Long-term surveillance of invasive pneumococcal disease: The impact of 10-valent pneumococcal conjugate vaccine in the metropolitan region of Salvador, Brazil.

BACKGROUND: In 2010, Brazil introduced the ten-valent pneumococcal conjugate vaccine (PCV10) in the national infant immunization program. Limited data on the long-term impact of PCV10 are available from lower-middle-income settings. We examined invasive pneumococcal disease (IPD) in Salvador, Bahia, over 11 years. METHODS: Prospective laboratory-based surveillance for IPD was carried out in 9 hospitals in the metropolitan region of Salvador from 2008 to 2018. IPD was defined as Streptococcus pneumoniae cultured from a normally sterile site. Serotype was determined by multiplex polymerase chain reaction and/or Quellung reaction. Incidence rates per 100,000 inhabitants were calculated for overall, vaccine-type, and non-vaccine-type IPD using census data as the denominator. Incidence rate ratios (IRRs) were calculated to compare rates during the early (2010-2012), intermediate (2013-2015), and late (2016-2018) post-PCV10 periods in comparison to the pre-PCV10 period (2008-2009). RESULTS: Pre-PCV10, overall IPD incidence among all ages was 2.48/100,000. After PCV10 introduction, incidence initially increased (early post-PCV10 IRR 3.80, 95% CI 1.18-1.99) and then declined to 0.38/100,000 late post-PCV10 (IRR 0.15; 95% CI 0.09-0.26). The greatest reductions in the late post-PCV10 period were observed in children aged ≤2 years, with no cases (IRR not calculated) and those ≥60 years (IRR 0.11, 95% CI 0.03-0.48). Late post-PCV10, significant reductions were observed for both PCV10 serotypes (IRR 0.02; 95% CI 0.0-0.15) and non-PCV10 serotypes (IRR 0.27; 95%CI 0.14-0.53). Non-PCV10 serotypes 15B, 12F, 3, 17F, and 19A became predominant late post-PCV10 without a significant increase in serotype-specific IPD incidence compared to pre-PCV10. CONCLUSION: Significant declines in IPD, including among adults not eligible for vaccination, suggest direct and indirect protection up to nine years after PCV10 introduction, without evidence of significant replacement disease. Continued surveillance is needed to monitor changes in non-vaccine serotypes and inform decisions about introducing higher valent PCVs.

Multi-country cross-sectional study of colonization with multidrug-resistant organisms: protocol and methods for the Antibiotic Resistance in Communities and Hospitals (ARCH) studies.

BACKGROUND: Antimicrobial resistance is a global health emergency. Persons colonized with multidrug-resistant organisms (MDROs) are at risk for developing subsequent multidrug-resistant infections, as colonization represents an important precursor to invasive infection. Despite reports documenting the worldwide dissemination of MDROs, fundamental questions remain regarding the burden of resistance, metrics to measure prevalence, and determinants of spread. We describe a multi-site colonization survey protocol that aims to quantify the population-based prevalence and associated risk factors for colonization with high-threat MDROs among community dwelling participants and patients admitted to hospitals within a defined population-catchment area. METHODS: Researchers in five countries (Bangladesh, Chile, Guatemala, Kenya, and India) will conduct a cross-sectional, population-based prevalence survey consisting of a risk factor questionnaire and collection of specimens to evaluate colonization with three high-threat MDROs: extended-spectrum cephalosporin-resistant Enterobacteriaceae (ESCrE), carbapenem-resistant Enterobacteriaceae (CRE), and methicillin-resistant Staphylococcus aureus (MRSA). Healthy adults residing in a household within the sampling area will be enrolled in addition to eligible hospitalized adults. Colonizing isolates of these MDROs will be compared by multilocus sequence typing (MLST) to routinely collected invasive clinical isolates, where available, to determine potential pathogenicity. A colonizing MDRO isolate will be categorized as potentially pathogenic if the MLST pattern of the colonizing isolate matches the MLST pattern of an invasive clinical isolate. The outcomes of this study will be estimates of the population-based prevalence of colonization with ESCrE, CRE, and MRSA; determination of the proportion of colonizing ESCrE, CRE, and MRSA with pathogenic characteristics based on MLST; identification of factors independently associated with ESCrE, CRE, and MRSA colonization; and creation an archive of ESCrE, CRE, and MRSA isolates for future study. DISCUSSION: This is the first study to use a common protocol to evaluate population-based prevalence and risk factors associated with MDRO colonization among community-dwelling and hospitalized adults in multiple countries with diverse epidemiological conditions, including low- and middle-income settings. The results will be used to better describe the global epidemiology of MDROs and guide the development of mitigation strategies in both community and healthcare settings. These standardized baseline surveys can also inform future studies seeking to further characterize MDRO epidemiology globally.

