Nosocomial TB in two neonatal intensive care units at a tertiary care centre: infection risk and outcomes.

BACKGROUND: Sick neonates in TB endemic areas are at risk of nosocomial TB exposure.OBJECTIVE: To evaluate outcomes following contact investigation and isoniazid preventive treatment (IPT) in sick neonates exposed to healthcare personnel (HCP) with pulmonary TB.METHODS: Investigations were conducted following two exposure events in different neonatal intensive care units (NICUs). Details of the infants´ physical examination, chest X-ray and exposure history were recorded. Infants without TB disease were prescribed a 9-month course of IPT and followed for ≥1 year.RESULTS: Ninety infants were exposed in NICU A and 231 in NICU B (n = 321). The overall proportions of completing the 9-month IPT was 164/265 (61.8%): 40/79 (50.6%) in NICU A and 124/186 (66.7%) in NICU B (P = 0.01). The overall incidence of TB was 10.2% (24/236): 7.5% in NICU A and 11.2% in NICU B (P = 0.39). Contact investigation beginning >111 days after exposure was a risk factor for TB infection (P = 0.02).CONCLUSION: The risk of TB following nosocomial exposure in sick neonates was high, particularly when contact investigation was delayed. Our findings underscore the importance of hospital policies that promote early detection of TB in HCP, reduce transmission in NICUs, and facilitate rapid case investigation.

Longitudinal sampling is required to maximize detection of intrahost A/H3N2 virus variants.

Seasonal human influenza viruses continually change antigenically to escape from neutralizing antibodies. It remains unclear how genetic variation in the intrahost virus population and selection at the level of individual hosts translates to the fast-paced evolution observed at the global level because emerging intrahost antigenic variants are rarely detected. We tracked intrahost variants in the hemagglutinin and neuraminidase surface proteins using longitudinally collected samples from 52 patients infected by A/H3N2 influenza virus, mostly young children, who received oseltamivir treatment. We identified emerging putative antigenic variants and oseltamivir-resistant variants, most of which remained detectable in samples collected at subsequent days, and identified variants that emerged intrahost immediately prior to increases in global rates. In contrast to most putative antigenic variants, oseltamivir-resistant variants rapidly increased to high frequencies in the virus population. Importantly, the majority of putative antigenic variants and oseltamivir-resistant variants were first detectable four or more days after onset of symptoms or start of treatment, respectively. Our observations demonstrate that de novo variants emerge, and may be positively selected, during the course of infection. Additionally, based on the 4-7 days post-treatment delay in emergence of oseltamivir-resistant variants in six out of the eight individuals with such variants, we find that limiting sample collection for routine surveillance and diagnostic testing to early timepoints after onset of symptoms can potentially preclude detection of emerging, positively selected variants.

Prospective multinational serosurveillance study of Bordetella pertussis infection among 10- to 18-year-old Asian children and adolescents.

OBJECTIVES: Bordetella pertussis continues to cause outbreaks worldwide. To assess the role of children and adolescent in transmission of pertussis in Asia, we performed a multinational serosurveillance study. METHODS: From July 2013 to June 2016, individuals aged 10 to 18 years who had not received any pertussis-containing vaccine within the prior year were recruited in 10 centres in Asia. Serum anti-pertussis toxin (PT) IgG was measured by ELISA. Demographic data and medical histories were obtained. In the absence of pertussis immunization, anti-PT IgG ≥62.5 IU/mL was interpreted as B. pertussis infection within 12 months prior, among them levels ≥125 IU/mL were further identified as infection within 6 months. RESULTS: A total of 1802 individuals were enrolled. Anti-PT IgG geometric mean concentration was 4.5, and 87 (4.8%) individuals had levels ≥62.5 IU/mL; among them, 73 (83.9%) had received three or more doses of pertussis vaccine before age 6 years. Of 30 participants with persistent cough during the past 6 months, one (3.3%) had level ≥125 IU/mL. There was no significant difference in proportions with anti-PT IgG ≥62.5 IU/mL among age groups (13-15 vs. 10-12 years, 16-18 vs. 10-12 years), between types of diphtheria, pertussis and tetanus (DTP; whole cell vs. acellular), number of doses before age 6 years within the DTP whole-cell pertussis vaccine (five vs. four doses) or acellular pertussis vaccine (five vs. four doses) and history of persistent cough during the past 6 months (yes vs. no). CONCLUSIONS: There is significant circulation of B. pertussis amongst Asian children and adolescents, with one in 20 having serologic evidence of recent infection regardless of vaccination background.

