host disease after allogeneic stem cell transplant in haematological disorders at Armed Forces Bone Marrow Transplant Centre, Rawalpindi from July 2001 to December 2004. Eighty-six patients with various haematological disorders namely aplastic anaemia [n=32], b-Thalassaemia [n=25], CML [n=22] ALL [n=3], AML [n=l] Fanconi's anaemia [n=2], and Gaucher's disease [n=l], underwent allogeneic stem cell transplantation. All patients received cyclosoprin, prednisolone and short course of methotrexate as GvHD prophylaxis. The patients who developed acute GvHD > grade-II or chronic extensive GvHD received steroids at a starting dose of 2 mg/kg body weight along with gradual increase in cyclosporine dosage [max dose 12.5 mg/kg]. The overall incidence of acute GvHD grade-II to IV was 44.2% [n=38/86] where as the incidence of chronic extensive GvHD was 14% [n=12/86]. Acute GvHD was 68% [n=17/25] in B-Thalassaemia, 50% [n=ll/22] in CML, 50% [n=2/4] in Acute Leukaemias and 25% [n=8/32] in Aplastic Anaemia. Chronic GvHD was 25% [n=l/4] in Acute Leukaemias, 18.8% [n=6/32] in Aplastic Anaemia, 18.2% [n=4/22] in CML and 4% [n=l/25] in B-Thalassaemia. The overall survival in acute GvHD was 84.2% [n=32] where as the overall survival in chronic GvHD was 50% [n=6]. The overall mortality in acute GvHD was 15.8% [n=6] and 50% in chronic GvHD [n=6]. The morbidity and mortality due to severe acute and chronic GvHD remains high despite standard prophylaxis against GvHD. New strategies are needed to prevent and treat GvHD

Frequency of tuberculosis in haematological malignancies and stem cell transplant recipients

To assess magnitude of tuberculosis [TB] in patients suffering from various haematological malignancies and stem cell transplant [SCT] recipients. Descriptive study. Oncology Department, Combined Military Hospital, Rawalpindi, and Armed Forces Bone Marrow Transplant Centre, Rawalpindi, from July 2001 to December 2002. Patients suffering from various haematological malignancies treated between July 2001 and December 2002 were included in the study. The hospital records and out-patient follow-up charts were reviewed for demographic information, diagnosis, clinical presentation, laboratory investigations, radiological and pathological examinations, sites involved in TB, methods of diagnosis, number and type of anti-tuberculosis drugs given and response to treatment. During the study period a total of 213 [including 25 allogeneic stem cell transplant [SCT] recipients] patients with different haematological disorders were treated. Out of these, 34, including 4 SCT recipients developed tuberculosis. Overall frequency of TB was 16%. Median age of TB patients was 33.5 years [range 8-80 years]. Median time between diagnosis of haematological disorders and tuberculosis was 21 weeks. Sites of involvement by TB were lung [18], disseminated [6], lymph node [5], pleura [2], spine [2] and pericardium [1]. Three of the patients died of TB; one undiagnosed, second with multi-drug resistant TB and the third soon after the start of anti-tuberculosis treatment while remaining 31 cases responded to anti-tuberculosis treatment. Tuberculosis is a major problem in immunocompromised patients and there is need to establish guidelines for TB chemoprophylaxis in our setup

Posttransplant Guillain Barre Syndrome

This case report describes a patient with severe aplastic anaemia, who developed Guillain Barre Syndrome [GBS] 10 weeks after allogeneic haematopoietic stem cell transplantation [HSCT] from HLA-matched siblingíyounger sister. GBS was preceded by pneumonia, herpes labialis and oral candidiasis a week earlier. Treatment with ventilatory management, intravenous human immunoglobulin [IVIg] and antimicrobials resulted in smooth recovery in thirty-one days