Factors associated with fatal cases of acute respiratory infection (ARI) among hospitalized patients in Guatemala.

BACKGROUND: Acute respiratory infection (ARI) is an important cause of mortality in children and adults. However, studies assessing risk factors for ARI-related deaths in low- and middle-income settings are limited. We describe ARI-related death and associated factors among children aged < 2 years and adults aged ≥18 years hospitalized with ARI in Guatemala. METHODS: We used respiratory illness surveillance data in Guatemala from 2007 to 2013. ARI was defined as evidence of acute infection and ≥ 1 sign/symptom of respiratory disease in hospitalized patients. Clinical, sociodemographic, and follow-up data were gathered. Nasopharyngeal/oropharyngeal swabs were collected from patients with ARI and tested for 6 respiratory viruses; urine was collected only from adults with ARI and tested for pneumococcal antigen. Blood cultures and chest radiographs were performed at the physician's discretion. Radiographs were interpreted per World Health Organization guidelines to classify endpoint pneumonia (i.e. suggestive of bacterial pneumonia). Multivariable logistic regression was used to compare characteristics of patients with fatal cases, including those who died in-hospital or were discharged in a moribund state, with those of patients with non-fatal cases. RESULTS: Among 4109 ARI cases identified in hospitalized children < 2 years old, 174 (4%) were fatal. Median age at admission was 4 and 6 months for children with fatal and non-fatal cases, respectively. Factors associated with fatality included low weight-for-age, low family income, heart disease, and endpoint pneumonia; breastfeeding and respiratory syncytial virus (RSV) detection were negatively associated with fatality. Among 1517 ARI cases identified in hospitalized adults ≥18 years, 181 (12%) episodes were fatal. Median age at admission was 57 years for adults with fatal and non-fatal cases. Low body mass index, male sex, kidney disease, and endpoint pneumonia were significantly more common among patients with fatal versus non-fatal cases. CONCLUSIONS: Our findings highlight some of the factors that must be addressed in order to reduce ARI-related mortality, including promotion of good nutrition, breastfeeding, management and prevention of chronic comorbidities, and poverty reduction. Although no specific pathogen increased risk for death, endpoint pneumonia was significantly associated with fatality, suggesting that the pneumococcal conjugate vaccine could contribute to future reductions in ARI-related mortality.

Effectiveness of 13-pneumococcal conjugate vaccine (PCV13) against invasive pneumococcal disease in children in the Dominican Republic.

BACKGROUND: Limited data are available on the effectiveness of 13-valent pneumococcal conjugate vaccine (PCV13) in resource-poor settings and PCV naïve populations. The Dominican Republic introduced PCV13 in September 2013 using a 2 + 1 schedule (2, 4, and 12 months) without a catch-up campaign. We evaluated PCV13 effectiveness against vaccine-type (VT) invasive pneumococcal disease (IPD) among children in the Dominican Republic. METHODS: We conducted a matched case-control study. A case-patient was defined as VT-IPD identified by culture or polymerase chain reaction (PCR) from a normally sterile-site in a hospitalized child who was age-eligible to have received ≥1 PCV13 dose. Four age- and neighborhood-matched controls were enrolled for each case-patient. We collected demographic, vaccination history, and risk factor data. Conditional logistic regression was performed. Vaccine effectiveness was calculated as (1- adjusted matched odds ratio for vaccination) X 100%. RESULTS: We enrolled 39 case-patients and 149 matched-controls. Most case-patients had pneumonia with pleural effusion (64%), followed by meningitis (28%) and septicemia (13%). The most common pneumococcal serotypes identified included 14 (18%), 3 (13%), 19A (10%), and 1 (8%). Fewer case-patients had ≥1 PCV13 dose as compared to controls (61.5% vs. 80.0%; p = 0.006). Adjusting for malnutrition and socioeconomic status, VE of ≥1 PCV13 dose compared to no doses was 67.2% (95% CI: 2.3% to 90.0%). Only 44% of controls were up-to-date for PCV13, suggesting low vaccine coverage in the population. CONCLUSIONS: We found that PCV13 provided individual protection against VT-IPD in this resource-poor setting with a PCV-naïve population, despite low PCV13 coverage. Expanding vaccination coverage might increase PCV13 impact.

