The utility of Xpert MTB/RIF performed on bronchial washings obtained in patients with suspected pulmonary tuberculosis in a high prevalence setting.

BACKGROUND: Xpert MTB/RIF has been shown to have a superior sensitivity to microscopy for acid fast bacilli (AFB) in sputum and has been recommended as a standard first line investigation for pulmonary tuberculosis (PTB). Bronchoscopy is a valuable tool in diagnosing PTB in sputum negative patients. There is limited data on the utility of Xpert MTB/RIF performed on bronchial lavage specimens. Our aim was to evaluate the diagnostic efficiency of Xpert MTB/RIF performed on bronchial washings in sputum scarce/negative patients with suspected PTB. METHODS: All patients with a clinical and radiological suspicion of PTB who underwent bronchoscopy between January 2013 and April 2014 were included. The diagnostic efficiencies of Xpert MTB/RIF and microscopy for AFB were compared to culture for Mycobacterium tuberculosis. RESULTS: Thirty nine of 112 patients were diagnosed with culture-positive PTB. Xpert MTB/RIF was positive in 36/39 with a sensitivity of 92.3% (95% CI 78-98%) for PTB, which was superior to that of smear microscopy (41%; 95% CI 26.0-57.8%, p = 0.005). The specificities of Xpert MTB/RIF and smear microscopy were 87.7% (95% CI 77.4-93.9%) and 98.6% (95% CI 91.6%-99.9%) respectively. Xpert MTB/RIF had a positive predictive value of 80% (95% CI; 65-89.9%) and negative predictive value of 95.5% (95% CI 86.6-98.8%). 3/9 patients with Xpert MTB/RIF positive culture negative results were treated for PTB based on clinical and radiological findings. CONCLUSION: Xpert MTB/RIF has a higher sensitivity than smear microscopy and similar specificity for the immediate confirmation of PTB in specimens obtained by bronchial washing, and should be utilised in patients with a high suspicion of pulmonary tuberculosis.

Genetic basis of rifampicin resistance in methicillin-resistant Staphylococcus aureus suggests clonal expansion in hospitals in Cape Town, South Africa.

BACKGROUND: Since 2001, several studies have reported high rifampicin resistance rates (45 - 100%) among methicillin-resistant Staphylococcus aureus (MRSA) isolates from South Africa. The authors previously characterised 100 MRSA isolates from hospitals in Cape Town, South Africa; forty-five percent of these isolates were rifampicin-resistant. The majority (44/45) corresponded to ST612-MRSA-IV, which is prevalent in South Africa, but has not been reported frequently elsewhere. The remaining rifampicin-resistant isolate corresponded to ST5-MRSA-I. The aim of this study was to investigate further the prevalence and genetic basis of rifampicin-resistance in MRSA isolates from hospitals in Cape Town. RESULTS: Between July 2007 and June 2011, the prevalence of rifampicin-resistant MRSA in hospitals in Cape Town ranged from 39.7% to 46.4%. Based on the results of the aforementioned study, nine ST612-MRSA-IV isolates, the rifampicin-resistant ST5-MRSA-I isolate, and two rifampicin-susceptible MRSA isolates were investigated. Four previously described ST612-MRSA-IV isolates, including two each from South Africa and Australia, were also included.The ST5-MRSA-I isolate carried a single mutational change, H481Y, commonly associated with high-level rifampicin resistance. All ST612-MRSA-IV isolates carried an uncommon double amino acid substitution in RpoB, H481N, I527M, whilst one of the Australian ST612-MRSA-IV isolates carried an additional mutation within rpoB, representing a novel rpoB genotype: H481N, I527M, K579R. All ST612-MRSA-IV isolates also shared a unique silent single nucleotide polymorphism (SNP) within rpoB. CONCLUSIONS: That local ST612-MRSA-IV isolates described here share an uncommon rpoB genotype and a unique silent SNP suggests this clone may have undergone clonal expansion in hospitals in Cape Town. Further, the data suggest that these isolates may be related to rifampicin-resistant ST612-MRSA-IV previously described in South Africa and Australia.

