Genomic epidemiology of carbapenemase-producing Gram-negative bacteria at the human-animal-environment interface in Djibouti city, Djibouti.

The emergence of carbapenem resistance is a major public health threat in sub-Saharan Africa but remains poorly understood, particularly at the human-animal-environment interface. This study provides the first One Health-based study on the epidemiology of Carbapenemase-Producing Gram-Negative Bacteria (CP-GNB) in Djibouti City, Djibouti, East Africa. In total, 800 community urine samples and 500 hospital specimens from humans, 270 livestock fecal samples, 60 fish samples, and 20 water samples were collected and tested for carbapenem resistance. The overall estimated CP-GNB prevalence was 1.9 % (32/1650 samples) and specifically concerned 0.3 % of community urine samples, 2.8 % of clinical specimens, 2.6 % of livestock fecal samples, 11.7 % of fish samples, and 10 % of water samples. The 32 CP-GNB included 19 Escherichia coli, seven Acinetobacter baumannii, five Klebsiella pneumoniae, and one Proteus mirabilis isolate. Short-read (Illumina) and long-read (Nanopore) genome sequencing revealed that carbapenem resistance was mainly associated with chromosomal carriage of blaNDM-1, blaOXA-23, blaOXA-48, blaOXA-66, and blaOXA-69 in A. baumannii, and with plasmid carriage in Enterobacterales (blaNDM-1 and blaOXA-181 in E. coli, blaNDM-1, blaNDM-5 and blaOXA-48 in K. pneumoniae, and blaNDM-1 in P. mirabilis). Moreover, 17/32 CP-GNB isolates belonged to three epidemic clones: (1) A. baumannii sequence type (ST) 1697,2535 that showed a distribution pattern consistent with intra- and inter-hospital dissemination; (2) E. coli ST10 that circulated at the human-animal-environment interface; and (3) K. pneumoniae ST147 that circulated at the human-environment interface. Horizontal exchanges probably contributed to carbapenem resistance dissemination in the city, especially the blaOXA-181-carrying ColKP3-IncX3 hybrid plasmid that was found in E. coli isolates belonging to different STs. Our study highlights that despite a relatively low CP-GNB prevalence in Djibouti City, plasmids harboring carbapenem resistance circulate in humans, animals and environment. Our findings stress the need to implement preventive and control measures for reducing the circulation of this potentially emerging public health threat.

Prevalence and Phenotypic and Molecular Characterization of Carbapenemase-Producing Gram-Negative Bacteria in Gabon.

Data collection and monitoring of carbapenemase-producing (CP) Gram-negative bacteria (GNB) are often limited. This study determined CP-GNB prevalence in Gabon and the genetic origins of the resistance genes. From January 2016 to March 2018, 869 clinically significant GNB isolates from inpatients and outpatients, and 19 fecal samples (inpatients) were analyzed in the main hospitals of Gabon. Fecal samples were screened using ChromID® CARBA SMART selective chromogenic medium biplates. Species were identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry. Antibiotic susceptibility was tested using the disk diffusion method on Müller-Hinton agar, and resistance genes were assessed by multiplex polymerase chain reaction and sequencing. Overall, 1.61% of clinical isolates (14 of 869) and 5.26% of fecal samples (1 of 19) were CP-GNB. The CP-GNB rate was higher among inpatients (2.98%) than outpatients (0.33%), in intensive care units (28.57%, 4 of 14), and in urine samples (35.71%, 5 of 14). The most common CP-GNB were Klebsiella pneumoniae (53.33%) and Acinetobacter baumannii (26.67%). blaOXA-48 was the predominant carbapenemase-encoding gene (40%), followed by blaNDM-5 (33.33%). The A. baumannii multilocus sequence types ST2 and ST78, Enterobacter cloacae ST78, Escherichia coli ST2, and K. pneumonia ST48 and ST147 were found. These data indicate that CP bacteria are present in clinical and carriage samples. Preventive measures are needed to avoid the spread of resistance genes.

Multidrug-Resistant Enterobacterales in Community-Acquired Urinary Tract Infections in Djibouti, Republic of Djibouti.