Nasopharyngeal carriage of Streptococcus pneumoniae among HIV-infected and -uninfected children <5 years of age before introduction of pneumococcal conjugate vaccine in Mozambique

Nasopharyngeal carriage is a precursor for pneumococcal disease and can be useful for evaluating pneumococcal conjugate vaccine (PCV) impact. We studied pre-PCV pneumococcal carriage among HIV-infected and -uninfected children in Mozambique. Between October 2012 and March 2013, we enrolled HIV-infected children age <5 years presenting for routine care at seven HIV clinics in 3 sites, including Maputo (urban-south), Nampula (urban-north), and Manhiça (rural-south). We also enrolled a random sample of HIV-uninfected children <5 years old from a demographic surveillance site in Manhiça. A single nasopharyngeal swab was obtained and cultured following enrichment in Todd Hewitt broth with yeast extract and rabbit serum. Pneumococcal isolates were serotyped by Quellung reaction and multiplex polymerase chain reaction. Factors associated with pneumococcal carriage were examined using logistic regression. Overall pneumococcal carriage prevalence was 80.5% (585/727), with similar prevalences among HIV-infected (81.5%, 339/416) and HIV-uninfected (79.1%, 246/311) children, and across age strata. Among HIV-infected, after adjusting for recent antibiotic use and hospitalization, there was no significant association between study site and colonization: Maputo (74.8%, 92/123), Nampula (83.7%, 82/98), Manhiça (84.6%, 165/195). Among HIV-uninfected, report of having been born to an HIV-infected mother was not associated with colonization. Among 601 pneumococcal isolates from 585 children, serotypes 19F (13.5%), 23F (13.1%), 6A (9.2%), 6B (6.2%) and 19A (5.2%) were most common. The proportion of serotypes included in the 10- and 13-valent vaccines was 44.9% and 61.7%, respectively, with no significant differences by HIV status or age group. Overall 36.9% (n = 268) of children were colonized with a PCV10 serotype and 49.7% (n = 361) with a PCV13 serotype. Pneumococcal carriage was common, with little variation by geographic region, age, or HIV status. PCV10 was introduced in April 2013; ongoing carriage studies will examine the benefits of PCV10 among HIV-infected and-uninfected children.

Burden of invasive pneumococcal disease among children in rural Mozambique: 2001-2012

: Invasive pneumococcal disease (IPD) is a major cause of illness and death among children worldwide. 10-valent pneumococcal conjugate vaccine (PCV10) was introduced as part of the Mozambican routine immunization program in April 2013. We characterized the IPD burden in a rural area of Mozambique before PCV introduction and estimated the potential impact of this intervention. Methods: We conducted population-based surveillance for IPD, defined as S. pneumoniae isolated from blood or cerebrospinal fluid, among children <5 years old admitted to Manhiça District Hospital, a referral hospital in a rural area with high prevalence of human immunodiciency virus infection. S. pneumoniae was identified using standard microbiologic methods and serotyped using sequential multiplex PCR or Quellung. IPD incidence was calculated among cases from a defined catchment area. Results: From January 2001 through December 2012, we isolated 768 cases of IPD, 498 (65%) of which were bacteraemic pneumonia episodes. A total of 391 (51%) were from the catchment area, yielding IPD incidence rates of 479, 390 and 107 episodes per 100,000 children-years at risk among children <12, 12-23 and 24-<60 months old, respectively. The overall IPD incidence fluctuated and showed a downward trend over time. In these same age groups, in-hospital death occurred in 48 (17%), 26 (12%), and 21 (13%) of all IPD cases, respectively. Overall 90% (543/603) of IPD isolates were available for serotyping; of those, 65% were covered by PCV10 and 83% by PCV13. Among 77 hospital deaths associated with serotyped IPD, 49% and 69% were caused by isolates included in the PCV10 and PCV13, respectively. Conclusions: We describe very high rates of IPD among children in rural Mozambique that were declining before PCV introduction. Children <1 year old have the greatest incidence and case fatality; although the rates remain high among older groups as well. Most IPD episodes and many deaths among children <5 years old will likely be prevented through PCV10 introduction in Mozambique.

