Invasive pneumococcal disease in persons with predisposing factors is dominated by non-vaccine serotypes in Southwest Sweden.

BACKGROUND: The pneumococcal conjugate vaccine PCV7 was introduced in Southwest Sweden in the child vaccination program in 2009, followed by PCV13 in 2010 and PCV10 in 2015. In this retrospective cohort study we assessed the pneumococcal serotype distribution in relation to predisposing factors, clinical manifestations and outcome during seven years after PCV introduction. METHODS: Clinical data from 1278 patients with 1304 episodes of invasive pneumococcal disease (IPD) between January 2009 and December 2015 in Region Västra Götaland, Sweden, were retrospectively collected from medical records. Pneumococcal isolates were serotyped by gel diffusion and/or Quellung reactions performed at the Public Health Agency in Sweden. Associations between serotypes and clinical characteristics were statistically evaluated by use of Fisher's exact test, Mann-Whitney U test and Logistic regression analysis, whereas IPD episodes caused by serotypes over time were analyzed by Mantel-Haenszel chi-square test. RESULTS: With the exception of serotype 3, the prevalence of PCV13 serotypes decreased during the study period, from 76% (n = 157) of all IPD episodes in 2009 to 25% (n = 42) in 2015 (p < 0.001) while non-PCV13 serotypes increased, mainly among patients ≥65 years and in patients with predisposing factors, including cardiovascular disease, pulmonary disease and malignancy (p < 0.001 for all). Patients with predisposing factors, including those with malignancy, immune deficiency or renal disease, were more likely to have IPD caused by a serotype not included in PCV13 rather than a vaccine-included serotype. Serotype 3 was associated with intensive care unit admissions while serotype 1 and 7F caused IPD among healthier and younger patients. PCV13 serotypes were associated with invasive pneumonia, and non-PCV13 serotypes were associated with bacteremia with unknown focus and with manifestations other than pneumonia or meningitis. CONCLUSIONS: Non-PCV13 serotypes caused the majority of IPD cases in Southwest Sweden, especially in patients ≥65 years and in patients with predisposing factors. Serotype 3, included in PCV13, was prevalent and often caused severe disease.

Bacteria and viruses in the upper respiratory tract of Congolese children with radiologically confirmed pneumonia.

BACKGROUND: Acute pneumonia remains a leading cause of death among children below 5 years of age in the Democratic Republic of the Congo (DR Congo), despite introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) in 2013. Potential pathogens in the nasopharynx of hospitalised children with pneumonia have not been studied previously in DR Congo. Here we compare clinical characteristics, risk factors and nasopharyngeal occurrence of bacteria and viruses between children with severe and non-severe pneumonia. METHODS: Between June 2015 and June 2017, 116 children aged from 2 to 59 months hospitalised due to radiologically confirmed pneumonia at Panzi referral university hospital, Bukavu, Eastern DR Congo were included in the study and sampled from nasopharynx. A multiplex real-time PCR assay for detection of 15 different viruses and 5 bacterial species was performed and another multiplex PCR assay was used for pneumococcal serotype/serogroup determination. RESULTS: During the study period 85 (73%) of the children with radiologically confirmed pneumonia met the WHO classification criteria of severe pneumonia and 31 (27%) had non-severe pneumonia. The fatality rate was 9.5%. Almost all (87%) children were treated with antibiotics before they were hospitalised, in most cases with amoxicillin (58%) or trimethoprim-sulfamethoxazole (20%). The frequency of potential pathogens in the nasopharynx of the children was high, and any viral or bacterial nucleic acids present at high levels, irrespective of species or type, were significantly associated with severe pneumonia as compared with non-severe cases (52% versus 29%, p = 0.032). White blood cell count > 20,000/µL and C-Reactive Protein > 75 mg/dL were associated with severe pneumonia at admission. Fatal outcome was in the multivariable analysis associated with having a congenital disease as an underlying condition. One or more pneumococcal serotypes/serogroups could be identified in 61 patients, and out of all identified serotypes 31/83 (37%) were non-PCV13 serotypes. CONCLUSIONS: The occurrence of any bacteria or any viruses at high levels was associated with severe pneumonia at admission. Children with congenital disorders might need a higher attention when having symptoms of acute respiratory infection, as developed pneumonia could lead to fatal outcome.

Long-lasting chronic high load carriage of Epstein-Barr virus is more common in young pediatric renal transplant recipients.

