Nina Langeland

Population-Based Hematologic and Immunologic Reference Values for a Healthy Ugandan Population

ABSTRACT To assess the validity of the reference values for hematologic and immunologic indices currently used in Africa, we evaluated blood samples from 3,311 human immunodeficiency virus (HIV)-negative Ugandans aged 1 week to 92 years. Erythrocyte, hemoglobin, and hematocrit levels and mean corpuscular volume all significantly increased with age (P < 0.001) and were independent of gender until the age of 13 years, after which the levels were higher in males than in females (P < 0.001). White blood cell, neutrophil, lymphocyte, basophil, and monocyte counts significantly declined with age until the age of 13 years (P < 0.001), with no differences by gender, while platelet counts declined with age (P < 0.001) and showed differences by gender only among adults older than age 24 years. CD4+- and CD8+-cell counts declined with age until the age of 18 years; thereafter, females had higher counts than males. The absolute values for many of these parameters differed from those reported for populations outside Africa, suggesting that it may be necessary to develop tables of reference values for hematologic and immunologic indices specific for the African population. This may be particularly important with regard to CD4+-cell counts among children because significant differences in absolute and percent CD4+-cell counts exist between the values for Western populations and the values for the population evaluated in our study. These differences could influence the decision to initiate antiretroviral therapy among children infected with HIV.

Randomized comparison of 12 or 24 weeks of peginterferon α‐2a and ribavirin in chronic hepatitis C virus genotype 2/3 infection

Previous trials investigating the efficacy of treatment durations shorter than the standard of 24 weeks for chronic hepatitis C virus (HCV) genotype 2/3 infections have yielded discordant results. The aims of this investigator‐initiated phase III study were to compare the efficacy of 12 or 24 weeks of treatment and to identify patients suitable for short‐term therapy. Three hundred eighty‐two genotype 2/3–infected patients [intention‐to‐treat (ITT) population] at 31 centers in Denmark, Finland, Norway, and Sweden were randomized to 12 or 24 weeks of peginterferon α‐2a (180 μg/week) plus ribavirin (800 mg/day). Twelve weeks of therapy was inferior to 24 weeks in the ITT population (sustained viral response [SVR] rates: 59% versus 78%, P < 0.0001) and in the subgroups of patients infected with genotype 2 (56% versus 82%, P = 0.006) or 3 (58% versus 78%, P = 0.0015). These differences were observed regardless of the fibrosis stage. Age and HCV‐RNA levels on days 7 and 29 were independent predictors of SVR. Short‐term treatment was useful in patients < 40 years old, especially if HCV‐RNA was undetectable on day 29, and also in patients ≥ 40 years old, provided that HCV‐RNA was below 1000 IU/mL on day 7 in addition to being undetectable on day 29. If neither of these two criteria were met for patients ≥ 40 years old, 24 weeks of therapy was superior (P < 0.0001). Conclusion: Peginterferon/ribavirin treatment for 12 weeks in HCV genotype 2/3 infection is overall inferior to 24 weeks of treatment but may be useful in some patients with a rapid initial clearance of virus. (HEPATOLOGY 2008.)

High Rate of Fatal Cases of Pediatric Septicemia Caused by Gram-Negative Bacteria with Extended-Spectrum Beta-Lactamases in Dar es Salaam, Tanzania

ABSTRACT Extended-spectrum beta-lactamases (ESBLs) were present in high proportions of Escherichia coli (25% [9 of 36]) and Klebsiella pneumoniae isolates (17% [9 of 52]) causing pediatric septicemia at a tertiary hospital in Tanzania. Patients with septicemia due to ESBL-producing organisms had a significantly higher fatality rate than those with non-ESBL isolates (71% versus 39%, P = 0.039). This is the first report of the CTX-M-15 genotype of ESBLs on the African continent and the first observation of SHV-12 genotype in an isolate of Salmonella enterica serotype Newport.

Giardiasis – why do the symptoms sometimes never stop?

Although giardiasis is considered by most medical practitioners to be an easily treated infection, prolonged symptoms due to, or following, Giardia duodenalis infection can have a significant impact on quality of life. Symptom recurrence, including abdominal symptoms and fatigue, can result from re-infection, treatment failure, disturbances in the gut mucosa or post-infection syndromes. In developed countries, these sequelae can have an enormous impact on quality of life; in developing countries, particularly in children, they add yet another burden to populations that are already disadvantaged. Here, we outline current knowledge, based on individual case sequelae from sporadic infections, observations of population effects following outbreaks and studies of phenotypic and genotypic diversity between morphologically identical isolates of parasites. We also raise further questions, looking for clues as to why giardiasis sometimes becomes an intrusive, long-term problem.

