Comparison of paediatric infectious disease deaths in public sector health facilities using different data sources in the Western Cape, South Africa (2007-2021).

BACKGROUND: Routinely collected population-wide health data are often used to understand mortality trends including child mortality, as these data are often available more readily or quickly and for lower geographic levels than population-wide mortality data. However, understanding the completeness and accuracy of routine health data sources is essential for their appropriate interpretation and use. This study aims to assess the accuracy of diagnostic coding for public sector in-facility childhood (age < 5 years) infectious disease deaths (lower respiratory tract infections [LRTI], diarrhoea, meningitis, and tuberculous meningitis [TBM]) in routine hospital information systems (RHIS) through comparison with causes of death identified in a child death audit system (Child Healthcare Problem Identification Programme [Child PIP]) and the vital registration system (Death Notification [DN] Surveillance) in the Western Cape, South Africa and to calculate admission mortality rates (number of deaths in admitted patients per 1000 live births) using the best available data from all sources. METHODS: The three data sources: RHIS, Child PIP, and DN Surveillance are integrated and linked by the Western Cape Provincial Health Data Centre using a unique patient identifier. We calculated the deduplicated total number of infectious disease deaths and estimated admission mortality rates using all three data sources. We determined the completeness of Child PIP and DN Surveillance in identifying deaths recorded in RHIS and the level of agreement for causes of death between data sources. RESULTS: Completeness of recorded in-facility infectious disease deaths in Child PIP (23/05/2007-08/02/2021) and DN Surveillance (2010-2013) was 70% and 69% respectively. The greatest agreement in infectious causes of death were for diarrhoea and LRTI: 92% and 84% respectively between RHIS and Child PIP, and 98% and 83% respectively between RHIS and DN Surveillance. In-facility infectious disease admission mortality rates decreased significantly for the province: 1.60 (95% CI: 1.37-1.85) to 0.73 (95% CI: 0.56-0.93) deaths per 1000 live births from 2007 to 2020. CONCLUSION: RHIS had accurate causes of death amongst children dying from infectious diseases, particularly for diarrhoea and LRTI, with declining in-facility admission mortality rates over time. We recommend integrating data sources to ensure the most accurate assessment of child deaths.

Using ceftazidime-avibactam for persistent carbapenem-resistant Serratia marcescens infection highlights antimicrobial stewardship challenges with new beta-lactam-inhibitor combination antibiotics.

The newer beta-lactam-inhibitor combination (BLIC) antibiotics are available in South Africa (SA) for the treatment of carbapenem-resistant Enterobacterales infections. We describe the successful use of ceftazidime-avibactam (CA) for the treatment of a child with persistent carbapenem-resistant Serratia marcescens bacteraemia, and the challenges faced using this lifesaving antibiotic, including access to susceptibility testing, procurement process, cost and complexity of deciding when, how and for how long to use it. Furthermore, the burden of carbapenem resistance is increasing in SA, and inappropriate use of CA and other newer BLIC antibiotics, such as ceftolozane-tazobactam, will inevitably endanger their longevity. A careful balance must be struck between removing unnecessary obstacles and delays in initiating these antibiotics for life-threatening infections, and additional antimicrobial stewardship-guided interventions aimed at preserving their therapeutic use.

A retrospective description of primary immuno-deficiency diseases at Red Cross War Memorial Children's Hospital, Cape Town, South Africa, 1975 - 2017.

