Is primary meningococcal arthritis in children more frequent than we expect? Two pediatric case reports revealed by molecular test.

BACKGROUND: Primary meningococcal arthritis is a rare infectious disease that occurs in less than 3% of meningococcal infections and is characterized by arthritis without meningitis, fever, rash, or hemodynamic instability Barahona [Case Rep Orthop 4696014:2017 ]. There are no validated clinical criteria that can be used for the diagnosis. We present two pediatric cases of atypical presentation of meningococcal disease revealed by molecular tests. CASE PRESENTATION: The clinical presentation of the two children (6- and 9-years-old) was characterized by signs of arthritis. By Real Time Polymerase Chain Reaction (RT-PCR), we identified N. meningitidis serogroup Y in the joint fluid in both cases. After specific antimicrobial treatment, the clinical conditions of the two patients quickly improved during hospitalization. CONCLUSIONS: We believe that the incidence of meningococcal arthritis could be underestimated in those settings where the use of RT-PCR is limited. Clearer data on the incidence of meningococcal disease would help to design specific treatments and the best possible national vaccine strategies [Fiji Sci Rep 23:39784, 2016, J Infect 67:385-90, 2013].

Altered natural killer cells subsets distribution in children with hepatitis C following vertical transmission.

BACKGROUND: Natural killer (NK) cells number, phenotypes and function have been evaluated in many studies in adults with hepatitis C as compared with healthy controls or dynamically during interferon-based and interferon-free treatments. Overall, in adults with chronic infection number of circulating NK cells has been reported to be lower when compared to spontaneous resolvers and healthy subjects. Different studies yielded inconsistent findings due to patient and virus heterogeneity. AIM: To evaluate NK cells in children according to the different outcomes of the infection. METHODS: In this cross-sectional study, we examined numbers and phenotypes of circulating NK cells from a homogenous cohort of Italian children with vertically acquired hepatitis C. RESULTS: We compared 31 children who developed chronic infection with nine who presented spontaneous clearance and 13 controls. CD56(+) CD3(-) NK cell numbers were consistently lower in the persistently infected group (P = 0.03 and 0.04). This decrease was due to depletions of CD56(dim) NK cells (P = 0.03 chronic infection vs. spontaneous clearance), while CD56(bright) NK cells were expanded (P = 0.03). No significant difference was found in the frequencies of CD56(+) CD16(+) and CD56(dim) CD16(-) cells. Perforin expression was higher in children with chronic infection (P = 0.03 vs. spontaneous clearance). CONCLUSIONS: Altered NK cells number and phenotypes could impact the outcome of HCV infection in children following vertical transmission. This study suggests for the first time that NK cells cytolytic function, featured by CD56(dim) cells, contributes to the elimination of HCV in children presenting spontaneous clearance.

Spiramycin/cotrimoxazole versus pyrimethamine/sulfonamide and spiramycin alone for the treatment of toxoplasmosis in pregnancy.

OBJECTIVE: To compare the effectiviness of spiramycin/cotrimoxazole (Sp/C) versus pyrimethamine/sulfonamide (Pyr/Sul) and spiramycin alone (Spy) on mother-to-child transmission of toxoplasmosis infection in pregnancy. STUDY DESIGN: Retrospective study of pregnant women evaluated for suspected toxoplasmosis between 1992 and 2011. RESULT: A total of 120 mothers and their 123 newborns were included. Prenatal treatment consisted of spiramycin in 43 mothers (35%), spiramycin/cotrimoxazole in 70 (56.9%) and pyrimethamine/sulfonamide in 10 (8.1%). A trend toward reduction in toxoplasmosis transmission was found when Sp/C was compared with Pyr/Sul and particularly with Spy alone (P=0.014). In particular, Spy increased the risk of congenital infection when compared with Sp/C (odds ratio (OR) 4.368; 95% CI: 1.253 to 15.219), but there was no significant reduction when Sp/C was compared with Pyr/Sul (OR 1.83; 95% CI: 0.184 to 18.274). CONCLUSION: The treatment based on Sp/C has significant efficacy in reducing maternal-fetal transmission of Toxoplasma gondii when compared with Pyr/Sul and particularly to Spy. Randomized controlled trials would be required.

Congenital cytomegalovirus infection: current strategies and future perspectives.

INTRODUCTION: Cytomegalovirus is the most common cause of congenital infections in humans and it produces considerable morbidity in newborns. AIMS: The present study reviews current concepts on epidemiology, clinical manifestations, diagnosis, treatment, future strategies and prognosis of children with congenital cytomegalovirus infection. RESULTS: Congenital cytomegalovirus infection can be symptomatic or not at birth, but about 10-20% of them all will exhibit neurological damage when followed up. Sensorineural hearing loss is the most frequent long-term consequence and is not manifest invariably at birth or in the neonatal period but in many cases becomes clinically apparent in later childhood. There are growing evidences that newborns with symptomatic congenital cytomegalovirus infection would benefit from treatment with either ganciclovir or valganciclovir, the most widely studied drugs in this setting. It is not yet clear if children with asymptomatic or pauci-symptomatic infection at birth would benefit from treatment. DISCUSSION: Studies evaluating treatment and long-term follow-up of infants with both symptomatic and asymptomatic infection are necessary, in order to definitely evaluate the short and long-term effectiveness and safety of both ganciclovir and valganciclovir and to identify risk factors associated to the development of long-term sequelae. In this way it will be possible to select those children that might benefit for treatment.

