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1.  HIV and syphilis prevalence trends among men who have sex with men in Guangxi, China: yearly cross-sectional surveys, 2008–2012 
BMC Infectious Diseases  2014;14:367.
Background
Men who have sex with men (MSM) represent the fastest growing key population for incident HIV cases in China. We examined five consecutive years of HIV and syphilis prevalence and risk factors data among MSM in Guangxi Province with the second highest estimated number of people living with HIV/AIDS (PLWHAs) in China in 2011.
Methods
We collected demographic and behavioral data from national sentinel surveillance and HIV/syphilis blood samples in five annual cross-sectional surveys from 2008 to 2012. We analyzed HIV and syphilis prevalence trends stratified by social/behavioral characteristics.
Results
HIV prevalence climbed steadily from 1.7% (95% confidence interval [CI]: 1.0 to 3.0) in 2008 to 3.7% (95% CI: 3.0 to 5.0) in 2012. Syphilis prevalence increased steadily from 5.1% (95% CI: 4.0 to 6.0) in 2008 to 8.4% (95% CI: 7.0 to 10.0) in 2012. HIV prevalence rose notably among MSM who were ≤25 years of age, never married, did not engage in sexual intercourse with women in the past six months, and had not been tested for HIV in the past year. Syphilis prevalence rose notably among MSM who were >25 years of age, ever married or living with a partner, and engaged in sexual intercourse with women in the past six months. HIV prevalence was much higher in MSM with current syphilis than without. Finally, current syphilis was the most significant predictor of HIV infection, and age was the most significant predictor of syphilis infection.
Conclusions
HIV and the syphilis prevalence expansion among MSM suggest an urgent public health prevention challenge for Guangxi provincial health officials. Risk factors for each infection differed such that all MSM, each of whom might be at risk of HIV, syphilis or both, should be targets for heavy intervention.
doi:10.1186/1471-2334-14-367
PMCID: PMC4091643  PMID: 24993252
HIV; Syphilis; Prevalence trends; MSM; China; Guangxi Province
2.  Serological prevalence and persistence of high-risk human papillomavirus infection among women in Santiago, Chile 
BMC Infectious Diseases  2014;14:361.
Background
Human papillomavirus (HPV) serology is a main factor for designing vaccination programs and surveillance strategies; nevertheless, there are few reports of HPV seroprevalence in the general population, especially in Latin America. This study aimed to describe high-risk HPV serological prevalence, persistence, and association with concurrent cervical infection, in Chilean women.
Methods
1021 women from the general population, aged 15–85 years, were studied in 2001 of whom 600 were reexamined in 2006. The assessments at both time points included cervical HPV DNA testing, HPV antibody testing, cervical cytology and a sociodemographic/behavioral questionnaire. HPV DNA and antibodies against L1 protein of types 16, 18, 31, 33, 35, 45, 52, and 58 were assessed by reverse line blot and multiplex serology, respectively.
Results
Seropositivity was high at both baseline (43.2%) and follow-up (50.2%) and increased with age (p < 0.001); corresponding DNA prevalences were 6.7% and 8.7%. DNA and seroprevalence were associated at baseline (p = 0.01 for any HPV). Early age at first sexual intercourse and having had two or more sexual partners were independently associated with seropositivity. Most (82.0%) initially seropositive women remained seropositive at follow-up; 21.6% of initially seronegative women seroconverted, reaching 17.5% among women older than 60 years of age. ASCUS or worse cytology was correlated with HPV DNA positivity but not with HPV seropositivity.
Conclusion
HPV seroprevalence studies are a useful tool for learning about the dynamics of HPV infection in a community. This study contributes to understanding the natural history of HPV infection and provides a baseline assessment before the incorporation of HPV vaccination into a national program.
doi:10.1186/1471-2334-14-361
PMCID: PMC4091743  PMID: 24990706
Human papillomavirus; Seropersistence; Cohort; Serology; Antibodies; Natural history
3.  The impact of central line insertion bundle on central line-associated bloodstream infection 
BMC Infectious Diseases  2014;14:356.
Background
Knowledge about the impact of each central line insertion bundle on central line-associated bloodstream infection (CLABSI) is limited.
Methods
A quality-improvement intervention, including education, central venous catheter (CVC) insertion bundle, process and outcome surveillance, have been introduced since March 2013. Outcome surveillances, including CLABSI per 1,000 catheter-days, CLABSI per 1,000 inpatient-days, and catheter utilization rates (days of catheter use divided by total inpatient-days), were measured. As a baseline measurement for a comparison, we retrospectively collected data from March 1, 2012 to December 31, 2012.
Results
During this 10-month period, there were a total of 687 CVC insertions, and 627 (91.2%) insertions were performed by intensivists. The rate of CLABSI significantly declined from 1.65 per 1000 catheter-day during the pre-intervention period to 0.65 per 1000 catheter-day post-intervention period (P = 0.039). CLABSI more likely developed in subjects in which a maximal sterile barrier was not used compared with subjects in which it was used (P = 0.03). Moreover, CVC inserted by non-intensivists were more likely to become infected than CVC inserted by intensivists (P = 0.010).
Conclusions
This multidisciplinary infection control intervention, including a central line insertion care bundle, can effectively reduce the rate of CLABSI. The impact of different care bundle varies, and a maximal sterile barrier precaution during catheter insertion is an essential component of the care line insertion bundle.
doi:10.1186/1471-2334-14-356
PMCID: PMC4085375  PMID: 24985729
Central line bundle; Central line-associated bloodstream infection; Intensivist
4.  Characterisation of inflammatory response, coagulation, and radiological findings in Katayama fever: a report of three cases at the Medical University of Vienna, Austria 
BMC Infectious Diseases  2014;14:357.
Background
Katayama fever is an acute clinical condition characterised by high fever, dry cough and general malaise occurring during early Schistosoma spp. infection. It is predominantly reported in travellers from non-endemic regions. Whereas the immunological response to Schistosoma infection is well characterised, alterations in inflammatory markers and coagulation in response to acute infection are poorly understood.
Methods
Here we report the clinical, laboratory and radiological characteristics of three returning travellers with Katayama fever. Inflammatory markers and coagulation status were assessed repeatedly during follow-up to characterise the host response to infection. Radiographic findings were correlated with clinical and laboratory markers.
