Demographic and Behavioural Factors in Tanzanian and Norwegian Patients with Sexually Transmitted Infections.

To evaluate whether differences in demographic or behavioural factors might explain differences in reported or diagnosed sexually transmitted infections (STI), we have compared data from 1097 Tanzanian and Norwegian STI patients. Most demographic data were similar, whereas some behavioural data differed. Norwegian patients reported significantly higher numbers of sexual partners than Tanzanian. Thirty-three percent of Tanzanian patients tested positive for HIV antibodies, females more often (43%) than males (26%). Approximately one-third and two-thirds of the female HIV-positive Tanzanian STI patients had already seroconverted at the age of 25 and 30 years, respectively. The national differences encountered probably reflect cultural differences, different panoramas of STI and a lower accessibility to optimal health services in Tanzania. Lack of expected statistical associations between some of the data in the Tanzanian STI group might question the validity of the retrospectively collected data in this group, or indicate that questions not included in the questionnaire might be of importance

Development of functional gastrointestinal disorders after Giardia lamblia infection

<p>Abstract</p> <p>Background</p> <p>Functional gastrointestinal disorders (FGID) may occur following acute gastroenteritis. This long-term complication has previously not been described after infection with the non-invasive protozoan <it>Giardia lamblia</it>. This study aims to characterize persistent abdominal symptoms elicited by <it>Giardia </it>infection according to Rome II criteria and symptoms scores.</p> <p>Methods</p> <p>Structured interview and questionnaires 12–30 months after the onset of <it>Giardia </it>infection, and at least 6 months after <it>Giardia </it>eradication, among 82 patients with persisting abdominal symptoms elicited by the <it>Giardia </it>infection. All had been evaluated to exclude other causes.</p> <p>Results</p> <p>We 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.</p> <p>Conclusion</p> <p>In 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 <it>Giardia </it>infection may elicit functional gastrointestinal diseases with food and stress related symptoms similar to FGID patients in general.</p

Stability of glycoprotein gene sequences of herpes simplex virus type 2 from primary to recurrent human infection, and diversity of the sequences among patients attending an STD clinic

Background: Herpes simplex virus type 2 (HSV-2) is sexually transmitted, leading to blisters and ulcers in the genito-anal region. After primary infection the virus is present in a latent state in neurons in sensory ganglia. Reactivation and production of new viral particles can cause asymptomatic viral shedding or new lesions. Establishment of latency, maintenance and reactivation involve silencing of genes, continuous suppression of gene activities and finally gene activation and synthesis of viral DNA. The purpose of the present work was to study the genetic stability of the virus during these events. Methods: HSV-2 was collected from 5 patients with true primary and recurrent infections, and the genes encoding glycoproteins B,G,E and I were sequenced. Results: No nucleotide substitution was observed in any patient, indicating genetic stability. However, since the total number of nucleotides in these genes is only a small part of the total genome, we cannot rule out variation in other regions. Conclusions: Although infections of cell cultures and animal models are useful for studies of herpes simplex virus, it is important to know how the virus behaves in the natural host. We observed that several glycoprotein gene sequences are stable from primary to recurrent infection. However, the virus isolates from the different patients were genetically different

Genetic determinants of macrolide and tetracycline resistance in penicillin non-susceptible Streptococcus pneumoniae isolates from people living with HIV in Dar es Salaam, Tanzania

