Non-vaccine serotype pneumococcal carriage in healthy infants in South Africa following introduction of the 13-valent pneumococcal conjugate vaccine.

BACKGROUND: Pneumococcal carriage studies provide a baseline for measuring the impact of pneumococcal conjugate vaccines (PCVs). The advent of conjugate vaccines has led to reductions in vaccine serotypes (VTs) in pneumococcal carriage. However, increasing non-vaccine serotypes (NVTs) remain a significant concern, necessitating continued surveillance of serotypes in the 13-valent PCV vaccine (PCV13) era. OBJECTIVES: To investigate pneumococcal carriage, serotype distribution and risk factors for pneumococcal colonisation among children presenting for routine immunisation at two clinics in Gauteng Province, South Africa (SA), 10 years after PCV introduction into the SA Expanded Programme on Immunisation (EPI-SA). METHODS: Nasopharyngeal swabs were collected from 322 healthy children aged between 6 weeks and 5 years at two clinic centres in 2014 and 2016. Demographic data, risk factors for colonisation and vaccination details were recorded. The pneumococcal isolates were serotyped and tested for antimicrobial susceptibility. RESULTS: Pneumococci were isolated from 138/316 healthy children (43.7%) presenting for routine immunisation at two clinics. The median age was 8.3 months and the age range 1.4 months - 5 years. Carriage varied across the age groups: 6 - 14 weeks 35.5%, 9 months 27.5%, 18 months 21.7%, and 5 years 15.2%. Risk factors significantly associated with pneumococcal colonisation included young age (9 - 18 months (odds ratio OR 3.5; 95% confidence interval (CI) 1.9 - 5.9), type of dwelling (single room (OR 8.1; 95% CI 1.3 - 52.3) or informal dwelling (OR 2.4; 95% CI 1.2 - 4.5)) and Haemophilus influenzae carriage (OR 5.6; 95% CI 0.6 - 2.5). Of the 26 serotypes detected, 19F (10/121; 8.3%) was the most frequent. The most frequent NVTs were 23B (16/121; 13.2%), 15B/C (14/121; 11.6 %) and 35B (11/121; 8.2%). Children aged 9 months carried the highest proportion of NVTs (33/101; 32.7%). Penicillin non-susceptibility was observed in 20 NVT isolates (20/36; 55.6%) and 2 VT isolates (2/36; 5.6%). CONCLUSIONS: The pneumococcal carriage prevalence described in our study varied across the age groups and was lower compared with other African studies that looked at pneumococcal carriage post PCV. The study gave insight into the common NVTs encountered at two immunisation clinics in Gauteng. Given that pneumococcal carriage precedes disease, common colonisers such as 15B/C and 35B may be sufficiently prevalent in carriage for expansion to result in significant disease replacement.

Factors associated with missed and delayed DTP3 vaccination in children aged 12 - 59 months in two communities in South Africa, 2012 - 2013.

BACKGROUND: Although immunisation services are available to all children in South Africa (SA), many children miss or have delays in receiving vaccines. There are limited data on factors associated with missed or delayed vaccination in children in this setting. OBJECTIVES: To assess vaccination coverage and factors associated with missed and delayed diphtheria-tetanus-pertussis vaccine third dose (DTP3) vaccination in children aged 12 - 59 months in two SA communities. METHODS: We used data from household-level healthcare utilisation surveys conducted in Soweto in 2012 and in Pietermaritzburg in 2013. Information on vaccination status was recorded from the Road to Health cards or vaccination history from clinics for children aged <5 years. Factors associated with missed or delayed DTP3 vaccination were assessed using unconditional logistic regression. RESULTS: Of a total of 847 eligible children aged 12 - 59 months, 716 had available vaccination information. Overall DTP3 vaccination coverage was high for both sites: 90.6% in Pietermaritzburg and 93.9% in Soweto. However, 32.6% and 25.2% of DTP3 vaccinations were delayed (received after 18 weeks of age) in Pietermaritzburg and Soweto, respectively. The median delay for DTP3 vaccinations was 4.7 weeks (interquartile range 1.7 - 23.0). Factors associated with delayed DTP3 vaccination included being born in 2010 (adjusted odds ratio (aOR) 3.0, 95% confidence interval (CI) 1.4 - 6.3) or 2011 (aOR 2.7, 95% CI 1.3 - 5.7) compared with being born in 2008, probably due to vaccine shortages; a low level of education of the primary caregiver, with children whose caregivers had completed secondary education having lower odds of delayed vaccination (aOR 0.5, 95% CI 0.3 - 0.9) than children whose caregivers only had primary education; and maternal HIV status, with unknown status (aOR 3.5, 95% CI 1.6 - 7.6) associated with higher odds of delay than positive status. Factors associated with missed DTP3 vaccination (not vaccinated by 12 months of age) included two or more children aged <5 years in a household (aOR 2.4, 95% CI 1.2 - 4.9) compared with one child, and household monthly income <ZAR500 (aOR 3.4, 95% CI 1.1 - 11.4) compared with ≥ZAR2 000. CONCLUSIONS: Despite high overall DTP3 coverage observed in two communities, many vaccinations were delayed. Vulnerable groups identified in this study should be targeted with improved vaccination services to enhance uptake and timeliness of vaccination.

