Mortality in relation to profiles of clinical features in Ghanaian severely undernourished children aged 0-59 months: an observational study.

Severe acute malnutrition (SAM) is associated with a complex pattern of various clinical conditions. We investigated how risk factors cluster in children with SAM, the relationship between clusters of risk factors and mortality as well as length of stay in children with SAM. A prospective observational study design was used. Data were extracted from medical records of 601 infants and children aged 0-59 months admitted and treated for SAM in three Ghanaian referral hospital between June 2013 and June 2018. Among the 601 medical records extracted, ninety-nine died. Three clusters of medical features clearly emerged from data analyses. Firstly, an association was defined by eye signs, pallor, diarrhoea and vomiting with gastrointestinal infections and malaria. In this cluster, pallor and eye signs were related to 2- to 5-fold increased mortality risk. Secondly, HIV, oedema, fast pulse, respiratory infections and tuberculosis; among those features, HIV increased child mortality risk by 2-fold. Thirdly, shock, convulsions, dermatitis, cold hands and feet, weak pulse, urinary tract infections and irritability were clustered. Among those features, cold hands and feet, dermatitis, convulsions and shock increased child mortality risk in a range of 2- to 9-fold. Medical conditions and clinical signs in children diagnosed with SAM associate in patterns and are related to clinical outcomes.

Severe acute malnutrition.

PURPOSE OF REVIEW: The mortality and morbidity associated with severe acute malnutrition (SAM) remain high. A summary of recent studies that are of interest to clinicians treating children with SAM is provided. RECENT FINDINGS: Three important themes emerged in 2015: the use of anthropometry in the diagnosis of SAM and its correlation with body composition; the composition of ready-to-use therapeutic feeds (RUTF); and an improved understanding of the pathophysiology of SAM. SUMMARY: Standard anthropometry does not accurately predict body composition and mid-upper arm circumference more accurately reflects fat mass in children. As single measure, mid-upper arm circumference identifies those children who are most likely to die from SAM and is not influenced by dehydration. However, a significant proportion of SAM children requiring treatment will not be detected. Present RUTF formulations are deficient in long chain polyunsaturated fatty acids. Current evidence suggests that preformed docosahexaenoic acid should be added and/or the content of linoleic acid reduced in RUTF. In contrast to an animal model, stabile children with SAM have the same cardiac index as children without SAM. The situation in haemodynamically unstable children is unknown, continued conservative use of intravenous fluids seems advisable. A reduction in variability of the faecal DNA virome may account for increased susceptibility to malnutrition in vulnerable children.

The diagnostic value and safety of transbronchial needle aspiration biopsy in children with mediastinal lymphadenopathy.

INTRODUCTION: Anterior mediastinal masses in children can have different causes which includes, Mycobacterium tuberculosis (MTB) or malignant lymphadenopathy. Transbronchial needle aspiration (TBNA) has been described as a safe and effective diagnostic procedure in adult patients with lung cancer. AIM: To describe the use of TBNA as a diagnostic test in children with large subcarinal lymphadenopathy and to determine the safety of the procedure in children. PATIENTS AND METHODS: Prospective descriptive study of children with subcarinal mediastinal lymph nodes who underwent TBNA. The majority of the children were referred due to treatment failure. Children were enrolled if the diagnosis remained unclear after computer tomography of the chest. RESULTS: Thirty patients were enrolled in this study; TBNA was done in 28 patients. A definitive diagnosis was made by TBNA in 54% (n = 15) of patients; MTB lymphadenopathy (n = 13), metastatic nephroblastoma (n = 1), and fibrosing mediastinitis (n = 1). In seven (25%) cases the TBNA was the sole source of the specimens from which the definitive diagnosis was made. No serious complications were encountered during or after the procedure. CONCLUSION: TBNA is a safe procedure in children with mediastinal lymphadenopathy of unknown cause resulting in a definitive diagnosis in 57% of cases. TBNA adds additional value to flexible bronchoscopy in the diagnosis of mediastinal lymphadenopathy in children.

CMV pneumonia in HIV-infected ventilated infants.