Corrigendum: Carriage of colistin-resistant Gram-negative bacteria in children from communities in Cape Town (Tuberculosis child multidrug-resistant preventive therapy trial sub-study).

[This corrects the article DOI: 10.4102/sajid.v36i1.241.].

Effect of antibiotics on the human microbiome: a systematic review.

BACKGROUND: Global antibiotic use has been increasing for decades. The gut microbiome, a key contributor to health, can be altered by antibiotics, which have been associated with both short- and long-term effects on the intestinal microbiome. The aim of this study was to summarize the effects of antibiotics on the diversity and composition of the human microbiota at different anatomical sites. METHODS: A systematic review was conducted according to PRISMA guidelines. PubMed, Scopus and Web of Science online databases were searched for studies that described the microbiome of any human bodily site pre- and post-antibiotic treatment using 16S rRNA gene sequencing. Increases or decreases in diversity, dissimilarity of microbial communities, and changes in taxonomic composition following antibiotic treatment were recorded as outcome measures. RESULTS: The review identified consistent changes in the microbiota following quinolone and metronidazole treatment, and showed that combination treatment may result in longer-term dysbiosis. The importance of longitudinal analysis, and a lack of studies in paediatric populations was highlighted. Heterogeneity in the methodology of included studies could have contributed to the inconsistent findings regarding the effect of most antibiotic classes on the microbiome. CONCLUSIONS: It is recommended that studies investigating the effect of antibiotics on the microbiome need to exclude participants exposed to antibiotics within 4 months preceding collection and analysis of baseline samples, and to include longitudinal analysis, particularly in the longer term. Further explorations need to be made into the functional implications of antibiotic-induced dysbiosis in the microbiome. SYSTEMATIC REVIEW REGISTRATION: PROSPERO (https://www.crd.york.ac.uk/prospero; Registration:CRD42020168991).

SafeHANDS: A Multimodal Hand Hygiene Intervention in a Resource-Limited Neonatal Unit.

BACKGROUND: Hand hygiene (HH) is a cornerstone of programmes to prevent healthcare associated infections (HAI) globally, but HH interventions are seldom reported from African neonatal units. METHODS: We conducted a quasi-experimental study evaluating the impact of a multi-modal intervention (SafeHANDS) on HH compliance rates, alcohol-based handrub (ABHR) usage, the Hand Hygiene Self-Assessment Framework (HHSAF) score, and healthcare-associated bloodstream infection (HA-BSI) rates at a 132-bed South African neonatal unit (4 wards and 1 neonatal intensive care unit [NICU]). The intervention included a campaign logo, HH training, maternal education leaflets, ABHR bottles for staff, and the setting of HH performance targets with feedback. Three 5-month study phases were completed in July 2020 (baseline), December 2020 (early) and May 2021 (intensive). RESULTS: A total of 2430 HH opportunities were observed: 1002 (41.3%) at baseline, 630 (25.9%) at early and 798 (32.8%) at intensive study phases. At baseline, the overall neonatal unit HH compliance rate was 61.6%, ABHR use was 70 mL/patient day, and the baseline HHSAF score was 'basic' (165). The overall neonatal unit HH compliance rate was unchanged from baseline to intensive phases (617/1002 [61.6%] vs. 497/798 [62.3%]; p = 0.797). The ABHR use remained similar between phases (70 versus 73 mL/patient day). The HHSAF score improved to 'intermediate' level (262). There was no change in the neonatal unit HA-BSI rate. CONCLUSION: Despite improvement in the HHSAF score, no improvement in overall HH compliance rates, ABHR usage, or HA-BSI rates was observed. Future HH interventions in resource-limited neonatal units should incorporate implementation science and behaviour modification strategies to better understand the barriers and facilitators of HH best practice.

