Chonnamet Techasaensiri

Vertical Dengue Infection Case Reports and Review

Two vertical dengue infection cases are presented, and 15 others are reviewed. Twelve mothers had fever 0–9 (median, 2) days antepartum. The fevers of 17 neonates occurred at 1–11 (median, 4) days of life and lasted for 1–5 (median, 3) days. Neonatal thrombocytopenia was detected at 1–11 (median, 6) days of life and lasted for 3–18 (median, 6) days; the lowest platelet counts were 5–75 × 103 (median, 19 × 103)/mm3. One neonate died.

Epidemiology and evolution of invasive pneumococcal disease caused by multidrug resistant serotypes of 19a in the 8 years after implementation of pneumococcal conjugate vaccine immunization in Dallas, Texas

Background: The heptavalent pneumococcal conjugate vaccine (PCV7) has significantly reduced vaccine-type invasive pneumococcal disease (IPD) in children. An increasing percentage of IPD cases are now caused by nonvaccine serotypes. The purpose of our observational study was to define the epidemiology of pneumococcal disease in Dallas, TX children for 8 years after implementation of PCV7 immunization. Methods: Streptococcus pneumoniae isolates from normally sterile sites were collected at Childrens Medical Center of Dallas from January 1, 1999 to December 31, 2008. Incidence of IPD was calculated using inpatient and emergency center admissions to Childrens Medical Center of Dallas as the denominator. Isolates were serotyped and penicillin and cefotaxime susceptibilities were determined. Serotype 19A isolates were further characterized by multilocus sequence typing. Results: Compared with the prevaccine period of 1999–2000, there was a significant reduction in the incidence of IPD from 2002 to 2008 (P < 0.05), although a significant increase in IPD incidence was observed from 2006 to 2008 (P = 0.038). The number of IPD cases caused by serotype 19A increased from 1999 to 2008 (P < 0.001). There were significant increases in penicillin and cefotaxime nonsusceptibile 19A isolates during this 10-year period (P < 0.001 and P = 0.004, respectively). The most common sequence type (ST) of the 19A isolates was ST-199 (42.7%). Clonal complex (cc-156) and cc-320 emerged in the period of 2005–2008 as penicillin and cefotaxime resistant 19A strains. Conclusions: In Dallas, PCV7 immunization reduced significantly the incidence of IPD caused by vaccine-type strains. A significant increase in IPD caused by serotype 19A was observed. The penicillin and cefotaxime nonsusceptible STs, not previously identified in Dallas, have recently become an important cause of IPD.

Analysis of Pulmonary Inflammation and Function in the Mouse and Baboon after Exposure to Mycoplasma pneumoniae CARDS Toxin

Mycoplasma pneumoniae produces an ADP-ribosylating and vacuolating toxin known as the CARDS (Community Acquired Respiratory Distress Syndrome) toxin that has been shown to be cytotoxic to mammalian cells in tissue and organ culture. In this study we tested the ability of recombinant CARDS (rCARDS) toxin to elicit changes within the pulmonary compartment in both mice and baboons. Animals responded to a respiratory exposure to rCARDS toxin in a dose and activity-dependent manner by increasing the expression of the pro-inflammatory cytokines IL-1α, 1β, 6, 12, 17, TNF-α and IFN-γ. There was also a dose-dependent increase in several growth factors and chemokines following toxin exposure including KC, IL-8, RANTES, and G-CSF. Increased expression of IFN-γ was observed only in the baboon; otherwise, mice and baboons responded to CARDS toxin in a very similar manner. Introduction of rCARDS toxin to the airways of mice or baboons resulted in a cellular inflammatory response characterized by a dose-dependent early vacuolization and cytotoxicity of the bronchiolar epithelium followed by a robust peribronchial and perivascular lymphocytic infiltration. In mice, rCARDS toxin caused airway hyper-reactivity two days after toxin exposure as well as prolonged airway obstruction. The changes in airway function, cytokine expression, and cellular inflammation correlate temporally and are consistent with what has been reported for M. pneumoniae infection. Altogether, these data suggest that the CARDS toxin interacts extensively with the pulmonary compartment and that the CARDS toxin is sufficient to cause prolonged inflammatory responses and airway dysfunction.

