Tropical distal renal tubular acidosis: clinical and epidemiological studies in 78 patients.

BACKGROUND: Distal renal tubular acidosis (dRTA) caused by mutations of the SLC4A1 gene encoding the erythroid and kidney isoforms of anion exchanger 1 (AE1 or band 3) has a high prevalence in some tropical countries, particularly Thailand, Malaysia, the Philippines and Papua New Guinea (PNG). Here the disease is almost invariably recessive and can result from either homozygous or compound heterozygous SLC4A1 mutations. METHODS: We have collected and reviewed our own and published data on tropical dRTA to provide a comprehensive series of clinical and epidemiological studies in 78 patients. RESULTS: Eight responsible SLC4A1 mutations have been described so far, four of them affecting multiple unrelated families. With the exception of the mutation causing South-East Asian ovalocytosis (SAO), none of these mutations has been reported outside the tropics, where dRTA caused by SLC4A1 mutations is much rarer and almost always dominant, resulting from mutations that are quite different from those found in the tropics. SLC4A1 mutations, including those causing dRTA, may cause morphological red cell changes, often with excess haemolysis. In dRTA, these red cell changes are usually clinically recessive and not present in heterozygotes. The high tropical prevalence of dRTA caused by SLC4A1 mutations is currently unexplained. CONCLUSION: A hypothesis suggesting that changes in red cell metabolism caused by these mutations might protect against malaria is put forward to explain the phenomenon, and a possible mechanism for this effect is proposed.

Neonatal post-intubation subglottic stenosis.

Acquired subglottic stenosis is a compication or neonatal endotracheal intubation. Although it is rare, it contributes significantly to the morbidity and physical well being of post extubated neonates. A 20-day old neonate, ventilated for meconium aspiration syndrome and persistent fetal circulation, presented with marked stridor and respiratory embarrassment. A stenosed subglottic area was found on rigid bronchoscopy. Anterior cricoid split was performed to relieve the obstruction. He is asymptomatic post operatively.

Antimicrobial susceptibility and distribution of non-typhoidal Salmonella serovars isolated in Malaysian children.

There is widespread resistance of Salmonella species to commonly prescribed antimicrobials the world over. We aimed to determine the antimicrobial susceptibility and serovar distribution of non-typhoidal Salmonella (NTS) isolated from blood cultures of Malaysian children. Positive isolates of NTS from blood cultures obtained from children admitted to the pediatric wards of University of Malaya Medical Center (UMMC), a large urban hospital from Kuala Lumpur (1991-2001), and Hospital Kota Bharu (HKB), from the predominantly rural state of Kelantan (1991-1999), Malaysia, were reviewed retrospectively. Serovar distribution and antimicrobial susceptibility were ascertained. A total of 64 and 55 isolates of NTS were obtained from blood cultures of children admitted to UMMC and HKB, respectively. The commonest serovar isolated was Salmonella enteritidis in both centers. The NTS isolated were highly sensitive to the antimicrobials tested: ampicillin 98 per cent, chloramphenicol 98 per cent, gentamicin 97 per cent, trimethoprim-sulfamethoxazole (TMP-SMX) 98 per cent, and ceftriaxone 100 per cent in UMMC; ampicillin 100 per cent, chloramphenicol 87 per cent, kanamycin 100 per cent, streptomycin 96 per cent, TMP-SMX 93 per cent, and tetracycline 89 per cent in HKB. There were only one and five multi-resistant isolates in UMMC and HKB, respectively. In conclusion, NTS isolated from blood cultures of Malaysian children from Kuala Lumpur and Kota Bharu were highly sensitive to commonly prescribed antibiotics. We speculate that this is due to the restriction of sales of antimicrobials in Malaysia except by prescription. Continuing vigilance and frequent antmicrobial surveillance is necessary.

Low prevalence of Cryptosporidium parvum in hospitalized children in Kota Bharu, Malaysia.