Neonatal sepsis and mortality in low-income and middle-income countries from a facility-based birth cohort: an international multisite prospective observational study.

BACKGROUND: Neonatal sepsis is a primary cause of neonatal mortality and is an urgent global health concern, especially within low-income and middle-income countries (LMICs), where 99% of global neonatal mortality occurs. The aims of this study were to determine the incidence and associations with neonatal sepsis and all-cause mortality in facility-born neonates in LMICs. METHODS: The Burden of Antibiotic Resistance in Neonates from Developing Societies (BARNARDS) study recruited mothers and their neonates into a prospective observational cohort study across 12 clinical sites from Bangladesh, Ethiopia, India, Pakistan, Nigeria, Rwanda, and South Africa. Data for sepsis-associated factors in the four domains of health care, maternal, birth and neonatal, and living environment were collected for all mothers and neonates enrolled. Primary outcomes were clinically suspected sepsis, laboratory-confirmed sepsis, and all-cause mortality in neonates during the first 60 days of life. Incidence proportion of livebirths for clinically suspected sepsis and laboratory-confirmed sepsis and incidence rate per 1000 neonate-days for all-cause mortality were calculated. Modified Poisson regression was used to investigate factors associated with neonatal sepsis and parametric survival models for factors associated with all-cause mortality. FINDINGS: Between Nov 12, 2015 and Feb 1, 2018, 29 483 mothers and 30 557 neonates were enrolled. The incidence of clinically suspected sepsis was 166·0 (95% CI 97·69-234·24) per 1000 livebirths, laboratory-confirmed sepsis was 46·9 (19·04-74·79) per 1000 livebirths, and all-cause mortality was 0·83 (0·37-2·00) per 1000 neonate-days. Maternal hypertension, previous maternal hospitalisation within 12 months, average or higher monthly household income, ward size (>11 beds), ward type (neonatal), living in a rural environment, preterm birth, perinatal asphyxia, and multiple births were associated with an increased risk of clinically suspected sepsis, laboratory-confirmed sepsis, and all-cause mortality. The majority (881 [72·5%] of 1215) of laboratory-confirmed sepsis cases occurred within the first 3 days of life. INTERPRETATION: Findings from this study highlight the substantial proportion of neonates who develop neonatal sepsis, and the high mortality rates among neonates with sepsis in LMICs. More efficient and effective identification of neonatal sepsis is needed to target interventions to reduce its incidence and subsequent mortality in LMICs. FUNDING: Bill & Melinda Gates Foundation.

A retrospective analysis of pathogen profile, antimicrobial resistance and mortality in neonatal hospital-acquired bloodstream infections from 2009-2018 at Tygerberg Hospital, South Africa.

BACKGROUND: Analysis of hospital-acquired bloodstream infection (HA-BSI) trends is important to monitor emerging antimicrobial resistance (AMR) threats and guide empiric antibiotic choices. METHODS: A retrospective 10-year review of neonatal HA-BSI was performed at Tygerberg Hospital's neonatal unit in Cape Town, South Africa. Neonatal clinical and laboratory data from 2014 to 2018 (Period 2) was compared with published data from 2009 to 2013 (Period 1). RESULTS: The neonatal unit's HA-BSI rate declined between periods from 3.9/1000 inpatient-days in Period 1 to 3.3/1000 inpatient-days in Period 2 (p = 0.002). Pathogen yield and blood culture contamination rate were unchanged (11.0% to 10.4%, p = 0.233; 5.1% to 5.3%, p = 0.636 respectively). Gram-negative pathogens predominated (1047/1636; 64.0%); Klebsiella species, Staphylococcus aureus, Serratia marcescens, Enterococcus species and Acinetobacter baumannii were the most frequent pathogens. Extended spectrum beta-lactamase production was observed in 319/432 (73.8%) of Klebsiella species, methicillin resistance in 171/246 (69.5%) of Staphylococcus aureus and extensive drug resistance in 115/137 (83.9%) of Acinetobacter species (2009-2018). The crude mortality rate of neonatal HA-BSI episodes increased from Period 1 to Period 2 from 139/717 (19.4%) to 179/718 (24.9%) (p = 0.014), but HA-BSI attributable mortality remained unchanged (97/139 [69.8%] vs 118/179 [65.9%], p = 0.542). The in-vitro activity of piperacillin-tazobactam and amikacin declined during Period 2 (74.6% to 61.4%; p<0.001). CONCLUSION: Although HA-BSI rates declined in the neonatal unit, antimicrobial resistance rates in BSI pathogens remained high. Continuous BSI surveillance is a valuable tool to detect changes in pathogen and AMR profiles and inform empiric antibiotic recommendations for neonatal units in resource-limited settings.