What causes symptoms suggestive of tuberculosis in HIV-positive people with negative initial investigations?

OBJECTIVE: To identify the causes of symptoms suggestive of tuberculosis (TB) among people living with the human immunodeficiency virus (PLHIV) in South Africa. METHODS: A consecutive sample of HIV clinic attendees with symptoms suggestive of TB (1 of cough, weight loss, fever or night sweats) at enrolment and at 3 months, and negative initial TB investigations, were systematically evaluated with standard protocols and diagnoses assigned using standard criteria. TB was 'confirmed' if Mycobacterium tuberculosis was identified within 6 months of enrolment, and 'clinical' if treatment started without microbiological confirmation. RESULTS: Among 103 participants, 50/103 were pre-antiretroviral therapy (ART) and 53/103 were on ART; respectively 68% vs. 79% were female; the median age was 35 vs. 45 years; the median CD4 count was 311 vs. 508 cells/mm³. Seventy-two (70%) had 5% measured weight loss and 50 (49%) had cough. The most common final diagnoses were weight loss due to severe food insecurity (n = 20, 19%), TB (n = 14, 14%: confirmed n = 7; clinical n = 7), other respiratory tract infection (n = 14, 14%) and post-TB lung disease (n = 9, 9%). The basis for TB diagnosis was imaging (n = 7), bacteriological confirmation from sputum (n = 4), histology, lumbar puncture and other (n = 1 each). CONCLUSION: PLHIV with persistent TB symptoms require further evaluation for TB using all available modalities, and for food insecurity in those with weight loss.

An isolated outbreak of diphtheria in South Africa, 2015.

An outbreak of respiratory diphtheria occurred in two health districts in the province of KwaZulu-Natal in South Africa in 2015. A multidisciplinary outbreak response team was involved in the investigation and management of the outbreak. Fifteen cases of diphtheria were identified, with ages ranging from 4 to 41 years. Of the 12 cases that were under the age of 18 years, 9 (75%) were not fully immunized for diphtheria. The case fatality was 27%. Ninety-three household contacts, 981 school or work contacts and 595 healthcare worker contacts were identified and given prophylaxis against Corynebacterium diphtheriae infection. A targeted vaccination campaign for children aged 6-15 years was carried out at schools in the two districts. The outbreak highlighted the need to improve diphtheria vaccination coverage in the province and to investigate the feasibility of offering diphtheria vaccines to healthcare workers.

Temporal association of infant immunisation with pneumococcal conjugate vaccine on the ecology of Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus nasopharyngeal colonisation in a rural South African community.