The emergence and spread of multidrug resistant Enterobacterales (MDR-E) are a global public health issue. This problem also concerns urinary tract infections (UTI), which are the second most frequent infections after respiratory infections. The objective of this study was to determine MDR-E frequency and to characterize MDR-E isolates from patients with community-acquired UTIs in Djibouti, Republic of Djibouti. From 800 clinical urinary samples collected at the Mer Rouge Laboratory, Djibouti, from January to July 2019, 142 were identified as Enterobacterales (age range of the 142 patients mean age is 42 years.) Mass spectrometry analysis of these isolates identified 117 Escherichia coli, 14 Klebsiella pneumoniae, 2 Proteus mirabilis, 4 Enterobacter spp., 4 Providencia stuartii and 1 Franconibacter helveticus. Antibiotic susceptibility testing (disk diffusion method) of these 142 isolates detected 68 MDR-E (68/142 = 48%): 65 extended-spectrum bêta lactamase- (ESBL), 2 carbapenemase- (one also ESBL), and 1 cephalosporinase-producer. Multiplex PCR and sequencing showed that the 65 ESBL-producing isolates carried genes encoding CTX-M enzymes (CTX-M-15 in 97% and CTX-M-9 in 3% of isolates). Two isolates harboured a gene encoding the OXA-48-like carbapenemase, and one the gene encoding the AmpC CMY-2 cephalosporinase. Genes implicated in resistance to quinolones (qnrB, aac (6')-Ib-cr, qnrD, oqxA and B) also were detected. Among the E. coli phylogroups, B2 was the most common phylogenetic group (21% of MDR-E isolates and 26% of non-MDR-E isolates), followed by A (14% and 12%), B1 (9% and 7%), D (3% and 3%), F (3% and 3%) and E (2% and 2%). This study highlights the high frequency of ESBL producers and the emergence of carbapenemase-producers among Enterobacterales causing community-acquired UTIs in Djibouti.

Online self-sampling kits for human immunodeficiency virus and other sexually transmitted infections: Feasibility, positivity rates, and factors associated with infections in France.

BACKGROUND: Men who have sex with men are increasingly diagnosed with sexually transmitted infections (STI) in France. To address this situation, quarterly screening for HIV combined with hepatitis B (HBV) and hepatitis C (HCV), as well as annual screening for C.trachomatis (CT) and N.gonorrhoeae (NG) are recommended. The MemoDepistages program offered an at-home screening solution for these infections. This study describes the feasibility of this screening process, the rate of positive test results, and the factors associated with positivity. METHODS: Participants were recruited online. Laboratories verified the quantity and quality of the samples. Logistic regression was used to determine the associated factors for infection. RESULTS: Overall, 1556 out of 1908 (81.6%) blood samples were tested for at least HIV. A total of eight participants (0.5%) were newly diagnosed with HIV and four with HCV (0.3%). No new infection was confirmed for HBV. Overall positivity was 9.3% for CT and 9.6% for NG. The highest positivity was reported in rectal swabs for CT (7.3%) and in pharyngeal swabs for NG (7.2%). Factors associated with extragenital CT/NG were age under 30 years (for pharyngeal and rectal infections) and having at least 10 partners in the past 6 months (p<0.001) (for pharyngeal infections only). CONCLUSIONS: The self-sampling kit for multiple STIs can perform comprehensive tests and identify new infections in young people, especially in extragenital sites.

Using the clinical information system and self-supervision to rationalize the need for antibiotic stewardship: An interventional study in a 2000-bed university hospital.

OBJECTIVES: To describe the usefulness of electronic medical records (EMRs) and a computerized physician order entry (CPOE) system to support and assess an antimicrobial stewardship programme (ASP). METHODS: At the study hospital, infectious diseases specialists supervise antimicrobial prescription when solicited by physicians in charge of patients. From January to October 2015, treatment days of antibiotic prescription, supervised or unsupervised by infectious disease specialists (SAP or UAP, respectively) in all wards, except intensive care units emergency department, bone marrow transplantation units, and paediatric units, were calculated. Embedding recommendations on carbapenem indications as a checklist into the CPOE system, a self-administered ASP was implemented in 2017. EMRs were reviewed to determine global compliance with carbapenem prescription guidelines (combining introduction of therapy and 72-h assessment) before and after implementation of a self-administered ASP in departments with a low SAP rate for these antibiotics. RESULTS: Among 16 090 prescriptions extracted, 19.9% were SAPs. Three patterns of prescription were identified. The first pattern (amoxicillin-clavulanate, ceftriaxone) was characterized by a high UAP rate in every department, the second pattern (cloxacillin, rifampin) was characterized by a high SAP rate in every department, and the third pattern (broad-spectrum beta-lactams) was characterized by heterogeneous distribution of SAP/UAP among departments. Carbapenem prescription was reviewed in five departments with a low SAP rate for carbapenems over 6 months: 94 before and 107 after implementation of the self-administered ASP. Global compliance with guidelines increased significantly from 22% to 37% (risk difference 15%, 95% confidence interval 2.3-28.5%; P=0.02). CONCLUSION: A clinical information system may help to rationalize antibiotic stewardship in a context of scarce medical resources. Mapping of antibiotic prescriptions and self-supervision are efficient, complementary and easy-to-implement tools.