Human parvovirus B19 nosocomial outbreak in healthcare personnel in a paediatric ward at a national tertiary referral centre in Thailand.

BACKGROUND: Nosocomial outbreaks of parvovirus B19 (pB19) have been reported, but they rarely occur among healthcare personnel (HCP). Susceptibility among pregnant HCP was the major concern. METHODS: An outbreak of pB19 among HCP is described in a paediatric ward with a cross-sectional serologic study in all HCP and patients exposed to the outbreak. Acute infection was diagnosed by polymerase chain reaction or positive anti-parvovirus B19 IgM. FINDINGS: Among 48 HCP (three pregnant) and 22 patients included in the outbreak serologic study, 11 (23%) HCP and two (9%) patients had acute infection. Of these, six HCP and no patients were symptomatic. Clinical manifestations included itchy rash (100%) and joint pain following resolution of rash (67%), with median rash duration of four days. Forty percent of HCP and 50% of patients had positive anti-parvovirus IgG, indicating previously immune status. HCP with acute infection and HCP who were susceptible without infection were younger than HCP with previous immunity (mean age 32.2 vs 40.5 years, respectively; P = 0.003). The attack rate was 38% among HCP and 18% among patients who were susceptible, respectively. The outbreak ended within two weeks following strict droplet precaution and segregation of symptomatic HCP. CONCLUSION: Parvovirus B19 infection may cause nosocomial outbreak with high attack rate among HCP. Outbreak control with droplet precaution was highly effective.

Psychosocial needs of perinatally HIV-infected youths in Thailand: lessons learnt from instructive counseling.

Identifying psychosocial needs of perinatally HIV-infected (pHIV) youth is a key step in ensuring good mental health care. We report psychosocial needs of pHIV youth identified using the "Youth Counseling Needs Survey" (YCS) and during individual counseling (IC) sessions. pHIV youth receiving care at two tertiary-care hospitals in Bangkok or at an orphanage in Lopburi province were invited to participate IC sessions. The youths' psychosocial needs were assessed using instructive IC sessions in four main areas: general health, reproductive health, mood, and psychosocial concerns. Prior to the IC session youth were asked to complete the YCS in which their concerns in the four areas were investigated. Issues identified from the YCS and the IC sessions were compared. During October 2010-July 2011, 150 (68.2%) of 220 eligible youths participated in the IC sessions and completed the YCS. Median age was 14 (range 11-18) years and 92 (61.3%) were female. Mean duration of the IC sessions was 36.5 minutes. One-hundred and thirty (86.7%) youths reported having at least one psychosocial problem discovered by either the IC session or the YCS. The most common problems identified during the IC session were poor health attitude and self-care (48.0%), lack of life skills (44.0%), lack of communication skills (40.0%), poor antiretroviral (ARV) adherence (38.7%), and low self-value (34.7%). The most common problems identified by the YCS were lack of communication skills (21.3%), poor health attitude and self-care (14.0%), and poor ARV adherence (12.7%). Youth were less likely to report psychosocial problems in the YCS than in the IC session. Common psychosocial needs among HIV-infected youth were issues about life skills, communication skills, knowledge on self-care, ARV adherence, and self-value. YCS can identify pHIV youths' psychosocial needs but might underestimate issues. Regular IC sessions are useful to detect problems and provide opportunities for counseling.

Safety and immunogenicity of a live attenuated Japanese encephalitis chimeric virus vaccine (IMOJEV®) in children.

JE-CV (IMOJEV®, Sanofi Pasteur, France) is a live attenuated virus vaccine constructed by inserting coding sequences of the prM and E structural proteins of the Japanese encephalitis SA14-14-2 virus into the genome of yellow fever 17D virus. Primary immunization with JE-CV requires a single dose of the vaccine. This article reviews clinical trials of JE-CV in children aged up to 6 years conducted in countries across South-East Asia. Strong and persistent antibody responses were observed after single primary and booster doses, with 97% of children seroprotected up to five years after booster vaccination. Models of long-term antibody persistence predict a median duration of protection of approximately 30 years after a booster dose. The safety and reactogenicity profiles of JE-CV primary and booster doses are comparable to other widely used childhood vaccines.