Effect of 10-valent pneumococcal conjugate vaccine on nasopharyngeal carriage of Streptococcus pneumoniae and Haemophilus influenzae among children in São Paulo, Brazil

In March 2010, Brazil introduced the 10-valent pneumococcal conjugate vaccine (PCV10) in the routine infant immunization program using a 4-dose schedule and catch-up for children <23 months. We investigated PCV10 effect on nasopharyngeal carriage with vaccine-type Streptococcus pneumoniae (Spn) and non-typeable Haemophilus influenzae (NTHi) among children in São Paulo city. Cross-sectional surveys were conducted in 2010 (baseline) and 2013 (post-PCV10). Healthy PCV-naïve children aged 12­23 months were recruited from primary health centers during immunization campaigns. Nasopharyngeal swabs were collected and tested for Hi; for Spn, all baseline and a stratified random sample of 400 post-PCV10 swabs were tested. We compared vaccine-type Spn and NTHi carriage prevalence pre-/post-PCV10, and used logistic regression to estimate PCV10 effectiveness (1-adjusted odds ratio 100%). Overall 501 children were included in the baseline and 1167 in the post-PCV10 survey (including 400 tested for Spn). Spn was detected in 40.3% of children at baseline and 48.8% post-PCV10; PCV10 serotypes were found in 19.8% and 1.8% respectively, representing a decline of 90.9% (p < 0.0001). Carriage of vaccine-related serotypes increased (10.8­21.0%, p < 0.0001), driven primarily by a rise in serotype 6C (1.8­11.2%, p < 0.0001); carriage of serotypes 6A and 19A did not significantly change. PCV10 effectiveness (4 doses) against vaccine-type carriage was 97.3% (95% confidence interval 88.7­99.3). NTHi prevalence increased from 26.0% (130/501) to 43.6% (509/1167, p < 0.0001); PCV10 vaccination seemed significantly associated with NTHi carriage, even after adjusting for other known risk factors. Carriage with PCV10 serotypes among toddlers declined dramatically following PCV10 introduction in São Paulo, Brazil. No protection of PCV10 against NTHi was observed. Our findings contribute to a growing body of evidence of PCV10 impact on vaccine-type carriage and highlight the importance of PCV10 as a tool to reduce the burden of pneumococcal disease in Brazil and globally

Effect of 10-valent pneumococcal conjugate vaccine on nasopharyngeal carriage of Streptococcus pneumoniae and Haemophilus influenzae among children in São Paulo, Brazil.

In March 2010, Brazil introduced the 10-valent pneumococcal conjugate vaccine (PCV10) in the routine infant immunization program using a 4-dose schedule and catch-up for children <23months. We investigated PCV10 effect on nasopharyngeal carriage with vaccine-type Streptococcus pneumoniae (Spn) and non-typeable Haemophilus influenzae (NTHi) among children in São Paulo city. Cross-sectional surveys were conducted in 2010 (baseline) and 2013 (post-PCV10). Healthy PCV-naïve children aged 12-23months were recruited from primary health centers during immunization campaigns. Nasopharyngeal swabs were collected and tested for Hi; for Spn, all baseline and a stratified random sample of 400 post-PCV10 swabs were tested. We compared vaccine-type Spn and NTHi carriage prevalence pre-/post-PCV10, and used logistic regression to estimate PCV10 effectiveness (1-adjusted odds ratio×100%). Overall 501 children were included in the baseline and 1167 in the post-PCV10 survey (including 400 tested for Spn). Spn was detected in 40.3% of children at baseline and 48.8% post-PCV10; PCV10 serotypes were found in 19.8% and 1.8% respectively, representing a decline of 90.9% (p<0.0001). Carriage of vaccine-related serotypes increased (10.8-21.0%, p<0.0001), driven primarily by a rise in serotype 6C (1.8-11.2%, p<0.0001); carriage of serotypes 6A and 19A did not significantly change. PCV10 effectiveness (4 doses) against vaccine-type carriage was 97.3% (95% confidence interval 88.7-99.3). NTHi prevalence increased from 26.0% (130/501) to 43.6% (509/1167, p<0.0001); PCV10 vaccination seemed significantly associated with NTHi carriage, even after adjusting for other known risk factors. Carriage with PCV10 serotypes among toddlers declined dramatically following PCV10 introduction in São Paulo, Brazil. No protection of PCV10 against NTHi was observed. Our findings contribute to a growing body of evidence of PCV10 impact on vaccine-type carriage and highlight the importance of PCV10 as a tool to reduce the burden of pneumococcal disease in Brazil and globally.

Indirect cohort analysis of 10-valent pneumococcal conjugate vaccine effectiveness against vaccine-type and vaccine-related invasive pneumococcal disease.