Results
Clinical symptoms were suggestive of a significant inflammatory response in all patients including high fever (>39°C), cough, and general malaise. Classical inflammatory markers including blood sedimentation rate, C-reactive protein, and serum amyloid A were only moderately elevated. Marked eosinophilia (33–42% of white blood cells) was observed and persisted despite anti-inflammatory and anthelminthic treatment for up to 32 weeks. Analysis of blood coagulation markers indicated increased coagulability reflected by elevated D-dimer values (0.57–1.17 μg/ml) and high thrombin generating potentials (peak thrombin activity: 311–384 nM). One patient showed particularly high levels of microparticle-associated tissue factor activity at initial presentation (1.64 pg/ml). Multiple pulmonary and hepatic opacities demonstrated by computed tomography (CT) scanning were associated with raised inflammatory markers in one patient.
Conclusions
The characterisation of the inflammatory response, blood coagulation parameters and radiological findings in three patients adds to our current understanding of Katayama fever and serves as a starting point for further systematic investigations of the pathophysiology of this acute helminthic infection.
doi:10.1186/1471-2334-14-357
PMCID: PMC4085376  PMID: 24985919
Schistosomiasis; Katayama; Inflammation; Coagulation; Radiology; Africa
5.  A peptide fragment from the human COX3 protein disrupts association of Mycobacterium tuberculosis virulence proteins ESAT-6 and CFP10, inhibits mycobacterial growth and mounts protective immune response 
BMC Infectious Diseases  2014;14:355.
Background
Tuberculosis (TB) is one of the most prevalent infectious diseases affecting millions worldwide. The currently available anti-TB drugs and vaccines have proved insufficient to contain this scourge, necessitating an urgent need for identification of novel drug targets and therapeutic strategies. The disruption of crucial protein-protein interactions, especially those that are responsible for virulence in Mycobacterium tuberculosis – for example the ESAT-6:CFP10 complex – are a worthy pursuit in this direction.
Methods
We therefore sought to improvise a method to attenuate M. tuberculosis while retaining the latter’s antigenic properties. We screened peptide libraries for potent ESAT-6 binders capable of dissociating CFP10 from ESAT-6. We assessed the disruption by a peptide named HCL2, of the ESAT-6:CFP10 complex and studied its effects on mycobacterial survival and virulence.
Results
We found that HCL2, derived from the human cytochrome c oxidase subunit 3 (COX3) protein, disrupts ESAT-6:CFP10 complex, binds ESAT-6 potently, disintegrates bacterial cell wall and inhibits extracellular as well as intracellular mycobacterial growth. In addition, an HCL2 expressing M. tuberculosis strain induces both Th1 and Th17 host protective responses.
Conclusions
Disruption of ESAT-6:CFP10 association could, therefore, be an alternate method for attenuating M. tuberculosis, and a possible route towards future vaccine generation.
doi:10.1186/1471-2334-14-355
PMCID: PMC4089558  PMID: 24985537
Tuberculosis; Human COX3; ESAT-6; CFP10; Protein-protein interactions; Th1; Th17
6.  CKR-L3, a deletion version CCR6-isoform shows coreceptor-activity for limited human and simian immunodeficiency viruses 
BMC Infectious Diseases  2014;14:354.
Background
The chemokine receptors (CKRs), mainly CCR5 and CXCR4 function as major coreceptors in infections caused by human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV). Approximately 20 G protein-coupled receptors (GPCRs) have been identified as minor coreceptors, alike CCR6 that we reported recently. Since CKR-L3 is indentified as a natural isoform of CCR6, we attempted in this study to explore the coreceptor function of CKR-L3.
Methods
NP-2 cells transduced with CD4-receptor (NP-2/CD4) normally remain resistant to HIV or SIV infection. However, the introduction of functional coreceptors can make these cells susceptible to these viruses. NP-2/CD4/CKR-L3 cells were produced to examine the coreceptor activity of CKR-L3. Likely, CCR6-isoform and the major coreceptors, CCR5 and CXCR4 were also examined in parallel. Presence of viral antigen in infected NP-2/CD4/coreceptor cells was detected by indirect immunofluorescence assay (IFA). The results were validated by detection of syncytia, proviral DNA and by measuring reverse transcriptase (RT) activities.
Results
HIV-2MIR and SIVsmE660 were found to infect NP-2/CD4/CKR-L3 cells, indicative of the coreceptor function of CKR-L3. Viral antigens appeared faster in NP-2/CD4/CKR-L3 cells than in NP-2/CD4/CCR6, indicating that CKR-L3 is a more efficient coreceptor. Moreover, syncytia formation was more rapid and RT release evidenced earlier and at higher levels with CKR-L3 than with CCR6. Sequence analysis in the C2-V3 envelope region of HIV-2MIR replicated through CKR-L3 and CCR6 coreceptor showed two and three amino acid substitutions respectively, in the C2 region compared to the CCR5-variant. The SIVsmE660-CKRL3 variant showed three amino acid substitutions in the V1 region, one change in the V2 and two changes in the C2 region. The SIVsmE660-CCR6 variant produced two changes in the V1 region, and three in the C2 region.
Conclusions
Isoform CKR-L3 exhibited coreceptor activity for limited primary HIV and SIV isolates with better efficiency than the parent CCR6-isoform. Amino acid substitutions in the envelope region of these viruses may confer selective pressure towards CKR-L3-use. CKR-L3 with other minor coreceptors may contribute to HIV and SIV pathogenesis including dissemination, trafficking and latency especially when major coreceptors become compromised. However, further works will be required to determine its clinical significance in HIV and SIV infection.
doi:10.1186/1471-2334-14-354
PMCID: PMC4089560  PMID: 24980635
HIV/SIV; Coreceptors; Chemokine receptors (CKRs); G protein-coupled receptors (GPCRs); CCR6 and CKR-L3
7.  Case-case-control study on factors associated with vanB vancomycin-resistant and vancomycin-susceptible enterococcal bacteraemia 
BMC Infectious Diseases  2014;14:353.
Background
Enterococci are a major cause of healthcare-associated infection. In Australia, vanB vancomycin-resistant enterococci (VRE) is the predominant genotype. There are limited data on the factors linked to vanB VRE bacteraemia. This study aimed to identify factors associated with vanB VRE bacteraemia, and compare them with those for vancomycin-susceptible enterococci (VSE) bacteraemia.
Methods
A case-case-control study was performed in two tertiary public hospitals in Victoria, Australia. VRE and VSE bacteraemia cases were compared with controls without evidence of enterococcal bacteraemia, but may have had infections due to other pathogens.