A large community outbreak of waterborne giardiasis-delayed detection in a non-endemic urban area.

BackgroundGiardia is not endemic in Norway, and more than 90% of reported cases acquire the infection abroad. In late October 2004, an increase in laboratory confirmed cases of giardiasis was reported in the city of Bergen. An investigation was started to determine the source and extent of the outbreak in order to implement control measures.MethodsCases were identified through the laboratory conducting giardia diagnostics in the area. All laboratory-confirmed cases were mapped based on address of residence, and attack rates and relative risks were calculated for each water supply zone. A case control study was conducted among people living in the central area of Bergen using age- and sex matched controls randomly selected from the population register.ResultsThe outbreak investigation showed that the outbreak started in late August and peaked in early October. A total of 1300 laboratory-confirmed cases were reported. Data from the Norwegian Prescription Database gave an estimate of 2500 cases treated for giardiasis probably linked to the outbreak. There was a predominance of women aged 20–29 years, with few children or elderly. The risk of infection for persons receiving water from the water supply serving Bergen city centre was significantly higher than for those receiving water from other supplies. Leaking sewage pipes combined with insufficient water treatment was the likely cause of the outbreak.ConclusionLate detection contributed to the large public health impact of this outbreak. Passive surveillance of laboratory-confirmed cases is not sufficient for timely detection of outbreaks with non-endemic infections.

Development of functional gastrointestinal disorders after Giardia lamblia infection

BackgroundFunctional gastrointestinal disorders (FGID) may occur following acute gastroenteritis. This long-term complication has previously not been described after infection with the non-invasive protozoan Giardia lamblia. This study aims to characterize persistent abdominal symptoms elicited by Giardia infection according to Rome II criteria and symptoms scores.MethodsStructured interview and questionnaires 12–30 months after the onset of Giardia infection, and at least 6 months after Giardia eradication, among 82 patients with persisting abdominal symptoms elicited by the Giardia infection. All had been evaluated to exclude other causes.ResultsWe found that 66 (80.5%) of the 82 patients had symptoms consistent with irritable bowel syndrome (IBS) and 17 (24.3%) patients had functional dyspepsia (FD) according to Rome II criteria. IBS was sub classified into D-IBS (47.0%), A-IBS (45.5%) and C-IBS (7.6%). Bloating, diarrhoea and abdominal pain were reported to be most severe. Symptoms exacerbation related to specific foods were reported by 45 (57.7%) patients and to physical or mental stress by 34 (44.7%) patients.ConclusionIn the presence of an IBS-subtype pattern consistent with post-infectious IBS (PI-IBS), and in the absence of any other plausible causes, we conclude that acute Giardia infection may elicit functional gastrointestinal diseases with food and stress related symptoms similar to FGID patients in general.

Identification of diarrheagenic Escherichia coli isolated from infants and children in Dar es Salaam, Tanzania

BackgroundRelatively few studies have been done in Tanzania to detect and classify diarrheagenic Escherichia coli (DEC) strains among children with diarrhea. This study aimed at investigating DEC among children in Dar es Salaam aged less than five years hospitalized due to acute/persistent diarrhea.MethodsDEC were isolated from stool samples collected from two hundred and eighty children with acute/persistent diarrhea at Muhimbili National Hospital and Ilala and Mwananyamala Municipal Hospitals in Dar es Salaam. A multiplex PCR system method was used to detect a species specific gene for E.coli and ten different virulence genes for detection of five pathogroups of DEC namely enteroaggregative- (EAEC), enteropathogenic- (EPEC), enterotoxigenic- (ETEC), enteroinvasive- (EIEC) and enterohemorghagic- Escherichia coli (EHEC).ResultsSixty-four patients (22.9%) harbored DEC. Forty-one of them (14.6%) were categorized as EAEC. Most of the EAEC (82.9%) were classified as typical EAEC possessing the aggR gene, and 92.6% carried the aat gene. Isolates from thirteen patients were EPEC (4.6%) and most of these (92.3%) were typical EPEC with both eae and bfpA genes. Ten isolates were identified as ETEC (3.6%) with only the heat stable toxin; either st1a or st1b but not both. Age wise, EAEC and EPEC were significantly more prevalent among the age group 0–6 months (p < 0.05). Genes for EHEC (stx1 and stx2) and EIEC (ial) were not detected in this study group.ConclusionThe results show a high proportion of DEC among Tanzanian children with diarrhea, with typical EAEC and typical EPEC predominating. The use of primers for both variants of ST1 (st1a and st1b) increased the sensitivity for detection of ETEC strains.

