Diffuse alveolar haemorrhage in children hospitalised in a tertiary­level hospital: A retrospective descriptive study.

Background: Diffuse alveolar haemorrhage (DAH) is considered a rare condition in children. There is no consensus on the management of DAH syndromes in Africa or other low- and middle-income countries. In this brief report, the clinical characteristics, management and outcomes of children treated for DAH in the Chris Hani Baragwanath Academic Hospital paediatric pulmonology unit in Johannesburg, South Africa are described. Fifteen children were included in this case series, of whom 11 (73.3%) presented with severe microcytic anaemia. Of the 11 children who had bronchoalveolar lavage, 9 (81.8%; 60.0% of the total) had haemosiderin-laden macrophages on microscopy. Only 5 children had a lung biopsy, of whom 3 (60.0%) had capillaritis. All the children were started on oral prednisone at presentation, and 11 (73.3%) received additional complementary treatment. Nine children (60.0%) had normal haemoglobin levels 1 year after initiation of treatment. Our series supports previous reports that DAH is uncommon in children. A large proportion of our patients responded well to treatment despite some resource limitations. What the study adds: The study provides additional data on children presenting with diffuse alveolar haemorrhage in a South African tertiary hospital. What are the implications of the findings: There is a need for South African pulmonologists to come together and conduct a national audit of these patients in different hospitals to determine the incidence in our country, as well as to inform a management plan in the presence or absence of specialised tests.

Outcomes of paediatric patients ventilated in a high-care area outside an intensive care unit.

BACKGROUND: Limited availability of paediatric intensive care beds in the public sector is a major challenge in South Africa. It often results in patients being ventilated in a high-care area (HCA) outside an intensive care setting. The outcomes of paediatric patients ventilated outside a paediatric intensive care unit (ICU) are not well documented. OBJECTIVES: To describe characteristics and outcomes of patients ventilated in a paediatric HCA. METHODS: A retrospective chart review of children (0 - 16 years) requiring mechanical ventilation in the HCA at Chris Hani Baragwanath Academic Hospital, Johannesburg, between 1 February and 31 October 2015 was performed. RESULTS: A total of 214 patients required mechanical ventilation during the study period. Fifty-four percent were male and 91.1% were HIV-negative. The most common diagnoses were acute lower respiratory tract infections (59.3% of the post-neonatal group, 28.8% of the neonatal group) and sepsis (6.8% of the post-neonatal group, 28.8% of the neonatal group). The ultimate rate of acceptance to an ICU was 69.0%. Only 41.6% of cases referred to an ICU were initially accepted, with limited bed availability being the main reason for refusal. Patients with respiratory illnesses were more likely and those with neurological illness less likely to be accepted to an ICU. Patients with low-risk diagnoses were more likely to be accepted than those with very high-risk diagnoses. The overall mortality rate was 32.2%, with 52.2% of these deaths occurring in the HCA. Patients aged 1 - 5 years had the highest mortality rate (48.0%). Lower respiratory tract infections (36.8%) and sepsis (20.6%) were the main causes of death. The mortality rate of suitable ICU candidates in the HCA was higher than that in an ICU (33.3% v. 24.3%). The standardised mortality ratio (SMR), as predicted by the Paediatric Index of Mortality 3 score, for all patients who died in the HCA was 3.3, while the SMR for patients who died in an ICU was 1.3. The odds ratio for mortality of suitable candidates ventilated in the HCA v. patients who were ventilated in an ICU was 1.80 (95% confidence interval 1.39 - 6.03). CONCLUSIONS: Although a reasonable number of paediatric patients ventilated in an HCA survive, survival is lower than in those ventilated in an ICU. However, offering life-supporting therapies in an HCA may offer benefit where ICU care is unavailable. Emphasis needs to be placed on improving access to ICU care as well as optimising the use of available resources.

A case of haemoptysis in a girl with Noonan syndrome.

Noonan syndrome (NS) is an autosomal dominant condition affecting 1 in 2 000 live births. It is characterised by distinctive physical features, congenital heart disease and multiple other comorbidities including haematological abnormalities. Haemoptysis is the expectoration of blood originating from the lower respiratory tract. It is uncommon in children but can be life threatening.Perfusion of the lower respiratory system arises from the pulmonary arterial circulation and the bronchial circulation, or bleeding may arise from either. In children, the most common causes of haemoptysis are respiratory tract infections, aspirated foreign bodies and bronchiectasis. We present a 7-year-old girl with recurrent haemoptysis.

Chylothorax in a child with rifampicin-resistant tuberculosis.

Chylothorax is rare in children. Only a few cases of tuberculosis (TB)-associated chylothorax have been reported. We present a child on standard four-drug TB treatment who presented with wheezing and a chylothorax. Bronchoscopy showed caseating lymph nodes, and rifampicin-resistant TB was identified from the bronchoalveolar lavage specimen. There was marked clinical and radiological improvement 1 month after starting multidrug-resistant (MDR) TB treatment and steroids. The association of chylothorax and MDR-TB has not been described in children. MDR-TB should be considered in children who fail adherent, empirically started drug-susceptible TB treatment.