BACKGROUND: The contributing role of cytomegalovirus (CMV) in infants treated for Pneumocystis jiroveci pneumonia (PJP) is unknown. High dose steroids used in the treatment of PJP may further immunocompromise these infants contributing to the development of CMV pneumonia. AIM: The aim of this study was to determine the role of CMV pneumonia in infants being ventilated for suspected PJP. METHODS: In this prospective study HIV infected infants being treated with trimethoprim-sulfamethoxazole (TMP/SMX) and ventilated for suspected PJP were included if they had not responded to treatment. Open lung biopsy was performed if there was no improvement in ventilatory requirements. RESULTS: Twenty-five HIV positive infants with a mean age of 3.3 months were included. Lung biopsy was performed in 17 (68%) and post-mortem lung tissue was obtained in 8 (32%). After evaluation of the histology, immunohistochemistry, and viral cultures from lung tissue, the most likely causes of pneumonia were: CMV and PJP dual infection 36% (n = 9), CMV pneumonia 36% (n = 9), and PJP 24% (n = 6). The pp65 test for CMV antigen was falsely negative in 24%. The mean blood CD4 count was 287/microl. There was an association between the CD4 lymphocyte status and the final diagnosis, with the CMV and PJP group (CD4 110/microl) having the lowest CD4 status (P = 0.0128). Pediatric Intensive Care Unit (PICU) mortality was 72% (n = 18) and in hospital mortality 88%. CONCLUSION: Of the ventilated infants failing to respond to treatment, 72% had histologically confirmed CMV pneumonia, probably accounting for the high mortality in this cohort. The incidence of CMV disease in HIV infected infants being ventilated for severe pneumonia warrants that ganciclovir is used empirically until CMV disease is excluded. The role of lung biopsy in these circumstances needs to be researched.

Tuberculous meningitis and miliary tuberculosis in young children.

OBJECTIVES: To document the clinical and diagnostic features of tuberculous meningitis (TBM) in young children with and without concomitant miliary tuberculosis (TB). METHODS: A retrospective comparative study. RESULTS: Of 104 children with TBM, 32 (31%), median age 17.0 months, had a miliary appearance on chest radiograph; 72 (69%), median age 30.5 months, had TBM only (P = 0.04). Mediastinal adenopathy was noted in 27 (84%) of the children with miliary TB and 33 (46%) of those with TBM only (P = 0.0005). The mean cerebrospinal fluid (CSF) lymphocyte and polymorphonuclear counts of all children (no significant differences between groups) were 137 x 10(6)/l and 38 x 10(6)/l and the mean protein and glucose concentrations were 1.45 g/l and 0.72 mmol/l, respectively. Polymorphonuclear leukocytes were predominant in the CSF of 17% of children, in 16% the CSF glucose was > 2.2 mmol/l and in 26% the CSF protein was < 0.8 g/l. On Mantoux testing 37 (65%) of 57 children with TBM only and 12 (48%) of 25 children with TBM and miliary TB had an induration of > or = 10 mm (P = 0.23). Ten children (10%) died, five (7%) who had TBM only and five (16%) who had TBM and miliary TB. CONCLUSION: Children with TBM and miliary TB were younger and more likely to have mediastinal adenopathy on chest radiography than those with TBM only. Diagnostic features and investigations in both groups may be misleading at times.

Factors influencing successful closure with indomethacin of the patent ductus arteriosus in premature infants.

The incidence of persistent patency of the ductus arteriosus (PDA) is inversely related to birth weight. A PDA contributes to pathological conditions in the neonate and timely closure in these low-L birth-L weight infants could potentially prevent these complications. Prostaglandin inhibition with indomethacin is one treatment strategy currently available. This retrospective descriptive study evaluated the parameters that influenced the effectiveness of indomethacin in closure of the PDA in 101 consecutive premature infants and the adverse effects of indomethacin in these infants. Independent variables found to increase the risk of unsuccessful closure with indomethacin significantly were caesarean section, lower haematocrit at delivery and severity of hyaline membrane disease. Non-L closure also resulted in prolonged ventilation. No significant adverse effects were recorded in the infants who received indomethacin but neonatal jaundice was more common in those infants who responded to indomethacin.

Diagnosis of haemodynamically significant patent ductus arteriosus in neonates-- is the ECG of diagnostic help?

