Neonatal Meningitis and Sepsis by Chryseobacterium indologenes: A Rare and Resistant Bacterium

Early neonatal meningitis with non-fermenting Gram negative bacilli (NFGNB) is rare, and whenever it occurrs, inanimate environment is usually implicated as the source. The authors report a case of neonatal meningitis and sepsis with Chryseobacterium indologenes, a rare non fermenting Gram negative bacterium with unusual antimicrobial susceptibility. Despite resistance to all the beta lactams, carbapenems and aminoglycosides, therapy with ciprofloxacin led to a favorable outcome.     

Transmission of multidrug-resistant tuberculosis

AIM: To compare the Mycobacterium tuberculosis isolates of adult index cases with multidrug-resistant (MDR) tuberculosis to the isolates obtained from their child contacts. PATIENTS AND METHODS: A 4-year prospective study in the Western Cape Province of South Africa. We evaluated 149 child contacts of 80 adult MDR pulmonary tuberculosis cases. This report includes those cases where a culture for M. tuberculosis was obtained from both the adult source case and the child contact. Isolates were compared by drug susceptibility pattern and restriction fragment length polymorphism analysis. RESULTS: Six adult-child pairs with cultures for M. tuberculosis were identified. Two children had contact with more than one adult tuberculosis case. One child received previous isoniazid prophylaxis. Drug susceptibility pattern and restriction fragment length polymorphism analysis were identical for five adult-child pairs. One child, with no other known source case, had a strain different from that of the identified source case, but the MDR M. tuberculosis strain with which he was infected was prevalent in the community in which he resided. All children responded well to treatment. CONCLUSION: This study confirms that most of the childhood contacts of adults with MDR tuberculosis are likely to be infected by these MDR source cases despite their exposure to other drug-susceptible adults with tuberculosis in some instances. Child contacts of adults with MDR tuberculosis should be treated according to the drug susceptibility patterns of the likely source cases' M. tuberculosis strains unless their own strain's susceptibility testing indicates otherwise. Contact tracing remains of fundamental importance in identifying children at risk.     

Culture confirmed multidrug resistant tuberculosis: diagnostic delay, clinical features, and outcome.

AIMS: To determine the delay in diagnosis of multidrug resistant (MDR) tuberculosis (TB), the correlation between drug susceptibility patterns of adult-child contact pairs, the effectiveness of treatment, and the outcome in these children. METHODS: MDR M tuberculosis culture results of children were prospectively collected during a four year period in the Western Cape Province of South Africa, an area with a TB incidence of 589/100 000 population, and a new MDR TB rate of 0.94%. Folder reviews were done to retrieve clinical information. Children not already on treatment at our MDR TB clinic or TB hospital were recalled and appropriate treatment was started. Follow up was done for as long as possible. RESULTS: Thirty nine children, median age 4.5 years at first TB diagnosis and 6.2 years on MDR culture confirmation, were seen. Delay in starting appropriate MDR treatment after TB diagnosis was a median of 2 days if MDR TB source cases were taken into account, but 246 days if the drug susceptibility pattern of the source case was not considered, and 283 days if there was no known tuberculosis source case. Correlation between the drug susceptibility results of the child's and adult source case's isolates was 68%. Seventeen children had smear positive tuberculosis, of whom 13 had cavitatory pulmonary disease. Eight children had central nervous system TB. Thirty six children were treated for MDR tuberculosis, of whom four died. CONCLUSIONS: Obtaining a detailed contact history is essential as a delay in starting appropriate MDR antituberculosis treatment has potentially serious consequences.     

Culture confirmed multidrug resistant tuberculosis: diagnostic delay, clinical features, and outcome