Viral coinfections in children with invasive pneumococcal disease.

Background: Respiratory viruses contribute to the seasonal pattern of invasive pneumococcal disease (IPD), but the impact of viral coinfections on the clinical characteristics and outcomes of patients with IPD have not been well defined. Objective: This study was designed to describe and compare the clinical presentations and outcomes of patients with IPD with or without viral coinfections. Design/Methods: Retrospective analyses of records of all children treated at Childrens Medical Center Dallas (CMCD) for IPD from July 2005 to June 2008. Viral studies included viral direct fluorescent antibody staining and culture. For comparisons, patients were classified in 3 groups: with positive, negative, and no viral studies performed. Results: A total of 129 patients were admitted to CMCD with IPD during the 3 year study; 57% were male. Ages ranged from 2 months to 18 years (median 25 months) and 48% were <2 years. Viral studies were performed in 82 (63%) patients, and 28 (34%) had positive results. The most common viruses isolated were influenza (7, 25%), rhinoviruses (6, 21%), adenoviruses (6, 21%), and RSV (5, 18%). Peaks of positive viral studies occurred in February and November which coincided with the peak numbers of patients admitted with IPD. Of 6 with adenovirus coinfection, 5 were admitted to Pediatric Intensive Care Unit (PICU). The most common pneumococcal serotypes were 19A (41, 32.5%), 7F (14, 11%), and 23A (13, 10.3%). Pneumonia (42%), bacteremia (22%), and meningitis (17%) were the most common clinical syndromes. There were no differences in duration of fever before admission, maximum temperatures during hospitalization and white blood cell counts, duration of fever and hospitalization between patients with positive and negative viral studies, but there was a trend for patient with positive viral studies to be admitted to PICU more frequently and to have longer PICU stay. Three of the 6 patients who died had documented viral coinfections (2 adenovirus, 1 parainfluenza 3), and all 3 had no underlying conditions. The other 3 patients who died had no viral studies performed. Duration of treatment ranged from 1 to –210 days (median 14), with no differences among the groups. Conclusions: Viral coinfections were common in children with IPD. Future prospective studies should include new PCR assays to characterize better the impact of viral coinfections in the occurrence and outcome of IPD.

Increase in Invasive Streptococcus Pneumoniae Infections in Children with Sickle Cell Disease since Pneumococcal Conjugate Vaccine Licensure

Invasive pneumococcal disease (IPD) in children with sickle cell disease has decreased with prophylactic penicillin, pneumococcal polysaccharide vaccine, and pneumococcal protein-conjugate vaccine usage. We report 10 IPD cases since pneumococcal protein-conjugate vaccine licensure, including a recent surge of non-vaccine serotypes. IPD continues to be a serious risk in sickle cell disease.

Variation in colonization, ADP-ribosylating and vacuolating cytotoxin, and pulmonary disease severity among mycoplasma pneumoniae strains.

RATIONALE Mycoplasma pneumoniae was recently discovered to produce an ADP-ribosylating and vacuolating cytotoxin, designated CARDS toxin, which is hypothesized to be a primary pathogenic mechanism responsible for M. pneumoniae-induced pulmonary inflammation. It is unknown if cytotoxin production varies with M. pneumoniae strain or if variation in cytotoxin production affects pulmonary disease severity. OBJECTIVES To examine the production of CARDS toxin by various strains of M. pneumoniae and compare the disease manifestations elicited by these strains in an experimental model of M. pneumoniae respiratory infection. METHODS BALB/c mice were inoculated once intranasally with SP4 broth (negative control) or three different M. pneumoniae strains: M129-B7, M129-B9, or S1. Mice were assessed at 1, 2, 4, 7, 10, and 14 days after inoculation. Outcome variables included comparisons among M. pneumoniae strains relative to bronchoalveolar lavage (BAL) M. pneumoniae quantitative culture, CARDS toxin-based PCR, and CARDS toxin protein determinations, as well as cytokine and chemokine concentrations. Graded lung histopathologic score (HPS) was also assessed. MEASUREMENTS AND MAIN RESULTS CARDS toxin concentrations were significantly increased in mice inoculated with strain S1 compared with mice inoculated with M129-B7 or M129-B9 strains. Quantitative M. pneumoniae culture and polymerase chain reaction were also significantly greater in mice infected with S1 strain compared with the other two strains, as were lung HPS and concentrations of IFN-γ, IL-12, IL-1α, macrophage inflammatory protein-1α, and keratinocyte-derived chemokine. In addition, a significant positive correlation was found between CARDS toxin concentration and lung HPS. CONCLUSIONS CARDS toxin concentrations in BAL are directly linked to the ability of specific M. pneumoniae strains to colonize, replicate, and persist, and elicit lung histopathology. This variation among strains may predict the range in severity of pulmonary disease observed among patients.