Epidemiology and microbiological features of anaerobic bacteremia in two French University hospitals.

Bacteremia implicating anaerobic bacteria (BIAB) represents 2-6% of all episodes of bacteremia and is associated with high mortality. In this retrospective study from June 2015 to December 2016, we compared BIAB frequency in two hospital centers in Montpellier (France): Montpellier university hospital (MUH) and a center specialized in cancer (ICM). Among the 2465 microbiologically relevant episodes of bacteremia, we identified 144 (5.8%) in which anaerobic bacteria were implicated. BIAB frequency was higher at ICM than MUH (10.4%, vs. 4.9%, p < 0.01). Poly-microbial bacteremia was more frequent among the BIAB episodes (31.9% vs. 11.0% for aerobic-only bacteremia, p < 0.01). Bacteroides and Clostridium were the most frequently identified genera of anaerobic bacteria (64 and 18 episodes, respectively), with the B. fragilis group (BFG) involved in 68/144 episodes. We could perform antibiotic susceptibility typing in 106 of the 144 anaerobic isolates, including 67 BFG isolates. All isolates but one were susceptible to metronidazole. In the BFG, sporadic resistant or intermediate results were found for amoxicillin-clavulanate (5/67), piperacillin-tazobactam (2/67) and imipenem (1/67). BFG isolates were susceptible also to cefoxitin (90.8%), rifampicin (97.0%) and tigecyclin (91.0%). Multidrug resistance in this group (7 isolates) was mostly due to acquired resistance to moxifloxacin, clindamycin and tigecyclin. This study shows that BIAB frequency can vary among hospitals and services. They should especially be taken into account in centers specialized in cancer treatment. However, the implicated bacteria remain frequently susceptible to the most used antibiotics used against anaerobic bacteria, although resistance does exist.

Clinical Characteristics of Mycoplasma genitalium and the Usefulness of Syndromic Management Among Women Living With Human Immunodeficiency Virus.

We report the clinical symptoms and examination findings of Mycoplasma genitalium (MG) in women living with human immunodeficiency virus in South Africa. If we relied on syndromic management alone to treat MG, only 15 of 46 MG-infected women would have received. appropriate treatment: sensitivity of 32.6% (95% confidence interval, 19.5-48.0) and specificity of 67.4% (95% confidence interval, 63.4-71.2).

Extended spectrum beta-lactamase-producing Klebsiella pneumoniae outbreak reveals incubators as pathogen reservoir in neonatal care center.

In the context of a 3-month extended-spectrum beta-lactamase-producing Klebsiella pneumonia (ESBL-KP) outbreak in a neonatal care center (NCC), hygiene practices and hospital environment were investigated. ESBL-KP strains isolated from patients and environment were compared by molecular typing. The density of incidence of multi-drug-resistant bacteria (MDRB) was calculated from January 2014 to September 2016. The 3-month ESBL-KP outbreak involved 19 patients. Clinical strains from the 19 patients displayed the same molecular profile between them, and with a strain isolated from an incubator after cleaning. Furthermore, 52.4% of incubator mattresses were positive for diverse pathogens. Hygiene practices were acceptable except for external practitioners and parents. In addition to classical infection control (IC) measures, the replacement of mattresses and the improvement of incubators disinfection stopped the outbreak. The protocol of disinfection was revised and microbiological control was implemented. A significant decrease of MDRB incidence was concomitant (p value = 0.03219) but 3 months later, MDRB incidence increased again.Conclusion: This investigation highlighted incubators and mattresses as critical materials associated to infectious risk in NCC. NCC and IC teams should implement efficient protocol for incubators disinfection and monitoring. What is Known: • Environment in neonatal intensive care units is often suspected as reservoir for Enterobacteriaceae outbreaks but is scarcely investigated. • Incubators and mattresses offer wet and warm conditions suitable for pathogens multiplication, but microbiological survey is not performed routinely for assessing bacterial contamination. What is New: • Incubators and mattresses serve as reservoir for pathogens and relay in outbreak. • An infection control protocol associating efficient disinfection and microbiology analysis is proposed.

