Monkeypox: How Globalization, Host Immunity, and Viral Evolution Create a New Pathogen.

Monkeypox is an Orthopoxvirus, endemic to West Africa and the Congo Basin. It causes an illness characterized by fever, myalgias, lymphadenopathy, and a disseminated vesicular rash. Although similar to smallpox, monkeypox is typically milder, with a lower mortality rate. Endemicity in Africa was previously reduced owing to cross-protection from smallpox vaccine but has been increasing since cessation of universal vaccination. Sporadic cases have been imported to the United States (US), with a few secondary cases. A large global outbreak in 2022 has demonstrated changing epidemiology and increased person-to-person transmission. In May 2022, a returned traveler in Massachusetts presented with monkeypox. As of October 7, 2022, 71,096 cases had been reported in 107 countries, and 26,577 of those were in the US. Most cases have been in younger people without previous smallpox vaccination and in men who have sex with men, a previously unrecognized mode of transmission. [Pediatr Ann. 2022;51(11):e431-e435.].

Nevirapine-associated rash with eosinophilia and systemic symptoms in a child with human immunodeficiency virus infection.

Drug rash with eosinophilia and systemic symptoms (DRESS Syndrome) associated with nevirapine treatment has not been previously reported in children. These findings can mimic other common illnesses, and treatment options are limited. We describe a 12-year-old girl infected with human immunodeficiency virus who developed hypersensitivity to nevirapine therapy. She was successfully treated with intravenous immune globulin.

Impact of the pneumococcal conjugate vaccine on serotype distribution and antimicrobial resistance of invasive Streptococcus pneumoniae isolates in Dallas, TX, children from 1999 through 2005.

BACKGROUND: Because the heptavalent pneumococcal conjugate vaccine has reduced vaccine-type invasive pneumococcal disease (IPD) in children, a greater proportion of IPD is now caused by nonvaccine (NVT) serotypes. We analyzed the serotypes, antimicrobial resistance profiles and genetic relatedness of Streptococcus pneumoniae responsible for IPD at Children's Medical Center of Dallas. METHODS: S. pneumoniae isolates were collected from January 1, 1999 through December 31, 2005. Incidence of IPD was calculated using inpatient and emergency center admissions to Children's Medical Center of Dallas as the denominator. Isolates were serotyped, and their penicillin and cefotaxime susceptibility determined. The 19A isolates were further characterized by pulsed-field gel electrophoresis, multilocus sequence typing and determination of penicillin-binding proteins and mef and erm genes. RESULTS: The incidence of IPD decreased from 93.6 cases/100,000 patients in 1999 to a nadir of 41 cases/100,000 patients in 2003 (P < 0.001). The number of IPD cases caused by serotype 19A increased, accounting for 40% of the cases of IPD in 2005. Penicillin and cefotaxime susceptibility of IPD isolates did not change from 1999 through 2005 (P = 0.687). There was a decrease in penicillin (P < 0.001) and cefotaxime (P = 0.034) susceptibility in NVT serotypes from 1999 to 2005. Molecular characterization of 19A isolates revealed a predominance of ST-199 (62%). Several highly penicillin-resistant and intermediately cefotaxime-resistant strains emerged in 2004 and 2005. CONCLUSIONS: In Dallas, heptavalent pneumococcal conjugate vaccine reduced the incidence of IPD from 1999 to 2005 by reducing the incidence of vaccine-type disease. NVT serotypes, particularly 19A, were prevalent and more resistant to antimicrobials in 2004 and 2005.

Antiretroviral Therapy in Children Less Than 24 Months of Age at Pediatric HIV Centers in Tanzania: 12-Month Clinical Outcomes and Survival.

BACKGROUND: Without antiretroviral therapy (ART), approximately one-half of HIV-infected infants will die by two years. In 2010, the World Health Organization (WHO) recommended that all HIV-infected infants < 24 months be initiated on ART regardless of their clinical/immunologic status. However, there remains little published data detailing cohorts of infants on ART in Sub-Saharan Africa. This study describes baseline characteristics and 12 month outcomes of a cohort of HIV-infected children < 24 months of age at pediatric HIV centers in Mwanza and Mbeya, Tanzania. MATERIALS AND METHODS: Retrospective chart review. INCLUSION CRITERIA: children < 24 months of age, initiated on ART at Baylor Children s Foundation Tanzania clinics, between March-December 2011. RESULTS: Baseline: Ninety-three children were initiated on ART at a median age of 13.4 months. Sixty-seven percent had severe immunosuppression and 31.5% had severe malnutrition. OUTCOME: Seventy-three patients were still in care at 12 month follow-up, there were four (4.3%) deaths, five (5.4%) patients transferred, and 11 (11.8%) loss to follow-up. Average CD4% was 32.7 (p < 0.001). Ninety percent of patients were WHO treatment stage I (p < 0.001). Eighty-six percent had normal nutritional status (p < 0.001). CONCLUSION: Our cohort of HIV infected children < 24 months initiated on ART did well clinically at 12 month outcomes despite being severely immunocompromised and malnourished at baseline. Nevirapine based regimens had good 12 month clinical outcomes, regardless of maternal exposure. Loss to follow-up rate was high for our cohort, demonstrating the need to develop strong mechanisms to counteract this.