BACKGROUND: Immunisation of children with pneumococcal conjugate vaccines (PCV) may affect the bacterial-ecology of the nasopharynx, including colonisation by Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus. The aim of this study was to evaluate the effect of infant PCV-immunisation on the nasopharyngeal ecology of these potentially pathogenic bacteria in a rural African setting. METHODS: Two cross sectional surveys were undertaken from May to October in 2009 (Period-1) which coincided with the introduction of 7-valent PCV (PCV7) and in May-October 2011 (Period-2). Consenting household members, where there was a child <2 years of age in residence, had nasopharyngeal swabs undertaken for culture. RESULTS: From Period-1 to Period-2 in children 0-2 years and 3-12 years, prevalence of overall S. pneumoniae colonisation decreased from 74.9% to 67.0% (p<0.001) and H. influenzae declined among children 3-12 years (55.1-45.3%, p<0.001) but not among those <2 years. The prevalence of S. aureus remained unchanged in all children. Competitive associations were found between S. pneumoniae and S. aureus and between H. influenzae and S. aureus among children. In individuals >12 years, the prevalence of colonisation decreased from 11.2% to 6.8%, 16.7% to 8.8% and 31.2% to 23.7% for S. pneumoniae, H. influenzae and S. aureus, respectively; p<0.001 for all comparions. Synergistic relationships for S. aureus with H. influenzae and S. pneumoniae were observed in both periods among this group.

[PREFERE - the German prostatic cancer study: questions and claims surrounding study initiation in January 2013]. / PREFERE - die Deutsche Prostatakrebsstudie : Fragen und Behauptungen rund um den Studienbeginn im Januar 2013.

The PREFERE study is a multicenter randomized study of patients with low or early intermediate risk for prostatic cancer. The four treatment options, radical prostatectomy, percutaneous irradiation therapy, permanent seed implantation and active surveillance recommended by the German S3 guidelines and international guidelines will be tested and compared with respect to effectiveness and potential side effects. Over a period of 4 years a total of 7,600 patients are to be recruited and assigned to 1 of these 4 therapy forms according to personal preference (by possible exclusion of 1 or 2 therapy options) in a 2-4 arm study design by randomization.

Antiferromagnetic order with atomic layer resolution in EuTe(111) films.

The temperature dependences of the magnetizations of individual atomic layers across an epitaxial antiferromagnetic EuTe film were derived from virtually background-free magnetic Bragg peaks with pronounced Laue oscillations recorded with soft x rays at the Eu-M5 resonance. The magnetizations of the outermost layers decrease significantly differently from those of bulk layers, in agreement with Heisenberg-Monte Carlo calculations. The results demonstrate the applicability of the method to complex ordering phenomena at surfaces and interfaces of thin films.

Impact of cotrimoxazole on non-susceptibility to antibiotics in Streptococcus pneumoniae carriage isolates among HIV-infected mineworkers in South Africa.

OBJECTIVES: To investigate risk factors for pneumococcal carriage and non-susceptibility among HIV-infected mineworkers in South Africa. METHODS: In a cross-sectional study, HIV clinic attendees were questioned about risk factors for pneumococcal carriage and antimicrobial non-susceptibility. Oropharyngeal and nasopharyngeal swabs were taken for pneumococcal culture, serotyping and susceptibility testing. RESULTS: Among 856 participants (854 male, median age 41.5years, median CD4 290cells/mm(3)), 294 (34.3%) were receiving cotrimoxazole prophylaxis. Overall, 75/856 (8.8%) carried S. pneumoniae; among those taking vs. not taking cotrimoxazole, 8.2% vs. 9.1% were carriers. Risk factors for pneumococcal carriage were living with a child (adjusted OR 2.12, 95% CI 1.06-4.62) and recent hospitalisation (adjusted OR 1.80; 95% CI 0.98-3.30). Among participants not taking cotrimoxazole, the prevalence of carriage was higher in individuals with lower CD4 counts. Comparing participants taking cotrimoxazole vs. not, 60.9% vs. 22.4% (p=0.001) isolates were non-susceptible to cotrimoxazole and 30.4% vs. 8.2% were non-susceptible to penicillin (p=0.014). Thirty three/72 (45.8%) isolates were paediatric serotypes/groups. Nasopharyngeal compared with oropharyngeal swabs had higher sensitivity in detecting carriage (53/75, 70.7% vs. 31/75, 41.3%), and adding oropharyngeal sampling increased detection from 6.2% to 8.8%. CONCLUSIONS: Non-susceptibility to cotrimoxazole and penicillin was more common among isolates from participants taking cotrimoxazole prophylaxis. Surveillance for antimicrobial susceptibility is important where prophylaxis is used. Treatment for pneumococcal disease should take into account a higher risk of non-susceptibility to antibiotics amongst individuals taking cotrimoxazole prophylaxis.