Effect of HIV diagnosis disclosure on psychosocial outcomes in Thai children with perinatal HIV infection.

A provider-assisted, counselling-based, paediatric HIV disclosure model was developed and implemented at two tertiary-care hospitals in Bangkok, Thailand. All undisclosed perinatally acquired HIV-infected children, aged 7-18 years, and their caretakers were offered the four-step disclosure service, including: screening, readiness assessments and preparation, disclosure sessions, and follow-up evaluations. To assess psychosocial outcomes of disclosure, we compared the scores of the Children Depression Inventory and the PedsQL 4.0™ at baseline and at two-month and six-month follow-up visits, and compared the scores of the Child Behavioral Checklist at baseline and at six-month follow-up. Disclosure was made to 186 children, 160 of whom completed post-disclosure assessments. The median Children's Depression Inventory score in 135 children decreased significantly from 11 at baseline to 8 at two-month and six-month follow-up (p < 0.01). The median PedsQL 4.0™ scores in 126 children increased significantly from 78 at baseline to 80 at two-month and 84 at six-month follow-up (p = 0.04). The median Child Behavioral Checklist scores were not significantly changed. In conclusion, paediatric HIV diagnosis disclosure using this model was found to have positive effect on the children's mood and quality of life, and no negative effect on children's behaviours. This disclosure programme should be expanded to improve the psychosocial health of HIV-infected children.

Cervical cytological abnormalities and HPV infection in perinatally HIV-infected adolescents.

BACKGROUND: Behaviourally HIV-infected adolescent females are at higher risk for abnormal cervical cytology and HPV infection compared to those who are uninfected, but data on perinatally HIV-infected adolescent females are lacking. METHODS: Cervical cytology, HPV infection and E6/E7 mRNA were assessed in sexually active 12-24-year-old adolescent females: perinatally HIV-infected (group 1, n = 40), behaviourally HIV-infected (group 2, n = 10), and HIV-uninfected (group 3, n = 10). RESULTS: Median age was lower in group 1 (18 years) than in groups 2 (24 years) and 3 (20.5 years) (P < 0.001), and median time since sexual debut was shorter: 2 vs 5 vs 4 years (P < 0.001). More trial participants in group 1 than group 2 were on antiretrovirals (90% vs 70%; P <0.001). Abnormal cervical cytology (atypical squamous cells of undetermined significance and higher) was observed in 30% (group 1), 40% (group 2) and 30% (group 3) (P = 0.92), whereas high-risk HPV infection was observed in 45%, 45% and 40%, respectively (P = 1.00). Positive E6/E7 mRNA was found in 28% of group 1, but not in other groups. High-risk HPV infection predicted abnormal cytology in all groups [OR 6.77, 95% confidence interval (CI) 1.99-23.0; P = 0.001). Additionally, plasma HIV RNA ≥50 copies/mL (OR 13.3, 95% CI 1.16-153.06; P = 0.04) predicted abnormal cytology in HIV-infected adolescent females. CONCLUSIONS: Despite the younger age and shorter time since sexual debut, cervical cytological abnormalities and HPV infection were as common in perinatally HIV-infected as in behaviourally infected and uninfected adolescents. HPV vaccination, pre-cancer screening and antiretroviral treatment in HIV-infected female adolescents should be implemented to minimise the risk of cervical cancer.

Factors associated with caretaker's readiness for disclosure of HIV diagnosis to HIV-infected children in Bangkok, Thailand.

To determine factors associated with caretaker's readiness to disclose an HIV diagnosis to their child, a prospective study was conducted among caretakers of HIV-infected children aged seven to 16 years who were receiving care at two paediatric HIV treatment centres in Bangkok. Caretakers were offered readiness preparation counselling and their perceptions on disclosure were assessed using a semi-structured questionnaire. Among caretakers who had participated in the readiness preparation process for at least one year, 71% (195/273) were ready for disclosure. Using logistic regression analysis, we found that child's age of nine years or older, child's severe immunosuppression, caretakers having prior discussion with their child about the illness, caretaker's perception that their child had the ability to understand the HIV diagnosis and to keep it secret, and caretaker's opinion that the proper age for disclosure is between seven and 12 years old were associated with caretaker's readiness for disclosure. These determinants may be useful for guiding disclosure readiness preparation counselling.