Carriage of colistin-resistant Gram-negative bacteria in children from communities in Cape Town (Tuberculosis child multidrug-resistant preventive therapy trial sub-study).

Colistin is a last-resort antibiotic against multidrug-resistant, Gram-negative bacteria. Colistin resistance has been described in the clinical settings in South Africa. However, information on carriage of these bacteria in communities is limited. This study investigated gastrointestinal carriage of colistin-resistant Escherichia coli and Klebsiella spp. and mcr genes in children from communities in Cape Town. Colistin-resistant E. coli was isolated from two participants (4%, 2/50), and mcr-1-mcr-9 genes were not detected. Gastrointestinal carriage of colistin-resistant Enterobacterales was rare; however, continuous extensive surveillance is necessary to determine the extent of carriage and its contribution to resistance observed in clinical settings.

Characterisation of mobile colistin resistance genes (mcr-3 and mcr-5) in river and storm water in regions of the Western Cape of South Africa.

BACKGROUND: Colistin is regarded as a last-resort antimicrobial against multi-drug resistant Gram-negative bacteria (GNB), therefore the dissemination of colistin resistance in the environment is of great concern. Horizontal transfer of mobile colistin resistance (mcr) genes to potential pathogens poses a serious problem. This study aimed to describe the presence of colistin resistant GNB and mcr genes in river and storm water in regions of the Western Cape. METHODS: Water samples were collected from three rivers during May 2019 and January 2020 and two storm water samples were collected in November 2019. Colistin resistant GNB were cultured on MacConkey agar containing colistin and identified by MALDI-TOF. Colistin resistance was confirmed using broth microdilution (BMD). mcr-1-5 genes were detected by PCR performed directly on the water samples and on the colistin resistant isolates. mcr functionality was assessed by BMD after cloning the mcr genes into pET-48b(+) and expression in SHuffle T7 E. coli. RESULTS: mcr-5.1 and various mcr-3 gene variants were detected in the Plankenburg-, Eerste- and Berg rivers and in storm water from Muizenberg, and only mcr-5.1 was detected in storm water from Fish Hoek. Colistin resistant GNB were isolated from all of the water sources. Aeromonas spp. were the most common colistin resistant organisms detected in the water sources; 25% (6/24) of colistin resistant Aeromonas spp. isolated from the Berg river contained novel mcr-3 variants; mcr-3.33 (n = 1), mcr-3.34 (n = 1) mcr-3.35 (n = 1) mcr-3.36 (n = 2) and mcr-3.37 (n = 1), which were confirmed to confer colistin resistance. CONCLUSIONS: The mcr-5.1 and mcr-3 colistin resistance gene variants were present in widely dispersed water sources in regions of the Western Cape. The mcr genes were only detected in water sampled downstream of and alongside communities, suggesting that their presence is driven by human influence/contamination. This is the first documentation of mcr-3 and mcr-5 gene variants in any setting in South Africa. Spill-over of these genes to communities could result in horizontal gene transfer to pathogenic bacteria, exacerbating the challenge of controlling multidrug resistant GNB infections.