Efficacy of increasing dosages of clarithromycin for treatment of experimental Mycoplasma pneumoniae pneumonia

OBJECTIVES Mycoplasma pneumoniae respiratory infection is a common cause of acute respiratory infection in children and adults. We evaluated the efficacy of increasing dosages of clarithromycin for the optimized therapy of M. pneumoniae respiratory infection in a mouse model. METHODS BALB/c mice were intranasally inoculated once with M. pneumoniae or SP4 broth (control). Groups of mice were treated with increasing dosages of clarithromycin (10, 25 or 75 mg/kg/day) or placebo subcutaneously daily. Groups of mice were evaluated after 1, 2, 3, 6 and 12 days of therapy. Outcome variables included quantitative M. pneumoniae culture, histopathological score of the lungs, bronchoalveolar lavage (BAL) cytokine/chemokine/growth factor concentrations and plethysmography after aerosolized methacholine to assess airway hyperresponsiveness. RESULTS Elevated dosages of clarithromycin resulted in greater antimicrobial efficacy with significantly reduced M. pneumoniae quantitative cultures (P < 0.05), as well as greater improvement in markers of disease severity with significantly reduced lung histopathology scores, BAL cytokine concentrations and airway hyperresponsiveness (P < 0.05). CONCLUSIONS Escalated dosing of clarithromycin resulted in significantly greater therapeutic efficacy in the treatment of experimental M. pneumoniae respiratory infection.

Pharmacokinetics of atazanavir/ritonavir among HIV-infected Thai children concomitantly taking tenofovir disoproxil fumarate.

Background: Atazanavir/ritonavir (ATV/r) is a recommended once-daily protease inhibitor. Tenofovir disoproxil fumarate (TDF) can reduce ATV exposure. The authors studied ATV pharmacokinetic (PK) parameters among children who received atazanavir/ritonavir co-administered with TDF. Methods: HIV-infected children aged 6–18 years with a body weight of 25–50 kg were eligible. Branded ATV 200 mg/capsule was taken with generic ritonavir 100 mg/tablet once daily plus TDF and lamivudine. A 24-hour PK study was performed at week 4 at t = 0 (pre-dose), 2, 4, 6, 8, 10, 12 and 24 hours. PK parameters were calculated using non-compartmental methods with WinNonlin software. Targeted ATV AUC0–24 was 15 mg h/L and Ctrough was 0.15 mg/L. Comparisons of geometric means of ATV PK parameters between different weight bands were made using regression models. Results: Eighteen HIV-infected children with a median (IQR) age of 13 (11–14) years were enrolled. Median (range) body weight and body surface area were 35 (25–42) kg and 1.21 (0.96–1.35) m2, respectively. Median (IQR) CD4 cell count was 735 (540–1233) cells/mm3. Median (range) of ATV was 164 (145–209) mg/m2. Geometric mean (SD) ATV AUC0–24 was 35.05 (1.06) mg h/L, and ATV Ctrough was 0.31 (1.13) mg/L. No child had ATV AUC0–24 or Ctrough below target levels. There were no significant differences in PK parameters among weight bands. Conclusion: Atazanavir/ritonavir 200/100 mg dosing provided adequate ATV AUC0–24 when used with TDF in HIV-infected Thai children weighing between 25 and 50 kg.