BACKGROUND: Epstein-Barr virus (EBV) infections can induce post-transplant lymphoproliferative disorder (PTLD). A chronic high load (CHL), as indicated by long-term high EBV DNA levels after transplantation, has been associated with an enhanced risk of PTLD. We aimed to evaluate incidence, time of occurrence, risk factors, and outcome of EBV CHL carrier state after pediatric renal transplantation. METHODS: A retrospective study of 58 children aged 1-17 years (median 10), who underwent renal transplantation between January 2004 and June 2017 at a single medical center. EBV IgG antibodies in serum were analyzed before and yearly after transplantation. EBV DNA in whole blood were analyzed weekly for the first 3 months post-transplant, monthly up to 1 year and then at least once yearly. CHL was defined as EBV DNA ≥ 4.2 log10 Geq/ml in > 50% of the samples during ≥ 6 months. RESULTS: At transplantation, 31 (53%) patients lacked EBV IgG and 25 (81%) of them developed primary EBV infection post-transplant. Of the 27 seropositive patients, 20 (74%) experienced reactivation of EBV. Altogether, 14 (24%) children developed CHL, starting at a median of 69 days post-transplant and lasting for a median time of 2.3 years (range 0.5-6.5), despite reduction of immunosuppression. Patients with CHL were younger and 11/14 were EBV seronegative at transplantation. No child developed PTLD during median clinical follow-up of 7.8 years (range 0.7-13). CONCLUSIONS: CHL was frequent, long lasting, and occurred mainly in young transplant recipients. The absence of PTLD suggests that monitoring of EBV DNA to guide immunosuppression was effective.

Cost-effectiveness of childhood pneumococcal vaccination program in Ethiopia: results from a quasi-experimental evaluation.

BACKGROUND: Ethiopia was among the 15 countries that, together accounted for 64% of the world's severe episodes of pneumonia among children below the age of 5 in 2011. To reduce this burden, the 10-valent pneumococcal conjugate vaccine (PCV 10) was introduced into the general childhood national immunization program in Ethiopia in 2011. However, there is little evidence on its cost-effectiveness, and the aim of this study was to estimate the cost-effectiveness of the introduction of PCV 10 vaccination in the Ethiopian setting. METHODS: The cost-effectiveness analysis was carried out based on a quasi-experimental evaluation of implementing PCV 10 at the Butajira rural health program site in Ethiopia. The intervention and the control groups consisted 876 and 1010 children, respectively. Using data from program site's surveillance system database as a framework, health outcome and vaccination data were collected from medical records, immunization registration books and reports. Disability- Adjusted Life Year (DALY) was a main health outcome metric complimented by incidence of acute lower respiratory infection/1000-person years. Vaccination and treatment costs were collected by document review and cross-sectional household survey. RESULTS: In the intervention cohort, 626 of 876 (71.5%) children received PCV 10 vaccination. Until the first year of life, the incidence of acute lower respiratory infection was higher in the intervention group. After the first year of life, the incidence rate was 35.2 per 1000-person years in the intervention group compared to 60.4 per 1000-person years in the control group. The incremental cost-effectiveness ratio (ICER) per averted DALY for the intervention group during the total follow-up period was (2013 US$) 394.3 (undiscounted) and 413.8 (discounted). The ICER per averted DALY excluding the first year of life was (2013 US$) 225 (undiscounted) and 292.7 (discounted). CONCLUSION: Compared to the WHO's suggested cost-effectiveness threshold value, the results indicate that the general childhood PCV 10 vaccination was a cost-effective intervention in the Butajira rural health program site.

High rate of antibiotic resistance among pneumococci carried by healthy children in the eastern part of the Democratic Republic of the Congo.

