Andrew Whitelaw

Publications (28) View all

• Article: Systemic shigellosis in South Africa.

  Karen H Keddy, Arvinda Sooka, Penny Crowther-Gibson, Vanessa Quan, Susan Meiring, Cheryl Cohen, Trusha Nana, Charlotte Sriruttan, Sharona Seetharam, Anwar Hoosen, Preneshni Naicker, Eugenne Elliott, Sumayya Haffejee, Andrew Whitelaw, Keith P Klugman
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  ABSTRACT: Systemic disease due to shigellae is associated with human immunodeficiency virus (HIV), malnutrition, and other immunosuppressed states. We examined the clinical and microbiologic characteristics of systemic shigellosis in South Africa, where rates of HIV infection are high. From 2003 to 2009, 429 cases of invasive shigellosis were identified through national laboratory-based surveillance. At selected sites, additional information was captured on HIV serostatus and outcome. Isolates were serotyped and antimicrobial susceptibility testing performed. Most cases of systemic shigellosis were diagnosed on blood culture (408 of 429 cases; 95%). HIV prevalence was 67% (80 of 120 cases), highest in patients aged 5-54 years, and higher among females (55 of 70 cases; 79%) compared with males (25 of 48 cases; 52%; P = .002). HIV-infected people were 4.1 times more likely to die than HIV-uninfected cases (case-fatality ratio, 29 of 78 HIV-infected people [37%] vs 5 of 40 HIV-uninfected people [13%]; P = .008; 95% confidence interval [CI], 1.5-11.8). The commonest serotype was Shigella flexneri 2a (89 of 292 serotypes [30.5%]). Pentavalent resistance occurred in 120 of 292 isolates (41.1%). There was no difference in multidrug resistance between HIV-infected patients (33 of 71 [46%]) and uninfected patients (12 of 33 [36%]; 95% CI, .65--3.55). Systemic shigellosis is associated with HIV-infected patients, primarily in older girls and women, potentially due to the burden of caring for sick children in the home; interventions need to be targeted here. Death rates are higher in HIV-infected versus uninfected individuals.
  Clinical Infectious Diseases 04/2012; 54(10):1448-54. · 9.15 Impact Factor
• Source

  Available from: Andrew D. Kerkhoff

  Article: Characteristics and early outcomes of patients with Xpert MTB/RIF-negative pulmonary tuberculosis diagnosed during screening before antiretroviral therapy.

  Stephen D Lawn, Andrew D Kerkhoff, Monica Vogt, Yonas Ghebrekristos, Andrew Whitelaw, Robin Wood
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  ABSTRACT: A proportion of patients with tuberculosis diagnosed by sputum culture during screening before antiretroviral therapy (ART) have false-negative Xpert MTB/RIF assay results (Xpert-negative tuberculosis). We determined the characteristics and early ART program outcomes of such patients. Adult patients who enrolled in a South African township ART service were systematically screened for pulmonary tuberculosis regardless of symptoms by testing paired sputum samples with Xpert MTB/RIF and liquid culture. The ART service provided follow-up for all patients, and early (90-day) programmatic outcomes were determined. Among 602 patients screened, 523 had ≥1 Xpert and culture result, yielding 89 culture-positive tuberculosis diagnoses. Of these, 37 (42%) of the patients with tuberculosis were Xpert-negative when a single sputum sample was tested, compared with 25 (28%) when 2 samples were tested. Compared with patients with Xpert-positive tuberculosis, those with Xpert-negative tuberculosis (using either definition) had substantially higher CD4 cell counts, lower plasma viral loads, higher hemoglobin concentrations, and higher body mass index. Their tuberculosis was also less advanced, with a lower frequency of prolonged cough (≥2 weeks), less extensive radiographic abnormalities, and a lower frequency of detectable lipoarabinomannan antigenuria and mycobacteriuria. Xpert-negative cases were all sputum smear negative with prolonged time to culture positivity (median, 21 days). Despite greater delays in starting tuberculosis treatment, Xpert-negative patients were less likely to die during follow-up. Compared to patients with Xpert-positive tuberculosis diagnosed during pre-ART screening, Xpert-negative cases had less advanced immunosuppression and less advanced tuberculosis and did not have adverse outcomes despite substantial delays in starting tuberculosis treatment.
  Clinical Infectious Diseases 02/2012; 54(8):1071-9. · 9.15 Impact Factor
• Article: ICU-Associated Acinetobacter baumannii Colonisation/Infection in a High HIV-Prevalence Resource-Poor Setting.