The aim of this prospective study was to determine the prevalence of Cryptosporidium parvum in hospitalized children in Kota Bharu, Malaysia. Over a 19 month study period, 258 stool samples were examined from 159 children; 109 with diarrhea and 50 controls without diarrhea. Modified Ziehl-Neelsen staining method and a polymerase chain reaction (PCR) assay were used to detect C. parvum and the samples were also examined for the presence of other intestinal parasites. Only 1 of the 109 (0.9%) children with acute diarrhea was positive for C. parvum by microscopy and PCR. Thirty-one percent of children were infested with other intestinal parasites, the most common being Ascaris lumbricoides and Trichuris trichiura. In conclusion, we found C. parvum to be an uncommon infective agent in hospitalized children with or without diarrhea in Kota Bharu, Malaysia.

Serum C-reactive protein concentrations in Malaysian children with enteric fever.

To investigate the role of serum C-reactive protein (CRP) in the diagnosis of typhoid fever, we studied 227 febrile Malaysian children hospitalized during a 12-month period. The children were: culture-positive for Salmonella typhi (Group 1; n = 108); culture-negative but with typical clinical features of typhoid fever (Group 2; n = 60); or had non-typhoidal illness (Group 3; n = 59). Group 1 children had the highest serum CRP concentrations (geometric mean [SD range]; 43 [12-150] mg/l vs. 26 [8-85] mg/l in Group 2 and 21 [4-110] mg/l in Group 3; p < 0.001). In regression analysis, age, patient group and fever duration were independently associated with serum CRP (p < 0.05) but gender was not. In Group 1 patients, there was a significant positive association between serum CRP and Widal O and H agglutinin titres. In receiver-operator characteristic (ROC) analysis of serum CRP for Groups 1 and 2 combined, compared with Group 3, the area under the curve (AUC) was 0.65. These data show that the serum CRP is highest in culture-positive children with enteric fever and reflects the immune response to the infection in this group. Nevertheless, serum CRP had relatively low sensitivity and specificity for confirmed or clinically diagnosed typhoid fever (68 and 58 per cent, respectively at 'cut-off' concentration 30.0 mg/l), and an AUC value only moderately above that associated with no predictive power (0.5). Although of limited use as a primary diagnostic test, a raised serum CRP may still have a place as one of a range of features that facilitate assessment of a febrile child in a typhoid-endemic area.

Epidemiology of Haemophilus influenzae invasive disease in hospitalised Kelantanese children, 1985-1994.

AIM: Data is lacking with regard to the epidemiology of invasive haemophilus influenzae (HI) disease in Malaysia. This study was carried out to document the epidemiology of invasive HI disease in hospitalised Kelantanese children. METHODS: We conducted a retrospective study of 65 children who had invasive HI disease from June 1985 to December 1994. Data regarding age, sex, duration of illness, weight, diagnosis, complications, duration of hospitalisation, outcome, full blood count and sensitivity pattern of HI to various antibiotics were reviewed. RESULTS: The age distribution varied from one day to 72 months with a mean of 13 months. Peak incidence occurred in the 7-12 months age group. Majority (89.1%) was below two years of age. The relative frequencies of the 75 clinical entities documented were as follows: meningitis 64%, pneumonia 29.3%, septicaemia 5.4%, and abscess 1.3%. In addition, 13.5% of cases had meningitis associated with pneumonia. Serotype b accounted for all strains in cases where serotyping was done. Anaemia (Hb < 10 g%) was seen in 71.4% of cases. Long term complications were noted in 41.5% of cases of meningitis. Case fatality rate was 12.3%. The percentage of HI strains sensitive to penicillin, ampicillin, chloramphenicol and co-trimoxazole were 83.7%, 87.7%, 98.2% and 89.7%, respectively. CONCLUSION: The data suggest that invasive HI disease causes considerable morbidity and mortality in Kelantanese children.

Rapid and reliable serological diagnosis of enteric fever: comparative sensitivity and specificity of Typhidot and Typhidot-M tests in febrile Malaysian children.