Aims: To determine the delay in diagnosis of multidrug resistant (MDR) tuberculosis (TB), the correlation between drug susceptibility patterns of adult-child contact pairs, the effectiveness of treatment, and the outcome in these children. Methods: MDR M tuberculosis culture results of children were prospectively collected during a four year period in the Western Cape Province of South Africa, an area with a TB incidence of 589/100 000 population, and a new MDR TB rate of 0.94%. Folder reviews were done to retrieve clinical information. Children not already on treatment at our MDR TB clinic or TB hospital were recalled and appropriate treatment was started. Follow up was done for as long as possible. Results: Thirty nine children, median age 4.5 years at first TB diagnosis and 6.2 years on MDR culture confirmation, were seen. Delay in starting appropriate MDR treatment after TB diagnosis was a median of 2 days if MDR TB source cases were taken into account, but 246 days if the drug susceptibility pattern of the source case was not considered, and 283 days if there was no known tuberculosis source case. Correlation between the drug susceptibility results of the child''s and adult source case''s isolates was 68%. Seventeen children had smear positive tuberculosis, of whom 13 had cavitatory pulmonary disease. Eight children had central nervous system TB. Thirty six children were treated for MDR tuberculosis, of whom four died. Conclusions: Obtaining a detailed contact history is essential as a delay in starting appropriate MDR antituberculosis treatment has potentially serious consequences.     

Failure of chemoprophylaxis with standard antituberculosis agents in child contacts of multidrug-resistant tuberculosis cases

BACKGROUND: There is little published information on optimal chemoprophylaxis for children with multidrug-resistant tuberculosis (MDR-TB) contacts. Current guidelines of World Health Organization suggest that isoniazid (INH), the standard first-line chemoprophylaxis, be used for those exposed to MDR-TB. METHODS: This is a retrospective review of medical records of 5 children residing in the Western Cape Province, South Africa, who developed MDR-TB while receiving conventional chemoprophylaxis with either INH or a combination of INH, rifampin, and pyrazinamide. RESULTS: Adult MDR-TB source cases were identified for all children and resistance patterns of patient and source case isolates matched in all cases. The median age of the patients was 0.4 years. One patient participated in a trial of INH chemoprophylaxis for HIV-infected children. Four HIV-uninfected infants presented with TB-related symptoms several months after being given chemoprophylaxis because of a known source case. Stigmata of TB were cough >3 weeks in 4, weight loss or a history of failing to thrive in 3, fever in 2 infants, and reported night sweats in 1. Chest radiographs at diagnosis revealed lymphadenopathy, lobar opacification, and airway narrowing. All patients were treated for varying time periods at a TB referral institution in the Western Cape. CONCLUSIONS: Standard, first-line anti-TB agents were inadequate to prevent MDR-TB in children exposed to MDR-TB contacts. Second-line chemoprophylaxis, reflecting the susceptibility profile of the source case's isolate, with at least 2 drugs with activity against the drug-resistant isolate for 6-12 months should be considered.     

Pneumonia and empyema caused by penicillin-resistant Neisseria meningitidis: a case report and literature review

Pneumonia is an uncommon manifestation of Neisseria meningitidis infection, and empyema is rarely reported. Uniform penicillin susceptibility has been assumed for meningococcal infections for many years, but decreased penicillin susceptibility has been recognized recently with increasing frequency. Breakpoints to define different categories of susceptibility were published recently by the Clinical and Laboratory Standards Institute. We report the case of a teenage girl with sepsis and extensive bilateral pneumonia with empyema caused by an N meningitidis isolate that was resistant to penicillin. Her protracted clinical course suggested that penicillin resistance contributed to her delayed recovery. Our experience with this patient suggests that susceptibility testing should be performed in every case of N meningitidis isolation, and treatment with a third-generation cephalosporin should be provided until the susceptibility results are known. Clinical suspicion of N meningitidis as a possible cause of respiratory symptoms accompanied by hypotension, even in the absence of a rash, may aid in diagnosis and therefore in the treatment and provision of prophylaxis to contacts of patients with meningococcal disease.     

RET promoter variations in familial African degenerative leiomyopathy (ADL): first report of a possible genetic-environmental interaction

African degenerative leiomyopathy (ADL, DL, Bantu pseudo-Hirschsprung??s disease) is a distinctive visceral myopathy, of unknown etiology, occurring in Africa. It has a classical clinical and histologic picture in young indigenous African children. It presents as intestinal pseudo-obstruction with a massive megacolon due to degeneration of smooth muscle without aganglionosis. Because of its late presentation and geographical and ethnic distribution, it is thought to be an acquired degenerative hollow visceral myopathy. Only one previous report of familial recurrence exists. The main Hirschsprung susceptibility gene RET is a potential candidate gene in this condition, because of its role in the development of the intrinsic innervation and ganglia of the smooth muscle layers of the gastro-intestinal tract. We report a second case of familial ADL recurrence and explore possible etiologic causes including variations of the RET gene. Multiple variations in the RET promoter were identified in this case which leads to the possibility of a genetic-environmental predisposition for this condition. We therefore hypothesize that RET may play a modulating role in ADL susceptibility (and possibly other visceral myopathies). It is possible that subtle malformations in the ENS may result from RET dysfunction which then predisposes the individual to environmental influences which initiate the later onset of muscle degeneration.     