Association between clinical and environmental factors and the gut microbiota profiles in young South African children.

Differences in the microbiota in populations over age and geographical locations complicate cross-study comparisons, and it is therefore essential to describe the baseline or control microbiota in each population. This includes the determination of the influence of demographic, clinical and environmental factors on the microbiota in a setting, and elucidates possible bias introduced by these factors, prior to further investigations. Little is known about the microbiota of children in South Africa after infancy. We provide a detailed description of the gut microbiota profiles of children from urban Cape Town and describe the influences of various clinical and environmental factors in different age groups during the first 5 years of life. Prevotella was the most common genus identified in the participants, and after infancy, the gut bacteria were dominated by Firmicutes and Bacteroidetes. In this setting, children exposed to antibiotics and indoor cooking fires were at the most risk for dysbiosis, showing significant losses in gut bacterial diversity.

Impact of 1% chlorhexidine gluconate bathing and emollient application on bacterial pathogen colonization dynamics in hospitalized preterm neonates - A pilot clinical trial.

BACKGROUND: Chlorhexidine gluconate (CHG) body washes and emollient application may modulate bacterial pathogen colonization and prevent neonatal hospital-acquired infections. METHODS: This pilot, non-randomized, open-label trial, enrolled preterm neonates (1000-1500g; day 1-3 of life) at a tertiary hospital in Cape Town, South Africa. Participants were sequentially allocated to 4 trial arms (n=20 each): 1% aqueous CHG (CHG), 1% CHG plus emollient (CHG+EM), emollient only (EM) and standard of care (SOC: no antiseptic/emollient). Trial treatment/s were applied daily for 10 days (d) post-enrolment, documenting neonatal skin condition score. Anterior nose, neck, umbilical and perianal swabs for bacterial culture were collected at d1, d3, d10 and d16 post-enrolment, (±1 day), reporting pathogen acquisition rates and semi-quantitative bacterial colony counts. (ClinicalTrials.gov identifier: NCT03896893; trial status: closed). FINDINGS: Eighty preterm neonates (mean gestational age 30 weeks [SD 2]) were enrolled between 4 March and 26 August 2019. The bacterial pathogen acquisition rate (comparing d1 and d16 swabs) varied from 33·9% [95%CI 22·9-47·0] at the umbilicus, 39·3% [95%CI 27·6-52·4] at the neck, to 71·4% [95%CI 58·5-81·7] at both the nose and perianal region. At d10, CHG babies had reduced bacterial density detected from neck, umbilicus, and perianal swabs compared to other groups (see Table 3). Following intervention cessation, colonization density was similar across all trial arms, but S. aureus colonization was more prevalent among EM and CHG+EM babies. Neonatal skin condition score improved in babies receiving emollient application (EM: -0·87 [95%CI 0·69-1·06] and CHG+EM: -0·73 [0·45-0·99]), compared to the SOC and CHG arms (Table 2); no CHG-related skin reactions occurred. INTERPRETATION: Bacterial colonization density was significantly reduced in babies receiving 1% CHG washes but colonization levels rebounded rapidly post-intervention. Emollient application improved skin condition but was associated with higher rates of S. aureus colonization. FUNDING: South African Medical Research Council; National Institutes of Health (TW010682).

Diagnostic utility of bronchoalveolar lavage in children with complicated intrathoracic tuberculosis.