Results
All VRE isolates had vanB genotype. Factors associated with vanB VRE bacteraemia were urinary catheter use within the last 30 days (OR 2.86, 95% CI 1.09-7.53), an increase in duration of metronidazole therapy (OR 1.65, 95% CI 1.17-2.33), and a higher Chronic Disease Score specific for VRE (OR 1.70, 95% CI 1.05-2.77). Factors linked to VSE bacteraemia were a history of gastrointestinal disease (OR 2.29, 95% CI 1.05-4.99) and an increase in duration of metronidazole therapy (OR 1.23, 95% CI 1.02-1.48). Admission into the haematology/oncology unit was associated with lower odds of VSE bacteraemia (OR 0.08, 95% CI 0.01-0.74).
Conclusions
This is the largest case-case-control study involving vanB VRE bacteraemia. Factors associated with the development of vanB VRE bacteraemia were different to those of VSE bacteraemia.
doi:10.1186/1471-2334-14-353
PMCID: PMC4091649  PMID: 24973797
Enterococci; Vancomycin-resistant; Vancomycin-susceptible; Bacteraemia
8.  Clinical and epidemiological characteristics of individuals resistant to M. tuberculosis infection in a longitudinal TB household contact study in Kampala, Uganda 
BMC Infectious Diseases  2014;14:352.
Background
Despite sustained exposure to a person with pulmonary tuberculosis (TB), some M. tuberculosis (Mtb) exposed individuals maintain a negative tuberculin skin test (TST). Our objective was to characterize these persistently negative TST (PTST-) individuals and compare them to TST converters (TSTC) and individuals who are TST positive at study enrollment.
Methods
During a TB household contact study in Kampala, Uganda, PTST-, TSTC, and TST + individuals were identified. PTST- individuals maintained a negative TST over a 2 year observation period despite prolonged exposure to an infectious tuberculosis (TB) case. Epidemiological and clinical characteristics were compared, a risk score developed by another group to capture risk for Mtb infection was computed, and an ordinal regression was performed.
Results
When analyzed independently, epidemiological risk factors increased in prevalence from PTST- to TSTC to TST+. An ordinal regression model suggested age (p < 0.01), number of windows (p < 0.01) and people (p = 0.07) in the home, and sleeping in the same room (p < 0.01) were associated with PTST- and TSTC. As these factors do not exist in isolation, we examined a risk score, which reflects an accumulation of risk factors. This compound exposure score did not differ significantly between PTST-, TSTC, and TST+, except for the 5–15 age group (p = 0.009).
Conclusions
Though many individual factors differed across all three groups, an exposure risk score reflecting a collection of risk factors did not differ for PTST-, TSTC and TST + young children and adults. This is the first study to rigorously characterize the epidemiologic risk profile of individuals with persistently negative TSTs despite close exposure to a person with TB. Additional studies are needed to characterize possible epidemiologic and host factors associated with this phenotype.
doi:10.1186/1471-2334-14-352
PMCID: PMC4091673  PMID: 24970328
Transmission risk factors; Latent Mtb infection; Exposure; Household characteristics; PPD test
9.  Is expanding HPV vaccination programs to include school-aged boys likely to be value-for-money: a cost-utility analysis in a country with an existing school-girl program 
BMC Infectious Diseases  2014;14:351.
Background
Similar to many developed countries, vaccination against human papillomavirus (HPV) is provided only to girls in New Zealand and coverage is relatively low (47% in school-aged girls for dose 3). Some jurisdictions have already extended HPV vaccination to school-aged boys. Thus, exploration of the cost-utility of adding boys’ vaccination is relevant. We modeled the incremental health gain and costs for extending the current girls-only program to boys, intensifying the current girls-only program to achieve 73% coverage, and extension of the intensive program to boys.
Methods
A Markov macro-simulation model, which accounted for herd immunity, was developed for an annual cohort of 12-year-olds in 2011 and included the future health states of: cervical cancer, pre-cancer (CIN I to III), genital warts, and three other HPV-related cancers. In each state, health sector costs, including additional health costs from extra life, and quality-adjusted life-years (QALYs) were accumulated. The model included New Zealand data on cancer incidence and survival, and other cause mortality (all by sex, age, ethnicity and deprivation).
Results
At an assumed local willingness-to-pay threshold of US$29,600, vaccination of 12-year-old boys to achieve the current coverage for girls would not be cost-effective, at US$61,400/QALY gained (95% UI $29,700 to $112,000; OECD purchasing power parities) compared to the current girls-only program, with an assumed vaccine cost of US$59 (NZ$113). This was dominated though by the intensified girls-only program; US$17,400/QALY gained (95% UI: dominant to $46,100). Adding boys to this intensified program was also not cost-effective; US$128,000/QALY gained, 95% UI: $61,900 to $247,000).
Vaccination of boys was not found to be cost-effective, even for additional scenarios with very low vaccine or program administration costs – only when combined vaccine and administration costs were NZ$125 or lower per dose was vaccination of boys cost-effective.
Conclusions
These results suggest that adding boys to the girls-only HPV vaccination program in New Zealand is highly unlikely to be cost-effective. In order for vaccination of males to become cost-effective in New Zealand, vaccine would need to be supplied at very low prices and administration costs would need to be minimised.
doi:10.1186/1471-2334-14-351
PMCID: PMC4082618  PMID: 24965837
10.  Adipokines, hormones related to body composition, and insulin resistance in HIV fat redistribution syndrome 
BMC Infectious Diseases  2014;14:347.
Background
Lipodystrophies are characterized by adipose tissue redistribution, insulin resistance (IR) and metabolic complications. Adipokines and hormones related to body composition may play an important role linking these alterations. Our aim was to evaluate adipocyte-derived hormones (adiponectin, leptin, resistin, TNF-α, PAI-1) and ghrelin plasma levels and their relationship with IR in HIV-infected patients according to the presence of lipodystrophy and fat redistribution.
Methods
Anthropometric and metabolic parameters, HOMA-IR, body composition by DXA and CT, and adipokines were evaluated in 217 HIV-infected patients on cART and 74 controls. Fat mass ratio defined lipodystrophy (L-FMR) was defined as the ratio of the percentage of the trunk fat mass to the percentage of the lower limb fat mass by DXA. Patient’s fat redistribution was classified into 4 different groups according the presence or absence of either clinical lipoatrophy or abdominal prominence: no lipodystrophy, isolated central fat accumulation (ICFA), isolated lipoatrophy and mixed forms (MXF). The associations between adipokines levels and anthropometric, metabolic and body composition were estimated by Spearman correlation.