High incidence of primary tuberculosis.

An usually high rate of both tuberculosis infection and active disease is reported in 11 of 38 nursery children in contact with a case of smear positive pulmonary tuberculosis, emphasising the susceptibility of young children to this disease. This report also underlines some important principles in case finding and disease control.     

High incidence of primary tuberculosis

An usually high rate of both tuberculosis infection and active disease is reported in 11 of 38 nursery children in contact with a case of smear positive pulmonary tuberculosis, emphasising the susceptibility of young children to this disease. This report also underlines some important principles in case finding and disease control.     

肿瘤坏死因子-αG-308A多态性与自发性早产遗传易感性的关联研究

目的探讨肿瘤坏死因子-α(TNF-α)G-308A多态性和自发性早产(SPTB)易感性的关联。方法收集753例SPTB患儿为病例组,681例足月新生儿为对照组,利用Sequenom Mass ARRAY~?SNP检测技术对TNF-α基因G-308A多态性位点进行单核苷酸多态性检测。结果病例组和对照组等位基因G、A分布频率之间的差异无统计学意义(P=0.35);GG、GA、AA基因型构成比之间的差异也无统计学意义(P=0.64)。Logistic回归分析发现TNF-α基因G-308A位点与SPTB的遗传易感性不相关(OR=0.85,95%CI:0.61~1.19,P=0.35)。结论 TNF-α基因G-308A多态性位点与SPTB遗传易感性不相关。     

Lambert–Eaton myasthenic syndrome in a 13-year-old girl with Xp11.22-p11.23 duplication

Lambert–Eaton myasthenic syndrome (LEMS) is an autoimmune disease of the presynaptic neuromuscular junction, typically occurring in adults as a paraneoplastic syndrome. Only rare cases have been reported in childhood. In most childhood cases, malignancies have not been detected but a propensity to autoimmune disease was noticed. Nevertheless, little is known about genetic factors that may contribute to the susceptibility of an individual to develop LEMS.We report on a 13-year-old girl, known with the Xp11.22-p11.23 duplication syndrome, who presented with severe non-paraneoplastic LEMS. The potential role of this microduplication syndrome in the development of LEMS is explored. Previous literature review of twelve Xp11.2 duplication syndrome patients showed that three of them suffered from various autoimmune diseases. The common duplicated region in those three patients and the presented case comprises 12 disease-associated genes including the FOXP3 (Forkhead Box P3) and WAS (Wiskott–Aldrich syndrome) gene, both implicated in immune function. However, it is unclear whether increased gene dosage of one or both of these genes can cause susceptibility to autoimmune diseases.In conclusion, the presented case emphasizes that autoimmune disease is a recurrent feature of the Xp11.2 duplication syndrome, which should be considered in the follow-up of these patients. The exact mechanism underlying this autoimmune propensity remains to be elucidated.     

Intrapartum rupture of the falciform ligament and umbilical vein. A rare cause of hemoperitoneum in the newborn

Intra-abdominal hemorrhage in the newborn is uncommon, but it must be considered in the first 48 hours of life in the infant with pallor, anemia, abdominal distension, and shock. The injured liver is the most common source of bleeding, with the spleen and kidney less often involved. In the case presented, the hallmarks of intra-abdominal hemorrhage were evident. Exploratory laparotomy revealed intraperitoneal bleeding emanating from the disruption of the umbilical vein and its enveloping falciform ligament. There was no other site of intra-abdominal bleeding and there were no intrinsic abnormalities of the umbilical cord or the placenta. Disruption of the intra-abdominal umbilical vein represented the sole source of intra-abdominal bleeding in this patient. The case is reported to document disruption of the intra-abdominal umbilical vein as a rare cause of neonatal hemoperitoneum.     

