Pattern and antimicrobial sensitivity of pathogens in acute bacterial meningitis beyond neonatal period at Ahmadu Bello University Teaching Hospital (ABUTH) Shika, Zaria

The causative agents of acute bacterial meningitis vary from time to time and from place to place. In addition, changes in pathogen’s sensitivity to antibiotics in use occur. The study was undertaken to identify the pattern and susceptibility of pathogens to antibiotics among children beyond neonatal period for prompt empirical treatment of this important cause of morbidity and mortality especially in developing countries.Objective. To identify the pattern and susceptibility of pathogens in acutebacterial meningitis among children aged one month to 12 years atABUTH Shika, Zaria.Method: This was a prospective study carried out in children presentingto Emergency Pediatric Unit of ABUTH Shika, Zaria, from October1st 2005 to September 30th, 2006. Children who met the inclusion criteriafor lumbar puncture were consecutively recruited. Cerebrospinalfluid (CSF) samples were collected for microscopy, culture, sensitivity,and Latex Particle Agglutination (LPA) test. Sixty-six (66) patientssatisfied the criteria for acute bacterial meningitis and were studied.Results: The prevalence of acute bacterial meningitis in this study was6.9%. Sixty-six patients with acute bacterial meningitis were identifiedusing 3 diagnostic methods (Gram stain, culture and LPA). The 3 commonest organisms were Streptococcus pneumoniae 34 (51.5%), Haemophilus influenzae 18 (27.3%), and Neisseria meningitidis 12(11.2%). The sensitivity of the isolates to three commonly used noncephalosporin antibiotics was chloramphenicol 74.4%, penicillin38.5%, and ampicillin 2.6%. The sensitivity to the cephalosporin wascefotaxime 97.4%, and ceftriaxone 89.7% while that to Ofloxacin, aquinolone, was 100%.Conclusion: The three commonest bacterial agents causing post neonatalmeningitis were Streptococcus pneumoniae, Haemophilus influenzae,and Neisseria meningitidis. There is an increasing resistance to the three commonly used non c e p h a l o s p o r i n a n t i b i o t i c s(chloramphenicol, ampicillin and penicillin) and hence, cefotaxime orceftriaxone should be used in the empirical treatment of children withsuspected acute bacterial meningitis beyond neonatal period

Pyuria as a diagnostic test for urinary tract infection in children with sickle cell anaemia in Zaria, Nigeria

Objective: This study aimed at determining the significance of pyuria as a screening test for UTI in children with sickle cell anaemia (SCA).Methods: Two hundred and seventy-two children with SCA, aged 6 months to 15 years, were studied out of which 185 (68.0%) were in stable state and 87 (32.0%) were in crises. Their urine was assessed for microscopy culture and sensitivity. Significant pyuria and bacteriuria was determined using standard methods. Results: Significant bacteriuria was detected in 22 (8.1%) of the 272 subjects with SCA. The prevalence of significant bacteriuria was higher among those in crisis (18/87; 20.7%) than in those in steady state (4/185; 2.2%) and the difference was statistically significant (χ2 = 27.323, p = 0.001). Of the 22 SCA subjects with confirmed UTI, 19 (86.4%) had significant pyuria with a sensitivity of 86.4%, specificity of 68.8%, and positive predictive value of 19.6%. The most common bacterial isolates were Escherichia coli 11 (50.0%) while the least isolated were Salmonella typhi 1 (4.6%).Conclusion: This study indicates that pyuria as a screening test for UTI is not very specific but very sensitive necessitating a more test to be done for diagnosis of UTI.Keywords: Sickle cell anaemia, bacteriuria, pyuria, childre

Significant bacteriuria in children with sickle cell anaemia in a Nigerian tertiary hospital