Etravirine in treatment-experienced, HIV-1-infected children and adolescents: 48-week safety, efficacy and resistance analysis of the phase II PIANO study.

OBJECTIVES: PIANO (Paediatric study of Intelence As an NNRTI Option; TMC125-C213; NCT00665847) assessed the safety/tolerability, antiviral activity and pharmacokinetics of etravirine plus an optimized background regimen (OBR) in treatment-experienced, HIV-1-infected children (≥ 6 to < 12 years) and adolescents (≥ 12 to < 18 years) over 48 weeks. METHODS: In a phase II, open-label, single-arm study, 101 treatment-experienced patients (41 children; 60 adolescents) with screening viral load (VL) ≥ 500 HIV-1 RNA copies/mL received etravirine 5.2 mg/kg (maximum dose 200 mg) twice a day (bid) plus OBR. RESULTS: Sixty-seven per cent of patients had previously used efavirenz or nevirapine. At week 48, the most common treatment-related grade ≥ 2 adverse event (AE) was rash (13%); 12% experienced grade 3 AEs. Only two grade 4 AEs occurred (both thrombocytopaenia, not etravirine related). At week 48, 56% of patients (68% children; 48% adolescents) achieved a virological response (VL<50 copies/mL; intent-to-treat, noncompleter=failure). Factors predictive of response were adherence > 95%, male sex, low baseline etravirine weighted genotypic score and high etravirine trough concentration (C0h ). Seventy-six patients (75%) completed the trial; most discontinuations occurred because of protocol noncompliance or AEs (8% each). Sixty-five per cent of patients were > 95% adherent by questionnaire and 39% by pill count. Forty-one patients experienced virological failure (VF; time-to-loss-of-virological-response non-VF-censored algorithm) (29 nonresponders; 12 rebounders). Of 30 patients with VF with paired baseline/endpoint genotypes, 18 (60%) developed nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations, most commonly Y181C. Mean etravirine area under the plasma concentration-time curve over 12 h (AUC0-12h ; 5216 ng h/mL) and C0h (346 ng/mL) were comparable to adult target values. CONCLUSIONS: Results with etravirine 5.2 mg/kg bid (with OBR) in this treatment-experienced paediatric population and etravirine 200 mg bid in treatment-experienced adults were comparable. Etravirine is an NNRTI option for treatment-experienced paediatric patients.

Drug-resistant tuberculosis in children in Thailand.

SETTING: Few data on drug-resistant (DR) tuberculosis (TB) in children are available in Thailand. OBJECTIVES: To evaluate the rate, clinical features and risk of DR-TB in children. DESIGN: Observational prospective study conducted in children diagnosed with TB at a tertiary care centre in Bangkok. RESULTS: Of 230 children diagnosed with TB, the median age was 6.5 years; 63% had identified adult source cases, and only 7% had received prior isoniazid treatment for latent tuberculous infection. Of the 195 (85%) specimens submitted, 57 (25%) were positive using culture or polymerase chain reaction. Of the 53 positive specimens available for drug susceptibility testing (DST), 18 (34%) had any resistance, 13 (24.5%) were mono-resistant, 2 (3.8%) polyresistant and 3 (5.7%) were multidrug-resistant. In multivariate analysis, prior TB treatment (P < 0.001), presence of atelectasis (P = 0.039) or lobar consolidation (P = 0.012) on chest X-ray were associated with DR-TB. DR-TB required longer treatment but there were no differences in rate of cure, treatment completion or death. CONCLUSIONS: The high rate of DR-TB underscores the importance of routine DST. History of treatment and drug susceptibility in source cases was useful in guiding initial treatment in children.

Lipodystrophy and reversal of facial lipoatrophy in perinatally HIV-infected children and adolescents after discontinuation of stavudine.