IL-19基因多态性与儿童乙型肝炎病毒易感性研究

目的 探讨白介素19（IL-19）基因的单核苷酸多态性（SNP）与儿童乙型肝炎病毒（HBV）易感性的关系。方法 采用病例对照研究,收集HBsAg阳性儿童136例（病例组）,HBsAg阴性的健康儿童297例（对照组）,应用PCR 聚合酶链反应和DNA测序法进行基因分型。结果 IL-19基因的rs1798位点的基因型在病例组和对照组人群中频率分布差异有统计学意义,病例组的CG 基因型的比例显著高于对照组（P < 0.05）;IL-19基因的rs2243191位点的基因型和等位基因在HBV感染高危儿童感染组和未感染组人群中频率分布差异有统计学意义,感染组TC、CC基因型以及C等位基因的比例显著高于未感染组（P < 0.05）。结论 IL-19 基因SNP 位点rs1798的基因多态性可能与儿童乙型肝炎易感性相关;rs2243191的基因多态性可能与HBV感染高危儿童突破感染易感性相关。     

Chronic granulomatous herpes encephalitis: a rare entity posing a diagnostic challenge

Herpesviruses can cause an acute, subacute, or chronic disease state in both immunocompetent and immunocompromised individuals. Herpes simplex virus (HSV) encephalitis is most often an acute monophasic disease process. Rarely, however, it may progress to a chronic state, and more rarely still to a granulomatous encephalitis. Prior studies have suggested that antiviral immunity with Toll-like receptors determines susceptibility to herpesviruses. The authors report the case of a 14-year-old girl with a remote history of treated HSV encephalitis, who had intractable seizures and worsening MR imaging changes that were concerning for either a neoplastic or an inflammatory process. She was found to have granulomatous herpes simplex encephalitis and had a low cytokine response to Toll-like receptor 3 stimulation.     

BREUS' MOLE: DNA SHOWS MASSIVE SUBCHORIONIC HEMATOMA IS MATERNAL IN ORIGIN

Breus' mole, a massive subchorionic placental hematoma, is associated with intrauterine growth retardation and second trimester stillbirth. It is relatively rare and, hence, is poorly understood. Initially, Breus' mole was thought to be a consequence of fetal demise, but subsequent observations in placentas of live - born infants as well as identification in prenatal ultrasounds prior to fetal demise discredited this tenet. A number of theories have been proposed to explain the etiology of Breus' mole; some suggest that it is a fetal hemorrhage, others claim a maternal thombosis. However, these theories are based entirely on speculation, and it is unclear from the literature whether the source of the hematoma is maternal or fetal. A macerated female fetus was delivered of a 31 - year - old G1 P0 woman at 24 weeks' gestation; the autopsy showed only marked intrauterine growth retardation while placental examination showed a massive subchorionic hematoma. DNAs extracted from portions of the fresh hematoma, placental villi (i.e., fetal tissue), and maternal blood were compared using molecular analyses. Polymerase chain reaction using primers that identify highly polymorphic loci distinguished fetal from maternal DNAs. This is the first case of Breus' mole analyzed using molecular methods; the source in this case is definitively maternal, suggesting the etiology is maternal thrombosis.     

Multifocal extranodal non-Hodgkin lymphoma involving both the lungs and brain in a child with primary immunodeficiency

Immunodeficiency is associated with increased susceptibility to infections and B-cell lymphoproliferative disorders, which range from polyclonal proliferations to monoclonal lymphomas. In primary immunodeficiencies, the true incidence of lymphoproliferative disorders has been estimated between 1.4% and 24%. Recurrent or chronic infections resulting in continuous antigen exposure result in abnormal B-cell proliferation and ultimately lymphoma. Immunosuppression leads to increase in likelihood of Epstein-Barr virus-associated malignancies. We report a case of the child with multifocal extranodal non-Hodgkin lymphoma involving both the lungs and brain in a case of primary immunodeficiency.     