High Prevalence of Multidrug-Resistant Escherichia coli in Urine Samples from Inpatients and Outpatients at a Tertiary Care Hospital in Sétif, Algeria.

The worldwide dissemination of multidrug-resistant (MDR) Enterobacteriaceae is a major public health issue. The aim of this study was to investigate the prevalence of MDR Escherichia coli (MDR-EC) isolates, in inpatients/outpatients with urinary tract infections at Sétif University Hospital (Algeria). Bacterial cultures were obtained from 426 of the 3,944 urine samples collected from January 2015 to February 2017. Among these cultures, 215 E. coli isolates were identified by mass spectrometry, and 38 (17.7%) were MDR-EC (disk diffusion method): 36 produced only extended-spectrum ß-lactamases (ESBL), one ESBL and a carbapenemase, and one only a cephalosporinase (double-disk synergy test). Multiplex PCR and sequencing analyses showed that 37 ESBL-producing isolates harbored genes encoding CTX-M enzymes (CTX-M-15 in 33 isolates, 89.19%; and CTX-M-14 group in four isolates, 10.81%). One CTX-M-15-producing isolate co-expressed also an OXA-48-like carbapenemase. Phylogenetic group analysis of the 37 ESBL-producing and 178 non-ESBL-producing isolates indicated that the most common phylogenetic group was B2 (54.05% of ESBL-producing and 48.31% of non-ESBL-producing isolates), followed by A and D for ESBL-, and by B1, A, and F for non-ESBL-producing isolates. This is the first report highlighting the presence of MDR-EC isolates that produce both CTX-M and OXA-48-like enzymes in Sétif, Algeria.

Prevalence and Antimicrobial Resistance of Mycoplasma genitalium Infection Among Women Living With Human Immunodeficiency Virus in South Africa: A Prospective Cohort Study.

This prospective cohort study of 622 women living with human immunodeficiency virus (HIV) from Johannesburg (2012) detected Mycoplasma genitalium in 7.4% (95% confidence interval [CI]: 5.5-9.7, 46/622), with detection more likely with lower CD4 counts(adjusted odds ratio [AOR] 1.02 per 10 cells/µL decrease, 95% CI: 1.00-1.03) and higher plasma HIV-1 RNA (AOR 1.15 per log copies/mL increase, 95% CI: 1.03-1.27). No mutations for macrolide/quinolone resistance was detected.

High-risk HPV detection and associated cervical lesions in a population of French menopausal women.

BACKGROUND: With population ageing, post-menopausal women represent a new group to be considered in cervical cancer screening strategies, including the significance of High Risk (HR)-HPV detection. OBJECTIVES: A retrospective analysis was conducted in a cohort of 406 menopausal women attending routine gynaecological consultation at the Hospital of Montpellier (France). STUDY DESIGN: All women benefited from a cervical smear and HR-HPV detection using Hybrid Capture 2 (HC2) test. The prevalence of cytological abnormalities, HR-HPV detection and risk factors associated with HR-HPV detection were analyzed. Evolution of both tests was evaluated in a sub-group of women with adequate follow-up. RESULTS: Five women (1.2%) had an abnormal cervical smear at baseline. HR-HPV was detected in 40 women (9.9%), including 36 women with normal cytology (9%). Risk factors associated with HR-HPV detection at enrolment were a previous history of Cervical Intraepithelial Neoplasia and a high socio-economic level, but not hormone replacement therapy. When cytology and HR-HPV detection were negative at enrolment, both remained negative for 95% (230/241) of women during follow-up (median duration of follow-up: 60 months). HR-HPV persistence was observed for 55% (18/33) of women with normal cytology and positive HR-HPV test. Finally, all women with a final diagnosis of high-grade (CIN2+) cervical lesion (N = 7) had a positive HR-HPV test with or without abnormal cytology. CONCLUSIONS: HR-HPV was detected in 9.9% of menopausal women. HR-HPV detection was a better predictor of CIN2+ lesions than cytology in this population. Women with previous CIN history should benefit from HR-HPV testing and need long term follow-up.