Empyema in children hospitalised at Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa: A retrospective study.

BACKGROUND: There is a paucity of information on empyema in children from low- and middle-income countries since the introduction of the pneumococcal conjugate vaccine. OBJECTIVES: To describe the aetiology and management of empyema in a setting of high HIV and tuberculosis (TB) prevalence. METHODS: A retrospective descriptive study was undertaken between January 2012 and December 2016 in children aged <14 years at a large secondary-tertiary referral hospital in Soweto, South Africa. Cases of empyema were identified through administrative databases. Clinical, laboratory and radiological data were extracted from patient records. RESULTS: We identified 65 cases of protocol-defined empyema, including 22 (33.8%) referred from surrounding hospitals. The median age at presentation was 53.2 months (interquartile range (IQR) 19.5 - 103.6). Thirteen patients (20.0%) were HIV-infected and 6 (9.2%) were HIV-exposed but uninfected. A bacterial pathogen was identified in 36 cases (55.3%). The commonest causative organisms were Staphylococcus aureus (14/65, 21.5%) and Streptococcus pneumoniae (5/65, 7.7%). Treatment for TB, initiated in 28 children (43.1%), was more frequent in HIV-infected children (10/13, 76.9%) (p=0.011); however, microbiological evidence of TB was present in only 5 cases (7.7%). Forty-three children (66.2%) had an intercostal drain (ICD) inserted and 16 (24.6%) a pigtail percutaneous catheter, while a fibrinolytic was only used in 6 (10.2%). Eight children (12.3%) had a thoracotomy and 7 (10.7%) had video-assisted thorascopic drainage, all of whom had a prior ICD inserted, a median of 20 days (IQR 10 - 33) before surgery. Overall, 7 children (10.8%) were mechanically ventilated and 1 (1.5%) died. CONCLUSIONS: Our study showed a dominance of S. aureus as a cause of empyema. A high proportion of HIV-infected children with empyema were initiated on TB treatment, highlighting challenges in managing TB-HIV co-infection. Although fibrinolytics or early surgery are recommended, neither practice was common in this setting.

The effect of topical calcipotriol or zinc on tuberculin skin tests in hospitalised South African children.

BACKGROUND: The tuberculin skin test (TST) is used to help diagnose tuberculosis (TB) in acutely ill hospitalised children. OBJECTIVE To investigate the potential augmentative effect of topical calcipotriol (a vitamin D analogue) or zinc on TST induration. METHODS: Three TSTs were performed among 64 hospitalised children; each site was covered with topical aqueous cream (control), calcipotriol or zinc and assessed 24 and 48 h later by investigators blinded to all topical applications. RESULTS: TSTs were reactive in 15 (23.4%) children, of whom 13 (20.3%) were TST-positive. Topical calcipotriol and zinc induced TST positivity in two children with reactive but negative control TSTs. These treatments, however, did not significantly increase TST positivity rates. In children with reactive TSTs, the median 48 h induration diameter was not significantly different between the control, calcipotriol- or zinc-treated groups, which were respectively 12.0 (25%-75% IQR 5.0 - 18.0), 14.0 (25%-75% IQR 10.0 - 15.0) and 12.0 (25%-75% IQR 8.0 - 15.0) mm. Topical treatments did not induce TST reactivity or TST positivity in children with culture-confirmed TB disease (n = 4), human immunodeficiency virus infection (n= 18) or kwashiorkor (n = 9). CONCLUSIONS: Topical calcipotriol or zinc does not induce TST reactivity or significantly increase TST positivity rates in acutely ill hospitalised children. However, further studies are required to assess the effects of topical treatments on TST positivity in severely malnourished children.

Paediatric spirometry guideline of the South African Thoracic Society: Part 1.

Spirometry forms an important component in the diagnosis and management of pulmonary diseases in children. In the paediatric setting, there are different challenges in terms of performance and interpretation of good quality and reliable tests. An awareness of the physiological and developmental aspects that exist in children is necessary to improve the quality and reliability of spirometry. We reviewed the recommendations on the technical aspects of performing spirometry in children, from the available guidelines and clinical trials. The focus was on the indications, methods and the interpretation of lung function tests in children <12 years of age. Reliable lung function testing can be performed in children, but an awareness of the limitations, the use of incentives and a dedicated lung function technologist are necessary. 

99Tcm-HIG accumulates in the synovial tissue of rats with adjuvant arthritis by binding to extracellular matrix proteins.