BACKGROUND: The primary immunodeficiency diseases (PIDs) constitute a diverse and ever-expanding group of inborn errors affecting a wide range of immune functions. They are not well documented in sub-Saharan Africa. OBJECTIVES: To describe the spectrum of PIDs at a tertiary paediatric hospital. METHODS: A retrospective descriptive study of PIDs diagnosed at Red Cross War Memorial Children's Hospital, Cape Town, South Africa (SA), between 1975 and 2017 was undertaken. RESULTS: We identified 252 children with PIDs, spanning eight of the nine categories listed in the 2017 classification of the International Union of Immunological Societies. Predominantly antibody deficiencies, combined immunodeficiencies with associated syndromic features, and immunodeficiencies affecting cellular and humoral immunity accounted for most children with PIDs (n=199, 79.0%). The mean age (standard deviation) at diagnosis was 46 (50) months, and the male/female ratio was 1.5:1. There was a history of parental consanguinity in 3 cases (1.2%). Recurrent infection was the most prevalent presenting phenotype, manifesting in 177 patients (70.2%). Genetic or chromosomal confirmation was obtained in 42/252 cases (16.7%). Common interventions used to prevent infection were antimicrobial prophylaxis and immunoglobulin replacement therapy, administered to 95 (37.7%) and 93 (36.9%) of the patients, respectively. Six of 7 children who underwent haematopoietic stem cell transplantation (HSCT) had successful outcomes. The 7th patient died 2 months after HSCT from overwhelming infection. Although we could not account for the children lost to follow-up during the study period, 53 deaths were confirmed (21.0%). CONCLUSIONS: Several challenges exist in the recognition and treatment of children with PIDs in our setting. These include limited access to genetic diagnostics and HSCT. Suboptimal treatment options contribute to the overall mortality of PIDs in SA.

Fulminant hepatitis B virus (HBV) infection in an infant following mother-to-child transmission of an e-minus HBV mutant: Time to relook at HBV prophylaxis in South African infants.

The prevalence of hepatitis B virus (HBV) infection in pregnant women is high in South Africa (SA), yet prophylaxis to prevent mother-to-child transmission (MTCT) falls short of international recommendations. We describe a 10-week-old infant who developed fulminant hepatic failure following MTCT. The mother was hepatitis e-antibody positive and had a viral load of only 760 IU/mL. Genetic analysis of virus from mother and infant showed that both had the G1896A mutation in the preC/C gene, which truncates hepatitis e antigen (HBeAg) during translation, causing an HBeAg-negative phenotype. HBeAg attenuates antiviral immune responses, and its absence was probably responsible for the infant's fulminant hepatitis, due to an uncontrolled immune attack on infected liver cells. Pregnant women are not tested for HBV infection in SA and MTCT rates are unknown. Addition of a birth dose of vaccine, HBV screening of pregnant women and antiviral prophylaxis to positive mothers should be prioritised.

Short-term outcomes of down-referral in provision of paediatric antiretroviral therapy at Red Cross War Memorial Children's Hospital, Cape Town, South Africa: A retrospective cohort study.

BACKGROUND: The large scale-up of paediatric HIV care necessitated down-referral of many children receiving antiretroviral therapy (ART) from Red Cross War Memorial Children's Hospital (RCWMCH), Cape Town, South Africa. Few published data exist on the outcomes of these children. OBJECTIVES: To assess outcomes of children receiving ART in the first 12 months after down-referral to primary healthcare (PHC) clinics and identify determinants of successful down-referral. METHODS: A retrospective cohort study of children <15 years of age who initiated ART at RCWMCH and were subsequently down-referred to one of two PHC clinics between January 2006 and December 2012 was completed. Baseline characteristics of patients and caregivers as well as CD4+ counts, viral loads (VLs) and weights were collected 6 and 12 months after down-referral. Outcomes included retention in care and viral suppression. RESULTS: Of 116 children down-referred to the two study PHC clinics, 81.9% arrived at the designated PHC clinic and a further 8.6% continued care at other clinics, the remaining 9.5% being lost to follow-up. Of those successfully down-referred, 11.4% took >8 weeks to present, possibly experiencing treatment interruption. At 12 months after down-referral, only 81.0% remained in care. No factors were associated with retention in care in multivariable analysis. For children who remained in care at the designated PHC clinics, the clinical and immunological gains achieved prior to down-referral were sustained through 12 months of follow-up, and 54.7% of this cohort had documented viral suppression at 12 months. However, if only children with VL results are considered, 75.9% (41/54) were virally suppressed 12 months after down-referral. CONCLUSIONS: Down-referral of children on ART is complex, with risk of loss to follow-up and treatment interruption.