BACKGROUND: Pneumococcal conjugate vaccines have been introduced in the infant immunisation programmes in many countries to reduce the rate of fatal pneumococcal infections. In the Democratic Republic of the Congo (DR Congo) a 13-valent vaccine (PCV13) was introduced in 2013. Data on the burden of circulating pneumococci among children after this introduction are lacking. In this study, we aimed to determine the risk factors related to pneumococcal carriage in healthy Congolese children after the vaccine introduction and to assess the antibiotic resistance rates and serotype distribution among the isolated pneumococci. METHODS: In 2014 and 2015, 794 healthy children aged one to 60 months attending health centres in the eastern part of DR Congo for immunisation or growth monitoring were included in the study. Data on socio-demographic and medical factors were collected by interviews with the children's caregivers. Nasopharyngeal swabs were obtained from all the children for bacterial culture, and isolated pneumococci were further tested for antimicrobial resistance using disc diffusion tests and, when indicated, minimal inhibitory concentration (MIC) determination, and for serotype/serogroup by molecular testing. RESULTS: The pneumococcal detection rate was 21%, being higher among children who had not received PCV13 vaccination, lived in rural areas, had an enclosed kitchen, were malnourished or presented with fever (p value < 0.05). The predominant serotypes were 19F, 11, 6A/B/C/D and 10A. More than 50% of the pneumococcal isolates belonged to a serotype/serogroup not included in PCV13. Eighty per cent of the isolates were not susceptible to benzylpenicillin and non-susceptibility to ampicillin and ceftriaxone was also high (42 and 37% respectively). Almost all the isolates (94%) were resistant to trimethoprim-sulphamethoxazole, while 43% of the strains were resistant to ≥3 antibiotics. CONCLUSIONS: Our study shows alarmingly high levels of reduced susceptibility to commonly used antibiotics in pneumococci carried by healthy Congolese children. This highlights the importance of local antibiotic resistance surveillance and indicates the needs for the more appropriate use of antibiotics in the area. The results further indicate that improved living conditions are needed to reduce the pneumococcal burden, in addition to PCV13 vaccination.

Long-term study showed that vaccination protected paediatric renal transplant recipients from life-threatening varicella zoster virus.

AIM: Renal transplant patients are particularly susceptible to highly contagious diseases due to their reduced immunity. We studied transplant recipients to gauge their varicella zoster virus (VZV) serology status over time and the outcome of any VZV infections. METHOD: This retrospective study comprised 85 children who underwent renal transplants in Gothenburg, Sweden, from 1986 to 2014, at a mean age of eight (1-18) years. The children's medical records were reviewed and 47 had the VZV infection pre-transplant and 38 had been vaccinated pre-transplant. Clinical outcomes were available for 85 children and serology results for 72. RESULTS: At transplantation, the VZV seropositivity rate was 50% in the vaccination group and 94% in the infection group and the antibody titres were significantly lower in the vaccination group (p = 0.031). During the median follow-up period of five years post-transplant, 28% of the vaccinated children and 97% of the infection group remained seropositive and the varicella infection affected eight children: one in the infection group and seven in the vaccination group. The herpes zoster was observed in two children in the infection group. CONCLUSION: This study demonstrated that VZV vaccination protected from symptomatic infections to a lesser extent than natural infection, but provided effective protection from life-threatening disease.

High prevalence and low cure rate of tuberculosis among patients with HIV in Xinjiang, China.

BACKGROUND: Tuberculosis and HIV co-epidemics are problems in many parts of the world. Xinjiang is a high tuberculosis and HIV prevalence area in China. We aimed to investigate the prevalence and cure rate of tuberculosis among HIV positive patients in Xinjiang. METHODS: In a retrospective study between 2006 and 2011, clinical and laboratory data on 333 patients with HIV and tuberculosis were compared to 2668 patients with HIV only. There were 31 HIV positive patients with no data on tuberculosis. RESULTS: The prevalence of tuberculosis co-infection among the HIV positive patients was 11% (95% CI 10-12%), significantly higher than the national figure in China of 2%. In most cases HIV was diagnosed late, with advanced immunodeficiency. The use of isoniazid preventive therapy was only 57.9% in patients without tuberculosis who fulfilled the criteria for receiving this prevention. The cure rate one year after diagnosis was 69.2%, which was lower than the officially reported 91.4% in all tuberculosis cases in Xinjiang in 2011. The hazard of not surviving over the five years was significantly higher in patients with HIV + tuberculosis compared to HIV only after adjusting for sex and Intravenous drug use with HR = 1.84 (95% CI 1.43-2.35; p < 0.0001). CONCLUSIONS: The prevalence of tuberculosis among HIV positive patients in Xinjiang was higher than in China taken as a whole, and HIV was diagnosed late, with underuse of isoniazid preventive therapy. The low cure rate and reduced survival can be due to late diagnosis of HIV and no testing for antibiotic resistance, together with insufficient control of adherence to the treatment regimens for tuberculosis and HIV.

Epidemiology of invasive pneumococcal infections: manifestations, incidence and case fatality rate correlated to age, gender and risk factors.