Our objective was to investigate the mechanism of accumulation of 99Tcm-labelled non-specific polyclonal human immunoglobulin (99Tcm-HIG) in inflamed synovial tissue (ST) in an experimental animal model of arthritis. Following 99Tcm-HIG scintigraphy, the in vivo localization of 99Tcm-HIG in the ST of knee joints of rats with adjuvant arthritis was studied using immunohistochemical techniques. In addition, the in vitro binding of 99Tcm-HIG to extracellular matrix proteins was analysed by means of immunohistochemistry and enzyme-linked immunosorbent assay (ELISA). After 99Tcm-HIG scintigraphy, 99Tcm-HI was detected in the ST of rats with adjuvant arthritis. 99Tcm-HIG was diffusely distributed and not bound to cells. In vitro incubation of 99Tcm-HIG on the ST of rats with adjuvant arthritis revealed binding of 99Tcm-HIG to inflamed, but not to non-inflamed, ST. In addition, specific binding of 99Tcm-HIG to fibronectin, fibrin, collagen type I and III was demonstrated by ELISA. We conclude that the accumulation of 99Tcm-HIG in inflamed ST can be explained by the binding of 99Tcm-HIG to extracellular matrix proteins.

Discrepancies between gastric mucosal and urinary pepsinogen A patterns and in vitro synthesis and secretion of human pepsinogen.

The relationship between electrophoretic pepsinogen A (PGA) patterns from urine and gastric mucosa was studied in healthy volunteers and in patients with various gastric disorders. Discrepancies between urinary and gastric PGA patterns were found in 63.3% of the individuals. In 9% of the subjects with these discrepancies, the phenotype class in urine was different from that in gastric mucosa. The differences were found in all diagnostic groups. The highest frequency of differences was found in patients with gastric ulcer. The differences were not related to the serum PGA level. More than 80% of the differences were caused by a lower relative intensity of pepsinogen A fraction 5 (Pg5) in urine than in gastric mucosa. The possible origin of differences in PGA isozymogen patterns was studied by organ culture of gastric biopsies. In vitro synthesis and secretion of pepsinogens were studied by electrophoresis and autoradiography. The synthesis rate of PGA in biopsies of 1-2 mm diameter was 40-100 ng/hr. Posttranslational modification of PGA isozymogens was demonstrated. Pg2 and part of Pg4 probably are secondary products of Pg3 and Pg5, respectively. In some individuals the secretion rate of Pg3 was low compared to the other isozymogens. The conversion of Pg3 into Pg2 and the differential secretion of the isozymogens may explain some of the discrepancies between gastric and urinary PGA patterns.

Low resolution structure of the influenza C glycoprotein determined by electron microscopy.

The influenza C glycoprotein is clearly seen to be a trimer in specimens prepared with uranyl stains. Three-dimensional reconstructions from naturally occurring hexagonal arrays show that at low resolution (approximately 30 A) the influenza C glycoprotein exhibits similar features to the haemagglutinin glycoprotein of influenza A. Both have a triangular stalk near the membrane. Further from the membrane, the stalk becomes broader and the monomers more separated, leaving an open centre. The molecule narrows at the top. The regions of greatest contact between adjacent trimers in the arrays are situated nearer the distal end of the molecule. These contact zones can be related to equivalent zones on the influenza A haemagglutinin. Differences between the structure of the influenza A haemagglutinin glycoprotein determined by X-ray analysis and reconstructions of the influenza C glycoprotein are greatest at either end of the molecule, where the reconstructions are least reliable. Ordered glycoprotein arrays have not been observed on influenza C virions incubated at low pH. The staining patterns of glycoproteins on intact virions are essentially determined by the pH at which the virus is incubated, and the stain type, but not the pH of the stain.

Influence of the stimulus repetition rate on brain-stem-evoked responses in man.

In order to record brain-stem-evoked responses as fast as possible, the influence of the stimulus repetition rate was investigated. The repetition frequency was varied from 2.5 to 80 Hz. The amplitudes of N2-N4 diminish uniformly with increasing stimulus rate. The repetition rate has little or no influence on the amplitude of N5; however, increasing the repetition frequency about 10 Hz causes an increase in the latencies of N2-N5. It seems that the decrease in the amplitude of N2-N4 and the increase in the latencies of N2-N5 are of cochlear origin, since the amplitude and the latency of the cochlear responses are influenced in the same way by the repetition rate as the above-mentioned brain stem responses.

Distribution of brain stem responses to acoustic stimuli over the human scalp.

Responses to acoustic stimuli are generated in neurons of nuclei on both sides of the brain stem. In order to determine whether there are electrode positions which can be used to record activity predominantly generated in the neurons of nuclei of one side, the distribution of brain stem responses to acoustic stimuli over the human scalp was investigated. The response is found to be maximum at the vertex, and diminishes gradually toward the nasion, inion and the mastoid process. There are no significant differences between responses to ipsi- and contralateral stimulation. It follows that there are no electrode positions, which can be used to record the activity generated in the neurons of nuclei of one side. There are, however, indications that monolateral pathology of brain stem nuclei may be detectable by comparing responses to stimuli presented on the right, the left and bilaterally.