INTRODUCTION: Bronchoscopy can be a useful tool in children with pulmonary tuberculosis (PTB) with severe disease potentially requiring intervention or in the face of diagnostic dilemmas. The aim of this study was to determine the value of Xpert MTB/RIF assay (Xpert) on bronchoalveolar lavage (BAL) samples in children with complicated PTB. METHODS: Retrospective analysis of children with clinically diagnosed PTB, who underwent routine bronchoscopy over a 5-year period at a large referral hospital. BAL and other respiratory samples were tested by microscopy, culture, and Xpert. We explored whether clinical, radiographic and bronchoscopy findings, and duration of antituberculosis treatment were associated with bacteriological confirmation. RESULTS: One hundred and twelve out of one hundred and forty-six (76.7%) children (median age 16 months) were on antituberculosis treatment for a median of 10 days at the time of bronchoscopy. Overall, bacteriological confirmation was achieved in 115 (78.7%), with 101 (69.2%) detected on BAL. Of those bacteriologically confirmed on BAL, 61.4% were positive by both Xpert and culture, 34.7% only by Xpert, and 3.9% only by culture. Sensitivity and specificity of Xpert compared with culture on BAL samples for children not on antituberculosis treatment were 94.1% (95% confidence interval [CI]: 71.3, 99.8) and 68.7% (95% CI: 41.3, 89.0), respectively. CONCLUSIONS: In children undergoing bronchoscopy for complicated PTB, Xpert testing of BAL had a high diagnostic yield in children already on antituberculosis treatment. Bronchoscopy should be considered if noninvasive respiratory specimens fail to confirm complicated TB.

The effect of storage conditions on microbial communities in stool.

Microbiome research has experienced a surge of interest in recent years due to the advances and reduced cost of next-generation sequencing technology. The production of high quality and comparable data is dependent on proper sample collection and storage and should be standardized as far as possible. However, this becomes challenging when samples are collected in the field, especially in resource-limited settings. We investigated the impact of different stool storage methods common to the TB-CHAMP clinical trial on the microbial communities in stool. Ten stool samples were subjected to DNA extraction after 48-hour storage at -80°C, room temperature and in a cooler-box, as well as immediate DNA extraction. Three stool DNA extraction kits were evaluated based on DNA yield and quality. Quantitative PCR was performed to determine the relative abundance of the two major gut phyla Bacteroidetes and Firmicutes, and other representative microbial groups. The bacterial populations in the frozen group closely resembled the immediate extraction group, supporting previous findings that storage at -80°C is equivalent to the gold standard of immediate DNA extraction. More variation was seen in the room temperature and cooler-box groups, which may be due to the growth temperature preferences of certain bacterial populations. However, for most bacterial populations, no significant differences were found between the storage groups. As seen in other microbiome studies, the variation between participant samples was greater than that related to differences in storage. We determined that the risk of introducing bias to microbial community profiling through differences in storage will likely be minimal in our setting.

Erratum to South African guideline for the management of community-acquired pneumonia in adults.

[This corrects the article DOI: 10.21037/jtd.2017.05.31.].

The Cape Town Clinical Decision Rule for Streptococcal Pharyngitis in Children.

BACKGROUND: Existing clinical decision rules (CDRs) to diagnose group A streptococcal (GAS) pharyngitis have not been validated in sub-Saharan Africa. We developed a locally applicable CDR while evaluating existing CDRs for diagnosing GAS pharyngitis in South African children. METHODS: We conducted a prospective cohort study and enrolled 997 children 3-15 years of age presenting to primary care clinics with a complaint of sore throat, and whose parents provided consent. Main outcome measures were signs and symptoms of pharyngitis and a positive GAS culture from a throat swab. Bivariate and multivariate analyses were used to develop the CDR. In addition, the diagnostic effectiveness of 6 existing rules for predicting a positive culture in our cohort was assessed. RESULTS: A total of 206 of 982 children (21%) had a positive GAS culture. Tonsillar swelling, tonsillar exudates, tender or enlarged anterior cervical lymph nodes, absence of cough and absence of rhinorrhea were associated with positive cultures in bivariate and multivariate analyses. Four variables (tonsillar swelling and one of tonsillar exudate, no rhinorrhea, no cough), when used in a cumulative score, showed 83.7% sensitivity and 32.2% specificity for GAS pharyngitis. Of existing rules tested, the rule by McIsaac et al had the highest positive predictive value (28%), but missed 49% of the culture-positive children who should have been treated. CONCLUSION: The new 4-variable CDR for GAS pharyngitis (ie, tonsillar swelling and one of tonsillar exudate, no rhinorrhea, no cough) outperformed existing rules for GAS pharyngitis diagnosis in children with symptomatic sore throat in Cape Town.