Background: Over one million yearly deaths are attributable to Streptococcus pneumoniae and people living with HIV are particularly vulnerable. Emerging penicillin non-susceptible Streptococcus pneumoniae (PNSP) challenges therapy of pneumococcal disease. The aim of this study was to determine the mechanisms of antibiotic resistance among PNSP isolates by next generation sequencing. Methods: We assessed 26 PNSP isolates obtained from the nasopharynx from 537 healthy human immunodeficiency virus (HIV) infected adults in Dar es Salaam, Tanzania, participating in the randomized clinical trial CoTrimResist (ClinicalTrials.gov identifier: NCT03087890, registered on 23rd March, 2017). Next generation whole genome sequencing on the Illumina platform was used to identify mechanisms of resistance to antibiotics among PNSP. Results: Fifty percent (13/26) of PNSP were resistant to erythromycin, of these 54% (7/13) and 46% (6/13) had MLSB phenotype and M phenotype respectively. All erythromycin resistant PNSP carried macrolide resistance genes; six isolates had mef(A)-msr(D), five isolates had both erm(B) and mef(A)-msr(D) while two isolates carried erm(B) alone. Isolates harboring the erm(B) gene had increased MIC (> 256 µg/mL) towards macrolides, compared to isolates without erm(B) gene (MIC 4-12 µg/mL) p < 0.001. Using the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines, the prevalence of azithromycin resistance was overestimated compared to genetic correlates. Tetracycline resistance was detected in 13/26 (50%) of PNSP and all the 13 isolates harbored the tet(M) gene. All isolates carrying the tet(M) gene and 11/13 isolates with macrolide resistance genes were associated with the mobile genetic element Tn6009 transposon family. Of 26 PNSP isolates, serotype 3 was the most common (6/26), and sequence type ST271 accounted for 15% (4/26). Serotypes 3 and 19 displayed high-level macrolide resistance and frequently carried both macrolide and tetracycline resistance genes. Conclusion: The erm(B) and mef(A)-msr(D) were common genes conferring resistance to MLSB in PNSP. Resistance to tetracycline was conferred by the tet(M) gene. Resistance genes were associated with the Tn6009 transposon.publishedVersio

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

BACKGROUND: Resistance 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. METHODS: Between 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. RESULTS: Thirty-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. CONCLUSION: This 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

Konsekvenser av foreslåtte endringer i aksjeloven § 3-8

Master's thesis in Accounting and AuditingAksjeloven § 3-8 regulerer avtaler inngått mellom et selskap og dets nærstående. Formålet med bestemmelsen er todelt. Bestemmelsen skal unngå omgåelse av redegjørelse ved tingsinnskudd. I tillegg skal den skape åpenhet og kontroll av avtaler hvor nærstående til et selskap har mulighet til å sette egne interesser foran selskapets. Ivaretas bestemmelsens formål vil den kunne bidra til å motvirke økonomisk kriminalitet. Bestemmelsen er kritisert for å være kostbar og tidkrevende som følge av omfattende saksbehandlingsregler i kombinasjon med usikkerheter knyttet til bestemmelsens omfang. Konsekvensen av at avtaler som ikke godkjennes i generalforsamlingen blir ugyldige, har medført at flere følger saksbehandlingsreglene enn hva bestemmelsen krever. I NOU 2016:22 har et lovutvalg foreslått forenklinger av aksjeloven hvor formålet er å redusere økonomiske og administrative byrder. I den forbindelse er aksjeloven § 3-8 foreslått endret med mål om å utarbeide en mer treffsikker og forutsigbar bestemmelse. Aksjelovutvalget har foreslått å erstatte krav om godkjennelse i generalforsamlingen med en meldeplikt til selskapets aksjeeiere. Foreslåtte endringene innebærer reduserte saksbehandlingsregler og endring av usikkerhetsmoment som har vært gjenstand for kritikk. Videre er terskelverdiene foreslått endret og personkretsen begrenset. Fjerning av krav om generalforsamlingsgodkjennelse flytter beslutningsmyndigheten til styret. Det innebærer at avtalene ikke kan bli ugyldige som følge av aksjeloven § 3-8. En slik endring stiller økt krav til at styret på eget initiativ gjennomføre tilstrekkelige vurderinger av inngåtte avtaler, og medfører økt risiko for at styret kan bli erstatningsansvarlige. Foreslåtte endringer av saksbehandlingsreglene medfører en mindre kostnadskrevende bestemmelse i tråd med aksjelovutvalgets formål. Meldeplikten vil informere aksjeeierne om inngåtte avtaler samtidig som endring av usikkerhetsmoment bidrar til en klar og forutsigbar bestemmelse. Bestemmelsen vil derimot ikke være treffsikker for alle avtaler den er ment å regulere. Det skyldes blant annet ulike interessenters vurdering av vesentlighet. I tillegg vil begrensning av personkrets og fjerning av et unntak øke risikoen for at aksjeeierne ikke vil motta informasjon om risikofylte avtaler. Foretas endringer slik at bestemmelsen også blir treffsikker for alle avtaler vil den ivareta hensynet til åpenhet og kontroll og kunne bidra til å motvirke økonomisk kriminalitet

