Max Klein

A randomized, controlled trial of vitamin A in children with severe measles.

Abstract Background. Measles kills about 2 million children annually, and there is no specific therapy for the disease. It has been suggested that vitamin A may be of benefit in the treatment of measles. Methods. We conducted a randomized, double-blind trial involving 189 children who were hospitalized at a regional center in South Africa because of measles complicated by pneumonia, diarrhea, or croup. The children (median age, 10 months) were assigned to receive either vitamin A (total dose, 400,000 IU of retinyl palmitate, given orally; n = 92) or placebo (n = 97), beginning within five days of the onset of the rash. At base line, the characteristics of the two groups were similar. Results. Although clinically apparent vitamin A deficiency is rare in this population, the childrens serum retinol levels were markedly depressed (mean [±SEM], 0.405±0.021 μmol per liter [11.6±0.6 /μg per deciliter]), and 92 percent of them had hyporetinemia (serum retinol level <0.7 μmol per liter [20 μg per deciliter]). Se...

Aetiology and outcome of pneumonia in human immunodeficiency virus-infected children hospitalized in South Africa.

To determine the aetiology and outcome of pneumonia in human immunodeficiency virus (HIV)‐infected children, we prospectively investigated 250 children hospitalized with pneumonia who were known or clinically suspected to be HIV‐positive, or who required intensive care support in Cape Town, South Africa. Blood culture, induced sputum or bronchoalveolar lavage nasopharyngeal aspirate and gastric lavage were performed. Of the total, 151 children (60.4%) were HIV‐infected. Pneumocystis carinii pneumonia (PCP), occurring in 19 (7.6%) children (15 HIV‐positive), was the AIDS‐defining infection in 20.3%. The incidence and type of bacteraemia (14.3%) were similar in HIV‐positive and HIV‐negative patients; S. pneumoniae (5%) and S. aureus (2%) were the predominant isolates. Sputum or BAL cultures yielded bacteria in 145 of 243 (60%) specimens; viruses were cultured in 37 (15.2%). Bacterial prevalence (including M. tuberculosis in 8%) and anti‐microbial resistance did not differ by HIV status except for S. aureus which was more common in HIV‐infected children. Thirty‐one (20%) HIV‐positive and 8 (8%) HIV‐negative children died [RR 1.16 (95% CI 1.05–1.28), p= 0.008]; using multiple logistic regression, PCP was the only risk factor for mortality (p= 0.03).

The etiology and outcome of pneumonia in human immunodeficiency virus-infected children admitted to intensive care in a developing country.

In developing countries, many human immunodeficiency virus (HIV)-infected children require intensive care unit (ICU) resources for pneumonia, but there is little information on the etiology of pneumonia or the impact of ICU intervention. Objective To compare the etiology and outcome of pneumonia in HIV-positive and seronegative children admitted to ICU. Design Prospective study. Setting Two pediatric ICUs linked to the University of Cape Town, South Africa. Patients Consecutive children admitted for pneumonia during 1998. Measurements and Main Results Clinical, demographic, ventilatory, and laboratory data were collected. Blood for testing was obtained. Induced sputum or nondirected bronchoalveolar lavage was performed for culture and Pneumocystis carinii identification; gastric lavage (GL) provided specimens for mycobacterial culture. Seventy-six children (21 [27.6%, 95% confidence interval {CI} = 18–39.1] HIV-positive) were enrolled. At admission, HIV infection was diagnosed in 15 of the 21 (71.4% [47.8–88.7]) HIV-positive patients. P. carinii pneumonia occurred in eight HIV-positive children (38% of HIV-infected patients) and one HIV-negative child. It was the acquired immunodeficiency syndrome (AIDS)-defining illness in seven children (47%). The incidence of bacteremia (15.3%) was similar in HIV-positive (15.8%) and HIV-negative children (15.1%), p = .94;Streptococcus pneumoniae and Staphylococcus aureus were the predominant isolates. Bacterial and viral isolates from sputum or bronchoalveolar lavage, including Mycobacterium tuberculosis in six (8%) children, did not differ by HIV status. Intermittent positive pressure ventilation was used in 8 of 21 (38%) HIV-positive children and 28 of 55 (51%) HIV-negative children, p = .32. Median days of intermittent positive pressure ventilation (3 [2–6]), ICU (5 [3–9.5]), and hospital (11 [7.5–19]) did not vary by HIV status. The in-hospital mortality rate for HIV-positive children (6 of 21 [28.6%]) was double that for seronegative patients (8 of 55[14.5%], relative risk [RR] 1.96 [0.77–4.99], p = .16). Conclusion More than a quarter of children admitted to ICU for pneumonia in this geographic area are HIV-positive; most are diagnosed with HIV at admission. P. carinii pneumonia is a common AIDS indicator disease. HIV-infected children admitted with pneumonia had a worse outcome than seronegative children, a difference that is rendered statistically insignificant by the small sample size.

Routine high-dose vitamin A therapy for children hospitalized with measles.

Measles is without specific therapy and remains important globally as a cause of childhood death. In controlled studies, high-dose vitamin A therapy (Hi-VAT)--with 400,000 IU vitamin A--has been demonstrated to markedly reduce measles-associated morbidity and mortality. We performed a retrospective study of the hospital records of 1720 children < 15 years of age who were hospitalized for measles, to determine the extent to which these findings, in research settings, are applicable to the case management of measles under conditions of routine hospital practice. The outcomes were studied of children hospitalized during two non-consecutive 2 year periods (1985-6 and 1989-90). A policy of Hi-VAT for all children hospitalized with measles was started during the intervening period. As compared with the group of children on standard therapy (n = 1061), children receiving Hi-VAT (n = 651) had a shorter hospital stay (mean 10 versus 13 days; P < 0.001), a lower requirement for intensive care (4.3 versus 10.5 per cent; P < 0.001), and a lower death rate (1.6 versus 5 per cent; P < 0.001). No adverse effects of Hi-VAT therapy were observed. We conclude that a policy of high dose oral vitamin A (400,000 IU) supplementation in measles provides benefits which are equivalent to those previously observed only in controlled research trials, that it is highly cost effective, and that it should form part of the routine case management of all children hospitalized with measles.

