Etienne Nel

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 bron-chopneumonia in 37, asthma often accompanied by segmental collapse in 9 and cavitating pneumonia in 3 children. On the one hand children in whom there were sufficient criteria to be considered probable cases of TB were subsequently thought not to have TB; on the other hand 11 (10%) of children with TB confirmed by culture of Mycobacterium tuberculosis from gastric aspirate had a normal chest radiograph.

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).

Neonatal Meningitis: Mortality, Cerebrospinal Fluid, and Microbiological findings.

This study describes the bacteriology, cerebrospinal fluid (CSF) findings, and mortality of neonatal meningitis over an 11-year period. The minimum incidence of neonatal meningitis at Tygerberg Hospital is 0.72/1000 live births/year. Eighty-eight patients were included in the study. Median birthweight and age at diagnosis were 2320 g and 12 days, respectively. CSF culture was positive in 77 (88 per cent), blood culture was positive in 51 (57 per cent), and Gram stain was positive in 58 (66 per cent). The most frequently cultured organisms were Group B Streptococcus, Klebsiella pneumoniae, and E. coli. Thirty (34 per cent) patients died, the majority within 72 h after admission. The death rate was significantly increased in babies with a birthweight of less than 1500 g (59 per cent). Increased total CSF protein was associated with an increased risk of death. Normal CSF cell count, total CSF protein and CSF glucose were found in six infants.

Diarrhoea and Malnutrition

Abstract The relationship between diarrhoea and malnutrition is bidirectional: diarrhoea leads to malnutrition while malnutrition aggravates the course of diarrhoea. Many factors contribute to the detrimental effect of diarrhoea on nutrition. Reduced intake (due to anorexia, vomiting, and withholding of feeds), maldigestion, malabsorption, increased nutrient losses, and the effects of the inflammatory response are some of the factors involved. High volume stool losses (greater than 30 ml/kg/day) are associated with a negative balance for protein, fat, and sugar absorption. Enteric infections often cause increased loss of endogenous proteins, particularly after invasive bacterial infections. Initially, the major emphasis of treatment of acute diarrhoea in children is the prevention and treatment of dehydration, electrolyte abnormalities and comorbid conditions. The objectives of diarrhoeal disease management are to prevent weight loss, to encourage catch-up growth during recovery, to shorten the duration and to decrease the impact of the diarrhoea on the child’s health. Addressing only diarrhoea or only food security is unlikely to be successful in decreasing the prevalence of malnutrition. Existing evidence provides some guidelines as to the optimal nutritional management of children with diarrhoea and novel treatments may prove to be valuable in future.

Composition of Follow-Up Formula for Young Children Aged 12-36 Months: Recommendations of an International Expert Group Coordinated by the Nutrition Association of Thailand and the Early Nutrition Academy

Background: There are no internationally agreed recommendations on compositional requirements of follow-up formula for young children (FUF-YC) aged 1-3 years. Aim: The aim of the study is to propose international compositional recommendations for FUF-YC. Methods: Compositional recommendations for FUF-YC were devised by expert consensus based on a detailed literature review of nutrient intakes and unmet needs in children aged 12-36 months. Results and Conclusions: Problematic nutrients with often inadequate intakes are the vitamins A, D, B12, C and folate, calcium, iron, iodine and zinc. If used, FUF-YC should be fed along with an age-appropriate mixed diet, usually contributing 1-2 cups (200-400 ml) of FUF-YC daily (approximately 15% of total energy intake). Protein from cows milk-based formula should provide 1.6-2.7 g/100 kcal. Fat content should be 4.4-6.0 g/100 kcal. Carbohydrate should contribute 9-14 g/100 kcal with >50% from lactose. If other sugars are added, they should not exceed 10% of total carbohydrates. Calcium should provide 200 mg/100 kcal. Other micronutrient contents/100 kcal should reach 15% of the World Health Organization/Food and Agriculture Organization recommended nutrient intake values. A guidance upper level that was 3-5 times of the minimum level was established. Countries may adapt compositional requirements, considering recommended nutrient intakes, habitual diets, nutritional status and existence of micronutrient programs to ensure adequacy while preventing excessive intakes.

Haematological abnormalities in children with tuberculosis.