Time for a culture change? Suboptimal compliance with blood culture standards at a district hospital in Cape Town.

BACKGROUND: The benchmark for contaminated blood cultures (BCs) is 3%. The South African (SA) guideline aims to optimise BC yield and reduce contamination. Data on BC collection practices in SA since the publication of the 2010 SA guideline are lacking. OBJECTIVE: To evaluate compliance with the national guideline for the optimal use of BCs and determine the BC contamination rate at a local district hospital. METHOD: An audit of compliance with 22 BC standards was conducted at a district hospital in Cape Town, SA. Standards were evaluated by reviewing clinical and laboratory data and by a clinician questionnaire. RESULTS: Of the 425 BCs reviewed, 12.5% had positive growth, and 4.5% grew contaminants. Only 33% of BC bottles contained the recommended fill volume of 8-10 mL, and 96.9% of patients had a single BC within a 24-hour period. Of all the BCs, only 7.8% had a combined blood volume of at least 20 mL. The yield of pathogens in BCs collected after antibiotic exposure was 4.9% compared with 7.5% for those cultures with no prior antibiotic exposure (p=0.3). The overall median needle-to-incubator transport time was 11 hours 25 minutes. CONCLUSION: The BC contamination rate was high and compliance with most standards was variable or not met. The findings may not be generalisable to other hospitals, and we recommend that each institution reviews its own BC practices. Recommendations made to hospital staff included a re-audit following implementation of these recommendations.

Group A streptococcal emm type prevalence among symptomatic children in Cape Town and potential vaccine coverage.

The molecular epidemiology of group A streptococcal pharyngeal infections in children in the Vanguard Community of Cape Town revealed 26 emm types among 157 isolates from 742 subjects. Coverage of a 30-valent vaccine is predicted to be 95% of pharyngitis cases in this population at high risk of rheumatic fever.

A comparison of cases of paediatric-onset and adult-onset cryptococcosis detected through population-based surveillance, 2005-2007.

OBJECTIVE: We compared the epidemiology of laboratory-confirmed paediatric cryptococcal disease with adult-onset disease in the South African population. METHODS: The study was an active, prospective, population-based, laboratory-based surveillance in South Africa. We compared cases of paediatric cryptococcosis (<15 years) with cases of adult-onset cryptococcosis that were reported to the surveillance programme between 1 January 2005 and 31 December 2007. The case definition was based on a positive India ink test, cryptococcal antigen test or cryptococcal culture. Clinical case data were obtained at enhanced surveillance sites. RESULTS: Of 16,192 incident episodes of cryptococcosis in South Africa, 361 (2%) episodes occurred among children. In 2007, incidence was one and 19 cases per 100,000 persons in the general paediatric and adult populations and was 47 and 120 cases per 100,000 persons for HIV-infected children and adults, respectively. Among children, a bimodal peak in incidence was evident in the less than 1-year age group and in the 5 age group. Most children (64%) and adults (63%) were severely immunocompromised (CD4 T-lymphocyte cell count < 50 cells/µl) at the time of diagnosis. On multivariable analysis, children were significantly more likely than adults to be male, diagnosed on blood culture, infected with Cryptococcus gattii, treated with amphotericin B and admitted for a longer stay in hospital. CONCLUSION: This series of 361 cases of paediatric cryptococcosis is by far the largest described to date. The diagnosis of cryptococcosis should be considered in the paediatric HIV-infected population, especially among those who are severely immunocompromised.