Relief of sleep-related oropharyngeal airway obstruction by continuous insufflation of the pharynx.

Sleep-related upper airway obstruction was treated by continuous insufflation of the pharynx (CIP) in 20 children. All had symptoms but only 1 qualified for a diagnosis of the obstructive sleep apnoea syndrome. Passage of warm humidified air through a thin nasopharyngeal tube at 2-10 litres/min (mean 3.5) relieved obstruction immediately in all patients. Relief was always clinically apparent and accompanied by reduced pleural pressure excursions during breathing. An index of the work of breathing (the product of breathing frequency and pleural pressure change per breath) fell by nearly 60% while patients were on CIP. Transcutaneous oxygen tension was monitored in 5 patients and was improved by CIP in each instance. Side-effects of CIP were minor and preventable with up to 72 days of continuous use. CIP is thus a simple and safe method that rapidly relieves severe oropharyngeal airway obstruction in children during sleep. Whether CIP is useful in domiciliary care or for adults has still to be established.

Surgical relief of acute airway obstruction due to primary tuberculosis

Primary pulmonary tuberculosis in children remains a leading cause of mortality and morbidity in developing countries. Thirteen children requiring urgent thoracotomy for relief of acute respiratory distress resulting from critical major airway narrowing caused by enlarged tuberculous mediastinal lymph nodes were admitted to two hospitals over a 4-year period. Ages ranged from 2 months to 10 years. The condition of each patient had deteriorated despite appropriate antituberculosis therapy and an oral corticosteroid. At operation, the enlarged tuberculous subcarinal or paratracheal lymph nodes or both were decompressed. Surgical complications included a bronchial tear and a pulmonary artery laceration. Additional procedures included a right upper lobectomy, two pneumonectomies, plication of a hemidiaphragm, and mobilization of two muscle flaps. Postoperatively all children showed dramatic improvement. The trachea to main bronchi diameter ratio improved by 49.1% on the left and 44.9% on the right in the immediate postoperative period. In children with respiratory distress produced by compression of the main bronchi between enlarged subcarinal and paratracheal lymph nodes, surgical decompression of the lymph nodes is indicated if there is no marked initial response to appropriate medical therapy. At operation, lymph nodes should be decompressed only by incision and curettage. Attempts at lymph node excision are associated with increased complications.

Adrenal suppression and Cushing’s syndrome secondary to ritonavir and budesonide

Ritonavir is a protease inhibitor used in combination therapy for advanced HIV infection. In South Africa lopinavir/ritonavir is first-line therapy for children under 3 years of age where there is a history of perinatal exposure to the non-nucleoside reverse transcriptase inhibitor (NNRTI) nevirapine. Ritonavir is a potent inhibitor of hepatic cytochrome P450-CYP3A4 iso-enzyme activity. Inhaled or intranasal corticosteroids are commonly used in children with recurrent lower airways obstruction, allergic rhinitis and chronic obstructive airways disease. Although systemic absorption of inhaled corticosteroids occurs, side-effects are uncommon at low or medium doses. Inhaled corticosteroids are metabolised by hepatic CYP3A4. Fluticasone, a corticosteroid used in children, is known to interact with ritonavir, resulting in high levels of corticosteroids, suppression of the adrenocortical axis and Cushing’s syndrome. There have been no reports of other inhaled corticosteroids causing adrenal suppression and Cushing’s syndrome. Budesonide and beclomethasone are reported to be associated with a lower risk of systemic side-effects than fluticasone, and a literature review suggested that they be used as an alternative to fluticasone given the risk of suppression of the adrenocortical axis. We report 3 cases of children presenting with a suppressed adrenocortical axis and Cushing’s syndrome as a consequence of budesonide and ritonavir co-therapy.

ASPHYXIA NEONATORUM CAUSED BY FOAMING

Abstract Twelve babies are described who were asphyxiated by profuse foam which formed in the airway after vigorous initial breaths. All recovered fully after resuscitation and none had subsequent breathing difficulties. Pregnancies were usually uncomplicated. Most infants were born at term and were normally developed for their gestational age. Eleven were born by caesarean section (commonly elective) and one by breech delivery. The absence of an effective chest squeeze in labour is suggested as the main cause of the syndrome.

Pressure-rate product and phase angle as measures of acute inspiratory upper airway obstruction in rhesus monkeys.

There are limited validated, objective, and minimally invasive techniques for the bedside evaluation of upper airway obstruction (UAO) in sick infants, despite its frequency in pediatric medicine. Prior techniques include pressure‐rate product (PRP), a product of esophageal pressure and respiratory rate and phase angles (PAs), a measure of asynchrony between ribcage and abdominal respiratory movements in infants with UAO. The purpose of this study is to validate the PRP and compare it to a previously validated PA in rhesus monkeys.

Questioning the UCT Lung Institute

To the Editor: The enthusiastic account of the 10th anniversary of UCTs Lung Institute (Pty) Ltd in the June issue1 raises many questions. Is medicine a caring profession or a business? Is it desirable that the replication of such initiatives be encouraged? Is it possible to replicate it even if one wanted to? Is the Institute sustainable in the light of its dependence on the exceptional ability and determination of a unique individual?