Associations of human gene EPB41L3 DNA methylation and cervical intraepithelial neoplasia in women living with HIV-1 in Africa.

OBJECTIVES: To evaluate associations of DNA methylation of the human tumour suppressor gene EPB41L3 with high-grade cervical intraepithelial neoplasia (CIN2+) and HIV-related factors among women living with HIV-1 (WLHIV) in Burkina Faso and South Africa. DESIGN: Case-control study of WLHIV aged 25-50 with histology-determined CIN2+ (cases, N = 152) and ≤CIN1 (controls, N = 210). METHODS: EPB41L3 methylation was measured by pyrosequencing of bisulphite converted DNA from exfoliated cervical specimens at baseline and 16 months later. Median methylation levels were compared across CIN grades using the Mann-Whitney test and Cuzick test for trend. EPB41L3 methylation levels were dichotomized into 'high' and 'low' using the 66.7 percentile point of the distribution in the controls. Associations of EPB41L3 methylation with HIV-related factors were estimated by logistic regression. RESULTS: Among 94 WLHIV in Burkina Faso and 268 in South Africa, median methylation levels at baseline for EPB41L3 increased with increasing CIN grade in both countries (P-trend <0.001).'High' methylation was more frequent among women with a longer time since HIV diagnosis in Burkina Faso [>5 years vs. ≤5 years; adjusted odds ratio (aOR) = 4.15, 95% CI 1.09-15.83, adjusted for age, CD4 count, high-risk HPV and CIN status], with low CD4 count in both countries (CD4 ≤200 vs. ≥350 cells/µl: aOR = 7.14, 95% CI 1.44-35.37 in Burkina Faso; aOR = 2.55, 95% CI 1.07-6.07 in South Africa), and with prolonged ART use in South Africa (ART >2 years vs. ART-naïve: aOR = 2.40, 95% CI: 1.23-4.69). CONCLUSION: Methylation of EPB41L3 DNA is elevated among WLHIV with CIN2+ and independently associated with lower CD4 count and ART use.

Prevalence, incidence and correlates of low risk HPV infection and anogenital warts in a cohort of women living with HIV in Burkina Faso and South Africa.

OBJECTIVE: To report the prevalence and incidence of low-risk human papillomavirus infection (LR-HPV) and anogenital warts (AGW) among women living with HIV (WLHIV) in Burkina Faso (BF) and South Africa (SA), and to explore HIV-related factors associated with these outcomes. METHODS: We enrolled 1238 WLHIV (BF = 615; SA = 623) aged 25-50 years and followed them at three time points (6, 12 and 16 months) after enrolment. Presence of AGW was assessed during gynaecological examination. Cervico-vaginal swabs for enrolment and month 16 follow-up visits were tested for HPV infection by Inno-LiPA® genotyping. Logistic regression was used to assess risk factors for prevalent infection or AGW. Cox regression was used to assess risk factors for incident AGW. RESULTS: Women in SA were more likely than those in BF to have prevalent LR-HPV infection (BF: 27.1% vs. SA: 40.9%; p<0.001) and incident LR-HPV infection (BF: 25.8% vs. SA: 31.6%, p = 0.05). Prevalence of persistent LR-HPV was similar in the two countries (BF: 33.3% vs. SA: 30.4%; p = 0.54), as were prevalence and incidence of AGW (Prevalence: BF: 7.5% vs. SA: 5.7%; p = 0.21; Incidence: BF: 2.47 vs. SA: 2.33 per 100 person-years; p = 0.41). HPV6 was associated with incident AGW (BF: adjusted Hazard Ratio (aHR) = 4.88; 95%CI: 1.36-17.45; SA: aHR = 5.02; 95%CI: 1.40-17.99). Prevalent LR-HPV (BF: adjusted Odds Ratio [aOR = 1.86]; 95%CI: 1.01-3.41; SA: aOR = 1.75; 95%CI: 0.88-3.48); persistent LR-HPV (BF: aOR = 1.92; 95%CI: 0.44-8.44; SA: aOR = 2.81; 95%CI: 1.07-7.41) and prevalent AGW (BF: aOR = 1.53; 95%CI: 0.61-3.87; SA: aOR = 4.11; 95%CI: 1.20-14.10) were each associated with low CD4+ counts (i.e. <200 vs. >500 cells/µL). Duration of ART and HIV plasma viral load were not associated with any LR-HPV infection or AGW outcomes. CONCLUSION: LR-HPV infection and AGW are common in WLHIV in sub-Saharan Africa. Type-specific HPV vaccines and effective ART with immunological reconstitution could reduce the burden of AGW in this population.