False-negative HIV-1 polymerase chain reaction in a 15-month-old boy with HIV-1 subtype C infection.

Polymerase chain reaction (PCR) testing is the gold standard for determining the HIV status in children <18 months of age. However, when clinical manifestations are not consistent with laboratory results, additional investigation is required. We report a 15-month-old HIV-exposed boy referred to our hospital after he had been admitted several times for infectious diseases. A rapid antibody test on the child was positive, while routine diagnostic HIV PCRs using the Roche COBAS Ampliprep/COBAS TaqMan HIV Qual Test were negative at 6 weeks, 6 months, 7 months and 15 months. In addition, the same PCR test performed on the HIV-infected mother was also negative. Alternative PCR and viral load assays using different primer sets detected HIV RNA or proviral DNA in both child and mother. Gag sequences from the child and his mother classified both infections as HIV-1 subtype C, with very rare mutations that may have resulted in PCR assay primer/probe mismatch. Consequently, the child was commenced on antiretroviral therapy and made a remarkable recovery. These findings indicate that more reliable PCR assays capable of detecting a wide range of HIV subtypes are desirable to circumvent the clinical problems created by false-negative PCR results.

Short-term treatment outcomes of children starting antiretroviral therapy in the intensive care unit, general medical wards and outpatient HIV clinics at Red Cross War Memorial Children's Hospital, Cape Town, South Africa: A retrospective cohort study.

BACKGROUND: Many HIV-infected children are initiated on antiretroviral therapy (ART) during hospitalisation in South Africa (SA). No published data on these outcomes exist. OBJECTIVES: To assess the short-term outcomes of children initiated on ART in the intensive care unit (ICU), general medical wards (GMWs) and outpatient HIV clinics (OHCs) at Red Cross War Memorial Children's Hospital (RCWMCH), Cape Town, SA. METHODS: We conducted a retrospective cohort study of HIV-infected children aged <13 years commenced on first-line ART between January 2008 and December 2011. Outcomes included death, virological suppression and changes in CD4 count. Kaplan-Meier estimates, multivariate Cox proportional hazard ratios and logistic regression were used to estimate outcomes at 6 months. RESULTS: One hundred and six children were commenced on ART in the ICU, 509 in the GMWs and 127 in the OHCs; 65.7% of all children were <12 months old. Of children qualifying for rapid ART initiation according to the 2013 national treatment guidelines, 182 (24.9%) started therapy within 7 days of diagnosis. Overall mortality was 6.4% (95% confidence interval (CI) 4.9 - 8.4). Of children remaining in care at RCWMCH, 51.0% achieved a CD4 percentage ≥25% and 62.3% a viral load ≤50 copies/mL 6 months after ART initiation. Mortality was higher in the ICU cohort (13.2%) than in the GMW and OHC cohorts (5.5% and 3.9%, respectively, log-rank p=0.004). Predictors of mortality included moderate underweight (adjusted hazard ratio (aHR) 2.4; 95% CI 1.1 - 5.2), severe underweight (aHR 3.2; 95% CI 1.6 - 6.5), absence of caregiver counselling sessions (aHR 2.9; 95% CI 1.4 - 6.0) and ART initiation in the ICU (aHR 2.6; 95% CI 1.4 - 4.9). CONCLUSION: These results highlight the importance of understanding the context in which children initiate ART, when comparing outcomes in different settings.

Adolescent and young pregnant women at increased risk of mother-to-child transmission of HIV and poorer maternal and infant health outcomes: A cohort study at public facilities in the Nelson Mandela Bay Metropolitan district, Eastern Cape, South Africa.