Microbiological culture methods for pediatric musculoskeletal infection: a guideline for optimal use.

BACKGROUND: Culture results affect the diagnosis and treatment of children with musculoskeletal infection. To our knowledge, no previous large-scale study has assessed the relative value of culture methods employed during the evaluation of these conditions. The purpose of this study was to identify an optimal culture strategy for pediatric musculoskeletal infection. METHODS: Children with musculoskeletal infection were retrospectively studied to assess culture results from the infection site or blood; culture type, including aerobic, anaerobic, fungal, and acid-fast bacteria (AFB); antibiotic exposure history; and clinical history of children with positive culture results. RESULTS: We studied 869 children, including 353 with osteomyelitis, 199 with septic arthritis, forty-two with pyomyositis, and 275 with abscess. The 4537 cultures processed included 1303 aerobic, 903 anaerobic, 340 fungal, 289 AFB, and 1702 blood. Of 3004 specimens sent during initial work-up, positive results occurred in 677 of 1049 aerobic cultures (64.5%), 140 of 763 blood cultures (18.3%), eighteen of 722 anaerobic cultures (2.5%), five of 251 fungal cultures (2.0%), and two of 219 AFB cultures (0.9%). Staphylococcus aureus was the most common pathogen isolated, from 428 (50.7%) of 844 children for whom blood or infection-site culture material was sent (methicillin-resistant S. aureus, 252; and oxacillin-sensitive S. aureus, 176). Cultures were negative in 206 (29.0%) of the 710 children for whom culture material from the site of infection was sent. Children with true-positive anaerobic, fungal, or AFB cultures had a history of immunocompromise, penetrating inoculation, or failed primary treatment. Antibiotic exposure prior to culture-sample acquisition did not interfere with aerobic culture results from the site of infection. CONCLUSIONS: Our findings suggest that anaerobic, fungal, and AFB cultures should not be routinely performed during the initial evaluation of children with hematogenous musculoskeletal infection. These cultures should be performed for children with immunocompromise, clinical suspicion of penetrating inoculation, or failed primary treatment.

Effect of the 7-valent pneumococcal conjugate vaccine on nasopharyngeal colonization by Streptococcus pneumoniae in the first 2 years of life.

BACKGROUND: Studies suggest that the 7-valent pneumococcal conjugate vaccine (PCV7) reduces carriage of vaccine-type (VT) Streptococcus pneumoniae (SP). We studied the effect of PCV7 on carriage of VT- and non-VT (NVT) SP, by studying the effect of PCV7 on nasopharyngeal (NP) colonization by VT and NVT SP during early childhood. METHODS: At 2 months of age, 278 infants were enrolled in this study. To determine carriage of SP, NP samples were obtained before each PCV7 dose, at 9 months of age, and 2-3 months after the booster dose of vaccine. RESULTS: The carriage of SP increased slightly, from 12% (95% confidence interval [CI], 8%-16%) of subjects at 2 months of age to 18% (95% CI, 13%-23%) at 4 months of age (P<.05). Carriage of SP remained in 24%-30% of subjects during subsequent months. Between the 12- and 18-month visits, the carriage rate of VT SP decreased significantly, from 18% (95% CI, 13%-23%) to 9% (95% CI, 5%-13%) of subjects (P=.001). The trend of a decrease in carriage of penicillin-nonsusceptible SP, from 16% of subjects (95% CI, 11%-21%) at the 12-15-month visit to 9% (95% CI, 5%-13%) at the 15-18-month visit, was found after the booster dose of vaccine. CONCLUSION: The reduction of VT-SP colonization and replacement by NVT SP after the booster dose of vaccine suggests the possibility that widespread vaccination will result in replacement of pneumococci mainly by antibiotic-susceptible NVT SP.

A proposed scoring system for assessment of severity of illness in pediatric acute hematogenous osteomyelitis using objective clinical and laboratory findings.

