Debbie A White

Phenotypic expression of the 3120+1G>A mutation in non-Caucasian children with cystic fibrosis in South Africa

INTRODUCTION Cystic fibrosis (CF) is the most common genetic disorder in Caucasians. Presentation of CF in non-Caucasians is less well studied. OBJECTIVE This audit was undertaken to determine the phenotypic expression of the 3120+1G>A mutation in black and mixed race children in South Africa. METHODS A multi-centre retrospective chart review of clinical, laboratory and spirometry data of non-Caucasian CF patients in four CF centres in South Africa was collected. Data was collected at diagnosis and after a five-year follow-up period. Ethical approval was granted for the study. RESULTS A total of 30 participants were enrolled of whom 14 (47%) were homozygous and 16 (53%) heterozygous for the 3120+1G>A mutation. The mean age of diagnosis was 13 months. Twenty-four (80%) patients had malnutrition (mean weight z-score -3.6) or failure to thrive (77%) at presentation. Twenty (67%) presented with non-specific abdominal symptoms, whilst fifteen (50%) had recurrent respiratory tract infections. Pseudomonas aeruginosa was detected at a mean age of 21 months. The mean FEV1 was 73% predicted (95% CI 54.0-91.1) at study entry and 68% predicted (95% CI 49.74-87.06) at follow-up. CONCLUSION Failure to thrive and a diagnosis of protein energy malnutrition (kwashiorkor) are the common presenting features of CF in children with the 3120+1G>A mutation. Meconium ileus is a rare presenting feature of CF in black and mixed race children with this deletion in South Africa.

Can a negative procalcitonin level guide antibiotic therapy in early-onset neonatal sepsis?

Background Procalcitonin (PCT) has been used in the diagnosis of early onset neonatal sepsis (EONS) in conjunction with other markers of infection and levels are highest at the onset of infection and decline over time. This study evaluated whether an initial negative PCT could be used to withhold antibiotics in neonates presenting with suspected EONS and if this level differed between premature and term babies. Methods Neonates undergoing evaluation for suspected sepsis in the Neonatal Unit, Johannesburg Hospital, South Africa, within 24 hours of birth between July and September 2004 were included. Patients were categorised into various categories of infection using risk factors for infection, white cell count (WCC), platelet count, C reactive protein (CRP) and blood culture results. Babies were started on empiric parenteral antibiotics as per unit protocols. PCT was correlated with infection categories. Results The final analysis included 194 babies, 131 premature and 63 terms. 145 had “no infection”, 47 “probable infection” and 2 “definite infection”. The mean PCT level (and range) in ng/ml for each category was 1.6 (0.5 – 37.5), 11.9 (0.5 – 150.4) and 6.7 (0.5 – 12.9) respectively. Using a cut off of 0.5ng/ml, the negative predictive value (NPV) of PCT was 80% and the positive predictive value (PPV) 39%. Increasing the cut off of PCT had no effect on the NPV. Receiver Operating Characteristic (ROC) analysis had an area under the curve of 0.631. Conclusions The NPV of PCT on admission for suspected EONS is better than the PPV, but not sufficiently reliable to exclude sepsis, even when using higher cut off values. PCT levels did not differ significantly between premature and term babies.

Viral Lower Respiratory Tract Infections

Lower respiratory tract infections in children are often viral in origin. Unfortunately in this time of significant antimicrobial resistance of infectious organisms, especially bacteria, there is still a tendency for clinicians to manage a child who coughs with antibiotics. In addition, the World Health Organization (WHO) has defined “pneumonia” as a condition that only occurs in children who have “fast breathing or chest wall indrawing”. That would delineate upper respiratory tract infections from those in the lower airway. However, in addition to pneumonia another important entity exists in the lower respiratory tract that is almost always viral in origin. This condition is acute viral bronchiolitis. The concept of “acute lower respiratory tract infection” (ALRTI) has emerged and it is becoming increasing evident from a number of studies that the infectious base of both acute pneumonia (AP) and acute bronchiolitis in children has a mixed etiology of microorganisms. Therefore, whilst certain clinical phenotypes do not require antibiotics the actual microbial etiology is much less distinct.

The bronchiolitis season is upon us – recommendations for the management and prevention of acute viral bronchiolitis

Despite being so common, bronchiolitis remains poorly diagnosed and managed. This article is intended as an update on issues pertaining to this condition.

Pulmonary alveolar proteinosis in a child from an informal settlement: 12 litres of fluid drained from the lungs and successful use of ECMO

Pulmonary alveolar proteinosis (PAP) is a rare cause of chronic interstitial lung disease, characterised by accumulation of pulmonary surfactant, respiratory insufficiency and an increased incidence of infections. The current standard therapy is whole-lung lavage to remove the accumulated surfactant. We report on a cachexic 12-year-old boy from an informal settlement in South Africa, presenting for the first time with PAP. Twelve litres of broncho-alveolar lavage fluid were drained under extracorporeal membrane oxygenation, and the patient gained 10 kg during his 2-month admission.

Cytomegalovirus pneumonia occuring soon after initiation of highly active antiretroviral therapy in an infant

A two-month-old HIV-infected infant was ventilated for very severe Pneumocystis jiroveci pneumonia. After successful extubation, he was started on antiretroviral therapy. He developed a proven cytomegalovirus infection, localising as pneumonia. This required repeated ventilation. He was extubated after six weeks and completed 32 days of ganciclovir.