Pediatric hepatitis C infection: to treat or not to treat...what's the best for the child?

OBJECTIVES: Pediatric hepatitis C mainly occurs through mother to child transmission, to date. Children usually present a mild disease, but they are not spared from its long-term complications. Thus this infection cannot be underestimated in children and intervention is necessary. Current treatment is based on the administration of pegylated-interferon associated with ribavirin, but few studies evaluated the efficacy and safety of this therapeutic protocol. Moreover, there is still no clarity on who, when and how to treat pediatric patients. This article, based on the information in literature, provides an overview of the main aspects of the disease, with particular attention to treatment. METHODOLOGY AND RESULTS: We describe the different treatment options available. About the association peginterferon plus ribavirin, we analyze thirteen non-randomized studies and one trial, found in recent literature. These studies are not directly compared because of differences in age, type of infection (vertical or not), viral genotypes and duration of treatment, between groups enrolled. The overall sustained viral response rate ranges from 28.6% to 81.8%. The rate of treatment success is higher in children infected with genotypes 2 and 3 than with other genotypes. The therapy does not induce severe adverse effects and children present better tolerance to antiviral than adults. CONCLUSIONS: The pharmacological efficacy of peginterferon and ribavirin seems to be proven by data collected in studies cited, but there are different opinions about who, when and how to treat children infected. Thus, further research is needed to define the best management of vertical acquired hepatitis C.

[Congenital toxoplasmosis treatment]

OBJECTIVES: Congenital toxoplasmosis is a particular manifestation of Toxoplasma gondii infection, which may present as a mild or severe neonatal disease. This pathology remains a difficult challenge in terms of therapy for the pediatrician and gynecologist. In this article we have set ourselves the objective to provide an overview of the main aspects of the disease, with particular attention to the treatment, based on the information in the literature. RESULTS: Two kinds of treatment are currently available: prenatal and postnatal. When pregnant women seroconvert, spiramycin is administered in order to prevent the mother-to-child transmission. When the fetal infection is confirmed the association of pyrimethamine and sulfadiazine is prescribed. After birth the specific therapy is based on the administration of pyrimethamine and sulfadiazine. However, to date, there is not strong evidence on the effectiveness of treatment, whether prenatal or postnatal. CONCLUSIONS: The studies undertaken so far have not given satisfactory answers. Double-blind randomized controlled trials would be required, but for obvious ethical reasons they cannot be achieved.

Management of central nervous system tuberculosis in children: light and shade.

BACKGROUND: Pediatric tuberculosis of the central nervous system (CNS-TB) is a severe form of extrapulmonary TB. It is most common in children between 6 months and 4 years of age. CNS-TB can present as meningitis and/or tuberculoma. In both situations, brain damage results from a cytokine-mediated inflammatory response, which causes vasculitis, obstructive hydrocephalus and cranial nerve palsy. Tumor necrosis factor alpha (TNF-alpha) is an important cytokine in this response. The prognosis of tuberculous meningitis (TBM) correlates most closely with the clinical stage of illness at the time treatment is started. Most patients in the 1st stage have a good outcome, whereas the management of patients in the 2nd and 3rd stage is still a clinical challenge, and the few patients who survive have permanent severe disabilities. Due to the important role of inflammation in CNS-TB pathogenesis, corticosteroids are routinely used in TBM or tuberculomas, in order to reduce death and disabling residual neurological deficits among survivors. Nevertheless, not all patients show a good response to standard anti-inflammatory treatment. Thalidomide is a drug with pleiotropic effects: it appears to downregulate production of TNF-alpha and other proinflammatory cytokines. Due to its anti-inflammatory effects, thalidomide has been evaluated as an adjunctive drug in the management of difficult-to-treat CNS-TB. MATERIALS AND METHODS: A literature review was carried out based on MEDLINE/pubmed database (1997/2010) searching for the following descriptors: corticosteroids and tuberculous meningitis (limits: review, all child); thalidomide and tuberculosis treatment; and tuberculous meningitis; and CNS-TB; and brain abscess; and TB clinical trial. AIMS: Literature review on the use of corticosteroids and thalidomide in the treatment of CNS-TB. RESULTS: The Cochrane review for randomized-controlled trials evaluating the use of steroids in TBM showed significantly reduced overall mortality, reduced death and severe residual disability in children. Regarding the use of thalidomide, a randomized controlled trial published in 2004 do not support the use of adjunctive high-dose thalidomide therapy in the treatment of TBM in children, but results from four case reports, one clinical trial and one placebo-controlled trial suggest the use of thalidomide in CNS-TB not responding to standard therapy. CONCLUSION: "Adjuvant" treatment with dexamethasone improves survival in patients with TBM but probably does not prevent disability. Thalidomide should not be used for the routine treatment, but it may be helpful as a "salvage therapy" in patients with TBM and tuberculomas not responding to anti-TB drugs and high dose corticosteroids. More studies should evaluate its not completely conclusive role.