Results
Leptin levels were lower in patients with FMR-L and isolated lipoatrophy, and higher in those with ICFA and MXF. Positive correlations were found between leptin and body fat (total, trunk, leg, arm fat evaluated by DXA, and total, visceral (VAT), subcutaneous adipose tissue (SAT), and VAT/SAT ratio evaluated by CT) regardless of FMR-L, and with HOMA-IR only in patients with FMR-L. Adiponectin correlated negatively with VAT, and its mean levels were lower in patients with ICFA and higher in those with no lipodystrophy. Resistin was not correlated with adipose tissue but positively correlated with HOMA-IR in FMR-L patients. PAI-1 levels were higher in MXF-patients and their levels were positively correlated with VAT in those with FMR-L. Ghrelin was higher in HIV-infected patients than controls despite BMI-matching.
Conclusion
The overall body fat reduction in HIV lipoatrophy was associated with low leptin plasma levels, and visceral fat accumulation was mainly associated with decreased plasma levels of adiponectin.
doi:10.1186/1471-2334-14-347
PMCID: PMC4079215  PMID: 24958357
Lipodystrophy; HIV; Adipokines; Body composition; Insulin resistance
11.  Carotid intima media thickness is associated with body fat abnormalities in HIV-infected patients 
BMC Infectious Diseases  2014;14:348.
Background
HIV-infected patients may be at increased risk of cardiovascular (CV) events, and lipodystrophy is generally associated with proatherogenic metabolic disturbances. Carotid intima-media thickness (cIMT) has been used as a surrogate marker for atherosclerosis and it has been shown to be an independent risk factor for CV disease. Our objective was to evaluate cIMT in HIV-infected patients on combined anti-retroviral therapy (cART) with and without lipodystrophy defined by fat mass ratio (L-FMR), and to determine the association of lipodystrophy and visceral obesity [(visceral (VAT), subcutaneous adipose tissue (SAT) volume and VAT/SAT ratio, objectively evaluated by CT scan] with cIMT.
Methods
Cross-sectional study of 199 HIV-infected patients. Body composition by DXA and abdominal CT, lipids, blood pressure, inflammatory markers, and cIMT by ultrasonography were performed. L-FMR was defined as the ratio of the percentage of trunk fat mass to the percentage of lower limb fat mass by DXA. Categorical variables were compared using the chi-square or Fisher’s exact test. Spearman correlation coefficients were estimated to study the association between cIMT and clinical and metabolic characteristics. Means of cIMT, adjusted for age, were calculated, using generalized linear models.
Results
L-FMR was present in 41.2% of patients and cIMT was higher in these patients [0.81 (0.24) vs. 0.76 (0.25); p = 0.037)]. Lipodystrophic patients had higher VAT and VAT/SAT ratio and lower SAT. cIMT was associated with lipodystrophy evaluated by FMR, trunk fat, total abdominal fat, VAT and VAT/SAT ratio. No association was observed between cIMT and leg fat mass. Using generalized linear models, cIMT means were adjusted for age and no significant differences remained after this adjustment. The adjusted mean of cIMT was 0.787 (95% CI: 0.751-0.823) in patients without lipodystrophy, and 0.775 (95% CI: 0.732-0.817) in those with lipodystrophy (p = 0.671).
Conclusions
HIV-infected patients on cART with lipodystrophy defined by FMR, had a significantly higher cIMT. Carotid IMT was also associated with classical cardiovascular risk factors. In these patients, visceral adipose tissue had a significant impact on cIMT, although age was the strongest associated factor.
doi:10.1186/1471-2334-14-348
PMCID: PMC4087129  PMID: 24958511
Lipodystrophy; HIV; Carotid intima media thickness; Fat mass ratio; Body composition
12.  Development of quality indicators for antimicrobial treatment in adults with sepsis 
BMC Infectious Diseases  2014;14:345.
Background
Outcomes in patients with sepsis are better if initial empirical antimicrobial use is appropriate. Several studies have shown that adherence to guidelines dictating appropriate antimicrobial use positively influences clinical outcome, shortens length of hospital stay and contributes to the containment of antibiotic resistance.
Quality indicators (QIs) can be systematically developed from these guidelines to define and measure appropriate antimicrobial use. We describe the development of a concise set of QIs to assess the appropriateness of antimicrobial use in adult patients with sepsis on a general medical ward or Intensive Care Unit (ICU).
Methods
A RAND-modified, five step Delphi procedure was used. A multidisciplinary panel of 14 experts appraised and prioritized 40 key recommendations from within the Dutch national guideline on antimicrobial use for adult hospitalized patients with sepsis (http://www.swab.nl/guidelines). A procedure to select QIs relevant to clinical outcome, antimicrobial resistance and costs was performed using two rounds of questionnaires with a face-to-face consensus meeting between the rounds over a period of three months.
Results
The procedure resulted in the selection of a final set of five QIs, namely: obtain cultures; prescribe empirical antimicrobial therapy according to the national guideline; start intravenous drug therapy; start antimicrobial treatment within one hour; and streamline antimicrobial therapy.
Conclusion
This systematic, stepwise method, which combined evidence and expert opinion, led to a concise and therefore feasible set of QIs for optimal antimicrobial use in hospitalized adult patients with sepsis. The next step will entail subjecting these quality indicators to an applicability test for their clinimetric properties and ultimately, using these QIs in quality-improvement projects. This information is crucial for antimicrobial stewardship teams to help set priorities and to focus improvement.
doi:10.1186/1471-2334-14-345
PMCID: PMC4078010  PMID: 24950718
Sepsis; Antimicrobial treatment; Quality indicator; Quality improvement; Appropriate antimicrobial use; Appropriate antibiotic use
13.  Russian gonococcal antimicrobial susceptibility programme (RU-GASP) – resistance in Neisseria gonorrhoeae during 2009–2012 and NG-MAST genotypes in 2011 and 2012 
BMC Infectious Diseases  2014;14:342.
Background
Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a major concern worldwide and gonococcal AMR surveillance globally is imperative for public health purposes. In Eastern Europe, gonococcal AMR surveillance is exceedingly rare. However, in 2004 the Russian gonococcal antimicrobial susceptibility programme (RU-GASP) was initiated. The aims of this study were to describe the prevalence and trends of gonococcal AMR from 2009 to 2012, and molecular epidemiological genotypes in 2011 and 2012 in Russia.