Background: Urinary tract infections (UTI) in children with sickle cell anemia (SCA) may result in long term morbidity and mortality due to chronic renaldysfunction.Objectives: To evaluate the prevalence of significant bacteriuria among children with SCA and to determine their antimicrobial sensitivity patterns of isolates.Methods: Two hundred and seventy two children with SCA in steady state (n = 185) and in crises (n = 87) aged 6 months to 15 years had their urine samples screened for significant bacteriuria. The urine samples were collected aseptically and incubated aerobically at 37‹C for 24 hours.Children whose urine samples yielded .105cfu/ ml of bacteria on two consecutive cultures were regarded as having significant bacteriuria. The antimicrobial sensitivity pattern of isolates was determined.Results: Significant bacteriuria was detected in 22 (8.1%) of the 272 subjects, 156 boys (57.4%) and 116 (42.6%) girls. The prevalence of significant bacteriuria was higher among those in crisis, 18 (20.7%) than among those in steady than, 4 (2.2%) state: ƒÔ2 = 27.323, p = 0.001. The most common organism isolated was Escherichia coli, 11 (50.0%). Theantibiotic with the best sensitivity was ceftriaxone. Most organisms were resistant to the commonly used ant ibiot ic s l ike cotrimoxazole, amoxicillin and ampicillin.Conclusion: The prevalence of significant bacteriuria was found to be higher in SCA subjects in crisis (20.7%) than among those in steady state (2.2%). The most prevalent urinary pathogens were sensitive to ceftriaxone but resistant to commonly used antibiotics.Keywords: Sickle Cell Anaemia, Children, Prevalence, Significant Bacteriuria 

Analysis of mtDNA sequence variants in colorectal adenomatous polyps

Colorectal tumors mostly arise from sporadic adenomatous polyps. Polyps are defined as a mass of cells that protrudes into the lumen of the colon. Adenomatous polyps are benign neoplasms that, by definition display some characteristics of dysplasia. It has been shown that polyps were benign tumors which may undergo malignant transformation. Adenomatous polyps have been classified into three histologic types; tubular, tubulovillous, and villous with increasing malignant potential. The ability to differentially diagnose these colorectal adenomatous polyps is important for therapeutic intervention. To date, little efforts have been directed to identifying genetic changes involved in adenomatous polyps. This study was designed to examine the relevance of mitochondrial genome alterations in the three adenomatous polyps. Using high resolution restriction endonucleases and PCR-based sequencing, fifty-seven primary fresh frozen tissues of adenomatous polyps (37 tumors and 20 matched surrounding normal tissues) obtained from the southern regional Cooperative Human Tissue Network (CHTN) and Grady Memorial Hospital at Atlanta were screened with three mtDNA regional primer pairs that spanned 5.9 kbp. Results from our data analyses revealed the presence of forty-four variants in some of these mitochondrial genes that the primers spanned; COX I, II, III, ATP 6, 8, CYT b, ND 5, 6 and tRNAs. Based on the MITODAT database as a sequence reference, 25 of the 44 (57%) variants observed were unreported. Notably, a heteroplasmic variant C8515G/T in the MT-ATP 8 gene and a germline variant 8327delA in the tRNAlys was observed in all the tissue samples of the three adenomatous polyps in comparison to the referenced database sequence. A germline variant G9055A in the MT-ATP 6 gene had a frequency of 100% (17/17) in tubular and 57% (13/23) in villous adenomas; no corresponding variant was in tubulovillous adenomas. Furthermore, A9006G variant at MT-ATP 6 gene was observed at frequency of 57% (13/23) in villous adenomas only. Interestingly, variants A9006G and G9055A were absent in the villous tissue samples that were clinicopathological designated as "polyvillous adenomas". Our current data provide a basis for continued investigation of certain mtDNA variants as predictors of the three adenomatous polyps in a larger number of clinicopathological specimens