The presence of a haemodynamically significant patent ductus arteriosis (PDA) in the premature newborn may contribute to the development of brochopulmonary dysplasia, intraventricular haemorrhage and necrotising enterocolitis. It is therefore essential that the diagnosis of such a PDA be made in time in order to intervene medically or surgically. Echocardiography is at present the prime diagnostic tool, but it is mainly available in tertiary hospitals. Chest roentgenography is of little diagnostic value especially in the presence of respiratory disease, which is often present in premature babies. Very little is known about the diagnostic value of the electrocardiogram (ECG) in premature babies. The aim of this study was to describe the standard 12-lead ECG findings in low-birth-weight babies with haemodynamically significant PDAs. Thirty-two babies with haemodynamically significant PDAs, as established by echocardiography, were included in the study. Standard 12-lead ECGs were done in all these babies. In 15 patients ECG abnormalities were found; only 22% had left atrial and left ventricular enlargement indicative of significant left-to-right shunting, while 78% had no ECG changes indicative of left-to-right shunting. In conclusion, the ECG cannot be used to identify haemodynamically significant PDAs.

Bone mineral density in long-term survivors of childhood cancer.

Bone mineral density (BMD) of the lumbar spine was measured in 97 long-term survivors of childhood cancer 5-23 years after diagnosis using dual-energy X-ray absorptiometry (DXA). They had been treated for acute leukemia (n = 22), brain tumors (n = 16), lymphomas (n = 16), Wilms' tumor (n = 10), neuroblastoma (n = 7) and other cancers (n = 26). The correlations between BMD and the Z-scores for weight for height, height for age and weight for age at diagnosis and follow-up were evaluated with stepwise multiple regression. Correlations with cumulative corticosteroid and radiation dose were examined with Spearman's correlation coefficient. The number of nature of fractures were noted. A BMD Z-score of below -2 was present in 13 and a BMD Z-score of -1 to -2 in 31 children. In total, a low BMD was observed in 45% of children. Height for age at follow-up correlated significantly with BMD Z-score. Increasing doses of cranial irradiation (18-54 Gy) were associated with lower BMD (p = 0.001, Spearman). This was true also for 22 children with acute lymphoblastic leukemia (ALL) who had received 18-24 Gy cranial irradiation (p = 0.04, Spearman). Fractures occurred in 14 children following trauma. The difference in BMD Z-scores of children with and without fractures did not achieve statistical significance although the majority of the children with fractures had low BMD Z-scores. The significant inverse correlation between height for age at follow-up and BMD must be interpreted with the realization that DXA is not a volumetric measurement of BMD and that short stature is associated with a smaller skeletal mass.

An analysis of prognostic variables in acute lymphocytic leukaemia in a heterogenous South African population.

The records of all 96 children below the age of 15 years diagnosed with acute lymphoblastic leukaemia at Tygerberg Hospital in the Republic of South Africa between 1983 and 1995 were reviewed to determine risk factors which may predict poor outcome. Age < 2 and > 8 years, and white cell count > 20 x 10(9)/l at diagnosis were significant predictors of poor outcome. Sex, FAB classification, immunophenotype, hepatomegaly, splenomegaly, BFM risk score, and the presence of mediastinal glands did not predict outcome. The presence of the established risk factors could not adequately explain the difference in 5-year event-free survival in the three ethnic groups which was 67 per cent in white, 17 per cent in black, and 38 per cent in children of mixed ethnic origin. In an attempt to improve survival in black children, our stratification of risk groups will in future be based on factors that include ethnicity, age and WCC > or = 20 x 10(9)/l at diagnosis. Pediatric oncology services in developing countries should adapt therapy to the risk factors of their local populations.

A prospective evaluation of children under the age of 5 years living in the same household as adults with recently diagnosed pulmonary tuberculosis.