We applied the indirect cohort method to estimate effectiveness of 10-valent pneumococcal conjugate vaccine (PCV10) among young children in Brazil. Cases of invasive pneumococcal disease (IPD), i.e., Streptococcus pneumoniae, detected in normally sterile fluid identified through laboratory-based surveillance and previously enrolled in a matched case-control effectiveness study are included. We estimated PCV10 effectiveness using multivariable logistic regression comparing PCV10 vaccination among children with vaccine-type or vaccine-related IPD vs. children with non-vaccine-type disease. The adjusted effectiveness of ≥ 1 doses against vaccine-type (72.8%, 95% confidence interval [CI] [44.1, 86.7]) and vaccine-related (61.3%, 95%CI [14.5, 82.5]) IPD were similar to the effectiveness observed in the original case-control study (which required enrollment >1200 controls). We also found significant protection of ≥ 1 dose against individual vaccine serotypes (14, 6B, 23F, 18C) and against vaccine-related serotype 19A. The indirect cohort methods leverages existing surveillance is a feasible approach for evaluating pneumococcal conjugate vaccines, particularly in resource-limited settings.

Incidence of Hospitalized Pneumococcal Pneumonia among Adults in Guatemala, 2008-2012.

BACKGROUND: Streptococcus pneumoniae is a leading cause of pneumonia worldwide. However, the burden of pneumococcal pneumonia among adults in low- and middle-income countries is not well described. METHODS: Data from 2008-2012 was analyzed from two surveillance sites in Guatemala to describe the incidence of pneumococcal pneumonia in adults. A case of hospitalized pneumococcal pneumonia was defined as a positive pneumococcal urinary antigen test or blood culture in persons aged ≥ 18 years hospitalized with an acute respiratory infection (ARI). RESULTS: Among 1595 adults admitted with ARI, 1363 (82%) had either urine testing (n = 1286) or blood culture (n = 338) performed. Of these, 188 (14%) had pneumococcal pneumonia, including 173 detected by urine only, 8 by blood culture only, and 7 by both methods. Incidence rates increased with age, with the lowest rate among 18-24 year-olds (2.75/100,000) and the highest among ≥65 year-olds (31.3/100,000). The adjusted incidence of hospitalized pneumococcal pneumonia was 18.6/100,000 overall, with in-hospital mortality of 5%. CONCLUSIONS: An important burden of hospitalized pneumococcal pneumonia in adults was described, particularly for the elderly. However, even adjusted rates likely underestimate the true burden of pneumococcal pneumonia in the community. These data provide a baseline against which to measure the indirect effects of the 2013 introduction of the pneumococcal conjugate vaccine in children in Guatemala.

Using Standardized Interpretation of Chest Radiographs to Identify Adults with Bacterial Pneumonia--Guatemala, 2007-2012.

BACKGROUND: Bacterial pneumonia is a leading cause of illness and death worldwide, but quantifying its burden is difficult due to insensitive diagnostics. Although World Health Organization (WHO) protocol standardizes pediatric chest radiograph (CXR) interpretation for epidemiologic studies of bacterial pneumonia, its validity in adults is unknown. METHODS: Patients (age ≥ 15 years) admitted with respiratory infections to two Guatemalan hospitals between November 2007 and March 2012 had urine and nasopharyngeal/oropharyngeal (NP/OP) swabs collected; blood cultures and CXR were also performed at physician clinical discretion. 'Any bacterial infection' was defined as a positive urine pneumococcal antigen test, isolation of a bacterial pneumonia pathogen from blood culture, or detection of an atypical bacterial pathogen by polymerase chain reaction (PCR) of nasopharyngeal/oropharyngeal (NP/OP) specimens. 'Viral infection' was defined as detection of viral pathogens by PCR of NP/OP specimens. CXRs were interpreted according to the WHO protocol as having 'endpoint consolidation', 'other infiltrate', or 'normal' findings. We examined associations between bacterial and viral infections and endpoint consolidation. FINDINGS: Urine antigen and/or blood culture results were available for 721 patients with CXR interpretations; of these, 385 (53%) had endpoint consolidation and 253 (35%) had other infiltrate. Any bacterial infection was detected in 119 (17%) patients, including 106 (89%) pneumococcal infections. Any bacterial infection (Diagnostic Odds Ratio [DOR] = 2.9; 95% confidence Interval (CI): 1.3-7.9) and pneumococcal infection (DOR = 3.4; 95% CI: 1.5-10.0) were associated with 'endpoint consolidation', but not 'other infiltrate' (DOR = 1.7; 95% CI: 0.7-4.9, and 1.7; 95% CI: 0.7-4.9 respectively). Viral infection was not significantly associated with 'endpoint consolidation', 'other infiltrate,' or 'normal' findings. INTERPRETATION: 'Endpoint consolidation' was associated with 'any bacterial infection,' specifically pneumococcal infection. Therefore, endpoint consolidation may be a useful surrogate for studies measuring the impact of interventions, such as conjugate vaccines, against bacterial pneumonia.

