Josefina Fernández

Prevention of Haemophilus influenzae Type b Colonization by Vaccination: Correlation with Serum Anti-Capsular IgG Concentration

Concentrations of serum anti-Haemophilus influenzae type b (anti-Hib) capsular polysaccharide (CPS) >/=0.15 and >/=1.0 microgram/mL are widely used as surrogates for protection against invasive Hib disease. However, the relationship between serum anti-Hib CPS following immunization and protection against colonization is not known, making it difficult to evaluate new Hib vaccines or combination vaccines. In the Dominican Republic, nasopharyngeal swabs were collected from 546 9-month-old infants who had received Hib conjugate vaccine at ages 2, 4, and 6 months and from 600 unvaccinated infants of the same age. The prevalence of Hib colonization was lower among vaccinated infants than among unvaccinated infants (0.9% vs. 2.3%). Among vaccinated infants, protection against colonization was significantly correlated with anti-Hib CPS concentrations >/=5 microgram/mL 1 month following the third dose of vaccine. These results suggest that the concentration of serum anti-Hib CPS needed for protection against colonization is greater than that needed for protection for invasive disease.

Functional Antibody Activity Elicited by Fractional Doses of Haemophilus influenzae Type b Conjugate Vaccine (Polyribosylribitol Phosphate-Tetanus Toxoid Conjugate)

ABSTRACT We evaluated the functional activities of antibodies, serum bactericidal activity (SBA), and immunoglobulin G (IgG) antibody avidity indices, using sodium thiocyanate (NaSCN) elution, elicited after vaccination with fractional doses of the Haemophilus influenzae type b conjugate (polyribosylribitol phosphate [PRP] conjugated to tetanus toxoid [PRP-T]) vaccine. A cohort of 600 infants from the Dominican Republic were randomized to receive one of three regimens of the PRP-T vaccine at ages 2, 4, and 6 months: full doses (10 μg of PRP antigen), one-half doses (5.0 μg), and one-third doses (3.3 μg) (J. Fernandez et al., Am. J. Trop. Med. Hyg. 62:485–490, 2000). Sixty serum samples, collected at age 7 months, with ≥2.0 μg of anti-PRP IgG per ml were randomly selected for avidity determinations. Geometric mean IgG concentrations were 13, 14, and 17 μg/ml for infants who received the full-dose (n = 19), one-half-dose (n = 19), and one-third-dose (n = 22) regimens, respectively. SBA geometric mean titers (1/dilution) were 85.0, 82.0, and 76.1 in sera from infants receiving the full-, one-half-, and one-third-dose regimens, respectively. Avidity indices (mean ± standard error weighted average of NaSCN molar concentration × serum dilution factor) were 71.9 ± 9.4, 123.6 ± 26.8, and 150.9 ± 24.9 for the full-, one-half-, and one-third-dose regimens, respectively. Upon comparison, the only significant difference (P = 0.024) found was a greater avidity index for sera from infants receiving the one-third-dose regimen than for sera from infants receiving the the full-dose regimen. We conclude that fractional doses elicit similar functional antibody activities in infants with ≥2 μg of anti-PRP IgG per ml, corresponding to 89, 90, and 97% of infants receiving three doses of either the full concentration or one-half or one-third of the labeled concentration, respectively. This approach offers an alternative strategy for the prevention of H. influenzae type b disease in countries with limited resources.

Impact of Haemophilus influenzae type b conjugate vaccine on bacterial meningitis in the Dominican Republic

OBJECTIVES Widespread use of Haemophilus influenzae type b (Hib) vaccines has dramatically reduced the burden of Hib disease throughout the Americas. Few studies have evaluated the impact of Hib vaccination on non-culture-confirmed disease. This study analyzed trends in probable bacterial meningitis before and after the introduction of Hib vaccine in the Dominican Republic and estimated vaccine effectiveness against Hib meningitis. METHODS Meningitis cases among children < 5 years of age were identified from admission records of the main pediatric hospital in Santo Domingo during 1998-2004. Laboratory criteria were used to classify meningitis cases with probable bacterial etiology; confirmed cases had positive bacterial culture or antigen detection in cerebrospinal fluid. Cumulative incidence rates of confirmed and probable bacterial meningitis were calculated for children living in the National District. Confirmed cases of Hib meningitis were enrolled in a case-control study with age- and neighborhood-matched control children to calculate vaccine effectiveness. RESULTS Before vaccine introduction, annual rates of meningitis with probable bacterial etiology were 49 cases per 100 000 children < 5 years old; Hib accounted for 60% of confirmed bacterial cases. During 2002-2004, after vaccine introduction, annual rates of probable bacterial meningitis were 65% lower at 16 cases per 100 000, and Hib accounted for 26% of confirmed cases. Rates of Hib meningitis and probable bacterial meningitis with no determined etiology declined by 13 and 17 cases per 100 000, respectively. CONCLUSIONS Introduction of Hib vaccine substantially reduced the incidence of confirmed and probable bacterial meningitis in the Dominican Republic. The estimated impact of Hib vaccination was twice as great when non-culture-confirmed disease was included.