Supraclavicular catheterization of the brachiocephalic vein: a way to prevent or reduce catheter maintenance-related complications in children.

Placement of a central venous catheter (CVC) in the brachiocephalic vein (BCV) via the ultrasound (US)-guided supraclavicular approach was recently described in children. We aimed to determine the CVC maintenance-related complications at this site compared to the others (i.e., the femoral, the subclavian, and the jugular). We performed a retrospective data collection of prospectively registered data on CVC in young children hospitalized in a pediatric intensive care unit (PICU) during a 4-year period (May 2011 to May 2015). The primary outcome was a composite of central line-associated bloodstream infection (CLABSI) and deep-vein thrombosis (CLAT) according to the CVC site. Two hundred and twenty-five children, with respective age and weight of 7.1 (1.3-40.1) months and 7.7 (3.6-16) kg, required 257 CVCs, including 147 (57.2%) inserted in the BCV. The risk of the primary outcome was lower in the BCV than in the other sites (5.4 vs 16.4%; OR: 0.29; 95% CI: 0.12-0.70; p = 0.006). CLABSI incidence density rate (2.8 vs 8.96 per 1000 catheter days, p < 0.001) and CLAT incidence rate (2.7 vs 10%, p = 0.016) were also lower at this site. CONCLUSION: BCV catheterization via the US-guided supraclavicular approach may decrease CVC maintenance-related complications in children hospitalized in a PICU. What is Known: • Placement of a central venous catheter (CVC) in children is associated with mechanical risks during insertion, and with infectious and thrombotic complications during its maintenance. • Ultrasound (US)-guided supraclavicular catheterization of the brachiocephalic vein (BCV) is feasible in infants and children. What is New: • This observational study suggested that BCV catheterization via the US-guided supraclavicular approach was associated with a lower risk of CVC insertion and maintenance-related complications, compared with the other catheterization sites.

Diagnostic value of human papillomavirus (HPV) 16 and HPV18 viral loads for the detection of high-grade cervical intraepithelial neoplasia (CIN2+) in a cohort of African women living with HIV.

BACKGROUND: African women living with HIV (WLHIV) are at high risk of cervical cancer but rarely adequately screened. Better strategies enabling identification of WLHIV with high-grade cervical intraepithelial lesions (CIN2+) are required. OBJECTIVES: To investigate the diagnostic value of HPV16 and HPV18 viral loads in a cohort of African WLHIV. DESIGN: HPV16 and HPV18 viral loads were determined by quantitation of the E6 gene DNA by real-time PCR in cervical specimens collected at baseline and endline (16 months) from 245 African WLHIV positive for HPV16 or/and HPV18. Cervical biopsies were graded using the histopathological CIN classification. RESULTS: Women with CIN2+ had higher viral load for HPV16 (p < 0.0001) or HPV18 (p = 0.03) than those without CIN2+. HPV16 viral load ≥3.59 log copies/1000 cells detected CIN2+ with sensitivity and specificity of 93.5% (95%CI: 81.7-98.3%) and 74.1% (95%CI: 66.3-80.6%), respectively, whereas HPV18 viral load ≥1.63 log copies/1000 cells detected CIN2+ with sensitivity and specificity of 59.1% (95%CI: 38.7-76.7%) and 66.9% (95%CI: 58.8-74.1%), respectively. A high baseline HPV16 viral load was significantly associated with persistence of, or progression to CIN2+ at endline; these findings were not observed for HPV18. CONCLUSIONS: HPV16 viral load is a powerful marker of CIN2+ in African WLHIV. HPV18 viral load is of lower diagnostic value in this population.

Epidemiology of high-risk human papillomavirus and cervical lesions in African women living with HIV/AIDS: effect of anti-retroviral therapy.