Effectiveness of ten-valent pneumococcal conjugate vaccine against invasive pneumococcal disease in Brazil: a matched case-control study.

BACKGROUND: In March 2010, Brazil introduced the ten-valent pneumococcal conjugate vaccine (PCV10), which was licensed based on non-inferiority of immunological correlates of protection compared with the seven-valent vaccine. The schedule comprised three primary doses at ages 2 months, 4 months, and 6 months, and a booster dose at age 12 months. A single catch-up dose was offered for children aged 12-23 months at the time of introduction. We assessed PCV10 effectiveness against invasive pneumococcal disease in Brazilian children. METHODS: Invasive pneumococcal disease, defined as isolation of Streptococcus pneumoniae from blood, cerebrospinal fluid, or another normally sterile site, was identified in children age-eligible for at least one PCV10 dose through laboratory-based and hospital-based surveillance in ten states in Brazil from March 1, 2010, until Dec 31, 2012. We aimed to identify four age-matched and neighbourhood-matched controls for each case. We used conditional logistic regression and calculated PCV10 effectiveness as (1-adjusted matched odds ratio) × 100% for vaccine-type and vaccine-related serotypes (ie, in the same serogroup as a vaccine serotype). FINDINGS: In 316 cases (median age 13·2 months, range 2·6-53·1) and 1219 controls (13·3 months, 2·6-53·1), the adjusted effectiveness of an age-appropriate PCV10 schedule was 83·8% (95% CI 65·9-92·3) against vaccine serotypes, and 77·9% (41·0-91·7) against vaccine-related serotypes. Serotype-specific effectiveness was shown for the two most common vaccine serotypes-14 (87·7%, 60·8-96·1) and 6B (82·8%, 23·8-96·1)-and serotype 19A (82·2%, 10·7-96·4), a serotype related to vaccine serotype 19F. A single catch-up dose in children aged 12-23 months was effective against vaccine-type disease (68·0%, 17·6-87·6). No significant effectiveness was shown against non-vaccine serotypes for age-appropriate or catch-up schedules. INTERPRETATION: In the routine immunisation programme in Brazil, PCV10 prevents invasive disease caused by vaccine serotypes. PCV10 might provide cross-protection against some vaccine-related serotypes. FUNDING: Brazilian Ministry of Health, Pan-American Health Organization, and US Centers for Disease Control and Prevention.

Aetiology of paediatric pneumonia with effusion in the Dominican Republic and the potential impact of pneumococcal conjugate vaccines.

Pleural effusion is a serious complication of pneumonia, and Streptococcus pneumoniae is a leading cause. We describe the aetiology of pneumonia with effusion among children in the Dominican Republic before the introduction of the 13-valent pneumococcal conjugate vaccine (PCV) in 2013 and the performance characteristics of a rapid immunochromatographic test (ICT) for detecting S. pneumoniae in pleural fluid. From July 2009 to June 2011, we enrolled children <15 years old admitted with pneumonia and pleural effusion to Robert Reid Cabral Children's Hospital, Dominican Republic. Pleural fluid was tested by culture, polymerase chain reaction (PCR) for bacterial (S. pyogenes, S. pneumoniae) and viral (respiratory syncytial virus and human rhinovirus) pathogens, and by ICT for S. pneumoniae. We calculated the performance of ICT and culture compared with PCR. Among 121 cases, the median age was 31 months (range 1 week to 14 years). Pleural fluid culture (n = 121) and PCR testing (n = 112) identified an aetiology in 85 (70.2%) cases, including 62 S. pneumoniae (51.2%) and 19 Staphylococcus aureus (15.7%). The viruses tested were not detected. The most prevalent pneumococcal serotypes were 14 (n = 20), 1 (n = 13), and 3 (n = 12). Serotype coverage of the 10- and 13-valent PCVs would be 70.5% and 95.1%, respectively. The sensitivity of point-of-care ICT was 100% (95% confidence interval [CI] 94.1%-100%), while specificity was 86.3% (95% CI 73.7%-94.3%). S. pneumoniae caused more than half of paediatric pneumonia with effusion cases; introduction of PCV in the Dominican Republic could reduce the burden by 36-49%. ICT is a practical, valid diagnostic tool for clinical care and surveillance in settings with limited laboratory capacity.