Methods
Gonococcal isolates from 12–46 surveillance sites distributed across Russia, obtained in 2009 (n = 1200), 2010 (n = 407), 2011 (n = 423), and 2012 (n = 106), were examined for antimicrobial susceptibility using agar dilution method. Gonococcal isolates from 2011 and 2012 were investigated with N. gonorrhoeae multi-antigen sequence typing (NG-MAST).
Results
During 2009–2012, the proportions of gonococcal isolates resistant to ciprofloxacin, penicillin G, azithromycin and spectinomycin ranged from 25.5% to 44.4%, 9.6% to 13.2%, 2.3% to 17.0% and 0.9% to 11.6%, respectively. Overall, the resistance level to penicillin G was stable, the resistance level to ciprofloxacin was decreasing, however, the level of resistance to azithromycin increased. All isolates were susceptible to ceftriaxone using the US CLSI breakpoints. However, using the European breakpoints 58 (2.7%) of the isolates were resistant to ceftriaxone. Interestingly, this proportion was decreasing, i.e. from 4.8% in 2009 to 0% in 2012.
Conclusions
In Russia, the diversified gonococcal population showed a high resistance to ciprofloxacin, penicillin G and azithromycin. In general, the MICs of ceftriaxone were relatively high, however, they were decreasing from 2009 to 2012. Ceftriaxone should be the first-line for empiric antimicrobial monotherapy of gonorrhoea in Russia. It is essential to further strengthen the surveillance of gonococcal AMR (ideally also gonorrhoea treatment failures) in Russia.
doi:10.1186/1471-2334-14-342
PMCID: PMC4075497  PMID: 24947981
Neisseria gonorrhoeae; Gonorrhoea; Antimicrobial resistance; National surveillance; Russian gonococcal antimicrobial susceptibility programme (RU-GASP); Extended-spectrum cephalosporins (ESCs); Ceftriaxone; Treatment; N. gonorrhoeae multiantigen sequence typing (NG-MAST); Russia
14.  Characterisation of acute respiratory infections at a United Kingdom paediatric teaching hospital: observational study assessing the impact of influenza A (2009 pdmH1N1) on predominant viral pathogens 
BMC Infectious Diseases  2014;14:343.
Background
According to the World Health Organisation, influenza A (2009 pdmH1N1) has moved into the post-pandemic phase, but there were still high numbers of infections occurring in the United Kingdom in 2010-11. It is therefore important to examine the burden of acute respiratory infections at a large children’s hospital to determine pathogen prevalence, occurrence of co-infection, prevalence of co-morbidities and diagnostic yield of sampling methods.
Methods
This was a retrospective study of respiratory virus aetiology in acute admissions to a paediatric teaching hospital in the North West of England between 1st April 2010 and 31st March 2011. Respiratory samples were analysed either with a rapid RSV test if the patient had symptoms suggestive of bronchiolitis, followed by multiplex PCR testing for ten respiratory viruses, or with multiplex PCR testing alone if the patient had suspected other ARI. Patient demographics and data regarding severity of illness, presence of co-morbidities and respiratory virus sampling method were retrieved from case notes.
Results
645 patients were admitted during the study period. 82/645 (12.7%) patients were positive for 2009 pdmH1N1, of whom 24 (29.2%) required PICU admission, with 7.3% mortality rate. Viral co-infection occurred in 48/645 (7.4%) patients and was not associated with more severe disease. Co-morbidities were present more frequently in older children, but there was no significant difference in prevalence of co-morbidity between 2009 pdmH1N1 patients and those with other ARI. NPA samples had the highest diagnostic yield with 192/210 (91.4%) samples yielding an organism.
Conclusions
Influenza A (2009 pdmH1N1) is an ongoing cause of occasionally severe disease affecting both healthy children and those with co-morbidities. Surveillance of viral pathogens provides valuable information on patterns of disease.
doi:10.1186/1471-2334-14-343
PMCID: PMC4091667  PMID: 24948099
H1N1; Influenza; Paediatrics; Virology; Co-morbidities
15.  Epidemiological and clinical characteristics of children who died from hand, foot and mouth disease in Vietnam, 2011 
BMC Infectious Diseases  2014;14:341.
Background
In 2011, a large outbreak of hand, foot and mouth disease (HFMD) in Vietnam resulted in 113,121 children seeking medical attention, of whom170 died. Understanding the epidemiology of fatal HFMD may improve treatment and help targeting prevention activities for vulnerable populations. We describe epidemiological and clinical characteristics of children who died from HFMD in Vietnam in 2011.
Methods
Clinical data were obtained through reviewing medical records of the deaths occurring from January through December 2011 in all hospitals in Vietnam. Hospitals reported any deaths among patients with laboratory-confirmed enterovirus (EV) infection to the Ministry of Health. Data were extracted from the national database.
Results
Of the 169 deaths reviewed for whom records were available, 87% were 3-year-old or younger, 69% were male, 18% attended daycare, 89% lived in Southern Vietnam, and 85% of the deaths occurred between May-October 2011. One hundred thirty (77%) cases sought treatment in a hospital within three days of onset of illness. Symptoms at admission included fever (98%), myoclonus (66%), vomiting (53%), oral ulcers (50%) and vesicular erythema (50%). One hundred six (75%) cases had leukocytosis and 91 (54%) had hyperglycemia. One hundred three (61%) tested positive for EV, of which 84 (82%) were positive for EV71.
Conclusions
Deaths associated with HFMD occurred throughout 2011 among males three years or younger who were cared for at home. The HFMD control program should focus on interventions at the household level. Clinicians should be alerted to symptoms suggestive of severe HFMD including fever, myoclonus, vomiting, oral ulcers and vesicles with high white blood cell count especially in young children.
doi:10.1186/1471-2334-14-341
PMCID: PMC4068316  PMID: 24942066
Hand foot and mouth disease; Clinical manifestation; Enterovirus; Vietnam
16.  Interpreting measures of tuberculosis transmission: a case study on the Portuguese population 
BMC Infectious Diseases  2014;14:340.
Background
Tuberculosis remains a high burden for Human society despite considerable investments in its control. Unique features in the history of infection and transmission dynamics of tuberculosis pose serious limitations on the direct interpretation of surveillance data and call for models that incorporate latent processes and simulate specific interventions.
Methods
A transmission model was adjusted to the dataset of active tuberculosis cases reported in Portugal between 2002 and 2009. We estimated key transmission parameters from the data (i.e. time to diagnosis, treatment length, default proportion, proportion of pulmonary TB cases). Using the adjusted model to the Portuguese case, we estimated the total burden of tuberculosis in Portugal. We further performed sensitivity analysis to heterogeneities in susceptibility to infection and exposure intensity.