BACKGROUND: Severity of illness in children with acute hematogenous osteomyelitis (AHO) is variable, ranging from mild, requiring short-duration antibiotic therapy without surgery, to severe, requiring intensive care, multiple surgeries and prolonged hospitalization. This study evaluates severity of illness among children with AHO using clinical and laboratory findings. METHODS: Fifty-six children with AHO, consecutively treated in 2009, were retrospectively studied. Objective clinical, radiographic and laboratory parameters related to severity of illness were gathered for each child. A physician panel was assembled to rank order objective clinical parameters, review clinical data and classify each child as mild, moderate or severe. Statistically significant parameters correlated with length of hospitalization were utilized to devise a severity of illness score and applied to the cohort of children for internal validation. RESULTS: The physician panel had perfect or substantial agreement regarding 7 parameters (ICU admission, intubation, pulmonary involvement, venous thrombosis, multifocal infection, surgeries and febrile days on antibiotics). Parameters that significantly correlated with total length of stay included: C-reactive protein values at admission (P < 0.0001), 48 hours (P < 0.0001) and 96 hours (P < 0.0002); febrile days on antibiotics (P < 0.0001); admission respiratory rate (P = 0.023) and evidence of disseminated disease (P = 0.016). A scoring system, derived from selected parameters, significantly differentiated children with AHO on the basis of causative organism, intensive care admission, surgeries, length of hospitalization, complications and physician panel assessment. CONCLUSIONS: Severity of illness score for AHO, derived from preliminary clinical and laboratory findings, is useful stratifying children with this disease. LEVEL OF EVIDENCE: Prognostic Level II.

Use of nucleoside reverse transcriptase inhibitor-only regimens in HIV-infected children and adolescents.

OBJECTIVE: In adults, nucleoside reverse transcriptase inhibitor-only antiretroviral regimens (NOARs) with ≥3 nucleoside reverse transcriptase inhibitors are less potent than highly active antiretroviral therapy (HAART). Published pediatric experience with NOARs is limited; thus, we wished to better define the virological, immunological and toxicological effects of NOARs in children and adolescents. METHODS: We analyzed data from NOAR-treated participants in LEGACY, a multicenter observational cohort study of HIV-infected children and adolescents. NOAR-treated case-participants were matched to participants without prior NOAR who initiated HAART during the same year for comparison. RESULTS: Of 575 participants with data from time of HIV diagnosis through 2006, 67 (12%) received NOARs for at least 24 weeks; most (46%) received the fixed dose combination of zidovudine/lamivudine/abacavir. NOAR use peaked in 2001 to 2002. NOAR-treated participants were significantly older and more treatment experienced than HAART-treated participants. Virologic outcomes, including the percentage of participants with a plasma HIV RNA viral load <400 copies/mL at week 24 (47% versus 34%) and the mean 24-week change in log10 plasma HIV RNA viral load from baseline (-0.63 versus -1.02), were similar between NOAR- and HAART-treated participants, but virologic rebound was more likely in NOAR-treated participants (77% versus 54%, P = 0.02). Increase in CD4 percentage points from baseline to 24 weeks was negligible in NOAR-treated participants compared with HAART-treated participants (0.95% versus 10.1%, P < 0.001). Anemia and leukopenia were more commonly reported with NOARs than HAART. DISCUSSION: Week 24 virologic outcomes were similar between NOAR- and HAART-treated participants, but NOAR durability was poorer and their use was associated with less immunologic reconstitution. NOARs should play a limited role in pediatric and adolescent antiretroviral therapy.

Methicillin-Resistant Staphylococcus aureus Infections in Human Immunodeficiency Virus-Infected Children and Adolescents.

Background. Methicillin-resistant Staphylococcus aureus (MRSA) infection incidence has increased in healthy US children. Our objective was to evaluate MRSA incidence and correlates in HIV-infected youth. Methods. The CDC-sponsored LEGACY study is a US multicenter chart abstraction study of HIV-infected youth. We identified MRSA infections among participants with ≥1 visit during 2006. We used bivariate and multivariable analyses to compare sociodemographic and HIV clinical factors between MRSA cases and noncases. Results. Fourteen MRSA infections (1 invasive, 12 soft tissue, 1 indeterminate) occurred among 1,813 subjects (11.1 infections/1,000 patient-years (PY), 95% CI: 11.06-11.14). Most (86%) isolates were clindamycin susceptible. Compared with noncases, MRSA cases were more likely older (17 versus 14 years), black (100% versus 69%), behaviorally HIV infected (43% versus 17%), and in Maryland (43% versus 7%) and had viral loads (VL) >1000 copies/mL (86% versus 51%) and lower mean CD4% (18% versus 27%) (all P < 0.05). In multivariate analysis, independent risk factors were Maryland care site (adjusted odds ratio (aOR) = 9.0), VL >1000 copies/mL (aOR = 5.9), and black race (aOR undefined). Conclusions. MRSA occurred at a rate of 11.1 infections/1,000 PY in HIV-infected youth but invasive disease was uncommon. Geographic location, black race, and increased VL, but not immunosuppression, were independently associated with MRSA risk.