HLA-G DNA sequence variants and risk of perinatal HIV-1 transmission

BACKGROUND: HLA-G gene is a non-classical MHC class 1 molecule that is highly expressed in the trophoblast at the maternal-fetal interface. In an attempt to elucidate possible immunological mechanisms facilitating protection of infants born to human immunodeficiency virus type (HIV-1) infected mothers, we have been studying genetic variations in the coding and untranslated regions of HLA-G antigen between HIV-1-infected mothers and their infected or uninfected infants. This study investigated whether HLA-G DNA sequence variants are associated with perinatal HIV-1 transmission. RESULTS: Genomic DNA samples were obtained from a nested case-control study of 34 mother-child pairs co-enrolled in a cohort of the Perinatal AIDS Collaborative Transmission Study in New York. The samples were from two groups predominantly of African-American and Hispanic origin: In the first group, both mother and child were HIV-1-infected; in the second group, only the mother was infected while the child remained uninfected. Genotyping of HLA-G gene were performed on the extracted DNA from peripheral blood mononuclear cells using PCR based sequencing and restriction fragment-length polymorphism analyses. Among the studied HLA-G exons, dissimilarities in HLA-G DNA sequence variants between the HIV-1 non-transmitting mother child pairs were mostly observed in exon 8-3'-untranslated region at nucleotide positions T3742A, C3743T, G3777C (P = 0.001). Non-transmitting HIV-1 mother child pairs exhibited dissimilarities at nucleotide position C3743T allele with decreased risk of perinatal HIV-1 transmission, compared with HIV-1 transmitting mother-child pairs carrying this allele (odds ratio 0.02 [95% confidence interval 0.00–0.15] P = 0.00001). In addition, heterozygous dissimilarities at nucleotide positions C634G and 714 insT/G in the 5'-upstream regulatory region were observed between the mother child pairs of the HIV-1-non-transmitting group while homozygous similarities of C634C, and either 714insG/G or mother-child pairs with similar 714insT/G were observed among the transmitting group in the same region. CONCLUSION: This study identified new variants in the HLA-G gene and provides further evidence that dissimilarities in the HLA-G DNA sequence variants could influence the transmission of HIV-1 from infected mothers to their infants

Strokes in children with sickle cell disease at the National Hospital Abuja Nigeria

Background: Strokes occur in sickle cell disease (SCD), and are associated with significant morbidity and mortality.Objectives: To determine the prevalence of strokes amongst childrenwith SCD, and document the major clinical features, complications, effect of treatment with chronic transfusion therapy (CTT) and outcome.Methods: A descriptive retrospective study of SCD children with strokes seen at the National Hospital Abuja, Nigeria over a 2.5 year period from January 2009 – June 2012. Data was collected by scrutinizing case files obtained from the hospital medical records unit. Information obtained included demographic data, clinical features, packed cell volume (PCV), brain imaging, long term neurologic deficits, effect of CTT, stroke recurrence and outcome.Results: There were 31 children with strokes among 596 children with SCD documented in the register, giving a prevalence of 5.2%. Twenty six (26) case notes were retrieved. There were 12 males and 14 females, M: F ratio of 0.9:1; mean age was 6.4 years (SD 3.4) range: 1 year 7 months – 14 years; mean PCV at the time of strokes was 21.1% (SD 3.9) range 14 –29%. All (100%) had Haemoglobin SS on electrophoresis. Presentationswere convulsions 18, inability to use limbs 11, weakness of limbs 10; long term neurological deficits were hemiplegia 11, cognition loss 11. Three (3) children had no deficits. Brain imaging (Computed Tomography Scan and Magnetic Resonance Imaging) done in 16 (61.5%) children showed cerebral atrophy in 10, acute cerebral infarcts in 9, chronic cerebral infarcts in 6, acute intra cranial haemorrhage in 1 and normal imagings in 4 children. Twelve (12) children (46.2%) children had recurrences of stroke ranging in number from 1 to 4, which occurred 6 months to 3 years afterthe initial stroke. There were no statistical significant differences between the children with recurrences of stroke compared to those without regarding the age, sex, weight or PCVs p > 0.05. Fifteen (15) children (57.7%) wereenrolled in CTT. Two (2) out of 7 children (28.6%) that had regular CTT had stroke recurrence; compared to 5 out of 11 children (45.4%) with no CTT (p > 0.05). Four (4) out of 6 (66.7%) children with irregular CTT and 1 of 2 children who stopped CTT had stroke recurrence.Outcome: 17 children were alive, 7 were lost to follow up, 1 died and 1 was referred to another center.Conclusion: Strokes were an important cause of morbidity in Nigerianchildren with SCD, with major long term neurologic deficits. CTT appearedbeneficial in preventing stroke recurrences. Primary prevention strategy by Trans Cranial Doppler ultrasound studies of the cerebral arteries, with the aim of promptly initiating appropriate preventive therapy for stroke is strongly advocated.Key words: Sickle cell disease, Stroke, Children, Chronic Transfusion Therap