Results
We calculated a mean time to diagnose of 2.81 months and treatment length of 8.80 months in Portugal. The proportion defaulting treatment was calculated as 0.04 and the proportion of pulmonary cases as 0.75. Using these values, we estimated a TB burden of 1.6 million infected persons, corresponding to more than 15% of the Portuguese population. We further described the sensitivity of these estimates to heterogeneity.
Conclusions
We showed that the model reproduces well the observed dynamics of the Portuguese data, thus demonstrating its adequacy for devising control strategies for TB and predicting the effects of interventions.
doi:10.1186/1471-2334-14-340
PMCID: PMC4069091  PMID: 24941996
Heterogeneity; Sojourn times; Transmission dynamics; Tuberculosis epidemiology
17.  Late-onset bloodstream infections of Very-Low-Birth-Weight infants: data from the Polish Neonatology Surveillance Network in 2009–2011 
BMC Infectious Diseases  2014;14:339.
Background
Late-Onset Bloodstream Infections (LO-BSI) continue to be one of the most important complications associated with hospitalization of infants born with very low birth weight (VLBW). The aims of this study were to assess the epidemiology of LO-BSI together with the risk factors and the distribution of causative pathogens at six Polish neonatal intensive care units that participated in the Polish Neonatology Surveillance Network from January 1, 2009 to December 31, 2011.
Methods
The surveillance covered 1,695 infants whose birth weights were <1501 grams (VLBW) in whom LO-BSI was diagnosed >72 hours after delivery. Case LO-BSI patients were defined according to NeoKISS.
Results
Four hundred twenty seven episodes of LO-BSI were diagnosed with a frequency of 25.3% and an incidence density of 6.7/1000 patient-days (pds). Results of our multivariate analysis demonstrated that surgical procedures and lower gestational age were significantly associated with the risk of LO-BSI. Intravascular catheters were used in infants with LO-BSI significantly more frequently and/or for longer duration: Central venous cathters (CVC) (OR 1.29) and Peripheral venous catheters (PVC) (OR 2.8), as well as, the total duration of total parenteral nutrition (13 vs. 29 days; OR 1.81). Occurrence of LO-BSI was significantly associated with increased the length of mechanical ventilation (MV) (OR 2.65) or the continuous positive airway pressure (CPAP) (OR 2.51), as well as, the duration of antibiotic use (OR 2.98). The occurrence of more than one infection was observed frequently (OR 9.2) with VLBW with LO-BSI. Microorganisms isolated in infants with LO-BSI were dominated by Gram-positive cocci, and predominantly by coagulase-negative staphylococci (62.5%).
Conclusions
Independent risk factor for LO-BSI in VLBV infants are: low gestational age and requirement for surgery. The incidence rates of LO-BSI especially CVC-BSI were higher in the Polish NICUs surveillance than those of other national networks, similar to the central- and peripheral utilization ratio.
doi:10.1186/1471-2334-14-339
PMCID: PMC4074408  PMID: 24939563
18.  Treatment outcomes from community-based drug resistant tuberculosis treatment programs: a systematic review and meta-analysis 
BMC Infectious Diseases  2014;14:333.
Background
There is increasing evidence that community-based treatment of drug resistant tuberculosis (DRTB) is a feasible and cost-effective alternative to centralized, hospital-based care. Although several large programs have reported favourable outcomes from community-based treatment, to date there has been no systematic assessment of community-based DRTB treatment program outcomes. The objective of this study was to synthesize available evidence on treatment outcomes from community based multi-drug resistant (MDRTB) and extensively drug resistant tuberculosis (XDRTB) treatment programs.
Methods
We performed a systematic review and meta-analysis of the published literature to examine treatment outcomes from community-based MDRTB and XDRTB treatment programs. Studies reporting outcomes from programs using community-based treatment strategies and reporting outcomes consistent with WHO guidelines were included for analysis. Treatment outcomes, including treatment success, default, failure, and death were pooled for analysis. Meta-regression was performed to examine for associations between treatment outcomes and program or patient factors.
Results
Overall 10 studies reporting outcomes on 1288 DRTB patients were included for analysis. Of this population, 65% [95% CI 59-71%] of patients had a successful outcome, 15% [95% CI 12-19%] defaulted, 13% [95% CI 9-18%] died, and 6% [95% CI 3-11%] failed treatment for a total of 35% [95% CI 29-41%] with unsuccessful treatment outcome. Meta-regression failed to identify any factors associated with treatment success, including study year, age of participants, HIV prevalence, XDRTB prevalence, treatment regimen, directly observed therapy (DOT) location or DOT provider.
Conclusions
Outcomes of community-based MDRTB and XDRTB treatment outcomes appear similar to overall treatment outcomes published in three systematic reviews on MDRTB therapy. Work is needed to delineate program characteristics associated with improved treatment outcomes.
doi:10.1186/1471-2334-14-333
PMCID: PMC4071022  PMID: 24938738
Tuberculosis; Multidrug-resistant; Treatment; Community based
19.  IgG, IgM and IgA antibodies against the novel polyprotein in active tuberculosis 
BMC Infectious Diseases  2014;14:336.
Background
The present study was aimed to evaluate whether IgG, IgM and IgA antibodies levels detected against a novel Mycobacterium tuberculosis polyprotein 38 F-64 F (with 38 F being the abbreviation for 38kD-ESAT6-CFP10 and 64 F for Mtb8.4-MPT64-TB16.3-Mtb8) are suitable for diagnosing active tuberculosis, and for monitoring the efficacy of chemotherapy on TB patients.
Methods
In this study, a total of 371 active TB patients without treatment were selected and categorized into S+/C+ group (n = 143), S-/C+ group (n = 106) or S-/C- group (n = 122). A series of serum samples were collected from 82 active TB patients who had undergone anti-TB chemotherapy for 0–6 months at one month interval. Humoral responses (IgG, IgM and IgA) were determined for the novel Mycobacterium tuberculosis polyprotein using indirect ELISA methods in all of serum samples.
Results
For S+/C+, S-/C+ and S-/C- active tuberculosis patients before anti-TB chemotherapy, the sensitivities of tests based on IgG were 65.7%, 46.2% and 52.5% respectively; the sensitivities based on IgM were 21.7%, 24.5% and 18.9%; and the sensitivities based on IgA were 25.2%, 17.9% and 23.8%. By combination of three isotypes, for all active tuberculosis patients, the test sensitivity increased to 70.4% with the specificity being 91.5%. After anti-TB chemotherapy, there were no significant differences between groups with different courses of anti-TB chemotherapy.