Over a 16 month period 307 children with suspected tuberculosis (TB) and an available full blood count (FBC) seen at Tygerberg Hospital in South Africa were evaluated and categorized as confirmed (A), probable (B), and no TB (C) according to WHO criteria. There was no difference in the mean age of the 168 group A (33.6 months), 83 group B (34.4 months), and the 56 group C (31.6 months) children. A lower mean haemoglobin (Hb 10.2 vs. 10.8 g/dl) was the only significantly different haematological parameter in children with TB compared with the comparison group (Group C). There were no differences in median total white cell count, neutrophils, lymphocytes, monocytes, platelets, or the proportion of children in each group with anaemia, microcytosis, neutrophilia, neutropenia, lymphocytosis, lymphopenia, monocytosis, thrombocytosis or thrombocytopenia. The most common haematological abnormalities in children with TB were the presence of anaemia, neutrophilia, and monocytosis but these changes were found with equal frequency in control patients. Although haematological abnormalities are fairly common in children with TB, in a developing country these abnormalities also occur frequently in children with other non-tuberculosis respiratory infections. An FBC has no diagnostic predictive value when investigating a child for TB.

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.

Swallowing abnormalities in HIV infected children: an important cause of morbidity

BackgroundSwallowing disorders, well recognised in adults, contribute to HIV-infection morbidity. Little data however is available for HIV-infected children. The purpose of this study is to describe swallowing disorders in a group of HIV-infected children in Africa after the introduction of combined anti-retroviral therapy.MethodsWe describe 25 HIV-infected children referred for possible swallowing disorders. Clinical and videofluoroscopic assessment of swallowing (VFSS), HIV stage, and respiratory and neurological examination were recorded.ResultsMedian age was 8 months (range 2.8-92) and 15 (60%) were male. Fifteen (60%) were referred for recurrent respiratory complaints, 4 (16%) for poor growth, 4 (16%) for poor feeding and 2 (8%) patients for respiratory complaints and either poor growth or feeding. Twenty patients (80%) had clinical evidence of swallowing abnormalities: 11 (44%) in the oral phase, 4 (16%) in the pharyngeal phase, and 5 (25%) in both the oral and pharyngeal phases. Thirteen patients had a videofluoroscopic assessment of which 6 (46%) where abnormal. Abnormalities were detected in the oral phase in 2, in the pharyngeal phase in 3, and in the oral and pharyngeal phase in 1; all of these patients also had evidence of respiratory involvement. Abnormal swallowing occurred in 85% of children with central nervous system disease. CNS disease was due to HIV encephalopathy (8) and miscellaneous central nervous system diseases (5). Three of 4 (75%) patients with thrush had an abnormal oral phase on assessment. No abnormalities of the oesophagus were found.ConclusionsThis report highlights the importance of swallowing disorders in HIV infected children. Most patients have functional rather than structural or mucosal abnormalities. VFSS makes an important contribution to the diagnosis and management of these patients.

Hepatitis B virus infection in HIV-exposed infants in the Western Cape, South Africa

Hepatitis B virus infection (HBV) is a significant public health problem in sub-Saharan Africa. Universal infant vaccination with the hepatitis B (HB) vaccine has been implemented within the South African Expanded Programme of Immunization since April 1995 with concomitant reduction in HBV infection in children. However, the first vaccine dose is only administered at six weeks of age. This delay may lead to a failure to reduce the risk of perinatal HBV transmission to infants born to HIV/HBV co-infected women, in whom HBV infection is often upregulated. The aim of this study was to determine the prevalence of HBV infection in babies born to HIV-infected mothers in the Western Cape, South Africa. HBV serological markers were tested in all infant serum samples and following HB viral load testing, sequencing and genotyping were also performed. Three of 1000 samples screened tested positive for HBsAg and HBV DNA. An additional infant tested positive for HBV DNA alone. All babies had received the HB vaccine at 6, 10 and 14 weeks. The prevalence of HBV infection was therefore 4/1000 (0.4%; 95% CI, 0.01-0.79%). Three of four infants and all four mothers were followed-up. Two infants were persistently positive for HBsAg with viral loads above 10(8) International Units per millilitre. All four maternal samples were positive for HBsAg and HBeAg and one was also positive for anti-HBe. Sequencing analysis of two mother-child HBV pairs showed 100% sequence identity. This study demonstrates HBV infection in HIV-exposed infants despite HB vaccination from 6 weeks of age. A more strategic approach is needed to prevent mother to child transmission of HBV, including screening of pregnant women, HBV-targeted antiviral therapy and HB birth dose vaccine.

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.