BACKGROUND: South Africa (SA) has the highest burden of childhood HIV infection globally, and has high rates of adolescent and youth pregnancy. OBJECTIVE: To explore risks associated with pregnancy in young HIV-infected women, we compared mother-to-child transmission (MTCT) of HIV and maternal and infant health outcomes according to maternal age categories. METHODS: A cohort of HIV-positive pregnant women and their infants were followed up at three sentinel surveillance facilities in the Nelson Mandela Bay Metropolitan (NMBM) district, Eastern Cape Province, SA. Young women were defined as 24 years old and adolescents as 19 years. The effect of younger maternal age categories on MTCT and maternal and child health outcomes was assessed using log-binomial and Cox regression controlling for confounding, using women aged > 24 years as the comparison group. RESULTS: Of 956 mothers, 312 (32.6%) were young women; of these, 65 (20.8%) were adolescents. The proportion of young pregnant women increased by 24% between 2009/10 and 2011/12 (from 28.3% to 35.1%). Young women had an increased risk of being unaware of their HIV status when booking (adjusted risk ratio (aRR) 1.37; 95% confidence interval (CI) 1.21 - 1.54), a reduced rate of antenatal antiretroviral therapy (ART) uptake (adjusted hazard ratio 0.46; 95% CI 0.31 - 0.67), reduced early infant HIV diagnosis (aRR 0.94; 95% CI 0.94 - 0.94), and increased MTCT (aRR 3.07; 95% CI 1.18 - 7.96; adjusted for ART use). Of all vertical transmissions, 56% occurred among young women. Additionally, adolescents had increased risks of first presentation during labour (aRR 3.78; 95% CI 1.06 - 13.4); maternal mortality (aRR 35.1; 95% CI 2.89 - 426) and stillbirth (aRR 3.33; 95% CI 1.53 - 7.25). CONCLUSION: An increasing proportion of pregnant HIV-positive women in NMBM were young, and they had increased MTCT and poorer maternal and infant outcomes than older women. Interventions targeting young women are increasingly needed to reduce pregnancy, HIV infection and MTCT and improve maternal and infant outcomes if SA is to attain its Millennium Development Goals.

Investigation and management of primary immunodeficiency in South African children.

The primary immunodeficiency diseases (PIDs) are inherited, non-communicable diseases that cause immunological dysfunction. PIDs are seldom reported in South Africa (SA). Based on a mid-2013 population estimate of 52.98 million and assuming that the prevalence of PIDs is similar to that in well-resourced settings, the total number of individuals with PIDs in our country should range between2 850 and 45 723. However, fewer than 500 cases of PID have been reported in SA. Between five and 15 new, fully characterised PIDs are reported annually. Our understanding of the physiology of the immune system has been substantially enhanced by these discoveries, and consequently the international classification of PIDs has been updated.

A novel CYBB mutation with the first genetically confirmed case of chronic granulomatous disease in South Africa.

A case of a child with chronic granulomatous disease (CGD) presenting with recurrent mycobacterial infections and invasive Aspergillus fumigatus disease is described. Genetic analysis confirmed X-linked CGD with a novel mutation in exon 10 of the CYBB gene - the first South African report of genetically confirmed CGD.

Impact of age and sex on mycobacterial immunity in an area of high tuberculosis incidence.

SETTING: The extent of immune reactivity measured by the tuberculin skin test (TST) and interferon-gamma (IFN-gamma) T-cell assays is usually not analysed. OBJECTIVE: To determine the impact of age and sex on assay positivity and on the extent of reactivity of both TST and T-cell assays in young persons in an area of South Africa with high TB transmission. RESULTS: Age had a strong impact on assay positivity for all seven immune phenotypes tested (P < 0.0007). Among positive responders, the extent of purified protein derivative (PPD) triggered IFN-gamma release (P < 0.003) was sensitive to age. ESAT-6 triggered IFN-gamma release (day 7, P = 0.03) and the frequency of PPD-specific IFN-gamma(+)CD4(+) (P = 0.03) and IFN-gamma(+)CD8(+) cells (P = 0.04) were weakly dependent on age. By contrast, the extent of TST induration was insensitive to age (P > 0.05), and sex had no significant impact on any phenotype measured (P > 0.05). The high proportion of positive responders in the 1-10 year age-group observed with long-term whole blood assays, but not with 3-day assays and TST, suggests that long-term whole blood assays may be confounded by bacille Calmette-Guérin vaccination in this age group. CONCLUSION: There is a significant impact of age, but not sex, on different assays of immune reactivity in this high TB transmission setting.