Conclusions
The novel Mycobacterium tuberculosis polyprotein 38 F-64 F represents potential antigen suitable for measuring IgG, IgM and IgA antibodies. However, the serodiagnostic test based on the 38 F-64 F polyprotein appears unsuitable for monitoring the efficacy of chemotherapy.
doi:10.1186/1471-2334-14-336
PMCID: PMC4071025  PMID: 24939009
Tuberculosis; Serodiagnosis; Polyprotein
20.  Microarray of surface-exposed proteins of rickettsia heilongjiangensis for serodiagnosis of Far-eastern spotted fever 
BMC Infectious Diseases  2014;14:332.
Background
Far-eastern spotted fever (FESF) is an important emerging infectious disease in Northeast Asia. The laboratory diagnosis of FESF in hospitals is mainly based on serological methods. However, these methods need to cultivate rickettsial cells as diagnostic antigens, which is both burdensome and dangerous.
Methods
Eleven surface-exposed proteins (SEPs) were identified in our previous study and their recombinant proteins (rSEPs) fabricated on a microarray were serologically analyzed with seventeen paired sera from patients suffered from FESF in this study.
Results
All the rSEPs showed sensitivities of between 53% and 82% to acute-phase sera and of between 65% and 82% to convalescent-phase sera, and all the rSEPs except rRplA showed specificities of between 80% and 95%. The combination assay of two, three, or four of the four rSEPs (rOmpA-2, rOmpB-3, rRpsB, and rSdhB) showed better sensitivities of between 76% and 94% to the acute-phase sera or between 82% and 100% to the convalescent-phase sera and acceptable specificities of between 75% and 90%.
Conclusions
Our results suggest that the four rSEPs are more likely candidate antigens for serological diagnosis of FESF.
doi:10.1186/1471-2334-14-332
PMCID: PMC4071148  PMID: 24938647
Far-eastern spotted fever; Rickettsia heilongjiangensis; Protein microarray; Serological diagnosis
21.  Serovar distribution, antimicrobial resistance profiles, and PFGE typing of Salmonella enterica strains isolated from 2007–2012 in Guangdong, China 
BMC Infectious Diseases  2014;14:338.
Background
Salmonella enterica includes the major serovars associated with human salmonellosis. In this study, 1764 clinical Salmonella enterica isolates from diarrhea outpatients were collected from fifteen cities in Guangdong province, China, between 2007 and 2012. These isolates represent all of the Salmonella isolates collected from the province during that period.
Methods
The isolates were characterized by serovar determination, antimicrobial susceptibility tests and PFGE fingerprint typing.
Results
The serovar distribution results demonstrated that Salmonella Typhimurium (n = 523, 29.65%) and Salmonella 4,5,12:i:- (n = 244, 13.83%) are the most common serovars causing infant salmonellosis, whereas Salmonella Enteritidis (n = 257, 14.57%) mainly causes human salmonellosis in adults. The serovar shift from Salmonella Enteritidis to Salmonella Typhimurium occurred in 2008. Antimicrobial susceptibility data showed a high burden of multidrug resistance (MDR) (n = 1128, 56.58%), and a 20%-30% increase in the number of isolates resistant to ciprofloxacin (n = 142, 8.05%) and third-generation cephalosporins (n = 88, 4.99%) from 2007–2012. Only 9.97% of isolates (n = 176) were fully susceptible to all agents tested. A high burden of MDR was observed in Salmonella Typhimurium and Salmonella 4,5,12:i:- for all age groups, and a reduced susceptibility to third-generation cephalosporins and quinolones occurred particularly in infants (≤6 years). The dominant PFGE patterns were JPXX01.GD0004, JEGX01.GD0006-7 and JNGX01.GD0006-7. ACSSuT was the predominant MDR profile in the Salmonella Typhimurium & 4,5,12:i:- complexes, while ASSuT-Nal and ASSu-Nal were the major MDR profiles in Salmonella Enteritidis. The predominant PFGE patterns of the Salmonella Typhimurium & 4,5,12:i:- complexes and Salmonella Stanley were most prevalent in infants (≤6 years). However, no obvious relationship was observed between these PFGE profiles and geographic location.
Conclusions
These data reveal the serovar distribution of isolates recovered from diarrhea patients, the characteristics of resistant strains and fingerprint typing in Guangdong from 2007 to 2012. These results highlight a serovar shift and a worrying percentage of MDR strains with increasing resistance to quinolones and third-generation cephalosporins. Thus, continued surveillance of Salmonella and their MDR profiles using combined molecular tools and efforts to control the rapid increase in antimicrobial resistance among Salmonella in Guangdong are needed.
doi:10.1186/1471-2334-14-338
PMCID: PMC4071211  PMID: 24939394
Salmonella enterica; Non-typhoidal Salmonella; Antimicrobial susceptibility; Ciprofloxacin; Cephalosporins; MDR; PFGE
22.  The significance of Notch ligand expression in the peripheral blood of children with hand, foot and mouth disease (HFMD) 
BMC Infectious Diseases  2014;14:337.
Background
Hand, foot and mouth disease (HFMD), a virus-induced infectious disease that usually affects infants and children, has an increased incidence in China in recent years. This study attempted to investigate the role of the Notch signaling pathway in the pathogenesis of HFMD.
Methods
Eighty-two children diagnosed with HFMD were enrolled into this study. The HFMD group was further divided into the uncomplicated HFMD and HFMD with encephalitis groups. The control group included 40 children who underwent elective surgery for treatment of inguinal hernias.
Results
Children with HFMD displayed significantly reduced CD3+, CD3+CD4+ and CD3+CD8+ cell subsets, but substantially enhanced CD3−CD19+ cell subset (p < 0.05 versus control subjects). The expression levels of Notch ligands Dll1 and Dll4 in the peripheral blood of the HFMD group were significantly higher than those in the control group (p < 0.05). There were statistically significant differences in CD3+, CD3+CD4+ and CD3−CD19+ cell subsets, but not in Notch ligand expression, between the uncomplicated HFMD and HFMD with encephalitis groups. Dll4 expression in HFMD subjects correlated negatively with the CD3+ and CD3+CD8+ cell subsets (p < 0.05), but positively with the CD3−CD19+ cell subset (p < 0.05). Furthermore, Dll4 expression in HFMD with encephalitis subjects correlated positively with total white blood cell (WBC) counts and total protein contents in cerebrospinal fluid (CSF) (p < 0.05).