Haemophilus influenzae type b disease among children in rural Mozambique: impact of vaccine introduction.

OBJECTIVE: Haemophilus influenzae type b (Hib) conjugate vaccine has dramatically reduced invasive Hib disease worldwide. Yet, data on protection against pneumonia and among children with HIV are limited. We evaluated the impact of Hib conjugate vaccine introduction in 2009 in a rural, high-HIV prevalence area in Mozambique. STUDY DESIGN: From 2006-2011, we conducted hospital-based surveillance for invasive Hib disease and clinical pneumonia (classified as severe and very severe) among children <5 years of age. Incidences calculated using population denominators were compared between baseline (2006-2008) and post-Hib conjugate vaccine (2010-2011) periods. Surveillance data for radiologically-confirmed pneumonia among children <2 years of age in 2011 were compared with baseline data from 2004-2006. RESULTS: Among 50 cases of invasive Hib disease, 5 occurred after Hib conjugate vaccine introduction; 1 case-patient was age-eligible for Hib conjugate vaccine (and had received 3 doses). Four post-Hib conjugate vaccine case-patients (including Hib conjugate vaccine failure) had HIV. Among children <1 and <5 years of age, significant reductions occurred in rates of invasive Hib disease (91% and 85%, respectively) and very severe pneumonia (29% and 34%, respectively). Radiologically-confirmed pneumonia incidence fell significantly (33%) in children <2 years of age. Severe pneumonia incidence did not decline. CONCLUSIONS: We demonstrate important reductions in invasive disease and pneumonia following Hib conjugate vaccine introduction in a high-HIV area. Continued surveillance is needed to monitor long-term Hib conjugate vaccine effects, particularly among children with HIV.

Effectiveness of the 7-valent pneumococcal conjugate vaccine against vaccine-type invasive disease among children in Uruguay: an evaluation using existing data.

The 7-valent pneumococcal conjugate vaccine (PCV7) was introduced into the routine immunization program in Uruguay in March 2008 with a 2-dose primary series (given at 2 and 4 months) plus a booster (at 12 months) and a catch-up campaign (two doses given at 15 and 17 months). We used a case-control methodology and existing laboratory surveillance and immunization registry data from Uruguay to evaluate PCV7 effectiveness against vaccine-type invasive pneumococcal disease (VT-IPD). Cases of VT-IPD (with pneumococcus obtained from a normally sterile site) were identified through the National Reference Laboratory. Age- and neighborhood-matched controls were obtained through a national immunization registry in which all children are enrolled at birth regardless of vaccine receipt; all eligible controls were included. Immunization status of cases and controls was assessed through the immunization registry, and conditional logistic regression was used to calculate PCV7 effectiveness. Between April 2008 and February 2010, 44 cases of VT-IPD among children<5 years were identified; 43 (98%) of those children were located in the registry. Among located case patients, 7 (16.3%) were age-eligible to have received at least one dose of PCV7. A total of 637 matched controls were included. Vaccine effectiveness was 91.3% (95% CI: 46.4, 98.6) for ≥ 1 PCV7 doses and 94.8% (95% CI: 43.1, 99.5) for ≥ 2 PCV7 doses. Using existing data we demonstrated high effectiveness of PCV7 against VT-IPD in Uruguay-a middle-income country using a 2-dose primary series plus a booster dose and a limited catch-up campaign. These data also highlight the utility of surveillance and high-quality immunization registries for evaluating the effectiveness of vaccines.

Critical issues in implementing a national integrated all-vaccine preventable disease surveillance system.

In 2007, the World Health Organization published the Global Framework for Immunization Monitoring and Surveillance (GFIMS) outlining measures to enhance national surveillance for vaccine preventable diseases (VPDs). The GFIMS emphasized that VPD surveillance should be integrated and placed in a 'unified framework' building upon the strengths of existing surveillance systems to prevent duplication of activities common to all surveillance systems and to minimize human resource and supply expenditures. Unfortunately, there was little experience in actually developing integrated VPD surveillance. We describe the process of developing operational guidance for ministries of health to implement such an integrated surveillance system for multiple VPDs.

Surveillance for hospitalized acute respiratory infection in Guatemala.