BACKGROUND: Incidence, manifestations and case-fatality rate (CFR) of invasive pneumococcal disease (IPD) vary with age and comorbidities. New vaccines, changing age distribution, prolonged survival among immunocompromised patients and improved sepsis management have created a need for an update of basic facts to inform vaccine recommendations. METHODS: Age, gender and comorbidities were related to manifestations and death for 2977 consecutive patients with IPD in a Swedish region with 1.5 million inhabitants during 13 years before introduction of pneumococcal conjugate vaccines (PCV) in the infant vaccination program. These data were related to population statistics and prevalence of several comorbidities, and compared with two previous studies giving a total follow-up of 45 years in the same area. RESULTS: The annual incidence was 15/100,000 for any IPD and 1.1/100,000 for meningitis; highest among elderly followed by children < 2 years. It was 2238/100,000 among myeloma patients, followed by chronic lymphatic leukemia, hemodialysis and lung cancer, but not elevated among asthma patients. CFR was 10 % among all patients, varying from 3 % below 18 years to 22 % ≥ 80 years. During 45 years, the IPD incidence increased threefold and CFR dropped from 20 to 10 %. Meningitis incidence remained stable (1.1/100,000/year) but CFR dropped from 33 to 13 %. IPD-specific mortality decreased among children <2 years from 3.1 to 0.46/100,000/year but tripled among those ≥65 years. CONCLUSIONS: IPD incidence and CFR vary widely between age and risk groups and over time even without general infant vaccination. Knowledge about specific epidemiological characteristics is important for informing and evaluating vaccination policies.

Cytomegalovirus infection and disease reduce 10-year cardiac allograft vasculopathy-free survival in heart transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) is associated with an increased risk of cardiac allograft vasculopathy (CAV), the major limiting factor for long-term survival after heart transplantation (HTx). The purpose of this study was to evaluate the impact of CMV infection during long-term follow-up after HTx. METHODS: A retrospective, single-centre study analyzed 226 HTx recipients (mean age 45 ± 13 years, 78 % men) who underwent transplantation between January 1988 and December 2000. The incidence and risk factors for CMV infection during the first year after transplantation were studied. Risk factors for CAV were included in an analyses of CAV-free survival within 10 years post-transplant. The effect of CMV infection on the grade of CAV was analyzed. RESULTS: Survival to 10 years post-transplant was higher in patients with no CMV infection (69 %) compared with patients with CMV disease (55 %; p = 0.018) or asymptomatic CMV infection (54 %; p = 0.053). CAV-free survival time was higher in patients with no CMV infection (6.7 years; 95 % CI, 6.0-7.4) compared with CMV disease (4.2 years; CI, 3.2-5.2; p < 0.001) or asymptomatic CMV infection (5.4 years; CI, 4.3-6.4; p = 0.013). In univariate analysis, recipient age, donor age, coronary artery disease (CAD), asymptomatic CMV infection and CMV disease were significantly associated with CAV-free survival. In multivariate regression analysis, CMV disease, asymptomatic CMV infection, CAD and donor age remained independent predictors of CAV-free survival at 10 years post-transplant. CONCLUSIONS: CAV-free survival was significantly reduced in patients with CMV disease and asymptomatic CMV infection compared to patients without CMV infection. These findings highlight the importance of close monitoring of CMV viral load and appropriate therapeutic strategies for preventing asymptomatic CMV infection.

Clinical evaluation of commercial nucleic acid amplification tests in patients with suspected sepsis.

BACKGROUND: Sepsis is a serious medical condition requiring timely administered, appropriate antibiotic therapy. Blood culture is regarded as the gold standard for aetiological diagnosis of sepsis, but it suffers from low sensitivity and long turnaround time. Thus, nucleic acid amplification tests (NAATs) have emerged to shorten the time to identification of causative microbes. The aim of the present study was to evaluate the clinical utility in everyday practice in the emergency department of two commercial NAATs in patients suspected with sepsis. METHODS: During a six-week period, blood samples were collected consecutively from all adult patients admitted to the general emergency department for suspicion of a community-onset sepsis and treated with intravenous antibiotics. Along with conventional blood cultures, multiplex PCR (Magicplex™) was performed on whole blood specimens whereas portions from blood culture bottles were used for analysis by microarray-based assay (Prove-it™). The aetiological significance of identified organisms was determined by two infectious disease physicians based on clinical presentation and expected pathogenicity. RESULTS: Among 382 episodes of suspected sepsis, clinically relevant microbes were detected by blood culture in 42 episodes (11%), by multiplex PCR in 37 episodes (9.7%), and by microarray in 32 episodes (8.4%). Although moderate agreement with blood culture (kappa 0.50), the multiplex PCR added diagnostic value by timely detection of 15 clinically relevant findings in blood culture-negative specimens. Results of the microarray corresponded very well to those of blood culture (kappa 0.90), but were available just marginally prior to blood culture results. CONCLUSIONS: The use of NAATs on whole blood specimens in adjunct to current culture-based methods provides a clinical add-on value by allowing for detection of organisms missed by blood culture. However, the aetiological significance of findings detected by NAATs should be interpreted with caution as the high analytical sensitivity may add findings that do not necessarily corroborate with the clinical diagnosis.