  Ntobeko B A Ntusi, Motasim Badri, Hoosain Khalfey, Andrew Whitelaw, Stephen Oliver, Jenna Piercy, Richard Raine, Ivan Joubert, Keertan Dheda
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  ABSTRACT: There are hardly any data about the incidence, risk factors and outcomes of ICU-associated A.baumannii colonisation/infection in HIV-infected and uninfected persons from resource-poor settings like Africa. We reviewed the case records of patients with A.baumannii colonisation/infection admitted into the adult respiratory and surgical ICUs in Cape Town, South Africa, from January 1 to December 31 2008. In contrast to colonisation, infection was defined as isolation of A.baumannii from any biological site in conjunction with a compatible clinical picture warranting treatment with antibiotics effective against A.baumannii. The incidence of A.baumannii colonisation/infection in 268 patients was 15 per 100 person-years, with an in-ICU mortality of 26.5 per 100 person-years. The average length of stay in ICU was 15 days (range 1-150). A.baumannii was most commonly isolated from the respiratory tract followed by the bloodstream. Independent predictors of mortality included older age (p = 0.02), low CD4 count if HIV-infected (p = 0.038), surgical intervention (p = 0.047), co-morbid Gram-negative sepsis (p = 0.01), high APACHE-II score (p = 0.001), multi-organ dysfunction syndrome (p = 0.012), and a positive blood culture for A.baumannii (p = 0.017). Of 21 A.baumannii colonised/infected HIV-positive persons those with clinical AIDS (CD4<200 cells/mm(3)) had significantly higher in-ICU mortality and were more likely to have a positive blood culture. Conclusion In this resource-poor setting A.baumannii infection in critically ill patients is common and associated with high mortality. HIV co-infected patients with advanced immunosuppression are at higher risk of death.
  PLoS ONE 01/2012; 7(12):e52452. · 4.09 Impact Factor
• Source

  Available from: Brenda Morrow

  Article: Improved detection of Pneumocystis jirovecii in upper and lower respiratory tract specimens from children with suspected pneumocystis pneumonia using real-time PCR: a prospective study.

  Catherine M Samuel, Andrew Whitelaw, Craig Corcoran, Brenda Morrow, Nei-Yuan Hsiao, Marco Zampoli, Heather J Zar
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  ABSTRACT: Pneumocystis pneumonia (PCP) is a major cause of hospitalization and mortality in HIV-infected African children. Microbiologic diagnosis relies predominantly on silver or immunofluorescent staining of a lower respiratory tract (LRT) specimens which are difficult to obtain in children. Diagnosis on upper respiratory tract (URT) specimens using PCR has been reported useful in adults, but data in children are limited. The main objectives of the study was (1) to compare the diagnostic yield of PCR with immunofluorescence (IF) and (2) to investigate the usefulness of upper compared to lower respiratory tract samples for diagnosing PCP in children. Children hospitalised at an academic hospital with suspected PCP were prospectively enrolled. An upper respiratory sample (nasopharyngeal aspirate, NPA) and a lower respiratory sample (induced sputum, IS or bronchoalveolar lavage, BAL) were submitted for real-time PCR and direct IF for the detection of Pneumocystis jirovecii. A control group of children with viral lower respiratory tract infections were investigated with PCR for PCP. 202 children (median age 3.3 [inter-quartile range, IQR 2.2 - 4.6] months) were enrolled. The overall detection rate by PCR was higher than by IF [180/349 (52%) vs. 26/349 (7%) respectively; p < 0.0001]. PCR detected more infections compared to IF in lower respiratory tract samples [93/166 (56%) vs. 22/166 (13%); p < 0.0001] and in NPAs [87/183 (48%) vs. 4/183 (2%); p < 0.0001]. Detection rates by PCR on upper (87/183; 48%) compared with lower respiratory tract samples (93/166; 56%) were similar (OR, 0.71; 95% CI, 0.46 - 1.11). Only 2/30 (6.6%) controls were PCR positive. Real-time PCR is more sensitive than IF for the detection of P. jirovecii in children with PCP. NPA samples may be used for diagnostic purposes when PCR is utilised. Wider implementation of PCR on NPA samples is warranted for diagnosing PCP in children.
  BMC Infectious Diseases 11/2011; 11:329. · 3.12 Impact Factor
• Article: Invasive disease due to Haemophilus influenzae serotype b ten years after routine vaccination, South Africa, 2003-2009.

  Anne von Gottberg, Cheryl Cohen, Andrew Whitelaw, Meera Chhagan, Brendan Flannery, Adam L Cohen, Linda de Gouveia, Mignon du Plessis, Shabir A Madhi, Keith P Klugman
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  ABSTRACT: South Africa started routine infant immunization against Haemophilus influenzae serotype b (Hib) disease in 1999 with an accelerated three-dose schedule of Hib conjugate vaccine (HibCV) without a booster dose. Following initial declines in Hib disease, national surveillance has identified increasing numbers of Hib disease episodes in fully vaccinated children. We reviewed national laboratory-based surveillance data from 2003 through 2009 for invasive Hib disease episodes among children <5 years, including HIV status and vaccination histories. We defined HibCV failures as invasive Hib disease in children at least four months of age who had received all recommended doses of HibCV. Despite high HibCV vaccination coverage, detection rates of Hib disease in children <5 years increased from 0.7 per 100,000 population in 2003 to 1.3/100,000 in 2009 (p<0.001). Among 263 episodes of invasive Hib disease among children with known vaccination status, 135 (51%) were classified as vaccine failures. Of vaccine failures, 55% occurred among case patients ≥18 months old. HIV status was documented for 90 children with vaccine failure; 53% were not HIV infected. Vaccine failures, which occurred in both HIV-infected and -uninfected children, comprised half of the rise in invasive Hib disease detected in South African children 10 years after national introduction of Hib vaccine. These findings suggest that HibCV recommendations may require revision. In November 2010, children in South Africa began receiving a booster dose of HibCV as part of a pentavalent vaccine.
  Vaccine 11/2011; 30(3):565-71. · 3.77 Impact Factor