High rate of antimicrobial resistance and multiple mutations in the dihydrofolate reductase gene among Streptococcus pneumoniae isolated from HIV-infected adults in a community setting in Tanzania

Objectives The aim of this study was to characterize molecular mechanisms of resistance to trimethoprim and other antibiotics in Streptococcus pneumoniae isolates from HIV-infected adults in Dar es Salaam, Tanzania. Methods A total of 1877 nasopharyngeal swabs were collected and screened for pneumococcal colonization from 537 newly diagnosed individuals with HIV at four clinic visits during a 1-year follow-up from 2017–2018 as part of the randomized clinical trial CoTrimResist (ClinicalTrials.gov ID: NCT03087890). Results A total of 76 pneumococcal isolates were obtained. Of the 70 isolates that could be serotyped, 42 (60.0%) were vaccine serotypes included in pneumococcal conjugate vaccine 23 (PCV23). The majority of isolates (73.7%; 56/76) were non-susceptible to penicillin (MICs of 0.06–2 μg/mL). Isolates were frequently resistant to co-trimoxazole (trimethoprim/sulfamethoxazole) (71.1%) but less so to azithromycin (22.4%), erythromycin (21.1%), chloramphenicol (18.4%), tetracycline (14.5%), clindamycin (10.5%) and levofloxacin (0%). Moreover, 26.3% were multidrug-resistant (resistant to ≥3 antibiotic classes). Vaccine-type pneumococci were resistant to more classes of antibiotics, were more frequently resistant to erythromycin, azithromycin, clindamycin and tetracycline, and had higher MICs to penicillin (median, 0.19 μg/mL; range, 0.002–1.5 μg/mL) compared with non-vaccine serotypes (median, 0.125 μg/mL; range, 0.012–0.25 μg/mL) (P = 0.003). Co-trimoxazole-resistant isolates carried from 1 to 11 different mutations in the dihydrofolate reductase (DHFR) gene, most commonly Ile100Leu (100%), Glu20Asp (91.8%), Glu94Asp (61.2%), Leu135Phe (57.1%), His26Tyr (53.1%), Asp92Ala (53.1%) and His120Gln (53.1%). Conclusion Streptococcus pneumoniae isolated from HIV-diagnosed patients were frequently non-susceptible to penicillin and co-trimoxazole. Most isolates carried multiple mutations in DHFR.publishedVersio

No difference in serum levels of B-cell activating receptor and antibodies against cytolethal distending toxin B and flagellin in post-infectious irritable bowel syndrome and chronic fatigue syndrome after Giardia infection

Background and Aim Functional gastrointestinal disorders (FGIDs) and chronic fatigue syndrome (CFS) frequently occur as comorbid conditions to each other. A shared etiology of these syndromes has been proposed because of their shared symptomatology and triggering by infections. Antibodies against the bacterial antigens cytolethal distending toxin B (CdtB) and flagellin have been proposed to be biomarkers of irritable bowel syndrome (IBS), especially diarrhea-predominant IBS (IBS-D). It is unknown if they may also be associated with comorbid conditions such as CFS. On the other hand, elevated level of B-cell activating factor (BAFF) has been associated with CFS and inflammatory bowel disease (IBD) and subjective food intolerance. Methods We evaluated serum levels of anti-flagellin and anti-CdtB using an in-house enzyme-linked immunosorbent assay (ELISA) and BAFF with a commercially available ELISA kit in a cohort of patients who developed fatigue syndromes and/or FGIDs after Giardia infection, by comparing them with healthy controls without these conditions. Results We did not find significant differences in circulating BAFF, anti-CdtB, or anti-flagellin antibody levels in these patient groups compared to healthy controls. Therefore, our results do not support a role for BAFF, anti-CdtB, or anti-flagellin antibodies as universal biomarkers for IBS or CFS. Conclusion BAFF, anti-CdtB, or anti-flagellin antibodies cannot be considered as universal biomarkers for IBS or CFS.publishedVersio