The Typhidot test, which detects IgM and IgG antibodies to a Salmonella typhi-specific outer membrane protein, is as sensitive as, and more specific than, the Widal test in the diagnosis of enteric fever in Malaysian children. It is easier and quicker to perform. In order to increase diagnostic accuracy in an area of high endemicity, the Typhidot-M test has been developed in which IgG is first removed. This theoretically allows improved detection of IgM, and thus would differentiate new from recent infections. We evaluated both tests in 134 unselected febrile children admitted to the General Hospital Kota Bharu, Malaysia. The children were divided into two groups: (i) those who were blood and/or stool culture positive for S. typhi and/or who had clinical features strongly suggestive of enteric fever (n = 62); and (ii) those who were both culture-negative and had clinical evidence of another diagnosis (n = 72). The sensitivity and specificity of the Typhidot and Typhidot-M tests were identical at 90.3 and 93.1%, respectively. Both tests had comparable sensitivity but greater specificity than those of the Widal test (91.9 and 80.6%, respectively). When used together, a positive result for Typhidot and/or Typhidot-M was more specific than either test alone (95.2%) but specificity was lower (87.5%). We conclude that the Typhidot and Typhidot-M tests have comparatively high diagnostic accuracy, suggesting that IgM can be detected in children who may have a predominant IgG response to S. typhi. Using these tests in combination increases the negative predictive value but at the cost of a lower positive predictive value.

Relative bradycardia is not a feature of enteric fever in children.

We investigated pulse-temperature relationships in 66 children with enteric fever (group 1) and in 76 with other infections (group 2). Group 1 children were older than group 2 children (mean age +/- SD, 91 +/- 36 vs. 66 +/- 32 months, respectively; P < .001) and had mean oral temperatures +/- SD similar to those of group 2 children (38.3 +/- 1.0 vs. 38.3 +/- 0.9 degrees C, respectively; P > .2); however, group 1 children had lower mean baseline pulse rates +/- SD than did group 2 children (119 +/- 25 vs. 127 +/- 28 beats/min, respectively; P < .001). In a multiple linear regression model, pulse rate was independently associated with age (inversely; P < .001) and oral temperature (positively; P < .006) but not with diagnostic group or gender (P > .5). After adjustment of the mean initial pulse rate +/- SD to age of 72 months, there was no difference between group 1 and group 2 children (126 +/- 24 vs. 126 +/- 20 beats/min, respectively; P > .5). From 4 to 72 hours after commencement of treatment, the mean oral temperature in group 1 patients was approximately 0.3 degrees C higher than that in group 2 patients, and the age-adjusted pulse rate was 5 beats/min higher in group 1 children than in group 2 children. These data suggest that relative bradycardia is not characteristic of enteric fever in children.

Non-radioisotopic glucose turnover in children with falciparum malaria and enteric fever.

To determine whether glucose turnover is increased in acute falciparum malaria compared to enteric fever in children, steady-state 6,6-D2-glucose turnover was measured in 9 Malaysian children with uncomplicated malaria (6 males and 3 females; median age 10 years, body weight 22 kg) and in 12 with uncomplicated enteric fever (8 males and 4 females; median age 10 years, body weight 24 kg) in acute illness, after quinine (5 malaria patients) and in convalescence. Baseline plasma glucose concentrations in malaria and enteric fever were similar (all values are medians [ranges in brackets]) 5.6 [3.2-11.3] vs. 5.5 [4.2-8.0] mmol/L), as were serum insulin levels (5.6 [0.4-26.5] vs. 6.8 [1.1-22.5] milliunits/L; P > 0.4). Glucose turnover in the malaria patients was higher than in patients with enteric fever (6.27 [2.71-6.87] vs. 5.20 [4.50-6.08] mg/kg.min; P = 0.02) and in convalescence (4.74 [3.35-6.79] mg/kg.min; P = 0.05 vs. acute malaria study), and fell after quinine together with a rise in serum insulin (P = 0.03). Basal plasma lactate concentrations were higher in enteric fever than in malaria (3.4 [1.8-6.4] vs. 0.8 [0.3-3.8] mmol/L; P < 0.0001) and correlated inversely with glucose turnover in this group (rs = -0.60; n = 12; P = 0.02). These data suggest that glucose turnover is 20% greater in malaria than in enteric fever. This might reflect increased non-insulin-mediated glucose uptake in falciparum malaria and/or impaired gluconeogenesis in enteric fever, and may have implications for metabolic complications and their clinical management in both infections.