Evaluation of Depression as a Risk Factor for Treatment Failure in Chronic Hepatitis C

The Major Depression Inventory (MDI) was used to estimate the value of routine medical interviews in diagnosing major depression among patients receiving peginterferon alfa‐2a and ribavirin therapy for chronic hepatitis C virus (HCV) infection (n = 325). According to criteria from the MDI and Diagnostic and Statistical Manual of Mental Disorders (DSM‐IV), 19 patients (6%) had major depression at baseline. An additional 114 (37%) developed depression while on HCV combination therapy, with baseline MDI score and female sex independently predicting the emergence of major depression during treatment in a multivariate analysis. Only 36 (32%) of the 114 patients developing major depression according to MDI/DSM‐IV criteria were correctly diagnosed during routine medical interviews. The emergence of major depression frequently led to premature discontinuation of peginterferon/ribavirin therapy, and an on‐treatment MDI score increment exceeding 30 points (i.e., a validated marker of idiopathic DSM‐IV major depression) was correlated with impaired outcome of HCV therapy (P = 0.02). This difference was even more pronounced among patients with an on‐treatment increase in MDI score greater than 35 points (P = 0.003). Conclusion: We conclude that (1) depressive symptoms among patients undergoing HCV therapy are commonly overlooked by routine clinical interviews, (2) the emergence of depression compromises the outcome of HCV therapy, and (3) the MDI scale may be useful in identifying patients at risk for treatment‐induced depression. (HEPATOLOGY 2010;)

Application of Genotyping during an Extensive Outbreak of Waterborne Giardiasis in Bergen, Norway, during Autumn and Winter 2004†

ABSTRACT During the autumn and winter of 2004 and 2005, an extensive outbreak of waterborne giardiasis occurred in Bergen, Norway. Over 1,500 patients were diagnosed with giardiasis. Analysis of water from the implicated source revealed low numbers of Giardia cysts, but the initial contamination event probably occurred up to 10 weeks previously. While sewage leakage from a residential area is now considered to be the probable source of contamination, during the episode waste from one particular septic tank was thought to be a possible source. Genotyping of cysts from the septic tank demonstrated that they were assemblage A cysts, although the sequences were not identical to any previously published sequences. For the β-giardin gene, the closest published subgenotype was subgenotype A3; for the gdh gene, the closest published subgenotype was subgenotype A2. Genotyping of cysts from 21 patient samples revealed that they were assemblage B cysts; thus, the septic tank was unlikely to be the contamination source. Sequencing of the β-giardin and gdh genes from patient samples and a comparison of the sequences gave complex results. For the β-giardin gene, three isolates had sequences identical to subgenotype B3 sequences. However, other isolates had between one and four single-nucleotide polymorphisms (SNPs). For the gdh gene, none of the sequences were identical to the sequence published for subgenotype B3, and the sequences had between one and three SNPs. One isolate, which was identical to subgenotype B3 at the β-giardin gene, was more similar to subgenotype B2 at the gdh gene. Grouping the isolates on the basis of SNPs resulted in different groups for the two genes. The results are discussed in relation to giardiasis in Norway and to other Giardia genotyping studies.

Extended Spectrum β-Lactamases among Gram-negative bacteria of nosocomial origin from an Intensive Care Unit of a tertiary health facility in Tanzania

BackgroundResistance to third generation cephalosporins due to acquisition and expression of extended spectrum β-lactamase (ESBL) enzymes among Gram-negative bacteria is on the increase. Presence of ESBL producing organisms has been reported to significantly affect the course and outcome of an infection. Therefore infections due to ESBL isolates continue to pose a challenge to infection management worldwide. The aim of this study was to determine the existence and to describe phenotypic and genotypic characteristics of ESBLs in an Intensive Care Unit (ICU) setting in Tanzania.MethodsBetween October 2002 and April 2003, clinical information and samples were collected from patients suspected to have nosocomial infections in an Intensive Care Unit of a tertiary hospital in Tanzania. The isolates were identified, tested for antimicrobial susceptibility and analysed for presence of ESBL genes.ResultsThirty-nine Gram-negative bacteria were isolated from clinical samples of 39 patients. These isolates included 13 Escherichia coli, 12 Enterobacter spp, 5 Pseudomonas spp, 4 Proteus spp, 2 Klebsiella. pneumoniae, 2 Citrobacter freundii and 1 Chryseomonas luteola. Eleven (28.2%) of these isolates were ESBL producing. The ESBL genes characterised were SHV-12, SHV-28 and CTX-M-15. The ESBL producing isolates were more resistant to gentamicin and ciprofloxacin than non-ESBL producing isolates.ConclusionThis study shows the presence of ESBL genes among Gram-negative bacteria in the ICU setting in Tanzania. There is a need to institute strict hospital infection control policy and a regular surveillance of resistance to antimicrobial agents.