Miriam Adhikari

Tuberculosis in the newborn: an emerging disease

BACKGROUND In spite of the global increase in tuberculosis, which is in part fueled by the HIV pandemic, tuberculosis in the perinatal period is rare, and to date it has not been directly associated with maternal or neonatal HIV infection. OBJECTIVES To detect tuberculosis in newborns from a province with epidemics of both tuberculosis and HIV infection and to analyze the profile of tuberculosis in their mothers. METHODS At King Edward VIII Hospital, in KwaZulu Natal, South Africa, during a 1-year period all neonates at the neonatal unit in whom a differential diagnosis of tuberculosis was considered were investigated. The clinical profiles, short term outcome and relationship to maternal tuberculosis and HIV infection were determined for those neonates in whom the diagnosis of tuberculosis was confirmed. RESULTS From the investigation of 77 neonates 11 with culture confirmed perinatal tuberculosis were identified. Six of these infants were born to mothers who had HIV and tuberculosis coinfection. Six of the 11 neonates could be classified as congenital tuberculosis. The predominant clinical findings were progressive pneumonia (9 of 11), pyrexia (9 of 11), growth retardation (7 of 11), hepatomegaly (6 of 11), splenomegaly (4 of 11) and meningitis (2 of 11). Seven of their mothers had evidence of current or past tuberculosis or had close contact with a tuberculosis case. One neonate and two mothers died within the first 3 months. CONCLUSIONS This is the first report of perinatal tuberculosis in association with maternal HIV and tuberculosis coinfection.

Post-dysenteric hemolytic uremic syndrome in children during an epidemic of Shigella dysentery in Kwazulu/Natal

Abstract. We report 81 of 107 cases of hemolytic uremic syndrome (HUS), admitted between July 1994 and February 1996, following an outbreak of Shigella dysenteriae type 1 dysentery in Kwazulu/Natal. All patients, excluding 1, were black with a mean age of 38 months (range 1 – 121); 50 (61.7%) were males. The mean duration of dysentery was 11.3 days (range 1 – 41) and HUS 15 days (range 1 – 91). Most patients had acute oliguric renal failure (90.1%); 42 (51.6%) required peritoneal dialysis. Complications included encephalopathy 30 (37.0%), convulsions 12 (14.8%) and hemiplegia 2 (2.3%), gastrointestinal perforation 8 (9.9%), protein losing enteropathy 26 (32.1%), toxic megacolon 4 (4.9%), rectal prolapse 5 (6.2%), hepatitis 11 (13.6%), myocarditis 5 (6.2%), congestive cardiac failure 3 (3.7%), cardiomyopathy 3 (3.7%), infective endocarditis 1 (1.2%), septicemia 15 (18.5%), disseminated intravascular coagulation 17 (21%). Leukemoid reactions were found in 74 (91.3%) patients, hyponatremia in 56 (69.1%), and hypoalbuminemia in 67 (82.7%). Stool culture for Shigella dysenteriae type I was positive in only 7 (8.6%) patients; Shiga toxin assays were not performed. Outcome was as follows: recovery 32 (39.5%), impaired renal function 8 (9.9%), chronic renal failure 26 (32.1%), end-stage renal disease 1 (1.2%), and death 14 (17.3%) patients.

NEPHROTIC SYNDROME IN SOUTH AFRICAN CHILDREN: CHANGING PERSPECTIVES OVER 20 YEARS

Abstract. We review our 20-year experience of 636 children with nephrotic syndrome (NS) in Durban, South Africa; 306 (48.2%) were blacks, 307 (48.2%) Indians and 23 (3.6%) were a mixed group (coloured); 91 (14.3%) could not be categorised and were excluded from the analysis. In Indian children, 134 of 286 (46.8%) had biopsy-proven minimal change NS (MCNS) and 94.8% of these were steroid sensitive (SS); 60 (21%) had SSNS but without renal biopsy; 59 (20.6%) had focal segmental glomerulosclerosis (FSGS), with only 4.4% of these being SS. In blacks, membranous nephropathy accounted for 40% of cases; 86.2% were associated with hepatitis B virus antigens. Typical SSNS continues to be uncommon among blacks. Only 14.4% had either biopsy-proven SS-MCNS or SSNS; 32 had MCNS lesions on biopsy, but 18 were steroid resistant (SR); 67 of 236 (28.4%) had FSGS, all of whom were SR. Among coloured patients, 5 of 23 (21.7%) had biopsy-proven SS-MCNS and or unbiopsied SSNS; 10 (43.5%) had FSGS and 6 of 23 (26.1%) had membranous nephropathy. Proliferative lesions were present in only 2 of 23 (8.6%) coloured patients and was uncommon in all population groups. Overall mortality was 3.1%. In brief, this is the largest reported series of NS among children in Africa and shows a typical pattern in Indians, an unusual pattern of histological types in blacks and an intermediate picture in coloureds.