Premastication as a route of pediatric HIV transmission: case-control and cross-sectional investigations.

BACKGROUND: Three cases of pediatric HIV transmission attributed to the feeding practice of premasticating food for children have been reported. The degree of risk that premastication poses for pediatric HIV transmission and the prevalence of this behavior among HIV-infected caregivers is unknown. METHODS: During December 2009 to February 2010, we conducted a case-control investigation of late-diagnosed HIV infection in children at 6 HIV clinics using in-person and telephone interviews. A cross-sectional investigation of premastication was conducted in concert with this case-control investigation. RESULTS: We compared 11 case-patients to 35 HIV-exposed controls of similar age. Sixteen (35%) of 46 children were fed premasticated food, 10 (22%) by an HIV-infected caregiver. Twenty-seven percent of case-patients received premasticated food from an HIV-infected caregiver compared with 20% of controls (odds ratio = 1.5; 95% confidence interval = 0.3 to 7.1). In the cross-sectional investigation, 48 (31%) of 154 primary caregivers of children aged ≥6 months reported the children received premasticated food from themselves or someone else. The prevalence of premastication decreased with increasing caregiver age and had been used to feed children aged 1-36 months. CONCLUSIONS: Premastication, a potential route of HIV transmission to children, was a common practice of caregivers. Public health officials and health care providers should educate the public about the potential risk of disease transmission via premastication.

Identification of a Candidate Streptococcus pneumoniae core genome and regions of diversity correlated with invasive pneumococcal disease.

Streptococcus pneumoniae is a leading cause of community-acquired pneumonia and gram-positive sepsis. While multiple virulence determinants have been identified, the combination of features that determines the propensity of an isolate to cause invasive pneumococcal disease (IPD) remains unknown. In this study, we determined the genetic composition of 42 invasive and 30 noninvasive clinical isolates of serotypes 6A, 6B, and 14 by comparative genomic hybridization. Comparison of the present/absent gene matrix (i.e., comparative genomic analysis [CGA]) identified a candidate core genome consisting of 1,553 genes (73% of the TIGR4 genome), 154 genes whose presence correlated with the ability to cause IPD, and 176 genes whose presence correlated with the noninvasive phenotype. Genes identified by CGA were cross-referenced with the published signature-tagged mutagenesis studies, which served to identify core and IPD-correlated genes required for in vivo passage. Among these, two pathogenicity islands, region of diversity 8a (RD8a), which encodes a neuraminidase and V-type sodium synthase, and RD10, which encodes PsrP, a protein homologous to the platelet adhesin GspB in Streptococcus gordonii, were identified. Mice infected with a PsrP mutant were delayed in the development of bacteremia and demonstrated reduced mortality versus wild-type-infected controls. Finally, the presence of seven RDs was determined to correlate with the noninvasive phenotype, a finding that suggests some RDs may contribute to asymptomatic colonization. In conclusion, RDs are unequally distributed between invasive and noninvasive isolates, RD8a and RD10 are correlated with the propensity of an isolate to cause IPD, and PsrP is required for full virulence in mice.

Pneumonia and septicemia caused by Burkholderia thailandensis in the United States.

Burkholderia thailandensis is closely related to Burkholderia pseudomallei, the causative agent of melioidosis. It is generally considered avirulent and previously has been reported to occur only in Southeast Asia. We report the first case of pneumonia and septicemia caused by B. thailandensis in the United States.

Mobilization of plasmacytoid and myeloid dendritic cells to mucosal sites in children with respiratory syncytial virus and other viral respiratory infections.

BACKGROUND: Respiratory syncytial virus (RSV) is the principal etiologic agent of bronchiolitis and viral pneumonia in infants and young children. Yet, many aspects of its immunopathogenesis are not well understood. METHODS: We analyzed the immune cells that are mobilized by RSV and other respiratory viruses, by studying nasal wash samples from children hospitalized with acute viral respiratory infections. RESULTS: RSV mobilizes virtually all blood immune cells, including myeloid dendritic cells (DCs) and plasmacytoid DCs (pDCs), to the nasal mucosa. DCs were also mobilized to the nasal mucosa of children with other viral respiratory infections. The increased number of pDCs in the nasal compartment significantly correlates with RSV load (P=.022), and it is associated with a significant decrease in the number of pDCs in the blood (P=.007). The influx of DCs in the nasal mucosa is not transient, as even higher numbers of both DC subsets were found in respiratory secretions weeks after the acute symptoms of RSV infection had resolved. Immunochemistry analysis of respiratory samples has demonstrated the presence of the RSV fusion protein within HLA-DR-positive cells. CONCLUSION: Infection with RSV and other respiratory viruses mobilizes DCs to the site of viral entry.