Haemophilus influenzae meningitis in Malaysia.

OBJECTIVE: To determine the pattern of postneonatal childhood meningitis in Malaysia. METHODS: Retrospective cross-sectional study involving five pediatric departments in Malaysia. RESULTS: There were 435 cases of clinical meningitis admitted to the five centers. More than 90% of the patients were <5 years old, and one-half were <6 months of age. The estimated overall incidence of childhood meningitis in the first 5 years of life was 76.7 per 100000 per year. However, of the 435 cases only 71 (16.3%) fulfilled laboratory diagnostic criteria and in only 58 of these was an organism isolated. Nearly one-half (48%) of all bacteriologically proved cases were caused by Haemophilus influenzae type b (Hib). The mortality rate was 12.5% and 21 patients (30%) suffered neurologic sequelae. CONCLUSIONS: More than one-half of all cases of culture-positive childhood bacterial meningitis were caused by Hib, although successful isolation of a pathogen occurred in only a small proportion of cases. For this reason the true incidence of Hib meningitis in Malaysia remains unknown. These findings are consistent with previous studies in Malaysia.

Dynamic assessment of parathyroid function in acute malaria.

OBJECTIVES: To investigate the dynamic parathyroid response to rapidly induced, sustained hypocalcaemia in patients with acute malaria and in healthy volunteers. DESIGN: Serum intact parathormone (PTH) concentrations were measured on samples taken before and during a variable-rate tri-sodium citrate infusion designed to 'clamp' the whole blood ionised calcium concentration 0.20 mmol L-1 below baseline for 120 min. SUBJECTS: Six Malaysian patients aged 17-42 years with acute malaria, four of whom were restudied in convalescence, and 12 healthy controls aged 19-36 years. MAIN OUTCOME MEASURES: Whole-blood ionised calcium and serum intact PTH concentrations. RESULTS: The mean (SD baseline ionised calcium was lower in the malaria patients than in controls (1.09 +/- 0.06 vs. 1.18 +/- 0.03 mmol L-1, respectively; P = 0.01) but PTH concentrations were similar (3.0 +/- 1.8 vs. 3.3 +/- 1.3 pmol L(-1); P = 0.33). Target whole-blood ionised calcium concentrations were achieved more rapidly in the controls than the patients (within 15 vs. 30 min) despite significantly more citrate being required in the patients (area under the citrate infusion-time curve 0.95 (0.25 vs. 0.57 +/- 0.09 mmol kg-1; P < 0.01). The ratio of the change in serum PTH to that in ionised calcium (delta PTH/ delta Ca2+), calculated to adjust for differences in initial rate of fall of ionised calcium, was similar during the first 5 min of the clamp (132 +/- 75 x 10(-6) vs. 131 +/- 43 x 10(-6) in patients and controls, respectively, P > 0.05), as were steady-state serum PTH levels during the second hour (7.0 +/- 2.2 pmol L-1 in each case). Convalescent patients had normal basal ionised calcium levels but the lowest serum intact PTH levels before and during the clamp, consistent with an increase in skeletal PTH sensitivity after treatment. CONCLUSIONS: There is a decreased ionised calcium 'set point' for basal PTH secretion but a normal PTH response to acute hypocalcaemia in malaria. Skeletal resistance may attenuate the effects of the PTH response but patients with malaria appear relatively resistant to the calcium chelating effects of citrated blood products.

Longevity of antibody responses to a Salmonella typhi-specific outer membrane protein: interpretation of a dot enzyme immunosorbent assay in an area of high typhoid fever endemicity.