[Transdermal and oral opioids for outpatient pain therapy. Comparing patients' characteristics by a claims data analysis]. / Transdermale und orale Opioide in der ambulanten Schmerztherapie. Vergleich von Patientencharakteristika anhand einer GKV-Datenanalyse.

Opioid prescriptions have increased in Germany in recent years. The usage of transdermal therapeutic systems has substantially driven this growth. The analysis was based on claims data of a German statutory health insurance (2001-2003). Statistical analysis applied univariate comparisons (exploratively only) as well as a multivariate logistic regression models. Patients in the transdermal group were older and the percentage of women was higher than in the oral group. Patients in the transdermal group received their opioids significantly more often from a GP. They had significantly less prescriptions for laxatives and antidepressants. The patients in both groups differed significantly with regard to a number of characteristics. The results indicate that GPs prefer transdermal opioids if prescribing strong-acting opioids.

Comparison of the effects of macrolides, amoxicillin, ceftriaxone, doxycycline, tobramycin and fluoroquinolones, on the production of pneumolysin by Streptococcus pneumoniae in vitro.

OBJECTIVES: To compare the effects of subinhibitory concentrations of amoxicillin, ceftriaxone, azithromycin, clarithromycin, erythromycin, telithromycin, clindamycin, ciprofloxacin, moxifloxacin, tobramycin and doxycycline on pneumolysin production by a macrolide-susceptible strain and two macrolide-resistant strains [erm(B) or mef(A)] of Streptococcus pneumoniae. METHODS: Pneumolysin was assayed using a functional procedure based on the influx of Ca(2+) into human neutrophils. RESULTS: Only the macrolides/macrolide-like agents caused significant attenuation of the production of pneumolysin, which was evident with all three strains of the pneumococcus. CONCLUSIONS: Macrolides, at sub-MICs, but not other classes of antibiotic, subvert the production of pneumolysin, even in the presence of (and irrespective of the mechanism of) macrolide resistance in S. pneumoniae.

Clarithromycin alone and in combination with ceftriaxone inhibits the production of pneumolysin by both macrolide-susceptible and macrolide-resistant strains of Streptococcus pneumoniae.

OBJECTIVES: To investigate the effects of clarithromycin (0.01-0.5 mg/L) alone or in combination with ceftriaxone (0.1 and 0.25 mg/L) on pneumolysin production by both macrolide-susceptible and -resistant [2 erm(B) positive and 2 mef(A) positive] strains of Streptococcus pneumoniae. METHODS: The bacteria were cultured for 6 h at 37 degrees C/5% CO(2) in tryptone soy broth, washed, enumerated and resuspended to 0.5-3 x 10(8) cfu/mL in tissue culture medium, RPMI 1640. After 16 h of incubation at 37 degrees C / 5% CO(2), pneumolysin was assayed in the bacteria-free supernatants, as well as in lysates, using a functional assay based on the influx of calcium into human neutrophils. RESULTS: Exposure of not only macrolide-susceptible strains, but also the macrolide-resistant strains, of S. pneumoniae to sub-MICs of clarithromycin resulted in dose-related inhibition of the pneumolysin production, whereas production of the toxin was unaffected by ceftriaxone. CONCLUSIONS: These observations demonstrate that even in the setting of macrolide resistance the production of pneumolysin, a key virulence factor of the pneumococcus, is attenuated by exposure of this microbial pathogen to clarithromycin.

Impact of conjugate Haemophilus influenzae type b (Hib) vaccine introduction in South Africa.