Conclusions
The Notch ligand Dll4 exhibits a strong correlation with the CD3+, CD3+CD8+ and CD3−CD19+ cell subsets in children with HFMD, indicating that the Notch signaling may be involved in the development of HFMD by affecting the number and status of peripheral lymphocytes.
doi:10.1186/1471-2334-14-337
PMCID: PMC4074334  PMID: 24939221
Notch signaling; Subsets of T lymphocytes; Hand; Foot and mouth disease; Children
23.  Microbial aetiology, outcomes, and costs of hospitalisation for community-acquired pneumonia; an observational analysis 
BMC Infectious Diseases  2014;14:335.
Background
The aim of this study was to investigate the clinical outcome and especially costs of hospitalisation for community-acquired pneumonia (CAP) in relation to microbial aetiology. This knowledge is indispensable to estimate cost-effectiveness of new strategies aiming to prevent and/or improve clinical outcome of CAP.
Methods
We performed our observational analysis in a cohort of 505 patients hospitalised with confirmed CAP between 2004 and 2010. Hospital administrative databases were extracted for all resource utilisation on a patient level. Resource items were grouped in seven categories: general ward nursing, nursing on ICU, clinical chemistry laboratory tests, microbiology exams, radiology exams, medication drugs, and other.linear regression analyses were conducted to identify variables predicting costs of hospitalisation for CAP.
Results
Streptococcus pneumoniae was the most identified causative pathogen (25%), followed by Coxiella burnetii (6%) and Haemophilus influenzae (5%). Overall median length of hospital stay was 8.5 days, in-hospital mortality rate was 4.8%.
Total median hospital costs per patient were €3,899 (IQR 2,911-5,684). General ward nursing costs represented the largest share (57%), followed by nursing on the intensive care unit (16%) and diagnostic microbiological tests (9%). In multivariate regression analysis, class IV-V Pneumonia Severity Index (indicative for severe disease), Staphylococcus aureus, or Streptococcus pneumonia as causative pathogen, were independent cost driving factors. Coxiella burnetii was a cost-limiting factor.
Conclusions
Median costs of hospitalisation for CAP are almost €4,000 per patient. Nursing costs are the main cause of these costs.. Apart from prevention, low-cost interventions aimed at reducing length of hospital stay therefore will most likely be cost-effective.
doi:10.1186/1471-2334-14-335
PMCID: PMC4078020  PMID: 24938861
Pneumonia; Bacterial infection; Health economist; Respiratory infection
24.  Cost effectiveness of a pentavalent rotavirus vaccine in Oman 
BMC Infectious Diseases  2014;14:334.
Background
Rotavirus gastroenteritis (RGE) is the leading cause of diarrhea in young children in Oman, incurring substantial healthcare and economic burden. We propose to formally assess the potential cost effectiveness of implementing universal vaccination with a pentavalent rotavirus vaccine (RV5) on reducing the health care burden and costs associated with rotavirus gastroenteritis (RGE) in Oman
Methods
A Markov model was used to compare two birth cohorts, including children who were administered the RV5 vaccination versus those who were not, in a hypothetical group of 65,500 children followed for their first 5 years of life in Oman. The efficacy of the vaccine in reducing RGE-related hospitalizations, emergency department (ED) and office visits, and days of parental work loss for children receiving the vaccine was based on the results of the Rotavirus Efficacy and Safety Trial (REST). The outcome of interest was cost per quality-adjusted life year (QALY) gained from health care system and societal perspectives.
Results
A universal RV5 vaccination program is projected to reduce, hospitalizations, ED visits, outpatient visits and parental work days lost due to rotavirus infections by 89%, 80%, 67% and 74%, respectively. In the absence of RV5 vaccination, RGE-related societal costs are projected to be 2,023,038 Omani Rial (OMR) (5,259,899 United States dollars [USD]), including 1,338,977 OMR (3,481,340 USD) in direct medical costs. However, with the introduction of RV5, direct medical costs are projected to be 216,646 OMR (563,280 USD). Costs per QALY saved would be 1,140 OMR (2,964 USD) from the health care payer perspective. An RV5 vaccination program would be considered cost saving, from the societal perspective.
Conclusions
Universal RV5 vaccination in Oman is likely to significantly reduce the health care burden and costs associated with rotavirus gastroenteritis and may be cost-effective from the payer perspective and cost saving from the societal perspective.
doi:10.1186/1471-2334-14-334
PMCID: PMC4078940  PMID: 24941946
Rotavirus; Vaccine; Cost effectiveness; Oman; Markov model
25.  Predictors of suboptimal CD4 response among women achieving virologic suppression in a randomized antiretroviral treatment trial, Africa 
BMC Infectious Diseases  2014;14:331.
Background
A subset of HIV-1 infected patients starting highly active antiretroviral treatment (HAART) experience suboptimal CD4 response (SCR) despite virologic suppression. We studied the rate of and risk factors for SCR among women starting HAART in the ACTG A5208 study conducted in 7 African countries. 741 HAART-naive women with screening CD4 count <200 cells/μL were randomized to start HAART with Tenofovir/Emtricitabine plus either Nevirapine or Lopinavir/Ritonavir.
Methods
This analysis includes the 625 women who remained on-study through 48 weeks without experiencing protocol-defined virologic failure. We defined SCR as < 100 CD4 cells/μL increase from baseline and absolute CD4 cell count < 350 cells/μL, both at 48 weeks after HAART initiation.
Results
The baseline characteristics for the 625 women prior to HAART initiation were: median age 33 years, screening CD4 count 134 cells/μL, and HIV-1 RNA 5.1 log10 copies/mL; 184 (29%) were WHO Stage 3 or 4.
Seventy one (11%) of these 625 women experienced SCR. Baseline factors independently associated with increased odds of SCR included older age, lower HIV-1 RNA, positive Hepatitis B surface antigen, and site location. At 96 weeks, only 6% of the SCR group had CD4 ≥ 350 cells/μL compared with 67% in the non SCR group.
Conclusion
After starting HAART, 11% of women with virologic suppression through 48 weeks experienced SCR. These patients were also less likely to achieve CD4 ≥ 350 cells/μL by 96 weeks. The underlying causes and long term clinical implications of SCR deserve further investigation.
Trial registration
Clinicaltrials.gov Identifier: NCT00089505
doi:10.1186/1471-2334-14-331
PMCID: PMC4083139  PMID: 24938526
HIV; Antiretroviral therapy; HAART; Immune response; CD4

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