SETTING: A South African suburb with a high tuberculosis incidence (> 800/100,000). OBJECTIVE: To determine the prevalence of tuberculosis infection and disease in children less than 5 years of age who were in close household contact with adults with pulmonary tuberculosis. DESIGN: Prospective clinical study. SUBJECTS: Children under 5 years of age (of whom > 98% had been BCG vaccinated in the neonatal period) in household contact with an adult with tuberculosis. INVESTIGATION: Clinical investigation, Mantoux skin testing, chest radiography, gastric aspirate culture for Mycobacterium tuberculosis. RESULTS: Of 155 children younger than 5 years in contact with 80 index cases (83% smear positive), 14% were infected and 34% diseased. Children aged under 2 years had more severe disease (endobronchial tuberculosis and bronchial compression). Of 154 household members aged over 5 years who were assessed, 17 had culture proven pulmonary tuberculosis (13 smear positive) and a further 16 were placed an antituberculosis treatment on the basis of radiological evidence. CONCLUSION: In a high tuberculosis incidence area evaluation of and chemoprophylaxis for childhood contacts of adults with pulmonary tuberculosis is a rewarding procedure. The detection of culture and smear positive pulmonary tuberculosis amongst adolescent and adult household contacts emphasizes the role of contact tracing in the detection of infectious cases of pulmonary tuberculosis and the prevention of the spread of tuberculosis.

Adenylate kinase activity in the cerebrospinal fluid of children with tuberculous meningitis and its relationship to neurological outcome.

Cerebrospinal fluid (CSF) adenylate kinase activity was determined in 88 children (mean age 32.6 months) at stage II (n = 40) and stage III (n = 48) tuberculous meningitis (TBM) at, or shortly after, the initiation of treatment, and at weekly intervals thereafter for the first month of treatment, and in 60 children (mean age 40 months) investigated for, but later considered not to have meningitis. CSF adenylate kinase activity in this latter group ranged from 0 to 1.27 u/l (mean 0.59 u/l). Mean CSF adenylate kinase activity during the first week of therapy in children at stage II TBM (2.95 u/l; range 0-9.22 u/l) differed significantly (p = 0.03) from that in children at stage III TBM (5.62 u/l; range 0-18.93 u/l). CSF adenylate kinase activity did not differ between children at stage II and stage III TBM during any of the 3 subsequent weeks. CSF adenylate kinase activity was not related to CSF cell count, total protein or glucose concentration or intracranial pressure at any point during the first month of treatment, but was related to CSF lactate during the first week of therapy (p = 0.001). Consecutive determinations of CSF adenylate kinase activity were available in 34 children. Although CSF adenylate kinase activity tended to increase or decrease in keeping with changes in clinical condition this was not always the case. The close relationship of CSF adenylate kinase activity and lactate concentrations suggests that adenylate kinase activity reflects hypoxic cerebral metabolism and it was unusual for children with increased CSF adenylate kinase activity at the time of diagnosis to be clinically normal on completion of 6 months of antituberculosis treatment. Any treatment modality which significantly reduced CSF adenylate kinase activity in children early in the course of TBM would probably be of clinical benefit to the patients.

Bronchopulmonary dysplasia in infants with respiratory distress syndrome in a developing country: a prospective single centre-based study.

UNLABELLED: The aim of this prospective study was to determine the incidence of bronchopulmonary dysplasia (BPD) in and the outcome of neonates ventilated for respiratory distress syndrome (RDS). The study was conducted in a developing country prior to the use of surfactant replacement therapy and the results are compared to published reports from the developed world. BPD was defined as oxygen dependency beyond day 28 of life. The incidence of BPD over a 9-month-period was 8.2% of all neonates requiring ventilation (n = 169) and 41% (n = 38) of neonates ventilated for RDS (n = 92). Of those neonates who developed BPD, 26% were still being ventilated on day 28. Of the infants, 21 (55%) developed type 1 BPD and 17 (45%) type 2 BPD. There was no statistical difference in the severity of lung disease on any of the study days between type 1 and type 2 BPD although neonates with type 2 BPD required assisted ventilation and supplemental oxygen for a longer period: 30 versus 12 days and 95 versus 49 days, respectively. Of those neonates who developed BPD, 8 (21%) died prior to discharge from hospital and a further 5 infants (17%) died subsequent to discharge. Of the latter five, three died from treatable causes (gastroenteritis n = 2, pneumonia n = 1). Of the 25 (83%) children seen at follow up, 68% were developing normally, 20% were classified as having suspect development and 12% had developed cerebral palsy at corrected postnatal ages of 12-24 months. None of the results differed significantly from those of neonates being ventilated in the developed world, except for the causes of post-discharge deaths. CONCLUSION: Health services providing ventilation for neonates in the developing world will have to take the needs of children with BPD into account when planning a neonatal service which should include among others a widely available and easily accessible primary health care system.