Association between Gc genotype and susceptibility to TB is dependent on vitamin D status.

Group-specific component (Gc) variants of vitamin D binding protein differ in their affinity for vitamin D metabolites that modulate antimycobacterial immunity. We conducted studies to determine whether Gc genotype associates with susceptibility to tuberculosis (TB). The following subjects were recruited into case-control studies: in the UK, 123 adult TB patients and 140 controls, all of Gujarati Asian ethnic origin; in Brazil, 130 adult TB patients and 78 controls; and in South Africa, 281 children with TB and 182 controls. Gc genotypes were determined and their frequency was compared between cases versus controls. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were obtained retrospectively for 139 Gujarati Asians, and case-control analysis was stratified by vitamin D status. Interferon (IFN)-gamma release assays were also performed on 36 Gujarati Asian TB contacts. The Gc2/2 genotype was strongly associated with susceptibility to active TB in Gujarati Asians, compared with Gc1/1 genotype (OR 2.81, 95% CI 1.19-6.66; p = 0.009). This association was preserved if serum 25(OH)D was <20 nmol.L(-1) (p = 0.01) but not if serum 25(OH)D was > or =20 nmol.L(-1) (p = 0.36). Carriage of the Gc2 allele was associated with increased PPD of tuberculin-stimulated IFN-gamma release in Gujarati Asian TB contacts (p = 0.02). No association between Gc genotype and susceptibility to TB was observed in other ethnic groups studied.

Disseminated bacille Calmette-Guérin disease in HIV-infected South African infants.

OBJECTIVE: To determine the population-based incidence of disseminated bacille Calmette-Guérin (BCG) disease in HIV-infected infants (aged

High incidence of tuberculosis among HIV-infected infants: evidence from a South African population-based study highlights the need for improved tuberculosis control strategies.

BACKGROUND: There are limited population-based estimates of tuberculosis incidence among human immunodeficiency virus (HIV)-infected and HIV-uninfected infants aged < or =12 months. We aimed to estimate the population-based incidence of culture-confirmed tuberculosis among HIV-infected and HIV-uninfected infants in the Western Cape Province, South Africa. METHODS: The incidences of pulmonary, extrapulmonary, and disseminated tuberculosis were estimated over a 3-year period (2004-2006) with use of prospective representative hospital surveillance data of the annual number of culture-confirmed tuberculosis cases among infants. The total number of HIV-infected and HIV-uninfected infants was calculated using population-based estimates of the total number of live infants and the annual maternal HIV prevalence and vertical HIV transmission rates. RESULTS: There were 245 infants with culture-confirmed tuberculosis. The overall incidences of tuberculosis were 1596 cases per 100,000 population among HIV-infected infants (95% confidence interval [CI], 1151-2132 cases per 100,000 population) and 65.9 cases per 100,000 population among HIV-uninfected infants (95% CI, 56-75 cases per 100,000 population). The relative risk of culture-confirmed tuberculosis among HIV-infected infants was 24.2 (95% CI, 17-34). The incidences of disseminated tuberculosis were 240.9 cases per 100,000 population (95% CI, 89-433 cases per 100,000 population) among HIV-infected infants and 14.1 cases per 100,000 population (95% CI, 10-18 cases per 100,000 population) among HIV-uninfected infants (relative risk, 17.1; 95% CI, 6-34). CONCLUSIONS: This study indicates the magnitude of the tuberculosis disease burden among HIV-infected infants and provides population-based comparative incidence rates of tuberculosis among HIV-infected infants. This high risk of tuberculosis among HIV-infected infants is of great concern and may be attributable to an increased risk of tuberculosis exposure, increased immune-mediated tuberculosis susceptibility, and/or possible limited protective effect of bacille Calmette-Guérin vaccination. Improved tuberculosis control strategies, including maternal tuberculosis screening, contact tracing of tuberculosis-exposed infants coupled with preventive chemotherapy, and effective vaccine strategies, are needed for infants in settings where HIV infection and tuberculosis are highly endemic.