Resistencia a antibióticos no betalactámicos de aislamientos invasores de Streptococcus pneumoniae en niños latinoamericanos: SIREVA II, 2000-2005

OBJECTIVE To examine the development of resistance to erythromycin, chloramphenicol, trimethoprim-sulfamethoxazole (TMP-SMZ), and vancomycin of the invasive isolates of Streptococcus pneumoniae obtained from children in 10 Latin American/Caribbean countries during six years of surveillance. METHODS Analysis of 8 993 isolates of S. pneumoniae recovered in 2000-2005 from children with invasive infections, who were less than 6 years of age, and from Argentina, Brazil, Chile, Colombia, Cuba, Dominican Republic, Mexico, Paraguay, Uruguay, or Venezuela. Antibiotic susceptibility was determined through the methods established and standardized by the SIREVA project. Multidrug resistance was defined as: resistance to three or more antibiotics of the same class; to the non-beta-lactams analyzed by this study; or, to the beta-lactams evaluated by a previous study, in which 37.8% of these isolates showed decreased susceptibility to penicillin. RESULTS Some degree of resistance was found to TMP-SMZ and erythromycin (56.4% and 15.4% of the isolates studied, respectively), with 4.6% highly resistant to chloramphenicol. All isolates were susceptible to vancomycin. The highest prevalence of TMP-SMZ resistance was observed in the pneumonia isolates; and that of erythromycin, in cases of sepsis (61.6% and 25.5%, respectively; P < 0.01). The highest prevalence of TMP-SMZ resistance was found in Brazil (71.9%), and that of erythromycin, in Mexico (38.2%) and Venezuela (32.9%). The 14, 6B, 19F, and 23F serotypes were most often associated with resistance to the antibiotics in the study. CONCLUSIONS High and increasing rates of isolates resistant to TMP-SMZ and erythromycin were observed, as well as a decreasing percentage of isolates resistant to chloramphenicol. These trends highlight differences among the countries studied.

Disease Severity and Mortality Caused by Dengue in a Dominican Pediatric Population

Millions are infected with dengue yearly. We evaluated the epidemiological and clinical characteristics of pediatric patients infected with dengue in the Dominican Republic. The applicability of World Health Organization (WHO) warning signs for predicting severe dengue and mortality was also studied. This study was a cross-sectional retrospective review of patients with a clinical diagnosis of dengue. Univariate and multivariate analyses were performed to evaluate characteristics associated with severity and mortality. The study included 796 subjects: 288 subjects were classified as dengue, 290 subjects had alarm signs, and 207 subjects were classified as severe dengue. Common findings included thrombocytopenia (96%), abdominal pain (71%), and vomiting (59%). The most important factors associated with severe dengue were rash (P < 0.01), severe thrombocytopenia (P < 0.01), and anemia (P < 0.01). These signs and symptoms were also associated with mortality. This study validates the current WHO warning signs of severity. Rash and severe thrombocytopenia may be early warning signs and need additional study.

Risk factors for intrathoracic tuberculosis in children from economic migrant populations of two Dominican Republic bateyes.

Objective: The objective of the current study was to identify risk factors for intrathoracic tuberculosis among children living in migrant populations in the Dominican Republic. Design: Cross-sectional study. Setting: Dominican Republic bateyes, economic migrant communities of Haitian origin. Participants: Children 18 months to 18 years of age. Main Exposure: Unpasteurized milk consumption. Outcome Measures: Probable or possible intrathoracic tuberculosis. Probable intrathoracic tuberculosis was defined as any child with a tuberculin skin test ≥10 mm (or >5 mm in the presence of a known immunocompromising condition or household contact with intrathoracic tuberculosis) or malnutrition in the setting of an abnormal chest radiograph with features of tuberculosis or lymph node disease. The diagnosis of “possible intrathoracic tuberculosis” was assigned if an abnormal chest radiograph had features that did not meet the definition of “probable intrathoracic tuberculosis.” Results: Probable or possible tuberculosis was diagnosed in 83 (20.8%) of 400 children. Unpasteurized milk consumption was identified as an independent risk factor for intrathoracic tuberculosis (adjusted odds ratio, 3.2; 95% confidence interval: 1.4–7.4) even after adjusting for Bacille Calmette-Guérin vaccination, household size, tuberculosis contacts and age and under varying assumptions about children diagnosed with “possible” tuberculosis. Conclusions: Our data raise the possibility that the high prevalence of tuberculosis in the Dominican Republic bateyes may be attributable to Mycobacterium bovis rather than Mycobacterium tuberculosis infection.

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.

Prescripción de antimicrobianos antes y después de una intervención educativa en un país donde el proceso de re-certificación no es obligatorio

Background: The trend in increased antibiotic prescription practices has been associated with higher health care costs and antibiotic resistance. This study examined the adequate or inappropriate antibiotic prescribing practices of health professionals, who work in public and private health centers in the Dominican Republic (DR), before and after their participation in an educational intervention. Methods: Using self-administered questionnaires developed by the Alliance for the Prudential Use of Antibiotics (APUA), this quasi-experimental study evaluated the responses of physicians before (n=525) and after (n=364) their participation in an educational intervention, from August 2006 to February 2007 and March to August 2008, respectively. Statistical analyses included simple proportions, odds ratio and 95% confidence intervals (IC95%). Alpha was set at 0.05. Results: Post-intervention responses improved understanding significantly regarding specific situations for the prescription of cephalosporins, penicillins, macrolides, quinolones, vancomycin and aminoglycosides. Physicians were more likely to respond incorrectly at baseline than post-intervention for cephalosporins (OR=4.2; IC95%:2.9-6.1; p=0.00001), penicillins (OR=1.9; IC95%:1.2-2.9; p=0.006), quinolones (OR=4.0; IC95%:2.5-6.6; p=0.00001)), macrolides (OR: 4.9 IC95%:3.0-7.9; p= 0,00001 vancomycin (OR=2.2; IC95%: 1.2-4.1; p=0.009) and aminoglycosides (OR=2.1; IC95%:1.3-3.3; p=0.002). Conclusions: Educational interventions for health professionals can improve knowledge when designed to target specific topics, including appropriate antibiotic prescribing practices in health centers. These findings reflect the need to initiate a re-certification process for Dominican physicians, which may impact the quality of attention for the users of health services in the DR.