A decade of experience with Mycobacterium tuberculosis culture from children: a seasonal influence on incidence of childhood tuberculosis.

SETTING: A tertiary care hospital in the Western Cape Province of South Africa from November 1983-October 1993. OBJECTIVE: Evaluation of the source of all cultures of Mycobacterium tuberculosis from children aged < 13 years and documentation of the mean time for culture with Löwenstein-Jensen (LJ) medium and a radiometric method (Bactec). RESULTS: One thousand six hundred and sixty cultures of M. tuberculosis were obtained from 1204 children (638 (53%) males and 566 (47%) females). The median time to a positive culture result was 65 days with LJ medium and 23 days with Bactec (P < 0.0001). Gastric aspirate provided 1298 cultures (78%) from 983 children (82%) of whom 52% were aged < 2 years. Ninety-six positive sputum specimens were from 79 children (7%) of whom 70% were > 5 years. Significantly more positive cultures were obtained during the late winter and early spring (P < 0.001), and a similar trend was found for tuberculous meningitis. CONCLUSION: The use of a radiometric culture method has expedited the confirmation of tuberculosis in childhood in our hospital. Even in children < 3 months of age the diagnosis of tuberculosis can often be confirmed by culture. The documented increase in childhood tuberculous disease in spring suggests an increased transmission of tuberculous infection in autumn and winter in our community.

Concentrations of interferon gamma, tumor necrosis factor alpha, and interleukin-1 beta in the cerebrospinal fluid of children treated for tuberculous meningitis.

Concentrations of interferon gamma (IFN-gamma) in the lumbar cerebrospinal fluid (CSF) of 30 children (mean age, 27 months) being treated for stage III (16 children) and stage II (14 children) tuberculosis meningitis (TBM) were determined by ELISA. Nine children with stage III TBM and six with stage II TBM received prednisone (4 mg/kg). Concentrations of IFN-gamma in 73 CSF specimens (18 from the first week of therapy, 20 from the second, 19 from the third, and 16 from the fourth) were determined. The mean concentrations were 780 pg/mL in the first week of therapy and 554 pg/mL, 529 pg/mL, and 269 pg/mL in the second, third, and fourth weeks, respectively. Tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta (IL-1beta) concentrations in 56 specimens from 23 of these same children were determined by ELISA. The mean CSF TNF-alpha concentration in 12 specimens obtained during the first week of therapy was 17 pg/mL, and the mean was 11 pg/mL during each of the subsequent weeks (14 specimens were evaluated in the second week and 15 specimens in the third and fourth weeks of therapy). Mean IL-1beta concentrations in these same groups of specimens were 52 pg/mL, 43 pg/mL, 42 pg/mL, and 18 pg/mL. No correlation could be shown between cytokine concentration and stage of disease, and no differences existed between those who did and those who did not receive prednisone. A significant decline in IL-1beta concentrations was shown during the 4-week period, but none in TNF-alpha or IFN-gamma concentrations was noted. Persistently high CSF INF-gamma concentrations in cases of TBM (as in cases of aseptic meningitis but not bacterial meningitis) at the time of diagnosis suggest an immune response fundamentally different from that in bacterial meningitis.

TB or not TB? An evaluation of children with an incorrect initial diagnosis of pulmonary tuberculosis.