Tuberculosis during early antiretroviral-induced immune reconstitution in HIV-infected children.

SETTING: Referral paediatric hospital, Cape Town, South Africa. OBJECTIVE: To describe the clinical manifestations of Mycobacterium tuberculosis (TB) associated disease in human immunodeficiency virus (HIV) infected children during early antiretroviral-induced immune reconstitution. DESIGN: Case series. RESULTS: Eleven patients with probable or culture confirmed TB were identified. Seven presented after a median 25 (range 8-54) days on highly active antiretroviral therapy (HAART) with pulmonary TB and one also had extra-pulmonary disease. Three of the patients had a prior history of TB and presented with relapse or recurrent disease. Four patients with TB developed a tuberculous paradoxical reaction; one died of suspected tuberculous immune reconstitution pneumonitis. The duration of pre-HAART anti-tuberculosis treatment and antiretroviral treatment ranged from 21 to 59 and 6 to 105 days, respectively, when they presented with a paradoxical reaction. Drug-resistant (isoniazid and rifampicin) TB was cultured from one patient with relapse disease. Chest radiograph features present during immune reconstitution were increasing or new intrathoracic lymphadenopathy, parenchymal infiltrates and pleural effusions. CONCLUSION: This report documents the clinical presentation of TB during the early phase of HAART which may be attributed to HAART-mediated immune reconstitution. More research is needed to improve the accuracy of TB diagnosis in HIV-infected children.

Short-term mortality and implementation of antiretroviral treatment for critically ill HIV-infected children in a developing country.

OBJECTIVE: To describe the short-term outcome of critically ill HIV-infected children with access to highly active antiretroviral therapy (HAART) in a developing region. METHODS: Prospective observational study conducted in a paediatric teaching hospital in Cape Town, South Africa. All children admitted to the paediatric intensive care unit (PICU) with suspected HIV infection were screened. Data are n (%) with 95% confidence intervals. RESULTS: Sixty eight of 96 HIV antibody-positive children, median age 3 months, were confirmed HIV-infected. Predicted PICU mortality was 0.42. Fifty one children (75%; 95% CI 65 to 85%) survived to PICU discharge, but hospital survival was only 51% (95% CI 40 to 63%). Limitation of intervention (LOI) decisions were a factor in the majority of PICU and ward deaths. Twenty one PICU survivors (31%; 95% CI 20 to 42%) commenced HAART, and two children were already on treatment. Nineteen children (28%) were considered to be established on HAART after 1 month. Thirteen HIV-infected children (19%; 95% CI 10 to 28%), representing 25% (95% CI 14 to 37%) of all PICU survivors, and 68% (95% CI 48 to 89%) of those PICU survivors who were established on HAART remain well on treatment after median 350 days. CONCLUSION: The majority of HIV-infected children survived to discharge from PICU, but only half survived to hospital discharge. LOI decisions, usually made in PICU, directly influenced short-term survival and the opportunity to commence HAART. Although few critically ill HIV-infected children survived to become established on HAART, the long-term outcome of children on HAART is encouraging and warrants further investigation.

Secretory leukocyte protease inhibitor and its potential interactions with elastase and cathepsin B in gingival crevicular fluid and saliva from patients with chronic periodontitis.