Clinical manifestations of invasive pneumococcal disease by vaccine and non-vaccine types.

Pneumococcal conjugated vaccines (PCVs) have shown protection against invasive pneumococcal disease by vaccine serotypes, but an increase in non-vaccine serotype disease has been observed. Type-specific effects on clinical manifestation need to be explored. Clinical data from 2096 adults and 192 children with invasive pneumococcal disease were correlated to pneumococcal molecular serotypes. Invasive disease potential for pneumococcal serotypes were calculated using 165 invasive and 550 carriage isolates from children. The invasive disease potential was lower for non-PCV13 compared to vaccine-type strains. Patients infected with non-PCV13 strains had more underlying diseases, were less likely to have pneumonia and, in adults, tended to have a higher mortality. Furthermore, patients infected with pneumococci belonging to clonal serotypes only expressing non-PCV13 capsules had a higher risk for septicaemia and mortality. PCV vaccination will probably lead to a decrease in invasive pneumococcal disease but an alteration in the clinical manifestation of invasive pneumococcal disease. Genetic lineages causing invasive pneumococcal disease in adults often express non-vaccine serotypes, which can expand after vaccination with an increased risk of infection in patients with underlying diseases.

Clinical outcomes of children with carbapenem-resistant Acinetobacter baumannii bacteremia.

BACKGROUND: A relentless increase in the rate of carbapenem-resistant among Acinetobacter baumannii has substantially reduced the access to effective antimicrobial regimens. Currently limited information is available regarding the prognosis or outcomes of children with blood stream infection caused by carbapenem resistant A. baumanii. OBJECTIVE: To determine the clinical outcomes and predictors for fatality among children with carbapenem-resistant A. baumannii (CRAB) bloodstream infection (BSI). MATERIAL AND METHOD: A retrospective descriptive study was conducted among children hospitalized at the Queen Sirikit National Institute of Child Health (Children's Hospital), Bangkok, Thailand. Those who had CRAB isolated from blood cultures during theperiod between October 2005 and September 2010 were included in the study. RESULTS: A total of 89 cases of BSI caused by CRAB were identified. The incidence was 1.2 cases per 1,000 hospitalized patients. The median age at onset of bacteremia was 62 days and 88% had at least one underlying comorbidity. The 2-week and 30-day case fatality rates were 39% and 42%, respectively. A large proportion of deaths (63%) occurred before blood culture results became available. Extended spectrum resistance, defined as resistance to all other first line antibiotics at the hospital, i.e., all cephalosporins, aminoglycoside, quinolone and carbapenems, was significantly associated with a higher 2-week case fatality rate (CFR) (48% compared with 23% among their counterpart, p = 0.028) and death at an earlier stage of the bacteremia (Kaplan-Meierp = 0.016). In univariate analysis, factors associated with 2-week case fatality include malignancy-associated febrile neutropenia, fever ≥2 days before the initiation of appropriate antibiotic, presence of septic shock, organ dysfunction, and being infected by extended spectrum resistant strains. Correspondingly, CFR of cases who received ≥1 appropriate empiric antibiotics within 24 hours of clinical suspicion appears to be lower albeit not reaching statistical significance, than their counterpart, i.e., the CFRs between the two groups were 10% vs. 23%, respectively (p = 0.675). Colistin susceptibility based on disc diffusion test remained high (100%) in this sample. Nevertheless, those who received colistin treatment had a 2-week CFR of 20%. On the other hand, none of the cases infected with sulbactam susceptible strain, who received sulbactam containing regimen (n = 15), died. No significant renal toxicity was observed among children receiving colistin treatment in our sample. CONCLUSION: Carbapenem resistant A. baumannii bacteremia exhibited a high fatality rate, which mainly occurred before the pathogen was known to the clinicians. Extended spectrum resistance was associated with high fatality rate. Early administration of effective empirical antibiotics such as colistin and sulbactam in this sample was associated with lower fatality rate among children affected by this condition.