Paediatric HIV/AIDS seen at Ahmadu Bello University Teaching Hospital Zaria, Nigeria

Background: Paediatric HIV/AIDS is an escalating problem of frightening proportion in Nigeria, although not much has been reported from our center. Method: A retrospective study of 35 children with the diagnosis of HIV/AIDS admitted into the Emergency Paediatric Unit (EPU) of Ahmadu Bello University Teaching Hospital (ABUTH) over a 3.4 year period between March 1998 and June 2001 was undertaken in order to determine the most common mode of presentation and also the most prevalent complicating infection among these patients. Results: The mean age of the patients was 2\ub11.8 years (range 2-144 months), with the majority 30 (85.7%) aged three years and below, and a male to female ratio of 2.1:1. The probable mode of infection was vertical in 88.6% patients, through blood transfusion in 8.6%, while the source of infection could not be established in one (2.8%) due to inadequate data. Multiple symptoms at presentation were common with fever and cough being the most frequent, occurring in 82.8% of patients, followed by diarrhea in 71.4% and weight loss in 60.0% of cases. The most common signs were wasting which was found in 74.3%, generalized lymphadenopathy in 68.6% and pyrexia in 54.3%. Commonly diagnosed infections were oral candidiasis, pneumonia and tuberculosis, seen in 60.0%, 45.7% and 31.4% respectively. Nine (25.7%) out of the 35 children died, 7(20.0%) were discharged against medical advice, 19 (54.3%) improved and were discharged to follow up, but all except four have been lost to follow up. Conclusion: Paediatric HIV/AIDS is becoming a major cause of childhood morbidity and mortality in our environment. The prevention of HIV infection in women particularly in the reproductive age group would go a long way in controlling the disease in Nigeria.Introduction: l'Infection \ue0 VIH/SIDA chez les enfants est un probl\ue8me galopant et d'une ampleur effrayante au Nig\ue9ria malgr\ue9 que peu de travaux ont \ue9t\ue9 rapport\ue9s dans notre centre. M\ue9thode: Une \ue9tude r\ue9trospective sur 35 enfants ayant chacun un diagnostic de VIH/SIDA admis au service des urgences p\ue9diatriques du Centre Hospitalier Universitaire Ahmadu Bello (ABUTH ZARIA) pendant une p\ue9riode de 3,4 ans a \ue9t\ue9 r\ue9alis\ue9e en vue de d\ue9terminer le plus fr\ue9quent mode de pr\ue9sentation et la plus fr\ue9quente infection parmi ces malades. R\ue9sultats: la moyenne d'\ue2ge de ces patients \ue9tait de 2\ub11,8 ans (varie entre 2 \ue0 144 mois), avec une majorit\ue9 85,7% \ue2g\ue9e de trois (3) ans ou moins et un rapport homme: femme de 2,1:1. Le mode de transmission probable \ue9tait vertical dans 88,6% des cas, \ue0 travers une transfusion sanguine dans 8,6% des cas et dans 2,8% des cas le mode de transmission n'a pas pu \ueatre \ue9tabli \ue0 cause d'une documentation et des donn\ue9es insuffisantes. Des sympt\uf4mes multiples ont \ue9t\ue9 un mode de pr\ue9sentation commun avec fi\ue8vre et toux constituant les plus fr\ue9quents sympt\uf4mes observ\ue9s chez 29 enfants (82,8%), suivi de la diarrh\ue9e dans 71,4% des cas et perte de poids et d\ue9faillance staturo-pond\ue9rale dans 60,0% des cas. Les signes cliniques les plus fr\ue9quents sont l'amaigrissement observ\ue9 dans 74,3% des cas, les ad\ue9nopathies g\ue9n\ue9ralis\ue9es dans 68,6% des cas et la fi\ue8vre dans 54,3% des cas. Les infections commun\ue9ment diagnostiqu\ue9es chez ces patients sont les candidiases orales, les pneumonies et la tuberculose avec pour incidence respectivement de 60,0%, 45,7% et 31,4%. Neuf (9) enfants sur les 35 admis sont d\ue9c\ue9d\ue9s (25,7%), 7 cas sont sortis de l'h\uf4pital contre la volont\ue9 m\ue9dicale soit 20,0%, 19 enfants (54,3%) se sont am\ue9lior\ue9s et sortis de l'h\uf4pital avec un suivi r\ue9gulier parmi lesquels quatre (4) \ue9taient perdus de vue. Conclusion: L'infection \ue0 VIH/SIDA en p\ue9diatrie devient de plus en plus une cause majeure de morbidit\ue9 et de mortalit\ue9 dans notre environnement. La pr\ue9vention de l'infection \ue0 VIH chez les femmes particuli\ue8rement en \ue2ge de procr\ue9er contribuerait positivement dans la lutte contre cette maladie au Nig\ue9ria