BACKGROUND AND OBJECTIVE: Elastase is carried into the oral cavity by gingival crevicular fluid (GCF) from periodontal lesions. Our study investigated the regulation of elastase activity by secretory leukocyte protease inhibitor (SLPI) and the possible action of another GCF protease on this protective salivary component. MATERIAL AND METHODS: Whole-mouth saliva (WMS), parotid saliva (PS) and GCF were obtained from 19 patients with periodontitis. The concentrations of active elastase and cathepsin B were determined using peptide substrates. SLPI and alpha1-proteinase inhibitor (alpha1PI) concentrations were determined using enzyme-linked immunosorbent assays (ELISAs). The molecular forms of SLPI were examined by immunoblotting. RESULTS: The molar concentrations of elastase, cathepsin B and alpha1PI were higher in GCF than in WMS and especially PS (p < 0.0002). The GCF SLPI concentrations were also higher than the WMS SLPI concentrations (p < 0.05). All WMS components increased with GCF content, significantly for elastase and SLPI (p < 0.002). In GCF, the concentration of alpha1PI was higher than the concentration of SLPI (p < 0.0002), while there was no significant difference for WMS. SLPI and elastase levels in GCF and WMS were inversely related (p < 0.005). In SLPI immunoblots, PS contained only the intact 14-kDa molecule of SLPI, while WMS also contained an 8-kDa fragment. For WMS there was a positive correlation between SLPI degradation and cathepsin B (p < 0.002). Incubation of WMS alone or of PS with GCF in the presence of cysteine proteinase activators caused SLPI immunoreactivity to shift to 8 kDa. CONCLUSION: For GCF, serum-derived alpha1PI is the major elastase inhibitor, but in WMS SLPI probably reduces activity. The inflamed gingivae can be an additional source of SLPI in the oral cavity, but here the molecule is apparently cleaved by GCF cysteine proteinases, such as cathepsin B.

Collagen degradation by interleukin-1beta-stimulated gingival fibroblasts is accompanied by release and activation of multiple matrix metalloproteinases and cysteine proteinases.

OBJECTIVE: Several collagenolytic matrix metalloproteinases (MMPs) have recently been identified in gingival fibroblasts, while secreted cysteine proteinases could also participate in connective tissue destruction in periodontitis. To clarify their involvement, we examined enzyme release during collagen breakdown by cultured cytokine-stimulated fibroblasts. MATERIALS AND METHODS: Gingival fibroblasts were derived from four chronic periodontitis patients and cultured on collagen gels in serum-free medium for 1-4 days. Collagenolysis was measured by hydroxyproline release into the medium. Proteinases were assessed by electrophoresis and immunoblotting. RESULTS: Adding interleukin-1beta resulted in progressive gel breakdown. This was associated particularly with a shift in MMP-1 band position from proenzyme to active enzyme and the appearance of active as well as proenzyme forms of cathepsin B. There was also partial processing of pro-MMP-13 and increased immunoreactivity for active cathepsin L. In addition, both pro-forms and active forms of MMP-8, membrane-type-1-MMP and MMP-2 were present in control and treated cultures. CONCLUSIONS: Fibroblast MMP-1 was most likely responsible for collagen dissolution in the culture model, while cathepsin B may have been part of an activation pathway. All studied proteinases contribute to extracellular matrix destruction in inflamed gingival tissue, where they probably activate each other in proteolytic cascades.

Contextualising the paediatric HIV epidemic: a review.

OBJECTIVE: To draw attention to the sub-optimal care that HIV-infected children are receiving in Africa. DATA SOURCES: Relevant published literature. DATA SYNTHESIS: Sub-optimal response to paediatric HIV infection has aggravated the negative impact that the epidemic has had on child health in Africa. Recently the African Network for the Care of Children Affected by HIV/AIDS (ANNECA) released an advocacy statement that called for the optimisation of prevention, diagnosis, treatment and care for children affected by the AIDS pandemic. Effective prevention strategies if comprehensively implemented, could prevent more than 500 000 paediatric infections per annum at current antenatal HIV prevalence rates. Improved care that includes universal utilisation of early diagnostic testing systems, cotrimoxazole prophylaxis, nutritional support and the timely introduction of antiretroviral therapy could improve the quality of life and lifespan of most infected children. CONCLUSION: Political leaders, public health officials and fellow child health professionals are urged to redouble their efforts to reverse the magnitude of the paediatric epidemic in Africa.