Primary drug-resistant tuberculosis in children. Correlation of drug-susceptibility patterns of matched patient and source case strains of Mycobacterium tuberculosis

The purpose of this study is to compare the drug-susceptibility patterns of Mycobacterium tuberculosis isolated from patients (children) and from their corresponding adult contacts. We wished to ascertain if the susceptibility pattern of the isolate from the adult contact could be used as a guide in the initial selection of the antituberculous drug regimen in the child. Strains resistant to one or more antituberculous drugs were emphasized in our study. For 120 children with positive cultures, adults were identified who had positive cultures and who were the source of the children's infections. All strains had susceptibility tests for isoniazid, streptomycin, aminosalicylic acid, ethionamide, and, when they became available, ethambutol and rifampin. There were 29 instances in which either the adult's and/or the child's strain were resistant to one or more antituberculous drugs. In 111 (92.5%) instances the organism isolated from the child and that from the adult contact had identical drug-susceptibility patterns. Fourteen (93%) of 15 of the adult/child pairs were both resistant to isoniazid. The drug-susceptibility pattern of isolates obtained from the source of a child's illness is useful as a guide in planning initial drug therapy. In addition, knowledge of isoniazid-resistant strains in adult contacts may alert the physician to the potential failure of isoniazid prophylaxis.     

Streptococcus pneumoniae sepsis in the newborn

Background: Streptococcus pneumoniae (SP) is an uncommon cause of neonatal sepsis. Aims: To report on the spectrum of morbidity associated with SP infections in the neonatal period. Methods: A case series of SP infection in the neonatal period was studied. Maternal and neonatal outcomes were noted. Results: Four cases of neonatal SP infection are reported, one of which was due to a strain with reduced susceptibility to penicillin. All four cases had very early onset of severe clinical disease with bacteremia and pneumonia. In one case a retrospective diagnosis of meningitis was made as well. Maternal illness was a feature in one of these infants. Conclusions: Although less common now than in the pre‐antibiotic era, Streptococcus pneumoniae remains a rare but important cause of neonatal sepsis and can mimic early onset Group B streptococcal sepsis. It is unclear whether current infant or adult pneumococcal immunisation programs might influence its incidence in the neonatal period. The potential for strains with reduced susceptibility to β‐lactam antibiotics to cause neonatal infection needs to be considered in relevant settings.     

Non-Hodgkin's lymphoma complicating acute lymphoblastic leukemia in remission

Second malignancies occurring in patients cured of childhood acute lymphoblastic leukemia (ALL) are rare but increasingly recognized. There are only three reported cases of non-Hodgkin's lymphoma complicating ALL in remission. We report here another case of B-cell-type large-cell lymphoma, presenting in the uterus of a 24-year-old woman, 16.5 years after the diagnosis of ALL was made. Although immune markers of the ALL were not available, it was thought to be unlikely that the second malignancy was a relapse of the original tumor. Due to the long latency period and the minimal exposure to alkylating agents, the role of chemotherapy seems to be insignificant in this case. The development of a second malignancy could be a manifestation of the basic susceptibility to cancer.     

维生素D受体基因多态性与中国汉族儿童结核病易感性的研究

目的　探讨维生素D受体（VDR）基因多态性与中国汉族儿童结核病易感性的关系。 方法　收集2005年1月至2008年3月北京儿童医院收治的125例汉族儿童 结核病患儿,以同期在北京儿童医院门诊行外科手术（如疝、牙齿矫正、鞘膜积液等）前查体的446例患儿作为对照,对照组无结核病史,X线胸片无异常,PPD皮 试硬结直径小于5 mm,按照年龄、性别以及居住地与病例组进行匹配,采用聚合酶链反应-限制性片段长度多态性分析（PCR-RFLP）检测VDR基因上的Fok I和Taq I位点多态性,采用SPSS 12.0软件对病例组和对照组的基因型和等位基因频率进行卡方检验。 结果　结核组和对照组Fok I位点的FF、Ff、ff基因型频率分别为 29.6%、51.2%、19.2%和27.6%、50.9%、21.5%;Taq I位点的TT、Tt、tt基因型频率分别为90.4%、9.6%、0和86.8%、13.0%、0.2%;结核组和对照组在基因型频率 和等位基因频率分布上差异均无统计学意义。将样本按性别进行分组比较后发现,不同性别中病例组和对照组儿童的基因型和等位基因频率之间的差异无统计学 意义。 结论　VDR基因上的Fok I和Taq I位点的多态性与中国汉族儿童结核病的易感性无明显相关性。