Limited clinical relevance of mitochondrial DNA mutation and gene expression analyses in ovarian cancer

<p>Abstract</p> <p>Background</p> <p>In recent years, numerous studies have investigated somatic mutations in mitochondrial DNA in various tumours. The observed high mutation rates might reflect mitochondrial deregulation; consequently, mutation analyses could be clinically relevant. The purpose of this study was to determine if mutations in the mitochondrial D-loop region and/or the level of mitochondrial gene expression could influence the clinical course of human ovarian carcinomas.</p> <p>Methods</p> <p>We sequenced a 1320-base-pair DNA fragment of the mitochondrial genome (position 16,000-750) in 54 cancer samples and in 44 corresponding germline control samples. In addition, six transcripts (<it>MT-ATP6, MT-CO1, MT-CYB, MT-ND1</it>, <it>MT-ND6</it>, and <it>MT-RNR1</it>) were quantified in 62 cancer tissues by real-time RT-PCR.</p> <p>Results</p> <p>Somatic mutations in the D-loop sequence were found in 57% of ovarian cancers. Univariate analysis showed no association between mitochondrial DNA mutation status or mitochondrial gene expression and any of the examined clinicopathologic parameters. A multivariate logistic regression model revealed that the expression of the mitochondrial gene <it>RNR1 </it>might be used as a predictor of tumour sensitivity to chemotherapy.</p> <p>Conclusion</p> <p>In contrast to many previously published papers, our study indicates rather limited clinical relevance of mitochondrial molecular analyses in ovarian carcinomas. These discrepancies in the clinical utility of mitochondrial molecular tests in ovarian cancer require additional large, well-designed validation studies.</p

High Level of Soluble HLA-G in the Female Genital Tract of Beninese Commercial Sex Workers Is Associated with HIV-1 Infection

Most HIV infections are transmitted across mucosal epithelium. Understanding the role of innate and specific mucosal immunity in susceptibility or protection against HIV infection, as well as the effect of HIV infection on mucosal immunity, are of fundamental importance. HLA-G is a powerful modulator of the immune response. The aim of this study was to investigate whether soluble HLA-G (sHLA-G) expression in the female genital tract is associated with HIV-1 infection.Genital levels of sHLA-G were determined in 52 HIV-1-uninfected and 44 antiretroviral naïve HIV-1-infected female commercial sex workers (CSWs), as well as 71 HIV-1-uninfected non-CSW women at low risk of exposure, recruited in Cotonou, Benin. HIV-1-infected CSWs had higher genital levels of sHLA-G compared with those in both the HIV-1-uninfected CSW (P = 0.009) and non-CSW groups (P = 0.0006). The presence of bacterial vaginosis (P = 0.008), and HLA-G*01:01:02 genotype (P = 0.002) were associated with higher genital levels of sHLA-G in the HIV-1-infected CSWs, whereas the HLA-G*01:04:04 genotype was also associated with higher genital level of sHLA-G in the overall population (P = 0.038). When adjustment was made for all significant variables, the increased expression of sHLA-G in the genital mucosa remained significantly associated with both HIV-1 infection (P = 0.02) and bacterial vaginosis (P = 0.03).This study demonstrates that high level of sHLA-G in the genital mucosa is independently associated with both HIV-1 infection and bacterial vaginosis