Unique acquisition of cytotoxic T-lymphocyte escape mutants in infant human immunodeficiency virus type 1 infection.

ABSTRACT The role of cytotoxic T-lymphocyte (CTL) escape in rapidly progressive infant human immunodeficiency virus type 1 (HIV-1) infection is undefined. The data presented here demonstrate that infant HIV-1-specific CTL can select for viral escape variants very early in life. These variants, furthermore, may be selected specifically in the infant, despite the same CTL specificity being present in the mother. Additionally, pediatric CTL activity may be compromised both by the transmission of maternal escape variants and by mother-to-child transmission of escape variants that originally arose in the father. The unique acquisition of these CTL escape forms may help to explain the severe nature of some pediatric HIV infections.

An outbreak of neonatal infection with Acinetobacter linked to contaminated suction catheters.

An outbreak of multi-drug resistant Acinetobacter spp. infection in the neonatal unit at King Edward VIII hospital in Durban, South Africa, is described. Nine out of a total of 218 neonates were infected during the study period. The outbreak was characterized by early onset infection [median postnatal age 3 days (range 1-23 days)] in pre-term babies [median gestational age 33 weeks (range 30-35 weeks)] with an attributable mortality of 22%. The source of the outbreak, determined by ribotyping, was presumed to be contaminated suction bottles and catheters in the neonatal admission room. Five neonates were successfully treated with ciprofloxacin and amikacin. Enforcement of strict infection control practices curtailed the outbreak.

Hepatitis B virus-associated nephropathy in black South African children

Abstract. Hepatitis B virus (HBV)-related membranous nephropathy (MN) is prominent in secondary nephrotic syndromes (NS) in Africa, but the features of this disease and the spectrum of associated glomerulopathies have not been adequately documented in black children. HBV was detected in 93 children with NS included in this study. In 70 patients the histological type was membranous; 46 were followed for a mean of 3.4 years (range 1–11 years). Spontaneous elimination of both HBsAg and HBeAg occurred in 10 (21.7%) patients; 16 (34.8%) cleared HBeAg alone. Co-existing liver disease occurred in 18 (25.7%) and hypocomplementemia (C3,C4) in 47.1% and 11.4% of children, respectively. Sixty-five (92.9%) patients had normal renal function, 1 (1.4%) impaired renal function, 3 (4.3%) chronic renal insufficiency, and 1 (1.4%) end-stage renal disease at last hospital visit. Twelve patients were in remission, all having cleared HBeAg. HBVMN was clinically indistinguishable from 24 children with idiopathic MN, although biochemical characteristics were different. This report delineates the natural history of HBV infection in black South African children with NS, the majority of whom have MN. Disease remission in HBVMN parallels elimination of HBV antigens, particularly HBeAg. Comparison of HBVMN with idiopathic MN revealed clinically indistinguishable characteristics but unexplained biochemical differences.

Etiology of Bacteremia in Young Infants in Six Countries

Background: Neonatal illness is a leading cause of death worldwide; sepsis is one of the main contributors. The etiologies of community-acquired neonatal bacteremia in developing countries have not been well characterized. Methods: Infants <2 months of age brought with illness to selected health facilities in Bangladesh, Bolivia, Ghana, India, Pakistan and South Africa were evaluated, and blood cultures taken if they were considered ill enough to be admitted to hospital. Organisms were isolated using standard culture techniques. Results: Eight thousand eight hundred and eighty-nine infants were recruited, including 3177 0–6 days of age and 5712 7–59 days of age; 10.7% (947/8889) had a blood culture performed. Of those requiring hospital management, 782 (54%) had blood cultures performed. Probable or definite pathogens were identified in 10.6% including 10.4% of newborns 0–6 days of age (44/424) and 10.9% of infants 7–59 days of age (39/358). Staphylococcus aureus was the most commonly isolated species (36/83, 43.4%) followed by various species of Gram-negative bacilli (39/83, 46.9%; Acinetobacter spp., Escherichia coli and Klebsiella spp. were the most common organisms). Resistance to second and third generation cephalosporins was present in more than half of isolates and 44% of the Gram-negative isolates were gentamicin-resistant. Mortality rates were similar in hospitalized infants with positive (5/71, 7.0%) and negative blood cultures (42/557, 7.5%). Conclusions: This large study of young infants aged 0–59 days demonstrated a broad array of Gram-positive and Gram-negative pathogens responsible for community-acquired bacteremia and substantial levels of antimicrobial resistance. The role of S. aureus as a pathogen is unclear and merits further investigation.