OBJECTIVE: To describe the effect of antiretroviral therapy (ART) and HIV-related factors on high-risk human papillomavirus (HR-HPV) and high-grade cervical intraepithelial neoplasia lesions (CIN2+) among women living with HIV/AIDS (WLHA) in sub-Saharan Africa. DESIGN: Prospective cohort of WLHA in Ouagadougou, Burkina Faso (BF) and Johannesburg, South Africa (SA). Recruitment was stratified by ART status. METHODS: At baseline and endline (median 16 months), cervical samples, and biopsies were analyzed for HPV genotyping (InnoLiPA) and by histology. Logistic regression was used to estimate associations of ART and HIV-related factors with HR-HPV and CIN2+ outcomes, and all results presented are adjusted for baseline CD4 cell count. RESULTS: Among 1238 enrolled WLHA (BF = 615; SA = 623), HR-HPV prevalence was 59.1% in BF and 79.1% in SA. CIN2+ prevalence was 5.8% in BF and 22.5% in SA. Compared with long-duration ART users (>2 years), HR-HPV prevalence was higher among short-duration ART users [≤2 years; adjusted prevalence ratio (aPR) = 1.24, 95% confidence interval (CI) 1.04-1.47] in BF, and CIN2+ prevalence was higher among short-duration ART users [adjusted odds ratio (aOR) = 1.99, 95% CI 1.12-3.54) and ART-naive participants (aOR = 1.87, 95% CI 1.11-3.17) in SA. Among 963 (77.8%) women seen at endline, HR-HPV persistence was 41.1% in BF and 30.2% in SA; CIN2+ incidence over 16-months was 1.2% in BF and 5.8% in SA. HR-HPV persistence was associated with being ART-naive in BF (aPR = 1.89, 95% CI 1.26-2.83), and with short-duration ART use (aPR = 1.78, 95% CI 1.11-2.86) and HIV-1 plasma viral load at least 1000 copies/ml (aPR = 2.87, 95% CI 1.63-5.05) in SA. CIN2+ incidence was reduced among women on ART in SA (aOR = 0.39, 95% CI 0.15-1.01). CONCLUSION: Prolonged and effective ART is important in controlling HR-HPV and the development of CIN2+.

Performance of careHPV for detecting high-grade cervical intraepithelial neoplasia among women living with HIV-1 in Burkina Faso and South Africa: HARP study.

BACKGROUND: The careHPV assay is a test for high-risk (HR) human papillomaviruses (HPV) detection designed to be affordable in resource-poor settings. We evaluated the performance of careHPV screening among 1052 women living with HIV/AIDS included in the HARP (HPV in Africa Research Partnership) study in Burkina Faso (BF) and South Africa (SA). METHODS: Cervical samples were tested for HR-HPV by the careHPV and the INNO-LiPA HPV genotyping Extra assays. All women had Pap smear testing, visual inspection with acetic acid/Lugol's iodine (VIA/VILI) and colposcopy. Cervical biopsies were obtained for participants who were HR-HPV DNA positive by careHPV or who had abnormalities detected on cytology, VIA/VILI or colposcopy. RESULTS: Overall, 45.1% of women had a positive careHPV test (46.5% in BF, 43.8% in SA). The careHPV positivity rate increased with the grade of cytological lesions. Sensitivity and specificity of careHPV for the diagnosis of CIN2+ (n=60, both countries combined) were 93.3% (95% confidence interval (CI): 83.8-98.2) and 57.9% (95% CI: 54.5-61.2), respectively. Specificity increased with CD4 count. careHPV had a similar clinical sensitivity but higher specificity than the INNO-LiPA assay for detection of CIN2+. CONCLUSIONS: Our results suggest that careHPV testing is a reliable tool for cervical cancer screening in HIV-1-infected women in sub-Saharan Africa.

Comparison of analytical and clinical performances of the digene HC2 HPV DNA assay and the INNO-LiPA HPV genotyping assay for detecting high-risk HPV infection and cervical neoplasia among HIV-positive African women.