Lipodystrophy (LD) was evaluated in 205 children receiving antiretroviral therapy by a single investigator: 51 (24.9%) had LD; 46 peripheral lipoatrophy, three central lipohypertrophy and two combined type. All cases of peripheral and combined LD also had facial lipoatrophy. Serial photographs were provided by the families to confirm the severity of facial lipoatrophy. Forty-six (95.8%) children with peripheral or combined LD, and 75 (48.7%) without LD were exposed to stavudine (d4T) for a median duration of 45.9 versus 26.4 months (P = 0.005). In multivariate analysis, exposure to d4T for more than three months was the only factor associated with peripheral or combined LD (P < 0.001). Noticeable improvement of facial lipoatrophy was found in 11/48 (22.9%) children after a mean duration of 45.6 months following d4T discontinuation, mostly occurring during early adolescence.

An infant with cartilage-hair hypoplasia due to a novel homozygous mutation in the promoter region of the RMRP gene associated with chondrodysplasia and severe immunodeficiency.

Cartilage-hair hypoplasia (CHH) is a rare autosomal-recessive disorder characterized by short-limbed dwarfism, sparse hair, and immune deficiency. It is caused by mutations in the RMRP gene, which encodes the RNA component of the mitochondrial RNA-processing ribonuclease (RNase MRP). Several mutations have been identified in its promoter region or transcribed sequence. However, homozygous mutations in the promoter region have been only reported in a patient with primary immunodeficiency without other features of CHH. We report on a Thai girl who first presented with chronic diarrhea, recurrent pneumonia, and severe failure to thrive, without apparently disproportionate dwarfism. The diagnosis of CHH was made after the severe wasting was corrected, and disproportionate growth became noticeable. The patient had the typical features of CHH, including sparse hair and metaphyseal abnormalities. The immunologic profiles were consistent with combined immune deficiency. Mutation analysis identified a novel homozygous mutation, g.-19_-25 dupACTACTC, in the promoter region of the RMRP gene. Identification of the mutation enabled us to provide a prenatal diagnosis in the subsequent pregnancy. This patient is the first CHH case with the characteristic features due to the homozygous mutation in the promoter region of the RMRP gene. The finding of severe immunodeficiency supports that promoter mutations markedly disrupt mRNA cleavage function, which causes cell-cycle impairment.

HIV-1 drug resistance mutations in children after failure of first-line nonnucleoside reverse transcriptase inhibitor-based antiretroviral therapy.

OBJECTIVES: The aim of the study was to assess the prevalence, predictors and patterns of genotypic resistance mutations in children after failure of World Health Organization-recommended initial nonnucleoside reverse transcriptase inhibitor (NNRTI)-based treatment regimens. METHODS: We carried out a multicentre retrospective study of genotyping tests performed for all HIV-infected children at eight paediatric centres in Thailand who experienced failure of NNRTI therapy at a time when virological monitoring was not routinely available. RESULTS: One hundred and twenty children were included in the study. Their median age (interquartile range) was 9.1 (6.8-11.0) years, the median duration of their NNRTI regimens was 23.7 (15.7-32.6) months, their median CD4 percentage was 12% (4-20%), and their median plasma HIV RNA at the time of genotype testing was 4.8 (4.3-5.2) log(10) HIV-1 RNA copies/mL. The nucleoside reverse transcriptase inhibitor (NRTI) resistance mutations found were as follows: 85% of the children had M184V/I, 23% had at least four thymidine analogue mutations, 12% had the Q151M complex, 5% had K65R, and 1% had the 69 insertion. Ninety-eight per cent of the children had at least one NNRTI resistance mutation, and 48% had etravirine mutation-weighted scores ≥4. CD4 percentage <15% prior to switching regimens [odds ratio (OR) 5.49; 95% confidence interval (CI) 2.02-14.93] and plasma HIV RNA>5 log(10) copies/mL (OR 2.46; 95% CI 1.04-5.82) were independent predictors of at least four thymidine analogue mutations, the Q151M complex or the 69 insertion. CONCLUSIONS: In settings without routine viral load monitoring, second-line antiretroviral therapy regimens should be designed assuming that clinical or immunological failure is associated with high rates of multi-NRTI resistance and NNRTI resistance, including resistance to etravirine.

Neonatal pasteurellosis: a review of reported cases.