Management of Steroid-Resistant Focal Segmental Glomerulosclerosis in Children Using Tacrolimus

Background: The use of tacrolimus in steroid-resistant (SR) focal segmental glomerulosclerosis (FSGS) has been reported in single and small series case reports. Aim: To determine the efficacy of tacrolimus in the management of SR FSGS in children. Study Design: This was a prospective study of 20 children with SR FSGS treated with tacrolimus (0.2–0.4 mg/kg/day in two divided doses over 12 h adjusted to a trough level between 7 and 15 ng/ml) for 12 months in combination with low-dose steroids. Other therapies included angiotensin-converting enzyme inhibitors, folic acid, multivitamins and lipid-lowering agents. Results: The mean age at study entry was 11.1 years (range 5.6–16.8). The mean duration of nephrotic syndrome before initiation of tacrolimus therapy was 4.7 years (range 2.1–7.6). At the end of the treatment period, 8 (40%) children were in complete remission, 9 (45%) were in partial remission, and 3 (15%) failed to respond. The average follow-up period following cessation of tacrolimus treatment was 27.5 months (range 13.7–43.7). At last hospital follow-up, 5 (25%) children were in complete remission, 10 (50%) in partial remission, and 2 (10%) in relapse. Three children died from dialysis-related complications following cessation of tacrolimus treatment. Adverse events included sepsis (2), nausea (2), diarrhea (2), anemia (4) and worsening of hypertension (4). Conclusion: Tacrolimus is a safe and effective treatment for SR FSGS. However, like cyclosporine, some children tend to relapse following cessation of treatment.

Aflatoxins and kwashiorkor in Durban, South Africa.

The present investigation has indicated that maize seeds stored under various simulated seasonal conditions show a spectrum of fungi that appear as a succession. The aflatoxin-producing fungus, Aspergillus flavus, is favoured by storage conditions of high temperature and humidity (summer and autumn seasons). This coincides with the more frequent admission of children suffering from kwashiorkor at King Edward VIII Hospital in Durban. Aflatoxin analysis was undertaken on 74 children diagnosed at King Edward VIII Hospital in Durban as cases of kwashiorkor, marasmus or underweight (Wellcome classification). The control group consisted of 35 age-matched patients with no symptoms of protein energy malnutrition. Aflatoxins were detected in serum and/or urine from all groups, including the controls. The serum/urine ratio was significantly higher in the kwashiorkor group than in the other groups. The control group, however, had a higher proportion of urine aflatoxins than the kwashiorkor group. These findings were interpreted in terms of impaired liver function in kwashiorkor. Aflatoxins may have a rôle in the pathogenesis of kwashiorkor, although the present findings do not indicate that they are a causal factor.

Tuberculosis in association with HIV/AIDS emerges as a major nonobstetric cause of maternal mortality in Sub-Saharan Africa.

Every year, approximately 250 000 African women die during pregnancy, delivery, or the puerperium. Maternal mortality rates due to infectious diseases in Sub‐Saharan Africa now supersede mortality from obstetric causes. Evidence is accumulating that tuberculosis associated with HIV/AIDS, malaria, sepsis, and other opportunistic infections are the main infectious causes of maternal deaths. Screening for these killer infections within prenatal healthcare programs is essential at this stage to prevent and treat causes of maternal mortality. The combination of proven effective interventions that avert the greatest number of maternal deaths should be prioritized and expanded to cover the greatest number of women at risk, and incorporated into a “prophylaxis and treatment community package of care.” The effectiveness of these “packages of care” will need to be determined subsequently. Maternal deaths from tuberculosis are now on the increase in the UK, and due diligence and watchful surveillance are required in European prenatal services.