Household air pollution and pneumococcal density related to nasopharyngeal inflammation in mothers and children in Ethiopia: A cross-sectional study.

BACKGROUND: Three billion people in low- and middle-income countries are exposed to household air pollution as they use biomass fuel for cooking. We investigated the associations between solid fuel use and nasopharyngeal (NP) inflammation, as well as the associations between high pneumococcal density and NP inflammation, in mothers and children in rural and urban Ethiopia. MATERIALS AND METHODS: Sixty pairs of mothers (median age, 30 years; range, 19-45 years) with a child (median age, 9 months; range, 1-24 months) were included from rural Butajira (n = 30) and urban Addis Ababa (n = 30) in Ethiopia. The cohort was randomly selected from a previous study of 545 mother/child pairs included 2016. Questionnaire-based data were collected which included fuel type used (solid: wood, charcoal, dung or crop waste; cleaner: electricity, liquefied petroleum gas). Nasopharyngeal (NP) samples were collected from all mothers and children and analyzed for the levels of 18 cytokines using a Luminex immunoassay. Pneumococcal DNA densities were measured by a real-time multiplex PCR and a high pneumococcal density was defined as a cyclic threshold (Ct) value ≤ 30. RESULTS: Mothers from rural areas had higher median CXCL8 levels in NP secretions than those from urban areas (8000 versus 1900 pg/mL; p < 0.01), while rural children had slightly higher IL-10 levels than those from the urban area (26 vs 13 pg/mL; p = 0.04). No associations between fuel type and cytokine levels were found. However, a high pneumococcal density was associated with higher levels of cytokines in both mothers (CCL4, CXCL8, IL-1ß, IL-6 and VEGF-A) and children (CCL4, CXCL8, IL-1ß, IL-6 and IL-18). CONCLUSIONS: No significant associations were found between solid fuel use and NP inflammation in Ethiopian mothers and children, but the inflammatory activity was higher in individuals living in the rural compared to the urban area. In addition, high cytokine levels were associated with high pneumococcal density in both mothers and children, indicating a significant impact of NP pathogens on inflammatory mediator levels in upper airways.

Co-occurrence of bacteria and viruses and serotype distribution of Streptococcus pneumoniae in the nasopharynx of Tanzanian children below 2 years of age following introduction of the PCV13.

Introduction: Pneumococcal conjugate vaccines have reduced severe disease attributed to vaccine-type pneumococci in children. However, the effect is dependent on serotype distribution in the population and disease development may be influenced by co-occurrence of viral and bacterial pathogens in the nasopharynx. Methods: Following introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) in Tanzania we performed repeated cross-sectional surveys, including 775 children below 2 years of age attending primary healthcare centers. All children were sampled from nasopharynx and pneumococci were detected by single-target PCR. Pneumococcal serotypes/groups and presence of viruses and other bacteria were determined by two multiplex PCR assays. Results: The prevalence of PCV13 vaccine-type pneumococci decreased by 50%, but residual vaccine-types were still detected in 21% of the children 2 years after PCV13 introduction. An increase in the non-vaccine-type 15 BC was observed. Pneumococci were often co-occurring with Haemophilus influenzae, and detection of rhino/enterovirus was associated with higher pneumococcal load. Discussion: We conclude that presence of residual vaccine-type and emerging non-vaccine-type pneumococci in Tanzanian children demand continued pneumococcal surveillance. High co-occurrence of viral and bacterial pathogens may contribute to the disease burden and indicate the need of multiple public health interventions to improve child health in Tanzania.