The objective of this study was to investigate the longevity of positive dot enzyme immunosorbent assay (dot EIA) results for IgM and IgG to a Salmonella typhi outer membrane protein in Malaysian children with enteric fever. The patients were children one month to 12 years of age with clinical evidence of typhoid fever, positive blood or stool cultures for S. typhi, and/or a positive Widal test result who were admitted over a two-year period to General Hospital (Kota Bharu, Malaysia). These patients received standard inpatient treatment for enteric fever including chloramphenicol therapy for 14 days. Dot EIA tests were performed as part of clinical and laboratory assessments on admission, at two weeks, and then at 3, 6, 9, 12, 15, 18, and 21 months postdischarge. Assessment of the longevity of positive dot EIA IgM and IgG titers was done by Kaplan-Meier analysis. In 94 evaluable patients, 28% were dot EIA IgM positive but IgG negative on admission, 50% were both IgM and IgG positive, and 22% were IgM negative and IgG positive. Mean persistence of IgM dot EIA positivity was 2.6 months (95% confidence interval = 2.0-3.1 months) and that of IgG was 5.4 months (4.5-6.3 months). There were no significant differences between the three subgroups. Thus, positive IgM and IgG results determined by dot EIA within four and seven months, respectively, following documented or suspected enteric fever in a child from an endemic area should be interpreted with caution. In other clinical situations, the dot EIA remains a rapid and reliable aid to diagnosis.

Serum lipid profiles in Malay mothers and neonates: a cross-sectional study.

OBJECTIVE: Preliminary epidemiological data suggest that dyslipidaemia contributes significantly to rising mortality due to atherosclerosis in Peninsular Malays. The aim of this study was to determine whether abnormal serum lipid profiles are present at birth in this population. METHODOLOGY: The patients were 487 non-diabetic Malay women who had an uncomplicated antenatal course and delivered healthy singleton babies at term. Cord blood and maternal post-partum venous blood samples were taken for assay of serum cholesterol and triglyceride concentrations using standard enzymatic methods. RESULTS: Maternal total serum cholesterol concentrations (mean +/- SD; 7.5 +/- 2.5 mmol/L) were higher than in other reported series (range of published means 5.2-6.5 mmol/L) with a correspondingly low high-density lipoprotein (HDL): total cholesterol ratio. The mean cord blood total serum cholesterol (1.7 +/- 1.0 mmol/L) was consistent with previously reported population means (1.5-1.9 mmol/L) but there was a relatively high low-density lipoprotein (LDL)-cholesterol and depressed HDL: cholesterol ratio. Significant correlations between maternal and neonatal serum total (P = 0.038) and especially HDL-cholesterol (P < 0.001) were observed. Maternal and cord blood serum triglyceride levels were comparable to those in other series. CONCLUSIONS: These cross-sectional data provide evidence that abnormal serum cholesterol profiles are found in pregnant Malay women and their neonates which may have implications for the prevalence of macrovascular disease in the Malay population.

Neonatal septic arthritis.

Neonatal septic arthritis has always been considered as separate from its counterpart in older children. The condition is uncommon but serious. Affected neonates usually survive, but with permanent skeletal deformities. Ten cases of neonatal septic arthritis were diagnosed between January 1989 and December 1993 in the neonatal intensive care units of two referral hospitals in the state of Kelantan, Malaysia. All except one neonate was born prematurely. The mean age of presentation was 15.6 days. Joint swelling (10/10), increased warmth (7/10) and erythema of the overlying skin (7/10) were the common presenting signs. Vague constitutional symptoms preceded the definitive signs of septic arthritis in all cases. The total white cell counts were raised with shift to the left. The knee (60%) was not commonly affected, followed by the hip (13%) and ankle (13%). Three neonates had multiple joint involvement. Coexistence of arthritis with osteomyelitis was observed in seven neonates. The commonest organism isolated was methicillin resistant Staphylococcus aureus (9/10). Needle aspiration was performed in nine neonates and one had incision with drainage. Follow up data was available for five neonates and two of these had skeletal morbidity. Early diagnosis by frequent examination of the joints, prompt treatment and control of nosocomial infection are important for management.

Acute respiratory tract infection: a community-based intervention study in Malaysia.

A community-based intervention trial was conducted in Kelantan, Malaysia with the aim of reducing severe acute respiratory tract (ARI) infection in children. Interventions included health education of mothers on childhood pneumonia and training of health staff on case management. In a house-to-house survey 1382 and 1107 children less than 5 years of age in the intervention and control areas, respectively, were followed up every 2 weeks over a 62-week period. The reduction in the incidence of severe ARI cases in the intervention area was significantly greater than in the control area (P < 0.05). The ARI mortality rates were low in both the intervention and control areas ( < 0.1%). Our results indicate that with relatively inexpensive methods and simple interventions, reduction of severe ARI may be effectively achieved. This has important implications for an ARI control programme in Malaysia and other developing countries.