BACKGROUND: Pasteurellosis is an uncommon infectious disease in humans mainly caused by Pasteurella multocida infection in neonates and has been rarely reported. OBJECTIVES: To review the literature and address the mode of transmission, clinical presentation, laboratory diagnosis, treatment, outcome and potential risk factors related to neonatal pasteurellosis. METHODS: A Medline all-languages database search for neonatal (birth-1 month) pasteurellosis cases after 1950 was conducted. Individual references from each publication were also reviewed to identify additional cases. RESULTS: Thirty-two cases were found, but detailed information was available for this review in only 25 cases. The median age was 14 days (range: birth-30 days). All were infected with P multocida. Animal exposure to cats and/or dogs was the major risk of infection: non-traumatic exposure in 11 (44%) cases, and traumatic exposure in 2 (8%) cases. Infections in 11 (44%) cases were classified as vertical transmission. The clinical features were most commonly bacteraemia with or without meningitis. The age at onset of 72 h or older was significantly associated with meningitis (> or = 72 h of age: 13/14 vs <72 h of age: 3/11, p = 0.002). The most used antibiotics were beta-lactam with or without aminoglycoside or chloramphenicol. The overall mortality was 20% (5/25). The age at presentation of <72 h, birth weight of <2500 g, and vertical transmission were independently associated with death. CONCLUSION: Pasteurellosis is a rare bacterial infection in neonates and should be considered in the cases of sepsis with history of exposure to domestic animal in either the patient or the mother.

Penicilliosis-associated hemophagocytic syndrome in a human immunodeficiency virus-infected child: the first case report in children.

Infection-associated hemophagocytic syndrome (IAHS) has been found in many systemic infectious conditions with a high mortality rate. Disseminated Penicillium marneffei infection is a common opportunistic condition among HIV-infected patients in many regions in Southeast Asia. We report the first case of IAHS caused by penicilliosis in an HIV-infected child who presented with cytopenias and recovered promptly after antifungal and intravenous immunoglobulin therapy.

A report case of Cyclospora and Cryptosporidium mixed infection in a HIV-negative child in Thailand.

The first case of cyclosporosis in a non HIV-infected child in Thailand, co-infected with Cryptosporidium, was reported. The patient was a 3 year-old malnourished orphan who presented with fever, abdominal distension and relapsing diarrhea. There was no leukocyte in her stool, however, numerous Cyclospora and Cryptosporidium oocysts were identified by modified acid-fast staining. The illness was cured by co-trimoxazole and fluid therapy. More coccidial infections in Thailand may be detected if modified acid-fast staining is routinely performed.

Nosocomial bloodstream infection in pediatric patients: Siriraj Hospital, Bangkok; 1996-1999.

A retrospective study on nosocomial bloodstream infection (NBSI) in pediatric patients hospitalized at Siriraj Hospital from January 1996 to December 1999 was performed. Of the 18,087 blood specimens sent for culture, 533 (3%) were positive for organisms after 72 hours of hospitalization and were defined as NBSI. The rate of NBSI detected in blood culture specimens was highest among neonates (5.2%). Gram-positive cocci and gram-negative rods caused NBSI in an equal proportion (46% and 44% respectively) and Candida caused 10 per cent of NBSI. Coagulase-negative staphylococci was the most common pathogen followed by K. pneumoniae and Enterobacter. Antibiogram showed that 15 of the 35 (43%) S. aureus identified were methicillin-resistant. Only 35-38 per cent of Enterobacteriaceae were sensitive to cefotaxime or ceftazidime. Cefoxitin was still effective against 95 per cent of K. pneumoniae. Compared with other third generation cephalosporins, combination of cefoperazone and betalactamase-inhibitor (sulbactam) possessed an increased in vitro efficacy against K. pneumoniae, Enterobacter, E. coli, Acinetobacter and non-fermentative gram-negative rods. Resistant rate of amikacin among all gram negative rods was 25-69 per cent. Ciprofloxacin sensitivity varied from 62-100 per cent among all gram-negative rods. Imipenem was excellent against all gram-negative rods with the sensitivity of 80-100 per cent. Epidemiological data of this study is important for the decision of the appropriate empirical antimicrobial treatment in our hospital.

Viral etiologies of encephalitis in Thai children.

A prospective study of childhood encephalitis was performed in Bangkok from 1996 through 1998. The viral agents identifiable in 26 (65%) of 40 children were dengue virus (8), Japanese encephalitis (6), herpes simplex virus (4), human herpes virus type 6 (3), mumps (2), enterovirus (1), varicella-zoster virus (VZV) (1) and rabies (1).