Lower incidence of CMV infection and acute rejections with valganciclovir prophylaxis in lung transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) is the most common opportunistic infection following lung transplantation. CMV replication in the lung allograft is described as accelerating the development of bronchiolitis obliterans syndrome (BOS). Finding a strategy to prevent CMV infection is an important issue. METHODS: We performed a retrospective, single-centre study of 114 lung transplant recipients (LTRs) who underwent lung transplantation from January 2001 to December 2006. In a smaller cohort of 88 CMV seropositive (R+) LTRs, three months of valganciclovir prophylaxis (2004-2006) was compared to three months of oral ganciclovir (2001-2003) with respect to the incidence of CMV infection/disease, the severity of CMV disease, acute rejection, BOS-free 4 year survival and 4 year survival. In the whole group of 114 LTRs the impact of CMV infection on long-term survival (BOS free 4 year survival and 6 year survival) was assessed. RESULTS: For the cohort of 88 CMV seropositive LTRs, the incidence of CMV infection/disease at one year was lower in the valganciclovir group compared to the ganciclovir group (24% vs. 54%, p = 0.003). There was a tendency towards reduced CMV disease, from 33% to 20% and a significant lower incidence of asymptomatic CMV infection (22% vs. 4%, p = 0.005). A lower incidence of acute rejection was observed in the valganciclovir group. However, there was no significant difference between the two groups in BOS free 4 year survival and 4 year survival.For the entire group of 114 LTRs, BOS-free 4 year survival for recipients with CMV disease was (32%, p = 0.005) and among those with asymptomatic CMV infection (36%, p = 0.061) as compared with patients without CMV infection (69%). Six year survival was lower among patients with CMV disease, (64%, p = 0.042) and asymptomatic CMV infection (55%, p = 0.018) than patients without CMV infection (84%). CONCLUSIONS: A lower incidence of CMV infection/disease and acute rejections was observed with valganciclovir (3 months) when compared to oral ganciclovir (3 months). The long-term impact of CMV infection/disease was significant for BOS-free survival and survival.

Invasive pneumococcal infections in Vellore, India: clinical characteristics and distribution of serotypes.

BACKGROUND: Streptococcus pneumoniae infection is a serious problem worldwide and the case fatality rate remains high. The aim of this study was to analyze the distribution of pneumococcal serotypes causing invasive pneumococcal disease (IPD), to survey the potential coverage of present and future vaccines, and to investigate differences between serotypes and groups of serotypes with regard to manifestation, case fatality rate, age, and other risk factors. METHODS: Isolates from 244 consecutive patients with IPD were collected at the Christian Medical College, Vellore, India between January 2007 and June 2011, and clinical data were obtained retrospectively. Clinical characteristics were analyzed both for individual serotypes and for those grouped as "invasive", "pediatric", or "vaccine" serotypes. RESULTS: The serotype coverage for the pneumococcal conjugated vaccines (PCV) PCV7, PCV10, PCV13, PCV15, and pneumococcal polysaccharide vaccine (PPV) PPV23 was 29%, 53%, 64%, 66%, and 73%, respectively. The proportion of IPD caused by vaccine types was lower than pre-vaccination studies from other parts of the world. In adults, serotype 1 was mainly isolated from previously healthy patients without risk factors for IPD. This serotype caused more pneumonia and less meningitis than other serotypes, as was also noted for the "invasive" serotypes (1, 5, and 7 F). CONCLUSIONS: The most common pneumococcal serotypes in this study behaved in similar ways to those in countries where the PCV has been introduced. Also, the most common serotypes in this study are included in the new PCVs. Therefore, a national program of childhood immunization with PCV10/13 in India is likely to be successful.

Human herpesvirus type 6 DNAemia and infection following allogeneic stem cell transplantation with a focus on long-term outcome.

Cases of human herpesvirus type 6 (HHV-6) infection and disease were retrospectively analysed in a cohort of 97 allogeneic haematopoietic stem cell transplantation (allo-SCT) patients in Gothenburg, Sweden (1997-2001). Altogether 54 of 97 (56%) patients were tested for HHV-6. HHV-6 DNAemia was detected in 15 of the tested patients at a median of 76 (range 24-387) days after SCT. Nine of these patients were treated against HHV-6 infection and disease for a total of 11 treatment episodes. The morbidity associated with HHV-6 DNAemia following allo-SCT was in most cases moderate. The overall 1-y survival among the patients with HHV-6 DNAemia was 11/15 (73%) and the 5-y survival was 10/15 (67%), which was not significantly different from the whole cohort.

Household fuel use and its association with potential respiratory pathogens among healthy mothers and children in Ethiopia.