OBJECTIVE: To analyse trends in reported invasive Haemophilus influenzae disease in South Africa within the first five years of introduction of conjugate Haemophilus influenzae type b (Hib) vaccine in the routine child immunization schedule. METHODS: We used national laboratory-based surveillance data to identify cases of invasive H. influenzae disease between July 1999 and June 2004, and submitted isolates for serotyping and antimicrobial susceptibility testing. FINDINGS: The absolute number of Hib cases (reported to the national surveillance system) among children below one year of age decreased by 65%, from 55 cases in 1999-2000 to 19 cases in 2003-04. Enhanced surveillance initiated in 2003, identified human immunodeficiency virus (HIV)-infection and incomplete vaccination as contributing factors for Hib transmission. The total number of laboratory-confirmed cases of H. influenzae remained unchanged because non-type b disease was being increasingly reported to the surveillance system concomitant with system enhancements. Children with non-typable disease were more likely to be HIV-positive (32 of 34, 94%) than children with Hib disease (10 of 14, 71%), P = 0.051. Recent Hib isolates were more likely to be multidrug resistant (2% in 1999-2000 versus 19% in 2003-04, P = 0.001). CONCLUSION: Data from a newly established national laboratory-based surveillance system showed a decrease in Hib disease burden among South African children following conjugate vaccine introduction and identified cases of non-typable disease associated with HIV infection.

Nosocomial outbreak of extended-spectrum beta-lactamase-producing Salmonella isangi in pediatric wards.

Since May 2000, extended-spectrum beta-lactamase-producing (ESBL) Salmonella Isangi were isolated from pediatric patients at a tertiary hospital. A total of 41 patients with positive cultures were reviewed, and the majority presented with gastroenteritis, fever, or both. One ESBL phenotype was noted in all isolates, and clonality was confirmed by pulsed-field gel electrophoresis. This is the first report of Salmonella sp. ESBL resistance in our hospital.

Outcome of cephalosporin treatment for serious infections due to apparently susceptible organisms producing extended-spectrum beta-lactamases: implications for the clinical microbiology laboratory.

Although extended-spectrum beta-lactamases (ESBLs) hydrolyze cephalosporin antibiotics, some ESBL-producing organisms are not resistant to all cephalosporins when tested in vitro. Some authors have suggested that screening klebsiellae or Escherichia coli for ESBL production is not clinically necessary, and when most recently surveyed the majority of American clinical microbiology laboratories did not make efforts to detect ESBLs. We performed a prospective, multinational study of Klebsiella pneumoniae bacteremia and identified 10 patients who were treated for ESBL-producing K. pneumoniae bacteremia with cephalosporins and whose infecting organisms were not resistant in vitro to the utilized cephalosporin. In addition, we reviewed 26 similar cases of severe infections which had previously been reported. Of these 36 patients, 4 had to be excluded from analysis. Of the remaining 32 patients, 100% (4 of 4) patients experienced clinical failure when MICs of the cephalosporin used for treatment were in the intermediate range and 54% (15 of 28) experienced failure when MICs of the cephalosporin used for treatment were in the susceptible range. Thus, it is clinically important to detect ESBL production by klebsiellae or E. coli even when cephalosporin MICs are in the susceptible range (

Utility of blood cultures and incidence of mycobacteremia in patients with suspected tuberculosis in a South African infectious disease referral hospital.

SETTING: A 500-bed government referral institution for patients with tuberculosis and other infectious diseases in Gauteng, South Africa. OBJECTIVES: To assess the usefulness of BACTEC blood cultures over and above that of other microbiological methods for the diagnosis of tuberculosis in patients who are suspected of suffering from tuberculosis. DESIGN: Mycobacterial blood cultures were obtained from patients presenting with symptoms suspicious of tuberculosis and where there was no clinical evidence of other infectious etiologies, and from patients who had failed tuberculosis treatment. RESULTS: Sixteen (22%) of 71 patients included in the study were positive for Mycobacterium tuberculosis on blood culture, while seven (10%) were positive for M. avium complex (MAC). Twelve (75%) of the patients with tuberculosis and positive blood cultures were however also positive for acid-fast bacilli on sputum smears and eight (50%) were initially diagnosed clinically and radiographically as localized pulmonary tuberculosis. Blood cultures positive for mycobacteria were only found among patients with human immunodeficiency virus infection (HIV). CONCLUSIONS: Bacteremia with M. tuberculosis complex was detected in HIV-infected patients with suspected tuberculosis, even in patients presenting with localized pulmonary infection on initial clinical assessment. Among patients with suspected tuberculosis, blood cultures were useful in diagnosing unsuspected MAC disease, but did not add to the diagnostic yield of conventional tests for tuberculosis used routinely, namely sputum microscopy and culture, or occasional biopsy specimens.