OBJECT: The aim of the study was to identify diagnoses that are confused with pulmonary tuberculosis in children. DESIGN: Prospective, investigative clinical study. SETTING: Tertiary care teaching hospital and an urban tuberculosis clinic in an area with a very high incidence of pulmonary tuberculosis (> 800 new cases/100,000/year). PATIENTS: Children suspected of having tuberculosis, children followed up for pulmonary infiltrates with eosinophilia and children with congenital pulmonary anomalies were investigated. INTERVENTION(s). None. OUTCOME MEASURE: Pulmonary tuberculosis was diagnosed using modified World Health Organisation criteria and the diagnoses of those children not suffering from pulmonary tuberculosis were analysed. RESULTS: Of the 354 children initially suspected of suffering from tuberculosis 71 (20%) were found to be suffering from other pulmonary disease, viz. pneumonia or bronchopneumonia (29%), bronchopneumonia with wheezing (18%), and asthma with lobar or segmental collapse (12%). Of 14 children suffering from pulmonary infiltrates with peripheral eosinophilia 6 (43%) were initially incorrectly diagnosed and treated for tuberculosis. Of 54 children with congenital pulmonary anomalies, 8 (15%) were treated for tuberculosis before the correct diagnosis was made. Congenital anomalies most often confused with tuberculosis were unilateral lung hypoplasia, bronchogenic cyst and tracheal bronchus with an anomalous lobe. CONCLUSIONS: The criteria for diagnosing tuberculosis in children is complicated in areas with a high incidence of tuberculosis and poor socio-economic circumstances where many children presenting with conditions other than tuberculosis will be in contact with an adult case of pulmonary tuberculosis. The commonest conditions confused with tuberculosis are pneumonia, bronchopneumonia and asthma. Pulmonary infiltrates with peripheral eosinophilia and congenital lung abnormalities should be considered especially if the children have an atypical clinical picture or do not respond to tuberculosis treatment.

Respiratory tuberculosis in childhood: the diagnostic value of clinical features and special investigations.

During a 16-month period children presenting to a pediatric outpatient facility from an area with a high tuberculosis incidence (> 400/100,000) and suspected of having respiratory tuberculosis (TB) were evaluated for close contact with adult pulmonary tuberculosis, weight loss, symptom duration, respiratory signs, lymphadenopathy and hepatosplenomegaly and by chest radiography and tuberculin testing (Mantoux or tine). Probable tuberculosis was diagnosed in 258 children and was confirmed in 109 (42%) patients with a mean age of 31 months by culture of Mycobacterium tuberculosis from gastric aspirate or another source. Eleven children with confirmed TB had a normal chest radiograph. After review of special investigations, clinical course and follow-up of the remaining 149 children, 86 children (58%) with a mean age of 32.4 months were considered to have probable TB and 63 (42%) with a mean age of 27 months not to have TB. Significantly fewer children in the "not TB" group than in the confirmed and probable TB groups had a close adult pulmonary tuberculosis contact (13 (21%) and 95 (49%), respectively; P < 0.01). There was no difference between the "not TB" group and the confirmed and probable TB groups in the proportion presenting with weight loss, cough or other respiratory symptoms, a symptom duration > 2 weeks, the presence of bronchial breathing, wheeze, hepatomegaly or splenomegaly or peripheral lymphadenopathy. Final diagnoses in the "not TB" group included bacterial or viral pneumonia or bronchopneumonia in 37, asthma often accompanied by segmental collapse in 9 and cavitating pneumonia in 3 children.(ABSTRACT TRUNCATED AT 250 WORDS)

Delay in the diagnosis, notification and initiation of treatment and compliance in children with tuberculosis.

SETTING: The mortality and morbidity from childhood tuberculosis may be influenced by the delay from the time of first symptoms until the start of and compliance with treatment. OBJECTIVE: This study investigated these delay periods and the compliance with therapy in children with tuberculosis. DESIGN: During the study period there were 49 children with probable and 123 with confirmed pulmonary tuberculosis (WHO criteria). The mean period from first symptoms until presentation was 4.3 weeks, from presentation until notification 5 weeks and from notification until therapy 0.9 weeks. 16% of children notified as having tuberculosis never received therapy. Significantly fewer children in the urban squatter communities received therapy than in urban settled (P = 0.02), rural agricultural (P = 0.0001) and rural settled (P = 0.09) communities. 12% of children did not complete their therapy. CONCLUSION: The delay in presentation ('patient delay') was shorter than the delay in diagnosis ('doctor delay'). Failure to trace children and to complete therapy was particularly likely to occur in urban squatter communities. Easier access to health care facilities may shorten the 'patient delay' while greater awareness of tuberculosis and proper investigation of children may shorten the 'doctor delay'.