Predominance of PVL-negative community-associated methicillin-resistant Staphylococcus aureus sequence type 8 in newly diagnosed HIV-infected adults, Tanzania

Difficult-to-treat infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are of concern in people living with HIV infection as they are more vulnerable to infection. We aimed to identify molecular characteristics of MRSA colonizing newly diagnosed HIV-infected adults in Tanzania. Individuals newly diagnosed with HIV infection were recruited in Dar es Salaam, Tanzania, from April 2017 to May 2018, as part of the randomized clinical trial CoTrimResist (ClinicalTrials.gov identifier: NCT03087890). Nasal/nasopharyngeal isolates of Staphylococcus aureus were susceptibility tested by disk diffusion method, and cefoxitin-resistant isolates were characterized by short-reads whole genome sequencing. Four percent (22/537) of patients carried MRSA in the nose/nasopharynx. MRSA isolates were frequently resistant towards gentamicin (95%), ciprofloxacin (91%), and erythromycin (82%) but less often towards trimethoprim-sulfamethoxazole (9%). Seventy-three percent had inducible clindamycin resistance. Erythromycin-resistant isolates harbored ermC (15/18) and LmrS (3/18) resistance genes. Ciprofloxacin resistance was mediated by mutations of the quinolone resistance-determining region (QRDR) sequence in the gyrA (S84L) and parC (S80Y) genes. All isolates belonged to the CC8 and ST8-SCCmecIV MRSA clone. Ninety-five percent of the MRSA isolates were spa-type t1476, and one exhibited spa-type t064. All isolates were negative for Panton-Valentine leucocidin (PVL) and arginine catabolic mobile element (ACME) type 1. All ST8-SCCmecIV-spa-t1476 MRSA clones from Tanzania were unrelated to the globally successful USA300 clone. Carriage of ST8 MRSA (non-USA300) was common among newly diagnosed HIV-infected adults in Tanzania. Frequent co-resistance to non-beta lactam antibiotics limits therapeutic options when infection occurs.publishedVersio

High prevalence of fecal carriage of extended spectrum β-lactamase-producing enterobacteriaceae among newly HIV-diagnosed adults in a community setting in Tanzania

Colonization in HIV-infected populations with extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE) is particularly worrisome in low-income settings. This study describes the prevalence of ESBL-PE carriage and associated risk factors among newly HIV-diagnosed adults in a community setting in Tanzania. A total of 595 newly diagnosed HIV-positive adults with a median age of 35 years with interquartile range (IQR) 29–42 years and a median CD4 count of 492 cells/μL (IQR 390–666 cells/μL) were recruited. Among these, 194/595 (32.6%, 95% confidence interval [CI] 28.9–36.6) were ESBL-PE carriers. Participants with low CD4 count (<350 cells/μL) had significantly higher prevalence of ESBL-PE carriage compared with those with CD4 count ≥350 cells/μL (26/58, 44.8%, vs. 168/537, 31.3%, p = 0.04). Antibiotic use in last 4 weeks (odds ratio [OR] 1.55, 95% CI 1.08–2.22, p = 0.02) and CD4 count <350 cells/μL (OR 1.78, 95% CI 1.03–3.09, p = 0.04) were independent risk factors for fecal carriage of ESBL-PE. In total, 244 isolates of ESBL-PE were isolated from 194 participants. Of these, 238/244 (97.5%) harbored blaCTX-M genes, with blaCTX-M-15 being predominant (219/238 (92%), followed by blaCTX-M-27 (9/238 (3.8%), blaCTX-M-14 (8/238 (3.4%), blaCTX-M-55 (1/238), and blaCTX-M 211/3 (1/238). blaSHV-2a genes were detected in four isolates, whereas the blaSHV-12 gene was detected in one isolate. Phenotypic carbapenemase-producing Enterobacteriaceae was detected in one HIV-positive person with CD4 count 132 cells/μL. In conclusion prevalence of ESBL-PE carriage is high among newly diagnosed HIV adults in Dar es Salaam, and is significantly associated antibiotic use and low CD4 count.publishedVersio