BACKGROUND: Over 90% of Ethiopians still rely on solid fuels for cooking food. The pollution from the burning process causes adverse respiratory outcomes including respiratory infections. This study aimed to assess the association of the pollution with nasopharyngeal occurrence of potential pathogens. METHODS: We conducted a comparative cross-sectional study in urban and rural settings in Ethiopia in 2016. Questionnaire-based data were collected from 168 mothers and 175 children aged below two years. Multiplex real-time PCR assays were performed on nasopharyngeal secretions for detection of bacteria and viruses and for the identification of pneumococcal serotypes/groups. RESULTS: High rates of bacteria and viruses in the nasopharynx were detected by PCR among both the children and the mothers. Among the detected viruses, enterovirus was more commonly detected among rural children than among children from urban areas. Streptococcus pneumoniae and Haemophilus influenzae were both more prevalent among children and mothers from rural areas compared with urban groups and among those using solid fuels compared with cleaner fuel users. Children from rural households using solid fuels and children whose mothers had educational status below high school had four times higher odds for detection of S. pneumoniae compared with those households using cleaner energy or those children having mothers with a higher educational status, respectively. One or more serotype/serogroup was identified in about 40% of the samples that were positive for pneumococci. Out of all identified serotypes/serogroups, 43% in the children and 45% in the mothers belonged to PCV13, indicating the larger majority of detected pneumococci being non-PCV13 serotypes. CONCLUSION: This study presented a high carriage rate of S. pneumoniae and H. influenzae among both children and their mothers, especially in rural areas and among solid fuel users. Thus, interventions should target cleaner energy sources to the public and promote maternal education.

Antibiotic use in children under 5 years of age in Northern Tanzania: a qualitative study exploring the experiences of the caring mothers.

BACKGROUND: Antimicrobial resistance is a serious threat to the global achievements in child health thus far. Previous studies have found high use of antibiotics in children in Northern Tanzania, but the experiences of the primary care-givers, who play a key role in accessing and administering antibiotics for the sick child, have remained largely unknown. Therefore, the aim of this study was to understand mothers' conceptions of antibiotic use in their children, which is of importance when forming strategies to improve antibiotic use in the community. METHOD: A qualitative study including eight focus group discussions with mothers of under-five children in Moshi urban and rural districts, Northern Tanzania, was performed during 2019. The discussions were recorded, transcribed verbatim, translated into English and analysed according to the phenomenographic approach. FINDINGS: Three conceptual themes emerged during analysis; (1) conceptions of disease and antibiotics, (2) accessing treatment and (3) administering antibiotics. Antibiotics were often perceived as a universal treatment for common symptoms or diseases in children with few side-effects. Although mothers preferred to attend a healthcare facility, unforeseen costs, long waits and lack of financial support from their husbands, posed barriers for healthcare seeking. However, pharmacies were perceived as a cheap and convenient option to access previously used or prescribed antibiotics. Some mothers sought advice from a trusted neighbour regarding when to seek healthcare, thus resembling the function of the community health worker. CONCLUSIONS: To improve antibiotic use in children under 5 years of age in Northern Tanzania, the precarious situation that women often find themselves in as they access treatment for their sick children needs to be taken into consideration. It is necessary to improve structures, including the healthcare system, socioeconomic inequalities and promoting gender equality both in the household and in the public arena to reduce misuse of antibiotics. Meanwhile, equipping community health workers to support Tanzanian women in appropriate healthcare seeking for their children, may be a feasible target for intervention.

The relationship between cerebrovascular complications and previously established use of antiplatelet therapy in left-sided infective endocarditis.

BACKGROUND: Cerebrovascular complications (CVC) in infective endocarditis (IE) are common. The only established treatments to reduce the incidence of CVC in IE are antibiotics and in selected cases early cardiac surgery. Potential effects of previously established antiplatelet therapy are under debate. METHODS: In a prospective cohort study in Sweden and Demark, the influence of previously established antiplatelet therapy on CVC incidence and mortality in IE was assessed using logistic regression models. RESULTS: Among 684 left-sided definite IE episodes, 23.0% were seen in patients on established antiplatelet therapy (96% acetylsalicylic acid). Patients on antiplatelet therapy were older and significantly more often had a history of congestive heart failure prior to IE diagnosis. No difference in CVC rate was seen between patients with and without ongoing antiplatelet therapy (23.6% vs 25.0%, adjusted odds ratio (AOR) 0.8, 95% confidence interval (CI) 0.48-1.5). Ischemic stroke, which occurred in 115 episodes (16.8%), was the most common cerebral lesion, and haemorrhagic complications were seen in 16 (2.3%) patients without correlation to chronic antiplatelet therapy. Unadjusted 1-y mortality was higher for patients on previously established antiplatelet therapy (33.8% vs 24.1%, odds ratio (OR) 1.6, 95% CI 1.1-2.4), but after adjustment for covariables associated with mortality an opposite statistical trend was seen (AOR 0.7, 95% CI 0.4-1.1). CONCLUSIONS: The incidence of symptomatic CVC in IE patients was not reduced by previously established antiplatelet therapy. One-y mortality was higher in patients on antiplatelet therapy in univariate analysis, but after multivariable modelling this association was lost.