Acute respiratory infections (ARI) are an important cause of illness and death worldwide, yet data on the etiology of ARI and the population-level burden in developing countries are limited. Surveillance for ARI was conducted at two hospitals in Guatemala. Patients admitted with at least one sign of acute infection and one sign or symptom of respiratory illness met the criteria for a case of hospitalized ARI. Nasopharyngeal/oropharyngeal swabs were collected and tested by polymerase chain reaction for adenovirus, parainfluenza virus types 1,2 and 3, respiratory syncytial virus, influenza A and B viruses, human metapneumovirus, Chlamydia pneumioniae, and Mycoplasma pneumoniae. Urine specimens were tested for Streptococcus pneumoniae antigen. Blood culture and chest radiograph were done at the discretion of the treating physician. Between November 2007 and December 2011, 3,964 case-patients were enrolled. While cases occurred among all age groups, 2,396 (60.4%) cases occurred in children <5 years old and 463 (11.7%) among adults ≥65 years old. Viruses were found in 52.6% of all case-patients and 71.8% of those aged <1 year old; the most frequently detected was respiratory syncytial virus, affecting 26.4% of case-patients. Urine antigen testing for Streptococcus pneumoniae performed for case-patients ≥15 years old was positive in 15.1% of those tested. Among 2,364 (59.6%) of case-patients with a radiograph, 907 (40.0%) had findings suggestive of bacterial pneumonia. Overall, 230 (5.9%) case-patients died during the hospitalization. Using population denominators, the observed hospitalized ARI incidence was 128 cases per 100,000, with the highest rates seen among children <1 year old (1,703 per 100,000), followed by adults ≥65 years old (292 per 100,000). These data, which demonstrate a substantial burden of hospitalized ARI in Guatemala due to a variety of pathogens, can help guide public health policies aimed at reducing the burden of illness and death due to respiratory infections.

Impact of vaccination against Haemophilus influenzae type b with and without a booster dose on meningitis in four South American countries.

To inform World Health Organization recommendations regarding use of Haemophilus influenzae type b (Hib) vaccines in national immunization programs, a multi-country evaluation of trends in Hib meningitis incidence and prevalence of nasopharyngeal Hib carriage was conducted in four South American countries using either a primary, three-dose immunization schedule without a booster dose or with a booster dose in the second year of life. Surveillance data suggest that high coverage of Hib conjugate vaccine sustained low incidence of Hib meningitis and low prevalence of Hib carriage whether or not a booster dose was used.

Survey of obstetrician-gynecologists in the United States about Chagas disease.

Chagas disease affects an estimated 300,000 people in the United States, and as many as 300 congenital infections are estimated to occur annually. The level of knowledge about Chagas disease among obstetricians-gynecologists in the United States has not been assessed. The American College of Obstetricians and Gynecologists surveyed a representative sample of 1,000 members about Chagas disease. Among 421 respondents, 68.2% (95% confidence interval [CI] = 63.5-72.6) described their knowledge level about Chagas disease as "very limited." Only 8.8% (95% CI = 6.2-12.0) knew the risk of congenital infection, and 7.4% (95% CI = 5.1-10.4) were aware that both acute and chronic maternal infections can lead to congenital transmission. The majority of respondents (77.9%; 95% CI = 73.5-81.9) reported "never" considering a diagnosis of Chagas disease among their patients from endemic countries. Most of those who did consider the diagnosis did so "rarely." Knowledge of Chagas disease among obstetricians-gynecologists in the United States is limited. Greater awareness may help to detect treatable congenital Chagas cases.

Geographic variation in the sensitivity of recombinant antigen-based rapid tests for chronic Trypanosoma cruzi infection.

Chagas disease affects 8-11 million people throughout the Americas. Early detection is crucial for timely treatment and to prevent non-vectorial transmission. Recombinant antigen-based rapid tests had high sensitivity and specificity in laboratory evaluations, but no Peruvian specimens were included in previous studies. We evaluated Stat-Pak and Trypanosoma Detect rapid tests in specimens from Bolivia and Peru. Specimens positive by three conventional assays were confirmed positives; specimens negative by two or more assays were confirmed negatives. In Bolivian specimens, Stat-Pak and Trypanosoma Detect tests were 87.5% and 90.7% sensitive, respectively; both showed 100% specificity. Sensitivity in Peruvian specimens was much lower: 26.6-33.0% (Stat-Pak) and 54.3-55.2% (Trypanosoma Detect); both had specificities > 98%. Even in Bolivian specimens, these sensitivities are inadequate for stand-alone screening. The low sensitivity in Peru may be related to parasite strain differences. Chagas disease rapid tests should be field tested in each geographic site before widespread implementation for screening.