Congenital dyserythropoietic anaemia: report of three cases.

Between January 1985 and June 1992, the Paediatric Department of Hospital Universiti Sains Malaysia has diagnosed congenital dyserythropoietic anaemia in three children, two of whom were siblings. The age of onset ranged from 1 to 3 years. All of them became transfusion-dependent before the age of 4 months. One of them was successfully treated with bone marrow transplantation.

Bruton's agammaglobulinaemia in a child presenting with cryptococcal empyema thoracis and periauricular pyogenic abscess.

We describe here a case of cryptococcal empyema thoracis and periauricular pyogenic abscess in a child with Bruton's agammaglobulinaemia. The cryptococcal empyema thoracis was treated with intravenous amphotericin B and intravenous fluconazole for six weeks followed by oral fluconazole. The pyogenic periauricular abscess was surgically drained and treated with intravenous ceftazidime and cloxacillin for two weeks. He also received monthly intravenous immunoglobulin.

Dynamic assessment of the electrocardiographic QT interval during citrate infusion in healthy volunteers.

OBJECTIVE: To investigate changes in the electrocardiographic QT interval during rapidly induced, sustained hypocalcaemia in healthy volunteers. DESIGN: Serial rate corrected QT measurements were made during and after a variable rate trisodium citrate infusion designed to "clamp" the whole blood ionised calcium concentration 0.20 mmol/l below baseline for 120 min. SUBJECTS: 12 healthy teetotallers aged 19- 36 years who were not receiving medication known to influence calcium homoeostasis. MAIN OUTCOME MEASURES: Whole blood ionised calcium concentration and QaTc intervals (onset of the Q wave to T wave apex divided by the square root of the RR interval). RESULTS: Mean (SD) ionised calcium concentration decreased from 1.18 (0.03) mmol/l preinfusion to values close to target (0.98 mmol/l) between 10 and 120 min. The QaTc interval lengthened from a baseline of 0.309 (0.021) to a maximum 0.343 (0.024) s0.5 at 10 min before returning to a stable level from 15 to 120 min (0.334 (0.023) and 0.330 (0.023) s0.5 respectively). The change from baseline of both variables expressed as a ratio (delta QaTc/ delta [Ca2+]) was greater during rapid induction of hypocalcaemia (at 5 and 10 min) than at other times during and after the infusion (P < 0.02). CONCLUSIONS: The disproportionate prolongation of QaTc interval during prompt induction of hypocalcaemia suggests rate dependency which can be represented by a hysteresis relation between (ionised calcium, QaTc) coordinates. This finding may have clinical implications.

Empyema thoracis in hospitalized children in Kelantan, Malaysia.

In this study, 31 cases of childhood empyema thoracis admitted over 4 1/2 years to the Hospital Universiti Sains Malaysia, in Kelantan, Malaysia, were retrospectively reviewed. Twenty-two males and nine females were included, with a mean age of 1.9 years (range: 26 days to 7 years). Frequent symptoms were fever, cough, and dyspnoea, while common signs were temperature above 38 degrees C, decreased breath sounds, dullness to chest percussion, and intercostal recession. Radiography demonstrated unilateral moderate to large effusions in 68 per cent of cases, while consolidated lung was seen in 45 per cent of patients. Pleural fluid cultures were positive for Staphylococcus aureus (48 per cent), Streptococcus pneumoniae (7 per cent), while no growth was seen in 42 per cent of cases. Ninety-four per cent of children had a blood leukocytosis above 10 000 cell/mm3, but blood cultures were negative in 21 out of 26 patients (81 per cent). Most cases were treated with a combination of intravenous antibiotics and chest tube drainage. Antibiotics and pleural tap(s) were used in the remainder. Patients stayed in hospital for an average of 20.7 days (range: 4-52 days). Surgical intervention was necessary in only four children. The mortality rate at the time of discharge was zero, with 100 per cent radiographic resolution among the 23 patients who were followed-up.