OBJECTIVES: To compare the Hybrid Capture 2 human papillomaviruses (HPV) DNA assay (HC2) and the INNO-LiPA HPV Genotyping Extra assay (INNO-LiPA) for cervical cancer screening in HIV-1-infected African women. DESIGN: The tests were compared for agreement in detecting high-risk HPV (hr-HPV) and performance to detect squamous intraepithelial lesions (SIL), by cytology, and cervical intraepithelial neoplasia, by histology, in cervical samples from 1224 women in Burkina Faso (N = 604) and South Africa (N = 620). RESULTS: When considering the 13 hr-HPV types detected by HC2, 634 (51.8%) and 849 (69.4%) samples were positive by HC2 and INNO-LiPA, respectively. Agreement between assays was 73.9% [adjusted kappa coefficient value, 0.44 (95% confidence interval: 0.43 to 0.53)]. Agreement improved with analysis restricted to women with high-grade cervical lesions [adjusted kappa coefficient value, 0.83 (95% confidence interval: 0.74 to 0.91)]. The prevalence of hr-HPV, as determined by HC2 and INNO-LiPA, was 34.5% and 54.5%, respectively, in samples with normal cytology, 48.0% and 68.0%, respectively, in samples with atypical squamous cells of undetermined significance, 51.8% and 75.2%, respectively, in samples with low-grade SIL, and 86.3% and 89.8%, respectively, in samples with high-grade SIL/atypical squamous cells that cannot exclude HSIL. Sensitivity, specificity, positive, and negative predictive values for the diagnosis of histological high-grade lesions (CIN2+) were 88.8%, 55.2%, 24.7% and 96.7%, and 92.5%, 35.1%, 19.1% and 96.6% for HC2 and INNO-LiPA, respectively. CONCLUSIONS: HC2 has lower analytical sensitivity but higher specificity than INNO-LiPA for diagnosing high-grade lesions; the 2 tests presented a comparable clinical sensitivity. HC2 might be suitable for cervical cancer screening in HIV-1-infected African women, but its use in resource-limited settings merits to be further evaluated in comparison with other prevention strategies.

Staphylococcus aureus in a neonatal care center: methicillin-susceptible strains should be a main concern.

BACKGROUND: In the context of a methicillin-susceptible Staphylococcus aureus (MSSA) outbreak, we aimed to improve our knowledge of S. aureus (SA) epidemiology in the neonatal care center (NCC) of a tertiary care teaching hospital. METHODS: We performed a complete one-year review of SA carrier, colonized or infected patients. Monthly prevalence and incidence of SA intestinal carriage, colonization and infection were calculated and the types of infection analysed. During the MSSA outbreak, strains were studied for antimicrobial resistance, content of virulence genes and comparative fingerprint in Pulsed-Field Gel Electrophoresis. Hand hygiene and catheter-related practices were assessed by direct observational audits. Environmental investigation was performed in search of a SA reservoir. RESULTS: Epidemiological analyses showed 2 or 3 prevalence peaks on a background of SA endemicity. In the NCC, during 2009, overall MSSA prevalence did not decrease below 5.5%, while mean MRSA prevalence was about 1.53%. Analysis of infection cases revealed that the outbreak corresponded to the emergence of catheter-related infections and was probably related to the relaxation in infection control practices in a context of high colonization pressure. Health care workers' white coats appeared as a potential environmental reservoir that could perpetuate SA circulation in the ward. CONCLUSION: This report emphasizes the importance of integrating MSSA along with methicillin-resistant SA in a program of epidemiological surveillance in the NCC.

Validation of nosocomial infection in neonatology: a new method for standardized surveillance.

BACKGROUND: Nosocomial infections (NIs) are a leading cause of mortality and morbidity in premature infants. We present a new method for detecting and confirming NIs in a neonatal intensive care unit. METHODS: Newborns with birth weight < 1,500 g or gestational age (GA) < 33 weeks were included prospectively over 2 years in a single-center tertiary neonatal intensive care unit. The computerized physician order entry system (CPOE) generated alerts when antibiotics were prescribed for at least 5 consecutive days and these cases were reviewed by an expert group following international recommendations. RESULTS: Four hundred sixty-one neonates were included, with a mean GA of 30 weeks (range, 26-32 weeks) and mean birth weight 1,270 g (range, 950-1600 g). The CPOE flagged 158 cases of potential NI, 85.1% of which were classified as true NI and 14.9% of which were false positive. Incidence and device-associated nosocomial bloodstream infection rates were 21.9% and 10.8 per 1,000 central venous catheter days, respectively. GA ≤ 28 weeks (odds ratio, 2.18; 95% confidence interval, 1.2-4) and > 7 central venous catheter days (odds ratio, 1.47; 95% confidence interval, 1.3-1.7) were independently associated with the risk of nosocomial bloodstream infection. CONCLUSION: Combining CPOE and interdisciplinary review may improve the accuracy of NI recording in a neonatal intensive care unit.